Modeling Human Steering Behavior During Path Following in Teleoperation of Unmanned Ground Vehicles.

PubMed

Mirinejad, Hossein; Jayakumar, Paramsothy; Ersal, Tulga

2018-04-01

This paper presents a behavioral model representing the human steering performance in teleoperated unmanned ground vehicles (UGVs). Human steering performance in teleoperation is considerably different from the performance in regular onboard driving situations due to significant communication delays in teleoperation systems and limited information human teleoperators receive from the vehicle sensory system. Mathematical models capturing the teleoperation performance are a key to making the development and evaluation of teleoperated UGV technologies fully simulation based and thus more rapid and cost-effective. However, driver models developed for the typical onboard driving case do not readily address this need. To fill the gap, this paper adopts a cognitive model that was originally developed for a typical highway driving scenario and develops a tuning strategy that adjusts the model parameters in the absence of human data to reflect the effect of various latencies and UGV speeds on driver performance in a teleoperated path-following task. Based on data collected from a human subject test study, it is shown that the tuned model can predict both the trend of changes in driver performance for different driving conditions and the best steering performance of human subjects in all driving conditions considered. The proposed model with the tuning strategy has a satisfactory performance in predicting human steering behavior in the task of teleoperated path following of UGVs. The established model is a suited candidate to be used in place of human drivers for simulation-based studies of UGV mobility in teleoperation systems.

From The Cover: Reconstruction of functionally normal and malignant human breast tissues in mice

NASA Astrophysics Data System (ADS)

Kuperwasser, Charlotte; Chavarria, Tony; Wu, Min; Magrane, Greg; Gray, Joe W.; Carey, Loucinda; Richardson, Andrea; Weinberg, Robert A.

2004-04-01

The study of normal breast epithelial morphogenesis and carcinogenesis in vivo has largely used rodent models. Efforts at studying mammary morphogenesis and cancer with xenotransplanted human epithelial cells have failed to recapitulate the full extent of development seen in the human breast. We have developed an orthotopic xenograft model in which both the stromal and epithelial components of the reconstructed mammary gland are of human origin. Genetic modification of human stromal cells before the implantation of ostensibly normal human mammary epithelial cells resulted in the outgrowth of benign and malignant lesions. This experimental model allows for studies of human epithelial morphogenesis and differentiation in vivo and underscores the critical role of heterotypic interactions in human breast development and carcinogenesis.

Generation of improved humanized mouse models for human infectious diseases

PubMed Central

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

2014-01-01

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

Measurement of Libby Amphibole (LA) Elongated Particle Dissolution Rates and Alteration of Size/Shape Distributions in Support of Human Dosimetry Model Development and Relative Potency Determinations

EPA Science Inventory

To maximize the value of toxicological data in development of human health risk assessment models of inhaled elongated mineral particles, improvements in human dosimetry modeling are needed. In order to extend the dosimetry model of deposited fibers (Asgharian et aI., Johnson 201...

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.

Genome-wide expression profiling of five mouse models identifies similarities and differences with human psoriasis.

PubMed

Swindell, William R; Johnston, Andrew; Carbajal, Steve; Han, Gangwen; Wohn, Christian; Lu, Jun; Xing, Xianying; Nair, Rajan P; Voorhees, John J; Elder, James T; Wang, Xiao-Jing; Sano, Shigetoshi; Prens, Errol P; DiGiovanni, John; Pittelkow, Mark R; Ward, Nicole L; Gudjonsson, Johann E

2011-04-04

Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis.

Development, Testing, and Validation of a Model-Based Tool to Predict Operator Responses in Unexpected Workload Transitions

NASA Technical Reports Server (NTRS)

Sebok, Angelia; Wickens, Christopher; Sargent, Robert

2015-01-01

One human factors challenge is predicting operator performance in novel situations. Approaches such as drawing on relevant previous experience, and developing computational models to predict operator performance in complex situations, offer potential methods to address this challenge. A few concerns with modeling operator performance are that models need to realistic, and they need to be tested empirically and validated. In addition, many existing human performance modeling tools are complex and require that an analyst gain significant experience to be able to develop models for meaningful data collection. This paper describes an effort to address these challenges by developing an easy to use model-based tool, using models that were developed from a review of existing human performance literature and targeted experimental studies, and performing an empirical validation of key model predictions.

The old and new face of craniofacial research: How animal models inform human craniofacial genetic and clinical data.

PubMed

Van Otterloo, Eric; Williams, Trevor; Artinger, Kristin Bruk

2016-07-15

The craniofacial skeletal structures that comprise the human head develop from multiple tissues that converge to form the bones and cartilage of the face. Because of their complex development and morphogenesis, many human birth defects arise due to disruptions in these cellular populations. Thus, determining how these structures normally develop is vital if we are to gain a deeper understanding of craniofacial birth defects and devise treatment and prevention options. In this review, we will focus on how animal model systems have been used historically and in an ongoing context to enhance our understanding of human craniofacial development. We do this by first highlighting "animal to man" approaches; that is, how animal models are being utilized to understand fundamental mechanisms of craniofacial development. We discuss emerging technologies, including high throughput sequencing and genome editing, and new animal repository resources, and how their application can revolutionize the future of animal models in craniofacial research. Secondly, we highlight "man to animal" approaches, including the current use of animal models to test the function of candidate human disease variants. Specifically, we outline a common workflow deployed after discovery of a potentially disease causing variant based on a select set of recent examples in which human mutations are investigated in vivo using animal models. Collectively, these topics will provide a pipeline for the use of animal models in understanding human craniofacial development and disease for clinical geneticist and basic researchers alike. Copyright © 2016 Elsevier Inc. All rights reserved.

Combining Modeling and Gaming for Predictive Analytics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riensche, Roderick M.; Whitney, Paul D.

2012-08-22

Many of our most significant challenges involve people. While human behavior has long been studied, there are recent advances in computational modeling of human behavior. With advances in computational capabilities come increases in the volume and complexity of data that humans must understand in order to make sense of and capitalize on these modeling advances. Ultimately, models represent an encapsulation of human knowledge. One inherent challenge in modeling is efficient and accurate transfer of knowledge from humans to models, and subsequent retrieval. The simulated real-world environment of games presents one avenue for these knowledge transfers. In this paper we describemore » our approach of combining modeling and gaming disciplines to develop predictive capabilities, using formal models to inform game development, and using games to provide data for modeling.« less

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.

Leadership Training for Special Educators.

ERIC Educational Resources Information Center

Berkeley, Terry R.; And Others

This paper describes a leadership model based on assumptions about connections between human development and organizational development, and the application of the model in leadership training for New Hampshire special education directors. The model assumes that four critical factors of human development outlined by Piaget and Meisels can be…

A model of human decision making in multiple process monitoring situations

NASA Technical Reports Server (NTRS)

Greenstein, J. S.; Rouse, W. B.

1982-01-01

Human decision making in multiple process monitoring situations is considered. It is proposed that human decision making in many multiple process monitoring situations can be modeled in terms of the human's detection of process related events and his allocation of attention among processes once he feels event have occurred. A mathematical model of human event detection and attention allocation performance in multiple process monitoring situations is developed. An assumption made in developing the model is that, in attempting to detect events, the human generates estimates of the probabilities that events have occurred. An elementary pattern recognition technique, discriminant analysis, is used to model the human's generation of these probability estimates. The performance of the model is compared to that of four subjects in a multiple process monitoring situation requiring allocation of attention among processes.

Genome-Wide Expression Profiling of Five Mouse Models Identifies Similarities and Differences with Human Psoriasis

PubMed Central

Swindell, William R.; Johnston, Andrew; Carbajal, Steve; Han, Gangwen; Wohn, Christian; Lu, Jun; Xing, Xianying; Nair, Rajan P.; Voorhees, John J.; Elder, James T.; Wang, Xiao-Jing; Sano, Shigetoshi; Prens, Errol P.; DiGiovanni, John; Pittelkow, Mark R.; Ward, Nicole L.; Gudjonsson, Johann E.

2011-01-01

Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis. PMID:21483750

Application of the Human Activity Assistive Technology model for occupational therapy research.

PubMed

Giesbrecht, Ed

2013-08-01

Theoretical models provide a framework for describing practice and integrating evidence into systematic research. There are few models that relate specifically to the provision of assistive technology in occupational therapy practice. The Human Activity Assistive Technology model is an enduring example that has continued to develop by integrating a social model of disability, concepts from occupational therapy theory and principles of assistive technology adoption and abandonment. This study first describes the core concepts of the Human Activity Assistive Technology model and reviews its development over three successive published versions. A review of the research literature reflects application of the model to clinical practice, study design, outcome measure selection and interpretation of results, particularly among occupational therapists. An evaluative framework is used to critique the adequacy of the Human Activity Assistive Technology model for practice and research, exploring attributes of clarity, simplicity, generality, accessibility and importance. Finally, recommendations are proposed for continued development of the model and research applications. Most of the existing research literature employs the Human Activity Assistive Technology model for background and study design; there is emerging evidence to support the core concepts as predictive factors. Although the concepts are generally simple, clear and applicable to occupational therapy practice and research, evolving terminology and outcomes become more complex with the conflation of integrated theories. The development of the Human Activity Assistive Technology model offers enhanced access and application for occupational therapists, but poses challenges to clarity among concepts. Suggestions are made for further development and applications of the model. © 2013 Occupational Therapy Australia.

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.

Predictivity of dog co-culture model, primary human hepatocytes and HepG2 cells for the detection of hepatotoxic drugs in humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Atienzar, Franck A., E-mail: franck.atienzar@ucb.com; Novik, Eric I.; Gerets, Helga H.

Drug Induced Liver Injury (DILI) is a major cause of attrition during early and late stage drug development. Consequently, there is a need to develop better in vitro primary hepatocyte models from different species for predicting hepatotoxicity in both animals and humans early in drug development. Dog is often chosen as the non-rodent species for toxicology studies. Unfortunately, dog in vitro models allowing long term cultures are not available. The objective of the present manuscript is to describe the development of a co-culture dog model for predicting hepatotoxic drugs in humans and to compare the predictivity of the canine modelmore » along with primary human hepatocytes and HepG2 cells. After rigorous optimization, the dog co-culture model displayed metabolic capacities that were maintained up to 2 weeks which indicates that such model could be also used for long term metabolism studies. Most of the human hepatotoxic drugs were detected with a sensitivity of approximately 80% (n = 40) for the three cellular models. Nevertheless, the specificity was low approximately 40% for the HepG2 cells and hepatocytes compared to 72.7% for the canine model (n = 11). Furthermore, the dog co-culture model showed a higher superiority for the classification of 5 pairs of close structural analogs with different DILI concerns in comparison to both human cellular models. Finally, the reproducibility of the canine system was also satisfactory with a coefficient of correlation of 75.2% (n = 14). Overall, the present manuscript indicates that the dog co-culture model may represent a relevant tool to perform chronic hepatotoxicity and metabolism studies. - Highlights: • Importance of species differences in drug development. • Relevance of dog co-culture model for metabolism and toxicology studies. • Hepatotoxicity: higher predictivity of dog co-culture vs HepG2 and human hepatocytes.« less

Bioengineered humanized livers as better three-dimensional drug testing model system.

PubMed

Vishwakarma, Sandeep Kumar; Bardia, Avinash; Lakkireddy, Chandrakala; Nagarapu, Raju; Habeeb, Md Aejaz; Khan, Aleem Ahmed

2018-01-27

To develop appropriate humanized three-dimensional ex-vivo model system for drug testing. Bioengineered humanized livers were developed in this study using human hepatic stem cells repopulation within the acellularized liver scaffolds which mimics with the natural organ anatomy and physiology. Six cytochrome P-450 probes were used to enable efficient identification of drug metabolism in bioengineered humanized livers. The drug metabolism study in bioengineered livers was evaluated to identify the absorption, distribution, metabolism, excretion and toxicity responses. The bioengineered humanized livers showed cellular and molecular characteristics of human livers. The bioengineered liver showed three-dimensional natural architecture with intact vasculature and extra-cellular matrix. Human hepatic cells were engrafted similar to the human liver. Drug metabolism studies provided a suitable platform alternative to available ex-vivo and in vivo models for identifying cellular and molecular dynamics of pharmacological drugs. The present study paves a way towards the development of suitable humanized preclinical model systems for pharmacological testing. This approach may reduce the cost and time duration of preclinical drug testing and further overcomes on the anatomical and physiological variations in xenogeneic systems.

Modeling Human Natural Killer Cell Development in the Era of Innate Lymphoid Cells

PubMed Central

Scoville, Steven D.; Freud, Aharon G.; Caligiuri, Michael A.

2017-01-01

Decades after the discovery of natural killer (NK) cells, their developmental pathways in mice and humans have not yet been completely deciphered. Accumulating evidence indicates that NK cells can develop in multiple tissues throughout the body. Moreover, detailed and comprehensive models of NK cell development were proposed soon after the turn of the century. However, with the recent identification and characterization of other subtypes of innate lymphoid cells (ILCs), which show some overlapping functional and phenotypic features with NK cell developmental intermediates, the distinct stages through which human NK cells develop from early hematopoietic progenitor cells remain unclear. Thus, there is a need to reassess and refine older models of NK cell development in the context of new data and in the era of ILCs. Our group has focused on elucidating the developmental pathway of human NK cells in secondary lymphoid tissues (SLTs), including tonsils and lymph nodes. Here, we provide an update of recent progress that has been made with regard to human NK cell development in SLTs, and we discuss these new findings in the context of contemporary models of ILC development. PMID:28396671

Modeling Human Natural Killer Cell Development in the Era of Innate Lymphoid Cells.

PubMed

Scoville, Steven D; Freud, Aharon G; Caligiuri, Michael A

2017-01-01

Decades after the discovery of natural killer (NK) cells, their developmental pathways in mice and humans have not yet been completely deciphered. Accumulating evidence indicates that NK cells can develop in multiple tissues throughout the body. Moreover, detailed and comprehensive models of NK cell development were proposed soon after the turn of the century. However, with the recent identification and characterization of other subtypes of innate lymphoid cells (ILCs), which show some overlapping functional and phenotypic features with NK cell developmental intermediates, the distinct stages through which human NK cells develop from early hematopoietic progenitor cells remain unclear. Thus, there is a need to reassess and refine older models of NK cell development in the context of new data and in the era of ILCs. Our group has focused on elucidating the developmental pathway of human NK cells in secondary lymphoid tissues (SLTs), including tonsils and lymph nodes. Here, we provide an update of recent progress that has been made with regard to human NK cell development in SLTs, and we discuss these new findings in the context of contemporary models of ILC development.

Humanized NOG mice as a model for tuberculosis vaccine-induced immunity: a comparative analysis with the mouse and guinea pig models of tuberculosis.

PubMed

Grover, Ajay; Troy, Amber; Rowe, Jenny; Troudt, JoLynn M; Creissen, Elizabeth; McLean, Jennifer; Banerjee, Prabal; Feuer, Gerold; Izzo, Angelo A

2017-09-01

The humanized mouse model has been developed as a model to identify and characterize human immune responses to human pathogens and has been used to better identify vaccine candidates. In the current studies, the humanized mouse was used to determine the ability of a vaccine to affect the immune response to infection with Mycobacterium tuberculosis. Both human CD4 + and CD8 + T cells responded to infection in humanized mice as a result of infection. In humanized mice vaccinated with either BCG or with CpG-C, a liposome-based formulation containing the M. tuberculosis antigen ESAT-6, both CD4 and CD8 T cells secreted cytokines that are known to be required for induction of protective immunity. In comparison to the C57BL/6 mouse model and Hartley guinea pig model of tuberculosis, data obtained from humanized mice complemented the data observed in the former models and provided further evidence that a vaccine can induce a human T-cell response. Humanized mice provide a crucial pre-clinical platform for evaluating human T-cell immune responses in vaccine development against M. tuberculosis. © 2017 John Wiley & Sons Ltd.

Recent Progresses in Incorporating Human Land-Water Management into Global Land Surface Models Toward Their Integration into Earth System Models

NASA Technical Reports Server (NTRS)

Pokhrel, Yadu N.; Hanasaki, Naota; Wada, Yoshihide; Kim, Hyungjun

2016-01-01

The global water cycle has been profoundly affected by human land-water management. As the changes in the water cycle on land can affect the functioning of a wide range of biophysical and biogeochemical processes of the Earth system, it is essential to represent human land-water management in Earth system models (ESMs). During the recent past, noteworthy progress has been made in large-scale modeling of human impacts on the water cycle but sufficient advancements have not yet been made in integrating the newly developed schemes into ESMs. This study reviews the progresses made in incorporating human factors in large-scale hydrological models and their integration into ESMs. The study focuses primarily on the recent advancements and existing challenges in incorporating human impacts in global land surface models (LSMs) as a way forward to the development of ESMs with humans as integral components, but a brief review of global hydrological models (GHMs) is also provided. The study begins with the general overview of human impacts on the water cycle. Then, the algorithms currently employed to represent irrigation, reservoir operation, and groundwater pumping are discussed. Next, methodological deficiencies in current modeling approaches and existing challenges are identified. Furthermore, light is shed on the sources of uncertainties associated with model parameterizations, grid resolution, and datasets used for forcing and validation. Finally, representing human land-water management in LSMs is highlighted as an important research direction toward developing integrated models using ESM frameworks for the holistic study of human-water interactions within the Earths system.

A survey of Applied Psychological Services' models of the human operator

NASA Technical Reports Server (NTRS)

Siegel, A. I.; Wolf, J. J.

1979-01-01

A historical perspective is presented in terms of the major features and status of two families of computer simulation models in which the human operator plays the primary role. Both task oriented and message oriented models are included. Two other recent efforts are summarized which deal with visual information processing. They involve not whole model development but a family of subroutines customized to add the human aspects to existing models. A global diagram of the generalized model development/validation process is presented and related to 15 criteria for model evaluation.

A model for the control mode man-computer interface dialogue

NASA Technical Reports Server (NTRS)

Chafin, R. L.

1981-01-01

A four stage model is presented for the control mode man-computer interface dialogue. It consists of context development, semantic development syntactic development, and command execution. Each stage is discussed in terms of the operator skill levels (naive, novice, competent, and expert) and pertinent human factors issues. These issues are human problem solving, human memory, and schemata. The execution stage is discussed in terms of the operators typing skills. This model provides an understanding of the human process in command mode activity for computer systems and a foundation for relating system characteristics to operator characteristics.

Vaccines against viral hemorrhagic fevers: non-human primate models.

PubMed

Carrion, Ricardo; Patterson, Jean L

2011-06-01

Viral hemorrhagic fevers are a group of disease syndromes caused by infection with certain RNA viruses. The disease is marked by a febrile response, malaise, coagulopathy and vascular permeability culminating in death. Case fatality rates can reach 90% depending on the etiologic agent. Currently, there is no approved antiviral treatment. Because of the high case fatality, risk of importation and the potential to use these agents as biological weapons, development of countermeasures to these agents is a high priority. The sporadic nature of disease outbreaks and the ethical issues associated with conducting a human trial for such diseases make human studies impractical; therefore, development of countermeasures must occur in relevant animal models. Non-human primates are superior models to study infectious disease because their immune system is similar to humans and they are good predictors of efficacy in vaccine development and other intervention strategies. This review article summarizes viral hemorrhagic fever non-human primate models.

[Human resources for health in Ecuador's new model of care].

PubMed

Espinosa, Verónica; de la Torre, Daniel; Acuña, Cecilia; Cadena, Cristina

2017-06-08

Describe strategies implemented by Ecuador's Ministry of Public Health (MPH) to strengthen human resources for health leadership and respond to the new model of care, as a part of the reform process in the period 2012-2015. A documentary review was carried out of primary and secondary sources on development of human resources for health before and after the reform. In the study period, Ecuador developed a new institutional and regulatory framework for developing human resources for health to respond to the requirements of a model of care based on primary health care. The MPH consolidated its steering role by forging strategic partnerships, implementing human resources planning methods, and making an unprecedented investment in health worker training, hiring, and wage increases. These elements constitute the initial core for development of human resources for health policy and a health-services study program consistent with the reform's objectives. Within the framework of the reform carried out from 2012 to 2015, intersectoral work by the MPH has led to considerable achievements in development of human resources for health. Notable achievements include strengthening of the steering role, development and implementation of standards and regulatory instruments, creation of new professional profiles, and hiring of professionals to implement the comprehensive health care model, which helped to solve problems carried over from the years prior to the reform.

A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever

PubMed Central

Marzi, Andrea; Banadyga, Logan; Haddock, Elaine; Thomas, Tina; Shen, Kui; Horne, Eva J.; Scott, Dana P.; Feldmann, Heinz; Ebihara, Hideki

2016-01-01

Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden hamster model of MHF using a hamster-adapted MARV variant Angola. Remarkably, this model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF hamster model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF. PMID:27976688

A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever.

PubMed

Marzi, Andrea; Banadyga, Logan; Haddock, Elaine; Thomas, Tina; Shen, Kui; Horne, Eva J; Scott, Dana P; Feldmann, Heinz; Ebihara, Hideki

2016-12-15

Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden hamster model of MHF using a hamster-adapted MARV variant Angola. Remarkably, this model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF hamster model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF.

hPSC-derived lung and intestinal organoids as models of human fetal tissue

PubMed Central

Aurora, Megan; Spence, Jason R.

2016-01-01

In vitro human pluripotent stem cell (hPSC) derived tissues are excellent models to study certain aspects of normal human development. Current research in the field of hPSC derived tissues reveals these models to be inherently fetal-like on both a morphological and gene expression level. In this review we briefly discuss current methods for differentiating lung and intestinal tissue from hPSCs into individual 3-dimensional units called organoids. We discuss how these methods mirror what is known about in vivo signaling pathways of the developing embryo. Additionally, we will review how the inherent immaturity of these models lends them to be particularly valuable in the study of immature human tissues in the clinical setting of premature birth. Human lung organoids (HLOs) and human intestinal organoids (HIOs) not only model normal development, but can also be utilized to study several important diseases of prematurity such as respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC). PMID:27287882

Model for Predicting the Performance of Planetary Suit Hip Bearing Designs

NASA Technical Reports Server (NTRS)

Cowley, Matthew S.; Margerum, Sarah; Hharvill, Lauren; Rajulu, Sudhakar

2012-01-01

Designing a space suit is very complex and often requires difficult trade-offs between performance, cost, mass, and system complexity. During the development period of the suit numerous design iterations need to occur before the hardware meets human performance requirements. Using computer models early in the design phase of hardware development is advantageous, by allowing virtual prototyping to take place. A virtual design environment allows designers to think creatively, exhaust design possibilities, and study design impacts on suit and human performance. A model of the rigid components of the Mark III Technology Demonstrator Suit (planetary-type space suit) and a human manikin were created and tested in a virtual environment. The performance of the Mark III hip bearing model was first developed and evaluated virtually by comparing the differences in mobility performance between the nominal bearing configurations and modified bearing configurations. Suited human performance was then simulated with the model and compared to actual suited human performance data using the same bearing configurations. The Mark III hip bearing model was able to visually represent complex bearing rotations and the theoretical volumetric ranges of motion in three dimensions. The model was also able to predict suited human hip flexion and abduction maximums to within 10% of the actual suited human subject data, except for one modified bearing condition in hip flexion which was off by 24%. Differences between the model predictions and the human subject performance data were attributed to the lack of joint moment limits in the model, human subject fitting issues, and the limited suit experience of some of the subjects. The results demonstrate that modeling space suit rigid segments is a feasible design tool for evaluating and optimizing suited human performance. Keywords: space suit, design, modeling, performance

A three-dimensional model of human lung development and disease from pluripotent stem cells.

PubMed

Chen, Ya-Wen; Huang, Sarah Xuelian; de Carvalho, Ana Luisa Rodrigues Toste; Ho, Siu-Hong; Islam, Mohammad Naimul; Volpi, Stefano; Notarangelo, Luigi D; Ciancanelli, Michael; Casanova, Jean-Laurent; Bhattacharya, Jahar; Liang, Alice F; Palermo, Laura M; Porotto, Matteo; Moscona, Anne; Snoeck, Hans-Willem

2017-05-01

Recapitulation of lung development from human pluripotent stem cells (hPSCs) in three dimensions (3D) would allow deeper insight into human development, as well as the development of innovative strategies for disease modelling, drug discovery and regenerative medicine. We report here the generation from hPSCs of lung bud organoids (LBOs) that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel 3D culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation. Infection in vitro with respiratory syncytial virus, which causes small airway obstruction and bronchiolitis in infants, led to swelling, detachment and shedding of infected cells into the organoid lumens, similar to what has been observed in human lungs. Introduction of mutation in HPS1, which causes an early-onset form of intractable pulmonary fibrosis, led to accumulation of extracellular matrix and mesenchymal cells, suggesting the potential use of this model to recapitulate fibrotic lung disease in vitro. LBOs therefore recapitulate lung development and may provide a useful tool to model lung disease.

Simulating human behavior for national security human interactions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernard, Michael Lewis; Hart, Dereck H.; Verzi, Stephen J.

2007-01-01

This 3-year research and development effort focused on what we believe is a significant technical gap in existing modeling and simulation capabilities: the representation of plausible human cognition and behaviors within a dynamic, simulated environment. Specifically, the intent of the ''Simulating Human Behavior for National Security Human Interactions'' project was to demonstrate initial simulated human modeling capability that realistically represents intra- and inter-group interaction behaviors between simulated humans and human-controlled avatars as they respond to their environment. Significant process was made towards simulating human behaviors through the development of a framework that produces realistic characteristics and movement. The simulated humansmore » were created from models designed to be psychologically plausible by being based on robust psychological research and theory. Progress was also made towards enhancing Sandia National Laboratories existing cognitive models to support culturally plausible behaviors that are important in representing group interactions. These models were implemented in the modular, interoperable, and commercially supported Umbra{reg_sign} simulation framework.« less

REAL-TIME MODELING OF MOTOR VEHICLE EMISSIONS FOR ESTIMATING HUMAN EXPOSURES NEAR ROADWAYS

EPA Science Inventory

The United States Environmental Protection Agency's (EPA) National Exposure Research Laboratory is developing a real-time model of motor vehicle emissions to improve the methodology for modeling human exposure to motor vehicle emissions. The overall project goal is to develop ...

Numerical human models for accident research and safety - potentials and limitations.

PubMed

Praxl, Norbert; Adamec, Jiri; Muggenthaler, Holger; von Merten, Katja

2008-01-01

The method of numerical simulation is frequently used in the area of automotive safety. Recently, numerical models of the human body have been developed for the numerical simulation of occupants. Different approaches in modelling the human body have been used: the finite-element and the multibody technique. Numerical human models representing the two modelling approaches are introduced and the potentials and limitations of these models are discussed.

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...

Microphysiological modeling of the reproductive tract: a fertile endeavor.

PubMed

Eddie, Sharon L; Kim, J Julie; Woodruff, Teresa K; Burdette, Joanna E

2014-09-01

Preclinical toxicity testing in animal models is a cornerstone of the drug development process, yet it is often unable to predict adverse effects and tolerability issues in human subjects. Species-specific responses to investigational drugs have led researchers to utilize human tissues and cells to better estimate human toxicity. Unfortunately, human cell-derived models are imperfect because toxicity is assessed in isolation, removed from the normal physiologic microenvironment. Microphysiological modeling often referred to as 'organ-on-a-chip' or 'human-on-a-chip' places human tissue into a microfluidic system that mimics the complexity of human in vivo physiology, thereby allowing for toxicity testing on several cell types, tissues, and organs within a more biologically relevant environment. Here we describe important concepts when developing a repro-on-a-chip model. The development of female and male reproductive microfluidic systems is critical to sex-based in vitro toxicity and drug testing. This review addresses the biological and physiological aspects of the male and female reproductive systems in vivo and what should be considered when designing a microphysiological human-on-a-chip model. Additionally, interactions between the reproductive tract and other systems are explored, focusing on the impact of factors and hormones produced by the reproductive tract and disease pathophysiology. © 2014 by the Society for Experimental Biology and Medicine.

A Community Framework for Integrative, Coupled Modeling of Human-Earth Systems

NASA Astrophysics Data System (ADS)

Barton, C. M.; Nelson, G. C.; Tucker, G. E.; Lee, A.; Porter, C.; Ullah, I.; Hutton, E.; Hoogenboom, G.; Rogers, K. G.; Pritchard, C.

2017-12-01

We live today in a humanized world, where critical zone dynamics are driven by coupled human and biophysical processes. First generation modeling platforms have been invaluable in providing insight into dynamics of biophysical systems and social systems. But to understand today's humanized planet scientifically and to manage it sustainably, we need integrative modeling of this coupled human-Earth system. To address both scientific and policy questions, we also need modeling that can represent variable combinations of human-Earth system processes at multiple scales. Simply adding more code needed to do this to large, legacy first generation models is impractical, expensive, and will make them even more difficult to evaluate or understand. We need an approach to modeling that mirrors and benefits from the architecture of the complexly coupled systems we hope to model. Building on a series of international workshops over the past two years, we present a community framework to enable and support an ecosystem of diverse models as components that can be interconnected as needed to facilitate understanding of a range of complex human-earth systems interactions. Models are containerized in Docker to make them platform independent. A Basic Modeling Interface and Standard Names ontology (developed by the Community Surface Dynamics Modeling System) is applied to make them interoperable. They are then transformed into RESTful micro-services to allow them to be connected and run in a browser environment. This enables a flexible, multi-scale modeling environment to help address diverse issues with combinations of smaller, focused, component models that are easier to understand and evaluate. We plan to develop, deploy, and maintain this framework for integrated, coupled modeling in an open-source collaborative development environment that can democratize access to advanced technology and benefit from diverse global participation in model development. We also present an initial proof-of-concept of this framework, coupling a widely used agricultural crop model (DSSAT) with a widely used hydrology model (TopoFlow).

Using GOMS and Bayesian plan recognition to develop recognition models of operator behavior

NASA Astrophysics Data System (ADS)

Zaientz, Jack D.; DeKoven, Elyon; Piegdon, Nicholas; Wood, Scott D.; Huber, Marcus J.

2006-05-01

Trends in combat technology research point to an increasing role for uninhabited vehicles in modern warfare tactics. To support increased span of control over these vehicles human responsibilities need to be transformed from tedious, error-prone and cognition intensive operations into tasks that are more supervisory and manageable, even under intensely stressful conditions. The goal is to move away from only supporting human command of low-level system functions to intention-level human-system dialogue about the operator's tasks and situation. A critical element of this process is developing the means to identify when human operators need automated assistance and to identify what assistance they need. Toward this goal, we are developing an unmanned vehicle operator task recognition system that combines work in human behavior modeling and Bayesian plan recognition. Traditionally, human behavior models have been considered generative, meaning they describe all possible valid behaviors. Basing behavior recognition on models designed for behavior generation can offers advantages in improved model fidelity and reuse. It is not clear, however, how to reconcile the structural differences between behavior recognition and behavior modeling approaches. Our current work demonstrates that by pairing a cognitive psychology derived human behavior modeling approach, GOMS, with a Bayesian plan recognition engine, ASPRN, we can translate a behavior generation model into a recognition model. We will discuss the implications for using human performance models in this manner as well as suggest how this kind of modeling may be used to support the real-time control of multiple, uninhabited battlefield vehicles and other semi-autonomous systems.

Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever

DTIC Science & Technology

2009-07-01

Microbiology. All Rights Reserved. Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever Kelly L. Warfield,* Steven B...mouse model has hampered an understanding of the pathogenesis and immunity of Marburg hemorrhagic fever (MHF), the disease caused by marburgvirus (MARV...cause severe hemorrhagic fevers in humans and non- human primates (27). The incubation time is estimated to be 3 to 21 days, with human case fatality

Functional structure and dynamics of the human nervous system

NASA Technical Reports Server (NTRS)

Lawrence, J. A.

1981-01-01

The status of an effort to define the directions needed to take in extending pilot models is reported. These models are needed to perform closed-loop (man-in-the-loop) feedback flight control system designs and to develop cockpit display requirements. The approach taken is to develop a hypothetical working model of the human nervous system by reviewing the current literature in neurology and psychology and to develop a computer model of this hypothetical working model.

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…

Development and Application of a Human PBPK Model for Bromodichloromethane (BDCM) to Investigate Impacts of Multi-Route Exposure

EPA Science Inventory

Due to its presence in water as a volatile disinfection byproduct, BDCM, which is mutagenic and a rodent carcinogen, poses a risk for exposure via multiple routes. We developed a refined human PBPK model for BDCM (including new chemical-specific human parameters) to evaluate the...

An anisotropic, hyperelastic model for skin: experimental measurements, finite element modelling and identification of parameters for human and murine skin.

PubMed

Groves, Rachel B; Coulman, Sion A; Birchall, James C; Evans, Sam L

2013-02-01

The mechanical characteristics of skin are extremely complex and have not been satisfactorily simulated by conventional engineering models. The ability to predict human skin behaviour and to evaluate changes in the mechanical properties of the tissue would inform engineering design and would prove valuable in a diversity of disciplines, for example the pharmaceutical and cosmetic industries, which currently rely upon experiments performed in animal models. The aim of this study was to develop a predictive anisotropic, hyperelastic constitutive model of human skin and to validate this model using laboratory data. As a corollary, the mechanical characteristics of human and murine skin have been compared. A novel experimental design, using tensile tests on circular skin specimens, and an optimisation procedure were adopted for laboratory experiments to identify the material parameters of the tissue. Uniaxial tensile tests were performed along three load axes on excised murine and human skin samples, using a single set of material parameters for each skin sample. A finite element model was developed using the transversely isotropic, hyperelastic constitutive model of Weiss et al. (1996) and was embedded within a Veronda-Westmann isotropic material matrix, using three fibre families to create anisotropic behaviour. The model was able to represent the nonlinear, anisotropic behaviour of the skin well. Additionally, examination of the optimal material coefficients and the experimental data permitted quantification of the mechanical differences between human and murine skin. Differences between the skin types, most notably the extension of the skin at low load, have highlighted some of the limitations of murine skin as a biomechanical model of the human tissue. The development of accurate, predictive computational models of human tissue, such as skin, to reduce, refine or replace animal models and to inform developments in the medical, engineering and cosmetic fields, is a significant challenge but is highly desirable. Concurrent advances in computer technology and our understanding of human physiology must be utilised to produce more accurate and accessible predictive models, such as the finite element model described in this study. Copyright © 2012 Elsevier Ltd. All rights reserved.

Meganucleases Revolutionize the Production of Genetically Engineered Pigs for the Study of Human Diseases.

PubMed

Redel, Bethany K; Prather, Randall S

2016-04-01

Animal models of human diseases are critically necessary for developing an in-depth knowledge of disease development and progression. In addition, animal models are vital to the development of potential treatments or even cures for human diseases. Pigs are exceptional models as their size, physiology, and genetics are closer to that of humans than rodents. In this review, we discuss the use of pigs in human translational research and the evolving technology that has increased the efficiency of genetically engineering pigs. With the emergence of the clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated (Cas) protein 9 system technology, the cost and time it takes to genetically engineer pigs has markedly decreased. We will also discuss the use of another meganuclease, the transcription activator-like effector nucleases , to produce pigs with severe combined immunodeficiency by developing targeted modifications of the recombination activating gene 2 (RAG2).RAG2mutant pigs may become excellent animals to facilitate the development of xenotransplantation, regenerative medicine, and tumor biology. The use of pig biomedical models is vital for furthering the knowledge of, and for treating human, diseases. © The Author(s) 2015.

Stochastic Human Exposure and Dose Simulation Model for Pesticides

EPA Science Inventory

SHEDS-Pesticides (Stochastic Human Exposure and Dose Simulation Model for Pesticides) is a physically-based stochastic model developed to quantify exposure and dose of humans to multimedia, multipathway pollutants. Probabilistic inputs are combined in physical/mechanistic algorit...

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

Learning as a Generative Process

ERIC Educational Resources Information Center

Wittrock, M. C.

2010-01-01

A cognitive model of human learning with understanding is introduced. Empirical research supporting the model, which is called the generative model, is summarized. The model is used to suggest a way to integrate some of the research in cognitive development, human learning, human abilities, information processing, and aptitude-treatment…

A Bayesian network approach to predicting nest presence of thefederally-threatened piping plover (Charadrius melodus) using barrier island features

USGS Publications Warehouse

Gieder, Katherina D.; Karpanty, Sarah M.; Fraser, James D.; Catlin, Daniel H.; Gutierrez, Benjamin T.; Plant, Nathaniel G.; Turecek, Aaron M.; Thieler, E. Robert

2014-01-01

Sea-level rise and human development pose significant threats to shorebirds, particularly for species that utilize barrier island habitat. The piping plover (Charadrius melodus) is a federally-listed shorebird that nests on barrier islands and rapidly responds to changes in its physical environment, making it an excellent species with which to model how shorebird species may respond to habitat change related to sea-level rise and human development. The uncertainty and complexity in predicting sea-level rise, the responses of barrier island habitats to sea-level rise, and the responses of species to sea-level rise and human development necessitate a modelling approach that can link species to the physical habitat features that will be altered by changes in sea level and human development. We used a Bayesian network framework to develop a model that links piping plover nest presence to the physical features of their nesting habitat on a barrier island that is impacted by sea-level rise and human development, using three years of data (1999, 2002, and 2008) from Assateague Island National Seashore in Maryland. Our model performance results showed that we were able to successfully predict nest presence given a wide range of physical conditions within the model’s dataset. We found that model predictions were more successful when the range of physical conditions included in model development was varied rather than when those physical conditions were narrow. We also found that all model predictions had fewer false negatives (nests predicted to be absent when they were actually present in the dataset) than false positives (nests predicted to be present when they were actually absent in the dataset), indicating that our model correctly predicted nest presence better than nest absence. These results indicated that our approach of using a Bayesian network to link specific physical features to nest presence will be useful for modelling impacts of sea-level rise- or human-related habitat change on barrier islands. We recommend that potential users of this method utilize multiple years of data that represent a wide range of physical conditions in model development, because the model performed less well when constructed using a narrow range of physical conditions. Further, given that there will always be some uncertainty in predictions of future physical habitat conditions related to sea-level rise and/or human development, predictive models will perform best when developed using multiple, varied years of data input.

Developing an OD-Intervention Metric System with the Use of Applied Theory-Building Methodology: A Work/Life-Intervention Example

ERIC Educational Resources Information Center

Morris, Michael Lane; Storberg-Walker, Julia; McMillan, Heather S.

2009-01-01

This article presents a new model, generated through applied theory-building research methods, that helps human resource development (HRD) practitioners evaluate the return on investment (ROI) of organization development (OD) interventions. This model, called organization development human-capital accounting system (ODHCAS), identifies…

The Development of Web-Based Collaborative Training Model for Enhancing Human Performances on ICT for Students in Banditpattanasilpa Institute

ERIC Educational Resources Information Center

Pumipuntu, Natawut; Kidrakarn, Pachoen; Chetakarn, Somchock

2015-01-01

This research aimed to develop the model of Web-based Collaborative (WBC) Training model for enhancing human performances on ICT for students in Banditpattanasilpa Institute. The research is divided into three phases: 1) investigating students and teachers' training needs on ICT web-based contents and performance, 2) developing a web-based…

Scoring of Decomposition: A Proposed Amendment to the Method When Using a Pig Model for Human Studies.

PubMed

Keough, Natalie; Myburgh, Jolandie; Steyn, Maryna

2017-07-01

Decomposition studies often use pigs as proxies for human cadavers. However, differences in decomposition sequences/rates relative to humans have not been scientifically examined. Descriptions of five main decomposition stages (humans) were developed and refined by Galloway and later by Megyesi. However, whether these changes/processes are alike in pigs is unclear. Any differences can have significant effects when pig models are used for human PMI estimation. This study compared human decomposition models to the changes observed in pigs. Twenty pigs (50-90 kg) were decomposed over five months and decompositional features recorded. Total body scores (TBS) were calculated. Significant differences were observed during early decomposition between pigs and humans. An amended scoring system to be used in future studies was developed. Standards for PMI estimation derived from porcine models may not directly apply to humans and may need adjustment. Porcine models, however, remain valuable to study variables influencing decomposition. © 2016 American Academy of Forensic Sciences.

Generation of the Human Biped Stance by a Neural Controller Able to Compensate Neurological Time Delay

PubMed Central

Jiang, Ping; Chiba, Ryosuke; Takakusaki, Kaoru; Ota, Jun

2016-01-01

The development of a physiologically plausible computational model of a neural controller that can realize a human-like biped stance is important for a large number of potential applications, such as assisting device development and designing robotic control systems. In this paper, we develop a computational model of a neural controller that can maintain a musculoskeletal model in a standing position, while incorporating a 120-ms neurological time delay. Unlike previous studies that have used an inverted pendulum model, a musculoskeletal model with seven joints and 70 muscular-tendon actuators is adopted to represent the human anatomy. Our proposed neural controller is composed of both feed-forward and feedback controls. The feed-forward control corresponds to the constant activation input necessary for the musculoskeletal model to maintain a standing posture. This compensates for gravity and regulates stiffness. The developed neural controller model can replicate two salient features of the human biped stance: (1) physiologically plausible muscle activations for quiet standing; and (2) selection of a low active stiffness for low energy consumption. PMID:27655271

Skin models for the testing of transdermal drugs

PubMed Central

Abd, Eman; Yousef, Shereen A; Pastore, Michael N; Telaprolu, Krishna; Mohammed, Yousuf H; Namjoshi, Sarika; Grice, Jeffrey E; Roberts, Michael S

2016-01-01

The assessment of percutaneous permeation of molecules is a key step in the evaluation of dermal or transdermal delivery systems. If the drugs are intended for delivery to humans, the most appropriate setting in which to do the assessment is the in vivo human. However, this may not be possible for ethical, practical, or economic reasons, particularly in the early phases of development. It is thus necessary to find alternative methods using accessible and reproducible surrogates for in vivo human skin. A range of models has been developed, including ex vivo human skin, usually obtained from cadavers or plastic surgery patients, ex vivo animal skin, and artificial or reconstructed skin models. Increasingly, largely driven by regulatory authorities and industry, there is a focus on developing standardized techniques and protocols. With this comes the need to demonstrate that the surrogate models produce results that correlate with those from in vivo human studies and that they can be used to show bioequivalence of different topical products. This review discusses the alternative skin models that have been developed as surrogates for normal and diseased skin and examines the concepts of using model systems for in vitro–in vivo correlation and the demonstration of bioequivalence. PMID:27799831

Challenges facing developers of CAD/CAM models that seek to predict human working postures

NASA Astrophysics Data System (ADS)

Wiker, Steven F.

2005-11-01

This paper outlines the need for development of human posture prediction models for Computer Aided Design (CAD) and Computer Aided Manufacturing (CAM) design applications in product, facility and work design. Challenges facing developers of posture prediction algorithms are presented and discussed.

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…

Product Use Scheduler: A Scheduling Module used in EPA’s Human Exposure Model

EPA Science Inventory

The scheduling model (SM) was developed for scheduling the use of consumer products in the U.S. EPA’s Human Exposure Model (HEM), an integrated modeling system to estimate human exposure to chemicals in household consumer products. The SM begins with year-long daily activit...

Modeling human-environmental systems

Treesearch

Morgan Grove; Charlie Schweik; Tom Evans; Glen Green

2002-01-01

This chapter focuses on the integration and development of environmental models that include human decision making. While many methodological and technical issues are common to all types of environmental models, our goal is to highlight the unique characteristics that need to be considered when modeling human-environmental dynamics and to identify future directions for...

Visualization and Rule Validation in Human-Behavior Representation

ERIC Educational Resources Information Center

Moya, Lisa Jean; McKenzie, Frederic D.; Nguyen, Quynh-Anh H.

2008-01-01

Human behavior representation (HBR) models simulate human behaviors and responses. The Joint Crowd Federate [TM] cognitive model developed by the Virginia Modeling, Analysis, and Simulation Center (VMASC) and licensed by WernerAnderson, Inc., models the cognitive behavior of crowds to provide credible crowd behavior in support of military…

Semantic Likelihood Models for Bayesian Inference in Human-Robot Interaction

NASA Astrophysics Data System (ADS)

Sweet, Nicholas

Autonomous systems, particularly unmanned aerial systems (UAS), remain limited in au- tonomous capabilities largely due to a poor understanding of their environment. Current sensors simply do not match human perceptive capabilities, impeding progress towards full autonomy. Recent work has shown the value of humans as sources of information within a human-robot team; in target applications, communicating human-generated 'soft data' to autonomous systems enables higher levels of autonomy through large, efficient information gains. This requires development of a 'human sensor model' that allows soft data fusion through Bayesian inference to update the probabilistic belief representations maintained by autonomous systems. Current human sensor models that capture linguistic inputs as semantic information are limited in their ability to generalize likelihood functions for semantic statements: they may be learned from dense data; they do not exploit the contextual information embedded within groundings; and they often limit human input to restrictive and simplistic interfaces. This work provides mechanisms to synthesize human sensor models from constraints based on easily attainable a priori knowledge, develops compression techniques to capture information-dense semantics, and investigates the problem of capturing and fusing semantic information contained within unstructured natural language. A robotic experimental testbed is also developed to validate the above contributions.

Human Granuloma In Vitro Model, for TB Dormancy and Resuscitation

PubMed Central

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. PMID:23308269

A three-dimensional model of human lung development and disease from pluripotent stem cells

PubMed Central

Chen, Ya-Wen; Huang, Sarah Xuelian; de Carvalho, Ana Luisa Rodrigues Toste; Ho, Siu-Hong; Islam, Mohammad Naimul; Volpi, Stefano; Notarangelo, Luigi D; Ciancanelli, Michael; Casanova, Jean-Laurent; Bhattacharya, Jahar; Liang, Alice F.; Palermo, Laura M; Porotto, Matteo; Moscona, Anne; Snoeck, Hans-Willem

2017-01-01

Recapitulation of lung development from human pluripotent stem cells (hPSCs) in three dimensions (3D) would allow deeper insight into human development, as well as the development of innovative strategies for disease modeling, drug discovery and regenerative medicine1. We report here the generation from hPSCs of lung bud organoids (LBOs) that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel 3D culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation. Infection in vitro with respiratory syncytial virus, which causes small airway obstruction and bronchiolitis in infants2, led to swelling, detachment and shedding of infected cells into the organoid lumens, similar to what has been observed in human lungs3. Introduction of mutation in HPS1, which causes an early-onset form of intractable pulmonary fibrosis4,5, led to accumulation of extracellular matrix and mesenchymal cells, suggesting the potential use of this model to recapitulate fibrotic lung disease in vitro. LBOs therefore recapitulate lung development and may provide a useful tool to model lung disease. PMID:28436965

Development of mathematical models of environmental physiology

NASA Technical Reports Server (NTRS)

Stolwijk, J. A. J.; Mitchell, J. W.; Nadel, E. R.

1971-01-01

Selected articles concerned with mathematical or simulation models of human thermoregulation are presented. The articles presented include: (1) development and use of simulation models in medicine, (2) model of cardio-vascular adjustments during exercise, (3) effective temperature scale based on simple model of human physiological regulatory response, (4) behavioral approach to thermoregulatory set point during exercise, and (5) importance of skin temperature in sweat regulation.

Local spatio-temporal analysis in vision systems

NASA Astrophysics Data System (ADS)

Geisler, Wilson S.; Bovik, Alan; Cormack, Lawrence; Ghosh, Joydeep; Gildeen, David

1994-07-01

The aims of this project are the following: (1) develop a physiologically and psychophysically based model of low-level human visual processing (a key component of which are local frequency coding mechanisms); (2) develop image models and image-processing methods based upon local frequency coding; (3) develop algorithms for performing certain complex visual tasks based upon local frequency representations, (4) develop models of human performance in certain complex tasks based upon our understanding of low-level processing; and (5) develop a computational testbed for implementing, evaluating and visualizing the proposed models and algorithms, using a massively parallel computer. Progress has been substantial on all aims. The highlights include the following: (1) completion of a number of psychophysical and physiological experiments revealing new, systematic and exciting properties of the primate (human and monkey) visual system; (2) further development of image models that can accurately represent the local frequency structure in complex images; (3) near completion in the construction of the Texas Active Vision Testbed; (4) development and testing of several new computer vision algorithms dealing with shape-from-texture, shape-from-stereo, and depth-from-focus; (5) implementation and evaluation of several new models of human visual performance; and (6) evaluation, purchase and installation of a MasPar parallel computer.

Competency-Based Human Resource Development Strategy

ERIC Educational Resources Information Center

Gangani, Noordeen T.; McLean, Gary N.; Braden, Richard A.

2004-01-01

This paper explores issues in developing and implementing a competency-based human resource development strategy. The paper summarizes a literature review on how competency models can improve HR performance. A case study is presented of American Medical Systems (AMS), a mid-sized health-care and medical device company, where the model is being…

The big challenges in modeling human and environmental well-being.

PubMed

Tuljapurkar, Shripad

2016-01-01

This article is a selective review of quantitative research, historical and prospective, that is needed to inform sustainable development policy. I start with a simple framework to highlight how demography and productivity shape human well-being. I use that to discuss three sets of issues and corresponding challenges to modeling: first, population prehistory and early human development and their implications for the future; second, the multiple distinct dimensions of human and environmental well-being and the meaning of sustainability; and, third, inequality as a phenomenon triggered by development and models to examine changing inequality and its consequences. I conclude with a few words about other important factors: political, institutional, and cultural.

The latest animal models of ovarian cancer for novel drug discovery.

PubMed

Magnotti, Elizabeth; Marasco, Wayne A

2018-03-01

Epithelial ovarian cancer is a heterogeneous disease classified into five subtypes, each with a different molecular profile. Most cases of ovarian cancer are diagnosed after metastasis of the primary tumor and are resistant to traditional platinum-based chemotherapeutics. Mouse models of ovarian cancer have been utilized to discern ovarian cancer tumorigenesis and the tumor's response to therapeutics. Areas covered: The authors provide a review of mouse models currently employed to understand ovarian cancer. This article focuses on advances in the development of orthotopic and patient-derived tumor xenograft (PDX) mouse models of ovarian cancer and discusses current humanized mouse models of ovarian cancer. Expert opinion: The authors suggest that humanized mouse models of ovarian cancer will provide new insight into the role of the human immune system in combating and augmenting ovarian cancer and aid in the development of novel therapeutics. Development of humanized mouse models will take advantage of the NSG and NSG-SGM3 strains of mice as well as new strains that are actively being derived.

An integrated land change model for projecting future climate and land change scenarios

USGS Publications Warehouse

Wimberly, Michael; Sohl, Terry L.; Lamsal, Aashis; Liu, Zhihua; Hawbaker, Todd J.

2013-01-01

Climate change will have myriad effects on ecosystems worldwide, and natural and anthropogenic disturbances will be key drivers of these dynamics. In addition to climatic effects, continual expansion of human settlement into fire-prone forests will alter fire regimes, increase human vulnerability, and constrain future forest management options. There is a need for modeling tools to support the simulation and assessment of new management strategies over large regions in the context of changing climate, shifting development patterns, and an expanding wildland-urban interface. To address this need, we developed a prototype land change simulator that combines human-driven land use change (derived from the FORE-SCE model) with natural disturbances and vegetation dynamics (derived from the LADS model) and incorporates novel feedbacks between human land use and disturbance regimes. The prototype model was implemented in a test region encompassing the Denver metropolitan area along with its surrounding forested and agricultural landscapes. Initial results document the feasibility of integrated land change modeling at a regional scale but also highlighted conceptual and technical challenges for this type of model integration. Ongoing development will focus on improving climate sensitivities and modeling constraints imposed by climate change and human population growth on forest management activities.

Evaluation of Human and Anthropomorphic Test Device Finite Element Models under Spaceflight Loading Conditions

NASA Technical Reports Server (NTRS)

Putnam, Jacob P.; Untaroiu, Costin; Somers. Jeffrey

2014-01-01

In an effort to develop occupant protection standards for future multipurpose crew vehicles, the National Aeronautics and Space Administration (NASA) has looked to evaluate the test device for human occupant restraint with the modification kit (THOR-K) anthropomorphic test device (ATD) in relevant impact test scenarios. With the allowance and support of the National Highway Traffic Safety Administration, NASA has performed a series of sled impact tests on the latest developed THOR-K ATD. These tests were performed to match test conditions from human volunteer data previously collected by the U.S. Air Force. The objective of this study was to evaluate the THOR-K finite element (FE) model and the Total HUman Model for Safety (THUMS) FE model with respect to the tests performed. These models were evaluated in spinal and frontal impacts against kinematic and kinetic data recorded in ATD and human testing. Methods: The FE simulations were developed based on recorded pretest ATD/human position and sled acceleration pulses measured during testing. Predicted responses by both human and ATD models were compared to test data recorded under the same impact conditions. The kinematic responses of the models were quantitatively evaluated using the ISO-metric curve rating system. In addition, ATD injury criteria and human stress/strain data were calculated to evaluate the risk of injury predicted by the ATD and human model, respectively. Results: Preliminary results show well-correlated response between both FE models and their physical counterparts. In addition, predicted ATD injury criteria and human model stress/strain values are shown to positively relate. Kinematic comparison between human and ATD models indicates promising biofidelic response, although a slightly stiffer response is observed within the ATD. Conclusion: As a compliment to ATD testing, numerical simulation provides efficient means to assess vehicle safety throughout the design process and further improve the design of physical ATDs. The assessment of the THOR-K and THUMS FE models in a spaceflight testing condition is an essential first step to implementing these models in the computational evaluation of spacecraft occupant safety. Promising results suggest future use of these models in the aerospace field.

Intergenerational transmission of adaptive functioning: a test of the interactionist model of SES and human development.

PubMed

Schofield, Thomas J; Martin, Monica J; Conger, Katherine J; Neppl, Tricia M; Donnellan, M Brent; Conger, Rand D

2011-01-01

The interactionist model (IM) of human development (R. D. Conger & M. B. Donellan, 2007) proposes that the association between socioeconomic status (SES) and human development involves a dynamic interplay that includes both social causation (SES influences human development) and social selection (individual characteristics affect SES). Using a multigenerational data set involving 271 families, the current study finds empirical support for the IM. Adolescent personality characteristics indicative of social competence, goal-setting, hard work, and emotional stability predicted later SES, parenting, and family characteristics that were related to the positive development of a third-generation child. Processes of both social selection and social causation appear to account for the association between SES and dimensions of human development indicative of healthy functioning across multiple generations. © 2011 The Authors. Child Development © 2011 Society for Research in Child Development, Inc.

Modeling human craniofacial disorders in Xenopus

PubMed Central

Dubey, Aditi; Saint-Jeannet, Jean-Pierre

2017-01-01

Purpose of Review Craniofacial disorders are among the most common human birth defects and present an enormous health care and social burden. The development of animal models has been instrumental to investigate fundamental questions in craniofacial biology and this knowledge is critical to understand the etiology and pathogenesis of these disorders. Recent findings The vast majority of craniofacial disorders arise from abnormal development of the neural crest, a multipotent and migratory cell population. Therefore, defining the pathogenesis of these conditions starts with a deep understanding of the mechanisms that preside over neural crest formation and its role in craniofacial development. Summary This review discusses several studies using Xenopus embryos to model human craniofacial conditions, and emphasizes the strength of this system to inform important biological processes as they relate to human craniofacial development and disease. PMID:28255527

The zebrafish eye—a paradigm for investigating human ocular genetics

PubMed Central

Richardson, R; Tracey-White, D; Webster, A; Moosajee, M

2017-01-01

Although human epidemiological and genetic studies are essential to elucidate the aetiology of normal and aberrant ocular development, animal models have provided us with an understanding of the pathogenesis of multiple developmental ocular malformations. Zebrafish eye development displays in depth molecular complexity and stringent spatiotemporal regulation that incorporates developmental contributions of the surface ectoderm, neuroectoderm and head mesenchyme, similar to that seen in humans. For this reason, and due to its genetic tractability, external fertilisation, and early optical clarity, the zebrafish has become an invaluable vertebrate system to investigate human ocular development and disease. Recently, zebrafish have been at the leading edge of preclinical therapy development, with their amenability to genetic manipulation facilitating the generation of robust ocular disease models required for large-scale genetic and drug screening programmes. This review presents an overview of human and zebrafish ocular development, genetic methodologies employed for zebrafish mutagenesis, relevant models of ocular disease, and finally therapeutic approaches, which may have translational leads in the future. PMID:27612182

QSAR models of human data can enrich or replace LLNA testing for human skin sensitization

PubMed Central

Alves, Vinicius M.; Capuzzi, Stephen J.; Muratov, Eugene; Braga, Rodolpho C.; Thornton, Thomas; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2016-01-01

Skin sensitization is a major environmental and occupational health hazard. Although many chemicals have been evaluated in humans, there have been no efforts to model these data to date. We have compiled, curated, analyzed, and compared the available human and LLNA data. Using these data, we have developed reliable computational models and applied them for virtual screening of chemical libraries to identify putative skin sensitizers. The overall concordance between murine LLNA and human skin sensitization responses for a set of 135 unique chemicals was low (R = 28-43%), although several chemical classes had high concordance. We have succeeded to develop predictive QSAR models of all available human data with the external correct classification rate of 71%. A consensus model integrating concordant QSAR predictions and LLNA results afforded a higher CCR of 82% but at the expense of the reduced external dataset coverage (52%). We used the developed QSAR models for virtual screening of CosIng database and identified 1061 putative skin sensitizers; for seventeen of these compounds, we found published evidence of their skin sensitization effects. Models reported herein provide more accurate alternative to LLNA testing for human skin sensitization assessment across diverse chemical data. In addition, they can also be used to guide the structural optimization of toxic compounds to reduce their skin sensitization potential. PMID:28630595

Mechanical Impedance Modeling of Human Arm: A survey

NASA Astrophysics Data System (ADS)

Puzi, A. Ahmad; Sidek, S. N.; Sado, F.

2017-03-01

Human arm mechanical impedance plays a vital role in describing motion ability of the upper limb. One of the impedance parameters is stiffness which is defined as the ratio of an applied force to the measured deformation of the muscle. The arm mechanical impedance modeling is useful in order to develop a better controller for system that interacts with human as such an automated robot-assisted platform for automated rehabilitation training. The aim of the survey is to summarize the existing mechanical impedance models of human upper limb so to justify the need to have an improved version of the arm model in order to facilitate the development of better controller of such systems with ever increase in complexity. In particular, the paper will address the following issue: Human motor control and motor learning, constant and variable impedance models, methods for measuring mechanical impedance and mechanical impedance modeling techniques.

Completion of the swine genome will simplify the production of swine as a large animal biomedical model

PubMed Central

2012-01-01

Background Anatomic and physiological similarities to the human make swine an excellent large animal model for human health and disease. Methods Cloning from a modified somatic cell, which can be determined in cells prior to making the animal, is the only method available for the production of targeted modifications in swine. Results Since some strains of swine are similar in size to humans, technologies that have been developed for swine can be readily adapted to humans and vice versa. Here the importance of swine as a biomedical model, current technologies to produce genetically enhanced swine, current biomedical models, and how the completion of the swine genome will promote swine as a biomedical model are discussed. Conclusions The completion of the swine genome will enhance the continued use and development of swine as models of human health, syndromes and conditions. PMID:23151353

Are animal models useful for studying human disc disorders/degeneration?

PubMed Central

Eisenstein, Stephen M.; Ito, Keita; Little, Christopher; Kettler, A. Annette; Masuda, Koichi; Melrose, James; Ralphs, Jim; Stokes, Ian; Wilke, Hans Joachim

2007-01-01

Intervertebral disc (IVD) degeneration is an often investigated pathophysiological condition because of its implication in causing low back pain. As human material for such studies is difficult to obtain because of ethical and government regulatory restriction, animal tissue, organs and in vivo models have often been used for this purpose. However, there are many differences in cell population, tissue composition, disc and spine anatomy, development, physiology and mechanical properties, between animal species and human. Both naturally occurring and induced degenerative changes may differ significantly from those seen in humans. This paper reviews the many animal models developed for the study of IVD degeneration aetiopathogenesis and treatments thereof. In particular, the limitations and relevance of these models to the human condition are examined, and some general consensus guidelines are presented. Although animal models are invaluable to increase our understanding of disc biology, because of the differences between species, care must be taken when used to study human disc degeneration and much more effort is needed to facilitate research on human disc material. PMID:17632738

DEVELOPMENT OF A HUMAN PHYSIOLOGICALLY-BASED PHARMACOKINETIC (PBPK) MODEL FOR INORGANIC ARSENIC AND ITS MONO- AND DI-METHYLATED METABOLITES

EPA Science Inventory

A physiologically-based pharmacokinetic (PBPK) model was developed to estimate levels of arsenic and its metabolites in human tissues and urine after oral exposure to either arsenate (As^V) or arsnite (As^III). The model consists of interconnected individual ...

Crazy like a fox. Validity and ethics of animal models of human psychiatric disease.

PubMed

Rollin, Michael D H; Rollin, Bernard E

2014-04-01

Animal models of human disease play a central role in modern biomedical science. Developing animal models for human mental illness presents unique practical and philosophical challenges. In this article we argue that (1) existing animal models of psychiatric disease are not valid, (2) attempts to model syndromes are undermined by current nosology, (3) models of symptoms are rife with circular logic and anthropomorphism, (4) any model must make unjustified assumptions about subjective experience, and (5) any model deemed valid would be inherently unethical, for if an animal adequately models human subjective experience, then there is no morally relevant difference between that animal and a human.

A Formal Investigation of Human Spatial Control Skills: Mathematical Formalization, Skill Development, and Skill Assessment

NASA Astrophysics Data System (ADS)

Li, Bin

Spatial control behaviors account for a large proportion of human everyday activities from normal daily tasks, such as reaching for objects, to specialized tasks, such as driving, surgery, or operating equipment. These behaviors involve intensive interactions within internal processes (i.e. cognitive, perceptual, and motor control) and with the physical world. This dissertation builds on a concept of interaction pattern and a hierarchical functional model. Interaction pattern represents a type of behavior synergy that humans coordinates cognitive, perceptual, and motor control processes. It contributes to the construction of the hierarchical functional model that delineates humans spatial control behaviors as the coordination of three functional subsystems: planning, guidance, and tracking/pursuit. This dissertation formalizes and validates these two theories and extends them for the investigation of human spatial control skills encompassing development and assessment. Specifically, this dissertation first presents an overview of studies in human spatial control skills encompassing definition, characteristic, development, and assessment, to provide theoretical evidence for the concept of interaction pattern and the hierarchical functional model. The following, the human experiments for collecting motion and gaze data and techniques to register and classify gaze data, are described. This dissertation then elaborates and mathematically formalizes the hierarchical functional model and the concept of interaction pattern. These theories then enables the construction of a succinct simulation model that can reproduce a variety of human performance with a minimal set of hypotheses. This validates the hierarchical functional model as a normative framework for interpreting human spatial control behaviors. The dissertation then investigates human skill development and captures the emergence of interaction pattern. The final part of the dissertation applies the hierarchical functional model for skill assessment and introduces techniques to capture interaction patterns both from the top down using their geometric features and from the bottom up using their dynamical characteristics. The validity and generality of the skill assessment is illustrated using two the remote-control flight and laparoscopic surgical training experiments.

Formation of an internal model of environment dynamics during upper limb reaching movements: a fuzzy approach.

PubMed

MacDonald, Chad; Moussavi, Zahra; Sarkodie-Gyan, Thompson

2007-01-01

This paper presents the development and simulation of a fuzzy logic based learning mechanism to emulate human motor learning. In particular, fuzzy inference was used to develop an internal model of a novel dynamic environment experienced during planar reaching movements with the upper limb. A dynamic model of the human arm was developed and a fuzzy if-then rule base was created to relate trajectory movement and velocity errors to internal model update parameters. An experimental simulation was performed to compare the fuzzy system's performance with that of human subjects. It was found that the dynamic model behaved as expected, and the fuzzy learning mechanism created an internal model that was capable of opposing the environmental force field to regain a trajectory closely resembling the desired ideal.

How Can We Assess and Evaluate the Competitive Advantage of a Country's Human Resource Development System?

ERIC Educational Resources Information Center

Oh, Hunseok; Ryu, Hyue-Hyun; Choi, Myungweon

2013-01-01

The purpose of this study was to develop an index to assess and evaluate the competitive advantage of a country's human resource development system. Based on an extensive literature review, a theoretical model of a human resource development system at the national level (named National Human Resource Development: NHRD) was constructed. The…

Reductions in global biodiversity loss predicted from conservation spending.

PubMed

Waldron, Anthony; Miller, Daniel C; Redding, Dave; Mooers, Arne; Kuhn, Tyler S; Nibbelink, Nate; Roberts, J Timmons; Tobias, Joseph A; Gittleman, John L

2017-11-16

Halting global biodiversity loss is central to the Convention on Biological Diversity and United Nations Sustainable Development Goals, but success to date has been very limited. A critical determinant of success in achieving these goals is the financing that is committed to maintaining biodiversity; however, financing decisions are hindered by considerable uncertainty over the likely impact of any conservation investment. For greater effectiveness, we need an evidence-based model that shows how conservation spending quantitatively reduces the rate of biodiversity loss. Here we demonstrate such a model, and empirically quantify how conservation investment reduced biodiversity loss in 109 countries (signatories to the Convention on Biological Diversity and Sustainable Development Goals), by a median average of 29% per country between 1996 and 2008. We also show that biodiversity changes in signatory countries can be predicted with high accuracy, using a dual model that balances the effects of conservation investment against those of economic, agricultural and population growth (human development pressures). Decision-makers can use this model to forecast the improvement that any proposed biodiversity budget would achieve under various scenarios of human development pressure, and then compare these forecasts to any chosen policy target. We find that the impact of spending decreases as human development pressures grow, which implies that funding may need to increase over time. The model offers a flexible tool for balancing the Sustainable Development Goals of human development and maintaining biodiversity, by predicting the dynamic changes in conservation finance that will be needed as human development proceeds.

Reductions in global biodiversity loss predicted from conservation spending

NASA Astrophysics Data System (ADS)

Waldron, Anthony; Miller, Daniel C.; Redding, Dave; Mooers, Arne; Kuhn, Tyler S.; Nibbelink, Nate; Roberts, J. Timmons; Tobias, Joseph A.; Gittleman, John L.

2017-11-01

Halting global biodiversity loss is central to the Convention on Biological Diversity and United Nations Sustainable Development Goals, but success to date has been very limited. A critical determinant of success in achieving these goals is the financing that is committed to maintaining biodiversity; however, financing decisions are hindered by considerable uncertainty over the likely impact of any conservation investment. For greater effectiveness, we need an evidence-based model that shows how conservation spending quantitatively reduces the rate of biodiversity loss. Here we demonstrate such a model, and empirically quantify how conservation investment between 1996 and 2008 reduced biodiversity loss in 109 countries (signatories to the Convention on Biological Diversity and Sustainable Development Goals), by a median average of 29% per country. We also show that biodiversity changes in signatory countries can be predicted with high accuracy, using a dual model that balances the effects of conservation investment against those of economic, agricultural and population growth (human development pressures). Decision-makers can use this model to forecast the improvement that any proposed biodiversity budget would achieve under various scenarios of human development pressure, and then compare these forecasts to any chosen policy target. We find that the impact of spending decreases as human development pressures grow, which implies that funding may need to increase over time. The model offers a flexible tool for balancing the Sustainable Development Goals of human development and maintaining biodiversity, by predicting the dynamic changes in conservation finance that will be needed as human development proceeds.

[Chest modelling and automotive accidents].

PubMed

Trosseille, Xavier

2011-11-01

Automobile development is increasingly based on mathematical modeling. Accurate models of the human body are now available and serve to develop new means of protection. These models used to consist of rigid, articulated bodies but are now made of several million finite elements. They are now capable of predicting some risks of injury. To develop these models, sophisticated tests were conducted on human cadavers. For example, chest modeling started with material characterization and led to complete validation in the automobile environment. Model personalization, based on medical imaging, will permit studies of the behavior and tolerances of the entire population.

Modelling dimercaptosuccinic acid (DMSA) plasma kinetics in humans.

PubMed

van Eijkeren, Jan C H; Olie, J Daniël N; Bradberry, Sally M; Vale, J Allister; de Vries, Irma; Meulenbelt, Jan; Hunault, Claudine C

2016-11-01

No kinetic models presently exist which simulate the effect of chelation therapy on lead blood concentrations in lead poisoning. Our aim was to develop a kinetic model that describes the kinetics of dimercaptosuccinic acid (DMSA; succimer), a commonly used chelating agent, that could be used in developing a lead chelating model. This was a kinetic modelling study. We used a two-compartment model, with a non-systemic gastrointestinal compartment (gut lumen) and the whole body as one systemic compartment. The only data available from the literature were used to calibrate the unknown model parameters. The calibrated model was then validated by comparing its predictions with measured data from three different experimental human studies. The model predicted total DMSA plasma and urine concentrations measured in three healthy volunteers after ingestion of DMSA 10 mg/kg. The model was then validated by using data from three other published studies; it predicted concentrations within a factor of two, representing inter-human variability. A simple kinetic model simulating the kinetics of DMSA in humans has been developed and validated. The interest of this model lies in the future potential to use it to predict blood lead concentrations in lead-poisoned patients treated with DMSA.

An integrated approach to develop, validate and operate thermo-physiological human simulator for the development of protective clothing.

PubMed

Psikuta, Agnes; Koelblen, Barbara; Mert, Emel; Fontana, Piero; Annaheim, Simon

2017-12-07

Following the growing interest in the further development of manikins to simulate human thermal behaviour more adequately, thermo-physiological human simulators have been developed by coupling a thermal sweating manikin with a thermo-physiology model. Despite their availability and obvious advantages, the number of studies involving these devices is only marginal, which plausibly results from the high complexity of the development and evaluation process and need of multi-disciplinary expertise. The aim of this paper is to present an integrated approach to develop, validate and operate such devices including technical challenges and limitations of thermo-physiological human simulators, their application and measurement protocol, strategy for setting test scenarios, and the comparison to standard methods and human studies including details which have not been published so far. A physical manikin controlled by a human thermoregulation model overcame the limitations of mathematical clothing models and provided a complementary method to investigate thermal interactions between the human body, protective clothing, and its environment. The opportunities of these devices include not only realistic assessment of protective clothing assemblies and equipment but also potential application in many research fields ranging from biometeorology, automotive industry, environmental engineering, and urban climate to clinical and safety applications.

An integrated approach to develop, validate and operate thermo-physiological human simulator for the development of protective clothing

PubMed Central

PSIKUTA, Agnes; KOELBLEN, Barbara; MERT, Emel; FONTANA, Piero; ANNAHEIM, Simon

2017-01-01

Following the growing interest in the further development of manikins to simulate human thermal behaviour more adequately, thermo-physiological human simulators have been developed by coupling a thermal sweating manikin with a thermo-physiology model. Despite their availability and obvious advantages, the number of studies involving these devices is only marginal, which plausibly results from the high complexity of the development and evaluation process and need of multi-disciplinary expertise. The aim of this paper is to present an integrated approach to develop, validate and operate such devices including technical challenges and limitations of thermo-physiological human simulators, their application and measurement protocol, strategy for setting test scenarios, and the comparison to standard methods and human studies including details which have not been published so far. A physical manikin controlled by a human thermoregulation model overcame the limitations of mathematical clothing models and provided a complementary method to investigate thermal interactions between the human body, protective clothing, and its environment. The opportunities of these devices include not only realistic assessment of protective clothing assemblies and equipment but also potential application in many research fields ranging from biometeorology, automotive industry, environmental engineering, and urban climate to clinical and safety applications. PMID:28966294

Models of acute and chronic pancreatitis.

PubMed

Lerch, Markus M; Gorelick, Fred S

2013-06-01

Animal models of acute and chronic pancreatitis have been created to examine mechanisms of pathogenesis, test therapeutic interventions, and study the influence of inflammation on the development of pancreatic cancer. In vitro models can be used to study early stage, short-term processes that involve acinar cell responses. Rodent models reproducibly develop mild or severe disease. One of the most commonly used pancreatitis models is created by administration of supraphysiologic concentrations of caerulein, an ortholog of cholecystokinin. Induction of chronic pancreatitis with factors thought to have a role in human disease, such as combinations of lipopolysaccharide and chronic ethanol feeding, might be relevant to human disease. Models of autoimmune chronic pancreatitis have also been developed. Most models, particularly of chronic pancreatitis, require further characterization to determine which features of human disease they include. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

The Emerging and Employed Worker: Planning for the Strategic Imperative.

ERIC Educational Resources Information Center

Geroy, Gary D.

This paper describes a series of four models around which plans can be developed to determine human development needs. It presents needs assessment models describing the process and participant interaction by which information is gathered to be used in education, training, funding, and/or other human resource development interventions to increase…

Engineering epithelial-stromal interactions in vitro for toxicology assessment.

PubMed

Belair, David G; Abbott, Barbara D

2017-05-01

Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue homeostasis. Epithelial-stromal interactions (ESIs) have historically been examined using mammalian models and ex vivo tissue recombination. Although these approaches have elucidated signaling mechanisms underlying embryonic morphogenesis processes and adult mammalian epithelial tissue function, they are limited by the availability of tissue, low throughput, and human developmental or physiological relevance. In this review, we describe how bioengineered ESIs, using either human stem cells or co-cultures of human primary epithelial and stromal cells, have enabled the development of human in vitro epithelial tissue models that recapitulate the architecture, phenotype, and function of adult human epithelial tissues. We discuss how the strategies used to engineer mature epithelial tissue models in vitro could be extrapolated to instruct the design of organotypic culture models that can recapitulate the structure of embryonic ectodermal tissues and enable the in vitro assessment of events critical to organ/tissue morphogenesis. Given the importance of ESIs towards normal epithelial tissue development and function, such models present a unique opportunity for toxicological screening assays to incorporate ESIs to assess the impact of chemicals on mature and developing epidermal tissues. Published by Elsevier B.V.

Engineering epithelial-stromal interactions in vitro for toxicology assessment

PubMed Central

Belair, David G.; Abbott, Barbara D.

2018-01-01

Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue homeostasis. Epithelial-stromal interactions (ESIs) have historically been examined using mammalian models and ex vivo tissue recombination. Although these approaches have elucidated signaling mechanisms underlying embryonic morphogenesis processes and adult mammalian epithelial tissue function, they are limited by the availability of tissue, low throughput, and human developmental or physiological relevance. In this review, we describe how bioengineered ESIs, using either human stem cells or co-cultures of human primary epithelial and stromal cells, have enabled the development of human in vitro epithelial tissue models that recapitulate the architecture, phenotype, and function of adult human epithelial tissues. We discuss how the strategies used to engineer mature epithelial tissue models in vitro could be extrapolated to instruct the design of organotypic culture models that can recapitulate the structure of embryonic ectodermal tissues and enable the in vitro assessment of events critical to organ/tissue morphogenesis. Given the importance of ESIs towards normal epithelial tissue development and function, such models present a unique opportunity for toxicological screening assays to incorporate ESIs to assess the impact of chemicals on mature and developing epidermal tissues. PMID:28285100

Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress.

PubMed

Zhang, Xiao-Liang; Pang, Wei; Hu, Xin-Tian; Li, Jia-Li; Yao, Yong-Gang; Zheng, Yong-Tang

2014-11-18

Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China's growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China's life sciences and pharmaceutical industry, and enhance China's position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China.

Drosophila Melanogaster as an Emerging Translational Model of Human Nephrolithiasis

PubMed Central

Miller, Joe; Chi, Thomas; Kapahi, Pankaj; Kahn, Arnold J.; Kim, Man Su; Hirata, Taku; Romero, Michael F.; Dow, Julian A.T.; Stoller, Marshall L.

2013-01-01

Purpose The limitations imposed by human clinical studies and mammalian models of nephrolithiasis have hampered the development of effective medical treatments and preventative measures for decades. The simple but elegant Drosophila melanogaster is emerging as a powerful translational model of human disease, including nephrolithiasis and may provide important information essential to our understanding of stone formation. We present the current state of research using D. melanogaster as a model of human nephrolithiasis. Materials and Methods A comprehensive review of the English language literature was performed using PUBMED. When necessary, authoritative texts on relevant subtopics were consulted. Results The genetic composition, anatomic structure and physiologic function of Drosophila Malpighian tubules are remarkably similar to those of the human nephron. The direct effects of dietary manipulation, environmental alteration, and genetic variation on stone formation can be observed and quantified in a matter of days. Several Drosophila models of human nephrolithiasis, including genetically linked and environmentally induced stones, have been developed. A model of calcium oxalate stone formation is among the most recent fly models of human nephrolithiasis. Conclusions The ability to readily manipulate and quantify stone formation in D. melanogaster models of human nephrolithiasis presents the urologic community with a unique opportunity to increase our understanding of this enigmatic disease. PMID:23500641

Development of the Integrated Communication Model

ERIC Educational Resources Information Center

Ho, Hua-Kuo

2008-01-01

Human communication is a critical issue in personal life. It also should be the indispensable core element of general education curriculum in universities and colleges. Based on literature analysis and the author's clinical observation, the importance of human communication, functions of model, and often seen human communication models were…

Development and translational imaging of a TP53 porcine tumorigenesis model

PubMed Central

Sieren, Jessica C.; Meyerholz, David K.; Wang, Xiao-Jun; Davis, Bryan T.; Newell, John D.; Hammond, Emily; Rohret, Judy A.; Rohret, Frank A.; Struzynski, Jason T.; Goeken, J. Adam; Naumann, Paul W.; Leidinger, Mariah R.; Taghiyev, Agshin; Van Rheeden, Richard; Hagen, Jussara; Darbro, Benjamin W.; Quelle, Dawn E.; Rogers, Christopher S.

2014-01-01

Cancer is the second deadliest disease in the United States, necessitating improvements in tumor diagnosis and treatment. Current model systems of cancer are informative, but translating promising imaging approaches and therapies to clinical practice has been challenging. In particular, the lack of a large-animal model that accurately mimics human cancer has been a major barrier to the development of effective diagnostic tools along with surgical and therapeutic interventions. Here, we developed a genetically modified porcine model of cancer in which animals express a mutation in TP53 (which encodes p53) that is orthologous to one commonly found in humans (R175H in people, R167H in pigs). TP53R167H/R167H mutant pigs primarily developed lymphomas and osteogenic tumors, recapitulating the tumor types observed in mice and humans expressing orthologous TP53 mutant alleles. CT and MRI imaging data effectively detected developing tumors, which were validated by histopathological evaluation after necropsy. Molecular genetic analyses confirmed that these animals expressed the R167H mutant p53, and evaluation of tumors revealed characteristic chromosomal instability. Together, these results demonstrated that TP53R167H/R167H pigs represent a large-animal tumor model that replicates the human condition. Our data further suggest that this model will be uniquely suited for developing clinically relevant, noninvasive imaging approaches to facilitate earlier detection, diagnosis, and treatment of human cancers. PMID:25105366

Engineering Large Animal Species to Model Human Diseases.

PubMed

Rogers, Christopher S

2016-07-01

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

Modeling Niemann Pick type C1 using human embryonic and induced pluripotent stem cells.

PubMed

Ordoñez, M Paulina; Steele, John W

2017-02-01

Data generated in Niemann Pick type C1 (NPC1) human embryonic and human induced pluripotent stem cell derived neurons complement on-going studies in animal models and provide the first example, in disease-relevant human cells, of processes that underlie preferential neuronal defects in a NPC1. Our work and that of other investigators in human neurons derived from stem cells highlight the importance of performing rigorous mechanistic studies in relevant cell types to guide drug discovery and therapeutic development, alongside of existing animal models. Through the use of human stem cell-derived models of disease, we can identify and discover or repurpose drugs that revert early events that lead to neuronal failure in NPC1. Together with the study of disease pathogenesis and efficacy of therapies in animal models, these strategies will fulfill the promise of stem cell technology in the development of new treatments for human diseases. This article is part of a Special Issue entitled SI: Exploiting human neurons. Copyright © 2016 Elsevier B.V. All rights reserved.

ANALYSIS OF HUMAN ACTIVITY DATA FOR USE IN MODELING ENVIRONMENTAL EXPOSURES

EPA Science Inventory

Human activity data are a critical part of exposure models being developed by the US EPA's National Exposure Research Laboratory (NERL). An analysis of human activity data within NERL's Consolidated Human Activity Database (CHAD) was performed in two areas relevant to exposure ...

How to become a top model: impact of animal experimentation on human Salmonella disease research.

PubMed

Tsolis, Renée M; Xavier, Mariana N; Santos, Renato L; Bäumler, Andreas J

2011-05-01

Salmonella serotypes are a major cause of human morbidity and mortality worldwide. Over the past decades, a series of animal models have been developed to advance vaccine development, provide insights into immunity to infection, and study the pathogenesis of human Salmonella disease. The successive introduction of new animal models, each suited to interrogate previously neglected aspects of Salmonella disease, has ushered in important conceptual advances that continue to have a strong and sustained influence on the ideas driving research on Salmonella serotypes. This article reviews important milestones in the use of animal models to study human Salmonella disease and identify research needs to guide future work.

An automated method to morph finite element whole-body human models with a wide range of stature and body shape for both men and women.

PubMed

Zhang, Kai; Cao, Libo; Fanta, Abeselom; Reed, Matthew P; Neal, Mark; Wang, Jenne-Tai; Lin, Chin-Hsu; Hu, Jingwen

2017-07-26

Field data analyses have shown that small female, obese, and/or older occupants are at increased risks of death and serious injury in motor-vehicle crashes compared with mid-size young men. The current adult finite element (FE) human models represent occupants in the same three body sizes (large male, mid-size male, and small female) as those for the contemporary adult crash dummies. Further, the time needed to develop an FE human model using the traditional method is measured in months or even years. In the current study, an improved regional mesh morphing method based on landmark-based radial basis function (RBF) interpolation was developed to rapidly morph a mid-size male FE human model into different geometry targets. A total of 100 human models with a wide range of human attributes were generated. A pendulum chest impact condition was applied to each model as an initial assessment of the resulting variability in response. The morphed models demonstrated mesh quality similar to the baseline model. The peak impact forces and chest deflections in the chest pendulum impacts varied substantially with different models, supportive of consideration of population variation in evaluating the occupant injury risks. The method developed in this study will enable future safety design optimizations targeting at various vulnerable populations that cannot be considered with the current models. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biofidelic Human Activity Modeling and Simulation with Large Variability

DTIC Science & Technology

2014-11-25

A systematic approach was developed for biofidelic human activity modeling and simulation by using body scan data and motion 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...that can replicate a human activity in 3D space with the true shape and true motion of a human. Using this approach, a model library was built to

Teaching Qualitative Research for Human Services Students: A Three-Phase Model

ERIC Educational Resources Information Center

Goussinsky, Ruhama; Reshef, Arie; Yanay-Ventura, Galit; Yassour-Borochowitz, Dalit

2011-01-01

Qualitative research is an inherent part of the human services profession, since it emphasizes the great and multifaceted complexity characterizing human experience and the sociocultural context in which humans act. In the department of human services at Emek Yezreel College, Israel, we have developed a three-phase model to ensure a relatively…

Improved physiologically based pharmacokinetic model for oral exposures to chromium in mice, rats, and humans to address temporal variation and sensitive populations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kirman, C.R., E-mail: ckirman@summittoxicology.com

A physiologically based pharmacokinetic (PBPK) model for hexavalent chromium [Cr(VI)] in mice, rats, and humans developed previously (Kirman et al., 2012, 2013), was updated to reflect an improved understanding of the toxicokinetics of the gastrointestinal tract following oral exposures. Improvements were made to: (1) the reduction model, which describes the pH-dependent reduction of Cr(VI) to Cr(III) in the gastrointestinal tract under both fasted and fed states; (2) drinking water pattern simulations, to better describe dosimetry in rodents under the conditions of the NTP cancer bioassay; and (3) parameterize the model to characterize potentially sensitive human populations. Important species differences, sourcesmore » of non-linear toxicokinetics, and human variation are identified and discussed within the context of human health risk assessment. - Highlights: • An improved version of the PBPK model for Cr(VI) toxicokinetics was developed. • The model incorporates data collected to fill important data gaps. • Model predictions for specific age groups and sensitive subpopulations are provided. • Implications to human health risk assessment are discussed.« less

Computational Modeling of Space Physiology

NASA Technical Reports Server (NTRS)

Lewandowski, Beth E.; Griffin, Devon W.

2016-01-01

The Digital Astronaut Project (DAP), within NASAs Human Research Program, develops and implements computational modeling for use in the mitigation of human health and performance risks associated with long duration spaceflight. Over the past decade, DAP developed models to provide insights into space flight related changes to the central nervous system, cardiovascular system and the musculoskeletal system. Examples of the models and their applications include biomechanical models applied to advanced exercise device development, bone fracture risk quantification for mission planning, accident investigation, bone health standards development, and occupant protection. The International Space Station (ISS), in its role as a testing ground for long duration spaceflight, has been an important platform for obtaining human spaceflight data. DAP has used preflight, in-flight and post-flight data from short and long duration astronauts for computational model development and validation. Examples include preflight and post-flight bone mineral density data, muscle cross-sectional area, and muscle strength measurements. Results from computational modeling supplement space physiology research by informing experimental design. Using these computational models, DAP personnel can easily identify both important factors associated with a phenomenon and areas where data are lacking. This presentation will provide examples of DAP computational models, the data used in model development and validation, and applications of the model.

Integrated Electronic Warfare Systems Aboard the United States Navy 21st Century Warship

DTIC Science & Technology

2009-12-01

automated operation using a Human-In-the-Loop that could be integrated into existing and future combat systems. A model was developed that demonstrates...complete range of automated operation using a Human-In-the-Loop that could be integrated into existing and future combat systems. A model was developed...44 1. Base Case Model

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…

Initial Attempts at Developing Appropriate Human Relations Experiences for Potential Teachers.

ERIC Educational Resources Information Center

Calliotte, James A.

This paper traces the development of a human relations program as part of the teacher education curriculum at the University of Maryland Baltimore County. Four approaches are presented--a basic encounter model, a cognitive model, a programed unit, and a final integrated model that is now being employed in the teacher education program. Each model…

Progress and Prospects for Genetic Modification of Nonhuman Primate Models in Biomedical Research

PubMed Central

Chan, Anthony W. S.

2013-01-01

The growing interest of modeling human diseases using genetically modified (transgenic) nonhuman primates (NHPs) is a direct result of NHPs (rhesus macaque, etc.) close relation to humans. NHPs share similar developmental paths with humans in their anatomy, physiology, genetics, and neural functions; and in their cognition, emotion, and social behavior. The NHP model within biomedical research has played an important role in the development of vaccines, assisted reproductive technologies, and new therapies for many diseases. Biomedical research has not been the primary role of NHPs. They have mainly been used for safety evaluation and pharmacokinetics studies, rather than determining therapeutic efficacy. The development of the first transgenic rhesus macaque (2001) revolutionized the role of NHP models in biomedicine. Development of the transgenic NHP model of Huntington's disease (2008), with distinctive clinical features, further suggested the uniqueness of the model system; and the potential role of the NHP model for human genetic disorders. Modeling human genetic diseases using NHPs will continue to thrive because of the latest advances in molecular, genetic, and embryo technologies. NHPs rising role in biomedical research, specifically pre-clinical studies, is foreseeable. The path toward the development of transgenic NHPs and the prospect of transgenic NHPs in their new role in future biomedicine needs to be reviewed. This article will focus on the advancement of transgenic NHPs in the past decade, including transgenic technologies and disease modeling. It will outline new technologies that may have significant impact in future NHP modeling and will conclude with a discussion of the future prospects of the transgenic NHP model. PMID:24174443

Mouse Models for Investigating the Developmental Bases of Human Birth Defects

PubMed Central

MOON, ANNE M.

2006-01-01

Clinicians and basic scientists share an interest in discovering how genetic or environmental factors interact to perturb normal development and cause birth defects and human disease. Given the complexity of such interactions, it is not surprising that 4% of human infants are born with a congenital malformation, and cardiovascular defects occur in nearly 1%. Our research is based on the fundamental hypothesis that an understanding of normal and abnormal development will permit us to generate effective strategies for both prevention and treatment of human birth defects. Animal models are invaluable in these efforts because they allow one to interrogate the genetic, molecular and cellular events that distinguish normal from abnormal development. Several features of the mouse make it a particularly powerful experimental model: it is a mammalian system with similar embryology, anatomy and physiology to humans; genes, proteins and regulatory programs are largely conserved between human and mouse; and finally, gene targeting in murine embryonic stem cells has made the mouse genome amenable to sophisticated genetic manipulation currently unavailable in any other model organism. PMID:16641221

Corneal cell culture models: a tool to study corneal drug absorption.

PubMed

Dey, Surajit

2011-05-01

In recent times, there has been an ever increasing demand for ocular drugs to treat sight threatening diseases such as glaucoma, age-related macular degeneration and diabetic retinopathy. As more drugs are developed, there is a great need to test in vitro permeability of these drugs to predict their efficacy and bioavailability in vivo. Corneal cell culture models are the only tool that can predict drug absorption across ocular layers accurately and rapidly. Cell culture studies are also valuable in reducing the number of animals needed for in vivo studies which can increase the cost of the drug developmental process. Currently, rabbit corneal cell culture models are used to predict human corneal absorption due to the difficulty in human corneal studies. More recently, a three dimensional human corneal equivalent has been developed using three different cell types to mimic the human cornea. In the future, human corneal cell culture systems need to be developed to be used as a standardized model for drug permeation.

Physiologically based pharmacokinetic modeling of tea catechin mixture in rats and humans.

PubMed

Law, Francis C P; Yao, Meicun; Bi, Hui-Chang; Lam, Stephen

2017-06-01

Although green tea ( Camellia sinensis) (GT) contains a large number of polyphenolic compounds with anti-oxidative and anti-proliferative activities, little is known of the pharmacokinetics and tissue dose of tea catechins (TCs) as a chemical mixture in humans. The objectives of this study were to develop and validate a physiologically based pharmacokinetic (PBPK) model of tea catechin mixture (TCM) in rats and humans, and to predict an integrated or total concentration of TCM in the plasma of humans after consuming GT or Polyphenon E (PE). To this end, a PBPK model of epigallocatechin gallate (EGCg) consisting of 13 first-order, blood flow-limited tissue compartments was first developed in rats. The rat model was scaled up to humans by replacing its physiological parameters, pharmacokinetic parameters and tissue/blood partition coefficients (PCs) with human-specific values. Both rat and human EGCg models were then extrapolated to other TCs by substituting its physicochemical parameters, pharmacokinetic parameters, and PCs with catechin-specific values. Finally, a PBPK model of TCM was constructed by linking three rat (or human) tea catechin models together without including a description for pharmacokinetic interaction between the TCs. The mixture PBPK model accurately predicted the pharmacokinetic behaviors of three individual TCs in the plasma of rats and humans after GT or PE consumption. Model-predicted total TCM concentration in the plasma was linearly related to the dose consumed by humans. The mixture PBPK model is able to translate an external dose of TCM into internal target tissue doses for future safety assessment and dose-response analysis studies in humans. The modeling framework as described in this paper is also applicable to the bioactive chemical in other plant-based health products.

An immunologic model for rapid vaccine assessment -- a clinical trial in a test tube.

PubMed

Higbee, Russell G; Byers, Anthony M; Dhir, Vipra; Drake, Donald; Fahlenkamp, Heather G; Gangur, Jyoti; Kachurin, Anatoly; Kachurina, Olga; Leistritz, Del; Ma, Yifan; Mehta, Riyaz; Mishkin, Eric; Moser, Janice; Mosquera, Luis; Nguyen, Mike; Parkhill, Robert; Pawar, Santosh; Poisson, Louis; Sanchez-Schmitz, Guzman; Schanen, Brian; Singh, Inderpal; Song, Haifeng; Tapia, Tenekua; Warren, William; Wittman, Vaughan

2009-09-01

While the duration and size of human clinical trials may be difficult to reduce, there are several parameters in pre-clinical vaccine development that may be possible to further optimise. By increasing the accuracy of the models used for pre-clinical vaccine testing, it should be possible to increase the probability that any particular vaccine candidate will be successful in human trials. In addition, an improved model will allow the collection of increasingly more-informative data in pre-clinical tests, thus aiding the rational design and formulation of candidates entered into clinical evaluation. An acceleration and increase in sophistication of pre-clinical vaccine development will thus require the advent of more physiologically-accurate models of the human immune system, coupled with substantial advances in the mechanistic understanding of vaccine efficacy, achieved by using this model. We believe the best viable option available is to use human cells and/or tissues in a functional in vitro model of human physiology. Not only will this more accurately model human diseases, it will also eliminate any ethical, moral and scientific issues involved with use of live humans and animals. An in vitro model, termed "MIMIC" (Modular IMmune In vitro Construct), was designed and developed to reflect the human immune system in a well-based format. The MIMIC System is a laboratory-based methodology that replicates the human immune system response. It is highly automated, and can be used to simulate a clinical trial for a diverse population, without putting human subjects at risk. The MIMIC System uses the circulating immune cells of individual donors to recapitulate each individual human immune response by maintaining the autonomy of the donor. Thus, an in vitro test system has been created that is functionally equivalent to the donor's own immune system and is designed to respond in a similar manner to the in vivo response. 2009 FRAME.

Development of induced glioblastoma by implantation of a human xenograft in Yucatan minipig as a large animal model.

PubMed

Khoshnevis, Mehrdad; Carozzo, Claude; Bonnefont-Rebeix, Catherine; Belluco, Sara; Leveneur, Olivia; Chuzel, Thomas; Pillet-Michelland, Elodie; Dreyfus, Matthieu; Roger, Thierry; Berger, François; Ponce, Frédérique

2017-04-15

Glioblastoma is the most common and deadliest primary brain tumor for humans. Despite many efforts toward the improvement of therapeutic methods, prognosis is poor and the disease remains incurable with a median survival of 12-14.5 months after an optimal treatment. To develop novel treatment modalities for this fatal disease, new devices must be tested on an ideal animal model before performing clinical trials in humans. A new model of induced glioblastoma in Yucatan minipigs was developed. Nine immunosuppressed minipigs were implanted with the U87 human glioblastoma cell line in both the left and right hemispheres. Computed tomography (CT) acquisitions were performed once a week to monitor tumor growth. Among the 9 implanted animals, 8 minipigs showed significant macroscopic tumors on CT acquisitions. Histological examination of the brain after euthanasia confirmed the CT imaging findings with the presence of an undifferentiated glioma. Yucatan minipig, given its brain size and anatomy (gyrencephalic structure) which are comparable to humans, provides a reliable brain tumor model for preclinical studies of different therapeutic METHODS: in realistic conditions. Moreover, the short development time, the lower cyclosporine and caring cost and the compatibility with the size of commercialized stereotactic frames make it an affordable and practical animal model, especially in comparison with large breed pigs. This reproducible glioma model could simulate human anatomical conditions in preclinical studies and facilitate the improvement of novel therapeutic devices, designed at the human scale from the outset. Copyright © 2017 Elsevier B.V. All rights reserved.

Experimental psychiatric illness and drug abuse models: from human to animal, an overview.

PubMed

Edwards, Scott; Koob, George F

2012-01-01

Preclinical animal models have supported much of the recent rapid expansion of neuroscience research and have facilitated critical discoveries that undoubtedly benefit patients suffering from psychiatric disorders. This overview serves as an introduction for the following chapters describing both in vivo and in vitro preclinical models of psychiatric disease components and briefly describes models related to drug dependence and affective disorders. Although there are no perfect animal models of any psychiatric disorder, models do exist for many elements of each disease state or stage. In many cases, the development of certain models is essentially restricted to the human clinical laboratory domain for the purpose of maximizing validity, whereas the use of in vitro models may best represent an adjunctive, well-controlled means to model specific signaling mechanisms associated with psychiatric disease states. The data generated by preclinical models are only as valid as the model itself, and the development and refinement of animal models for human psychiatric disorders continues to be an important challenge. Collaborative relationships between basic neuroscience and clinical modeling could greatly benefit the development of new and better models, in addition to facilitating medications development.

Progression of pathogenic events in cynomolgus macaques infected with variola virus.

PubMed

Wahl-Jensen, Victoria; Cann, Jennifer A; Rubins, Kathleen H; Huggins, John W; Fisher, Robert W; Johnson, Anthony J; de Kok-Mercado, Fabian; Larsen, Thomas; Raymond, Jo Lynne; Hensley, Lisa E; Jahrling, Peter B

2011-01-01

Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections - an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions.

3-D Model of the Human Respiratory System

EPA Science Inventory

The U.S. EPA’s Office of Research and Development (ORD) has developed a 3-D computational fluid dynamics (CFD) model of the human respiratory system that allows for the simulation of particulate based contaminant deposition and clearance, while being adaptable for age, ethnicity,...

CPAS Parachute Testing, Model Development, & Verification

NASA Technical Reports Server (NTRS)

Romero, Leah M.

2013-01-01

Capsule Parachute Assembly System (CPAS) is the human rated parachute system for the Orion vehicle used during re-entry. Similar to Apollo parachute design. Human rating requires additional system redundancy. A Government Furnished Equipment (GFE) project responsible for: Design; Development testing; Performance modeling; Fabrication; Qualification; Delivery

To grow or not to grow: Hair morphogenesis and human genetic hair disorders

PubMed Central

Duverger, Olivier; Morasso, Maria I.

2014-01-01

Mouse models have greatly helped in elucidating the molecular mechanisms involved in hair formation and regeneration. Recent publications have reviewed the genes involved in mouse hair development based on the phenotype of transgenic, knockout and mutant animal models. While much of this information has been instrumental in determining molecular aspects of human hair development and cycling, mice exhibit a specific pattern of hair morphogenesis and hair distribution throughout the body that cannot be directly correlated to human hair. In this mini-review, we discuss specific aspects of human hair follicle development and present an up-to-date summary of human genetic disorders associated with abnormalities in hair follicle morphogenesis, structure or regeneration. PMID:24361867

Postures and Motions Library Development for Verification of Ground Crew Human Systems Integration Requirements

NASA Technical Reports Server (NTRS)

Jackson, Mariea Dunn; Dischinger, Charles; Stambolian, Damon; Henderson, Gena

2012-01-01

Spacecraft and launch vehicle ground processing activities require a variety of unique human activities. These activities are being documented in a Primitive motion capture library. The Library will be used by the human factors engineering in the future to infuse real to life human activities into the CAD models to verify ground systems human factors requirements. As the Primitive models are being developed for the library the project has selected several current human factors issues to be addressed for the SLS and Orion launch systems. This paper explains how the Motion Capture of unique ground systems activities are being used to verify the human factors analysis requirements for ground system used to process the STS and Orion vehicles, and how the primitive models will be applied to future spacecraft and launch vehicle processing.

Postures and Motions Library Development for Verification of Ground Crew Human Factors Requirements

NASA Technical Reports Server (NTRS)

Stambolian, Damon; Henderson, Gena; Jackson, Mariea Dunn; Dischinger, Charles

2013-01-01

Spacecraft and launch vehicle ground processing activities require a variety of unique human activities. These activities are being documented in a primitive motion capture library. The library will be used by human factors engineering analysts to infuse real to life human activities into the CAD models to verify ground systems human factors requirements. As the primitive models are being developed for the library, the project has selected several current human factors issues to be addressed for the Space Launch System (SLS) and Orion launch systems. This paper explains how the motion capture of unique ground systems activities is being used to verify the human factors engineering requirements for ground systems used to process the SLS and Orion vehicles, and how the primitive models will be applied to future spacecraft and launch vehicle processing.

Application of chimeric mice with humanized liver for study of human-specific drug metabolism.

PubMed

Bateman, Thomas J; Reddy, Vijay G B; Kakuni, Masakazu; Morikawa, Yoshio; Kumar, Sanjeev

2014-06-01

Human-specific or disproportionately abundant human metabolites of drug candidates that are not adequately formed and qualified in preclinical safety assessment species pose an important drug development challenge. Furthermore, the overall metabolic profile of drug candidates in humans is an important determinant of their drug-drug interaction susceptibility. These risks can be effectively assessed and/or mitigated if human metabolic profile of the drug candidate could reliably be determined in early development. However, currently available in vitro human models (e.g., liver microsomes, hepatocytes) are often inadequate in this regard. Furthermore, the conduct of definitive radiolabeled human ADME studies is an expensive and time-consuming endeavor that is more suited for later in development when the risk of failure has been reduced. We evaluated a recently developed chimeric mouse model with humanized liver on uPA/SCID background for its ability to predict human disposition of four model drugs (lamotrigine, diclofenac, MRK-A, and propafenone) that are known to exhibit human-specific metabolism. The results from these studies demonstrate that chimeric mice were able to reproduce the human-specific metabolite profile for lamotrigine, diclofenac, and MRK-A. In the case of propafenone, however, the human-specific metabolism was not detected as a predominant pathway, and the metabolite profiles in native and humanized mice were similar; this was attributed to the presence of residual highly active propafenone-metabolizing mouse enzymes in chimeric mice. Overall, the data indicate that the chimeric mice with humanized liver have the potential to be a useful tool for the prediction of human-specific metabolism of xenobiotics and warrant further investigation.

An integrated modeling framework for exploring flow regime and water quality changes with increasing biofuel crop production in the U.S. Corn Belt

NASA Astrophysics Data System (ADS)

Yaeger, Mary A.; Housh, Mashor; Cai, Ximing; Sivapalan, Murugesu

2014-12-01

To better address the dynamic interactions between human and hydrologic systems, we develop an integrated modeling framework that employs a System of Systems optimization model to emulate human development decisions which are then incorporated into a watershed model to estimate the resulting hydrologic impacts. The two models are run interactively to simulate the coevolution of coupled human-nature systems, such that reciprocal feedbacks between hydrologic processes and human decisions (i.e., human impacts on critical low flows and hydrologic impacts on human decisions on land and water use) can be assessed. The framework is applied to a Midwestern U.S. agricultural watershed, in the context of proposed biofuels development. This operation is illustrated by projecting three possible future coevolution trajectories, two of which use dedicated biofuel crops to reduce annual watershed nitrate export while meeting ethanol production targets. Imposition of a primary external driver (biofuel mandate) combined with different secondary drivers (water quality targets) results in highly nonlinear and multiscale responses of both the human and hydrologic systems, including multiple tradeoffs, impacting the future coevolution of the system in complex, heterogeneous ways. The strength of the hydrologic response is sensitive to the magnitude of the secondary driver; 45% nitrate reduction target leads to noticeable impacts at the outlet, while a 30% reduction leads to noticeable impacts that are mainly local. The local responses are conditioned by previous human-hydrologic modifications and their spatial relationship to the new biofuel development, highlighting the importance of past coevolutionary history in predicting future trajectories of change.

Genetics of human hydrocephalus

PubMed Central

Williams, Michael A.; Rigamonti, Daniele

2006-01-01

Human hydrocephalus is a common medical condition that is characterized by abnormalities in the flow or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. Human hydrocephalus can be classified into two clinical forms, congenital and acquired. Hydrocephalus is one of the complex and multifactorial neurological disorders. A growing body of evidence indicates that genetic factors play a major role in the pathogenesis of hydrocephalus. An understanding of the genetic components and mechanism of this complex disorder may offer us significant insights into the molecular etiology of impaired brain development and an accumulation of the cerebrospinal fluid in cerebral compartments during the pathogenesis of hydrocephalus. Genetic studies in animal models have started to open the way for understanding the underlying pathology of hydrocephalus. At least 43 mutants/loci linked to hereditary hydrocephalus have been identified in animal models and humans. Up to date, 9 genes associated with hydrocephalus have been identified in animal models. In contrast, only one such gene has been identified in humans. Most of known hydrocephalus gene products are the important cytokines, growth factors or related molecules in the cellular signal pathways during early brain development. The current molecular genetic evidence from animal models indicate that in the early development stage, impaired and abnormal brain development caused by abnormal cellular signaling and functioning, all these cellular and developmental events would eventually lead to the congenital hydrocephalus. Owing to our very primitive knowledge of the genetics and molecular pathogenesis of human hydrocephalus, it is difficult to evaluate whether data gained from animal models can be extrapolated to humans. Initiation of a large population genetics study in humans will certainly provide invaluable information about the molecular and cellular etiology and the developmental mechanisms of human hydrocephalus. This review summarizes the recent findings on this issue among human and animal models, especially with reference to the molecular genetics, pathological, physiological and cellular studies, and identifies future research directions. PMID:16773266

Deep Neural Networks as a Computational Model for Human Shape Sensitivity

PubMed Central

Op de Beeck, Hans P.

2016-01-01

Theories of object recognition agree that shape is of primordial importance, but there is no consensus about how shape might be represented, and so far attempts to implement a model of shape perception that would work with realistic stimuli have largely failed. Recent studies suggest that state-of-the-art convolutional ‘deep’ neural networks (DNNs) capture important aspects of human object perception. We hypothesized that these successes might be partially related to a human-like representation of object shape. Here we demonstrate that sensitivity for shape features, characteristic to human and primate vision, emerges in DNNs when trained for generic object recognition from natural photographs. We show that these models explain human shape judgments for several benchmark behavioral and neural stimulus sets on which earlier models mostly failed. In particular, although never explicitly trained for such stimuli, DNNs develop acute sensitivity to minute variations in shape and to non-accidental properties that have long been implicated to form the basis for object recognition. Even more strikingly, when tested with a challenging stimulus set in which shape and category membership are dissociated, the most complex model architectures capture human shape sensitivity as well as some aspects of the category structure that emerges from human judgments. As a whole, these results indicate that convolutional neural networks not only learn physically correct representations of object categories but also develop perceptually accurate representational spaces of shapes. An even more complete model of human object representations might be in sight by training deep architectures for multiple tasks, which is so characteristic in human development. PMID:27124699

Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche

NASA Astrophysics Data System (ADS)

Shao, Yue; Taniguchi, Kenichiro; Gurdziel, Katherine; Townshend, Ryan F.; Xue, Xufeng; Yong, Koh Meng Aw; Sang, Jianming; Spence, Jason R.; Gumucio, Deborah L.; Fu, Jianping

2017-04-01

Amniogenesis--the development of amnion--is a critical developmental milestone for early human embryogenesis and successful pregnancy. However, human amniogenesis is poorly understood due to limited accessibility to peri-implantation embryos and a lack of in vitro models. Here we report an efficient biomaterial system to generate human amnion-like tissue in vitro through self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking the in vivo implantation environment. We show that biophysical niche factors act as a switch to toggle hPSC self-renewal versus amniogenesis under self-renewal-permissive biochemical conditions. We identify a unique molecular signature of hPSC-derived amnion-like cells and show that endogenously activated BMP-SMAD signalling is required for the amnion-like tissue development by hPSCs. This study unveils the self-organizing and mechanosensitive nature of human amniogenesis and establishes the first hPSC-based model for investigating peri-implantation human amnion development, thereby helping advance human embryology and reproductive medicine.

Development of a Physiologically Based Model to Describe the Pharmacokinetics of Methylphenidate in Juvenile and Adult Humans and Nonhuman Primates

PubMed Central

Yang, Xiaoxia; Morris, Suzanne M.; Gearhart, Jeffery M.; Ruark, Christopher D.; Paule, Merle G.; Slikker, William; Mattison, Donald R.; Vitiello, Benedetto; Twaddle, Nathan C.; Doerge, Daniel R.; Young, John F.; Fisher, Jeffrey W.

2014-01-01

The widespread usage of methylphenidate (MPH) in the pediatric population has received considerable attention due to its potential effect on child development. For the first time a physiologically based pharmacokinetic (PBPK) model has been developed in juvenile and adult humans and nonhuman primates to quantitatively evaluate species- and age-dependent enantiomer specific pharmacokinetics of MPH and its primary metabolite ritalinic acid. The PBPK model was first calibrated in adult humans using in vitro enzyme kinetic data of MPH enantiomers, together with plasma and urine pharmacokinetic data with MPH in adult humans. Metabolism of MPH in the small intestine was assumed to account for the low oral bioavailability of MPH. Due to lack of information, model development for children and juvenile and adult nonhuman primates primarily relied on intra- and interspecies extrapolation using allometric scaling. The juvenile monkeys appear to metabolize MPH more rapidly than adult monkeys and humans, both adults and children. Model prediction performance is comparable between juvenile monkeys and children, with average root mean squared error values of 4.1 and 2.1, providing scientific basis for interspecies extrapolation of toxicity findings. Model estimated human equivalent doses in children that achieve similar internal dose metrics to those associated with pubertal delays in juvenile monkeys were found to be close to the therapeutic doses of MPH used in pediatric patients. This computational analysis suggests that continued pharmacovigilance assessment is prudent for the safe use of MPH. PMID:25184666

Assessing the feasibility, cost, and utility of developing models of human performance in aviation

NASA Technical Reports Server (NTRS)

Stillwell, William

1990-01-01

The purpose of the effort outlined in this briefing was to determine whether models exist or can be developed that can be used to address aviation automation issues. A multidisciplinary team has been assembled to undertake this effort, including experts in human performance, team/crew, and aviation system modeling, and aviation data used as input to such models. The project consists of two phases, a requirements assessment phase that is designed to determine the feasibility and utility of alternative modeling efforts, and a model development and evaluation phase that will seek to implement the plan (if a feasible cost effective development effort is found) that results from the first phase. Viewgraphs are given.

Development of a Human Motor Model for the Evaluation of an Integrated Alerting and Notification Flight Deck System

NASA Technical Reports Server (NTRS)

Daiker, Ron; Schnell, Thomas

2010-01-01

A human motor model was developed on the basis of performance data that was collected in a flight simulator. The motor model is under consideration as one component of a virtual pilot model for the evaluation of NextGen crew alerting and notification systems in flight decks. This model may be used in a digital Monte Carlo simulation to compare flight deck layout design alternatives. The virtual pilot model is being developed as part of a NASA project to evaluate multiple crews alerting and notification flight deck configurations. Model parameters were derived from empirical distributions of pilot data collected in a flight simulator experiment. The goal of this model is to simulate pilot motor performance in the approach-to-landing task. The unique challenges associated with modeling the complex dynamics of humans interacting with the cockpit environment are discussed, along with the current state and future direction of the model.

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. Copyright © 2016 the American Physiological Society.

A human model for primate personality

PubMed Central

2017-01-01

In this article, I review the literature to determine how successful the latent trait theory model of personality from differential psychology has been for studying personality in non-human primates. The evidence for the success of this model is quite good, and offers insights and directions for personality research in primates and other animals. This, I conclude, stems from (i) the human trait model's simplicity, and (ii) the fact that the human differential model of personality developed in the face of harsh criticism, which led researchers to test and refine their models. PMID:29021170

Teaching Human Genetics with Mustard: Rapid Cycling "Brassica rapa" (Fast Plants Type) as a Model for Human Genetics in the Classroom Laboratory

ERIC Educational Resources Information Center

Wendell, Douglas L.; Pickard, Dawn

2007-01-01

We have developed experiments and materials to model human genetics using rapid cycling "Brassica rapa", also known as Fast Plants. Because of their self-incompatibility for pollination and the genetic diversity within strains, "B. rapa" can serve as a relevant model for human genetics in teaching laboratory experiments. The experiment presented…

The Microphysiology Systems Database for Analyzing and Modeling Compound Interactions with Human and Animal Organ Models

PubMed Central

Vernetti, Lawrence; Bergenthal, Luke; Shun, Tong Ying; Taylor, D. Lansing

2016-01-01

Abstract Microfluidic human organ models, microphysiology systems (MPS), are currently being developed as predictive models of drug safety and efficacy in humans. To design and validate MPS as predictive of human safety liabilities requires safety data for a reference set of compounds, combined with in vitro data from the human organ models. To address this need, we have developed an internet database, the MPS database (MPS-Db), as a powerful platform for experimental design, data management, and analysis, and to combine experimental data with reference data, to enable computational modeling. The present study demonstrates the capability of the MPS-Db in early safety testing using a human liver MPS to relate the effects of tolcapone and entacapone in the in vitro model to human in vivo effects. These two compounds were chosen to be evaluated as a representative pair of marketed drugs because they are structurally similar, have the same target, and were found safe or had an acceptable risk in preclinical and clinical trials, yet tolcapone induced unacceptable levels of hepatotoxicity while entacapone was found to be safe. Results demonstrate the utility of the MPS-Db as an essential resource for relating in vitro organ model data to the multiple biochemical, preclinical, and clinical data sources on in vivo drug effects. PMID:28781990

Energy evaluation of protection effectiveness of anti-vibration gloves.

PubMed

Hermann, Tomasz; Dobry, Marian Witalis

2017-09-01

This article describes an energy method of assessing protection effectiveness of anti-vibration gloves on the human dynamic structure. The study uses dynamic models of the human and the glove specified in Standard No. ISO 10068:2012. The physical models of human-tool systems were developed by combining human physical models with a power tool model. The combined human-tool models were then transformed into mathematical models from which energy models were finally derived. Comparative energy analysis was conducted in the domain of rms powers. The energy models of the human-tool systems were solved using numerical simulation implemented in the MATLAB/Simulink environment. The simulation procedure demonstrated the effectiveness of the anti-vibration glove as a method of protecting human operators of hand-held power tools against vibration. The desirable effect is achieved by lowering the flow of energy in the human-tool system when the anti-vibration glove is employed.

A Model for the Creation of Human-Generated Metadata within Communities

ERIC Educational Resources Information Center

Brasher, Andrew; McAndrew, Patrick

2005-01-01

This paper considers situations for which detailed metadata descriptions of learning resources are necessary, and focuses on human generation of such metadata. It describes a model which facilitates human production of good quality metadata by the development and use of structured vocabularies. Using examples, this model is applied to single and…

Toward a 3D model of human brain development for studying gene/environment interactions

PubMed Central

2013-01-01

This project aims to establish and characterize an in vitro model of the developing human brain for the purpose of testing drugs and chemicals. To accurately assess risk, a model needs to recapitulate the complex interactions between different types of glial cells and neurons in a three-dimensional platform. Moreover, human cells are preferred over cells from rodents to eliminate cross-species differences in sensitivity to chemicals. Previously, we established conditions to culture rat primary cells as three-dimensional aggregates, which will be humanized and evaluated here with induced pluripotent stem cells (iPSCs). The use of iPSCs allows us to address gene/environment interactions as well as the potential of chemicals to interfere with epigenetic mechanisms. Additionally, iPSCs afford us the opportunity to study the effect of chemicals during very early stages of brain development. It is well recognized that assays for testing toxicity in the developing brain must consider differences in sensitivity and susceptibility that arise depending on the time of exposure. This model will reflect critical developmental processes such as proliferation, differentiation, lineage specification, migration, axonal growth, dendritic arborization and synaptogenesis, which will probably display differences in sensitivity to different types of chemicals. Functional endpoints will evaluate the complex cell-to-cell interactions that are affected in neurodevelopment through chemical perturbation, and the efficacy of drug intervention to prevent or reverse phenotypes. The model described is designed to assess developmental neurotoxicity effects on unique processes occurring during human brain development by leveraging human iPSCs from diverse genetic backgrounds, which can be differentiated into different cell types of the central nervous system. Our goal is to demonstrate the feasibility of the personalized model using iPSCs derived from individuals with neurodevelopmental disorders caused by known mutations and chromosomal aberrations. Notably, such a human brain model will be a versatile tool for more complex testing platforms and strategies as well as research into central nervous system physiology and pathology. PMID:24564953

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.

Modeling Viral Infectious Diseases and Development of Antiviral Therapies Using Human Induced Pluripotent Stem Cell-Derived Systems.

PubMed

Trevisan, Marta; Sinigaglia, Alessandro; Desole, Giovanna; Berto, Alessandro; Pacenti, Monia; Palù, Giorgio; Barzon, Luisa

2015-07-13

The recent biotechnology breakthrough of cell reprogramming and generation of induced pluripotent stem cells (iPSCs), which has revolutionized the approaches to study the mechanisms of human diseases and to test new drugs, can be exploited to generate patient-specific models for the investigation of host-pathogen interactions and to develop new antimicrobial and antiviral therapies. Applications of iPSC technology to the study of viral infections in humans have included in vitro modeling of viral infections of neural, liver, and cardiac cells; modeling of human genetic susceptibility to severe viral infectious diseases, such as encephalitis and severe influenza; genetic engineering and genome editing of patient-specific iPSC-derived cells to confer antiviral resistance.

Complete Plasmodium falciparum liver-stage development in liver-chimeric mice

PubMed Central

Vaughan, Ashley M.; Mikolajczak, Sebastian A.; Wilson, Elizabeth M.; Grompe, Markus; Kaushansky, Alexis; Camargo, Nelly; Bial, John; Ploss, Alexander; Kappe, Stefan H.I.

2012-01-01

Plasmodium falciparum, which causes the most lethal form of human malaria, replicates in the host liver during the initial stage of infection. However, in vivo malaria liver-stage (LS) studies in humans are virtually impossible, and in vitro models of LS development do not reconstitute relevant parasite growth conditions. To overcome these obstacles, we have adopted a robust mouse model for the study of P. falciparum LS in vivo: the immunocompromised and fumarylacetoacetate hydrolase–deficient mouse (Fah–/–, Rag2–/–, Il2rg–/–, termed the FRG mouse) engrafted with human hepatocytes (FRG huHep). FRG huHep mice supported vigorous, quantifiable P. falciparum LS development that culminated in complete maturation of LS at approximately 7 days after infection, providing a relevant model for LS development in humans. The infections allowed observations of previously unknown expression of proteins in LS, including P. falciparum translocon of exported proteins 150 (PTEX150) and exported protein-2 (EXP-2), components of a known parasite protein export machinery. LS schizonts exhibited exoerythrocytic merozoite formation and merosome release. Furthermore, FRG mice backcrossed to the NOD background and repopulated with huHeps and human red blood cells supported reproducible transition from LS infection to blood-stage infection. Thus, these mice constitute reliable models to study human LS directly in vivo and demonstrate utility for studies of LS–to–blood-stage transition of a human malaria parasite. PMID:22996664

Complete Plasmodium falciparum liver-stage development in liver-chimeric mice.

PubMed

Vaughan, Ashley M; Mikolajczak, Sebastian A; Wilson, Elizabeth M; Grompe, Markus; Kaushansky, Alexis; Camargo, Nelly; Bial, John; Ploss, Alexander; Kappe, Stefan H I

2012-10-01

Plasmodium falciparum, which causes the most lethal form of human malaria, replicates in the host liver during the initial stage of infection. However, in vivo malaria liver-stage (LS) studies in humans are virtually impossible, and in vitro models of LS development do not reconstitute relevant parasite growth conditions. To overcome these obstacles, we have adopted a robust mouse model for the study of P. falciparum LS in vivo: the immunocompromised and fumarylacetoacetate hydrolase-deficient mouse (Fah-/-, Rag2-/-, Il2rg-/-, termed the FRG mouse) engrafted with human hepatocytes (FRG huHep). FRG huHep mice supported vigorous, quantifiable P. falciparum LS development that culminated in complete maturation of LS at approximately 7 days after infection, providing a relevant model for LS development in humans. The infections allowed observations of previously unknown expression of proteins in LS, including P. falciparum translocon of exported proteins 150 (PTEX150) and exported protein-2 (EXP-2), components of a known parasite protein export machinery. LS schizonts exhibited exoerythrocytic merozoite formation and merosome release. Furthermore, FRG mice backcrossed to the NOD background and repopulated with huHeps and human red blood cells supported reproducible transition from LS infection to blood-stage infection. Thus, these mice constitute reliable models to study human LS directly in vivo and demonstrate utility for studies of LS-to-blood-stage transition of a human malaria parasite.

Methodologies for Development of Patient Specific Bone Models from Human Body CT Scans

NASA Astrophysics Data System (ADS)

Chougule, Vikas Narayan; Mulay, Arati Vinayak; Ahuja, Bharatkumar Bhagatraj

2016-06-01

This work deals with development of algorithm for physical replication of patient specific human bone and construction of corresponding implants/inserts RP models by using Reverse Engineering approach from non-invasive medical images for surgical purpose. In medical field, the volumetric data i.e. voxel and triangular facet based models are primarily used for bio-modelling and visualization, which requires huge memory space. On the other side, recent advances in Computer Aided Design (CAD) technology provides additional facilities/functions for design, prototyping and manufacturing of any object having freeform surfaces based on boundary representation techniques. This work presents a process to physical replication of 3D rapid prototyping (RP) physical models of human bone from various CAD modeling techniques developed by using 3D point cloud data which is obtained from non-invasive CT/MRI scans in DICOM 3.0 format. This point cloud data is used for construction of 3D CAD model by fitting B-spline curves through these points and then fitting surface between these curve networks by using swept blend techniques. This process also can be achieved by generating the triangular mesh directly from 3D point cloud data without developing any surface model using any commercial CAD software. The generated STL file from 3D point cloud data is used as a basic input for RP process. The Delaunay tetrahedralization approach is used to process the 3D point cloud data to obtain STL file. CT scan data of Metacarpus (human bone) is used as the case study for the generation of the 3D RP model. A 3D physical model of the human bone is generated on rapid prototyping machine and its virtual reality model is presented for visualization. The generated CAD model by different techniques is compared for the accuracy and reliability. The results of this research work are assessed for clinical reliability in replication of human bone in medical field.

Integrating the Advanced Human Eye Model (AHEM) and optical instrument models to model complete visual optical systems inclusive of the typical or atypical eye

NASA Astrophysics Data System (ADS)

Donnelly, William J., III

2012-06-01

PURPOSE: To present a commercially available optical modeling software tool to assist the development of optical instrumentation and systems that utilize and/or integrate with the human eye. METHODS: A commercially available flexible eye modeling system is presented, the Advanced Human Eye Model (AHEM). AHEM is a module that the engineer can use to perform rapid development and test scenarios on systems that integrate with the eye. Methods include merging modeled systems initially developed outside of AHEM and performing a series of wizard-type operations that relieve the user from requiring an optometric or ophthalmic background to produce a complete eye inclusive system. Scenarios consist of retinal imaging of targets and sources through integrated systems. Uses include, but are not limited to, optimization, telescopes, microscopes, spectacles, contact and intraocular lenses, ocular aberrations, cataract simulation and scattering, and twin eye model (binocular) systems. RESULTS: Metrics, graphical data, and exportable CAD geometry are generated from the various modeling scenarios.

Standardisation of digital human models.

PubMed

Paul, Gunther; Wischniewski, Sascha

2012-01-01

Digital human models (DHM) have evolved as useful tools for ergonomic workplace design and product development, and found in various industries and education. DHM systems which dominate the market were developed for specific purposes and differ significantly, which is not only reflected in non-compatible results of DHM simulations, but also provoking misunderstanding of how DHM simulations relate to real world problems. While DHM developers are restricted by uncertainty about the user need and lack of model data related standards, users are confined to one specific product and cannot exchange results, or upgrade to another DHM system, as their previous results would be rendered worthless. Furthermore, origin and validity of anthropometric and biomechanical data is not transparent to the user. The lack of standardisation in DHM systems has become a major roadblock in further system development, affecting all stakeholders in the DHM industry. Evidently, a framework for standardising digital human models is necessary to overcome current obstructions. Practitioner Summary: This short communication addresses a standardisation issue for digital human models, which has been addressed at the International Ergonomics Association Technical Committee for Human Simulation and Virtual Environments. It is the outcome of a workshop at the DHM 2011 symposium in Lyon, which concluded steps towards DHM standardisation that need to be taken.

Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress

PubMed Central

ZHANG, Xiao-Liang; PANG, Wei; HU, Xin-Tian; LI, Jia-Li; YAO, Yong-Gang; ZHENG, Yong-Tang

2014-01-01

Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China’s growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China’s life sciences and pharmaceutical industry, and enhance China’s position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China. PMID:25465081

Large Mammalian Animal Models of Heart Disease

PubMed Central

Camacho, Paula; Fan, Huimin; Liu, Zhongmin; He, Jia-Qiang

2016-01-01

Due to the biological complexity of the cardiovascular system, the animal model is an urgent pre-clinical need to advance our knowledge of cardiovascular disease and to explore new drugs to repair the damaged heart. Ideally, a model system should be inexpensive, easily manipulated, reproducible, a biological representative of human disease, and ethically sound. Although a larger animal model is more expensive and difficult to manipulate, its genetic, structural, functional, and even disease similarities to humans make it an ideal model to first consider. This review presents the commonly-used large animals—dog, sheep, pig, and non-human primates—while the less-used other large animals—cows, horses—are excluded. The review attempts to introduce unique points for each species regarding its biological property, degrees of susceptibility to develop certain types of heart diseases, and methodology of induced conditions. For example, dogs barely develop myocardial infarction, while dilated cardiomyopathy is developed quite often. Based on the similarities of each species to the human, the model selection may first consider non-human primates—pig, sheep, then dog—but it also depends on other factors, for example, purposes, funding, ethics, and policy. We hope this review can serve as a basic outline of large animal models for cardiovascular researchers and clinicians. PMID:29367573

Development of a physiologically based pharmacokinetic model for assessment of human exposure to bisphenol A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Xiaoxia, E-mail: xiaoxia.yang@fda.hhs.gov; Doerge, Daniel R.; Teeguarden, Justin G.

A previously developed physiologically based pharmacokinetic (PBPK) model for bisphenol A (BPA) in adult rhesus monkeys was modified to characterize the pharmacokinetics of BPA and its phase II conjugates in adult humans following oral ingestion. Coupled with in vitro studies on BPA metabolism in the liver and the small intestine, the PBPK model was parameterized using oral pharmacokinetic data with deuterated-BPA (d{sub 6}-BPA) delivered in cookies to adult humans after overnight fasting. The availability of the serum concentration time course of unconjugated d{sub 6}-BPA offered direct empirical evidence for the calibration of BPA model parameters. The recalibrated PBPK adult humanmore » model for BPA was then evaluated against published human pharmacokinetic studies with BPA. A hypothesis of decreased oral uptake was needed to account for the reduced peak levels observed in adult humans, where d{sub 6}-BPA was delivered in soup and food was provided prior to BPA ingestion, suggesting the potential impact of dosing vehicles and/or fasting on BPA disposition. With the incorporation of Monte Carlo analysis, the recalibrated adult human model was used to address the inter-individual variability in the internal dose metrics of BPA for the U.S. general population. Model-predicted peak BPA serum levels were in the range of pM, with 95% of human variability falling within an order of magnitude. This recalibrated PBPK model for BPA in adult humans provides a scientific basis for assessing human exposure to BPA that can serve to minimize uncertainties incurred during extrapolations across doses and species. - Highlights: • A PBPK model predicts the kinetics of bisphenol A (BPA) in adult humans. • Serum concentrations of aglycone BPA are available for model calibration. • Model predicted peak BPA serum levels for adult humans were in the range of pM. • Model predicted 95% of human variability fell within an order of magnitude.« less

Amplifying human ability through autonomics and machine learning in IMPACT

NASA Astrophysics Data System (ADS)

Dzieciuch, Iryna; Reeder, John; Gutzwiller, Robert; Gustafson, Eric; Coronado, Braulio; Martinez, Luis; Croft, Bryan; Lange, Douglas S.

2017-05-01

Amplifying human ability for controlling complex environments featuring autonomous units can be aided by learned models of human and system performance. In developing a command and control system that allows a small number of people to control a large number of autonomous teams, we employ an autonomics framework to manage the networks that represent mission plans and the networks that are composed of human controllers and their autonomous assistants. Machine learning allows us to build models of human and system performance useful for monitoring plans and managing human attention and task loads. Machine learning also aids in the development of tactics that human supervisors can successfully monitor through the command and control system.

Animal models of age related macular degeneration

PubMed Central

Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

2013-01-01

Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

Microenvironmental Regulation of Mammary Carcinogenesis

DTIC Science & Technology

2008-06-01

cells. These models share many of the hallmarks of multistage human breast cancer development including histological disease progression and immune cell... developed by Muller and colleagues20, represents a reasonable recapitulation of late-stage human breast cancer as determined by histological progression ...Annual Progress Report d. Develop a profile of proteolytic activities in normal and neoplastic mammary tissues from mouse models of mammary

Women, Human Development, and Learning. ERIC Digest.

ERIC Educational Resources Information Center

Kerka, Sandra

A growing body of literature is questioning whether existing models of human development apply equally to men and women. Prevailing theories of human development have been criticized for being based on research with primarily male subjects of similar ethnic, racial, or class backgrounds. Some research supports the viewpoint that women have…

Socio-hydrologic modeling to understand and mediate the competition for water between agriculture development and environmental health: Murrumbidgee River basin, Australia

NASA Astrophysics Data System (ADS)

van Emmerik, T. H. M.; Li, Z.; Sivapalan, M.; Pande, S.; Kandasamy, J.; Savenije, H. H. G.; Chanan, A.; Vigneswaran, S.

2014-10-01

Competition for water between humans and ecosystems is set to become a flash point in the coming decades in many parts of the world. An entirely new and comprehensive quantitative framework is needed to establish a holistic understanding of that competition, thereby enabling the development of effective mediation strategies. This paper presents a modeling study centered on the Murrumbidgee River basin (MRB). The MRB has witnessed a unique system dynamics over the last 100 years as a result of interactions between patterns of water management and climate driven hydrological variability. Data analysis has revealed a pendulum swing between agricultural development and restoration of environmental health and ecosystem services over different stages of basin-scale water resource development. A parsimonious, stylized, quasi-distributed coupled socio-hydrologic system model that simulates the two-way coupling between human and hydrological systems of the MRB is used to mimic and explain dominant features of the pendulum swing. The model consists of coupled nonlinear ordinary differential equations that describe the interaction between five state variables that govern the co-evolution: reservoir storage, irrigated area, human population, ecosystem health, and environmental awareness. The model simulations track the propagation of the external climatic and socio-economic drivers through this coupled, complex system to the emergence of the pendulum swing. The model results point to a competition between human "productive" and environmental "restorative" forces that underpin the pendulum swing. Both the forces are endogenous, i.e., generated by the system dynamics in response to external drivers and mediated by humans through technology change and environmental awareness, respectively. Sensitivity analysis carried out with the model further reveals that socio-hydrologic modeling can be used as a tool to explain or gain insight into observed co-evolutionary dynamics of diverse human-water coupled systems. This paper therefore contributes to the ultimate development of a generic modeling framework that can be applied to human-water coupled systems in different climatic and socio-economic settings.

School Effectiveness in Ecological Perspective.

ERIC Educational Resources Information Center

Bronfenbrenner, Urie; Hamilton, Stephen F.

This report focuses on the learning and development of primary and secondary school children, employing an "ecology of human development" model. This model is defined as involving the scientific study of the accommodation between growing human beings and the changing immediate settings in which they live and learn. The conceptual framework for the…

Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans

EPA Pesticide Factsheets

Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans (Presented by James McKim, Ph.D., DABT, Founder and Chief Science Officer, CeeTox) (5/25/2012)

Research Summary 3-D Computational Fluid Dynamics (CFD) Model Of The Human Respiratory System

EPA Science Inventory

The U.S. EPA’s Office of Research and Development (ORD) has developed a 3-D computational fluid dynamics (CFD) model of the human respiratory system that allows for the simulation of particulate based contaminant deposition and clearance, while being adaptable for age, ethnicity,...

Neoclassical and Institutional Economics as Foundations for Human Resource Development Theory

ERIC Educational Resources Information Center

Wang, Greg G.; Holton, Elwood F., III

2005-01-01

In an effort to more comprehensively understand economics as a foundation of human resource development (HRD), this article reviews economic theories and models pertinent to HRD research and theory building. By examining neoclassical and neoinstitutional schools of contemporary economics, especially the screening model and the internal labor…

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…

Development of a physiologically based pharmacokinetic model for bisphenol A in pregnant mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawamoto, Yuko; Matsuyama, Wakoto; Wada, Masahiro

Bisphenol A (BPA) is a weakly estrogenic monomer used to produce polymers for food contact and other applications, so there is potential for oral exposure of humans to trace amounts via ingestion. To date, no physiologically based pharmacokinetic (PBPK) model has been located for BPA in pregnant mice with or without fetuses. An estimate by a mathematical model is essential since information on humans is difficult to obtain experimentally. The PBPK model was constructed based on the pharmacokinetic data of our experiment following single oral administration of BPA to pregnant mice. The risk assessment of bisphenol A (BPA) on themore » development of human offspring is an important issue. There have been limited data on the exposure level of human fetuses to BPA (e.g. BPA concentration in cord blood) and no information is available on the pharmacokinetics of BPA in humans with or without fetuses. In the present study, we developed a physiologically based pharmacokinetic (PBPK) model describing the pharmacokinetics of BPA in a pregnant mouse with the prospect of future extrapolation to humans. The PBPK model was constructed based on the pharmacokinetic data of an experiment we executed on pregnant mice following single oral administration of BPA. The model could describe the rapid transfer of BPA through the placenta to the fetus and the slow disappearance from fetuses. The simulated time courses after three-time repeated oral administrations of BPA by the constructed model fitted well with the experimental data, and the simulation for the 10 times lower dose was also consistent with the experiment. This suggested that the PBPK model for BPA in pregnant mice was successfully verified and is highly promising for extrapolation to humans who are expected to be exposed more chronically to lower doses.« less

Physiologically Based Pharmacokinetic Model for Terbinafine in Rats and Humans

PubMed Central

Hosseini-Yeganeh, Mahboubeh; McLachlan, Andrew J.

2002-01-01

The aim of this study was to develop a physiologically based pharmacokinetic (PB-PK) model capable of describing and predicting terbinafine concentrations in plasma and tissues in rats and humans. A PB-PK model consisting of 12 tissue and 2 blood compartments was developed using concentration-time data for tissues from rats (n = 33) after intravenous bolus administration of terbinafine (6 mg/kg of body weight). It was assumed that all tissues except skin and testis tissues were well-stirred compartments with perfusion rate limitations. The uptake of terbinafine into skin and testis tissues was described by a PB-PK model which incorporates a membrane permeability rate limitation. The concentration-time data for terbinafine in human plasma and tissues were predicted by use of a scaled-up PB-PK model, which took oral absorption into consideration. The predictions obtained from the global PB-PK model for the concentration-time profile of terbinafine in human plasma and tissues were in close agreement with the observed concentration data for rats. The scaled-up PB-PK model provided an excellent prediction of published terbinafine concentration-time data obtained after the administration of single and multiple oral doses in humans. The estimated volume of distribution at steady state (Vss) obtained from the PB-PK model agreed with the reported value of 11 liters/kg. The apparent volume of distribution of terbinafine in skin and adipose tissues accounted for 41 and 52%, respectively, of the Vss for humans, indicating that uptake into and redistribution from these tissues dominate the pharmacokinetic profile of terbinafine. The PB-PK model developed in this study was capable of accurately predicting the plasma and tissue terbinafine concentrations in both rats and humans and provides insight into the physiological factors that determine terbinafine disposition. PMID:12069977

Animal models of human immunodeficiency virus infection. Public Health Service Animal Models Committee.

PubMed

Spertzel, R O

1989-12-01

The search for a model of HIV infection continues. While much of the initial work focussed on animal models of AIDS, more recent efforts have sought animal models of HIV infection in which one or more signs of AIDS may be reproduced. Most initial small animal modelling efforts were negative and many such efforts remain unpublished. In 1988, the Public Health Service (PHS) AIDS Animal Model Committee conducted a survey among PHS agencies to identify published and unpublished data on animal models of HIV. To date, the chimpanzee is the only animal to be reliably infected with HIV albeit without development of signs and symptoms normally associated with human AIDS. One recent study has shown the gibbon to be similarly susceptible to infection with HIV. Mice carrying a chimera of elements of the human immune system have been shown to support the growth of HIV and F1 progeny of transgenic mice containing intact copies of HIV proviral DNA, have developed a disease that resembles some aspects of human AIDS. Rabbits, baboons and rhesus monkeys have also been shown to be infected under certain conditions and/or with selected strains of HIV but again without the development of AIDS symptomatology. This report briefly summarizes published and available unpublished data on these efforts to develop an animal model of HIV infection.

The Application of Humanized Mouse Models for the Study of Human Exclusive Viruses.

PubMed

Vahedi, Fatemeh; Giles, Elizabeth C; Ashkar, Ali A

2017-01-01

The symbiosis between humans and viruses has allowed human tropic pathogens to evolve intricate means of modulating the human immune response to ensure its survival among the human population. In doing so, these viruses have developed profound mechanisms that mesh closely with our human biology. The establishment of this intimate relationship has created a species-specific barrier to infection, restricting the virus-associated pathologies to humans. This specificity diminishes the utility of traditional animal models. Humanized mice offer a model unique to all other means of study, providing an in vivo platform for the careful examination of human tropic viruses and their interaction with human cells and tissues. These types of animal models have provided a reliable medium for the study of human-virus interactions, a relationship that could otherwise not be investigated without questionable relevance to humans.

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 and other research.

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.

Animal models for Ebola and Marburg virus infections

PubMed Central

Nakayama, Eri; Saijo, Masayuki

2013-01-01

Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics. PMID:24046765

Animal models for Ebola and Marburg virus infections.

PubMed

Nakayama, Eri; Saijo, Masayuki

2013-09-05

Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics.

To grow or not to grow: hair morphogenesis and human genetic hair disorders.

PubMed

Duverger, Olivier; Morasso, Maria I

2014-01-01

Mouse models have greatly helped in elucidating the molecular mechanisms involved in hair formation and regeneration. Recent publications have reviewed the genes involved in mouse hair development based on the phenotype of transgenic, knockout and mutant animal models. While much of this information has been instrumental in determining molecular aspects of human hair development and cycling, mice exhibit a specific pattern of hair morphogenesis and hair distribution throughout the body that cannot be directly correlated to human hair. In this mini-review, we discuss specific aspects of human hair follicle development and present an up-to-date summary of human genetic disorders associated with abnormalities in hair follicle morphogenesis, structure or regeneration. Published by Elsevier Ltd.

On quantum models of the human mind.

PubMed

Wang, Hongbin; Sun, Yanlong

2014-01-01

Recent years have witnessed rapidly increasing interests in developing quantum theoretical models of human cognition. Quantum mechanisms have been taken seriously to describe how the mind reasons and decides. Papers in this special issue report the newest results in the field. Here we discuss why the two levels of commitment, treating the human brain as a quantum computer and merely adopting abstract quantum probability principles to model human cognition, should be integrated. We speculate that quantum cognition models gain greater modeling power due to a richer representation scheme. Copyright © 2013 Cognitive Science Society, Inc.

Validating Human Performance Models of the Future Orion Crew Exploration Vehicle

NASA Technical Reports Server (NTRS)

Wong, Douglas T.; Walters, Brett; Fairey, Lisa

2010-01-01

NASA's Orion Crew Exploration Vehicle (CEV) will provide transportation for crew and cargo to and from destinations in support of the Constellation Architecture Design Reference Missions. Discrete Event Simulation (DES) is one of the design methods NASA employs for crew performance of the CEV. During the early development of the CEV, NASA and its prime Orion contractor Lockheed Martin (LM) strived to seek an effective low-cost method for developing and validating human performance DES models. This paper focuses on the method developed while creating a DES model for the CEV Rendezvous, Proximity Operations, and Docking (RPOD) task to the International Space Station. Our approach to validation was to attack the problem from several fronts. First, we began the development of the model early in the CEV design stage. Second, we adhered strictly to M&S development standards. Third, we involved the stakeholders, NASA astronauts, subject matter experts, and NASA's modeling and simulation development community throughout. Fourth, we applied standard and easy-to-conduct methods to ensure the model's accuracy. Lastly, we reviewed the data from an earlier human-in-the-loop RPOD simulation that had different objectives, which provided us an additional means to estimate the model's confidence level. The results revealed that a majority of the DES model was a reasonable representation of the current CEV design.

Metabolism and physiologically based pharmacokinetic modeling of flumioxazin in pregnant animals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takaku, Tomoyuki, E-mail: takakut@sc.sumitomo-chem.co.jp; Nagahori, Hirohisa; Sogame, Yoshihisa

A physiologically based pharmacokinetic (PBPK) model was developed to predict the concentration of flumioxazin, in the blood and fetus of pregnant humans during a theoretical accidental intake (1000 mg/kg). The data on flumioxazin concentration in pregnant rats (30 mg/kg po) was used to develop the PBPK model in pregnant rats using physiological parameters and chemical specific parameters. The rat PBPK model developed was extrapolated to a human model. Liver microsomes of female rats and a mixed gender of humans were used for the in vitro metabolism study. To determine the % of flumioxazin absorbed after administration at a dose ofmore » 1000 mg/kg assuming maximum accidental intake, the biliary excretion study of [phenyl-U-{sup 14}C]flumioxazin was conducted in bile duct-cannulated female rats (Crl:CD (SD)) to collect and analyze the bile, urine, feces, gastrointestinal tract, and residual carcass. The % of flumioxazin absorbed at a dose of 1000 mg/kg in rats was low (12.3%) by summing up {sup 14}C of the urine, bile, and residual carcass. The pregnant human model that was developed demonstrated that the maximum flumioxazin concentration in the blood and fetus of a pregnant human at a dose of 1000 mg/kg po was 0.86 μg/mL and 0.68 μg/mL, respectively, which is much lower than K{sub m} (202.4 μg/mL). Because the metabolism was not saturated and the absorption rate was low at a dose of 1000 mg/kg, the calculated flumioxazin concentration in pregnant humans was thought to be relatively low, considering the flumioxazin concentration in pregnant rats at a dose of 30 mg/kg. For the safety assessment of flumioxazin, these results would be useful for further in vitro toxicology experiments. - Highlights: • A PBPK model of flumioxazin in pregnant humans was developed. • Simulated flumioxazin concentration in pregnant humans was relatively low. • The results would be useful for further in vitro toxicology experiments.« less

Reflection of a Year Long Model-Driven Business and UI Modeling Development Project

NASA Astrophysics Data System (ADS)

Sukaviriya, Noi; Mani, Senthil; Sinha, Vibha

Model-driven software development enables users to specify an application at a high level - a level that better matches problem domain. It also promises the users with better analysis and automation. Our work embarks on two collaborating domains - business process and human interactions - to build an application. Business modeling expresses business operations and flows then creates business flow implementation. Human interaction modeling expresses a UI design, its relationship with business data, logic, and flow, and can generate working UI. This double modeling approach automates the production of a working system with UI and business logic connected. This paper discusses the human aspects of this modeling approach after a year long of building a procurement outsourcing contract application using the approach - the result of which was deployed in December 2008. The paper discusses in multiple areas the happy endings and some heartache. We end with insights on how a model-driven approach could do better for humans in the process.

Comparing statistical and machine learning classifiers: alternatives for predictive modeling in human factors research.

PubMed

Carnahan, Brian; Meyer, Gérard; Kuntz, Lois-Ann

2003-01-01

Multivariate classification models play an increasingly important role in human factors research. In the past, these models have been based primarily on discriminant analysis and logistic regression. Models developed from machine learning research offer the human factors professional a viable alternative to these traditional statistical classification methods. To illustrate this point, two machine learning approaches--genetic programming and decision tree induction--were used to construct classification models designed to predict whether or not a student truck driver would pass his or her commercial driver license (CDL) examination. The models were developed and validated using the curriculum scores and CDL exam performances of 37 student truck drivers who had completed a 320-hr driver training course. Results indicated that the machine learning classification models were superior to discriminant analysis and logistic regression in terms of predictive accuracy. Actual or potential applications of this research include the creation of models that more accurately predict human performance outcomes.

Supportive accountability: a model for providing human support to enhance adherence to eHealth interventions.

PubMed

Mohr, David C; Cuijpers, Pim; Lehman, Kenneth

2011-03-10

The effectiveness of and adherence to eHealth interventions is enhanced by human support. However, human support has largely not been manualized and has usually not been guided by clear models. The objective of this paper is to develop a clear theoretical model, based on relevant empirical literature, that can guide research into human support components of eHealth interventions. A review of the literature revealed little relevant information from clinical sciences. Applicable literature was drawn primarily from organizational psychology, motivation theory, and computer-mediated communication (CMC) research. We have developed a model, referred to as "Supportive Accountability." We argue that human support increases adherence through accountability to a coach who is seen as trustworthy, benevolent, and having expertise. Accountability should involve clear, process-oriented expectations that the patient is involved in determining. Reciprocity in the relationship, through which the patient derives clear benefits, should be explicit. The effect of accountability may be moderated by patient motivation. The more intrinsically motivated patients are, the less support they likely require. The process of support is also mediated by the communications medium (eg, telephone, instant messaging, email). Different communications media each have their own potential benefits and disadvantages. We discuss the specific components of accountability, motivation, and CMC medium in detail. The proposed model is a first step toward understanding how human support enhances adherence to eHealth interventions. Each component of the proposed model is a testable hypothesis. As we develop viable human support models, these should be manualized to facilitate dissemination.

Active numerical model of human body for reconstruction of falls from height.

PubMed

Milanowicz, Marcin; Kędzior, Krzysztof

2017-01-01

Falls from height constitute the largest group of incidents out of approximately 90,000 occupational accidents occurring each year in Poland. Reconstruction of the exact course of a fall from height is generally difficult due to lack of sufficient information from the accident scene. This usually results in several contradictory versions of an incident and impedes, for example, determination of the liability in a judicial process. In similar situations, in many areas of human activity, researchers apply numerical simulation. They use it to model physical phenomena to reconstruct their real course over time; e.g. numerical human body models are frequently used for investigation and reconstruction of road accidents. However, they are validated in terms of specific road traffic accidents and are considerably limited when applied to the reconstruction of other types of accidents. The objective of the study was to develop an active numerical human body model to be used for reconstruction of accidents associated with falling from height. Development of the model involved extension and adaptation of the existing Pedestrian human body model (available in the MADYMO package database) for the purposes of reconstruction of falls from height by taking into account the human reaction to the loss of balance. The model was developed by using the results of experimental tests of the initial phase of the fall from height. The active numerical human body model covering 28 sets of initial conditions related to various human reactions to the loss of balance was developed. The application of the model was illustrated by using it to reconstruct a real fall from height. From among the 28 sets of initial conditions, those whose application made it possible to reconstruct the most probable version of the incident was selected. The selection was based on comparison of the results of the reconstruction with information contained in the accident report. Results in the form of estimated injuries overlap with the real injuries sustained by the casualty. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

Transgenic nude mouse with green fluorescent protein expression-based human glioblastoma multiforme animal model with EGFR expression and invasiveness.

PubMed

Tan, Guo-Wei; Lan, Fo-Lin; Gao, Jian-Guo; Jiang, Cai-Mou; Zhang, Yi; Huang, Xiao-Hong; Ma, Yue-Hong; Shao, He-Dui; He, Xue-Yang; Chen, Jin-Long; Long, Jian-Wu; Xiao, Hui-Sheng; Guo, Zhi-Tong; Diao, Yi

2012-08-01

Previously, we developed an orthotopic xenograft model of human glioblastoma multiforme (GBM) with high EGFR expression and invasiveness in Balb/c nu/nu nude mice. Now we also developed the same orthotopic xenograft model in transgenic nude mice with green fluorescent protein (GFP) expression. The present orthotopic xenografts labeled by phycoerythrin fluorescing red showed high EGFR expression profile, and invasive behavior under a bright green-red dual-color fluorescence background. A striking advantage in the present human GBM model is that the change of tumor growth can be observed visually instead of sacrificing animals in our further antitumor therapy studies.

Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus

PubMed Central

Rubins, Kathleen H.; Huggins, John W.; Fisher, Robert W.; Johnson, Anthony J.; de Kok-Mercado, Fabian; Larsen, Thomas; Raymond, Jo Lynne; Hensley, Lisa E.; Jahrling, Peter B.

2011-01-01

Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections – an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions. PMID:21998632

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.

Development of a Mouse Model of Helicobacter pylori Infection that Mimics Human Disease

NASA Astrophysics Data System (ADS)

Marchetti, Marta; Arico, Beatrice; Burroni, Daniela; Figura, Natale; Rappuoli, Rino; Ghiara, Paolo

1995-03-01

The human pathogen Helicobacter pylori is associated with gastritis, peptic ulcer disease, and gastric cancer. The pathogenesis of H. pylori infection in vivo was studied by adapting fresh clinical isolates of bacteria to colonize the stomachs of mice. A gastric pathology resembling human disease was observed in infections with cytotoxin-producing strains but not with noncytotoxic strains. Oral immunization with purified H. pylori antigens protected mice from bacterial infection. This mouse model will allow the development of therapeutic agents and vaccines against H. pylori infection in humans.

Human mobility: Models and applications

NASA Astrophysics Data System (ADS)

Barbosa, Hugo; Barthelemy, Marc; Ghoshal, Gourab; James, Charlotte R.; Lenormand, Maxime; Louail, Thomas; Menezes, Ronaldo; Ramasco, José J.; Simini, Filippo; Tomasini, Marcello

2018-03-01

Recent years have witnessed an explosion of extensive geolocated datasets related to human movement, enabling scientists to quantitatively study individual and collective mobility patterns, and to generate models that can capture and reproduce the spatiotemporal structures and regularities in human trajectories. The study of human mobility is especially important for applications such as estimating migratory flows, traffic forecasting, urban planning, and epidemic modeling. In this survey, we review the approaches developed to reproduce various mobility patterns, with the main focus on recent developments. This review can be used both as an introduction to the fundamental modeling principles of human mobility, and as a collection of technical methods applicable to specific mobility-related problems. The review organizes the subject by differentiating between individual and population mobility and also between short-range and long-range mobility. Throughout the text the description of the theory is intertwined with real-world applications.

A One Health Approach to Hypertrophic Cardiomyopathy

PubMed Central

Ueda, Yu; Stern, Joshua A.

2017-01-01

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease in humans and results in significant morbidity and mortality. Research over the past 25 years has contributed enormous insight into this inherited disease particularly in the areas of genetics, molecular mechanisms, and pathophysiology. Our understanding continues to be limited by the heterogeneity of clinical presentations with various genetic mutations associated with HCM. Transgenic mouse models have been utilized especially studying the genotypic and phenotypic interactions. However, mice possess intrinsic cardiac and hemodynamic differences compared to humans and have limitations preventing their direct translation. Other animal models of HCM have been studied or generated in part to overcome these limitations. HCM in cats shows strikingly similar molecular, histopathological, and genetic similarities to human HCM, and offers an important translational opportunity for the study of this disease. Recently, inherited left ventricular hypertrophy in rhesus macaques was identified and collaborative investigations have been conducted to begin to develop a non-human primate HCM model. These naturally-occurring large-animal models may aid in advancing our understanding of HCM and developing novel therapeutic approaches to this disease. This review will highlight the features of HCM in humans and the relevant available and developing animal models of this condition. PMID:28955182

Humanizing the Technological Learning Experience: The Role of Support Services as Socialization in a Human Resource Development Distance Education Program.

ERIC Educational Resources Information Center

Hatcher, Tim; Craig, Bob

The University of Arkansas developed a distance education (DE) baccalaureate degree program in human resource development (HRD) that may serve as a model for developing DE at any level. The program, which was designed on the basis of a statewide needs assessment and competencies researched by the American Society for Training and Development, is…

Muscle-driven finite element simulation of human foot movements.

PubMed

Spyrou, L A; Aravas, N

2012-01-01

This paper describes a finite element scheme for realistic muscle-driven simulation of human foot movements. The scheme is used to simulate human ankle plantar flexion. A three-dimensional anatomically detailed finite element model of human foot and lower leg is developed and the idea of generating natural foot movement based entirely on the contraction of the plantar flexor muscles is used. The bones, ligaments, articular cartilage, muscles, tendons, as well as the rest soft tissues of human foot and lower leg are included in the model. A realistic three-dimensional continuum constitutive model that describes the biomechanical behaviour of muscles and tendons is used. Both the active and passive properties of muscle tissue are accounted for. The materials for bones and ligaments are considered as homogeneous, isotropic and linearly elastic, whereas the articular cartilage and the rest soft tissues (mainly fat) are defined as hyperelastic materials. The model is used to estimate muscle tissue deformations as well as stresses and strains that develop in the lower leg muscles during plantar flexion of the ankle. Stresses and strains that develop in Achilles tendon during such a movement are also investigated.

Interfacing models of wildlife habitat and human development to predict the future distribution of puma habitat

USGS Publications Warehouse

Burdett, Christopher L.; Crooks, Kevin R.; Theobald, David M.; Wilson, Kenneth R.; Boydston, Erin E.; Lyren, Lisa A.; Fisher, Robert N.; Vickers, T. Winston; Morrison, Scott A.; Boyce, Walter M.

2010-01-01

The impact of human land uses on ecological systems typically differ relative to how extensively natural conditions are modified. Exurban development is intermediate-intensity residential development that often occurs in natural landscapes. Most species-habitat models do not evaluate the effects of such intermediate levels of human development and even fewer predict how future development patterns might affect the amount and configuration of habitat. We addressed these deficiencies by interfacing a habitat model with a spatially-explicit housing-density model to study the effect of human land uses on the habitat of pumas (Puma concolor) in southern California. We studied the response of pumas to natural and anthropogenic features within their home ranges and how mortality risk varied across a gradient of human development. We also used our housing-density model to estimate past and future housing densities and model the distribution of puma habitat in 1970, 2000, and 2030. The natural landscape for pumas in our study area consisted of riparian areas, oak woodlands, and open, conifer forests embedded in a chaparral matrix. Pumas rarely incorporated suburban or urban development into their home ranges, which is consistent with the hypothesis that the behavioral decisions of individuals can be collectively manifested as population-limiting factors at broader spatial scales. Pumas incorporated rural and exurban development into their home ranges, apparently perceiving these areas as modified, rather than non-habitat. Overall, pumas used exurban areas less than expected and showed a neutral response to rural areas. However, individual pumas that selected for or showed a neutral response to exurban areas had a higher risk of mortality than pumas that selected against exurban habitat. Exurban areas are likely hotspots for puma-human conflict in southern California. Approximately 10% of our study area will transform from exurban, rural, or undeveloped areas to suburban or urban by 2030, and 35% of suitable puma habitat on private land in 1970 will have been lost by 2030. These land-use changes will further isolate puma populations in southern California, but the ability to visualize these changes had provided a new tool for developing proactive conservation solutions.

EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice.

PubMed

Yi, Diao; Hua, Tian Xin; Lin, Huang Yan

2011-03-01

Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.

Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Asgharian, Bahman; Price, Owen; McClellan, Gene

2012-11-01

The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of themore » animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 µm in size were examined for endotracheal and and up to 5 µm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Finally, future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model.« less

Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans

PubMed Central

Asgharian, Bahman; Price, Owen; McClellan, Gene; Corley, Rick; Einstein, Daniel R.; Jacob, Richard E.; Harkema, Jack; Carey, Stephan A.; Schelegle, Edward; Hyde, Dallas; Kimbell, Julia S.; Miller, Frederick J.

2016-01-01

The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of the animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 μm in size were examined for endotracheal and and up to 5 μm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model. PMID:23121298

3D Models of Immunotherapy

Cancer.gov

This collaborative grant is developing 3D models of both mouse and human biology to investigate aspects of therapeutic vaccination in order to answer key questions relevant to human cancer immunotherapy.

Microvesicating effects of sulfur mustard on an in vitro human skin model.

PubMed

Hayden, Patrick J; Petrali, John P; Stolper, Gina; Hamilton, Tracey A; Jackson, George R; Wertz, Philip W; Ito, Susumu; Smith, William J; Klausner, Mitchell

2009-10-01

Bis-(beta-chloroethyl) sulfide (SM) is a potent skin vesicant previously used for chemical warfare. Progress in determination of the mechanistic basis of SM pathology, and development of prophylactic and/or therapeutic countermeasures to SM exposure has been hampered by lack of physiologically relevant models of human skin. The current work evaluated a newly developed tissue engineered full-thickness human skin model in a completely in vitro approach to investigation of SM-induced dermal pathology. The model was first characterized with regard to overall morphology, lipid composition, basement membrane (BM) composition and ultrastructural features that are important targets of SM pathologic activity. Well-developed BM ultrastructural features were observed at the dermal-epidermal junction (DEJ), thus demonstrating successful resolution of a primary deficiency of models previously evaluated for SM studies. Studies were then conducted to evaluate histopathological effects of SM on the model. Good replication of in vivo effects was observed, including apoptosis of basal keratinocytes (KC) and microblister formation at the DEJ. Tissue engineered skin models with well-developed basement membrane structures thus appear to be useful tools for in vitro mechanistic studies of SM vesicant activity and development of preventive/therapeutic approaches for SM pathology.

Simulation of light transport in arthritic- and non-arthritic human fingers

NASA Astrophysics Data System (ADS)

Milanic, Matija; Paluchowski, Lukasz A.; Randeberg, Lise L.

2014-03-01

Rheumatoid arthritis is a disease that frequently leads to joint destruction. It has high incidence rates worldwide, and the disease significantly reduces patient's quality of life due to pain, swelling and stiffness of the affected joints. Early diagnosis is necessary to improve course of the disease, therefore sensitive and accurate diagnostic tools are required. Optical imaging techniques have capability for early diagnosis and monitoring of arthritis. As compared to conventional diagnostic techniques optical technique is a noninvasive, noncontact and fast way of collecting diagnostic information. However, a realistic model of light transport in human joints is needed for understanding and developing of such optical diagnostic tools. The aim of this study is to develop a 3D numerical model of light transport in a human finger. The model will guide development of a hyperspectral imaging (HSI) diagnostic modality for arthritis in human fingers. The implemented human finger geometry is based on anatomical data. Optical data of finger tissues are adjusted to represent either an arthritic or an unaffected finger. The geometry and optical data serve as input into a 3D Monte Carlo method, which calculate diffuse reflectance, transmittance and absorbed energy distributions. The parameters of the model are optimized based on HIS-measurements of human fingers. The presented model serves as an important tool for understanding and development of HSI as an arthritis diagnostic modality. Yet, it can be applied to other optical techniques and finger diseases.

PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR HUMAN EXPOSURES TO METHYL TERTIARY-BUTYL ETHER

EPA Science Inventory

Humans can be exposed by inhalation, ingestion, or dermal absorption to methyl tertiary-butyl ether (MTBE), an oxygenated fuel additive, from contaminated water sources. The purpose of this research was to develop a physiologically based pharmacokinetic model describing in human...

Development of a Human Physiologically Based Pharmacokinetics (PBPK) Model For Dermal Permeability for Lindane

EPA Science Inventory

Lindane is a neurotoxicant used for the treatment of lice and scabies present on human skin. Due to its pharmaceutical application, an extensive pharmacokinetic database exists in humans. Mathematical diffusion models allow for calculation of lindane skin permeability coefficient...

Socio-hydrologic modeling to understand and mediate the competition for water between agriculture development and environmental health: Murrumbidgee River Basin, Australia

NASA Astrophysics Data System (ADS)

van Emmerik, T. H. M.; Li, Z.; Sivapalan, M.; Pande, S.; Kandasamy, J.; Savenije, H. H. G.; Chanan, A.; Vigneswaran, S.

2014-03-01

Competition for water between humans and ecosystems is set to become a flash point in the coming decades in many parts of the world. An entirely new and comprehensive quantitative framework is needed to establish a holistic understanding of that competition, thereby enabling the development of effective mediation strategies. This paper presents a modeling study centered on the Murrumbidgee River Basin (MRB). The MRB has witnessed a unique system dynamics over the last 100 years as a result of interactions between patterns of water management and climate driven hydrological variability. Data analysis has revealed a pendulum swing between agricultural development and restoration of environmental health and ecosystem services over different stages of basin scale water resource development. A parsimonious, stylized, quasi-distributed coupled socio-hydrologic system model that simulates the two-way coupling between human and hydrological systems of the MRB is used to mimic dominant features of the pendulum swing. The model consists of coupled nonlinear ordinary differential equations that describe the interaction between five state variables that govern the co-evolution: reservoir storage, irrigated area, human population, ecosystem health, and a measure of environmental awareness. The model simulations track the propagation of the external climatic and socio-economic drivers through this coupled, complex system to the emergence of the pendulum swing. The model results point to a competition between human "productive" and environmental "restorative" forces that underpin the pendulum swing. Both the forces are endogenous, i.e., generated by the system dynamics in response to external drivers and mediated by humans through technology change and environmental awareness, respectively. We propose this as a generalizable modeling framework for coupled human hydrological systems that is potentially transferable to systems in different climatic and socio-economic settings.

Reprogramming of human cancer cells to pluripotency for models of cancer progression

PubMed Central

Kim, Jungsun; Zaret, Kenneth S

2015-01-01

The ability to study live cells as they progress through the stages of cancer provides the opportunity to discover dynamic networks underlying pathology, markers of early stages, and ways to assess therapeutics. Genetically engineered animal models of cancer, where it is possible to study the consequences of temporal-specific induction of oncogenes or deletion of tumor suppressors, have yielded major insights into cancer progression. Yet differences exist between animal and human cancers, such as in markers of progression and response to therapeutics. Thus, there is a need for human cell models of cancer progression. Most human cell models of cancer are based on tumor cell lines and xenografts of primary tumor cells that resemble the advanced tumor state, from which the cells were derived, and thus do not recapitulate disease progression. Yet a subset of cancer types have been reprogrammed to pluripotency or near-pluripotency by blastocyst injection, by somatic cell nuclear transfer and by induced pluripotent stem cell (iPS) technology. The reprogrammed cancer cells show that pluripotency can transiently dominate over the cancer phenotype. Diverse studies show that reprogrammed cancer cells can, in some cases, exhibit early-stage phenotypes reflective of only partial expression of the cancer genome. In one case, reprogrammed human pancreatic cancer cells have been shown to recapitulate stages of cancer progression, from early to late stages, thus providing a model for studying pancreatic cancer development in human cells where previously such could only be discerned from mouse models. We discuss these findings, the challenges in developing such models and their current limitations, and ways that iPS reprogramming may be enhanced to develop human cell models of cancer progression. PMID:25712212

Use of genome editing tools in human stem cell-based disease modeling and precision medicine.

PubMed

Wei, Yu-da; Li, Shuang; Liu, Gai-gai; Zhang, Yong-xian; Ding, Qiu-rong

2015-10-01

Precision medicine emerges as a new approach that takes into account individual variability. The successful conduct of precision medicine requires the use of precise disease models. Human pluripotent stem cells (hPSCs), as well as adult stem cells, can be differentiated into a variety of human somatic cell types that can be used for research and drug screening. The development of genome editing technology over the past few years, especially the CRISPR/Cas system, has made it feasible to precisely and efficiently edit the genetic background. Therefore, disease modeling by using a combination of human stem cells and genome editing technology has offered a new platform to generate " personalized " disease models, which allow the study of the contribution of individual genetic variabilities to disease progression and the development of precise treatments. In this review, recent advances in the use of genome editing in human stem cells and the generation of stem cell models for rare diseases and cancers are discussed.

Human Development Theories: A Comparison of Classic Human Development Theorists and the Implications for a Model of Developmental Social Interaction.

ERIC Educational Resources Information Center

Ollhoff, Jim

This paper explores several theories of human development, with particular attention to the development of social interaction. Part 1 compares and contrasts major developmental theories, including those of Freud, Erikson, Piaget, Kohlberg, Kegan, Fowler, and Selman. From birth to 1 year, infants are laying the foundation that will guide their…

The contributions of human factors on human error in Malaysia aviation maintenance industries

NASA Astrophysics Data System (ADS)

Padil, H.; Said, M. N.; Azizan, A.

2018-05-01

Aviation maintenance is a multitasking activity in which individuals perform varied tasks under constant pressure to meet deadlines as well as challenging work conditions. These situational characteristics combined with human factors can lead to various types of human related errors. The primary objective of this research is to develop a structural relationship model that incorporates human factors, organizational factors, and their impact on human errors in aviation maintenance. Towards that end, a questionnaire was developed which was administered to Malaysian aviation maintenance professionals. Structural Equation Modelling (SEM) approach was used in this study utilizing AMOS software. Results showed that there were a significant relationship of human factors on human errors and were tested in the model. Human factors had a partial effect on organizational factors while organizational factors had a direct and positive impact on human errors. It was also revealed that organizational factors contributed to human errors when coupled with human factors construct. This study has contributed to the advancement of knowledge on human factors effecting safety and has provided guidelines for improving human factors performance relating to aviation maintenance activities and could be used as a reference for improving safety performance in the Malaysian aviation maintenance companies.

DEVELOPMENT OF 3-D COMPUTER MODELS OF HUMAN LUNG MORPHOLOGY FOR IMPROOVED RISK ASSESSMENT OF INHALED PARTICULATE MATTER

EPA Science Inventory

DEVELOPMENT OF 3-D COMPUTER MODELS OF HUMAN LUNG MORPHOLOGY FOR IMPROVED RISK ASSESSMENT OF INHALED PARTICULATE MATTER

Jeffry D. Schroeter, Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC 27599; Ted B. Martonen, ETD, NHEERL, USEPA, RTP, NC 27711; Do...

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.

Human pluripotent stem cell models of Fragile X syndrome.

PubMed

Bhattacharyya, Anita; Zhao, Xinyu

2016-06-01

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism. The causal mutation in FXS is a trinucleotide CGG repeat expansion in the FMR1 gene that leads to human specific epigenetic silencing and loss of Fragile X Mental Retardation Protein (FMRP) expression. Human pluripotent stem cells (PSCs), including human embryonic stem cells (ESCs) and particularly induced PSCs (iPSCs), offer a model system to reveal cellular and molecular events underlying human neuronal development and function in FXS. Human FXS PSCs have been established and have provided insight into the epigenetic silencing of the FMR1 gene as well as aspects of neuronal development. Copyright © 2015 Elsevier Inc. All rights reserved.

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 during the real-time testing were investigated in the human modeling analyses. In some cases, the opposite was true where preliminary human modeling analyses provided the design engineers with critical issues that needed to be addressed further. This extensive approach provided an effective means to fully address ergonomic design considerations and accurately identify critical issues.

A mechanical model predicts morphological abnormalities in the developing human brain

NASA Astrophysics Data System (ADS)

Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

2014-07-01

The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism.

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 ...

Rational Design of Mouse Models for Cancer Research.

PubMed

Landgraf, Marietta; McGovern, Jacqui A; Friedl, Peter; Hutmacher, Dietmar W

2018-03-01

The laboratory mouse is widely considered as a valid and affordable model organism to study human disease. Attempts to improve the relevance of murine models for the investigation of human pathologies led to the development of various genetically engineered, xenograft and humanized mouse models. Nevertheless, most preclinical studies in mice suffer from insufficient predictive value when compared with cancer biology and therapy response of human patients. We propose an innovative strategy to improve the predictive power of preclinical cancer models. Combining (i) genomic, tissue engineering and regenerative medicine approaches for rational design of mouse models with (ii) rapid prototyping and computational benchmarking against human clinical data will enable fast and nonbiased validation of newly generated models. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cognition in Space Workshop. 1; Metrics and Models

NASA Technical Reports Server (NTRS)

Woolford, Barbara; Fielder, Edna

2005-01-01

"Cognition in Space Workshop I: Metrics and Models" was the first in a series of workshops sponsored by NASA to develop an integrated research and development plan supporting human cognition in space exploration. The workshop was held in Chandler, Arizona, October 25-27, 2004. The participants represented academia, government agencies, and medical centers. This workshop addressed the following goal of the NASA Human System Integration Program for Exploration: to develop a program to manage risks due to human performance and human error, specifically ones tied to cognition. Risks range from catastrophic error to degradation of efficiency and failure to accomplish mission goals. Cognition itself includes memory, decision making, initiation of motor responses, sensation, and perception. Four subgoals were also defined at the workshop as follows: (1) NASA needs to develop a human-centered design process that incorporates standards for human cognition, human performance, and assessment of human interfaces; (2) NASA needs to identify and assess factors that increase risks associated with cognition; (3) NASA needs to predict risks associated with cognition; and (4) NASA needs to mitigate risk, both prior to actual missions and in real time. This report develops the material relating to these four subgoals.

Can the silkworm (Bombyx mori) be used as a human disease model?

PubMed

Tabunoki, Hiroko; Bono, Hidemasa; Ito, Katsuhiko; Yokoyama, Takeshi

2016-02-01

Bombyx mori (silkworm) is the most famous lepidopteran in Japan. B. mori has long been used in the silk industry and also as a model insect for agricultural research. In recent years, B. mori has attracted interest in its potential for use in pathological analysis of model animals. For example, the human macular carotenoid transporter was discovered using information of B. mori carotenoid transporter derived from yellow-cocoon strain. The B. mori carotenoid transport system is useful in human studies. To develop a human disease model, we characterized the human homologs of B. mori, and by constructing KAIKO functional annotation pipeline, and to analyze gene expression profile of a unique B. mori mutant strain using microarray analysis. As a result, we identified a novel molecular network involved in Parkinson's disease. Here we describe the potential use of a spontaneous mutant silkworm strain as a human disease model. We also summarize recent progress in the application of genomic information for annotation of human homologs in B. mori. The B. mori mutant will provide a clue to pathological mechanisms, and the findings will be helpful for the development of therapies and for medical drug discovery.

Formulation development of retrocyclin 1 analog RC-101 as an anti-HIV vaginal microbicide product.

PubMed

Sassi, A B; Cost, M R; Cole, A L; Cole, A M; Patton, D L; Gupta, P; Rohan, L C

2011-05-01

RC-101 is a synthetic microbicide analog of retrocyclin, which has shown in vitro activity against X4 and R5 HIV-1. In an effort to develop a safe and effective RC-101 vaginal microbicide product, we assessed safety in ex vivo macaque and human models and efficacy using in vitro and ex vivo models. A polyvinyl-alcohol vaginal film containing RC-101 (100 μg/film) was developed. Formulation assessment was conducted by evaluating disintegration, drug content, mechanical properties, and stability. Efficacy was evaluated by in vitro peripheral blood mononuclear cells (PBMC) assay and ex vivo human ectocervical tissue explant model. Ex vivo safety studies were conducted by exposing RC-101 to an excised monkey reproductive tract and excised human ectocervical tissue. RC-101 100 μg films were shown to be safe to human and monkey tissue and effective against HIV-1 in vitro and ex vivo in human ectocervical tissue. The 90% inhibitory concentration (IC90) for RC-101 films at 2,000 μg (IC90=57.5 μM) using an ex vivo model was 10-fold higher than the IC90 observed using an in vitro model (IC90=5.0 μM). RC-101 films were stable for 1 month at 25°C, with in vitro bioactivity maintained for up to 6 months. RC-101 was developed in a quick-dissolve film formulation that was shown to be safe in an ex vivo model and effective in in vitro and ex vivo models. RC-101 film formulations were shown to maintain bioactivity for a period of 6 months. Findings from the present study contribute to the development of a safe and effective topical microbicide product.

The use of analytical models in human-computer interface design

NASA Technical Reports Server (NTRS)

Gugerty, Leo

1991-01-01

Some of the many analytical models in human-computer interface design that are currently being developed are described. The usefulness of analytical models for human-computer interface design is evaluated. Can the use of analytical models be recommended to interface designers? The answer, based on the empirical research summarized here, is: not at this time. There are too many unanswered questions concerning the validity of models and their ability to meet the practical needs of design organizations.

Cougar response to a gradient of human development

DOE PAGES

Maletzke, Benjamin; Kertson, Brian; Swanson, Mark; ...

2017-07-07

Human populations continue to increase and transform Earth's ecosystems. For large carnivores, human development reduces habitat abundance, alters predator–prey dynamics, and increases the risk of mortality, which may threaten the viability of many populations. To investigate how the cougar ( Puma concolor) responds to a gradient of human development in four areas in Washington, USA, we used utilization distributions, county tax parcel data, Weibull modeling analysis, and multiple comparison techniques. Cougars used wildland areas the majority of the time (79% ± 2%, n = 112 cougars), with use decreasing as housing densities increased. When present in human-developed areas in easternmore » Washington, 99% of the habitat that cougars used had housing densities ≤76.5 residences/km 2, which was <846.0 residences/km 2 observed in western Washington ( P < 0.01). Cougars used areas in western Washington with greater housing density likely because of the clustered nature of housing developments, the connectivity with greenbelts and forested corridors, and security cover of dense maritime vegetation. Our findings suggest a consistent, albeit nuanced response by cougars to human development that may be used by wildlife managers, landscape planners, and environmental educators to guide and enhance their efforts to minimize the impacts of human development on cougars and reduce the potential for conflicts with people. In conclusion, our model may also provide guidance for thresholds of human development for other adaptable large carnivores.« less

Cougar response to a gradient of human development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maletzke, Benjamin; Kertson, Brian; Swanson, Mark

Human populations continue to increase and transform Earth's ecosystems. For large carnivores, human development reduces habitat abundance, alters predator–prey dynamics, and increases the risk of mortality, which may threaten the viability of many populations. To investigate how the cougar ( Puma concolor) responds to a gradient of human development in four areas in Washington, USA, we used utilization distributions, county tax parcel data, Weibull modeling analysis, and multiple comparison techniques. Cougars used wildland areas the majority of the time (79% ± 2%, n = 112 cougars), with use decreasing as housing densities increased. When present in human-developed areas in easternmore » Washington, 99% of the habitat that cougars used had housing densities ≤76.5 residences/km 2, which was <846.0 residences/km 2 observed in western Washington ( P < 0.01). Cougars used areas in western Washington with greater housing density likely because of the clustered nature of housing developments, the connectivity with greenbelts and forested corridors, and security cover of dense maritime vegetation. Our findings suggest a consistent, albeit nuanced response by cougars to human development that may be used by wildlife managers, landscape planners, and environmental educators to guide and enhance their efforts to minimize the impacts of human development on cougars and reduce the potential for conflicts with people. In conclusion, our model may also provide guidance for thresholds of human development for other adaptable large carnivores.« less

Screening Vaccine Formulations in Fresh Human Whole Blood.

PubMed

Hakimi, Jalil; Aboutorabian, Sepideh; To, Frederick; Ausar, Salvador F; Rahman, Nausheen; Brookes, Roger H

2017-01-01

Monitoring the immunological functionality of vaccine formulations is critical for vaccine development. While the traditional approach using established animal models has been relatively effective, the use of animals is costly and cumbersome, and animal models are not always reflective of a human response. The development of a human-based approach would be a major step forward in understanding how vaccine formulations might behave in humans. Here, we describe a platform methodology using fresh human whole blood (hWB) to monitor adjuvant-modulated, antigen-specific responses to vaccine formulations, which is amenable to analysis by standard immunoassays as well as a variety of other analytical techniques.

Advancing coupled human-earth system models: The integrated Earth System Model Project

NASA Astrophysics Data System (ADS)

Thomson, A. M.; Edmonds, J. A.; Collins, W.; Thornton, P. E.; Hurtt, G. C.; Janetos, A. C.; Jones, A.; Mao, J.; Chini, L. P.; Calvin, K. V.; Bond-Lamberty, B. P.; Shi, X.

2012-12-01

As human and biogeophysical models develop, opportunities for connections between them evolve and can be used to advance our understanding of human-earth systems interaction in the context of a changing climate. One such integration is taking place with the Community Earth System Model (CESM) and the Global Change Assessment Model (GCAM). A multi-disciplinary, multi-institution team has succeeded in integrating the GCAM integrated assessment model of human activity into CESM to dynamically represent the feedbacks between changing climate and human decision making, in the context of greenhouse gas mitigation policies. The first applications of this capability have focused on the feedbacks between climate change impacts on terrestrial ecosystem productivity and human decisions affecting future land use change, which are in turn connected to human decisions about energy systems and bioenergy production. These experiments have been conducted in the context of the RCP4.5 scenario, one of four pathways of future radiative forcing being used in CMIP5, which constrains future human-induced greenhouse gas emissions from energy and land activities to stabilize radiative forcing at 4.5 W/m2 (~650 ppm CO2 -eq) by 2100. When this pathway is run in GCAM with the climate feedback on terrestrial productivity from CESM, there are implications for both the land use and energy system changes required for stabilization. Early findings indicate that traditional definitions of radiative forcing used in scenario development are missing a critical component of the biogeophysical consequences of land use change and their contribution to effective radiative forcing. Initial full coupling of the two global models has important implications for how climate impacts on terrestrial ecosystems changes the dynamics of future land use change for agriculture and forestry, particularly in the context of a climate mitigation policy designed to reduce emissions from land use as well as energy systems. While these initial experiments have relied on offline coupling methodologies, current and future experiments are utilizing a single model code developed to integrate GCAM into CESM as a component of the land model. This unique capability facilitates many new applications to scientific questions arising from human and biogeophysical systems interaction. Future developments will further integrate the energy system decisions and greenhouse gas emissions as simulated in GCAM with the appropriate climate and land system components of CESM.

Development of Newborn and Infant Vaccines

PubMed Central

Sanchez-Schmitz, Guzman; Levy, Ofer

2014-01-01

Vaccines for early-life immunization are a crucial biomedical intervention to reduce global morbidity and mortality, yet their developmental path has been largely ad hoc, empiric, and inconsistent. Immune responses of human newborns and infants are distinct and cannot be predicted from those of human adults or animal models. Therefore, understanding and modeling age-specific human immune responses will be vital to the rational design and development of safe and effective vaccines for newborns and infants. PMID:21734174

Human iPSC-derived neurons and lymphoblastoid cells for personalized medicine research in neuropsychiatric disorders.

PubMed

Gurwitz, David

2016-09-01

The development and clinical implementation of personalized medicine crucially depends on the availability of high-quality human biosamples; animal models, although capable of modeling complex human diseases, cannot reflect the large variation in the human genome, epigenome, transcriptome, proteome, and metabolome. Although the biosamples available from public biobanks that store human tissues and cells may represent the large human diversity for most diseases, these samples are not always sufficient for developing biomarkers for patient-tailored therapies for neuropsychiatric disorders. Postmortem human tissues are available from many biobanks; nevertheless, collections of neuronal human cells from large patient cohorts representing the human diversity remain scarce. Two tools are gaining popularity for personalized medicine research on neuropsychiatric disorders: human induced pluripotent stem cell-derived neurons and human lymphoblastoid cell lines. This review examines and contrasts the advantages and limitations of each tool for personalized medicine research.

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

Computational analysis of the human sinus node action potential: model development and effects of mutations

PubMed Central

Fabbri, Alan; Fantini, Matteo; Wilders, Ronald

2017-01-01

Key points We constructed a comprehensive mathematical model of the spontaneous electrical activity of a human sinoatrial node (SAN) pacemaker cell, starting from the recent Severi–DiFrancesco model of rabbit SAN cells.Our model is based on electrophysiological data from isolated human SAN pacemaker cells and closely matches the action potentials and calcium transient that were recorded experimentally.Simulated ion channelopathies explain the clinically observed changes in heart rate in corresponding mutation carriers, providing an independent qualitative validation of the model.The model shows that the modulatory role of the ‘funny current’ (I f) in the pacing rate of human SAN pacemaker cells is highly similar to that of rabbit SAN cells, despite its considerably lower amplitude.The model may prove useful in the design of experiments and the development of heart‐rate modulating drugs. Abstract The sinoatrial node (SAN) is the normal pacemaker of the mammalian heart.  Over several decades, a large amount of data on the ionic mechanisms underlying the spontaneous electrical activity of SAN pacemaker cells has been obtained, mostly in experiments on single cells isolated from rabbit SAN. This wealth of data has allowed the development of mathematical models of the electrical activity of rabbit SAN pacemaker cells. The present study aimed to construct a comprehensive model of the electrical activity of a human SAN pacemaker cell using recently obtained electrophysiological data from human SAN pacemaker cells.  We based our model on the recent Severi–DiFrancesco model of a rabbit SAN pacemaker cell. The action potential and calcium transient of the resulting model are close to the experimentally recorded values. The model has a much smaller ‘funny current’ (I f) than do rabbit cells, although its modulatory role is highly similar. Changes in pacing rate upon the implementation of mutations associated with sinus node dysfunction agree with the clinical observations. This agreement holds for both loss‐of‐function and gain‐of‐function mutations in the HCN4, SCN5A and KCNQ1 genes, underlying ion channelopathies in I f, fast sodium current and slow delayed rectifier potassium current, respectively. We conclude that our human SAN cell model can be a useful tool in the design of experiments and the development of drugs that aim to modulate heart rate. PMID:28185290

Directional and sectional ride comfort estimation using an integrated human biomechanical-seat foam model

NASA Astrophysics Data System (ADS)

Mohajer, Navid; Abdi, Hamid; Nahavandi, Saeid; Nelson, Kyle

2017-09-01

In the methodology of objective measurement of ride comfort, application of a Human Biomechanical Model (HBM) is valuable for Whole Body Vibration (WBV) analysis. In this study, using a computational Multibody System (MBS) approach, development of a 3D passive HBM for a seated human is considered. For this purpose, the existing MBS-based HBMs of seated human are briefly reviewed first. The Equations of Motion (EoM) for the proposed model are then obtained and the simulation results are shown and compared with idealised ranges of experimental results suggested in the literature. The human-seat interaction is established using a nonlinear vibration model of foam with respect to the sectional behaviour of the seat foam. The developed system is then used for ride comfort estimation offered by a ride dynamic model. The effects of human weight, road class, and vehicle speed on the vibration of the human body segments in different directions are studied. It is shown that the there is a high correlation (more than 99.2%) between the vibration indices of the proposed HBM-foam model and the corresponding ISO 2631 WBV indices. In addition, relevant ISO 2631 indices that show a high correlation with the directional vibration of the head are identified.

Human airway epithelial cell cultures for modeling respiratory syncytial virus infection.

PubMed

Pickles, Raymond J

2013-01-01

Respiratory syncytial virus (RSV) is an important human respiratory pathogen with narrow species tropism. Limited availability of human pathologic specimens during early RSV-induced lung disease and ethical restrictions for RSV challenge studies in the lower airways of human volunteers has slowed our understanding of how RSV causes airway disease and greatly limited the development of therapeutic strategies for reducing RSV disease burden. Our current knowledge of RSV infection and pathology is largely based on in vitro studies using nonpolarized epithelial cell-lines grown on plastic or in vivo studies using animal models semipermissive for RSV infection. Although these models have revealed important aspects of RSV infection, replication, and associated inflammatory responses, these models do not broadly recapitulate the early interactions and potential consequences of RSV infection of the human columnar airway epithelium in vivo. In this chapter, the pro et contra of in vitro models of human columnar airway epithelium and their usefulness in respiratory virus pathogenesis and vaccine development studies will be discussed. The use of such culture models to predict characteristics of RSV infection and the correlation of these findings to the human in vivo situation will likely accelerate our understanding of RSV pathogenesis potentially identifying novel strategies for limiting the severity of RSV-associated airway disease.

Age-dependent Fourier model of the shape of the isolated ex vivo human crystalline lens.

PubMed

Urs, Raksha; Ho, Arthur; Manns, Fabrice; Parel, Jean-Marie

2010-06-01

To develop an age-dependent mathematical model of the zero-order shape of the isolated ex vivo human crystalline lens, using one mathematical function, that can be subsequently used to facilitate the development of other models for specific purposes such as optical modeling and analytical and numerical modeling of the lens. Profiles of whole isolated human lenses (n=30) aged 20-69, were measured from shadow-photogrammetric images. The profiles were fit to a 10th-order Fourier series consisting of cosine functions in polar-co-ordinate system that included terms for tilt and decentration. The profiles were corrected using these terms and processed in two ways. In the first, each lens was fit to a 10th-order Fourier series to obtain thickness and diameter, while in the second, all lenses were simultaneously fit to a Fourier series equation that explicitly include linear terms for age to develop an age-dependent mathematical model for the whole lens shape. Thickness and diameter obtained from Fourier series fits exhibited high correlation with manual measurements made from shadow-photogrammetric images. The root-mean-squared-error of the age-dependent fit was 205 microm. The age-dependent equations provide a reliable lens model for ages 20-60 years. The contour of the whole human crystalline lens can be modeled with a Fourier series. Shape obtained from the age-dependent model described in this paper can be used to facilitate the development of other models for specific purposes such as optical modeling and analytical and numerical modeling of the lens. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Rabbit and Nonhuman Primate Models of Toxin-Targeting Human Anthrax Vaccines

PubMed Central

Phipps, Andrew J.; Premanandan, Christopher; Barnewall, Roy E.; Lairmore, Michael D.

2004-01-01

The intentional use of Bacillus anthracis, the etiological agent of anthrax, as a bioterrorist weapon in late 2001 made our society acutely aware of the importance of developing, testing, and stockpiling adequate countermeasures against biological attacks. Biodefense vaccines are an important component of our arsenal to be used during a biological attack. However, most of the agents considered significant threats either have been eradicated or rarely infect humans alive today. As such, vaccine efficacy cannot be determined in human clinical trials but must be extrapolated from experimental animal models. This article reviews the efficacy and immunogenicity of human anthrax vaccines in well-defined animal models and the progress toward developing a rugged immunologic correlate of protection. The ongoing evaluation of human anthrax vaccines will be dependent on animal efficacy data in the absence of human efficacy data for licensure by the U.S. Food and Drug Administration. PMID:15590776

Towards using musculoskeletal models for intelligent control of physically assistive robots.

PubMed

Carmichael, Marc G; Liu, Dikai

2011-01-01

With the increasing number of robots being developed to physically assist humans in tasks such as rehabilitation and assistive living, more intelligent and personalized control systems are desired. In this paper we propose the use of a musculoskeletal model to estimate the strength of the user, from which information can be utilized to improve control schemes in which robots physically assist humans. An optimization model is developed utilizing a musculoskeletal model to estimate human strength in a specified dynamic state. Results of this optimization as well as methods of using it to observe muscle-based weaknesses in task space are presented. Lastly potential methods and problems in incorporating this model into a robot control system are discussed.

Micropatterned coculture of primary human hepatocytes and supportive cells for the study of hepatotropic pathogens.

PubMed

March, Sandra; Ramanan, Vyas; Trehan, Kartik; Ng, Shengyong; Galstian, Ani; Gural, Nil; Scull, Margaret A; Shlomai, Amir; Mota, Maria M; Fleming, Heather E; Khetani, Salman R; Rice, Charles M; Bhatia, Sangeeta N

2015-12-01

The development of therapies and vaccines for human hepatropic pathogens requires robust model systems that enable the study of host-pathogen interactions. However, in vitro liver models of infection typically use either hepatoma cell lines that exhibit aberrant physiology or primary human hepatocytes in culture conditions in which they rapidly lose their hepatic phenotype. To achieve stable and robust in vitro primary human hepatocyte models, we developed micropatterned cocultures (MPCCs), which consist of primary human hepatocytes organized into 2D islands that are surrounded by supportive fibroblast cells. By using this system, which can be established over a period of days, and maintained over multiple weeks, we demonstrate how to recapitulate in vitro hepatic life cycles for the hepatitis B and C viruses and the Plasmodium pathogens P. falciparum and P. vivax. The MPCC platform can be used to uncover aspects of host-pathogen interactions, and it has the potential to be used for drug and vaccine development.

Animal Models of Human Granulocyte Diseases

PubMed Central

Schäffer, Alejandro A.; Klein, Christoph

2012-01-01

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

Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models.

PubMed

Smits, Jos P H; Niehues, Hanna; Rikken, Gijs; van Vlijmen-Willems, Ivonne M J J; van de Zande, Guillaume W H J F; Zeeuwen, Patrick L J M; Schalkwijk, Joost; van den Bogaard, Ellen H

2017-09-19

The strong societal urge to reduce the use of experimental animals, and the biological differences between rodent and human skin, have led to the development of alternative models for healthy and diseased human skin. However, the limited availability of primary keratinocytes to generate such models hampers large-scale implementation of skin models in biomedical, toxicological, and pharmaceutical research. Immortalized cell lines may overcome these issues, however, few immortalized human keratinocyte cell lines are available and most do not form a fully stratified epithelium. In this study we compared two immortalized keratinocyte cell lines (N/TERT1, N/TERT2G) to human primary keratinocytes based on epidermal differentiation, response to inflammatory mediators, and the development of normal and inflammatory human epidermal equivalents (HEEs). Stratum corneum permeability, epidermal morphology, and expression of epidermal differentiation and host defence genes and proteins in N/TERT-HEE cultures was similar to that of primary human keratinocytes. We successfully generated N/TERT-HEEs with psoriasis or atopic dermatitis features and validated these models for drug-screening purposes. We conclude that the N/TERT keratinocyte cell lines are useful substitutes for primary human keratinocytes thereby providing a biologically relevant, unlimited cell source for in vitro studies on epidermal biology, inflammatory skin disease pathogenesis and therapeutics.

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 ...

Acquiring neural signals for developing a perception and cognition model

NASA Astrophysics Data System (ADS)

Li, Wei; Li, Yunyi; Chen, Genshe; Shen, Dan; Blasch, Erik; Pham, Khanh; Lynch, Robert

2012-06-01

The understanding of how humans process information, determine salience, and combine seemingly unrelated information is essential to automated processing of large amounts of information that is partially relevant, or of unknown relevance. Recent neurological science research in human perception, and in information science regarding contextbased modeling, provides us with a theoretical basis for using a bottom-up approach for automating the management of large amounts of information in ways directly useful for human operators. However, integration of human intelligence into a game theoretic framework for dynamic and adaptive decision support needs a perception and cognition model. For the purpose of cognitive modeling, we present a brain-computer-interface (BCI) based humanoid robot system to acquire brainwaves during human mental activities of imagining a humanoid robot-walking behavior. We use the neural signals to investigate relationships between complex humanoid robot behaviors and human mental activities for developing the perception and cognition model. The BCI system consists of a data acquisition unit with an electroencephalograph (EEG), a humanoid robot, and a charge couple CCD camera. An EEG electrode cup acquires brainwaves from the skin surface on scalp. The humanoid robot has 20 degrees of freedom (DOFs); 12 DOFs located on hips, knees, and ankles for humanoid robot walking, 6 DOFs on shoulders and arms for arms motion, and 2 DOFs for head yaw and pitch motion. The CCD camera takes video clips of the human subject's hand postures to identify mental activities that are correlated to the robot-walking behaviors. We use the neural signals to investigate relationships between complex humanoid robot behaviors and human mental activities for developing the perception and cognition model.

A Temporal Chromatin Signature in Human Embryonic Stem Cells Identifies Regulators of Cardiac Development

PubMed Central

Paige, Sharon L.; Thomas, Sean; Stoick-Cooper, Cristi L.; Wang, Hao; Maves, Lisa; Sandstrom, Richard; Pabon, Lil; Reinecke, Hans; Pratt, Gabriel; Keller, Gordon; Moon, Randall T.; Stamatoyannopoulos, John; Murry, Charles E.

2012-01-01

Summary Directed differentiation of human embryonic stem cells (ESCs) into cardiovascular cells provides a model for studying molecular mechanisms of human cardiovascular development. Though it is known that chromatin modification patterns in ESCs differ markedly from those in lineage-committed progenitors and differentiated cells, the temporal dynamics of chromatin alterations during differentiation along a defined lineage have not been studied. We show that differentiation of human ESCs into cardiovascular cells is accompanied by programmed temporal alterations in chromatin structure that distinguish key regulators of cardiovascular development from other genes. We used this temporal chromatin signature to identify regulators of cardiac development, including the homeobox gene MEIS2. We demonstrate using the zebrafish model that MEIS2 is critical for proper heart tube formation and subsequent cardiac looping. Temporal chromatin signatures should be broadly applicable to other models of stem cell differentiation to identify regulators and provide key insights into major developmental decisions. PMID:22981225

Developing Library GIS Services for Humanities and Social Science: An Action Research Approach

ERIC Educational Resources Information Center

Kong, Ningning; Fosmire, Michael; Branch, Benjamin Dewayne

2017-01-01

In the academic libraries' efforts to support digital humanities and social science, GIS service plays an important role. However, there is no general service model existing about how libraries can develop GIS services to best engage with digital humanities and social science. In this study, we adopted the action research method to develop and…

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.

HSC extrinsic sex-related and intrinsic autoimmune disease-related human B-cell variation is recapitulated in humanized mice.

PubMed

Borsotti, Chiara; Danzl, Nichole M; Nauman, Grace; Hölzl, Markus A; French, Clare; Chavez, Estefania; Khosravi-Maharlooei, Mohsen; Glauzy, Salome; Delmotte, Fabien R; Meffre, Eric; Savage, David G; Campbell, Sean R; Goland, Robin; Greenberg, Ellen; Bi, Jing; Satwani, Prakash; Yang, Suxiao; Bathon, Joan; Winchester, Robert; Sykes, Megan

2017-10-24

B cells play a major role in antigen presentation and antibody production in the development of autoimmune diseases, and some of these diseases disproportionally occur in females. Moreover, immune responses tend to be stronger in female vs male humans and mice. Because it is challenging to distinguish intrinsic from extrinsic influences on human immune responses, we used a personalized immune (PI) humanized mouse model, in which immune systems were generated de novo from adult human hematopoietic stem cells (HSCs) in immunodeficient mice. We assessed the effect of recipient sex and of donor autoimmune diseases (type 1 diabetes [T1D] and rheumatoid arthritis [RA]) on human B-cell development in PI mice. We observed that human B-cell levels were increased in female recipients regardless of the source of human HSCs or the strain of immunodeficient recipient mice. Moreover, mice injected with T1D- or RA-derived HSCs displayed B-cell abnormalities compared with healthy control HSC-derived mice, including altered B-cell levels, increased proportions of mature B cells and reduced CD19 expression. Our study revealed an HSC-extrinsic effect of recipient sex on human B-cell reconstitution. Moreover, the PI humanized mouse model revealed HSC-intrinsic defects in central B-cell tolerance that recapitulated those in patients with autoimmune diseases. These results demonstrate the utility of humanized mouse models as a tool to better understand human immune cell development and regulation.

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. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Quantifying Astronaut Tasks: Robotic Technology and Future Space Suit Design

NASA Technical Reports Server (NTRS)

Newman, Dava

2003-01-01

The primary aim of this research effort was to advance the current understanding of astronauts' capabilities and limitations in space-suited EVA by developing models of the constitutive and compatibility relations of a space suit, based on experimental data gained from human test subjects as well as a 12 degree-of-freedom human-sized robot, and utilizing these fundamental relations to estimate a human factors performance metric for space suited EVA work. The three specific objectives are to: 1) Compile a detailed database of torques required to bend the joints of a space suit, using realistic, multi- joint human motions. 2) Develop a mathematical model of the constitutive relations between space suit joint torques and joint angular positions, based on experimental data and compare other investigators' physics-based models to experimental data. 3) Estimate the work envelope of a space suited astronaut, using the constitutive and compatibility relations of the space suit. The body of work that makes up this report includes experimentation, empirical and physics-based modeling, and model applications. A detailed space suit joint torque-angle database was compiled with a novel experimental approach that used space-suited human test subjects to generate realistic, multi-joint motions and an instrumented robot to measure the torques required to accomplish these motions in a space suit. Based on the experimental data, a mathematical model is developed to predict joint torque from the joint angle history. Two physics-based models of pressurized fabric cylinder bending are compared to experimental data, yielding design insights. The mathematical model is applied to EVA operations in an inverse kinematic analysis coupled to the space suit model to calculate the volume in which space-suited astronauts can work with their hands, demonstrating that operational human factors metrics can be predicted from fundamental space suit information.

integrated Earth System Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, Andew; Di Vittorio, Alan; Collins, William

The integrated Earth system model (iESM) has been developed as a new tool for projecting the joint human/climate system. The iESM is based upon coupling an integrated assessment model (IAM) and an Earth system model (ESM) into a common modeling infrastructure. IAMs are the primary tool for describing the human-Earth system, including the sources of global greenhouse gases (GHGs) and short-lived species (SLS), land use and land cover change (LULCC), and other resource-related drivers of anthropogenic climate change. ESMs are the primary scientific tools for examining the physical, chemical, and biogeochemical impacts of human-induced changes to the climate system. Themore » iESM project integrates the economic and human-dimension modeling of an IAM and a fully coupled ESM within a single simulation system while maintaining the separability of each model if needed. Both IAM and ESM codes are developed and used by large communities and have been extensively applied in recent national and international climate assessments. By introducing heretofore-omitted feedbacks between natural and societal drivers, we can improve scientific understanding of the human-Earth system dynamics. Potential applications include studies of the interactions and feedbacks leading to the timing, scale, and geographic distribution of emissions trajectories and other human influences, corresponding climate effects, and the subsequent impacts of a changing climate on human and natural systems.« less

Evaluation of an intact, an ACL-deficient, and a reconstructed human knee joint finite element model.

PubMed

Vairis, Achilles; Stefanoudakis, George; Petousis, Markos; Vidakis, Nectarios; Tsainis, Andreas-Marios; Kandyla, Betina

2016-02-01

The human knee joint has a three-dimensional geometry with multiple body articulations that produce complex mechanical responses under loads that occur in everyday life and sports activities. Understanding the complex mechanical interactions of these load-bearing structures is of use when the treatment of relevant diseases is evaluated and assisting devices are designed. The anterior cruciate ligament (ACL) in the knee is one of four main ligaments that connects the femur to the tibia and is often torn during sudden twisting motions, resulting in knee instability. The objective of this work is to study the mechanical behavior of the human knee joint and evaluate the differences in its response for three different states, i.e., intact, ACL-deficient, and surgically treated (reconstructed) knee. The finite element models corresponding to these states were developed. For the reconstructed model, a novel repair device was developed and patented by the author in previous work. Static load cases were applied, as have already been presented in a previous work, in order to compare the calculated results produced by the two models the ACL-deficient and the surgically reconstructed knee joint, under the exact same loading conditions. Displacements were calculated in different directions for the load cases studied and were found to be very close to those from previous modeling work and were in good agreement with experimental data presented in literature. The developed finite element model for both the intact and the ACL-deficient human knee joint is a reliable tool to study the kinematics of the human knee, as results of this study show. In addition, the reconstructed human knee joint model had kinematic behavior similar to the intact knee joint, showing that such reconstruction devices can restore human knee stability to an adequate extent.

Building Futurism into the Institution's Strategic Planning and Human Resource Development Model.

ERIC Educational Resources Information Center

Groff, Warren H.

A process for building futurism into the institution's strategic planning and human resource development model is described. It is an attempt to assist faculty and staff to understand the future and the formulation and revision of professional goals in relation to an image of the future. A conceptual framework about the changing nature of human…

Prioritizing Conservation of Ungulate Calving Resources in Multiple-Use Landscapes

PubMed Central

Dzialak, Matthew R.; Harju, Seth M.; Osborn, Robert G.; Wondzell, John J.; Hayden-Wing, Larry D.; Winstead, Jeffrey B.; Webb, Stephen L.

2011-01-01

Background Conserving animal populations in places where human activity is increasing is an ongoing challenge in many parts of the world. We investigated how human activity interacted with maternal status and individual variation in behavior to affect reliability of spatially-explicit models intended to guide conservation of critical ungulate calving resources. We studied Rocky Mountain elk (Cervus elaphus) that occupy a region where 2900 natural gas wells have been drilled. Methodology/Principal Findings We present novel applications of generalized additive modeling to predict maternal status based on movement, and of random-effects resource selection models to provide population and individual-based inference on the effects of maternal status and human activity. We used a 2×2 factorial design (treatment vs. control) that included elk that were either parturient or non-parturient and in areas either with or without industrial development. Generalized additive models predicted maternal status (parturiency) correctly 93% of the time based on movement. Human activity played a larger role than maternal status in shaping resource use; elk showed strong spatiotemporal patterns of selection or avoidance and marked individual variation in developed areas, but no such pattern in undeveloped areas. This difference had direct consequences for landscape-level conservation planning. When relative probability of use was calculated across the study area, there was disparity throughout 72–88% of the landscape in terms of where conservation intervention should be prioritized depending on whether models were based on behavior in developed areas or undeveloped areas. Model validation showed that models based on behavior in developed areas had poor predictive accuracy, whereas the model based on behavior in undeveloped areas had high predictive accuracy. Conclusions/Significance By directly testing for differences between developed and undeveloped areas, and by modeling resource selection in a random-effects framework that provided individual-based inference, we conclude that: 1) amplified selection or avoidance behavior and individual variation, as responses to increasing human activity, complicate conservation planning in multiple-use landscapes, and 2) resource selection behavior in places where human activity is predictable or less dynamic may provide a more reliable basis from which to prioritize conservation action. PMID:21297866

Systems Approach to Understanding Electromechanical Activity in the Human Heart

PubMed Central

Rudy, Yoram; Ackerman, Michael J.; Bers, Donald M.; Clancy, Colleen E.; Houser, Steven R.; London, Barry; McCulloch, Andrew D.; Przywara, Dennis A.; Rasmusson, Randall L.; Solaro, R. John; Trayanova, Natalia A.; Van Wagoner, David R.; Varró, András; Weiss, James N.; Lathrop, David A.

2010-01-01

The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of cardiologists, cardiac electrophysiologists, cell biophysicists, and computational modelers on August 20 and 21, 2007, in Washington, DC, to advise the NHLBI on new research directions needed to develop integrative approaches to elucidate human cardiac function. The workshop strove to identify limitations in the use of data from nonhuman animal species for elucidation of human electromechanical function/activity and to identify what specific information on ion channel kinetics, calcium handling, and dynamic changes in the intracellular/extracellular milieu is needed from human cardiac tissues to develop more robust computational models of human cardiac electromechanical activity. This article summarizes the workshop discussions and recommendations on the following topics: (1) limitations of animal models and differences from human electrophysiology, (2) modeling ion channel structure/function in the context of whole-cell electrophysiology, (3) excitation–contraction coupling and regulatory pathways, (4) whole-heart simulations of human electromechanical activity, and (5) what human data are currently needed and how to obtain them. The recommendations can be found on the NHLBI Web site at http://www.nhlbi.nih.gov/meetings/workshops/electro.htm. PMID:18779456

Genome-scale modeling of human metabolism - a systems biology approach.

PubMed

Mardinoglu, Adil; Gatto, Francesco; Nielsen, Jens

2013-09-01

Altered metabolism is linked to the appearance of various human diseases and a better understanding of disease-associated metabolic changes may lead to the identification of novel prognostic biomarkers and the development of new therapies. Genome-scale metabolic models (GEMs) have been employed for studying human metabolism in a systematic manner, as well as for understanding complex human diseases. In the past decade, such metabolic models - one of the fundamental aspects of systems biology - have started contributing to the understanding of the mechanistic relationship between genotype and phenotype. In this review, we focus on the construction of the Human Metabolic Reaction database, the generation of healthy cell type- and cancer-specific GEMs using different procedures, and the potential applications of these developments in the study of human metabolism and in the identification of metabolic changes associated with various disorders. We further examine how in silico genome-scale reconstructions can be employed to simulate metabolic flux distributions and how high-throughput omics data can be analyzed in a context-dependent fashion. Insights yielded from this mechanistic modeling approach can be used for identifying new therapeutic agents and drug targets as well as for the discovery of novel biomarkers. Finally, recent advancements in genome-scale modeling and the future challenge of developing a model of whole-body metabolism are presented. The emergent contribution of GEMs to personalized and translational medicine is also discussed. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells

DTIC Science & Technology

2014-10-01

AD_________________ Award Number: W81XWH-13-1-0325 TITLE: Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using ...Genetically Engineered Mouse Models and Human Circulating Tumor Cells PRINCIPAL INVESTIGATOR: Jeffrey Engelman MD PhD CONTRACTING ORGANIZATION ...Novel Therapeutic Approaches in Small Cell Lung 5a. CONTRACT NUMBER W81XWH-13-1-0325 Carcinoma Using Genetically Engineered Mouse Models and 5b

Development and validation of a human biomechanical model for rib fracture and thorax injuries in blunt impact.

PubMed

Cai, Zhihua; Lan, Fengchong; Chen, Jiqing

2015-07-01

From 1990 to approximately 50,000-120,000 people die annually of road traffic accidents in China. Traffic accidents are the main cause of death of Chinese adults aged 15-45 years. This study aimed to determine the biomechanical response and injury tolerance of the human body in traffic accidents. The subject was a 35-year-old male with a height of 170 cm, weight of 70 kg and Chinese characteristics at the 50th percentile. Geometry was generated by computed tomography and magnetic resonance imaging. A human-body biomechanical model was then developed. The model featured in great detail the main anatomical characteristics of skeletal tissues, soft tissues and internal organs, including the head, neck, shoulder, thoracic cage, abdomen, spine, pelvis, pleurae and lungs, heart, aorta, arms, legs, and other muscle tissues and skeletons. The material properties of all tissues in the human body model were obtained from the literature. Material properties were developed in the LS-DYNA code to simulate the mechanical behaviour of the biological tissues in the human body. The model was validated against cadaver responses to frontal and side impact. The predicted model response reasonably agreed with the experimental data, and the model can further be used to evaluate thoracic injury in real-world crashes. We believe that the transportation industry can use numerical models in the future to simultaneously reduce physical testing and improve automotive safety.

Development of an errorable car-following driver model

NASA Astrophysics Data System (ADS)

Yang, H.-H.; Peng, H.

2010-06-01

An errorable car-following driver model is presented in this paper. An errorable driver model is one that emulates human driver's functions and can generate both nominal (error-free), as well as devious (with error) behaviours. This model was developed for evaluation and design of active safety systems. The car-following data used for developing and validating the model were obtained from a large-scale naturalistic driving database. The stochastic car-following behaviour was first analysed and modelled as a random process. Three error-inducing behaviours were then introduced. First, human perceptual limitation was studied and implemented. Distraction due to non-driving tasks was then identified based on the statistical analysis of the driving data. Finally, time delay of human drivers was estimated through a recursive least-square identification process. By including these three error-inducing behaviours, rear-end collisions with the lead vehicle could occur. The simulated crash rate was found to be similar but somewhat higher than that reported in traffic statistics.

Esterase Activity and Intracellular Localization in Reconstructed Human Epidermal Cultured Skin Models.

PubMed

Tokudome, Yoshihiro; Katayanagi, Mishina; Hashimoto, Fumie

2015-06-01

Reconstructed human epidermal culture skin models have been developed for cosmetic and pharmaceutical research. This study evaluated the total and carboxyl esterase activities (i.e., Km and Vmax , respectively) and localization in two reconstructed human epidermal culture skin models (LabCyte EPI-MODEL [Japan Tissue Engineering] and EpiDerm [MatTek/Kurabo]). The usefulness of the reconstruction cultured epidermis was also verified by comparison with human and rat epidermis. Homogenized epidermal samples were fractioned by centrifugation. p-nitrophenyl acetate and 4-methylumbelliferyl acetate were used as substrates of total esterase and carboxyl esterase, respectively. Total and carboxyl esterase activities were present in the reconstructed human epidermal culture skin models and were localized in the cytosol. Moreover, the activities and localization were the same as those in human and rat epidermis. LabCyte EPI-MODEL and EpiDerm are potentially useful for esterase activity prediction in human epidermis.

Esterase Activity and Intracellular Localization in Reconstructed Human Epidermal Cultured Skin Models

PubMed Central

Katayanagi, Mishina; Hashimoto, Fumie

2015-01-01

Background Reconstructed human epidermal culture skin models have been developed for cosmetic and pharmaceutical research. Objective This study evaluated the total and carboxyl esterase activities (i.e., Km and Vmax, respectively) and localization in two reconstructed human epidermal culture skin models (LabCyte EPI-MODEL [Japan Tissue Engineering] and EpiDerm [MatTek/Kurabo]). The usefulness of the reconstruction cultured epidermis was also verified by comparison with human and rat epidermis. Methods Homogenized epidermal samples were fractioned by centrifugation. p-nitrophenyl acetate and 4-methylumbelliferyl acetate were used as substrates of total esterase and carboxyl esterase, respectively. Results Total and carboxyl esterase activities were present in the reconstructed human epidermal culture skin models and were localized in the cytosol. Moreover, the activities and localization were the same as those in human and rat epidermis. Conclusion LabCyte EPI-MODEL and EpiDerm are potentially useful for esterase activity prediction in human epidermis. PMID:26082583

Latest animal models for anti-HIV drug discovery.

PubMed

Sliva, Katja

2015-02-01

HIV research is limited by the fact that lentiviruses are highly species specific. The need for appropriate models to promote research has led to the development of many elaborate surrogate animal models. This review looks at the history of animal models for HIV research. Although natural animal lentivirus infections and chimeric viruses such as chimera between HIV and simian immunodeficiency virus and simian-tropic HIV are briefly discussed, the main focus is on small animal models, including the complex design of the 'humanized' mouse. The review also traces the historic evolution and milestones as well as depicting current models and future prospects for HIV research. HIV research is a complex and challenging task that is highly manpower-, money- and time-consuming. Besides factors such as hypervariability and latency, the lack of appropriate animal models that exhibit and recapitulate the entire infectious process of HIV, is one of the reasons behind the failure to eliminate the lentivirus from the human population. This obstacle has led to the exploitation and further development of many sophisticated surrogate animal models for HIV research. While there is no animal model that perfectly mirrors and mimics HIV infections in humans, there are a variety of host species and viruses that complement each other. Combining the insights from each model, and critically comparing the results obtained with data from human clinical trials should help expand our understanding of HIV pathogenesis and drive future drug development.

A review and assessment of land-use change models: dynamics of space, time, and human choice

Treesearch

Chetan Agarwal; Glen M. Green; J. Morgan Grove; Tom P. Evans; Charles M. Schweik

2002-01-01

A review of different types of land-use change models incorporating human processes. Presents a framework to compare land-use change models in terms of scale (both spatial and temporal) and complexity, and how well they incorporate space, time, and human decisionmaking. Examines a summary set of 250 relevant citations and develops a bibliography of 136 papers. From...

Expression of HLA Class II Molecules in Humanized NOD.Rag1KO.IL2RgcKO Mice Is Critical for Development and Function of Human T and B Cells

PubMed Central

Danner, Rebecca; Chaudhari, Snehal N.; Rosenberger, John; Surls, Jacqueline; Richie, Thomas L.; Brumeanu, Teodor-Doru; Casares, Sofia

2011-01-01

Background Humanized mice able to reconstitute a surrogate human immune system (HIS) can be used for studies on human immunology and may provide a predictive preclinical model for human vaccines prior to clinical trials. However, current humanized mouse models show sub-optimal human T cell reconstitution and limited ability to support immunoglobulin class switching by human B cells. This limitation has been attributed to the lack of expression of Human Leukocyte Antigens (HLA) molecules in mouse lymphoid organs. Recently, humanized mice expressing HLA class I molecules have been generated but showed little improvement in human T cell reconstitution and function of T and B cells. Methods We have generated NOD.Rag1KO.IL2RγcKO mice expressing HLA class II (HLA-DR4) molecules under the I-Ed promoter that were infused as adults with HLA-DR-matched human hematopoietic stem cells (HSC). Littermates lacking expression of HLA-DR4 molecules were used as control. Results HSC-infused HLA-DR4.NOD.Rag1KO.IL-2RγcKO mice developed a very high reconstitution rate (>90%) with long-lived and functional human T and B cells. Unlike previous humanized mouse models reported in the literature and our control mice, the HLA-DR4 expressing mice reconstituted serum levels (natural antibodies) of human IgM, IgG (all four subclasses), IgA, and IgE comparable to humans, and elicited high titers of specific human IgG antibodies upon tetanus toxoid vaccination. Conclusions Our study demonstrates the critical role of HLA class II molecules for development of functional human T cells able to support immunoglobulin class switching and efficiently respond to vaccination. PMID:21611197

Numerical modeling of particle generation from ozone reactions with human-worn clothing in indoor environments

NASA Astrophysics Data System (ADS)

Rai, Aakash C.; Lin, Chao-Hsin; Chen, Qingyan

2015-02-01

Ozone-terpene reactions are important sources of indoor ultrafine particles (UFPs), a potential health hazard for human beings. Humans themselves act as possible sites for ozone-initiated particle generation through reactions with squalene (a terpene) that is present in their skin, hair, and clothing. This investigation developed a numerical model to probe particle generation from ozone reactions with clothing worn by humans. The model was based on particle generation measured in an environmental chamber as well as physical formulations of particle nucleation, condensational growth, and deposition. In five out of the six test cases, the model was able to predict particle size distributions reasonably well. The failure in the remaining case demonstrated the fundamental limitations of nucleation models. The model that was developed was used to predict particle generation under various building and airliner cabin conditions. These predictions indicate that ozone reactions with human-worn clothing could be an important source of UFPs in densely occupied classrooms and airliner cabins. Those reactions could account for about 40% of the total UFPs measured on a Boeing 737-700 flight. The model predictions at this stage are indicative and should be improved further.

Chimeric animal models in human stem cell biology.

PubMed

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

2009-01-01

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

Modeling driver behavior in a cognitive architecture.

PubMed

Salvucci, Dario D

2006-01-01

This paper explores the development of a rigorous computational model of driver behavior in a cognitive architecture--a computational framework with underlying psychological theories that incorporate basic properties and limitations of the human system. Computational modeling has emerged as a powerful tool for studying the complex task of driving, allowing researchers to simulate driver behavior and explore the parameters and constraints of this behavior. An integrated driver model developed in the ACT-R (Adaptive Control of Thought-Rational) cognitive architecture is described that focuses on the component processes of control, monitoring, and decision making in a multilane highway environment. This model accounts for the steering profiles, lateral position profiles, and gaze distributions of human drivers during lane keeping, curve negotiation, and lane changing. The model demonstrates how cognitive architectures facilitate understanding of driver behavior in the context of general human abilities and constraints and how the driving domain benefits cognitive architectures by pushing model development toward more complex, realistic tasks. The model can also serve as a core computational engine for practical applications that predict and recognize driver behavior and distraction.

Developing the Practising Model in Physical Education: An Expository Outline Focusing on Movement Capability

ERIC Educational Resources Information Center

Barker, D. M.; Aggerholm, K.; Standal, O.; Larsson, H.

2018-01-01

Background: Physical educators currently have a number of pedagogical (or curricular) models at their disposal. While existing models have been well-received in educational contexts, these models seek to extend students' capacities within a limited number of "human activities" (Arendt, 1958). The activity of "human practising,"…

SHEDS-Multimedia Model Version 3 (a) Technical Manual; (b) User Guide; and (c) Executable File to Launch SAS Program and Install Model

EPA Science Inventory

Reliable models for assessing human exposures are important for understanding health risks from chemicals. The Stochastic Human Exposure and Dose Simulation model for multimedia, multi-route/pathway chemicals (SHEDS-Multimedia), developed by EPA’s Office of Research and Developm...

Illustrating a Model-Game-Model Paradigm for Using Human Wargames in Analysis

DTIC Science & Technology

2017-02-01

Working Paper Illustrating a Model- Game -Model Paradigm for Using Human Wargames in Analysis Paul K. Davis RAND National Security Research...paper proposes and illustrates an analysis-centric paradigm (model- game -model or what might be better called model-exercise-model in some cases) for...to involve stakehold- ers in model development from the outset. The model- game -model paradigm was illustrated in an application to crisis planning

Construction and application of 3D model sequence to illustrate the development of the human embryo

NASA Astrophysics Data System (ADS)

Mizuta, Shinobu; Kakusho, Koh; Minekura, Yutaka; Minoh, Michihiko; Nakatsu, Tomoko; Shiota, Kohei

2002-05-01

Embryology is one of the basic subjects in medical education, to learn the process of human development especially from fertilization to birth. The shape deformation in the development of human embryo is one of the most important points to be comprehended, but it is difficult to illustrate the deformation by texts, 2D drawings, photographs and so on, because it is extremely complicated. The purpose of our research is to construct a 3D model sequence to illustrate the deformation of human embryo, and to make the model sequence into the teaching materials for medical education. Firstly, 3D images of the specimens of human embryo were acquired using MR microscopy. Next, an initial 3D model sequence was manually modified by comparing with the features of the acquired images under the supervision of medical doctors, because the images were influenced not only by the noise or limitation of resolution in MR image acquisition, but also by the variation of shape depending on the difference of subject. Using the constructed 3D model sequence, CG animations and an interactive VRML system were composed as the teaching materials for embryology. These materials were quite helpful to understand the shape deformation compared with the conventional materials.

The Use of Behavior Models for Predicting Complex Operations

NASA Technical Reports Server (NTRS)

Gore, Brian F.

2010-01-01

Modeling and simulation (M&S) plays an important role when complex human-system notions are being proposed, developed and tested within the system design process. National Aeronautics and Space Administration (NASA) as an agency uses many different types of M&S approaches for predicting human-system interactions, especially when it is early in the development phase of a conceptual design. NASA Ames Research Center possesses a number of M&S capabilities ranging from airflow, flight path models, aircraft models, scheduling models, human performance models (HPMs), and bioinformatics models among a host of other kinds of M&S capabilities that are used for predicting whether the proposed designs will benefit the specific mission criteria. The Man-Machine Integration Design and Analysis System (MIDAS) is a NASA ARC HPM software tool that integrates many models of human behavior with environment models, equipment models, and procedural / task models. The challenge to model comprehensibility is heightened as the number of models that are integrated and the requisite fidelity of the procedural sets are increased. Model transparency is needed for some of the more complex HPMs to maintain comprehensibility of the integrated model performance. This will be exemplified in a recent MIDAS v5 application model and plans for future model refinements will be presented.

Design strategies for human & earth systems modeling to meet emerging multi-scale decision support needs

NASA Astrophysics Data System (ADS)

Spak, S.; Pooley, M.

2012-12-01

The next generation of coupled human and earth systems models promises immense potential and grand challenges as they transition toward new roles as core tools for defining and living within planetary boundaries. New frontiers in community model development include not only computational, organizational, and geophysical process questions, but also the twin objectives of more meaningfully integrating the human dimension and extending applicability to informing policy decisions on a range of new and interconnected issues. We approach these challenges by posing key policy questions that require more comprehensive coupled human and geophysical models, identify necessary model and organizational processes and outputs, and work backwards to determine design criteria in response to these needs. We find that modular community earth system model design must: * seamlessly scale in space (global to urban) and time (nowcasting to paleo-studies) and fully coupled on all component systems * automatically differentiate to provide complete coupled forward and adjoint models for sensitivity studies, optimization applications, and 4DVAR assimilation across Earth and human observing systems * incorporate diagnostic tools to quantify uncertainty in couplings, and in how human activity affects them * integrate accessible community development and application with JIT-compilation, cloud computing, game-oriented interfaces, and crowd-sourced problem-solving We outline accessible near-term objectives toward these goals, and describe attempts to incorporate these design objectives in recent pilot activities using atmosphere-land-ocean-biosphere-human models (WRF-Chem, IBIS, UrbanSim) at urban and regional scales for policy applications in climate, energy, and air quality.

Preclinical models for interrogating drug action in human cancers using Stable Isotope Resolved Metabolomics (SIRM).

PubMed

Lane, Andrew N; Higashi, Richard M; Fan, Teresa W-M

2016-07-01

In this review we compare the advantages and disadvantages of different model biological systems for determining the metabolic functions of cells in complex environments, how they may change in different disease states, and respond to therapeutic interventions. All preclinical drug-testing models have advantages and drawbacks. We compare and contrast established cell, organoid and animal models with ex vivo organ or tissue culture and in vivo human experiments in the context of metabolic readout of drug efficacy. As metabolism reports directly on the biochemical state of cells and tissues, it can be very sensitive to drugs and/or other environmental changes. This is especially so when metabolic activities are probed by stable isotope tracing methods, which can also provide detailed mechanistic information on drug action. We have developed and been applying Stable Isotope-Resolved Metabolomics (SIRM) to examine metabolic reprogramming of human lung cancer cells in monoculture, in mouse xenograft/explant models, and in lung cancer patients in situ (Lane et al. 2011; T. W. Fan et al. 2011; T. W-M. Fan et al. 2012; T. W. Fan et al. 2012; Xie et al. 2014b; Ren et al. 2014a; Sellers et al. 2015b). We are able to determine the influence of the tumor microenvironment using these models. We have now extended the range of models to fresh human tissue slices, similar to those originally described by O. Warburg (Warburg 1923), which retain the native tissue architecture and heterogeneity with a paired benign versus cancer design under defined cell culture conditions. This platform offers an unprecedented human tissue model for preclinical studies on metabolic reprogramming of human cancer cells in their tissue context, and response to drug treatment (Xie et al. 2014a). As the microenvironment of the target human tissue is retained and individual patient's response to drugs is obtained, this platform promises to transcend current limitations of drug selection for clinical trials or treatments. Development of ex vivo human tissue and animal models with humanized organs including bone marrow and liver show considerable promise for analyzing drug responses that are more relevant to humans. Similarly using stable isotope tracer methods with these improved models in advanced stages of the drug development pipeline, in conjunction with tissue biopsy is expected significantly to reduce the high failure rate of experimental drugs in Phase II and III clinical trials.

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.

An analysis of dental development in Pleistocene Homo using skeletal growth and chronological age.

PubMed

Šešelj, Maja

2017-07-01

This study takes a new approach to interpreting dental development in Pleistocene Homo in comparison with recent modern humans. As rates of dental development and skeletal growth are correlated given age in modern humans, using age and skeletal growth in tandem yields more accurate dental development estimates. Here, I apply these models to fossil Homo to obtain more individualized predictions and interpretations of their dental development relative to recent modern humans. Proportional odds logistic regression models based on three recent modern human samples (N = 181) were used to predict permanent mandibular tooth development scores in five Pleistocene subadults: Homo erectus/ergaster, Neanderthals, and anatomically modern humans (AMHs). Explanatory variables include a skeletal growth indicator (i.e., diaphyseal femoral length), and chronological age. AMHs Lagar Velho 1 and Qafzeh 10 share delayed incisor development, but exhibit considerable idiosyncratic variation within and across tooth types, relative to each other and to the reference samples. Neanderthals Dederiyeh 1 and Le Moustier 1 exhibit delayed incisor coupled with advanced molar development, but differences are reduced when femoral diaphysis length is considered. Dental development in KNM-WT 15,000 Homo erectus/ergaster, while advanced for his age, almost exactly matches the predictions once femoral length is included in the models. This study provides a new interpretation of dental development in KNM-WT 15000 as primarily reflecting his faster rates of skeletal growth. While the two AMH specimens exhibit considerable individual variation, the Neanderthals exhibit delayed incisor development early and advanced molar development later in ontogeny. © 2017 Wiley Periodicals, Inc.

Dynamics of coupled human-landscape systems

NASA Astrophysics Data System (ADS)

Werner, B. T.; McNamara, D. E.

2007-11-01

A preliminary dynamical analysis of landscapes and humans as hierarchical complex systems suggests that strong coupling between the two that spreads to become regionally or globally pervasive should be focused at multi-year to decadal time scales. At these scales, landscape dynamics is dominated by water, sediment and biological routing mediated by fluvial, oceanic, atmospheric processes and human dynamics is dominated by simplifying, profit-maximizing market forces and political action based on projection of economic effect. Also at these scales, landscapes impact humans through patterns of natural disasters and trends such as sea level rise; humans impact landscapes by the effect of economic activity and changes meant to mitigate natural disasters and longer term trends. Based on this analysis, human-landscape coupled systems can be modeled using heterogeneous agents employing prediction models to determine actions to represent the nonlinear behavior of economic and political systems and rule-based routing algorithms to represent landscape processes. A cellular model for the development of New Orleans illustrates this approach, with routing algorithms for river and hurricane-storm surge determining flood extent, five markets (home, labor, hotel, tourism and port services) connecting seven types of economic agents (home buyers/laborers, home developers, hotel owners/ employers, hotel developers, tourists, port services developer and port services owners/employers), building of levees or a river spillway by political agents and damage to homes, hotels or port services within cells determined by the passage or depth of flood waters. The model reproduces historical aspects of New Orleans economic development and levee construction and the filtering of frequent small-scale floods at the expense of large disasters.

FRamework Assessing Notorious Contributing Influences for Error (FRANCIE): Perspective on Taxonomy Development to Support Error Reporting and Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lon N. Haney; David I. Gertman

2003-04-01

Beginning in the 1980s a primary focus of human reliability analysis was estimation of human error probabilities. However, detailed qualitative modeling with comprehensive representation of contextual variables often was lacking. This was likely due to the lack of comprehensive error and performance shaping factor taxonomies, and the limited data available on observed error rates and their relationship to specific contextual variables. In the mid 90s Boeing, America West Airlines, NASA Ames Research Center and INEEL partnered in a NASA sponsored Advanced Concepts grant to: assess the state of the art in human error analysis, identify future needs for human errormore » analysis, and develop an approach addressing these needs. Identified needs included the need for a method to identify and prioritize task and contextual characteristics affecting human reliability. Other needs identified included developing comprehensive taxonomies to support detailed qualitative modeling and to structure meaningful data collection efforts across domains. A result was the development of the FRamework Assessing Notorious Contributing Influences for Error (FRANCIE) with a taxonomy for airline maintenance tasks. The assignment of performance shaping factors to generic errors by experts proved to be valuable to qualitative modeling. Performance shaping factors and error types from such detailed approaches can be used to structure error reporting schemes. In a recent NASA Advanced Human Support Technology grant FRANCIE was refined, and two new taxonomies for use on space missions were developed. The development, sharing, and use of error taxonomies, and the refinement of approaches for increased fidelity of qualitative modeling is offered as a means to help direct useful data collection strategies.« less

Operational forecasting of human-biometeorological conditions

NASA Astrophysics Data System (ADS)

Giannaros, T. M.; Lagouvardos, K.; Kotroni, V.; Matzarakis, A.

2018-03-01

This paper presents the development of an operational forecasting service focusing on human-biometeorological conditions. The service is based on the coupling of numerical weather prediction models with an advanced human-biometeorological model. Human thermal perception and stress forecasts are issued on a daily basis for Greece, in both point and gridded format. A user-friendly presentation approach is adopted for communicating the forecasts to the public via the worldwide web. The development of the presented service highlights the feasibility of replacing standard meteorological parameters and/or indices used in operational weather forecasting activities for assessing the thermal environment. This is of particular significance for providing effective, human-biometeorology-oriented, warnings for both heat waves and cold outbreaks.

Community Based Educational Model on Water Conservation Program

NASA Astrophysics Data System (ADS)

Sudiajeng, L.; Parwita, I. G. L.; Wiraga, I. W.; Mudhina, M.

2018-01-01

The previous research showed that there were indicators of water crisis in the northern and eastern part of Denpasar city and most of coastal area experienced on seawater intrusion. The recommended water conservation programs were rainwater harvesting and educate the community to develop a water saving and environmentally conscious culture. This research was conducted to built the community based educational model on water conservation program through ergonomics SHIP approach which placed the human aspect as the first consideration, besides the economic and technically aspects. The stakeholders involved in the program started from the problem analyses to the implementation and the maintenance as well. The model was built through three main steps, included determination of accepted design; building the recharge wells by involving local communities; guidance and assistance in developing a water saving and environmentally conscious culture for early childhood, elementary and junior high school students, community and industry. The program was implemented based on the “TRIHITA KARANA” concept, which means the relationship between human to God, human-to-human, and human to environment. Through the development of the model, it is expected to grow a sense of belonging and awareness from the community to maintain the sustainability of the program.

New tools for linking human and earth system models: The Toolbox for Human-Earth System Interaction & Scaling (THESIS)

NASA Astrophysics Data System (ADS)

O'Neill, B. C.; Kauffman, B.; Lawrence, P.

2016-12-01

Integrated analysis of questions regarding land, water, and energy resources often requires integration of models of different types. One type of integration is between human and earth system models, since both societal and physical processes influence these resources. For example, human processes such as changes in population, economic conditions, and policies govern the demand for land, water and energy, while the interactions of these resources with physical systems determine their availability and environmental consequences. We have begun to develop and use a toolkit for linking human and earth system models called the Toolbox for Human-Earth System Integration and Scaling (THESIS). THESIS consists of models and software tools to translate, scale, and synthesize information from and between human system models and earth system models (ESMs), with initial application to linking the NCAR integrated assessment model, iPETS, with the NCAR earth system model, CESM. Initial development is focused on urban areas and agriculture, sectors that are both explicitly represented in both CESM and iPETS. Tools are being made available to the community as they are completed (see https://www2.cgd.ucar.edu/sections/tss/iam/THESIS_tools). We discuss four general types of functions that THESIS tools serve (Spatial Distribution, Spatial Properties, Consistency, and Outcome Evaluation). Tools are designed to be modular and can be combined in order to carry out more complex analyses. We illustrate their application to both the exposure of population to climate extremes and to the evaluation of climate impacts on the agriculture sector. For example, projecting exposure to climate extremes involves use of THESIS tools for spatial population, spatial urban land cover, the characteristics of both, and a tool to bring urban climate information together with spatial population information. Development of THESIS tools is continuing and open to the research community.

Humanization of pediatric care in the world: focus and review of existing models and measurement tools.

PubMed

Tripodi, Marina; Siano, Maria Anna; Mandato, Claudia; De Anseris, Anna Giulia Elena; Quitadamo, Paolo; Guercio Nuzio, Salvatore; Viggiano, Claudia; Fasolino, Francesco; Bellopede, Annalisa; Annunziata, Maria; Massa, Grazia; Pepe, Francesco Maria; De Chiara, Maria; Siani, Paolo; Vajro, Pietro

2017-08-30

The term "humanization" indicates the process by which people try to make something more human and civilized, more in line with what is believed to be the human nature. The humanization of care is an important and not yet a well-defined issue which includes a wide range of aspects related to the approach to the patient and care modalities. In pediatrics, the humanization concept is even vaguer due to the dual involvement of both the child and his/her family and by the existence of multiple proposed models. The present study aims to analyze the main existing humanization models regarding pediatric care, and the tools for assessing its grade. The main Humanization care programs have been elaborated and developed both in America (Brazil, USA) and Europe. The North American and European models specifically concern pediatric care, while the model developed in Brazil is part of a broader program aimed at all age groups. The first emphasis is on the importance of the family in child care, the second emphasis is on the child's right to be a leader, to be heard and to be able to express its opinion on the program's own care. Several tools have been created and used to evaluate humanization of care programs and related aspects. None, however, had been mutually compared. The major models of humanization care and the related assessment tools here reviewed highlight the urgent need for a more unifying approach, which may help in realizing health care programs closer to the young patient's and his/her family needs.

Zika viral infection and neutralizing human antibody response in a BLT humanized mouse model.

PubMed

Schmitt, Kimberly; Charlins, Paige; Veselinovic, Milena; Kinner-Bibeau, Lauren; Hu, Shuang; Curlin, James; Remling-Mulder, Leila; Olson, Ken E; Aboellail, Tawfik; Akkina, Ramesh

2018-02-01

Many murine and non-human primate animal models have been recently developed to understand Zika viral pathogenesis. However, a major limitation with these models is the inability to directly examine the human-specific immune response. Here, we utilized a BLT humanized mouse model endowed with a transplanted human immune system. Plasma viremia could be detected within 48h after viral challenge and viremia persisted for as long as 220 days in some mice. Neutralizing human antibody was detected in infected mice and mouse sera showed reactivity with the viral envelope and capsid proteins in a radio-immunoprecipitation assay. Human monocytes/macrophages, B cells and hematopoietic stem cells in the bone marrow were found to be virus infected. These data establish that BLT mice are permissive for Zika viral infection and are capable of generating viral-specific human immune responses thus providing a human surrogate model for future testing of vaccine and antiviral therapeutic candidates. Copyright © 2017 Elsevier Inc. All rights reserved.

Overview of genetically engineered mouse models of colorectal carcinoma to enable translational biology and drug development.

PubMed

Roper, Jatin; Martin, Eric S; Hung, Kenneth E

2014-06-16

Preclinical models for colorectal cancer (CRC) are critical for translational biology and drug development studies to characterize and treat this condition. Mouse models of human cancer are particularly popular because of their relatively low cost, short life span, and ease of use. Genetically engineered mouse models (GEMMs) of CRC are engineered from germline or somatic modification of critical tumor suppressor genes and/or oncogenes that drive mutations in human disease. Detailed in this overview are the salient features of several useful colorectal cancer GEMMs and their value as tools for translational biology and preclinical drug development. Copyright © 2014 John Wiley & Sons, Inc.

A cross-species analysis method to analyze animal models' similarity to human's disease state

PubMed Central

2012-01-01

Background Animal models are indispensable tools in studying the cause of human diseases and searching for the treatments. The scientific value of an animal model depends on the accurate mimicry of human diseases. The primary goal of the current study was to develop a cross-species method by using the animal models' expression data to evaluate the similarity to human diseases' and assess drug molecules' efficiency in drug research. Therefore, we hoped to reveal that it is feasible and useful to compare gene expression profiles across species in the studies of pathology, toxicology, drug repositioning, and drug action mechanism. Results We developed a cross-species analysis method to analyze animal models' similarity to human diseases and effectiveness in drug research by utilizing the existing animal gene expression data in the public database, and mined some meaningful information to help drug research, such as potential drug candidates, possible drug repositioning, side effects and analysis in pharmacology. New animal models could be evaluated by our method before they are used in drug discovery. We applied the method to several cases of known animal model expression profiles and obtained some useful information to help drug research. We found that trichostatin A and some other HDACs could have very similar response across cell lines and species at gene expression level. Mouse hypoxia model could accurately mimic the human hypoxia, while mouse diabetes drug model might have some limitation. The transgenic mouse of Alzheimer was a useful model and we deeply analyzed the biological mechanisms of some drugs in this case. In addition, all the cases could provide some ideas for drug discovery and drug repositioning. Conclusions We developed a new cross-species gene expression module comparison method to use animal models' expression data to analyse the effectiveness of animal models in drug research. Moreover, through data integration, our method could be applied for drug research, such as potential drug candidates, possible drug repositioning, side effects and information about pharmacology. PMID:23282076

A cross-species analysis method to analyze animal models' similarity to human's disease state.

PubMed

Yu, Shuhao; Zheng, Lulu; Li, Yun; Li, Chunyan; Ma, Chenchen; Li, Yixue; Li, Xuan; Hao, Pei

2012-01-01

Animal models are indispensable tools in studying the cause of human diseases and searching for the treatments. The scientific value of an animal model depends on the accurate mimicry of human diseases. The primary goal of the current study was to develop a cross-species method by using the animal models' expression data to evaluate the similarity to human diseases' and assess drug molecules' efficiency in drug research. Therefore, we hoped to reveal that it is feasible and useful to compare gene expression profiles across species in the studies of pathology, toxicology, drug repositioning, and drug action mechanism. We developed a cross-species analysis method to analyze animal models' similarity to human diseases and effectiveness in drug research by utilizing the existing animal gene expression data in the public database, and mined some meaningful information to help drug research, such as potential drug candidates, possible drug repositioning, side effects and analysis in pharmacology. New animal models could be evaluated by our method before they are used in drug discovery. We applied the method to several cases of known animal model expression profiles and obtained some useful information to help drug research. We found that trichostatin A and some other HDACs could have very similar response across cell lines and species at gene expression level. Mouse hypoxia model could accurately mimic the human hypoxia, while mouse diabetes drug model might have some limitation. The transgenic mouse of Alzheimer was a useful model and we deeply analyzed the biological mechanisms of some drugs in this case. In addition, all the cases could provide some ideas for drug discovery and drug repositioning. We developed a new cross-species gene expression module comparison method to use animal models' expression data to analyse the effectiveness of animal models in drug research. Moreover, through data integration, our method could be applied for drug research, such as potential drug candidates, possible drug repositioning, side effects and information about pharmacology.

Leveraging Small Aquarium Fishes to Advance Understanding of Environmentally Influenced Human Disorders and Diseases

EPA Science Inventory

Small aquarium fishes provide a model organism that recapitulates the development, physiology and specific disease processes present in humans without the many limitations of rodent-based models currently in use. Fish models offer advantages in cost, rapid life-cycles, and extern...

POPULATION EXPOSURE AND DOSE MODEL FOR AIR TOXICS: A BENZENE CASE STUDY

EPA Science Inventory

The EPA's National Exposure Research Laboratory (NERL) is developing a human exposure and dose model called the Stochastic Human Exposure and Dose Simulation model for Air Toxics (SHEDS-AirToxics) to characterize population exposure to air toxics in support of the National Air ...

AN EXAMPLE OF MODEL STRUCTURE DIFFERENCES USING SENSITIVITY ANALYSES IN PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELS OF TRICHLOROETHYLENE IN HUMANS

EPA Science Inventory

Abstract Trichloroethylene (TCE) is an industrial chemical and an environmental contaminant. TCE and its metabolites may be carcinogenic and affect human health. Physiologically based pharmacokinetic (PBPK) models that differ in compartmentalization are developed for TCE metabo...

Virtual Habitat -a dynamic simulation of closed life support systems -human model status

NASA Astrophysics Data System (ADS)

Markus Czupalla, M. Sc.; Zhukov, Anton; Hwang, Su-Au; Schnaitmann, Jonas

In order to optimize Life Support Systems on a system level, stability questions must be in-vestigated. To do so the exploration group of the Technical University of Munich (TUM) is developing the "Virtual Habitat" (V-HAB) dynamic LSS simulation software. V-HAB shall provide the possibility to conduct dynamic simulations of entire mission scenarios for any given LSS configuration. The Virtual Habitat simulation tool consists of four main modules: • Closed Environment Module (CEM) -monitoring of compounds in a closed environment • Crew Module (CM) -dynamic human simulation • P/C Systems Module (PCSM) -dynamic P/C subsystems • Plant Module (PM) -dynamic plant simulation The core module of the simulation is the dynamic and environment sensitive human module. Introduced in its basic version in 2008, the human module has been significantly updated since, increasing its capabilities and maturity significantly. In this paper three newly added human model subsystems (thermal regulation, digestion and schedule controller) are introduced touching also on the human stress subsystem which is cur-rently under development. Upon the introduction of these new subsystems, the integration of these into the overall V-HAB human model is discussed, highlighting the impact on the most important I/F. The overall human model capabilities shall further be summarized and presented based on meaningful test cases. In addition to the presentation of the results, the correlation strategy for the Virtual Habitat human model shall be introduced assessing the models current confidence level and giving an outlook on the future correlation strategy. Last but not least, the remaining V-HAB mod-ules shall be introduced shortly showing how the human model is integrated into the overall simulation.

Materials used to simulate physical properties of human skin.

PubMed

Dąbrowska, A K; Rotaru, G-M; Derler, S; Spano, F; Camenzind, M; Annaheim, S; Stämpfli, R; Schmid, M; Rossi, R M

2016-02-01

For many applications in research, material development and testing, physical skin models are preferable to the use of human skin, because more reliable and reproducible results can be obtained. This article gives an overview of materials applied to model physical properties of human skin to encourage multidisciplinary approaches for more realistic testing and improved understanding of skin-material interactions. The literature databases Web of Science, PubMed and Google Scholar were searched using the terms 'skin model', 'skin phantom', 'skin equivalent', 'synthetic skin', 'skin substitute', 'artificial skin', 'skin replica', and 'skin model substrate.' Articles addressing material developments or measurements that include the replication of skin properties or behaviour were analysed. It was found that the most common materials used to simulate skin are liquid suspensions, gelatinous substances, elastomers, epoxy resins, metals and textiles. Nano- and micro-fillers can be incorporated in the skin models to tune their physical properties. While numerous physical skin models have been reported, most developments are research field-specific and based on trial-and-error methods. As the complexity of advanced measurement techniques increases, new interdisciplinary approaches are needed in future to achieve refined models which realistically simulate multiple properties of human skin. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Some Considerations Necessary for a Viable Theory of Human Memory.

ERIC Educational Resources Information Center

Sietsema, Douglas J.

Empirical research is reviewed in the area of cognitive psychology pertaining to models of human memory. Research evidence and theoretical considerations are combined to develop guidelines for future theory development related to the human memory. The following theoretical constructs and variables are discussed: (1) storage versus process…

Three-Dimensional Mechanical Model of the Human Spine and the Versatility of its Use

NASA Astrophysics Data System (ADS)

Sokol, Milan; Velísková, Petra; Rehák, Ľuboš; Žabka, Martin

2014-03-01

The aim of the work is oriented towards the simulation or modeling of the lumbar and thoracic human spine as a load-bearing 3D system in a computer program (ANSYS). The human spine model includes a determination of the geometry based on X-ray pictures of frontal and lateral projections. For this reason, another computer code, BMPCOORDINATES, was developed as an aid to obtain the most precise and realistic model of the spine. Various positions, deformations, scoliosis, rotation and torsion can be modelled. Once the geometry is done, external loading on different spinal segments is entered; consequently, the response could be analysed. This can contribute a lot to medical practice as a tool for diagnoses, and developing implants or other artificial instruments for fixing the spine.

Analysis and synthesis of laughter

NASA Astrophysics Data System (ADS)

Sundaram, Shiva; Narayanan, Shrikanth

2004-10-01

There is much enthusiasm in the text-to-speech community for synthesis of emotional and natural speech. One idea being proposed is to include emotion dependent paralinguistic cues during synthesis to convey emotions effectively. This requires modeling and synthesis techniques of various cues for different emotions. Motivated by this, a technique to synthesize human laughter is proposed. Laughter is a complex mechanism of expression and has high variability in terms of types and usage in human-human communication. People have their own characteristic way of laughing. Laughter can be seen as a controlled/uncontrolled physiological process of a person resulting from an initial excitation in context. A parametric model based on damped simple harmonic motion to effectively capture these diversities and also maintain the individuals characteristics is developed here. Limited laughter/speech data from actual humans and synthesis ease are the constraints imposed on the accuracy of the model. Analysis techniques are also developed to determine the parameters of the model for a given individual or laughter type. Finally, the effectiveness of the model to capture the individual characteristics and naturalness compared to real human laughter has been analyzed. Through this the factors involved in individual human laughter and their importance can be better understood.

Developing deterioration models for Wyoming bridges.

DOT National Transportation Integrated Search

2016-05-01

Deterioration models for the Wyoming Bridge Inventory were developed using both stochastic and deterministic models. : The selection of explanatory variables is investigated and a new method using LASSO regression to eliminate human bias : in explana...

Fatal autoimmunity in mice reconstituted with human hematopoietic stem cells encoding defective FOXP3

PubMed Central

Goettel, Jeremy A.; Biswas, Subhabrata; Lexmond, Willem S.; Yeste, Ada; Passerini, Laura; Patel, Bonny; Yang, Siyoung; Sun, Jiusong; Ouahed, Jodie; Shouval, Dror S.; McCann, Katelyn J.; Horwitz, Bruce H.; Mathis, Diane; Milford, Edgar L.; Notarangelo, Luigi D.; Roncarolo, Maria-Grazia; Fiebiger, Edda; Marasco, Wayne A.; Bacchetta, Rosa; Quintana, Francisco J.; Pai, Sung-Yun; Klein, Christoph; Muise, Aleixo M.

2015-01-01

Mice reconstituted with a human immune system provide a tractable in vivo model to assess human immune cell function. To date, reconstitution of murine strains with human hematopoietic stem cells (HSCs) from patients with monogenic immune disorders have not been reported. One obstacle precluding the development of immune-disease specific “humanized” mice is that optimal adaptive immune responses in current strains have required implantation of autologous human thymic tissue. To address this issue, we developed a mouse strain that lacks murine major histocompatibility complex class II (MHC II) and instead expresses human leukocyte antigen DR1 (HLA-DR1). These mice displayed improved adaptive immune responses when reconstituted with human HSCs including enhanced T-cell reconstitution, delayed-type hypersensitivity responses, and class-switch recombination. Following immune reconstitution of this novel strain with HSCs from a patient with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, associated with aberrant FOXP3 function, mice developed a lethal inflammatory disorder with multiorgan involvement and autoantibody production mimicking the pathology seen in affected humans. This humanized mouse model permits in vivo evaluation of immune responses associated with genetically altered HSCs, including primary immunodeficiencies, and should facilitate the study of human immune pathobiology and the development of targeted therapeutics. PMID:25833964

The Human Exposure Model (HEM): A Tool to Support Rapid Assessment of Human Health Impacts from Near-Field Consumer Product Exposures

EPA Science Inventory

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 exposur...

Management Education: Reflective Learning on Human Interaction

ERIC Educational Resources Information Center

Clydesdale, Greg

2016-01-01

Purpose: This paper aims to describe an attempt to develop a more effective technique to teach self-awareness and relationship skills. Design/methodology/approach: A journal is used in combination with a model of human nature. The model lists human characteristics that the management trainee must identify in themselves and others they interact…

Human-arm-and-hand-dynamic model with variability analyses for a stylus-based haptic interface.

PubMed

Fu, Michael J; Cavuşoğlu, M Cenk

2012-12-01

Haptic interface research benefits from accurate human arm models for control and system design. The literature contains many human arm dynamic models but lacks detailed variability analyses. Without accurate measurements, variability is modeled in a very conservative manner, leading to less than optimal controller and system designs. This paper not only presents models for human arm dynamics but also develops inter- and intrasubject variability models for a stylus-based haptic device. Data from 15 human subjects (nine male, six female, ages 20-32) were collected using a Phantom Premium 1.5a haptic device for system identification. In this paper, grip-force-dependent models were identified for 1-3-N grip forces in the three spatial axes. Also, variability due to human subjects and grip-force variation were modeled as both structured and unstructured uncertainties. For both forms of variability, the maximum variation, 95 %, and 67 % confidence interval limits were examined. All models were in the frequency domain with force as input and position as output. The identified models enable precise controllers targeted to a subset of possible human operator dynamics.

Modeling for intra-body communication with bone effect.

PubMed

Pun, S H; Gao, Y M; Mak, P U; Du, M; Vai, M I

2009-01-01

Intra-body communication (IBC) is a new, different "wireless" communication technique based on the human tissue. This short range "wireless" communication technology provides an alternative solution to wearable sensors, home health system, telemedicine and implanted devices. The development of the IBC enables the possibilities of providing less complexity and convenient communication methodologies for these devices. By regarding human tissue as communication channel, IBC making use of the conductivities properties of human tissue to send electrical signal from transmitter to receiver. In this paper, the authors proposed a new mathematical model for galvanic coupling type IBC based on a human limb. Starting from the electromagnetic theory, the authors treat human tissue as volume conductor, which is in analogous with the bioelectric phenomena analysis. In order to explain the mechanism of galvanic coupling type technique of IBC, applying the quasi-static approximation, the governing equation can be reduced to Laplace Equation. Finally, the analytical model is evaluated with on-body measurement for testing its performance. The comparison result shows that the developed mathematical model can provide good approximation for galvanic coupling type IBC on human limb under low operating frequencies.

Of Mice, Cattle, and Humans: The Immunology and Treatment of River Blindness

PubMed Central

Allen, Judith E.; Adjei, Ohene; Bain, Odile; Hoerauf, Achim; Hoffmann, Wolfgang H.; Makepeace, Benjamin L.; Schulz-Key, Hartwig; Tanya, Vincent N.; Trees, Alexander J.; Wanji, Samuel; Taylor, David W.

2008-01-01

River blindness is a seriously debilitating disease caused by the filarial parasite Onchocerca volvulus, which infects millions in Africa as well as in South and Central America. Research has been hampered by a lack of good animal models, as the parasite can only develop fully in humans and some primates. This review highlights the development of two animal model systems that have allowed significant advances in recent years and hold promise for the future. Experimental findings with Litomosoides sigmodontis in mice and Onchocerca ochengi in cattle are placed in the context of how these models can advance our ability to control the human disease. PMID:18446236

Development and Translational Application of a Minimal Physiologically Based Pharmacokinetic Model for a Monoclonal Antibody against Interleukin 23 (IL-23) in IL-23-Induced Psoriasis-Like Mice.

PubMed

Chen, Xi; Jiang, Xiling; Doddareddy, Rajitha; Geist, Brian; McIntosh, Thomas; Jusko, William J; Zhou, Honghui; Wang, Weirong

2018-04-01

The interleukin (IL)-23/T h 17/IL-17 immune pathway has been identified to play an important role in the pathogenesis of psoriasis. Many therapeutic proteins targeting IL-23 or IL-17 are currently under development for the treatment of psoriasis. In the present study, a mechanistic pharmacokinetics (PK)/pharmacodynamics (PD) study was conducted to assess the target-binding and disposition kinetics of a monoclonal antibody (mAb), CNTO 3723, and its soluble target, mouse IL-23, in an IL-23-induced psoriasis-like mouse model. A minimal physiologically based pharmacokinetic model with target-mediated drug disposition features was developed to quantitatively assess the kinetics and interrelationship between CNTO 3723 and exogenously administered, recombinant mouse IL-23 in both serum and lesional skin site. Furthermore, translational applications of the developed model were evaluated with incorporation of human PK for ustekinumab, an anti-human IL-23/IL-12 mAb developed for treatment of psoriasis, and human disease pathophysiology information in psoriatic patients. The results agreed well with the observed clinical data for ustekinumab. Our work provides an example on how mechanism-based PK/PD modeling can be applied during early drug discovery and how preclinical data can be used for human efficacious dose projection and guide decision making during early clinical development of therapeutic proteins. Copyright © 2018 by The Author(s).

Early stress and human behavioral development: emerging evolutionary perspectives.

PubMed

Del Giudice, M

2014-08-01

Stress experienced early in life exerts a powerful, lasting influence on development. Converging empirical findings show that stressful experiences become deeply embedded in the child's neurobiology, with an astonishing range of long-term effects on cognition, emotion, and behavior. In contrast with the prevailing view that such effects are the maladaptive outcomes of 'toxic' stress, adaptive models regard them as manifestations of evolved developmental plasticity. In this paper, I offer a brief introduction to adaptive models of early stress and human behavioral development, with emphasis on recent theoretical contributions and emerging concepts in the field. I begin by contrasting dysregulation models of early stress with their adaptive counterparts; I then introduce life history theory as a unifying framework, and review recent work on predictive adaptive responses (PARs) in human life history development. In particular, I discuss the distinction between forecasting the future state of the environment (external prediction) and forecasting the future state of the organism (internal prediction). Next, I present the adaptive calibration model, an integrative model of individual differences in stress responsivity based on life history concepts. I conclude by examining how maternal-fetal conflict may shape the physiology of prenatal stress and its adaptive and maladaptive effects on postnatal development. In total, I aim to show how theoretical work from evolutionary biology is reshaping the way we think about the role of stress in human development, and provide researchers with an up-to-date conceptual map of this fascinating and rapidly evolving field.

Analytic Guided-Search Model of Human Performance Accuracy in Target- Localization Search Tasks

NASA Technical Reports Server (NTRS)

Eckstein, Miguel P.; Beutter, Brent R.; Stone, Leland S.

2000-01-01

Current models of human visual search have extended the traditional serial/parallel search dichotomy. Two successful models for predicting human visual search are the Guided Search model and the Signal Detection Theory model. Although these models are inherently different, it has been difficult to compare them because the Guided Search model is designed to predict response time, while Signal Detection Theory models are designed to predict performance accuracy. Moreover, current implementations of the Guided Search model require the use of Monte-Carlo simulations, a method that makes fitting the model's performance quantitatively to human data more computationally time consuming. We have extended the Guided Search model to predict human accuracy in target-localization search tasks. We have also developed analytic expressions that simplify simulation of the model to the evaluation of a small set of equations using only three free parameters. This new implementation and extension of the Guided Search model will enable direct quantitative comparisons with human performance in target-localization search experiments and with the predictions of Signal Detection Theory and other search accuracy models.

Development of ferret as a human lung cancer model by injecting4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

USDA-ARS?s Scientific Manuscript database

Development of new animal lung cancer models that are relevant to human lung carcinogenesis is important for lung cancer research. Previously we have shown the induction of lung tumor in ferrets (Mustela putorius furo) exposed to both tobacco smoke and a tobacco carcinogen (4-(N-methyl-N-nitrosamino...

Advanced Collaborative Environments Supporting Systems Integration and Design

DTIC Science & Technology

2003-03-01

concurrently view a virtual system or product model while maintaining natural, human communication . These virtual systems operate within a computer-generated...These environments allow multiple individuals to concurrently view a virtual system or product model while simultaneously maintaining natural, human ... communication . As a result, TARDEC researchers and system developers are using this advanced high-end visualization technology to develop future

Genetically engineered mouse models and human osteosarcoma

PubMed Central

2012-01-01

Osteosarcoma is the most common form of bone cancer. Pivotal insight into the genes involved in human osteosarcoma has been provided by the study of rare familial cancer predisposition syndromes. Three kindreds stand out as predisposing to the development of osteosarcoma: Li-Fraumeni syndrome, familial retinoblastoma and RecQ helicase disorders, which include Rothmund-Thomson Syndrome in particular. These disorders have highlighted the important roles of P53 and RB respectively, in the development of osteosarcoma. The association of OS with RECQL4 mutations is apparent but the relevance of this to OS is uncertain as mutations in RECQL4 are not found in sporadic OS. Application of the knowledge or mutations of P53 and RB in familial and sporadic OS has enabled the development of tractable, highly penetrant murine models of OS. These models share many of the cardinal features associated with human osteosarcoma including, importantly, a high incidence of spontaneous metastasis. The recent development of these models has been a significant advance for efforts to improve our understanding of the genetics of human OS and, more critically, to provide a high-throughput genetically modifiable platform for preclinical evaluation of new therapeutics. PMID:23036272

A Competency-Based Human Resource Development Strategy

ERIC Educational Resources Information Center

Gangani, Noordeen; McLean, Gary N.; Braden, Richard A.

2006-01-01

This article explores some of the major issues in developing and implementing a competency-based human resource development strategy. The article summarizes a brief literature review on how competency models can be developed and implemented to improve employee performance. A case study is presented of American Medical Systems (AMS), a mid-sized…

Maturity Level of Organizations Integrating Organizational Development with Human Resource Development.

ERIC Educational Resources Information Center

Herman, Jerry J.; Herman, Janice L.

1994-01-01

Future organizations must integrate their human-resource development requirements with organizational development requirements to survive and prosper. A totally integrated systems model will feature 10 crucial elements. Leaders must understand that their organizations pass through developmental stages (from infancy to maturity); at each stage,…

The Development of a Modelling Solution to Address Manpower and Personnel Issues Using the IPME

DTIC Science & Technology

2010-11-01

training for a military system. It deals with the number of personnel spaces and available people. One of the main concerns in this domain is to...are often addressed by examining existing solutions for similar systems and/or a trial-and-error method based on human-in- the -loop tests. Such an...significant effort and resources on the development of a human performance modelling software, the Integrated Performance Modelling Environment (IPME

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.

Translational Modeling in Schizophrenia: Predicting Human Dopamine D2 Receptor Occupancy.

PubMed

Johnson, Martin; Kozielska, Magdalena; Pilla Reddy, Venkatesh; Vermeulen, An; Barton, Hugh A; Grimwood, Sarah; de Greef, Rik; Groothuis, Geny M M; Danhof, Meindert; Proost, Johannes H

2016-04-01

To assess the ability of a previously developed hybrid physiology-based pharmacokinetic-pharmacodynamic (PBPKPD) model in rats to predict the dopamine D2 receptor occupancy (D2RO) in human striatum following administration of antipsychotic drugs. A hybrid PBPKPD model, previously developed using information on plasma concentrations, brain exposure and D2RO in rats, was used as the basis for the prediction of D2RO in human. The rat pharmacokinetic and brain physiology parameters were substituted with human population pharmacokinetic parameters and human physiological information. To predict the passive transport across the human blood-brain barrier, apparent permeability values were scaled based on rat and human brain endothelial surface area. Active efflux clearance in brain was scaled from rat to human using both human brain endothelial surface area and MDR1 expression. Binding constants at the D2 receptor were scaled based on the differences between in vitro and in vivo systems of the same species. The predictive power of this physiology-based approach was determined by comparing the D2RO predictions with the observed human D2RO of six antipsychotics at clinically relevant doses. Predicted human D2RO was in good agreement with clinically observed D2RO for five antipsychotics. Models using in vitro information predicted human D2RO well for most of the compounds evaluated in this analysis. However, human D2RO was under-predicted for haloperidol. The rat hybrid PBPKPD model structure, integrated with in vitro information and human pharmacokinetic and physiological information, constitutes a scientific basis to predict the time course of D2RO in man.

What, if anything, can monkeys tell us about human amnesia when they can’t say anything at all?

PubMed Central

Murray, Elisabeth A.; Wise, Steven P.

2010-01-01

Despite a half century of development, the orthodox monkey model of human amnesia needs improvement, in part because of two problems inherent in animal models of advanced human cognition. First, animal models are perforce comparative, but the principles of comparative and evolutionary biology have not featured prominently in developing the orthodox model. Second, no one understands the relationship between human consciousness and cognition in other animals, but the orthodox model implicitly assumes a close correspondence. If we treat these two difficulties with the deference they deserve, monkeys can tell us a lot about human amnesia and memory. Three future contributions seem most likely: (1) an improved monkey model, one refocused on the hippocampus rather than on the medial temporal lobe as a whole; (2) a better understanding of cortical areas unique to primates, especially the granular prefrontal cortex; and (3), taking the two together, insight into prefrontal-hippocampal interactions. We propose that interactions among the granular prefrontal areas create the kind of cross-domain, analogical and self-referential knowledge that underlies advanced cognition in modern humans. When these products of frontal-lobe function interact with the hippocampus, and its ancestral function in navigation, what emerges is the human ability to embed ourselves in scenarios — real and imagined, self-generated and received — thereby creating a coherent, conscious life experience. PMID:20097215

A Research Roadmap for Computation-Based Human Reliability Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boring, Ronald; Mandelli, Diego; Joe, Jeffrey

2015-08-01

The United States (U.S.) Department of Energy (DOE) is sponsoring research through the Light Water Reactor Sustainability (LWRS) program to extend the life of the currently operating fleet of commercial nuclear power plants. The Risk Informed Safety Margin Characterization (RISMC) research pathway within LWRS looks at ways to maintain and improve the safety margins of these plants. The RISMC pathway includes significant developments in the area of thermalhydraulics code modeling and the development of tools to facilitate dynamic probabilistic risk assessment (PRA). PRA is primarily concerned with the risk of hardware systems at the plant; yet, hardware reliability is oftenmore » secondary in overall risk significance to human errors that can trigger or compound undesirable events at the plant. This report highlights ongoing efforts to develop a computation-based approach to human reliability analysis (HRA). This computation-based approach differs from existing static and dynamic HRA approaches in that it: (i) interfaces with a dynamic computation engine that includes a full scope plant model, and (ii) interfaces with a PRA software toolset. The computation-based HRA approach presented in this report is called the Human Unimodels for Nuclear Technology to Enhance Reliability (HUNTER) and incorporates in a hybrid fashion elements of existing HRA methods to interface with new computational tools developed under the RISMC pathway. The goal of this research effort is to model human performance more accurately than existing approaches, thereby minimizing modeling uncertainty found in current plant risk models.« less

A novel model of human skin pressure ulcers in mice.

PubMed

Maldonado, Andrés A; Cristóbal, Lara; Martín-López, Javier; Mallén, Mar; García-Honduvilla, Natalio; Buján, Julia

2014-01-01

Pressure ulcers are a prevalent health problem in today's society. The shortage of suitable animal models limits our understanding and our ability to develop new therapies. This study aims to report on the development of a novel and reproducible human skin pressure ulcer model in mice. Male non-obese, diabetic, severe combined immunodeficiency mice (n = 22) were engrafted with human skin. A full-thickness skin graft was placed onto 4×3 cm wounds created on the dorsal skin of the mice. Two groups with permanent grafts were studied after 60 days. The control group (n = 6) was focused on the process of engraftment. Evaluations were conducted with photographic assessment, histological analysis and fluorescence in situ hybridization (FISH) techniques. The pressure ulcer group (n = 12) was created using a compression device. A pressure of 150 mmHg for 8 h, with a total of three cycles of compression-release was exerted. Evaluations were conducted with photographic assessment and histological analysis. Skin grafts in the control group took successfully, as shown by visual assessment, FISH techniques and histological analysis. Pressure ulcers in the second group showed full-thickness skin loss with damage and necrosis of all the epidermal and dermal layers (ulcer stage III) in all cases. Complete repair occurred after 40 days. An inexpensive, reproducible human skin pressure ulcer model has been developed. This novel model will facilitate the development of new clinically relevant therapeutic strategies that can be tested directly on human skin.

Elements of episodic-like memory in animal models.

PubMed

Crystal, Jonathon D

2009-03-01

Representations of unique events from one's past constitute the content of episodic memories. A number of studies with non-human animals have revealed that animals remember specific episodes from their past (referred to as episodic-like memory). The development of animal models of memory holds enormous potential for gaining insight into the biological bases of human memory. Specifically, given the extensive knowledge of the rodent brain, the development of rodent models of episodic memory would open new opportunities to explore the neuroanatomical, neurochemical, neurophysiological, and molecular mechanisms of memory. Development of such animal models holds enormous potential for studying functional changes in episodic memory in animal models of Alzheimer's disease, amnesia, and other human memory pathologies. This article reviews several approaches that have been used to assess episodic-like memory in animals. The approaches reviewed include the discrimination of what, where, and when in a radial arm maze, dissociation of recollection and familiarity, object recognition, binding, unexpected questions, and anticipation of a reproductive state. The diversity of approaches may promote the development of converging lines of evidence on the difficult problem of assessing episodic-like memory in animals.

A physical multifield model predicts the development of volume and structure in the human brain

NASA Astrophysics Data System (ADS)

Rooij, Rijk de; Kuhl, Ellen

2018-03-01

The prenatal development of the human brain is characterized by a rapid increase in brain volume and a development of a highly folded cortex. At the cellular level, these events are enabled by symmetric and asymmetric cell division in the ventricular regions of the brain followed by an outwards cell migration towards the peripheral regions. The role of mechanics during brain development has been suggested and acknowledged in past decades, but remains insufficiently understood. Here we propose a mechanistic model that couples cell division, cell migration, and brain volume growth to accurately model the developing brain between weeks 10 and 29 of gestation. Our model accurately predicts a 160-fold volume increase from 1.5 cm3 at week 10 to 235 cm3 at week 29 of gestation. In agreement with human brain development, the cortex begins to form around week 22 and accounts for about 30% of the total brain volume at week 29. Our results show that cell division and coupling between cell density and volume growth are essential to accurately model brain volume development, whereas cell migration and diffusion contribute mainly to the development of the cortex. We demonstrate that complex folding patterns, including sinusoidal folds and creases, emerge naturally as the cortex develops, even for low stiffness contrasts between the cortex and subcortex.

Investigation of in-body path loss in different human subjects for localization of capsule endoscope.

PubMed

Ara, Perzila; Cheng, Shaokoon; Heimlich, Michael; Dutkiewicz, Eryk

2015-01-01

Recent developments in capsule endoscopy have highlighted the need for accurate techniques to estimate the location of a capsule endoscope. A highly accurate location estimation of a capsule endoscope in the gastrointestinal (GI) tract in the range of several millimeters is a challenging task. This is mainly because the radio-frequency signals encounter high loss and a highly dynamic channel propagation environment. Therefore, an accurate path-loss model is required for the development of accurate localization algorithms. This paper presents an in-body path-loss model for the human abdomen region at 2.4 GHz frequency. To develop the path-loss model, electromagnetic simulations using the Finite-Difference Time-Domain (FDTD) method were carried out on two different anatomical human models. A mathematical expression for the path-loss model was proposed based on analysis of the measured loss at different capsule locations inside the small intestine. The proposed path-loss model is a good approximation to model in-body RF propagation, since the real measurements are quite infeasible for the capsule endoscopy subject.

A mouse model for the human pathogen Salmonella Typhi

PubMed Central

Song, Jeongmin; Willinger, Tim; Rongvaux, Anthony; Eynon, Elizabeth E.; Stevens, Sean; Manz, Markus G.; Flavell, Richard A.; Galán, Jorge E.

2010-01-01

SUMMARY Salmonella enterica serovar Typhi (S. Typhi) is the cause of typhoid fever, a life-threatening disease of humans. The lack of an animal model due to S. typhi's strict human host specificity has been a significant obstacle in the understanding of its pathogenesis and the development of a safe and effective vaccine against typhoid fever. We report here the development of a mouse model for S. Typhi infection. We showed that immunodeficient Rag2 -/- γc -/- mice engrafted with human fetal liver hematopoietic stem and progenitor cells were able to support S. Typhi replication and persistent infection. A S. Typhi strain carrying a mutation in a gene required for its virulence in humans was not able to replicate in these humanized mice. In contrast, another mutant strain unable to produce the recently identified typhoid toxin, exhibited increased replication suggesting a potential role for this toxin in the establishment of persistent infection. Furthermore, infected animals mounted a human innate and adaptive immune response to S. Typhi resulting in the production of cytokines and pathogen-specific antibodies. These results therefore indicate that this animal model can be used to study S. Typhi pathogenesis and to evaluate potential vaccine candidates against typhoid fever. PMID:20951970

DEVELOPMENT OF REAL-TIME SITE-SPECIFIC MICROSCALE EMISSION FACTOR MODEL FOR THE ASSESSMENT OF HUMAN EXPOSURE TO MOTOR VEHICLE EMISSIONS

EPA Science Inventory

The United States Environmental Protection Agency's (EPA) National Expsoure Research Laboratory (NERL) has initiated a project to improve the methodology for modeling urban-scale human exposure to mobile source emissions. The modeling project has started by considering the nee...

A predictive model for biomimetic plate type broadband frequency sensor

NASA Astrophysics Data System (ADS)

Ahmed, Riaz U.; Banerjee, Sourav

2016-04-01

In this work, predictive model for a bio-inspired broadband frequency sensor is developed. Broadband frequency sensing is essential in many domains of science and technology. One great example of such sensor is human cochlea, where it senses a frequency band of 20 Hz to 20 KHz. Developing broadband sensor adopting the physics of human cochlea has found tremendous interest in recent years. Although few experimental studies have been reported, a true predictive model to design such sensors is missing. A predictive model is utmost necessary for accurate design of selective broadband sensors that are capable of sensing very selective band of frequencies. Hence, in this study, we proposed a novel predictive model for the cochlea-inspired broadband sensor, aiming to select the frequency band and model parameters predictively. Tapered plate geometry is considered mimicking the real shape of the basilar membrane in the human cochlea. The predictive model is intended to develop flexible enough that can be employed in a wide variety of scientific domains. To do that, the predictive model is developed in such a way that, it can not only handle homogeneous but also any functionally graded model parameters. Additionally, the predictive model is capable of managing various types of boundary conditions. It has been found that, using the homogeneous model parameters, it is possible to sense a specific frequency band from a specific portion (B) of the model length (L). It is also possible to alter the attributes of `B' using functionally graded model parameters, which confirms the predictive frequency selection ability of the developed model.

Modeling How, When, and What Is Learned in a Simple Fault-Finding Task

ERIC Educational Resources Information Center

Ritter, Frank E.; Bibby, Peter A.

2008-01-01

We have developed a process model that learns in multiple ways while finding faults in a simple control panel device. The model predicts human participants' learning through its own learning. The model's performance was systematically compared to human learning data, including the time course and specific sequence of learned behaviors. These…

Situation awareness-based agent transparency for human-autonomy teaming effectiveness

NASA Astrophysics Data System (ADS)

Chen, Jessie Y. C.; Barnes, Michael J.; Wright, Julia L.; Stowers, Kimberly; Lakhmani, Shan G.

2017-05-01

We developed the Situation awareness-based Agent Transparency (SAT) model to support human operators' situation awareness of the mission environment through teaming with intelligent agents. The model includes the agent's current actions and plans (Level 1), its reasoning process (Level 2), and its projection of future outcomes (Level 3). Human-inthe-loop simulation experiments have been conducted (Autonomous Squad Member and IMPACT) to illustrate the utility of the model for human-autonomy team interface designs. Across studies, the results consistently showed that human operators' task performance improved as the agents became more transparent. They also perceived transparent agents as more trustworthy.

Human Hemato-Lymphoid System Mice: Current Use and Future Potential for Medicine

PubMed Central

Rongvaux, Anthony; Takizawa, Hitoshi; Strowig, Till; Willinger, Tim; Eynon, Elizabeth E.

2014-01-01

To directly study complex human hemato-lymphoid system physiology and respective system-associated diseases in vivo, human-to-mouse xenotransplantation models for human blood and blood-forming cells and organs have been developed over the past three decades. We here review the fundamental requirements and the remarkable progress made over the past few years in improving these systems, the current major achievements reached by use of these models, and the future challenges to more closely model and study human health and disease and to achieve predictive preclinical testing of both prevention measures and potential new therapies. PMID:23330956

Mouse Models of Human T Lymphotropic Virus Type-1–Associated Adult T-Cell Leukemia/Lymphoma

PubMed Central

Zimmerman, B.; Niewiesk, S.; Lairmore, M. D.

2011-01-01

Human T-lymphotropic virus type-1 (HTLV-1), the first human retrovirus discovered, is the causative agent of adult T-cell leukemia/lymphoma (ATL) and a number of lymphocyte-mediated inflammatory conditions including HTLV-1–associated myelopathy/tropical spastic paraparesis. Development of animal models to study the pathogenesis of HTLV-1–associated diseases has been problematic. Mechanisms of early infection and cell-to-cell transmission can be studied in rabbits and nonhuman primates, but lesion development and reagents are limited in these species. The mouse provides a cost-effective, highly reproducible model in which to study factors related to lymphoma development and the preclinical efficacy of potential therapies against ATL. The ability to manipulate transgenic mice has provided important insight into viral genes responsible for lymphocyte transformation. Expansion of various strains of immunodeficient mice has accelerated the testing of drugs and targeted therapy against ATL. This review compares various mouse models to illustrate recent advances in the understanding of HTLV-1–associated ATL development and how improvements in these models are critical to the future development of targeted therapies against this aggressive T-cell lymphoma. PMID:20442421

Generation of genetically-engineered animals using engineered endonucleases.

PubMed

Lee, Jong Geol; Sung, Young Hoon; Baek, In-Jeoung

2018-05-17

The key to successful drug discovery and development is to find the most suitable animal model of human diseases for the preclinical studies. The recent emergence of engineered endonucleases is allowing for efficient and precise genome editing, which can be used to develop potentially useful animal models for human diseases. In particular, zinc finger nucleases, transcription activator-like effector nucleases, and the clustered regularly interspaced short palindromic repeat systems are revolutionizing the generation of diverse genetically-engineered experimental animals including mice, rats, rabbits, dogs, pigs, and even non-human primates that are commonly used for preclinical studies of the drug discovery. Here, we describe recent advances in engineered endonucleases and their application in various laboratory animals. We also discuss the importance of genome editing in animal models for more closely mimicking human diseases.

Human pluripotent stem cell models of autism spectrum disorder: emerging frontiers, opportunities, and challenges towards neuronal networks in a dish.

PubMed

Aigner, Stefan; Heckel, Tobias; Zhang, Jitao D; Andreae, Laura C; Jagasia, Ravi

2014-03-01

Autism spectrum disorder (ASD) is characterized by deficits in language development and social cognition and the manifestation of repetitive and restrictive behaviors. Despite recent major advances, our understanding of the pathophysiological mechanisms leading to ASD is limited. Although most ASD cases have unknown genetic underpinnings, animal and human cellular models of several rare, genetically defined syndromic forms of ASD have provided evidence for shared pathophysiological mechanisms that may extend to idiopathic cases. Here, we review our current knowledge of the genetic basis and molecular etiology of ASD and highlight how human pluripotent stem cell-based disease models have the potential to advance our understanding of molecular dysfunction. We summarize landmark studies in which neuronal cell populations generated from human embryonic stem cells and patient-derived induced pluripotent stem cells have served to model disease mechanisms, and we discuss recent technological advances that may ultimately allow in vitro modeling of specific human neuronal circuitry dysfunction in ASD. We propose that these advances now offer an unprecedented opportunity to help better understand ASD pathophysiology. This should ultimately enable the development of cellular models for ASD, allowing drug screening and the identification of molecular biomarkers for patient stratification.

Next-generation models of human cardiogenesis via genome editing.

PubMed

Lian, Xiaojun; Xu, Jiejia; Li, Jinsong; Chien, Kenneth R

2014-09-18

Cardiogenesis is one of the earliest and most important steps during human development and is orchestrated by discrete families of heart progenitors, which build distinct regions of the fetal heart. For the past decade, a lineage map for the distinct subsets of progenitors that generate the embryonic mammalian heart has begun to lay a foundation for the development of new strategies for rebuilding the adult heart after injury, an unmet clinical need for the vast majority of patients with end-stage heart failure who are not heart transplant recipients. The studies also have implications for the root causes of congenital heart disease, which affects 1 in 50 live births, the most prevalent malformations in children. Although much of this insight has been generated in murine models, it is becoming increasingly clear that there can be important divergence with principles and pathways for human cardiogenesis, as well as for regenerative pathways. The development of human stem cell models, coupled with recent advances in genome editing with RNA-guided endonucleases, offers a new approach for the primary study of human cardiogenesis. In addition, application of the technology to the in vivo setting in large animal models, including nonhuman primates, has opened the door to genome-edited large animal models of adult and congenital heart disease, as well as a detailed mechanistic dissection of the more diverse and complex set of progenitor families and pathways, which guide human cardiogenesis. Implications of this new technology for a new generation of human-based, genetically tractable systems are discussed, along with potential therapeutic applications. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Repositioning the knee joint in human body FE models using a graphics-based technique.

PubMed

Jani, Dhaval; Chawla, Anoop; Mukherjee, Sudipto; Goyal, Rahul; Vusirikala, Nataraju; Jayaraman, Suresh

2012-01-01

Human body finite element models (FE-HBMs) are available in standard occupant or pedestrian postures. There is a need to have FE-HBMs in the same posture as a crash victim or to be configured in varying postures. Developing FE models for all possible positions is not practically viable. The current work aims at obtaining a posture-specific human lower extremity model by reconfiguring an existing one. A graphics-based technique was developed to reposition the lower extremity of an FE-HBM by specifying the flexion-extension angle. Elements of the model were segregated into rigid (bones) and deformable components (soft tissues). The bones were rotated about the flexion-extension axis followed by rotation about the longitudinal axis to capture the twisting of the tibia. The desired knee joint movement was thus achieved. Geometric heuristics were then used to reposition the skin. A mapping defined over the space between bones and the skin was used to regenerate the soft tissues. Mesh smoothing was then done to augment mesh quality. The developed method permits control over the kinematics of the joint and maintains the initial mesh quality of the model. For some critical areas (in the joint vicinity) where element distortion is large, mesh smoothing is done to improve mesh quality. A method to reposition the knee joint of a human body FE model was developed. Repositions of a model from 9 degrees of flexion to 90 degrees of flexion in just a few seconds without subjective interventions was demonstrated. Because the mesh quality of the repositioned model was maintained to a predefined level (typically to the level of a well-made model in the initial configuration), the model was suitable for subsequent simulations.

A framework for human-hydrologic system model development integrating hydrology and water management: application to the Cutzamala water system in Mexico

NASA Astrophysics Data System (ADS)

Wi, S.; Freeman, S.; Brown, C.

2017-12-01

This study presents a general approach to developing computational models of human-hydrologic systems where human modification of hydrologic surface processes are significant or dominant. A river basin system is represented by a network of human-hydrologic response units (HHRUs) identified based on locations where river regulations happen (e.g., reservoir operation and diversions). Natural and human processes in HHRUs are simulated in a holistic framework that integrates component models representing rainfall-runoff, river routing, reservoir operation, flow diversion and water use processes. We illustrate the approach in a case study of the Cutzamala water system (CWS) in Mexico, a complex inter-basin water transfer system supplying the Mexico City Metropolitan Area (MCMA). The human-hydrologic system model for CWS (CUTZSIM) is evaluated in terms of streamflow and reservoir storages measured across the CWS and to water supplied for MCMA. The CUTZSIM improves the representation of hydrology and river-operation interaction and, in so doing, advances evaluation of system-wide water management consequences under altered climatic and demand regimes. The integrated modeling framework enables evaluation and simulation of model errors throughout the river basin, including errors in representation of the human component processes. Heretofore, model error evaluation, predictive error intervals and the resultant improved understanding have been limited to hydrologic processes. The general framework represents an initial step towards fuller understanding and prediction of the many and varied processes that determine the hydrologic fluxes and state variables in real river basins.

Gene Editing and Human Pluripotent Stem Cells: Tools for Advancing Diabetes Disease Modeling and Beta-Cell Development.

PubMed

Millette, Katelyn; Georgia, Senta

2017-10-05

This review will focus on the multiple approaches to gene editing and address the potential use of genetically modified human pluripotent stem cell-derived beta cells (SC-β) as a tool to study human beta-cell development and model their function in diabetes. We will explore how new variations of CRISPR/Cas9 gene editing may accelerate our understanding of beta-cell developmental biology, elucidate novel mechanisms that establish and regulate beta-cell function, and assist in pioneering new therapeutic modalities for treating diabetes. Improvements in CRISPR/Cas9 target specificity and homology-directed recombination continue to advance its use in engineering stem cells to model and potentially treat disease. We will review how CRISPR/Cas9 gene editing is informing our understanding of beta-cell development and expanding the therapeutic possibilities for treating diabetes and other diseases. Here we focus on the emerging use of gene editing technology, specifically CRISPR/Cas9, as a means of manipulating human gene expression to gain novel insights into the roles of key factors in beta-cell development and function. Taken together, the combined use of SC-β cells and CRISPR/Cas9 gene editing will shed new light on human beta-cell development and function and accelerate our progress towards developing new therapies for patients with diabetes.

Spatial durbin error model for human development index in Province of Central Java.

NASA Astrophysics Data System (ADS)

Septiawan, A. R.; Handajani, S. S.; Martini, T. S.

2018-05-01

The Human Development Index (HDI) is an indicator used to measure success in building the quality of human life, explaining how people access development outcomes when earning income, health and education. Every year HDI in Central Java has improved to a better direction. In 2016, HDI in Central Java was 69.98 %, an increase of 0.49 % over the previous year. The objective of this study was to apply the spatial Durbin error model using angle weights queen contiguity to measure HDI in Central Java Province. Spatial Durbin error model is used because the model overcomes the spatial effect of errors and the effects of spatial depedency on the independent variable. Factors there use is life expectancy, mean years of schooling, expected years of schooling, and purchasing power parity. Based on the result of research, we get spatial Durbin error model for HDI in Central Java with influencing factors are life expectancy, mean years of schooling, expected years of schooling, and purchasing power parity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, Paul A.; Cooper, Candice Frances; Burnett, Damon J.

Light body armor development for the warfighter is based on trial-and-error testing of prototype designs against ballistic projectiles. Torso armor testing against blast is virtually nonexistent but necessary to ensure adequate protection against injury to the heart and lungs. In this report, we discuss the development of a high-fidelity human torso model, it's merging with the existing Sandia Human Head-Neck Model, and development of the modeling & simulation (M&S) capabilities necessary to simulate wound injury scenarios. Using the new Sandia Human Torso Model, we demonstrate the advantage of virtual simulation in the investigation of wound injury as it relates tomore » the warfighter experience. We present the results of virtual simulations of blast loading and ballistic projectile impact to the tors o with and without notional protective armor. In this manner, we demonstrate the ad vantages of applying a modeling and simulation approach to the investigation of wound injury and relative merit assessments of protective body armor without the need for trial-and-error testing.« less

A quantitative framework to evaluate modeling of cortical development by neural stem cells

PubMed Central

Stein, Jason L.; de la Torre-Ubieta, Luis; Tian, Yuan; Parikshak, Neelroop N.; Hernandez, Israel A.; Marchetto, Maria C.; Baker, Dylan K.; Lu, Daning; Hinman, Cassidy R.; Lowe, Jennifer K.; Wexler, Eric M.; Muotri, Alysson R.; Gage, Fred H.; Kosik, Kenneth S.; Geschwind, Daniel H.

2014-01-01

Summary Neural stem cells have been adopted to model a wide range of neuropsychiatric conditions in vitro. However, how well such models correspond to in vivo brain has not been evaluated in an unbiased, comprehensive manner. We used transcriptomic analyses to compare in vitro systems to developing human fetal brain and observed strong conservation of in vivo gene expression and network architecture in differentiating primary human neural progenitor cells (phNPCs). Conserved modules are enriched in genes associated with ASD, supporting the utility of phNPCs for studying neuropsychiatric disease. We also developed and validated a machine learning approach called CoNTExT that identifies the developmental maturity and regional identity of in vitro models. We observed strong differences between in vitro models, including hiPSC-derived neural progenitors from multiple laboratories. This work provides a systems biology framework for evaluating in vitro systems and supports their value in studying the molecular mechanisms of human neurodevelopmental disease. PMID:24991955

Chemically induced skin carcinogenesis: Updates in experimental models (Review)

PubMed Central

NEAGU, MONICA; CARUNTU, CONSTANTIN; CONSTANTIN, CAROLINA; BODA, DANIEL; ZURAC, SABINA; SPANDIDOS, DEMETRIOS A.; TSATSAKIS, ARISTIDIS M.

2016-01-01

Skin cancer is one of the most common malignancies affecting humans worldwide, and its incidence is rapidly increasing. The study of skin carcinogenesis is of major interest for both scientific research and clinical practice and the use of in vivo systems may facilitate the investigation of early alterations in the skin and of the mechanisms involved, and may also lead to the development of novel therapeutic strategies for skin cancer. This review outlines several aspects regarding the skin toxicity testing domain in mouse models of chemically induced skin carcinogenesis. There are important strain differences in view of the histological type, development and clinical evolution of the skin tumor, differences reported decades ago and confirmed by our hands-on experience. Using mouse models in preclinical testing is important due to the fact that, at the molecular level, common mechanisms with human cutaneous tumorigenesis are depicted. These animal models resemble human skin cancer development, in that genetic changes caused by carcinogens and pro-inflammatory cytokines, and simultaneous inflammation sustained by pro-inflammatory cytokines and chemokines favor tumor progression. Drugs and environmental conditions can be tested using these animal models. keeping in mind the differences between human and rodent skin physiology. PMID:26986013

Development of a strain rate dependent material model of human cortical bone for computer-aided reconstruction of injury mechanisms.

PubMed

Asgharpour, Zahra; Zioupos, Peter; Graw, Matthias; Peldschus, Steffen

2014-03-01

Computer-aided methods such as finite-element simulation offer a great potential in the forensic reconstruction of injury mechanisms. Numerous studies have been performed on understanding and analysing the mechanical properties of bone and the mechanism of its fracture. Determination of the mechanical properties of bones is made on the same basis used for other structural materials. The mechanical behaviour of bones is affected by the mechanical properties of the bone material, the geometry, the loading direction and mode and of course the loading rate. Strain rate dependency of mechanical properties of cortical bone has been well demonstrated in literature studies, but as many of these were performed on animal bones and at non-physiological strain rates it is questionable how these will apply in the human situations. High strain-rates dominate in a lot of forensic applications in automotive crashes and assault scenarios. There is an overwhelming need to a model which can describe the complex behaviour of bone at lower strain rates as well as higher ones. Some attempts have been made to model the viscoelastic and viscoplastic properties of the bone at high strain rates using constitutive mathematical models with little demonstrated success. The main objective of the present study is to model the rate dependent behaviour of the bones based on experimental data. An isotropic material model of human cortical bone with strain rate dependency effects is implemented using the LS-DYNA material library. We employed a human finite element model called THUMS (Total Human Model for Safety), developed by Toyota R&D Labs and the Wayne State University, USA. The finite element model of the human femur is extracted from the THUMS model. Different methods have been employed to develop a strain rate dependent material model for the femur bone. Results of one the recent experimental studies on human femur have been employed to obtain the numerical model for cortical femur. A forensic application of the model is explained in which impacts to the arm have been reconstructed using the finite element model of THUMS. The advantage of the numerical method is that a wide range of impact conditions can be easily reconstructed. Impact velocity has been changed as a parameter to find the tolerance levels of injuries to the lower arm. The method can be further developed to study the assaults and the injury mechanism which can lead to severe traumatic injuries in forensic cases. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

[Representation and mathematical analysis of human crystalline lens].

PubMed

Tălu, Stefan; Giovanzana, Stefano; Tălu, Mihai

2011-01-01

The surface of human crystalline lens can be described and analyzed using mathematical models based on parametric representations, used in biomechanical studies and 3D solid modeling of the lens. The mathematical models used in lens biomechanics allow the study and the behavior of crystalline lens on variables and complex dynamic loads. Also, the lens biomechanics has the potential to improve the results in the development of intraocular lenses and cataract surgery. The paper presents the most representative mathematical models currently used for the modeling of human crystalline lens, both optically and biomechanically.

Recent advances in animal model experimentation in autism research.

PubMed

Tania, Mousumi; Khan, Md Asaduzzaman; Xia, Kun

2014-10-01

Autism, a lifelong neuro-developmental disorder is a uniquely human condition. Animal models are not the perfect tools for the full understanding of human development and behavior, but they can be an important place to start. This review focused on the recent updates of animal model research in autism. We have reviewed the publications over the last three decades, which are related to animal model study in autism. Animal models are important because they allow researchers to study the underlying neurobiology in a way that is not possible in humans. Improving the availability of better animal models will help the field to increase the development of medicines that can relieve disabling symptoms. Results from the therapeutic approaches are encouraging remarkably, since some behavioral alterations could be reversed even when treatment was performed on adult mice. Finding an animal model system with similar behavioral tendencies as humans is thus vital for understanding the brain mechanisms, supporting social motivation and attention, and the manner in which these mechanisms break down in autism. The ongoing studies should therefore increase the understanding of the biological alterations associated with autism as well as the development of knowledge-based treatments therapy for those struggling with autism. In this review, we have presented recent advances in research based on animal models of autism, raising hope for understanding the disease biology for potential therapeutic intervention to improve the quality of life of autism individuals.

Animal and Human Tissue Models of Vertical Listeria monocytogenes Transmission and Implications for Other Pregnancy-Associated Infections.

PubMed

Lowe, David E; Robbins, Jennifer R; Bakardjiev, Anna I

2018-06-01

Intrauterine infections lead to serious complications for mother and fetus, including preterm birth, maternal and fetal death, and neurological sequelae in the surviving offspring. Improving maternal and child heath is a global priority. Yet, the development of strategies to prevent and treat pregnancy-related diseases has lagged behind progress made in other medical fields. One of the challenges is finding tractable model systems that replicate the human maternal-fetal interface. Animal models offer the ability to study pathogenesis and host defenses in vivo However, the anatomy of the maternal-fetal interface is highly divergent across species. While many tools are available to study host responses in the pregnant mouse model, other animals have placentas that are more similar to that of humans. Here we describe new developments in animal and human tissue models to investigate the pathogenesis of listeriosis at the maternal-fetal interface. We highlight gaps in existing knowledge and make recommendations on how they can be filled. Copyright © 2018 American Society for Microbiology.

Avian models with spontaneous autoimmune diseases

PubMed Central

Wick, Georg; Andersson, Leif; Hala, Karel; Gershwin, M. Eric; Selmi, Carlo F.; Erf, Gisela F.; Lamont, Susan J.; Sgonc, Roswitha

2012-01-01

Autoimmune diseases in human patients only become clinically manifest when the disease process has developed to a stage where functional compensation by the afflicted organ or system is not possible any more. In order to understand the initial etiologic and pathogenic events that are generally not yet accessible in humans, appropriate animal models are required. In this respect, spontaneously developing models - albeit rare – reflect the situation in humans much more closely than experimentally induced models, including knockout and transgenic mice. The present review describes three spontaneous chicken models for human autoimmune diseases, the Obese strain (OS) with a Hashimoto-like autoimmune thyroiditis, the University of California at Davis lines 200 and 206 (UCD-200 and 206) with a scleroderma-like disease and the amelanotic Smyth line with a vitiligo-like syndrome (SLV). Special emphasis is given to the new opportunities to unravel the genetic basis of these diseases in view of the recently completed sequencing of the chicken genome. PMID:17145302

On the Importance of Comparative Research for the Understanding of Human Behavior and Development: A Reply to Gottlieb & Lickliter (2004)

ERIC Educational Resources Information Center

Maestripieri, Dario

2005-01-01

Comparative behavioral research is important for a number of reasons and can contribute to the understanding of human behavior and development in many different ways. Research with animal models of human behavior and development can be a source not only of general principles and testable hypotheses but also of empirical information that may be…

Building Innovation Capacity: The Role of Human Capital Formation in Enterprises--A Review of the Literature. Occasional Paper

ERIC Educational Resources Information Center

Smith, Andrew; Courvisanos, Jerry; Tuck, Jacqueline; McEachern, Steven

2011-01-01

This literature review examines the role of human capital formation in building innovative capacity in firms. The aim of the review is to develop a model of human capital development factors to be used as a basis for a larger research project where the factors that develop innovation capacity in enterprises will be investigated. The review finds…

Is the use of animals in biomedical research still necessary in 2002? Unfortunately, "yes".

PubMed

Festing, Michael F W

2004-06-01

The use of laboratory animals in the year 2002 is essential both to maintain human health and to develop new treatments for the many diseases that still plague humans. The suggestion by Greek and Greek in Sacred Cows and Golden Geese in 2000, that animal experiments are invalid because animals are different from humans, shows clearly that they do not understand the philosophical basis for the use of models in science and every day life. Models only need to resemble the thing being modelled (the target) in a few key respects. A map of Brooklyn Botanic Garden is a useful model, but it differs from the garden in many respects. There are many examples where studies on animals and in vitro alternatives result in accurate predictions of human responses even though the models differ from humans in other ways. In the drug development model, validation is done in clinical trials. Models are also used in the discovery of fundamental processes shared by some, or all, living organisms. The laws of genetics were first discovered by using garden peas, but they are equally applicable to humans. It is because of the ethical, rather than scientific, objections to the use of animals that all scientists are urged to find alternatives according to the principles of reduction, refinement and replacement, laid down by Russell and Burch in 1959.

Human Brain Modeling with Its Anatomical Structure and Realistic Material Properties for Brain Injury Prediction.

PubMed

Atsumi, Noritoshi; Nakahira, Yuko; Tanaka, Eiichi; Iwamoto, Masami

2018-05-01

Impairments of executive brain function after traumatic brain injury (TBI) due to head impacts in traffic accidents need to be obviated. Finite element (FE) analyses with a human brain model facilitate understanding of the TBI mechanisms. However, conventional brain FE models do not suitably describe the anatomical structure in the deep brain, which is a critical region for executive brain function, and the material properties of brain parenchyma. In this study, for better TBI prediction, a novel brain FE model with anatomical structure in the deep brain was developed. The developed model comprises a constitutive model of brain parenchyma considering anisotropy and strain rate dependency. Validation was performed against postmortem human subject test data associated with brain deformation during head impact. Brain injury analyses were performed using head acceleration curves obtained from reconstruction analysis of rear-end collision with a human whole-body FE model. The difference in structure was found to affect the regions of strain concentration, while the difference in material model contributed to the peak strain value. The injury prediction result by the proposed model was consistent with the characteristics in the neuroimaging data of TBI patients due to traffic accidents.

Population Physiologically-Based Pharmacokinetic Modeling for the Human Lactational Transfer of PCB 153 with Consideration of Worldwide Human Biomonitoring Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Redding, Laurel E.; Sohn, Michael D.; McKone, Thomas E.

2008-03-01

We developed a physiologically based pharmacokinetic model of PCB 153 in women, and predict its transfer via lactation to infants. The model is the first human, population-scale lactational model for PCB 153. Data in the literature provided estimates for model development and for performance assessment. Physiological parameters were taken from a cohort in Taiwan and from reference values in the literature. We estimated partition coefficients based on chemical structure and the lipid content in various body tissues. Using exposure data in Japan, we predicted acquired body burden of PCB 153 at an average childbearing age of 25 years and comparemore » predictions to measurements from studies in multiple countries. Forward-model predictions agree well with human biomonitoring measurements, as represented by summary statistics and uncertainty estimates. The model successfully describes the range of possible PCB 153 dispositions in maternal milk, suggesting a promising option for back estimating doses for various populations. One example of reverse dosimetry modeling was attempted using our PBPK model for possible exposure scenarios in Canadian Inuits who had the highest level of PCB 153 in their milk in the world.« less

Basic research needed for stimulating the development of behavioral technologies

PubMed Central

Mace, F. Charles

1994-01-01

The costs of disconnection between the basic and applied sectors of behavior analysis are reviewed, and some solutions to these problems are proposed. Central to these solutions are collaborations between basic and applied behavioral scientists in programmatic research that addresses the behavioral basis and solution of human behavior problems. This kind of collaboration parallels the deliberate interactions between basic and applied researchers that have proven to be so profitable in other scientific fields, such as medicine. Basic research questions of particular relevance to the development of behavioral technologies are posed in the following areas: response allocation, resistance to change, countercontrol, formation and differentiation/discrimination of stimulus and response classes, analysis of low-rate behavior, and rule-governed behavior. Three interrelated strategies to build connections between the basic and applied analysis of behavior are identified: (a) the development of nonhuman animal models of human behavior problems using operations that parallel plausible human circumstances, (b) replication of the modeled relations with human subjects in the operant laboratory, and (c) tests of the generality of the model with actual human problems in natural settings. PMID:16812734

Modeling the lung: Design and development of tissue engineered macro- and micro-physiologic lung models for research use.

PubMed

Nichols, Joan E; Niles, Jean A; Vega, Stephanie P; Argueta, Lissenya B; Eastaway, Adriene; Cortiella, Joaquin

2014-09-01

Respiratory tract specific cell populations, or tissue engineered in vitro grown human lung, have the potential to be used as research tools to mimic physiology, toxicology, pathology, as well as infectious diseases responses of cells or tissues. Studies related to respiratory tract pathogenesis or drug toxicity testing in the past made use of basic systems where single cell populations were exposed to test agents followed by evaluations of simple cellular responses. Although these simple single-cell-type systems provided good basic information related to cellular responses, much more can be learned from cells grown in fabricated microenvironments which mimic in vivo conditions in specialized microfabricated chambers or by human tissue engineered three-dimensional (3D) models which allow for more natural interactions between cells. Recent advances in microengineering technology, microfluidics, and tissue engineering have provided a new approach to the development of 2D and 3D cell culture models which enable production of more robust human in vitro respiratory tract models. Complex models containing multiple cell phenotypes also provide a more reasonable approximation of what occurs in vivo without the confounding elements in the dynamic in vivo environment. The goal of engineering good 3D human models is the formation of physiologically functional respiratory tissue surrogates which can be used as pathogenesis models or in the case of 2D screening systems for drug therapy evaluation as well as human toxicity testing. We hope that this manuscript will serve as a guide for development of future respiratory tract model systems as well as a review of conventional models. © 2014 by the Society for Experimental Biology and Medicine.

Controlled human infection models for vaccine development: Zika virus debate.

PubMed

Gopichandran, Vijayaprasad

2018-01-01

An ethics panel, convened by the National Institute of Health and other research bodies in the USA, disallowed researchers from the Johns Hopkins University and University of Vermont from performing controlled human infection of healthy volunteers to develop a vaccine against Zika virus infection. The members published their ethical analysis and recommendations in February 2017. They have elaborated on the risks posed by human challenge with Zika virus to the volunteers and other uninvolved third parties and have systematically analysed the social value of such a human challenge experiment. They have also posited some mandatory ethical requirements which should be met before allowing the infection of healthy volunteers with the Zika virus. This commentary elaborates on the debate on the ethics of the human challenge model for the development of a Zika virus vaccine and the role of systematic ethical analysis in protecting the interests of research participants. It further analyses the importance of this debate to the development of a Zika vaccine in India.

A Single-Cell Roadmap of Lineage Bifurcation in Human ESC Models of Embryonic Brain Development.

PubMed

Yao, Zizhen; Mich, John K; Ku, Sherman; Menon, Vilas; Krostag, Anne-Rachel; Martinez, Refugio A; Furchtgott, Leon; Mulholland, Heather; Bort, Susan; Fuqua, Margaret A; Gregor, Ben W; Hodge, Rebecca D; Jayabalu, Anu; May, Ryan C; Melton, Samuel; Nelson, Angelique M; Ngo, N Kiet; Shapovalova, Nadiya V; Shehata, Soraya I; Smith, Michael W; Tait, Leah J; Thompson, Carol L; Thomsen, Elliot R; Ye, Chaoyang; Glass, Ian A; Kaykas, Ajamete; Yao, Shuyuan; Phillips, John W; Grimley, Joshua S; Levi, Boaz P; Wang, Yanling; Ramanathan, Sharad

2017-01-05

During human brain development, multiple signaling pathways generate diverse cell types with varied regional identities. Here, we integrate single-cell RNA sequencing and clonal analyses to reveal lineage trees and molecular signals underlying early forebrain and mid/hindbrain cell differentiation from human embryonic stem cells (hESCs). Clustering single-cell transcriptomic data identified 41 distinct populations of progenitor, neuronal, and non-neural cells across our differentiation time course. Comparisons with primary mouse and human gene expression data demonstrated rostral and caudal progenitor and neuronal identities from early brain development. Bayesian analyses inferred a unified cell-type lineage tree that bifurcates between cortical and mid/hindbrain cell types. Two methods of clonal analyses confirmed these findings and further revealed the importance of Wnt/β-catenin signaling in controlling this lineage decision. Together, these findings provide a rich transcriptome-based lineage map for studying human brain development and modeling developmental disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

A rapid method for selecting suitable animal species for studying pathogen interactions with plasma protein ligands in vivo.

PubMed

Naudin, Clément; Schumski, Ariane; Salo-Ahen, Outi M H; Herwald, Heiko; Smeds, Emanuel

2017-05-01

Species tropism constitutes a serious problem for developing relevant animal models of infection. Human pathogens can express virulence factors that show specific selectivity to human proteins, while their affinity for orthologs from other species can vary significantly. Suitable animal species must be used to analyse whether virulence factors are potential targets for drug development. We developed an assay that rapidly predicts applicable animal species for studying virulence factors binding plasma proteins. We used two well-characterized Staphylococcus aureus proteins, SSL7 and Efb, to develop an ELISA-based inhibition assay using plasma from different animal species. The interaction between SSL7 and human C5 and the binding of Efb to human fibrinogen and human C3 was studied. Affinity experiments and Western blot analyses were used to validate the assay. Human, monkey and cat plasma interfered with binding of SSL7 to human C5. Binding of Efb to human fibrinogen was blocked in human, monkey, gerbil and pig plasma, while human, monkey, gerbil, rabbit, cat and guinea pig plasma inhibited the binding of Efb to human C3. These results emphasize the importance of choosing correct animal models, and thus, our approach is a rapid and cost-effective method that can be used to prevent unnecessary animal experiments. © 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

A study of a steering system algorithm for pleasure boats based on stability analysis of a human-machine system model

NASA Astrophysics Data System (ADS)

Ikeda, Fujio; Toyama, Shigehiro; Ishiduki, Souta; Seta, Hiroaki

2016-09-01

Maritime accidents of small ships continue to increase in number. One of the major factors is poor manoeuvrability of the Manual Hydraulic Steering Mechanism (MHSM) in common use. The manoeuvrability can be improved by using the Electronic Control Steering Mechanism (ECSM). This paper conducts stability analyses of a pleasure boat controlled by human models in view of path following on a target course, in order to establish design guidelines for the ECSM. First, to analyse the stability region, the research derives the linear approximated model in a planar global coordinate system. Then, several human models are assumed to develop closed-loop human-machine controlled systems. These human models include basic proportional, derivative, integral and time-delay actions. The stability analysis simulations for those human-machine systems are carried out. The results show that the stability region tends to spread as a ship's velocity increases in the case of the basic proportional human model. The derivative action and time-delay action of human models are effective in spreading the stability region in their respective ranges of frontal gazing points.

Disease modeling using human induced pluripotent stem cells: lessons from the liver.

PubMed

Gieseck, Richard L; Colquhoun, Jennifer; Hannan, Nicholas R F

2015-01-01

Human pluripotent stem cells (hPSCs) have the capacity to differentiate into any of the hundreds of distinct cell types that comprise the human body. This unique characteristic has resulted in considerable interest in the field of regenerative medicine, given the potential for these cells to be used to protect, repair, or replace diseased, injured, and aged cells within the human body. In addition to their potential in therapeutics, hPSCs can be used to study the earliest stages of human development and to provide a platform for both drug screening and disease modeling using human cells. Recently, the description of human induced pluripotent stem cells (hIPSCs) has allowed the field of disease modeling to become far more accessible and physiologically relevant, as pluripotent cells can be generated from patients of any genetic background. Disease models derived from hIPSCs that manifest cellular disease phenotypes have been established to study several monogenic diseases; furthermore, hIPSCs can be used for phenotype-based drug screens to investigate complex diseases for which the underlying genetic mechanism is unknown. As a result, the use of stem cells as research tools has seen an unprecedented growth within the last decade as researchers look for in vitro disease models which closely mimic in vivo responses in humans. Here, we discuss the beginnings of hPSCs, starting with isolation of human embryonic stem cells, moving into the development and optimization of hIPSC technology, and ending with the application of hIPSCs towards disease modeling and drug screening applications, with specific examples highlighting the modeling of inherited metabolic disorders of the liver. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Comparative Pathogenesis of Autoimmune Diabetes in Humans, NOD Mice, and Canines: Has a Valuable Animal Model of Type 1 Diabetes Been Overlooked?

PubMed Central

O’Kell, Allison L.; Wasserfall, Clive; Catchpole, Brian; Davison, Lucy J.; Hess, Rebecka S.; Kushner, Jake A.

2017-01-01

Despite decades of research in humans and mouse models of disease, substantial gaps remain in our understanding of pathogenic mechanisms underlying the development of type 1 diabetes. Furthermore, translation of therapies from preclinical efforts capable of delaying or halting β-cell destruction has been limited. Hence, a pressing need exists to identify alternative animal models that reflect human disease. Canine insulin deficiency diabetes is, in some cases, considered to follow autoimmune pathogenesis, similar to NOD mice and humans, characterized by hyperglycemia requiring lifelong exogenous insulin therapy. Also similar to human type 1 diabetes, the canonical canine disorder appears to be increasing in prevalence. Whereas islet architecture in rodents is distinctly different from humans, canine pancreatic endocrine cell distribution is more similar. Differences in breed susceptibility alongside associations with MHC and other canine immune response genes parallel that of different ethnic groups within the human population, a potential benefit over NOD mice. The impact of environment on disease development also favors canine over rodent models. Herein, we consider the potential for canine diabetes to provide valuable insights for human type 1 diabetes in terms of pancreatic histopathology, impairment of β-cell function and mass, islet inflammation (i.e., insulitis), and autoantibodies specific for β-cell antigens. PMID:28533295

Investigation into metastatic processes and the therapeutic effects of gemcitabine on human pancreatic cancer using an orthotopic SUIT-2 pancreatic cancer mouse model

PubMed Central

Higuchi, Tamami; Yokobori, Takehiko; Naito, Tomoharu; Kakinuma, Chihaya; Hagiwara, Shinji; Nishiyama, Masahiko; Asao, Takayuki

2018-01-01

Prognosis of pancreatic cancer is poor, thus the development of novel therapeutic drugs is necessary. During preclinical studies, appropriate models are essential for evaluating drug efficacy. The present study sought to determine the ideal pancreatic cancer mouse model for reliable preclinical testing. Such a model could accurately reflect human pancreatic cancer phenotypes and predict future clinical trial results. Systemic pathology analysis was performed in an orthotopic transplantation model to prepare model mice for use in preclinical studies, mimicking the progress of human pancreatic cancer. The location and the timing of inoculated cancer cell metastases, pathogenesis and cause of fatality were analyzed. Furthermore, the efficacy of gemcitabine, a key pancreatic cancer drug, was evaluated in this model where liver metastasis and peritoneal dissemination occur. Results indicated that the SUIT-2 orthotopic pancreatic cancer model was similar to the phenotypic sequential progression of human pancreatic cancer, with extra-pancreatic invasion, intra-peritoneal dissemination and other hematogenous organ metastases. Notably, survival was prolonged by administering gemcitabine to mice with metastasized pancreatic cancer. Furthermore, the detailed effects of gemcitabine on the primary tumor and metastatic tumor lesions were pathologically evaluated in mice. The present study indicated the model accurately depicted pancreatic cancer development and metastasis. Furthermore, the detailed effects of pancreatic cancer drugs on the primary tumor and on metastatic tumor lesions. We present this model as a potential new standard for new drug development in pancreatic cancer. PMID:29435042

Analysis of an algae-based CELSS. I - Model development

NASA Technical Reports Server (NTRS)

Holtzapple, Mark T.; Little, Frank E.; Makela, Merry E.; Patterson, C. O.

1989-01-01

A steady state chemical model and computer program have been developed for a life support system and applied to trade-off studies. The model is based on human demand for food and oxygen determined from crew metabolic needs. The model includes modules for water recycle, waste treatment, CO2 removal and treatment, and food production. The computer program calculates rates of use and material balance for food, O2, the recycle of human waste and trash, H2O, N2, and food production/supply. A simple noniterative solution for the model has been developed using the steady state rate equations for the chemical reactions. The model and program have been used in system sizing and subsystem trade-off studies of a partially closed life support system.

Analysis of an algae-based CELSS. Part 1: model development

NASA Technical Reports Server (NTRS)

Holtzapple, M. T.; Little, F. E.; Makela, M. E.; Patterson, C. O.

1989-01-01

A steady state chemical model and computer program have been developed for a life support system and applied to trade-off studies. The model is based on human demand for food and oxygen determined from crew metabolic needs. The model includes modules for water recycle, waste treatment, CO2 removal and treatment, and food production. The computer program calculates rates of use and material balance for food. O2, the recycle of human waste and trash, H2O, N2, and food production supply. A simple non-iterative solution for the model has been developed using the steady state rate equations for the chemical reactions. The model and program have been used in system sizing and subsystem trade-off studies of a partially closed life support system.

Development of a landscape integrity model framework to support regional conservation planning.

PubMed

Walston, Leroy J; Hartmann, Heidi M

2018-01-01

Land managers increasingly rely upon landscape assessments to understand the status of natural resources and identify conservation priorities. Many of these landscape planning efforts rely on geospatial models that characterize the ecological integrity of the landscape. These general models utilize measures of habitat disturbance and human activity to map indices of ecological integrity. We built upon these modeling frameworks by developing a Landscape Integrity Index (LII) model using geospatial datasets of the human footprint, as well as incorporation of other indicators of ecological integrity such as biodiversity and vegetation departure. Our LII model serves as a general indicator of ecological integrity in a regional context of human activity, biodiversity, and change in habitat composition. We also discuss the application of the LII framework in two related coarse-filter landscape conservation approaches to expand the size and connectedness of protected areas as regional mitigation for anticipated land-use changes.

Development of a landscape integrity model framework to support regional conservation planning

PubMed Central

Hartmann, Heidi M.

2018-01-01

Land managers increasingly rely upon landscape assessments to understand the status of natural resources and identify conservation priorities. Many of these landscape planning efforts rely on geospatial models that characterize the ecological integrity of the landscape. These general models utilize measures of habitat disturbance and human activity to map indices of ecological integrity. We built upon these modeling frameworks by developing a Landscape Integrity Index (LII) model using geospatial datasets of the human footprint, as well as incorporation of other indicators of ecological integrity such as biodiversity and vegetation departure. Our LII model serves as a general indicator of ecological integrity in a regional context of human activity, biodiversity, and change in habitat composition. We also discuss the application of the LII framework in two related coarse-filter landscape conservation approaches to expand the size and connectedness of protected areas as regional mitigation for anticipated land-use changes. PMID:29614093

Human Resource Development to Facilitate Experiential Learning: The Case of Yahoo Japan

ERIC Educational Resources Information Center

Matsuo, Makoto

2015-01-01

Although work experiences are recognized as important mechanisms for developing leaders in organizations, existing research has focused primarily on work assignments rather than on human resource development (HRD) systems that promote experiential learning of managers. The primary goal of this study was to develop an HRD model for facilitating…

SU-E-J-93: Development of Pre-Contoured Human Model Library in DICOM-RT Format for the Epidemiological Study of the Radiotherapy Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pyakuryal, A; Lee, C; Lee, C

Purpose: Prior to 3D conformal radiation therapy planning, patient anatomy information was mostly limited to 2D beams-eye-view from the conventional simulator. To analyze the outcomes of such treatments for radiation late effects, 3D computational human models are often used in commercial treatment planning systems (TPSs). However, several underlying difficulties such as time-consuming manual delineation procedures of a large number of structures in the model have always limited its applications. Primary objective of this work was to develop a human model library for the epidemiological study by converting 3D-surface model organs to DICOM-RT format (DICOM-RT structure) using an in-house built software.more » We converted the ICRP reference human models to DICOM-RT models, which can be readily adopted for various dose calculations. Methods: MATLAB based code were utilized to convert the contour drawings extracted in text-format from the 3D graphic-tool, Rhinoceros into DICOM-RT structure format for 50 different organs of each model using a 16GB dual-core processor. The conversion periods were measured for each DICOM-RT models, and the reconstructed structure volumes were validated against the original 3D-surface models in the TPS. Ten reference hybrid whole-body models (8-pediatric and 2-adults) were automatically processed to create DICOM-RT computational human model library. Results: Mean contour conversion period was found to be 580 (N=2) and 394.5 (N=8) seconds for 50 organs in the adult and pediatric models respectively. A good agreement for large organs (NRMSD <1.0%) and small organs (NRMSD <7.7%) was also observed between the original volumes and corresponding DICOM-RT structure volumes of the organs. Conclusion: The ICRP reference human models were converted into DICOM-RT format to support the epidemiological study using a large cohort of conventional radiotherapy patients. Due to its DICOM-compatibility, the library may be implemented to many other different applications. We also expect to develop the library by including additional models in future.« less

Xenotransplantation as a model for human testicular development.

PubMed

Hutka, Marsida; Smith, Lee B; Mitchell, Rod T

The developing male reproductive system may be sensitive to disruption by a wide range of exogenous 'endocrine disruptors'. In-utero exposure to environmental chemicals and pharmaceuticals have been hypothesized to have an impact in the increasing incidence of male reproductive disorders. The vulnerability to adverse effects as a consequence of such exposures is elevated during a specific 'window of susceptibility' in fetal life referred to as the masculinisation programing window (MPW). Exposures that occur during prepuberty, such as chemotherapy treatment for cancer during childhood, may also affect future fertility. Much of our current knowledge about fetal and early postnatal human testicular development derives from studies conducted in animal models predictive for humans. Therefore, over recent years, testicular transplantation has been employed as a 'direct' approach to understand the development of human fetal and prepubertal testis in health and disease. In this review we describe the potential use of human testis xenotransplantation to study testicular development and its application for (i) assessing the effects of environmental exposures in humans, and (ii) establishing fertility preservation options for prepubertal boys with cancer. Copyright © 2017 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Artificial retina model for the retinally blind based on wavelet transform

NASA Astrophysics Data System (ADS)

Zeng, Yan-an; Song, Xin-qiang; Jiang, Fa-gang; Chang, Da-ding

2007-01-01

Artificial retina is aimed for the stimulation of remained retinal neurons in the patients with degenerated photoreceptors. Microelectrode arrays have been developed for this as a part of stimulator. Design such microelectrode arrays first requires a suitable mathematical method for human retinal information processing. In this paper, a flexible and adjustable human visual information extracting model is presented, which is based on the wavelet transform. With the flexible of wavelet transform to image information processing and the consistent to human visual information extracting, wavelet transform theory is applied to the artificial retina model for the retinally blind. The response of the model to synthetic image is shown. The simulated experiment demonstrates that the model behaves in a manner qualitatively similar to biological retinas and thus may serve as a basis for the development of an artificial retina.

Dynamic Simulation of Human Thermoregulation and Heat Transfer for Spaceflight Applications

NASA Technical Reports Server (NTRS)

Miller, Thomas R.; Nelson, David A.; Bue, Grant; Kuznetz, Lawrence

2011-01-01

Models of human thermoregulation and heat transfer date from the early 1970s and have been developed for applications ranging from evaluating thermal comfort in spacecraft and aircraft cabin environments to predicting heat stress during EVAs. Most lumped or compartment models represent the body as an assemblage cylindrical and spherical elements which may be subdivided into layers to describe tissue heterogeneity. Many existing models are of limited usefulness in asymmetric thermal environments, such as may be encountered during an EVA. Conventional whole-body clothing models also limit the ability to describe local surface thermal and evaporation effects in sufficient detail. A further limitation is that models based on a standard man model are not readily scalable to represent large or small subjects. This work describes development of a new human thermal model derived from the 41-node man model. Each segment is divided into four concentric, constant thickness cylinders made up of a central core surrounded by muscle, fat, and skin, respectively. These cylinders are connected by the flow of blood from a central blood pool to each part. The central blood pool is updated at each time step, based on a whole-body energy balance. Results show the model simulates core and surface temperature histories, sweat evaporation and metabolic rates which generally are consistent with controlled exposures of human subjects. Scaling rules are developed to enable simulation of small and large subjects (5th percentile and 95th percentile). Future refinements will include a clothing model that addresses local surface insulation and permeation effects and developing control equations to describe thermoregulatory effects such as may occur with prolonged weightlessness or with aging.

The Asian Human Resource Approach in Global Perspective.

ERIC Educational Resources Information Center

Cummings, William K.

1995-01-01

Challenges the prevailing Western approach to education by asserting that several Asian nations have and are developing a distinctive approach to human resource development. Describes characteristics of this approach and contrasts it to the Western model. (CFR)

Healthy Eating--A Human Development Intervention Perspective.

ERIC Educational Resources Information Center

D'Augelli, Anthony R.

1981-01-01

Describes limitations of the psychological view that has dominated obesity research. The "brand" of psychology represented is assessed on its conceptual strengths, its implications for intervention program development, and its consequences for the delivery of services to people in communities. Suggests use of a human development model.…

Three-Dimensional Visualization with Large Data Sets: A Simulation of Spreading Cortical Depression in Human Brain

PubMed Central

Ertürk, Korhan Levent; Şengül, Gökhan

2012-01-01

We developed 3D simulation software of human organs/tissues; we developed a database to store the related data, a data management system to manage the created data, and a metadata system for the management of data. This approach provides two benefits: first of all the developed system does not require to keep the patient's/subject's medical images on the system, providing less memory usage. Besides the system also provides 3D simulation and modification options, which will help clinicians to use necessary tools for visualization and modification operations. The developed system is tested in a case study, in which a 3D human brain model is created and simulated from 2D MRI images of a human brain, and we extended the 3D model to include the spreading cortical depression (SCD) wave front, which is an electrical phoneme that is believed to cause the migraine. PMID:23258956

A Qualitative Model of Human Interaction with Complex Dynamic Systems

NASA Technical Reports Server (NTRS)

Hess, Ronald A.

1987-01-01

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

A qualitative model of human interaction with complex dynamic systems

NASA Technical Reports Server (NTRS)

Hess, Ronald A.

1987-01-01

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

A Mouse to Human Search for Plasma Proteome Changes Associated with Pancreatic Tumor Development

PubMed Central

Faca, Vitor M; Song, Kenneth S; Wang, Hong; Zhang, Qing; Krasnoselsky, Alexei L; Newcomb, Lisa F; Plentz, Ruben R; Gurumurthy, Sushma; Redston, Mark S; Pitteri, Sharon J; Pereira-Faca, Sandra R; Ireton, Renee C; Katayama, Hiroyuki; Glukhova, Veronika; Phanstiel, Douglas; Brenner, Dean E; Anderson, Michelle A; Misek, David; Scholler, Nathalie; Urban, Nicole D; Barnett, Matt J; Edelstein, Cim; Goodman, Gary E; Thornquist, Mark D; McIntosh, Martin W; DePinho, Ronald A; Bardeesy, Nabeel; Hanash, Samir M

2008-01-01

Background The complexity and heterogeneity of the human plasma proteome have presented significant challenges in the identification of protein changes associated with tumor development. Refined genetically engineered mouse (GEM) models of human cancer have been shown to faithfully recapitulate the molecular, biological, and clinical features of human disease. Here, we sought to exploit the merits of a well-characterized GEM model of pancreatic cancer to determine whether proteomics technologies allow identification of protein changes associated with tumor development and whether such changes are relevant to human pancreatic cancer. Methods and Findings Plasma was sampled from mice at early and advanced stages of tumor development and from matched controls. Using a proteomic approach based on extensive protein fractionation, we confidently identified 1,442 proteins that were distributed across seven orders of magnitude of abundance in plasma. Analysis of proteins chosen on the basis of increased levels in plasma from tumor-bearing mice and corroborating protein or RNA expression in tissue documented concordance in the blood from 30 newly diagnosed patients with pancreatic cancer relative to 30 control specimens. A panel of five proteins selected on the basis of their increased level at an early stage of tumor development in the mouse was tested in a blinded study in 26 humans from the CARET (Carotene and Retinol Efficacy Trial) cohort. The panel discriminated pancreatic cancer cases from matched controls in blood specimens obtained between 7 and 13 mo prior to the development of symptoms and clinical diagnosis of pancreatic cancer. Conclusions Our findings indicate that GEM models of cancer, in combination with in-depth proteomic analysis, provide a useful strategy to identify candidate markers applicable to human cancer with potential utility for early detection. PMID:18547137

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 forward to critically evaluate and improve animal models of human disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Preclinical Testing of Antihuman CD28 Fab' Antibody in a Novel Nonhuman Primate Small Animal Rodent Model of Xenogenic Graft-Versus-Host Disease.

PubMed

Hippen, Keli L; Watkins, Benjamin; Tkachev, Victor; Lemire, Amanda M; Lehnen, Charles; Riddle, Megan J; Singh, Karnail; Panoskaltsis-Mortari, Angela; Vanhove, Bernard; Tolar, Jakub; Kean, Leslie S; Blazar, Bruce R

2016-12-01

Graft-versus-host disease (GVHD) is a severe complication of hematopoietic stem cell transplantation. Current therapies to prevent alloreactive T cell activation largely cause generalized immunosuppression and may result in adverse drug, antileukemia and antipathogen responses. Recently, several immunomodulatory therapeutics have been developed that show efficacy in maintaining antileukemia responses while inhibiting GVHD in murine models. To analyze efficacy and better understand immunological tolerance, escape mechanisms, and side effects of clinical reagents, testing of species cross-reactive human agents in large animal GVHD models is critical. We have previously developed and refined a nonhuman primate (NHP) large animal GVHD model. However, this model is not readily amenable to semi-high throughput screening of candidate clinical reagents. Here, we report a novel, optimized NHP xenogeneic GVHD (xeno-GVHD) small animal model that recapitulates many aspects of NHP and human GVHD. This model was validated using a clinically available blocking, monovalent anti-CD28 antibody (FR104) whose effects in a human xeno-GVHD rodent model are known. Because human-reactive reagents may not be fully cross-reactive or effective in vivo on NHP immune cells, this NHP xeno-GVHD model provides immunological insights and direct testing on NHP-induced GVHD before committing to the intensive NHP studies that are being increasingly used for detailed evaluation of new immune therapeutic strategies before human trials.

Targeting VEGF in canine oxygen-induced retinopathy - a model for human retinopathy of prematurity.

PubMed

McLeod, D Scott; Lutty, Gerard A

2016-01-01

Development of the dog superficial retinal vasculature is similar to the mechanism of human retinal vasculature development; they both develop by vasculogenesis, differentiation, and assembly of vascular precursors called angioblasts. Canine oxygen-induced retinopathy (OIR) was first developed by Arnall Patz in an effort to experimentally determine the effects of hyperoxia on the development of the retinal vasculature. The canine OIR model has many characteristics in common with human retinopathy of prematurity. Exposure of 1-day-old dogs to hyperoxia for 4 days causes a vaso-obliteration throughout the retina. Vasoproliferation, after the animals have returned to room air, is robust. The initial small preretinal neovascular formations anastomose to form large preretinal membranes that eventually cause tractional retinal folds. The end-stage pathology of the canine model is similar to stage IV human retinopathy of prematurity. Therefore, canine OIR is an excellent forum to evaluate the response to drugs targeting VEGF and its receptors. Evaluation of an antibody to VEGF-R2 and the VEGF-Trap demonstrated that doses should be titered down so that preretinal neovascularization is inhibited but retinal revascularization is able to proceed, vascularizing peripheral retina and preventing it from being a source of VEGF.

Modeling congenital disease and inborn errors of development in Drosophila melanogaster

PubMed Central

Moulton, Matthew J.; Letsou, Anthea

2016-01-01

ABSTRACT Fly models that faithfully recapitulate various aspects of human disease and human health-related biology are being used for research into disease diagnosis and prevention. Established and new genetic strategies in Drosophila have yielded numerous substantial successes in modeling congenital disorders or inborn errors of human development, as well as neurodegenerative disease and cancer. Moreover, although our ability to generate sequence datasets continues to outpace our ability to analyze these datasets, the development of high-throughput analysis platforms in Drosophila has provided access through the bottleneck in the identification of disease gene candidates. In this Review, we describe both the traditional and newer methods that are facilitating the incorporation of Drosophila into the human disease discovery process, with a focus on the models that have enhanced our understanding of human developmental disorders and congenital disease. Enviable features of the Drosophila experimental system, which make it particularly useful in facilitating the much anticipated move from genotype to phenotype (understanding and predicting phenotypes directly from the primary DNA sequence), include its genetic tractability, the low cost for high-throughput discovery, and a genome and underlying biology that are highly evolutionarily conserved. In embracing the fly in the human disease-gene discovery process, we can expect to speed up and reduce the cost of this process, allowing experimental scales that are not feasible and/or would be too costly in higher eukaryotes. PMID:26935104

Placental transfer and metabolism: an overview of the experimental models utilizing human placental tissue.

PubMed

Myllynen, Päivi; Vähäkangas, Kirsi

2013-02-01

Over the decades several ex vivo and in vitro models which utilize delivered human placenta have been developed to study various placental functions. The use of models originating from human placenta to study transplacental transfer and related mechanisms is an attractive option because human placenta is relatively easily available for experimental studies. After delivery placenta has served its purpose and is usually disposed of. The purpose of this review is to give an overview of the use of human placental models for the studies on human placental transfer and related mechanisms such as transporter functions and xenobiotic metabolism. Human placental perfusion, the most commonly used continuous cell lines, primary cells and tissue culture, as well as subcellular fractions are briefly introduced and their major advantages and disadvantages are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Proactive learning for artificial cognitive systems

NASA Astrophysics Data System (ADS)

Lee, Soo-Young

2010-04-01

The Artificial Cognitive Systems (ACS) will be developed for human-like functions such as vision, auditory, inference, and behavior. Especially, computational models and artificial HW/SW systems will be devised for Proactive Learning (PL) and Self-Identity (SI). The PL model provides bilateral interactions between robot and unknown environment (people, other robots, cyberspace). For the situation awareness in unknown environment it is required to receive audiovisual signals and to accumulate knowledge. If the knowledge is not enough, the PL should improve by itself though internet and others. For human-oriented decision making it is also required for the robot to have self-identify and emotion. Finally, the developed models and system will be mounted on a robot for the human-robot co-existing society. The developed ACS will be tested against the new Turing Test for the situation awareness. The Test problems will consist of several video clips, and the performance of the ACSs will be compared against those of human with several levels of cognitive ability.

Synthetic cognitive development. Where intelligence comes from

NASA Astrophysics Data System (ADS)

Weinbaum (Weaver), D.; Veitas, V.

2017-01-01

The human cognitive system is a remarkable exemplar of a general intelligent system whose competence is not confined to a specific problem domain. Evidently, general cognitive competences are a product of a prolonged and complex process of cognitive development. Therefore, the process of cognitive development is a primary key to understanding the emergence of intelligent behavior. This paper develops the theoretical foundations for a model that generalizes the process of cognitive development. The model aims to provide a realistic scheme for the synthesis of scalable cognitive systems with an open-ended range of capabilities. Major concepts and theories of human cognitive development are introduced and briefly explored, focusing on the enactive approach to cognition and the concept of sense-making. The initial scheme of human cognitive development is then generalized by introducing the philosophy of individuation and the abstract mechanism of transduction. The theory of individuation provides the ground for the necessary paradigmatic shift from cognitive systems as given products to cognitive development as a formative process of self-organization. Next, the conceptual model is specified as a scalable scheme of networks of agents. The mechanisms of individuation are formulated in context-independent information theoretical terms. Finally, the paper discusses two concrete aspects of the generative model - mechanisms of transduction and value modulating systems. These are topics of further research towards an implementable architecture.

The Analysis of the Contribution of Human Factors to the In-Flight Loss of Control Accidents

NASA Technical Reports Server (NTRS)

Ancel, Ersin; Shih, Ann T.

2012-01-01

In-flight loss of control (LOC) is currently the leading cause of fatal accidents based on various commercial aircraft accident statistics. As the Next Generation Air Transportation System (NextGen) emerges, new contributing factors leading to LOC are anticipated. The NASA Aviation Safety Program (AvSP), along with other aviation agencies and communities are actively developing safety products to mitigate the LOC risk. This paper discusses the approach used to construct a generic integrated LOC accident framework (LOCAF) model based on a detailed review of LOC accidents over the past two decades. The LOCAF model is comprised of causal factors from the domain of human factors, aircraft system component failures, and atmospheric environment. The multiple interdependent causal factors are expressed in an Object-Oriented Bayesian belief network. In addition to predicting the likelihood of LOC accident occurrence, the system-level integrated LOCAF model is able to evaluate the impact of new safety technology products developed in AvSP. This provides valuable information to decision makers in strategizing NASA's aviation safety technology portfolio. The focus of this paper is on the analysis of human causal factors in the model, including the contributions from flight crew and maintenance workers. The Human Factors Analysis and Classification System (HFACS) taxonomy was used to develop human related causal factors. The preliminary results from the baseline LOCAF model are also presented.

Induction of Human Blood Group A Antigen Expression on Mouse Cells, Using Lentiviral Gene Transduction

PubMed Central

Fan, Xiaohu; Lang, Haili; Zhou, Xianpei; Zhang, Li; Yin, Rong; Maciejko, Jessica; Giannitsos, Vasiliki; Motyka, Bruce; Medin, Jeffrey A.; Platt, Jeffrey L.

2010-01-01

Abstract The ABO histo-blood group system is the most important antigen system in transplantation medicine, yet no small animal model of the ABO system exists. To determine the feasibility of developing a murine model, we previously subcloned the human α-1,2-fucosyltransferase (H-transferase, EC 2.4.1.69) cDNA and the human α-1,3-N-acetylgalactosaminyltransferase (A-transferase, EC 2.4.1.40) cDNA into lentiviral vectors to study their ability to induce human histo-blood group A antigen expression on mouse cells. Herein we investigated the optimal conditions for human A and H antigen expression in murine cells. We determined that transduction of a bicistronic lentiviral vector (LvEF1-AH-trs) resulted in the expression of A antigen in a mouse endothelial cell line. We also studied the in vivo utility of this vector to induce human A antigen expression in mouse liver. After intrahepatic injection of LvEF1-AH-trs, A antigen expression was observed on hepatocytes as detected by immunohistochemistry and real-time RT-PCR. In human group A erythrocyte-sensitized mice, A antigen expression in the liver was associated with tissue damage, and deposition of antibody and complement. These results suggest that this gene transfer strategy can be used to simulate the human ABO blood group system in a murine model. This model will facilitate progress in the development of interventions for ABO-incompatible transplantation and transfusion scenarios, which are difficult to develop in clinical or large animal settings. PMID:20163247

A Framework for Human Performance Criteria for Advanced Reactor Operational Concepts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacques V Hugo; David I Gertman; Jeffrey C Joe

2014-08-01

This report supports the determination of new Operational Concept models needed in support of the operational design of new reactors. The objective of this research is to establish the technical bases for human performance and human performance criteria frameworks, models, and guidance for operational concepts for advanced reactor designs. The report includes a discussion of operating principles for advanced reactors, the human performance issues and requirements for human performance based upon work domain analysis and current regulatory requirements, and a description of general human performance criteria. The major findings and key observations to date are that there is some operatingmore » experience that informs operational concepts for baseline designs for SFR and HGTRs, with the Experimental Breeder Reactor-II (EBR-II) as a best-case predecessor design. This report summarizes the theoretical and operational foundations for the development of a framework and model for human performance criteria that will influence the development of future Operational Concepts. The report also highlights issues associated with advanced reactor design and clarifies and codifies the identified aspects of technology and operating scenarios.« less

The human footprint in the west: a large-scale analysis of anthropogenic impacts.

USGS Publications Warehouse

Leu, M.; Hanser, S.E.; Knick, S.T.

2008-01-01

Anthropogenic features such as urbanization, roads, and power lines, are increasing in western United States landscapes in response to rapidly growing human populations. However, their spatial effects have not been evaluated. Our goal was to model the human footprint across the western United States. We first delineated the actual area occupied by anthropogenic features, the physical effect area. Next, we developed the human footprint model based on the ecological effect area, the zone influenced by features beyond their physical presence, by combining seven input models: three models quantified top-down anthropogenic influences of synanthropic predators (avian predators, domestic dog and cat presence risk), and four models quantified bottom-up anthropogenic influences on habitat (invasion of exotic plants, human-caused fires, energy extraction, and anthropogenic wildland fragmentation). Using independent bird population data, we found bird abundance of four synanthropic species to correlate positively with human footprint intensity and negatively for three of the six species influenced by habitat fragmentation. We then evaluated the extent of the human footprint in relation to terrestrial (ecoregions) and aquatic systems (major rivers and lakes), regional management and conservation status, physical environment, and temporal changes in human actions. The physical effect area of anthropogenic features covered 13% of the western United States with agricultural land (9.8%) being most dominant. High-intensity human footprint areas (class 8–10) overlapped highly productive low-elevation private landholdings and covered 7% of the western United States compared to 48% for low-intensity areas (class 1–3), which were confined to low-productivity high-elevation federal landholdings. Areas within 1 km of rivers were more affected by the human footprint compared to lakes. Percentage human population growth was higher in low-intensity human footprint areas. The disproportional regional effects of the human footprint on landscapes in the western United States create a challenge to management of ecosystems and wildlife populations. Using footprint models, managers can plan land use actions, develop restoration scenarios, and identify areas of high conservation value at local landscapes within a regional context. Moreover, human footprint models serve as a tool to stratify landscapes for studies investigating floral and faunal response to human disturbance intensity gradients.

Open Innovation at NASA: A New Business Model for Advancing Human Health and Performance Innovations

NASA Technical Reports Server (NTRS)

Davis, Jeffrey R.; Richard, Elizabeth E.; Keeton, Kathryn E.

2014-01-01

This paper describes a new business model for advancing NASA human health and performance innovations and demonstrates how open innovation shaped its development. A 45 percent research and technology development budget reduction drove formulation of a strategic plan grounded in collaboration. We describe the strategy execution, including adoption and results of open innovation initiatives, the challenges of cultural change, and the development of virtual centers and a knowledge management tool to educate and engage the workforce and promote cultural change.

The importance of the Non Obese Diabetic (NOD) mouse model in autoimmune diabetes

PubMed Central

Pearson, James A; Wong, F. Susan; Wen, Li

2016-01-01

Type 1 Diabetes (T1D) is an autoimmune disease characterized by the pancreatic infiltration of immune cells resulting in T cell-mediated destruction of the insulin-producing beta cells. The successes of the Non Obese Diabetic (NOD) mouse model have come in multiple forms including identifying key genetic and environmental risk factors e.g. Idd loci and effects of microorganisms including the gut microbiota, respectively, and how they may contribute to disease susceptibility and pathogenesis. Furthermore, the NOD model also provides insights into the roles of the innate immune cells as well as the B cells in contributing to the T cell-mediated disease. Unlike many autoimmune disease models, the NOD mouse develops spontaneous disease and has many similarities to human T1D. Through exploiting these similarities many targets have been identified for immune-intervention strategies. Although many of these immunotherapies did not have a significant impact on human T1D, they have been shown to be effective in the NOD mouse in early stage disease, which is not equivalent to trials in newly-diagnosed patients with diabetes. However, the continued development of humanized NOD mice would enable further clinical developments, bringing T1D research to a new translational level. Therefore, it is the aim of this review to discuss the importance of the NOD model in identifying the roles of the innate immune system and the interaction with the gut microbiota in modifying diabetes susceptibility. In addition, the role of the B cells will also be discussed with new insights gained through B cell depletion experiments and the impact on translational developments. Finally, this review will also discuss the future of the NOD mice and the development of humanized NOD mice, providing novel insights into human T1D. PMID:26403950

Enhancing Interdisciplinary Human System Risk Research Through Modeling and Network Approaches

NASA Technical Reports Server (NTRS)

Mindock, Jennifer; Lumpkins, Sarah; Shelhamer, Mark

2015-01-01

NASA's Human Research Program (HRP) supports research to reduce human health and performance risks inherent in future human space exploration missions. Understanding risk outcomes and contributing factors in an integrated manner allows HRP research to support development of efficient and effective mitigations from cross-disciplinary perspectives, and to enable resilient human and engineered systems for spaceflight. The purpose of this work is to support scientific collaborations and research portfolio management by utilizing modeling for analysis and visualization of current and potential future interdisciplinary efforts.

Space Exploration Supply Chain Modeling, Simulation and Analysis Using the SCOR Model

NASA Technical Reports Server (NTRS)

Zapata, Edgar; Callinan, Mike; Fayez, Sam

2006-01-01

sustained and affordable human and robotic program to explore the solar system and beyond. Extend human presence across the solar system, starting with a human return to the Moon by the year 2020, in preparation for human exploration of Mars and other destinations. Develop the innovative technologies, knowledge, and infrastructure both to explore and to support decisions about the destinations for human exploration; and promote international and commercial participation in exploration to further U.S. scientific, security, and economic interests

Comparative Computational Modeling of Airflows and Vapor Dosimetry in the Respiratory Tracts of Rat, Monkey, and Human

PubMed Central

Corley, Richard A.

2012-01-01

Computational fluid dynamics (CFD) models are useful for predicting site-specific dosimetry of airborne materials in the respiratory tract and elucidating the importance of species differences in anatomy, physiology, and breathing patterns. We improved the imaging and model development methods to the point where CFD models for the rat, monkey, and human now encompass airways from the nose or mouth to the lung. A total of 1272, 2172, and 135 pulmonary airways representing 17±7, 19±9, or 9±2 airway generations were included in the rat, monkey and human models, respectively. A CFD/physiologically based pharmacokinetic model previously developed for acrolein was adapted for these anatomically correct extended airway models. Model parameters were obtained from the literature or measured directly. Airflow and acrolein uptake patterns were determined under steady-state inhalation conditions to provide direct comparisons with prior data and nasal-only simulations. Results confirmed that regional uptake was sensitive to airway geometry, airflow rates, acrolein concentrations, air:tissue partition coefficients, tissue thickness, and the maximum rate of metabolism. Nasal extraction efficiencies were predicted to be greatest in the rat, followed by the monkey, and then the human. For both nasal and oral breathing modes in humans, higher uptake rates were predicted for lower tracheobronchial tissues than either the rat or monkey. These extended airway models provide a unique foundation for comparing material transport and site-specific tissue uptake across a significantly greater range of conducting airways in the rat, monkey, and human than prior CFD models. PMID:22584687

Development and Evaluation of a New Air Exchange Rate Algorithm for the Stochastic Human Exposure and Dose Simulation Model

EPA Science Inventory

between-home and between-city variability in residential pollutant infiltration. This is likely a result of differences in home ventilation, or air exchange rates (AER). The Stochastic Human Exposure and Dose Simulation (SHEDS) model is a population exposure model that uses a pro...

Human Exposure Model (HEM): A modular, web-based application to characterize near-field chemical exposures and releases

EPA Science Inventory

The U.S. EPA’s Chemical Safety and Sustainability research program is developing the Human Exposure Model (HEM) to assess near-field exposures to chemicals that occur in various populations over the entire life cycle of a consumer product. The model will be implemented as a...

Chlorpyrifos PBPK/PD model for multiple routes of exposure.

PubMed

Poet, Torka S; Timchalk, Charles; Hotchkiss, Jon A; Bartels, Michael J

2014-10-01

1. Chlorpyrifos (CPF) is an important pesticide used to control crop insects. Human Exposures to CPF will occur primarily through oral exposure to residues on foods. A physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model has been developed that describes the relationship between oral, dermal and inhalation doses of CPF and key events in the pathway for cholinergic effects. The model was built on a prior oral model that addressed age-related changes in metabolism and physiology. This multi-route model was developed in rats and humans to validate all scenarios in a parallelogram design. 2. Critical biological effects from CPF exposure require metabolic activation to CPF oxon, and small amounts of metabolism in tissues will potentially have a great effect on pharmacokinetics and pharmacodynamic outcomes. Metabolism (bioactivation and detoxification) was therefore added in diaphragm, brain, lung and skin compartments. Pharmacokinetic data are available for controlled human exposures via the oral and dermal routes and from oral and inhalation studies in rats. The validated model was then used to determine relative dermal versus inhalation uptake from human volunteers exposed to CPF in an indoor scenario.

An Analysis of the Educational Value of Low-Fidelity Anatomy Models as External Representations

ERIC Educational Resources Information Center

Chan, Lap Ki; Cheng, Maurice M. W.

2011-01-01

Although high-fidelity digital models of human anatomy based on actual cross-sectional images of the human body have been developed, reports on the use of physical models in anatomy teaching continue to appear. This article aims to examine the common features shared by these physical models and analyze their educational value based on the…

Process-based model with flood control measures towards more realistic global flood modeling

NASA Astrophysics Data System (ADS)

Tang, Q.; Zhang, X.; Wang, Y.; Mu, M.; Lv, A.; Li, Z.

2017-12-01

In the profoundly human-influenced era, the Anthropocene, increased amount of land was developed in flood plains and many flood control measures were implemented to protect people and infrastructures placed in the flood-prone areas. These human influences (for example, dams and dykes) have altered peak streamflow and flood risk, and are already an integral part of flood. However, most of the process-based flood models have yet to taken into account the human influences. In this study, we used a hydrological model together with an advanced hydrodynamic model to assess flood risk at the Baiyangdian catchment. The Baiyangdian Lake is the largest shallow freshwater lake in North China, and it was used as a flood storage area in the past. A new development hub for the Beijing-Tianjin-Hebei economic triangle, namely the Xiongan new area, was recently established in the flood-prone area around the lake. The shuttle radar topography mission (SRTM) digital elevation model (DEMs) was used to parameterize the hydrodynamic model simulation, and the inundation estimates were compared with published flood maps and observed inundation area during the extreme historical flood events. A simple scheme was carried out to consider the impacts of flood control measures, including the reservoirs in the headwaters and the dykes to be built. By comparing model simulations with and without the influences of flood control measures, we demonstrated the importance of human influences in altering the inundated area and depth under design flood conditions. Based on the SRTM DEM and dam and reservoir data in the Global Reservoir and Dam (GRanD) database, we further discuss the potential to develop a global flood model with human influences.

Measurement and modelling of x-direction apparent mass of the seated human body-cushioned seat system.

PubMed

Stein, George Juraj; Múcka, Peter; Chmúrny, Rudolf; Hinz, Barbara; Blüthner, Ralph

2007-01-01

For modelling purposes and for evaluation of driver's seat performance in the vertical direction various mechano-mathematical models of the seated human body have been developed and standardized by the ISO. No such models exist hitherto for human body sitting in an upright position in a cushioned seat upper part, used in industrial environment, where the fore-and-aft vibrations play an important role. The interaction with the steering wheel has to be taken into consideration, as well as, the position of the human body upper torso with respect to the cushioned seat back as observed in real driving conditions. This complex problem has to be simplified first to arrive at manageable simpler models, which still reflect the main problem features. In a laboratory study accelerations and forces in x-direction were measured at the seat base during whole-body vibration in the fore-and-aft direction (random signal in the frequency range between 0.3 and 30 Hz, vibration magnitudes 0.28, 0.96, and 2.03 ms(-2) unweighted rms). Thirteen male subjects with body masses between 62.2 and 103.6 kg were chosen for the tests. They sat on a cushioned driver seat with hands on a support and backrest contact in the lumbar region only. Based on these laboratory measurements a linear model of the system-seated human body and cushioned seat in the fore-and-aft direction has been developed. The model accounts for the reaction from the steering wheel. Model parameters have been identified for each subject-measured apparent mass values (modulus and phase). The developed model structure and the averaged parameters can be used for further bio-dynamical research in this field.

Challenges and advances in mouse modeling for human pancreatic tumorigenesis and metastasis

PubMed Central

Qiu, Wanglong

2013-01-01

Pancreatic cancer is critical for developed countries, where its rate of diagnosis has been increasing steadily annually. In the past decade, the advances of pancreatic cancer research have not contributed to the decline in mortality rates from pancreatic cancer—the overall 5-year survival rate remains about 5% low. This number only underscores an obvious urgency for us to better understand the biological features of pancreatic carcinogenesis, to develop early detection methods, and to improve novel therapeutic treatments. To achieve these goals, animal modeling that faithfully recapitulates the whole process of human pancreatic cancer is central to making the advancements. In this review, we summarize the currently available animal models for pancreatic cancer and the advances in pancreatic cancer animal modeling. We compare and contrast the advantages and disadvantages of three major categories of these models: (1) carcinogen-induced; (2) xenograft and allograft; and (3) genetically engineered mouse models. We focus more on the genetically engineered mouse models, a category which has been rapidly expanded recently for their capacities to mimic human pancreatic cancer and metastasis, and highlight the combinations of these models with various newly developed strategies and cell-lineage labeling systems. PMID:23114842

Creating new realities: program development and dissemination.

PubMed Central

Fixsen, D L; Blase, K A

1993-01-01

Program development and dissemination in human services present challenges and opportunities for social scientists. Over the past 27 years the Teaching-Family Model of group home treatment has moved from prototype development to widespread dissemination across North America. Reviewing concepts in industry related to product development and dissemination, the application of these concepts to a human services delivery system, and program replication and dissemination data offer information about how innovative human services can be widely adapted and adopted. PMID:8307838

Human immune system mouse models of Ebola virus infection.

PubMed

Spengler, Jessica R; Prescott, Joseph; Feldmann, Heinz; Spiropoulou, Christina F

2017-08-01

Human immune system (HIS) mice, immunodeficient mice engrafted with human cells (with or without donor-matched tissue), offer a unique opportunity to study pathogens that cause disease predominantly or exclusively in humans. Several HIS mouse models have recently been used to study Ebola virus (EBOV) infection and disease. The results of these studies are encouraging and support further development and use of these models in Ebola research. HIS mice provide a small animal model to study EBOV isolates, investigate early viral interactions with human immune cells, screen vaccines and therapeutics that modulate the immune system, and investigate sequelae in survivors. Here we review existing models, discuss their use in pathogenesis studies and therapeutic screening, and highlight considerations for study design and analysis. Finally, we point out caveats to current models, and recommend future efforts for modeling EBOV infection in HIS mice. Published by Elsevier B.V.

Direct 3D cell-printing of human skin with functional transwell system.

PubMed

Kim, Byoung Soo; Lee, Jung-Seob; Gao, Ge; Cho, Dong-Woo

2017-06-06

Three-dimensional (3D) cell-printing has been emerging as a promising technology with which to build up human skin models by enabling rapid and versatile design. Despite the technological advances, challenges remain in the development of fully functional models that recapitulate complexities in the native tissue. Moreover, although several approaches have been explored for the development of biomimetic human skin models, the present skin models based on multistep fabrication methods using polydimethylsiloxane chips and commercial transwell inserts could be tackled by leveraging 3D cell-printing technology. In this paper, we present a new 3D cell-printing strategy for engineering a 3D human skin model with a functional transwell system in a single-step process. A hybrid 3D cell-printing system was developed, allowing for the use of extrusion and inkjet modules at the same time. We began by revealing the significance of each module in engineering human skin models; by using the extrusion-dispensing module, we engineered a collagen-based construct with polycaprolactone (PCL) mesh that prevented the contraction of collagen during tissue maturation; the inkjet-based dispensing module was used to uniformly distribute keratinocytes. Taking these features together, we engineered a human skin model with a functional transwell system; the transwell system and fibroblast-populated dermis were consecutively fabricated by using the extrusion modules. Following this process, keratinocytes were uniformly distributed onto the engineered dermis by the inkjet module. Our transwell system indicates a supportive 3D construct composed of PCL, enabling the maturation of a skin model without the aid of commercial transwell inserts. This skin model revealed favorable biological characteristics that included a stabilized fibroblast-stretched dermis and stratified epidermis layers after 14 days. It was also observed that a 50 times reduction in cost was achieved and 10 times less medium was used than in a conventional culture. Collectively, because this single-step process opens up chances for versatile designs, we envision that our cell-printing strategy could provide an attractive platform in engineering various human skin models.

Physiologically based pharmacokinetic modeling of deltamethrin: Development of a rat and human diffusion-limited model

EPA Science Inventory

Mirfazaelian et al. (2006) developed a physiologically based pharmacokinetic (PBPK) model for the pyrethroid pesticide deltamethrin in the rat. This model describes gastrointestinal tract absorption as a saturable process mediated by phase III efflux transporters which pump delta...

Models of Purposive Human Organization: A Comparative Study

DTIC Science & Technology

1984-02-01

develop techniques for organizational diagnosis with the D-M model, to be followed by intervention by S-T methodology. 2. Introduction 2.1. Background In...relational and object data for Dinnat-Murphree model construction. 2. Develop techniques for organizational diagnosis with the Dinnat-Murphree model

Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID "Meet the Experts" 2015 Workshop Summary.

PubMed

Akkina, Ramesh; Allam, Atef; Balazs, Alejandro B; Blankson, Joel N; Burnett, John C; Casares, Sofia; Garcia, J Victor; Hasenkrug, Kim J; Kashanchi, Fatah; Kitchen, Scott G; Klein, Florian; Kumar, Priti; Luster, Andrew D; Poluektova, Larisa Y; Rao, Mangala; Sanders-Beer, Brigitte E; Shultz, Leonard D; Zack, Jerome A

2016-02-01

The number of humanized mouse models for the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and other infectious diseases has expanded rapidly over the past 8 years. Highly immunodeficient mouse strains, such as NOD/SCID/gamma chain(null) (NSG, NOG), support better human hematopoietic cell engraftment. Another improvement is the derivation of highly immunodeficient mice, transgenic with human leukocyte antigens (HLAs) and cytokines that supported development of HLA-restricted human T cells and heightened human myeloid cell engraftment. Humanized mice are also used to study the HIV reservoir using new imaging techniques. Despite these advances, there are still limitations in HIV immune responses and deficits in lymphoid structures in these models in addition to xenogeneic graft-versus-host responses. To understand and disseminate the improvements and limitations of humanized mouse models to the scientific community, the NIH sponsored and convened a meeting on April 15, 2015 to discuss the state of knowledge concerning these questions and best practices for selecting a humanized mouse model for a particular scientific investigation. This report summarizes the findings of the NIH meeting.

Animal Models in Cardiovascular Research: Hypertension and Atherosclerosis

PubMed Central

Ng, Chun-Yi; Jaarin, Kamsiah

2015-01-01

Hypertension and atherosclerosis are among the most common causes of mortality in both developed and developing countries. Experimental animal models of hypertension and atherosclerosis have become a valuable tool for providing information on etiology, pathophysiology, and complications of the disease and on the efficacy and mechanism of action of various drugs and compounds used in treatment. An animal model has been developed to study hypertension and atherosclerosis for several reasons. Compared to human models, an animal model is easily manageable, as compounding effects of dietary and environmental factors can be controlled. Blood vessels and cardiac tissue samples can be taken for detailed experimental and biomolecular examination. Choice of animal model is often determined by the research aim, as well as financial and technical factors. A thorough understanding of the animal models used and complete analysis must be validated so that the data can be extrapolated to humans. In conclusion, animal models for hypertension and atherosclerosis are invaluable in improving our understanding of cardiovascular disease and developing new pharmacological therapies. PMID:26064920

Aquatic Contaminant and Mercury Simulation Modules Developed for Hydrologic and Hydraulic Models

DTIC Science & Technology

2016-07-01

through the food chain. Human health may also be affected by ingesting contaminated water or fish. As a result, the criteria for protecting human...ER D C/ EL T R- 16 -8 Environmental Quality Technology Research Program Aquatic Contaminant and Mercury Simulation Modules Developed...Quality Technology Research Program ERDC/EL TR-16-8 July 2016 Aquatic Contaminant and Mercury Simulation Modules Developed for Hydrologic and

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

X chromosome inactivation in human pluripotent stem cells as a model for human development: back to the drawing board?

PubMed

Geens, Mieke; Chuva De Sousa Lopes, Susana M

2017-09-01

Human pluripotent stem cells (hPSC), both embryonic and induced (hESC and hiPSC), are regarded as a valuable in vitro model for early human development. In order to fulfil this promise, it is important that these cells mimic as closely as possible the in vivo molecular events, both at the genetic and epigenetic level. One of the most important epigenetic events during early human development is X chromosome inactivation (XCI), the transcriptional silencing of one of the two X chromosomes in female cells. XCI is important for proper development and aberrant XCI has been linked to several pathologies. Recently, novel data obtained using high throughput single-cell technology during human preimplantation development have suggested that the XCI mechanism is substantially different from XCI in mouse. It has also been suggested that hPSC show higher complexity in XCI than the mouse. Here we compare the available recent data to understand whether XCI during human preimplantation can be properly recapitulated using hPSC. We will summarize what is known on the timing and mechanisms of XCI during human preimplantation development. We will compare this to the XCI patterns that are observed during hPSC derivation, culture and differentiation, and comment on the cause of the aberrant XCI patterns observed in hPSC. Finally, we will discuss the implications of the aberrant XCI patterns on the applicability of hPSC as an in vitro model for human development and as cell source for regenerative medicine. Combinations of the following keywords were applied as search criteria in the PubMed database: X chromosome inactivation, preimplantation development, embryonic stem cells, induced pluripotent stem cells, primordial germ cells, differentiation. Recent single-cell RNASeq data have shed new light on the XCI process during human preimplantation development. These indicate a gradual inactivation on both XX chromosomes, starting from Day 4 of development and followed by a random choice to inactivate one of them, instead of the mechanism in mice where imprinted XCI is followed by random XCI. We have put these new findings in perspective using previous data obtained in human (and mouse) embryos. In addition, there is an ongoing discussion whether or not hPSC lines show X chromosome reactivation upon derivation, mimicking the earliest embryonic cells, and the XCI states observed during culture of hPSC are highly variable. Recent studies have shown that hPSC rapidly progress to highly aberrant XCI patterns and that this process is probably driven by suboptimal culture conditions. Importantly, these aberrant XCI states seem to be inherited by the differentiated hPSC-progeny. The aberrant XCI states (and epigenetic instability) observed in hPSC throw a shadow on their applicability as an in vitro model for development and disease modelling. Moreover, as the aberrant XCI states observed in hPSC seem to shift to a more malignant phenotype, this may also have important consequences for the safety aspect of using hPSC in the clinic. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

A tissue-engineered humanized xenograft model of human breast cancer metastasis to bone

PubMed Central

Thibaudeau, Laure; Taubenberger, Anna V.; Holzapfel, Boris M.; Quent, Verena M.; Fuehrmann, Tobias; Hesami, Parisa; Brown, Toby D.; Dalton, Paul D.; Power, Carl A.; Hollier, Brett G.; Hutmacher, Dietmar W.

2014-01-01

ABSTRACT The skeleton is a preferred homing site for breast cancer metastasis. To date, treatment options for patients with bone metastases are mostly palliative and the disease is still incurable. Indeed, key mechanisms involved in breast cancer osteotropism are still only partially understood due to the lack of suitable animal models to mimic metastasis of human tumor cells to a human bone microenvironment. In the presented study, we investigate the use of a human tissue-engineered bone construct to develop a humanized xenograft model of breast cancer-induced bone metastasis in a murine host. Primary human osteoblastic cell-seeded melt electrospun scaffolds in combination with recombinant human bone morphogenetic protein 7 were implanted subcutaneously in non-obese diabetic/severe combined immunodeficient mice. The tissue-engineered constructs led to the formation of a morphologically intact ‘organ’ bone incorporating a high amount of mineralized tissue, live osteocytes and bone marrow spaces. The newly formed bone was largely humanized, as indicated by the incorporation of human bone cells and human-derived matrix proteins. After intracardiac injection, the dissemination of luciferase-expressing human breast cancer cell lines to the humanized bone ossicles was detected by bioluminescent imaging. Histological analysis revealed the presence of metastases with clear osteolysis in the newly formed bone. Thus, human tissue-engineered bone constructs can be applied efficiently as a target tissue for human breast cancer cells injected into the blood circulation and replicate the osteolytic phenotype associated with breast cancer-induced bone lesions. In conclusion, we have developed an appropriate model for investigation of species-specific mechanisms of human breast cancer-related bone metastasis in vivo. PMID:24713276

Improving the physiological realism of experimental models.

PubMed

Vinnakota, Kalyan C; Cha, Chae Y; Rorsman, Patrik; Balaban, Robert S; La Gerche, Andre; Wade-Martins, Richard; Beard, Daniel A; Jeneson, Jeroen A L

2016-04-06

The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide an in silico platform for drug screening. Ultimately, these models rely on the analysis and integration of experimental data. As such, the success of VPH depends on the availability of physiologically realistic experimental models (E-Models) of human organ function that can be parametrized to test the numerical models. Here, the current state of suitable E-models, ranging from in vitro non-human cell organelles to in vivo human organ systems, is discussed. Specifically, challenges and recent progress in improving the physiological realism of E-models that may benefit the VPH project are highlighted and discussed using examples from the field of research on cardiovascular disease, musculoskeletal disorders, diabetes and Parkinson's disease.

UTCI-Fiala multi-node model of human heat transfer and temperature regulation

NASA Astrophysics Data System (ADS)

Fiala, Dusan; Havenith, George; Bröde, Peter; Kampmann, Bernhard; Jendritzky, Gerd

2012-05-01

The UTCI-Fiala mathematical model of human temperature regulation forms the basis of the new Universal Thermal Climate Index (UTC). Following extensive validation tests, adaptations and extensions, such as the inclusion of an adaptive clothing model, the model was used to predict human temperature and regulatory responses for combinations of the prevailing outdoor climate conditions. This paper provides an overview of the underlying algorithms and methods that constitute the multi-node dynamic UTCI-Fiala model of human thermal physiology and comfort. Treated topics include modelling heat and mass transfer within the body, numerical techniques, modelling environmental heat exchanges, thermoregulatory reactions of the central nervous system, and perceptual responses. Other contributions of this special issue describe the validation of the UTCI-Fiala model against measured data and the development of the adaptive clothing model for outdoor climates.

Modeling the Western Diet for Preclinical Investigations.

PubMed

Hintze, Korry J; Benninghoff, Abby D; Cho, Clara E; Ward, Robert E

2018-05-01

Rodent models have been invaluable for biomedical research. Preclinical investigations with rodents allow researchers to investigate diseases by using study designs that are not suitable for human subjects. The primary criticism of preclinical animal models is that results are not always translatable to humans. Some of this lack of translation is due to inherent differences between species. However, rodent models have been refined over time, and translatability to humans has improved. Transgenic animals have greatly aided our understanding of interactions between genes and disease and have narrowed the translation gap between humans and model animals. Despite the technological innovations of animal models through advances in genetics, relatively little attention has been given to animal diets. Namely, developing diets that replicate what humans eat will help make animal models more relevant to human populations. This review focuses on commonly used rodent diets that are used to emulate the Western dietary pattern in preclinical studies of obesity and type 2 diabetes, nonalcoholic liver disease, maternal nutrition, and colorectal cancer.

ANIMAL MODELS OF COGNITIVE DEVELOPMENT IN NEUROTOXICITY

EPA Science Inventory

The thesis of this chapter has been that spatial delayed alternation versus position discrimination learning can serve as a valuable rodent model of cognitive development in neurotoxicology. his model captures dual process conceptualizations of memory in human neuropsychology and...

The Fruit Fly Drosophila melanogaster as a Model for Aging Research.

PubMed

Brandt, Annely; Vilcinskas, Andreas

2013-01-01

: Average human life expectancy is increasing and so is the impact on society of aging and age-related diseases. Here we highlight recent advances in the diverse and multidisciplinary field of aging research, focusing on the fruit fly Drosophila melanogaster, an excellent model system in which to dissect the genetic and molecular basis of the aging processes. The conservation of human disease genes in D. melanogaster allows the functional analysis of orthologues implicated in human aging and age-related diseases. D. melanogaster models have been developed for a variety of age-related processes and disorders, including stem cell decline, Alzheimer's disease, and cardiovascular deterioration. Understanding the detailed molecular events involved in normal aging and age-related diseases could facilitate the development of strategies and treatments that reduce their impact, thus improving human health and increasing longevity.

An approach for development of alternative test methods based on mechanisms of skin irritation.

PubMed

Osborne, R; Perkins, M A

1994-02-01

Recent advances in techniques for culture of human skin cells have led to their potential for use as in vitro models for skin irritation testing to augment or replace existing rabbit skin patch tests. Our work is directed towards the development of cultured human skin cells, together with endpoints that can be linked to in vivo mechanisms of skin irritation, as in vitro models for prediction of human skin irritation, and for study of mechanisms of contact irritant dermatitis. Three types of commercial human skin cell cultures have been evaluated, epidermal keratinocytes and partially or fully cornified keratinocyte-dermal fibroblast co-cultures. Human epidermal keratinocyte cultures (Clonetics) were treated with product ingredients and formulations, and the extent of cell damage was assessed by incorporation of the vital dye neutral red. Cell damage correlated with human skin patch data for ingredient chemicals with the exception of acids and alkalis, but did not correlate with skin irritation to surfactant-containing product formulations. Cultures of human skin equivalents were evaluated as potential models for measurement of responses to test materials that could not be measured in the keratinocyte/neutral red assay. We developed a battery of in vitro endpoints to measure responses to prototype ingredients and formulations in human epidermal keratinocyte-dermal fibroblast co-cultures grown on a nylon mesh ('Skin2' from Advanced Tissue Sciences) or on a collagen gel ('Testskin' from Organogenesis). The endpoints measure cytotoxicity (neutral red and MTT vital dye staining, lactate dehydrogenase and N-acetyl glucosaminidase release, glucose utilization) and inflammatory mediator (prostaglandin E2) release. Initial experiments indicate a promising correlation between responses of the Skin2 model to prototype surfactants and in vivo human skin irritation. The responses of Testskin cultures to acids and alkalis help to prove the concept that a topical application model can measure responses to these materials. These results suggest that human skin cell models can provide useful systems for preclinical skin irritation assessments, as alternatives to rabbits, for at least certain classes of test substances.

Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindle-like (ASPM related primary) microcephaly disease.

PubMed

Li, Rui; Sun, Le; Fang, Ai; Li, Peng; Wu, Qian; Wang, Xiaoqun

2017-11-01

The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex. Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases. Several previous efforts have shown to grow neural organoid in culture dishes successfully, however we demonstrate a new paradigm that recapitulates neocortical development process with VZ, OSVZ formation and the lamination organization of cortical layer structure. In addition, using patient-specific induced pluripotent stem cells (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient, we demonstrate neurogenesis defects result in defective neuronal activity in patient organoids, suggesting a new strategy to study human developmental diseases in central nerve system.

Building a Formal Model of a Human-Interactive System: Insights into the Integration of Formal Methods and Human Factors Engineering

NASA Technical Reports Server (NTRS)

Bolton, Matthew L.; Bass, Ellen J.

2009-01-01

Both the human factors engineering (HFE) and formal methods communities are concerned with finding and eliminating problems with safety-critical systems. This work discusses a modeling effort that leveraged methods from both fields to use model checking with HFE practices to perform formal verification of a human-interactive system. Despite the use of a seemingly simple target system, a patient controlled analgesia pump, the initial model proved to be difficult for the model checker to verify in a reasonable amount of time. This resulted in a number of model revisions that affected the HFE architectural, representativeness, and understandability goals of the effort. If formal methods are to meet the needs of the HFE community, additional modeling tools and technological developments are necessary.

Finite-element modeling of the human neurocranium under functional anatomical aspects.

PubMed

Mall, G; Hubig, M; Koebke, J; Steinbuch, R

1997-08-01

Due to its functional significance the human skull plays an important role in biomechanical research. The present work describes a new Finite-Element model of the human neurocranium. The dry skull of a middle-aged woman served as a pattern. The model was developed using only the preprocessor (Mentat) of a commercial FE-system (Marc). Unlike that of other FE models of the human skull mentioned in the literature, the geometry in this model was designed according to functional anatomical findings. Functionally important morphological structures representing loci minoris resistentiae, especially the foramina and fissures of the skull base, were included in the model. The results of two linear static loadcase analyses in the region of the skull base underline the importance of modeling from the functional anatomical point of view.

Small animal models of cardiovascular disease: tools for the study of the roles of metabolic syndrome, dyslipidemia, and atherosclerosis.

PubMed

Russell, James C; Proctor, Spencer D

2006-01-01

Cardiovascular disease, the leading cause of death in much of the modern world, is the common symptomatic end stage of a number of distinct diseases and, therefore, is multifactorial and polygenetic in character. The two major underlying causes are disorders of lipid metabolism and metabolic syndrome. The ability to develop preventative and ameliorative treatments will depend on animal models that mimic human disease processes. The focus of this review is to identify suitable animal models and insights into cardiovascular disease achieved to date using such models. The ideal animal model of cardiovascular disease will mimic the human subject metabolically and pathophysiologically, will be large enough to permit physiological and metabolic studies, and will develop end-stage disease comparable to those in humans. Given the complex multifactorial nature of cardiovascular disease, no one species will be suitable for all studies. Potential larger animal models are problematic due to cost, ethical considerations, or poor pathophysiological comparability to humans. Rabbits require high-cholesterol diets to develop cardiovascular disease, and there are no rabbit models of metabolic syndrome. Spontaneous mutations in rats provide several complementary models of obesity, hyperlipidemia, insulin resistance, and type 2 diabetes, one of which spontaneously develops cardiovascular disease and ischemic lesions. The mouse, like normal rats, is characteristically resistant to cardiovascular disease, although genetically altered strains respond to cholesterol feeding with atherosclerosis, but not with end-stage ischemic lesions. The most useful and valid species/strains for the study of cardiovascular disease appear to be small rodents, rats, and mice. This fragmented field would benefit from a consensus on well-characterized appropriate models for the study of different aspects of cardiovascular disease and a renewed emphasis on the biology of underlying diseases.

Biological Tools to Study the Effects of Environmental Contaminants at the Feto–Maternal Interface

PubMed Central

Mannelli, Chiara; Ietta, Francesca; Avanzati, Anna Maria; Skarzynski, Dariusz

2015-01-01

The identification of reproductive toxicants is a major scientific challenge for human health. Prenatal life is the most vulnerable and important time span of human development. For obvious ethical reasons, in vivo models cannot be used in human pregnancy, and animal models do not perfectly reflect human physiology. This review describes the in vitro test models representative of the human feto–maternal interface and the effects of environmental chemicals with estrogen-like activity, mainly bisphenol A and para-nonylphenol, with a particular emphasis on the effects at low, nontoxic doses similar to concentrations commonly detected in the population. PMID:26740808

Theorizing Strategic Human Resource Development: Linking Financial Performance and Sustainable Competitive Advantage

ERIC Educational Resources Information Center

Hu, Po

2007-01-01

This paper is to explore potential new underlying theory of strategic human resource development based on critiques of current theoretical foundations of HRD. It offers a new definition and model of Strategic HRD based on resource-based view of firm and human resource, with linkage to financial performance and competitiveness. Proposed new model…

Testing the Human Capital Development Model: The Case of Apprenticeships in Turkey

ERIC Educational Resources Information Center

Akpinar, Taner; Gün, Servet

2016-01-01

Human capital theory was developed to study how individual agents make rational choices or how they invest in human capital to maximize their welfare. One of the leading founders of this perspective, Becker, argues that schooling, on-the-job training, medical care, migration and searching for information about prices and incomes are different…

Operator function modeling: An approach to cognitive task analysis in supervisory control systems

NASA Technical Reports Server (NTRS)

Mitchell, Christine M.

1987-01-01

In a study of models of operators in complex, automated space systems, an operator function model (OFM) methodology was extended to represent cognitive as well as manual operator activities. Development continued on a software tool called OFMdraw, which facilitates construction of an OFM by permitting construction of a heterarchic network of nodes and arcs. Emphasis was placed on development of OFMspert, an expert system designed both to model human operation and to assist real human operators. The system uses a blackboard method of problem solving to make an on-line representation of operator intentions, called ACTIN (actions interpreter).

Development of an Implantable WBAN Path-Loss Model for Capsule Endoscopy

NASA Astrophysics Data System (ADS)

Aoyagi, Takahiro; Takizawa, Kenichi; Kobayashi, Takehiko; Takada, Jun-Ichi; Hamaguchi, Kiyoshi; Kohno, Ryuji

An implantable WBAN path-loss model for a capsule endoscopy which is used for examining digestive organs, is developed by conducting simulations and experiments. First, we performed FDTD simulations on implant WBAN propagation by using a numerical human model. Second, we performed FDTD simulations on a vessel that represents the human body. Third, we performed experiments using a vessel of the same dimensions as that used in the simulations. On the basis of the results of these simulations and experiments, we proposed the gradient and intercept parameters of the simple path-loss in-body propagation model.

Sustainable development education, practice, and research: an indigenous model of sustainable development at the College of Menominee Nation, Keshena, WI, USA

Treesearch

Michael J. Dockry; Katherine Hall; William Van Lopik; Christopher M. Caldwell

2015-01-01

The College of Menominee Nation Sustainable Development Institute's theoretical model (SDI model) conceptualizes sustainable development as the process of maintaining the balance and reconciling the inherent tensions among six dimensions of sustainability: land and sovereignty; natural environment #including human beings); institutions; technology; economy; and...

Cognitive Model of Trust Dynamics Predicts Human Behavior within and between Two Games of Strategic Interaction with Computerized Confederate Agents

PubMed Central

Collins, Michael G.; Juvina, Ion; Gluck, Kevin A.

2016-01-01

When playing games of strategic interaction, such as iterated Prisoner's Dilemma and iterated Chicken Game, people exhibit specific within-game learning (e.g., learning a game's optimal outcome) as well as transfer of learning between games (e.g., a game's optimal outcome occurring at a higher proportion when played after another game). The reciprocal trust players develop during the first game is thought to mediate transfer of learning effects. Recently, a computational cognitive model using a novel trust mechanism has been shown to account for human behavior in both games, including the transfer between games. We present the results of a study in which we evaluate the model's a priori predictions of human learning and transfer in 16 different conditions. The model's predictive validity is compared against five model variants that lacked a trust mechanism. The results suggest that a trust mechanism is necessary to explain human behavior across multiple conditions, even when a human plays against a non-human agent. The addition of a trust mechanism to the other learning mechanisms within the cognitive architecture, such as sequence learning, instance-based learning, and utility learning, leads to better prediction of the empirical data. It is argued that computational cognitive modeling is a useful tool for studying trust development, calibration, and repair. PMID:26903892

UTILIZATION OF A PBPK MODEL TO PREDICT THE DISTRIBUTION OF 2, 3, 7-8 TETRACHLORODIBENZO-P-DIOXIN (TCDD) IN HUMANS DURING CRITICAL WINDOWS OF DEVELOPMENT

EPA Science Inventory

Utilization of A PBPK model to predict the distribution of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) in humans during critical windows of development.
C Emond1, MJ DeVito2 and LS Birnbaum2
1National Research Council, US EPA, ORD, NHEERL, (ETD, PK), RTP, NC, 27711, USA 2 US...

Biological and medical applications of a brain-on-a-chip

PubMed Central

2016-01-01

The desire to develop and evaluate drugs as potential countermeasures for biological and chemical threats requires test systems that can also substitute for the clinical trials normally crucial for drug development. Current animal models have limited predictivity for drug efficacy in humans as the large majority of drugs fails in clinical trials. We have limited understanding of the function of the central nervous system and the complexity of the brain, especially during development and neuronal plasticity. Simple in vitro systems do not represent physiology and function of the brain. Moreover, the difficulty of studying interactions between human genetics and environmental factors leads to lack of knowledge about the events that induce neurological diseases. Microphysiological systems (MPS) promise to generate more complex in vitro human models that better simulate the organ’s biology and function. MPS combine different cell types in a specific three-dimensional (3D) configuration to simulate organs with a concrete function. The final aim of these MPS is to combine different “organoids” to generate a human-on-a-chip, an approach that would allow studies of complex physiological organ interactions. The recent discovery of induced pluripotent stem cells (iPSCs) gives a range of possibilities allowing cellular studies of individuals with different genetic backgrounds (e.g., human disease models). Application of iPSCs from different donors in MPS gives the opportunity to better understand mechanisms of the disease and can be a novel tool in drug development, toxicology, and medicine. In order to generate a brain-on-a-chip, we have established a 3D model from human iPSCs based on our experience with a 3D rat primary aggregating brain model. After four weeks of differentiation, human 3D aggregates stain positive for different neuronal markers and show higher gene expression of various neuronal differentiation markers compared to 2D cultures. Here we present the applications and challenges of this emerging technology. PMID:24912505

A Novel Model of Asymptomatic Plasmodium Parasitemia That Recapitulates Elements of the Human Immune Response to Chronic Infection

PubMed Central

Baccarella, Alyssa; Craft, Joshua F.; Boyle, Michelle J.; McIntyre, Tara I.; Wood, Matthew D.; Thorn, Kurt S.; Anidi, Chioma; Bayat, Aqieda; Chung, Me Ree; Hamburger, Rebecca; Kim, Chris Y.; Pearman, Emily; Pham, Jennifer; Tang, Jia J.; Boon, Louis; Kamya, Moses R.; Dorsey, Grant; Feeney, Margaret E.; Kim, Charles C.

2016-01-01

In humans, immunity to Plasmodium sp. generally takes the form of protection from symptomatic malaria (i.e., 'clinical immunity') rather than infection ('sterilizing immunity'). In contrast, mice infected with Plasmodium develop sterilizing immunity, hindering progress in understanding the mechanistic basis of clinical immunity. Here we present a novel model in which mice persistently infected with P. chabaudi exhibit limited clinical symptoms despite sustaining patent parasite burdens for many months. Characterization of immune responses in persistently infected mice revealed development of CD4+ T cell exhaustion, increased production of IL-10, and expansion of B cells with an atypical surface phenotype. Additionally, persistently infected mice displayed a dramatic increase in circulating nonclassical monocytes, a phenomenon that we also observed in humans with both chronic Plasmodium exposure and asymptomatic infection. Following pharmacological clearance of infection, previously persistently infected mice could not control a secondary challenge, indicating that persistent infection disrupts the sterilizing immunity that typically develops in mouse models of acute infection. This study establishes an animal model of asymptomatic, persistent Plasmodium infection that recapitulates several central aspects of the immune response in chronically exposed humans. As such, it provides a novel tool for dissection of immune responses that may prevent development of sterilizing immunity and limit pathology during infection. PMID:27583554

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.

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.

SIMULATING FISH ASSEMBLAGE DYNAMICS IN RIVER NETWORKS

EPA Science Inventory

My recently retired colleague, Joan Baker, and I have developed a prototype computer simulation model for studying the effects of human and non-human alterations of habitats and species availability on fish assemblage populations. The fish assemblage model, written in R, is a sp...

Modeling of human operator dynamics in simple manual control utilizing time series analysis. [tracking (position)

NASA Technical Reports Server (NTRS)

Agarwal, G. C.; Osafo-Charles, F.; Oneill, W. D.; Gottlieb, G. L.

1982-01-01

Time series analysis is applied to model human operator dynamics in pursuit and compensatory tracking modes. The normalized residual criterion is used as a one-step analytical tool to encompass the processes of identification, estimation, and diagnostic checking. A parameter constraining technique is introduced to develop more reliable models of human operator dynamics. The human operator is adequately modeled by a second order dynamic system both in pursuit and compensatory tracking modes. In comparing the data sampling rates, 100 msec between samples is adequate and is shown to provide better results than 200 msec sampling. The residual power spectrum and eigenvalue analysis show that the human operator is not a generator of periodic characteristics.

Cognitive Aspects of Power in a Two-Level Game

NASA Astrophysics Data System (ADS)

Juvina, Ion; Lebiere, Christian; Martin, Jolie; Gonzalez, Cleotilde

The Intergroup Prisoner's Dilemma with Intragroup Power Dynamics (IPD^2) is a new game paradigm for studying human behavior in conflict situations. IPD^2 adds the concept of intragroup power to an intergroup version of the standard Iterated Prisoner's Dilemma game. We conducted an exploratory laboratory study in which individual human participants played the game against computer strategies of various complexities. We also developed a cognitive model of human decision making in this game. The model was run in place of the human participant under the same conditions as in the laboratory study. Results from the human study and the model simulations are presented and discussed, emphasizing the value of including intragroup power in game theoretic models of conflict.

Acute radiation risk models

NASA Astrophysics Data System (ADS)

Smirnova, Olga

Biologically motivated mathematical models, which describe the dynamics of the major hematopoietic lineages (the thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems) in acutely/chronically irradiated humans are developed. These models are implemented as systems of nonlinear differential equations, which variables and constant parameters have clear biological meaning. It is shown that the developed models are capable of reproducing clinical data on the dynamics of these systems in humans exposed to acute radiation in the result of incidents and accidents, as well as in humans exposed to low-level chronic radiation. Moreover, the averaged value of the "lethal" dose rates of chronic irradiation evaluated within models of these four major hematopoietic lineages coincides with the real minimal dose rate of lethal chronic irradiation. The demonstrated ability of the models of the human thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems to predict the dynamical response of these systems to acute/chronic irradiation in wide ranges of doses and dose rates implies that these mathematical models form an universal tool for the investigation and prediction of the dynamics of the major human hematopoietic lineages for a vast pattern of irradiation scenarios. In particular, these models could be applied for the radiation risk assessment for health of astronauts exposed to space radiation during long-term space missions, such as voyages to Mars or Lunar colonies, as well as for health of people exposed to acute/chronic irradiation due to environmental radiological events.

Zebrafish and Streptococcal Infections.

PubMed

Saralahti, A; Rämet, M

2015-09-01

Streptococcal bacteria are a versatile group of gram-positive bacteria capable of infecting several host organisms, including humans and fish. Streptococcal species are common colonizers of the human respiratory and gastrointestinal tract, but they also cause some of the most common life-threatening, invasive infections in humans and aquaculture. With its unique characteristics and efficient tools for genetic and imaging applications, the zebrafish (Danio rerio) has emerged as a powerful vertebrate model for infectious diseases. Several zebrafish models introduced so far have shown that zebrafish are suitable models for both zoonotic and human-specific infections. Recently, several zebrafish models mimicking human streptococcal infections have also been developed. These models show great potential in providing novel information about the pathogenic mechanisms and host responses associated with human streptococcal infections. Here, we review the zebrafish infection models for the most relevant streptococcal species: the human-specific Streptococcus pneumoniae and Streptococcus pyogenes, and the zoonotic Streptococcus iniae and Streptococcus agalactiae. The recent success and the future potential of these models for the study of host-pathogen interactions in streptococcal infections are also discussed. © 2015 The Foundation for the Scandinavian Journal of Immunology.

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.

Toward Realism in Human Performance Simulation

DTIC Science & Technology

2004-01-01

toward the development of improved human-like performance of synthetic agents. However, several serious problems continue to challenge researchers and... developers . Developers have insufficient behavioral knowledge. To date, models of emotivity and behavior that have been commercialized still tend...Bindiganavale, 1999). There has even been significant development of architectures to produce animated characters that react appropriately to a small

Out of Africa: modern human origins special feature: explaining worldwide patterns of human genetic variation using a coalescent-based serial founder model of migration outward from Africa.

PubMed

DeGiorgio, Michael; Jakobsson, Mattias; Rosenberg, Noah A

2009-09-22

Studies of worldwide human variation have discovered three trends in summary statistics as a function of increasing geographic distance from East Africa: a decrease in heterozygosity, an increase in linkage disequilibrium (LD), and a decrease in the slope of the ancestral allele frequency spectrum. Forward simulations of unlinked loci have shown that the decline in heterozygosity can be described by a serial founder model, in which populations migrate outward from Africa through a process where each of a series of populations is formed from a subset of the previous population in the outward expansion. Here, we extend this approach by developing a retrospective coalescent-based serial founder model that incorporates linked loci. Our model both recovers the observed decline in heterozygosity with increasing distance from Africa and produces the patterns observed in LD and the ancestral allele frequency spectrum. Surprisingly, although migration between neighboring populations and limited admixture between modern and archaic humans can be accommodated in the model while continuing to explain the three trends, a competing model in which a wave of outward modern human migration expands into a series of preexisting archaic populations produces nearly opposite patterns to those observed in the data. We conclude by developing a simpler model to illustrate that the feature that permits the serial founder model but not the archaic persistence model to explain the three trends observed with increasing distance from Africa is its incorporation of a cumulative effect of genetic drift as humans colonized the world.

Early-life experiences and the development of adult diseases with a focus on mental illness: The Human Birth Theory.

PubMed

Maccari, Stefania; Polese, Daniela; Reynaert, Marie-Line; Amici, Tiziana; Morley-Fletcher, Sara; Fagioli, Francesca

2017-02-07

In mammals, early adverse experiences, including mother-pup interactions, shape the response of an individual to chronic stress or to stress-related diseases during adult life. This has led to the elaboration of the theory of the developmental origins of health and disease, in particular adult diseases such as cardiovascular and metabolic disorders. In addition, in humans, as stated by Massimo Fagioli's Human Birth Theory, birth is healthy and equal for all individuals, so that mental illness develop exclusively in the postnatal period because of the quality of the relationship in the first year of life. Thus, this review focuses on the importance of programming during the early developmental period on the manifestation of adult diseases in both animal models and humans. Considering the obvious differences between animals and humans we cannot systematically move from animal models to humans. Consequently, in the first part of this review, we will discuss how animal models can be used to dissect the influence of adverse events occurring during the prenatal and postnatal periods on the developmental trajectories of the offspring, and in the second part, we will discuss the role of postnatal critical periods on the development of mental diseases in humans. Epigenetic mechanisms that cause reversible modifications in gene expression, driving the development of a pathological phenotype in response to a negative early postnatal environment, may lie at the core of this programming, thereby providing potential new therapeutic targets. The concept of the Human Birth Theory leads to a comprehension of the mental illness as a pathology of the human relationship immediately after birth and during the first year of life. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Polyurethane acrylates as effective substrates for sustained in vitro culture of human myotubes.

PubMed

Andriani, Yosephine; Chua, Jason Min-Wen; Chua, Benjamin Yan-Jiang; Phang, In Yee; Shyh-Chang, Ng; Tan, Wui Siew

2017-07-15

Muscular disease has debilitating effects with severe damage leading to death. Our knowledge of muscle biology, disease and treatment is largely derived from non-human cell models, even though non-human cells are known to differ from human cells in their biochemical responses. Attempts to develop highly sought after in vitro human cell models have been plagued by early cell delamination and difficulties in achieving human myotube culture in vitro. In this work, we developed polyurethane acrylate (PUA) materials to support long-term in vitro culture of human skeletal muscle tissue. Using a constant base with modulated crosslink density we were able to vary the material modulus while keeping surface chemistry and roughness constant. While previous studies have focused on materials that mimic soft muscle tissue with stiffness ca. 12kPa, we investigated materials with tendon-like surface moduli in the higher 150MPa to 2.4GPa range, which has remained unexplored. We found that PUA of an optimal modulus within this range can support human myoblast proliferation, terminal differentiation and sustenance beyond 35days, without use of any extracellular protein coating. Results show that PUA materials can serve as effective substrates for successful development of human skeletal muscle cell models and are suitable for long-term in vitro studies. We developed polyurethane acrylates (PUA) to modulate the human skeletal muscle cell growth and maturation in vitro by controlling surface chemistry, morphology and tuning material's stiffness. PUA was able to maintain muscle cell viability for over a month without any detectable signs of material degradation. The best performing PUA prevented premature cell detachment from the substrate which often hampered long-term muscle cell studies. It also supported muscle cell maturation up to the late stages of differentiation. The significance of these findings lies in the possibility to advance studies on muscle cell biology, disease and therapy by using human muscle cells instead of relying on the widely used animal-based in vitro models. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Next generation human skin constructs as advanced tools for drug development.

PubMed

Abaci, H E; Guo, Zongyou; Doucet, Yanne; Jacków, Joanna; Christiano, Angela

2017-11-01

Many diseases, as well as side effects of drugs, manifest themselves through skin symptoms. Skin is a complex tissue that hosts various specialized cell types and performs many roles including physical barrier, immune and sensory functions. Therefore, modeling skin in vitro presents technical challenges for tissue engineering. Since the first attempts at engineering human epidermis in 1970s, there has been a growing interest in generating full-thickness skin constructs mimicking physiological functions by incorporating various skin components, such as vasculature and melanocytes for pigmentation. Development of biomimetic in vitro human skin models with these physiological functions provides a new tool for drug discovery, disease modeling, regenerative medicine and basic research for skin biology. This goal, however, has long been delayed by the limited availability of different cell types, the challenges in establishing co-culture conditions, and the ability to recapitulate the 3D anatomy of the skin. Recent breakthroughs in induced pluripotent stem cell (iPSC) technology and microfabrication techniques such as 3D-printing have allowed for building more reliable and complex in vitro skin models for pharmaceutical screening. In this review, we focus on the current developments and prevailing challenges in generating skin constructs with vasculature, skin appendages such as hair follicles, pigmentation, immune response, innervation, and hypodermis. Furthermore, we discuss the promising advances that iPSC technology offers in order to generate in vitro models of genetic skin diseases, such as epidermolysis bullosa and psoriasis. We also discuss how future integration of the next generation human skin constructs onto microfluidic platforms along with other tissues could revolutionize the early stages of drug development by creating reliable evaluation of patient-specific effects of pharmaceutical agents. Impact statement Skin is a complex tissue that hosts various specialized cell types and performs many roles including barrier, immune, and sensory functions. For human-relevant drug testing, there has been a growing interest in building more physiological skin constructs by incorporating different skin components, such as vasculature, appendages, pigment, innervation, and adipose tissue. This paper provides an overview of the strategies to build complex human skin constructs that can faithfully recapitulate human skin and thus can be used in drug development targeting skin diseases. In particular, we discuss recent developments and remaining challenges in incorporating various skin components, availability of iPSC-derived skin cell types and in vitro skin disease models. In addition, we provide insights on the future integration of these complex skin models with other organs on microfluidic platforms as well as potential readout technologies for high-throughput drug screening.

Integrative biology approach identifies cytokine targeting strategies for psoriasis.

PubMed

Perera, Gayathri K; Ainali, Chrysanthi; Semenova, Ekaterina; Hundhausen, Christian; Barinaga, Guillermo; Kassen, Deepika; Williams, Andrew E; Mirza, Muddassar M; Balazs, Mercedesz; Wang, Xiaoting; Rodriguez, Robert Sanchez; Alendar, Andrej; Barker, Jonathan; Tsoka, Sophia; Ouyang, Wenjun; Nestle, Frank O

2014-02-12

Cytokines are critical checkpoints of inflammation. The treatment of human autoimmune disease has been revolutionized by targeting inflammatory cytokines as key drivers of disease pathogenesis. Despite this, there exist numerous pitfalls when translating preclinical data into the clinic. We developed an integrative biology approach combining human disease transcriptome data sets with clinically relevant in vivo models in an attempt to bridge this translational gap. We chose interleukin-22 (IL-22) as a model cytokine because of its potentially important proinflammatory role in epithelial tissues. Injection of IL-22 into normal human skin grafts produced marked inflammatory skin changes resembling human psoriasis. Injection of anti-IL-22 monoclonal antibody in a human xenotransplant model of psoriasis, developed specifically to test potential therapeutic candidates, efficiently blocked skin inflammation. Bioinformatic analysis integrating both the IL-22 and anti-IL-22 cytokine transcriptomes and mapping them onto a psoriasis disease gene coexpression network identified key cytokine-dependent hub genes. Using knockout mice and small-molecule blockade, we show that one of these hub genes, the so far unexplored serine/threonine kinase PIM1, is a critical checkpoint for human skin inflammation and potential future therapeutic target in psoriasis. Using in silico integration of human data sets and biological models, we were able to identify a new target in the treatment of psoriasis.

Stanford/NASA-Ames Center of Excellence in model-based human performance

NASA Technical Reports Server (NTRS)

Wandell, Brian A.

1990-01-01

The human operator plays a critical role in many aeronautic and astronautic missions. The Stanford/NASA-Ames Center of Excellence in Model-Based Human Performance (COE) was initiated in 1985 to further our understanding of the performance capabilities and performance limits of the human component of aeronautic and astronautic projects. Support from the COE is devoted to those areas of experimental and theoretical work designed to summarize and explain human performance by developing computable performance models. The ultimate goal is to make these computable models available to other scientists for use in design and evaluation of aeronautic and astronautic instrumentation. Within vision science, two topics have received particular attention. First, researchers did extensive work analyzing the human ability to recognize object color relatively independent of the spectral power distribution of the ambient lighting (color constancy). The COE has supported a number of research papers in this area, as well as the development of a substantial data base of surface reflectance functions, ambient illumination functions, and an associated software package for rendering and analyzing image data with respect to these spectral functions. Second, the COE supported new empirical studies on the problem of selecting colors for visual display equipment to enhance human performance in discrimination and recognition tasks.

Development, fabrication, and modeling of highly sensitive conjugated polymer based piezoresistive sensors in electronic skin applications

NASA Astrophysics Data System (ADS)

Khalili, Nazanin; Naguib, Hani E.; Kwon, Roy H.

2016-04-01

Human intervention can be replaced through development of tools resulted from utilizing sensing devices possessing a wide range of applications including humanoid robots or remote and minimally invasive surgeries. Similar to the five human senses, sensors interface with their surroundings to stimulate a suitable response or action. The sense of touch which arises in human skin is among the most challenging senses to emulate due to its ultra high sensitivity. This has brought forth novel challenging issues to consider in the field of biomimetic robotics. In this work, using a multiphase reaction, a polypyrrole (PPy) based hydrogel is developed as a resistive type pressure sensor with an intrinsically elastic microstructure stemming from three dimensional hollow spheres. Furthermore, a semi-analytical constriction resistance model accounting for the real contact area between the PPy hydrogel sensors and the electrode along with the dependency of the contact resistance change on the applied load is developed. The model is then solved using a Monte Carlo technique and the sensitivity of the sensor is obtained. The experimental results showed the good tracking ability of the proposed model.

How to Develop and Interpret a Credibility Assessment of Numerical Models for Human Research: NASA-STD-7009 Demystified

NASA Technical Reports Server (NTRS)

Nelson, Emily S.; Mulugeta, Lealem; Walton, Marlei; Myers, Jerry G.

2014-01-01

In the wake of the Columbia accident, the NASA-STD-7009 [1] credibility assessment was developed as a unifying platform to describe model credibility and the uncertainties in its modeling predictions. This standard is now being adapted by NASAs Human Research Program to cover a wide range of numerical models for human research. When used properly, the standard can improve the process of code development by encouraging the use of best practices. It can also give management more insight in making informed decisions through a better understanding of the models capabilities and limitations.To a newcomer, the abstractions presented in NASA-STD-7009 and the sheer volume of information that must be absorbed can be overwhelming. This talk is aimed at describing the credibility assessment, which is the heart of the standard, in plain terms. It will outline how to develop a credibility assessment under the standard. It will also show how to quickly interpret the graphs and tables that result from the assessment and how to drill down from the top-level view to the foundation of the assessment. Finally, it will highlight some of the resources that are available for further study.

The impact of corruption on the sustainable development of human capital

NASA Astrophysics Data System (ADS)

Absalyamova, Svetlana; Absalyamov, Timur; Khusnullova, Asiya; Mukhametgalieva, Chulpan

2016-08-01

The article explains the use of the human capital sustainable development index (HCSDI) to assess the quality of the reproduction of human capital. The paper provides the algorithm for calculating HCSDI and its components. Authors estimated cross-country differences of HCSDI and developed econometric model of the impact of corruption on HCSDI. The use of this model has allowed to reveal the mechanism and assess the impact of corruption on HCSDI and its components. The results of econometric analysis revealed a negative multiplier effect: an increase in the corruption of the socio-economic system of the state by 1% caused HCSDI reduce by more than 1%. The results and conclusions may be proxy-assessments of the socio-economic consequences of violations of the stability of reproduction of human capital in the conditions of the growth of corruption in the country

Integration of Human Reliability Analysis Models into the Simulation-Based Framework for the Risk-Informed Safety Margin Characterization Toolkit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boring, Ronald; Mandelli, Diego; Rasmussen, Martin

2016-06-01

This report presents an application of a computation-based human reliability analysis (HRA) framework called the Human Unimodel for Nuclear Technology to Enhance Reliability (HUNTER). HUNTER has been developed not as a standalone HRA method but rather as framework that ties together different HRA methods to model dynamic risk of human activities as part of an overall probabilistic risk assessment (PRA). While we have adopted particular methods to build an initial model, the HUNTER framework is meant to be intrinsically flexible to new pieces that achieve particular modeling goals. In the present report, the HUNTER implementation has the following goals: •more » Integration with a high fidelity thermal-hydraulic model capable of modeling nuclear power plant behaviors and transients • Consideration of a PRA context • Incorporation of a solid psychological basis for operator performance • Demonstration of a functional dynamic model of a plant upset condition and appropriate operator response This report outlines these efforts and presents the case study of a station blackout scenario to demonstrate the various modules developed to date under the HUNTER research umbrella.« less

SIGNAL DETECTION BEHAVIOR IN HUMANS AND RATS: A COMPARISON WITH MATCHED TASKS.

EPA Science Inventory

Animal models of human cognitive processes are essential for studying the neurobiological mechanisms of these processes and for developing therapies for intoxication and neurodegenerative diseases. A discrete-trial signal detection task was developed for assessing sustained atten...

Networks for image acquisition, processing and display

NASA Technical Reports Server (NTRS)

Ahumada, Albert J., Jr.

1990-01-01

The human visual system comprises layers of networks which sample, process, and code images. Understanding these networks is a valuable means of understanding human vision and of designing autonomous vision systems based on network processing. Ames Research Center has an ongoing program to develop computational models of such networks. The models predict human performance in detection of targets and in discrimination of displayed information. In addition, the models are artificial vision systems sharing properties with biological vision that has been tuned by evolution for high performance. Properties include variable density sampling, noise immunity, multi-resolution coding, and fault-tolerance. The research stresses analysis of noise in visual networks, including sampling, photon, and processing unit noises. Specific accomplishments include: models of sampling array growth with variable density and irregularity comparable to that of the retinal cone mosaic; noise models of networks with signal-dependent and independent noise; models of network connection development for preserving spatial registration and interpolation; multi-resolution encoding models based on hexagonal arrays (HOP transform); and mathematical procedures for simplifying analysis of large networks.

Animal Models of Hemophilia and Related Bleeding Disorders

PubMed Central

Lozier, Jay N.; Nichols, Timothy C.

2013-01-01

Animal models of hemophilia and related diseases are important for development of novel treatments and to understand the pathophysiology of bleeding disorders in humans. Testing in animals with the equivalent human disorder provides informed estimates of doses and measures of efficacy, which aids in design of human trials. Many models of hemophilia A, hemophilia B, and von Willebrand disease have been developed from animals with spontaneous mutations (hemophilia A dogs, rats, sheep; hemophilia B dogs; and von Willebrand disease pigs and dogs), or by targeted gene disruption in mice to create hemophilia A, B, or VWD models. Animal models have been used to generate new insights into the pathophysiology of each bleeding disorder and also to perform pre-clinical assessments of standard protein replacement therapies as well as novel gene transfer technology. Both the differences between species and differences in underlying causative mutations must be considered in choosing the best animal for a specific scientific study PMID:23956467

A Human Systems Integration Perspective to Evaluating Naval Aviation Mishaps and Developing Intervention Strategies

DTIC Science & Technology

2009-12-01

SWISS CHEESE ” MODEL........................................... 16 1. Errors and Violations...16 Figure 5. Reason’s Swiss Cheese Model (After: Reason, 1990, p. 208) ........... 20 Figure 6. The HFACS Swiss Cheese Model of...become more complex. E. REASON’S “ SWISS CHEESE ” MODEL Reason’s (1990) book, Human Error, is generally regarded as the seminal work on the subject

Alternatives to In Vivo Draize Rabbit Eye and Skin Irritation Tests with a Focus on 3D Reconstructed Human Cornea-Like Epithelium and Epidermis Models

PubMed Central

Lee, Miri; Hwang, Jee-Hyun; Lim, Kyung-Min

2017-01-01

Human eyes and skin are frequently exposed to chemicals accidentally or on purpose due to their external location. Therefore, chemicals are required to undergo the evaluation of the ocular and dermal irritancy for their safe handling and use before release into the market. Draize rabbit eye and skin irritation test developed in 1944, has been a gold standard test which was enlisted as OECD TG 404 and OECD TG 405 but it has been criticized with respect to animal welfare due to invasive and cruel procedure. To replace it, diverse alternatives have been developed: (i) For Draize eye irritation test, organotypic assay, in vitro cytotoxicity-based method, in chemico tests, in silico prediction model, and 3D reconstructed human cornea-like epithelium (RhCE); (ii) For Draize skin irritation test, in vitro cytotoxicity-based cell model, and 3D reconstructed human epidermis models (RhE). Of these, RhCE and RhE models are getting spotlight as a promising alternative with a wide applicability domain covering cosmetics and personal care products. In this review, we overviewed the current alternatives to Draize test with a focus on 3D human epithelium models to provide an insight into advancing and widening their utility. PMID:28744350

A novel canine model for prostate cancer.

PubMed

Keller, Jill M; Schade, George R; Ives, Kimberly; Cheng, Xu; Rosol, Thomas J; Piert, Morand; Siddiqui, Javed; Roberts, William W; Keller, Evan T

2013-06-01

No existing animal model fully recapitulates all features of human prostate cancer. The dog is the only large mammal, besides humans, that commonly develops spontaneous prostate cancer. Canine prostate cancer features many similarities with its human counterpart. We sought to develop a canine model of prostate cancer that would more fully represent the features of human prostate cancer than existing models. The Ace-1 canine prostate cancer cell line was injected transabdominally under transrectal ultrasound (TRUS) guidance into the prostates of immunosuppressed, intact, adult male dogs. Tumor progression was monitored by TRUS imaging. Some dogs were subjected to positron emission tomography (PET) for tumor detection. Time of euthanasia was determined based on tumor size, impingement on urethra, and general well-being. Euthanasia was followed by necropsy and histopathology. Ace-1 tumor cells grew robustly in every dog injected. Tumors grew in subcapsular and parenchymal regions of the prostate. Tumor tissue could be identified using PET. Histological findings were similar to those observed in human prostate cancer. Metastases to lungs and lymph nodes were detected, predominantly in dogs with intraprostatic tumors. We have established a minimally invasive dog model of prostate cancer. This model may be valuable for studying prostate cancer progression and distant metastasis. Copyright © 2013 Wiley Periodicals, Inc.

Bioprinting technologies for disease modeling.

PubMed

Memic, Adnan; Navaei, Ali; Mirani, Bahram; Cordova, Julio Alvin Vacacela; Aldhahri, Musab; Dolatshahi-Pirouz, Alireza; Akbari, Mohsen; Nikkhah, Mehdi

2017-09-01

There is a great need for the development of biomimetic human tissue models that allow elucidation of the pathophysiological conditions involved in disease initiation and progression. Conventional two-dimensional (2D) in vitro assays and animal models have been unable to fully recapitulate the critical characteristics of human physiology. Alternatively, three-dimensional (3D) tissue models are often developed in a low-throughput manner and lack crucial native-like architecture. The recent emergence of bioprinting technologies has enabled creating 3D tissue models that address the critical challenges of conventional in vitro assays through the development of custom bioinks and patient derived cells coupled with well-defined arrangements of biomaterials. Here, we provide an overview on the technological aspects of 3D bioprinting technique and discuss how the development of bioprinted tissue models have propelled our understanding of diseases' characteristics (i.e. initiation and progression). The future perspectives on the use of bioprinted 3D tissue models for drug discovery application are also highlighted.

A New Presentation and Exploration of Human Cerebral Vasculature Correlated with Surface and Sectional Neuroanatomy

ERIC Educational Resources Information Center

Nowinski, Wieslaw L.; Thirunavuukarasuu, Arumugam; Volkau, Ihar; Marchenko, Yevgen; Aminah, Bivi; Gelas, Arnaud; Huang, Su; Lee, Looi Chow; Liu, Jimin; Ng, Ting Ting; Nowinska, Natalia G.; Qian, Guoyu Yu; Puspitasari, Fiftarina; Runge, Val M.

2009-01-01

The increasing complexity of human body models enabled by advances in diagnostic imaging, computing, and growing knowledge calls for the development of a new generation of systems for intelligent exploration of these models. Here, we introduce a novel paradigm for the exploration of digital body models illustrating cerebral vasculature. It enables…

The rabbit as a model for studying lung disease and stem cell therapy.

PubMed

Kamaruzaman, Nurfatin Asyikhin; Kardia, Egi; Kamaldin, Nurulain 'Atikah; Latahir, Ahmad Zaeri; Yahaya, Badrul Hisham

2013-01-01

No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy.

The Rabbit as a Model for Studying Lung Disease and Stem Cell Therapy

PubMed Central

Kamaruzaman, Nurfatin Asyikhin; Kamaldin, Nurulain ‘Atikah; Latahir, Ahmad Zaeri; Yahaya, Badrul Hisham

2013-01-01

No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy. PMID:23653896

Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

PubMed Central

Williams, Jonathan M.

2017-01-01

ABSTRACT Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems. PMID:28151409

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.

Toxicokinetic Model Development for the Insensitive Munitions Component 2,4-Dinitroanisole.

PubMed

Sweeney, Lisa M; Goodwin, Michelle R; Hulgan, Angela D; Gut, Chester P; Bannon, Desmond I

2015-01-01

The Armed Forces are developing new explosives that are less susceptible to unintentional detonation (insensitive munitions [IMX]). 2,4-Dinitroanisole (DNAN) is a component of IMX. Toxicokinetic data for DNAN are required to support interpretation of toxicology studies and refinement of dose estimates for human risk assessment. Male Sprague-Dawley rats were dosed by gavage (5, 20, or 80 mg DNAN/kg), and blood and tissue samples were analyzed to determine the levels of DNAN and its metabolite 2,4-dinitrophenol (DNP). These data and data from the literature were used to develop preliminary physiologically based pharmacokinetic (PBPK) models. The model simulations indicated saturable metabolism of DNAN in rats at higher tested doses. The PBPK model was extrapolated to estimate the toxicokinetics of DNAN and DNP in humans, allowing the estimation of human-equivalent no-effect levels of DNAN exposure from no-observed adverse effect levels determined in laboratory animals, which may guide the selection of exposure limits for DNAN. © The Author(s) 2015.

Identification and experimental validation of damping ratios of different human body segments through anthropometric vibratory model in standing posture.

PubMed

Gupta, T C

2007-08-01

A 15 degrees of freedom lumped parameter vibratory model of human body is developed, for vertical mode vibrations, using anthropometric data of the 50th percentile US male. The mass and stiffness of various segments are determined from the elastic modulii of bones and tissues and from the anthropometric data available, assuming the shape of all the segments is ellipsoidal. The damping ratio of each segment is estimated on the basis of the physical structure of the body in a particular posture. Damping constants of various segments are calculated from these damping ratios. The human body is modeled as a linear spring-mass-damper system. The optimal values of the damping ratios of the body segments are estimated, for the 15 degrees of freedom model of the 50th percentile US male, by comparing the response of the model with the experimental response. Formulating a similar vibratory model of the 50th percentile Indian male and comparing the frequency response of the model with the experimental response of the same group of subjects validate the modeling procedure. A range of damping ratios has been considered to develop a vibratory model, which can predict the vertical harmonic response of the human body.

ASSESSING RESIDENTIAL EXPOSURE USING THE STOCHASTIC HUMAN EXPOSURE AND DOSE SIMULATION (SHEDS) MODEL

EPA Science Inventory

As part of a workshop sponsored by the Environmental Protection Agency's Office of Research and Development and Office of Pesticide Programs, the Aggregate Stochastic Human Exposure and Dose Simulation (SHEDS) Model was used to assess potential aggregate residential pesticide e...

Stochastic Human Exposure and Dose Simulation for Air Toxics

EPA Science Inventory

The Stochastic Human Exposure and Dose Simulation model for Air Toxics (SHEDS-AirToxics) is a multimedia, multipathway population-based exposure and dose model for air toxics developed by the US EPA's National Exposure Research Laboratory (NERL). SHEDS-AirToxics uses a probabili...

DEVELOPMENT OF A MODEL FOR REAL TIME CO CONCENTRATIONS NEAR ROADWAYS

EPA Science Inventory

Although emission standards for mobile sources continue to be tightened, tailpipe emissions in urban areas continue to be a major source of human exposure to air toxics. Current human exposure models using simplified assumptions based on fixed air monitoring stations and region...

Status and Problems of Humanities Education with Respect to Pharmacy Education.

PubMed

Ishikawa, Satoko

2017-01-01

In 2006, a model core curriculum in pharmaceutical studies was developed prior to the outset of the 6-year pharmacy degree. In the 10 years that followed, medical care and life science technology has progressed, pharmaceutical laws have been revised, and the responsibilities of pharmacists have increased. In response to such social changes and needs, the Model Core Curriculum for Pharmacy Education was revised in December 2013. In order to play an active role as a pharmacist in any medical workplace, it is important for pharmacy students to develop their communication skills and attitudes in order to foster the trust of their patients and other medical professionals. In the new Model Core Curriculum, education in the humanities is clearly described as a foundation to pharmaceutical education, which pertains to the clinical role of a pharmacist; hence, each pharmacy school has outlined strategies for students to learn bioethics and medical ethics, and to develop communication skills. Today, although the importance of humanities education is rapidly increasing, it is difficult to immediately evaluate the outcome of learning humanities subjects and communication. Such an evaluation requires a longer-term perspective. This paper describes the status and problems of humanities education as a component of pharmacy education, and considers future directions of research in humanities education with respect to pharmacy education.

Cognitive computing and eScience in health and life science research: artificial intelligence and obesity intervention programs.

PubMed

Marshall, Thomas; Champagne-Langabeer, Tiffiany; Castelli, Darla; Hoelscher, Deanna

2017-12-01

To present research models based on artificial intelligence and discuss the concept of cognitive computing and eScience as disruptive factors in health and life science research methodologies. The paper identifies big data as a catalyst to innovation and the development of artificial intelligence, presents a framework for computer-supported human problem solving and describes a transformation of research support models. This framework includes traditional computer support; federated cognition using machine learning and cognitive agents to augment human intelligence; and a semi-autonomous/autonomous cognitive model, based on deep machine learning, which supports eScience. The paper provides a forward view of the impact of artificial intelligence on our human-computer support and research methods in health and life science research. By augmenting or amplifying human task performance with artificial intelligence, cognitive computing and eScience research models are discussed as novel and innovative systems for developing more effective adaptive obesity intervention programs.

Engineered in vitro disease models.

PubMed

Benam, Kambez H; Dauth, Stephanie; Hassell, Bryan; Herland, Anna; Jain, Abhishek; Jang, Kyung-Jin; Karalis, Katia; Kim, Hyun Jung; MacQueen, Luke; Mahmoodian, Roza; Musah, Samira; Torisawa, Yu-suke; van der Meer, Andries D; Villenave, Remi; Yadid, Moran; Parker, Kevin K; Ingber, Donald E

2015-01-01

The ultimate goal of most biomedical research is to gain greater insight into mechanisms of human disease or to develop new and improved therapies or diagnostics. Although great advances have been made in terms of developing disease models in animals, such as transgenic mice, many of these models fail to faithfully recapitulate the human condition. In addition, it is difficult to identify critical cellular and molecular contributors to disease or to vary them independently in whole-animal models. This challenge has attracted the interest of engineers, who have begun to collaborate with biologists to leverage recent advances in tissue engineering and microfabrication to develop novel in vitro models of disease. As these models are synthetic systems, specific molecular factors and individual cell types, including parenchymal cells, vascular cells, and immune cells, can be varied independently while simultaneously measuring system-level responses in real time. In this article, we provide some examples of these efforts, including engineered models of diseases of the heart, lung, intestine, liver, kidney, cartilage, skin and vascular, endocrine, musculoskeletal, and nervous systems, as well as models of infectious diseases and cancer. We also describe how engineered in vitro models can be combined with human inducible pluripotent stem cells to enable new insights into a broad variety of disease mechanisms, as well as provide a test bed for screening new therapies.

Open-source approaches for the repurposing of existing or failed candidate drugs: learning from and applying the lessons across diseases

PubMed Central

Allarakhia, Minna

2013-01-01

Repurposing has the objective of targeting existing drugs and failed, abandoned, or yet-to-be-pursued clinical candidates to new disease areas. The open-source model permits for the sharing of data, resources, compounds, clinical molecules, small libraries, and screening platforms to cost-effectively advance old drugs and/or candidates into clinical re-development. Clearly, at the core of drug-repurposing activities is collaboration, in many cases progressing beyond the open sharing of resources, technology, and intellectual property, to the sharing of facilities and joint program development to foster drug-repurposing human-capacity development. A variety of initiatives under way for drug repurposing, including those targeting rare and neglected diseases, are discussed in this review and provide insight into the stakeholders engaged in drug-repurposing discovery, the models of collaboration used, the intellectual property-management policies crafted, and human capacity developed. In the case of neglected tropical diseases, it is suggested that the development of human capital be a central aspect of drug-repurposing programs. Open-source models can support human-capital development through collaborative data generation, open compound access, open and collaborative screening, preclinical and possibly clinical studies. Given the urgency of drug development for neglected tropical diseases, the review suggests elements from current repurposing programs be extended to the neglected tropical diseases arena. PMID:23966771

Open-source approaches for the repurposing of existing or failed candidate drugs: learning from and applying the lessons across diseases.

PubMed

Allarakhia, Minna

2013-01-01

Repurposing has the objective of targeting existing drugs and failed, abandoned, or yet-to-be-pursued clinical candidates to new disease areas. The open-source model permits for the sharing of data, resources, compounds, clinical molecules, small libraries, and screening platforms to cost-effectively advance old drugs and/or candidates into clinical re-development. Clearly, at the core of drug-repurposing activities is collaboration, in many cases progressing beyond the open sharing of resources, technology, and intellectual property, to the sharing of facilities and joint program development to foster drug-repurposing human-capacity development. A variety of initiatives under way for drug repurposing, including those targeting rare and neglected diseases, are discussed in this review and provide insight into the stakeholders engaged in drug-repurposing discovery, the models of collaboration used, the intellectual property-management policies crafted, and human capacity developed. In the case of neglected tropical diseases, it is suggested that the development of human capital be a central aspect of drug-repurposing programs. Open-source models can support human-capital development through collaborative data generation, open compound access, open and collaborative screening, preclinical and possibly clinical studies. Given the urgency of drug development for neglected tropical diseases, the review suggests elements from current repurposing programs be extended to the neglected tropical diseases arena.

Engineering a humanized bone organ model in mice to study bone metastases.

PubMed

Martine, Laure C; Holzapfel, Boris M; McGovern, Jacqui A; Wagner, Ferdinand; Quent, Verena M; Hesami, Parisa; Wunner, Felix M; Vaquette, Cedryck; De-Juan-Pardo, Elena M; Brown, Toby D; Nowlan, Bianca; Wu, Dan Jing; Hutmacher, Cosmo Orlando; Moi, Davide; Oussenko, Tatiana; Piccinini, Elia; Zandstra, Peter W; Mazzieri, Roberta; Lévesque, Jean-Pierre; Dalton, Paul D; Taubenberger, Anna V; Hutmacher, Dietmar W

2017-04-01

Current in vivo models for investigating human primary bone tumors and cancer metastasis to the bone rely on the injection of human cancer cells into the mouse skeleton. This approach does not mimic species-specific mechanisms occurring in human diseases and may preclude successful clinical translation. We have developed a protocol to engineer humanized bone within immunodeficient hosts, which can be adapted to study the interactions between human cancer cells and a humanized bone microenvironment in vivo. A researcher trained in the principles of tissue engineering will be able to execute the protocol and yield study results within 4-6 months. Additive biomanufactured scaffolds seeded and cultured with human bone-forming cells are implanted ectopically in combination with osteogenic factors into mice to generate a physiological bone 'organ', which is partially humanized. The model comprises human bone cells and secreted extracellular matrix (ECM); however, other components of the engineered tissue, such as the vasculature, are of murine origin. The model can be further humanized through the engraftment of human hematopoietic stem cells (HSCs) that can lead to human hematopoiesis within the murine host. The humanized organ bone model has been well characterized and validated and allows dissection of some of the mechanisms of the bone metastatic processes in prostate and breast cancer.

Integrating the social sciences to understand human-water dynamics

NASA Astrophysics Data System (ADS)

Carr, G.; Kuil, L., Jr.

2017-12-01

Many interesting and exciting socio-hydrological models have been developed in recent years. Such models often aim to capture the dynamic interplay between people and water for a variety of hydrological settings. As such, peoples' behaviours and decisions are brought into the models as drivers of and/or respondents to the hydrological system. To develop and run such models over a sufficiently long time duration to observe how the water-human system evolves the human component is often simplified according to one or two key behaviours, characteristics or decisions (e.g. a decision to move away from a drought or flood area; a decision to pump groundwater, or a decision to plant a less water demanding crop). To simplify the social component, socio-hydrological modellers often pull knowledge and understanding from existing social science theories. This requires them to negotiate complex territory, where social theories may be underdeveloped, contested, dynamically evolving, or case specific and difficult to generalise or upscale. A key question is therefore, how can this process be supported so that the resulting socio-hydrological models adequately describe the system and lead to meaningful understanding of how and why it behaves as it does? Collaborative interdisciplinary research teams that bring together social and natural scientists are likely to be critical. Joint development of the model framework requires specific attention to clarification to expose all underlying assumptions, constructive discussion and negotiation to reach agreement on the modelled system and its boundaries. Mutual benefits to social scientists can be highlighted, i.e. socio-hydrological work can provide insights for further exploring and testing social theories. Collaborative work will also help ensure underlying social theory is made explicit, and may identify ways to include and compare multiple theories. As socio-hydrology progresses towards supporting policy development, approaches that brings in stakeholders and non-scientist participants to develop the conceptual modelling framework will become essential. They are also critical for fully understanding human-water dynamics.

Label-free detection of protein molecules secreted from an organ-on-a-chip model for drug toxicity assays

NASA Astrophysics Data System (ADS)

Morales, Andres W.; Zhang, Yu S.; Aleman, Julio; Alerasool, Parissa; Dokmeci, Mehmet R.; Khademhosseini, Ali; Ye, Jing Yong

2016-03-01

Clinical attrition is about 30% from failure of drug candidates due to toxic side effects, increasing the drug development costs significantly and slowing down the drug discovery process. This partly originates from the fact that the animal models do not accurately represent human physiology. Hence there is a clear unmet need for developing drug toxicity assays using human-based models that are complementary to traditional animal models before starting expensive clinical trials. Organ-on-a-chip techniques developed in recent years have generated a variety of human organ models mimicking different human physiological conditions. However, it is extremely challenging to monitor the transient and long-term response of the organ models to drug treatments during drug toxicity tests. First, when an organ-on-a-chip model interacts with drugs, a certain amount of protein molecules may be released into the medium due to certain drug effects, but the amount of the protein molecules is limited, since the organ tissue grown inside microfluidic bioreactors have minimum volume. Second, traditional fluorescence techniques cannot be utilized for real-time monitoring of the concentration of the protein molecules, because the protein molecules are continuously secreted from the tissue and it is practically impossible to achieve fluorescence labeling in the dynamically changing environment. Therefore, direct measurements of the secreted protein molecules with a label-free approach is strongly desired for organs-on-a-chip applications. In this paper, we report the development of a photonic crystal-based biosensor for label-free assays of secreted protein molecules from a liver-on-a-chip model. Ultrahigh detection sensitivity and specificity have been demonstrated.

Niclosamide rescues microcephaly in a humanized in vivo model of Zika infection using human induced neural stem cells

PubMed Central

Boorgu, Devi Sai Sri Kavya; Levin, Michael; Kaplan, David L.

2018-01-01

ABSTRACT Zika virus (ZIKV) is a mosquito-transmitted flavivirus with a causative link to microcephaly, a condition resulting in reduced cranial size and brain abnormalities. Despite recent progress, there is a current lack of in vivo models that permit the study of systemic virus on human neurons in a developing organism that replicates the pathophysiology of human disease. Furthermore, no treatment to date has been reported to reduce ZIKV-induced microcephaly. We tested the effects of ZIKV on human induced neural stem cells (hiNSCs) in vitro and found that infected hiNSCs secrete inflammatory cytokines, display altered differentiation, and become apoptotic. We also utilized this in vitro system to assess the therapeutic effects of niclosamide, an FDA-approved anthelminthic, and found that it decreases ZIKV production, partially restores differentiation, and prevents apoptosis in hiNSCs. We intracranially injected hiNSCs into developing chicks, subjected them to systemic ZIKV infection via the chorioallantoic membrane (CAM), a tissue similar in structure and function to the mammalian placenta, and found that humanized ZIKV-infected embryos developed severe microcephaly including smaller crania, decreased forebrain volume and enlarged ventricles. Lastly, we utilized this humanized model to show that CAM-delivery of niclosamide can partially rescue ZIKV-induced microcephaly and attenuate infection of hiNSCs in vivo. This article has an associated First Person interview with the first author of the paper. PMID:29378701

Ontological modelling of knowledge management for human-machine integrated design of ultra-precision grinding machine

NASA Astrophysics Data System (ADS)

Hong, Haibo; Yin, Yuehong; Chen, Xing

2016-11-01

Despite the rapid development of computer science and information technology, an efficient human-machine integrated enterprise information system for designing complex mechatronic products is still not fully accomplished, partly because of the inharmonious communication among collaborators. Therefore, one challenge in human-machine integration is how to establish an appropriate knowledge management (KM) model to support integration and sharing of heterogeneous product knowledge. Aiming at the diversity of design knowledge, this article proposes an ontology-based model to reach an unambiguous and normative representation of knowledge. First, an ontology-based human-machine integrated design framework is described, then corresponding ontologies and sub-ontologies are established according to different purposes and scopes. Second, a similarity calculation-based ontology integration method composed of ontology mapping and ontology merging is introduced. The ontology searching-based knowledge sharing method is then developed. Finally, a case of human-machine integrated design of a large ultra-precision grinding machine is used to demonstrate the effectiveness of the method.

Spontaneous onset and transplant models of the Vk*MYC mouse show immunological sequelae comparable to human multiple myeloma.

PubMed

Cooke, Rachel E; Gherardin, Nicholas A; Harrison, Simon J; Quach, Hang; Godfrey, Dale I; Prince, Miles; Koldej, Rachel; Ritchie, David S

2016-09-06

The Vk*MYC transgenic and transplant mouse models of multiple myeloma (MM) are well established as a research tool for anti-myeloma drug discovery. However, little is known of the immune response in these models. Understanding the immunological relevance of these models is of increasing importance as immunotherapeutic drugs are developed against MM. We set out to examine how cellular immunity is affected in Vk*MYC mouse models and compare that to the immunology of patients with newly diagnosed and relapsed/refractory MM. We found that there were significant immunological responses in mice developing either spontaneous (transgenic) or transplanted MM as a consequence of the degree of tumor burden. Particularly striking were the profound B cell lymphopenia and the expansion of CD8(+) effector memory T cells within the lymphocyte population that progressively developed with advancing disease burden, mirroring changes seen in human MM. High disease burden was also associated with increased inflammatory cytokine production by T lymphocytes, which is more fitting with relapsed/refractory MM in humans. These findings have important implications for the application of this mouse model in the development of MM immunotherapies. Trial registration LitVacc ANZCTR trial ID ACTRN12613000344796; RevLite ANZCTR trial ID NCT00482261.

Career Development.

ERIC Educational Resources Information Center

1996

This document consists of four papers presented during a symposium on career development moderated by David Bjorkquist at the 1996 conference of the Academy of Human Resource Development (AHRD). "A Mentoring Model for Career Development" (Mary Finnegan) describes a study that created a model based on the assumption that mentoring is an essential…

Commentary: The Ontogeny of Human Memory: Where Are We Going?

ERIC Educational Resources Information Center

Lavenex, Pamela Banta; Lavenex, Pierre

2015-01-01

In 1995, Nelson explored the relation between early memory development and corresponding changes in brain development, and conceptualized this knowledge in a coherent theoretical framework (Nelson, 1995). In their review, Jabe's and Nelson provide an update of Nelson's 1995 cognitive neuroscience model of human memory development. In this article,…

Annual Research Review: What is Resilience within the Social Ecology of Human Development?

ERIC Educational Resources Information Center

Ungar, Michael; Ghazinour, Mehdi; Richter, Jorg

2013-01-01

Background: The development of Bronfenbrenner's bio-social-ecological systems model of human development parallels advances made to the theory of resilience that progressively moved from a more individual (micro) focus on traits to a multisystemic understanding of person-environment reciprocal processes. Methods: This review uses…

Scaling a Human Body Finite Element Model with Radial Basis Function Interpolation

DTIC Science & Technology

Human body models are currently used to evaluate the body’s response to a variety of threats to the Soldier. The ability to adjust the size of human...body models is currently limited because of the complex shape changes that are required. Here, a radial basis function interpolation method is used to...morph the shape on an existing finite element mesh. Tools are developed and integrated into the Blender computer graphics software to assist with

Improving the physiological realism of experimental models

PubMed Central

Vinnakota, Kalyan C.; Cha, Chae Y.; Rorsman, Patrik; Balaban, Robert S.; La Gerche, Andre; Wade-Martins, Richard; Beard, Daniel A.

2016-01-01

The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide an in silico platform for drug screening. Ultimately, these models rely on the analysis and integration of experimental data. As such, the success of VPH depends on the availability of physiologically realistic experimental models (E-Models) of human organ function that can be parametrized to test the numerical models. Here, the current state of suitable E-models, ranging from in vitro non-human cell organelles to in vivo human organ systems, is discussed. Specifically, challenges and recent progress in improving the physiological realism of E-models that may benefit the VPH project are highlighted and discussed using examples from the field of research on cardiovascular disease, musculoskeletal disorders, diabetes and Parkinson's disease. PMID:27051507

The use of BLT humanized mice to investigate the immune reconstitution of the gastrointestinal tract.

PubMed

Wahl, Angela; Victor Garcia, J

2014-08-01

The gastrointestinal (GI) track represents an important battlefield where pathogens first try to gain entry into a host. It is also a universe where highly diverse and ever changing inhabitants co-exist in an exceptional equilibrium without parallel in any other organ system of the body. The gut as an organ has its own well-developed and fully functional immune organization that is similar and yet different in many important ways to the rest of the immune system. Both a compromised and an overactive immune system in the gut can have dire and severe consequences to human health. It has therefore been of great interest to develop animal models that recapitulate key aspects of the human condition to better understand the interplay of the host immune system with its friends and its foes. However, reconstitution of the GI tract in humanized mice has been difficult and highly variable in different systems. A better molecular understanding of the development of the gut immune system in mice has provided critical cues that have been recently used to develop novel humanized mouse models that fully recapitulate the genesis and key functions of the gut immune system of humans. Of particular interest is the presence of human gut-associated lymphoid tissue (GALT) aggregates in the gut of NOD/SCID BLT humanized mice that demonstrate the faithful development of bona fide human plasma cells capable of migrating to the lamina propria and producing human IgA1 and IgA2. Copyright © 2014 Elsevier B.V. All rights reserved.

Computer-aided design of the human aortic root.

PubMed

Ovcharenko, E A; Klyshnikov, K U; Vlad, A R; Sizova, I N; Kokov, A N; Nushtaev, D V; Yuzhalin, A E; Zhuravleva, I U

2014-11-01

The development of computer-based 3D models of the aortic root is one of the most important problems in constructing the prostheses for transcatheter aortic valve implantation. In the current study, we analyzed data from 117 patients with and without aortic valve disease and computed tomography data from 20 patients without aortic valvular diseases in order to estimate the average values of the diameter of the aortic annulus and other aortic root parameters. Based on these data, we developed a 3D model of human aortic root with unique geometry. Furthermore, in this study we show that by applying different material properties to the aortic annulus zone in our model, we can significantly improve the quality of the results of finite element analysis. To summarize, here we present four 3D models of human aortic root with unique geometry based on computational analysis of ECHO and CT data. We suggest that our models can be utilized for the development of better prostheses for transcatheter aortic valve implantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

DengueME: A Tool for the Modeling and Simulation of Dengue Spatiotemporal Dynamics †

PubMed Central

de Lima, Tiago França Melo; Lana, Raquel Martins; de Senna Carneiro, Tiago Garcia; Codeço, Cláudia Torres; Machado, Gabriel Souza; Ferreira, Lucas Saraiva; de Castro Medeiros, Líliam César; Davis Junior, Clodoveu Augusto

2016-01-01

The prevention and control of dengue are great public health challenges for many countries, particularly since 2015, as other arboviruses have been observed to interact significantly with dengue virus. Different approaches and methodologies have been proposed and discussed by the research community. An important tool widely used is modeling and simulation, which help us to understand epidemic dynamics and create scenarios to support planning and decision making processes. With this aim, we proposed and developed DengueME, a collaborative open source platform to simulate dengue disease and its vector’s dynamics. It supports compartmental and individual-based models, implemented over a GIS database, that represent Aedes aegypti population dynamics, human demography, human mobility, urban landscape and dengue transmission mediated by human and mosquito encounters. A user-friendly graphical interface was developed to facilitate model configuration and data input, and a library of models was developed to support teaching-learning activities. DengueME was applied in study cases and evaluated by specialists. Other improvements will be made in future work, to enhance its extensibility and usability. PMID:27649226

Overview of NASARTI (NASA Radiation Track Image) Program: Highlights of the Model Improvement and the New Results

NASA Technical Reports Server (NTRS)

Ponomarev, Artem L.; Plante, I.; George, Kerry; Cornforth, M. N.; Loucas, B. D.; Wu, Honglu

2014-01-01

This presentation summarizes several years of research done by the co-authors developing the NASARTI (NASA Radiation Track Image) program and supporting it with scientific data. The goal of the program is to support NASA mission to achieve a safe space travel for humans despite the perils of space radiation. The program focuses on selected topics in radiation biology that were deemed important throughout this period of time, both for the NASA human space flight program and to academic radiation research. Besides scientific support to develop strategies protecting humans against an exposure to deep space radiation during space missions, and understanding health effects from space radiation on astronauts, other important ramifications of the ionizing radiation were studied with the applicability to greater human needs: understanding the origins of cancer, the impact on human genome, and the application of computer technology to biological research addressing the health of general population. The models under NASARTI project include: the general properties of ionizing radiation, such as particular track structure, the effects of radiation on human DNA, visualization and the statistical properties of DSBs (DNA double-strand breaks), DNA damage and repair pathways models and cell phenotypes, chromosomal aberrations, microscopy data analysis and the application to human tissue damage and cancer models. The development of the GUI and the interactive website, as deliverables to NASA operations teams and tools for a broader research community, is discussed. Most recent findings in the area of chromosomal aberrations and the application of the stochastic track structure are also presented.

Strengths and Weaknesses of Pre-Clinical Models for Human Melanoma Treatment: Dawn of Dogs’ Revolution for Immunotherapy

PubMed Central

Barutello, Giuseppina; Rolih, Valeria; Arigoni, Maddalena; Tarone, Lidia; Conti, Laura

2018-01-01

Despite several therapeutic advances, malignant melanoma still remains a fatal disease for which novel and long-term curative treatments are needed. The successful development of innovative therapies strongly depends on the availability of appropriate pre-clinical models. For this purpose, several mouse models holding the promise to provide insight into molecular biology and clinical behavior of melanoma have been generated. The most relevant ones and their contribution for the advancement of therapeutic approaches for the treatment of human melanoma patients will be here summarized. However, as models, mice do not recapitulate all the features of human melanoma, thus their strengths and weaknesses need to be carefully identified and considered for the translation of the results into the human clinics. In this panorama, the concept of comparative oncology acquires a priceless value. The revolutionary importance of spontaneous canine melanoma as a translational model for the pre-clinical investigation of melanoma progression and treatment will be here discussed, with a special consideration to the development of innovative immunotherapeutic approaches. PMID:29534457

Final Report: PAGE: Policy Analytics Generation Engine

DTIC Science & Technology

2016-08-12

develop a parallel framework for it. We also developed policies and methods by which a group of defensive resources (e.g. checkpoints) could be...Sarit Kraus. Learning to Reveal Information in Repeated Human -Computer Negotiation, Human -Agent Interaction Design and Models Workshop 2012. 04-JUN...Joseph Keshet, Sarit Kraus. Predicting Human Strategic Decisions Using Facial Expressions, International Joint Conference on Artificial

The necessity of animal models in pain research.

PubMed

Mogil, Jeffrey S; Davis, Karen D; Derbyshire, Stuart W

2010-10-01

There exists currently a fair degree of introspection in the pain research community about the value of animal research. This review represents a defense of animal research in pain. We discuss the inherent advantage of animal models over human research as well as the crucial complementary roles animal studies play vis-à-vis human imaging and genetic studies. Finally, we discuss recent developments in animal models of pain that should improve the relevance and translatability of findings using laboratory animals. We believe that pain research using animal models is a continuing necessity-to understand fundamental mechanisms, identify new analgesic targets, and inform, guide and follow up human studies-if novel analgesics are to be developed for the treatment of chronic pain. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Structured models of infectious disease: inference with discrete data

PubMed Central

Metcalf, C.J.E.; Lessler, J.; Klepac, P.; Morice, A.; Grenfell, B.T.; Bjørnstad, O.N.

2014-01-01

The usage of structured population models can make substantial contributions to public health, particularly for infections where clinical outcomes vary over age. There are three theoretical challenges in implementing such analyses: i) developing an appropriate framework that models both demographic and epidemiological transitions; ii) parameterizing the framework, where parameters may be based on data ranging from the biological course of infection, basic patterns of human demography, specific characteristics of population growth, and details of vaccination regimes implemented; and iii) evaluating public health strategies in the face of changing human demography. We illustrate the general approach by developing a model of rubella in Costa Rica. The demographic profile of this infection is a crucial aspect of its public health impact, and we use a transient perturbation analysis to explore the impact of changing human demography on immunization strategies implemented. PMID:22178687

Genetically Engineered Cancer Models, But Not Xenografts, Faithfully Predict Anticancer Drug Exposure in Melanoma Tumors

PubMed Central

Combest, Austin J.; Roberts, Patrick J.; Dillon, Patrick M.; Sandison, Katie; Hanna, Suzan K.; Ross, Charlene; Habibi, Sohrab; Zamboni, Beth; Müller, Markus; Brunner, Martin; Sharpless, Norman E.

2012-01-01

Background. Rodent studies are a vital step in the development of novel anticancer therapeutics and are used in pharmacokinetic (PK), toxicology, and efficacy studies. Traditionally, anticancer drug development has relied on xenograft implantation of human cancer cell lines in immunocompromised mice for efficacy screening of a candidate compound. The usefulness of xenograft models for efficacy testing, however, has been questioned, whereas genetically engineered mouse models (GEMMs) and orthotopic syngeneic transplants (OSTs) may offer some advantages for efficacy assessment. A critical factor influencing the predictability of rodent tumor models is drug PKs, but a comprehensive comparison of plasma and tumor PK parameters among xenograft models, OSTs, GEMMs, and human patients has not been performed. Methods. In this work, we evaluated the plasma and tumor dispositions of an antimelanoma agent, carboplatin, in patients with cutaneous melanoma compared with four different murine melanoma models (one GEMM, one human cell line xenograft, and two OSTs). Results. Using microdialysis to sample carboplatin tumor disposition, we found that OSTs and xenografts were poor predictors of drug exposure in human tumors, whereas the GEMM model exhibited PK parameters similar to those seen in human tumors. Conclusions. The tumor PKs of carboplatin in a GEMM of melanoma more closely resembles the tumor disposition in patients with melanoma than transplanted tumor models. GEMMs show promise in becoming an improved prediction model for intratumoral PKs and response in patients with solid tumors. PMID:22993143

Accurate Prediction of Drug-Induced Liver Injury Using Stem Cell-Derived Populations

PubMed Central

Szkolnicka, Dagmara; Farnworth, Sarah L.; Lucendo-Villarin, Baltasar; Storck, Christopher; Zhou, Wenli; Iredale, John P.; Flint, Oliver

2014-01-01

Despite major progress in the knowledge and management of human liver injury, there are millions of people suffering from chronic liver disease. Currently, the only cure for end-stage liver disease is orthotopic liver transplantation; however, this approach is severely limited by organ donation. Alternative approaches to restoring liver function have therefore been pursued, including the use of somatic and stem cell populations. Although such approaches are essential in developing scalable treatments, there is also an imperative to develop predictive human systems that more effectively study and/or prevent the onset of liver disease and decompensated organ function. We used a renewable human stem cell resource, from defined genetic backgrounds, and drove them through developmental intermediates to yield highly active, drug-inducible, and predictive human hepatocyte populations. Most importantly, stem cell-derived hepatocytes displayed equivalence to primary adult hepatocytes, following incubation with known hepatotoxins. In summary, we have developed a serum-free, scalable, and shippable cell-based model that faithfully predicts the potential for human liver injury. Such a resource has direct application in human modeling and, in the future, could play an important role in developing renewable cell-based therapies. PMID:24375539

CYP3A5 Mediates Effects of Cocaine on Human Neocorticogenesis: Studies using an In Vitro 3D Self-Organized hPSC Model with a Single Cortex-Like Unit.

PubMed

Lee, Chun-Ting; Chen, Jia; Kindberg, Abigail A; Bendriem, Raphael M; Spivak, Charles E; Williams, Melanie P; Richie, Christopher T; Handreck, Annelie; Mallon, Barbara S; Lupica, Carl R; Lin, Da-Ting; Harvey, Brandon K; Mash, Deborah C; Freed, William J

2017-02-01

Because of unavoidable confounding variables in the direct study of human subjects, it has been difficult to unravel the effects of prenatal cocaine exposure on the human fetal brain, as well as the cellular and biochemical mechanisms involved. Here, we propose a novel approach using a human pluripotent stem cell (hPSC)-based 3D neocortical organoid model. This model retains essential features of human neocortical development by encompassing a single self-organized neocortical structure, without including an animal-derived gelatinous matrix. We reported previously that prenatal cocaine exposure to rats during the most active period of neural progenitor proliferation induces cytoarchitectural changes in the embryonic neocortex. We also identified a role of CYP450 and consequent oxidative ER stress signaling in these effects. However, because of differences between humans and rodents in neocorticogenesis and brain CYP metabolism, translation of the research findings from the rodent model to human brain development is uncertain. Using hPSC 3D neocortical organoids, we demonstrate that the effects of cocaine are mediated through CYP3A5-induced generation of reactive oxygen species, inhibition of neocortical progenitor cell proliferation, induction of premature neuronal differentiation, and interruption of neural tissue development. Furthermore, knockdown of CYP3A5 reversed these cocaine-induced pathological phenotypes, suggesting CYP3A5 as a therapeutic target to mitigate the deleterious neurodevelopmental effects of prenatal cocaine exposure in humans. Moreover, 3D organoid methodology provides an innovative platform for identifying adverse effects of abused psychostimulants and pharmaceutical agents, and can be adapted for use in neurodevelopmental disorders with genetic etiologies.

Heparin-based hydrogels induce human renal tubulogenesis in vitro.

PubMed

Weber, Heather M; Tsurkan, Mikhail V; Magno, Valentina; Freudenberg, Uwe; Werner, Carsten

2017-07-15

Dialysis or kidney transplantation is the only therapeutic option for end stage renal disease. Accordingly, there is a large unmet clinical need for new causative therapeutic treatments. Obtaining robust models that mimic the complex nature of the human kidney is a critical step in the development of new therapeutic strategies. Here we establish a synthetic in vitro human renal tubulogenesis model based on a tunable glycosaminoglycan-hydrogel platform. In this system, renal tubulogenesis can be modulated by the adjustment of hydrogel mechanics and degradability, growth factor signaling, and the presence of insoluble adhesion cues, potentially providing new insights for regenerative therapy. Different hydrogel properties were systematically investigated for their ability to regulate renal tubulogenesis. Hydrogels based on heparin and matrix metalloproteinase cleavable peptide linker units were found to induce the morphogenesis of single human proximal tubule epithelial cells into physiologically sized tubule structures. The generated tubules display polarization markers, extracellular matrix components, and organic anion transport functions of the in vivo renal proximal tubule and respond to nephrotoxins comparable to the human clinical response. The established hydrogel-based human renal tubulogenesis model is thus considered highly valuable for renal regenerative medicine and personalized nephrotoxicity studies. The only cure for end stage kidney disease is kidney transplantation. Hence, there is a huge need for reliable human kidney models to study renal regeneration and establish alternative treatments. Here we show the development and application of an in vitro human renal tubulogenesis model using heparin-based hydrogels. To the best of our knowledge, this is the first system where human renal tubulogenesis can be monitored from single cells to physiologically sized tubule structures in a tunable hydrogel system. To validate the efficacy of our model as a drug toxicity platform, a chemotherapy drug was incubated with the model, resulting in a drug response similar to human clinical pathology. The established model could have wide applications in the field of nephrotoxicity and renal regenerative medicine and offer a reliable alternative to animal models. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Entropy generation method to quantify thermal comfort.

PubMed

Boregowda, S C; Tiwari, S N; Chaturvedi, S K

2001-12-01

The present paper presents a thermodynamic approach to assess the quality of human-thermal environment interaction and quantify thermal comfort. The approach involves development of entropy generation term by applying second law of thermodynamics to the combined human-environment system. The entropy generation term combines both human thermal physiological responses and thermal environmental variables to provide an objective measure of thermal comfort. The original concepts and definitions form the basis for establishing the mathematical relationship between thermal comfort and entropy generation term. As a result of logic and deterministic approach, an Objective Thermal Comfort Index (OTCI) is defined and established as a function of entropy generation. In order to verify the entropy-based thermal comfort model, human thermal physiological responses due to changes in ambient conditions are simulated using a well established and validated human thermal model developed at the Institute of Environmental Research of Kansas State University (KSU). The finite element based KSU human thermal computer model is being utilized as a "Computational Environmental Chamber" to conduct series of simulations to examine the human thermal responses to different environmental conditions. The output from the simulation, which include human thermal responses and input data consisting of environmental conditions are fed into the thermal comfort model. Continuous monitoring of thermal comfort in comfortable and extreme environmental conditions is demonstrated. The Objective Thermal Comfort values obtained from the entropy-based model are validated against regression based Predicted Mean Vote (PMV) values. Using the corresponding air temperatures and vapor pressures that were used in the computer simulation in the regression equation generates the PMV values. The preliminary results indicate that the OTCI and PMV values correlate well under ideal conditions. However, an experimental study is needed in the future to fully establish the validity of the OTCI formula and the model. One of the practical applications of this index is that could it be integrated in thermal control systems to develop human-centered environmental control systems for potential use in aircraft, mass transit vehicles, intelligent building systems, and space vehicles.

Entropy generation method to quantify thermal comfort

NASA Technical Reports Server (NTRS)

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

2001-01-01

The present paper presents a thermodynamic approach to assess the quality of human-thermal environment interaction and quantify thermal comfort. The approach involves development of entropy generation term by applying second law of thermodynamics to the combined human-environment system. The entropy generation term combines both human thermal physiological responses and thermal environmental variables to provide an objective measure of thermal comfort. The original concepts and definitions form the basis for establishing the mathematical relationship between thermal comfort and entropy generation term. As a result of logic and deterministic approach, an Objective Thermal Comfort Index (OTCI) is defined and established as a function of entropy generation. In order to verify the entropy-based thermal comfort model, human thermal physiological responses due to changes in ambient conditions are simulated using a well established and validated human thermal model developed at the Institute of Environmental Research of Kansas State University (KSU). The finite element based KSU human thermal computer model is being utilized as a "Computational Environmental Chamber" to conduct series of simulations to examine the human thermal responses to different environmental conditions. The output from the simulation, which include human thermal responses and input data consisting of environmental conditions are fed into the thermal comfort model. Continuous monitoring of thermal comfort in comfortable and extreme environmental conditions is demonstrated. The Objective Thermal Comfort values obtained from the entropy-based model are validated against regression based Predicted Mean Vote (PMV) values. Using the corresponding air temperatures and vapor pressures that were used in the computer simulation in the regression equation generates the PMV values. The preliminary results indicate that the OTCI and PMV values correlate well under ideal conditions. However, an experimental study is needed in the future to fully establish the validity of the OTCI formula and the model. One of the practical applications of this index is that could it be integrated in thermal control systems to develop human-centered environmental control systems for potential use in aircraft, mass transit vehicles, intelligent building systems, and space vehicles.

Generation of transgenic monkeys with human inherited genetic disease.

PubMed

Chan, Anthony W S; Yang, Shang-Hsun

2009-09-01

Modeling human diseases using nonhuman primates including chimpanzee, rhesus, cynomolgus, marmoset and squirrel monkeys has been reported in the past decades. Due to the high similarity between nonhuman primates and humans, including genome constitution, cognitive behavioral functions, anatomical structure, metabolic, reproductive, and brain functions; nonhuman primates have played an important role in understanding physiological functions of the human body, clarifying the underlying mechanism of human diseases, and the development of novel treatments for human diseases. However, nonhuman primate research has been restricted to cognitive, behavioral, biochemical and pharmacological approaches of human diseases due to the limitation of gene transfer technology in nonhuman primates. The recent advancement in transgenic technology that has led to the generation of the first transgenic monkey in 2001 and a transgenic monkey model of Huntington's disease (HD) in 2008 has changed that focus. The creation of transgenic HD monkeys that replicate key pathological features of human HD patients further suggests the crucial role of nonhuman primates in the future development of biomedicine. These successes have opened the door to genetic manipulation in nonhuman primates and a new era in modeling human inherited genetic disorders. We focused on the procedures in creating transgenic Huntington's disease monkeys, but our work can be applied to transgenesis in other nonhuman primate species.

Review on modeling heat transfer and thermoregulatory responses in human body.

PubMed

Fu, Ming; Weng, Wenguo; Chen, Weiwang; Luo, Na

2016-12-01

Several mathematical models of human thermoregulation have been developed, contributing to a deep understanding of thermal responses in different thermal conditions and applications. In these models, the human body is represented by two interacting systems of thermoregulation: the controlling active system and the controlled passive system. This paper reviews the recent research of human thermoregulation models. The accuracy and scope of the thermal models are improved, for the consideration of individual differences, integration to clothing models, exposure to cold and hot conditions, and the changes of physiological responses for the elders. The experimental validated methods for human subjects and manikin are compared. The coupled method is provided for the manikin, controlled by the thermal model as an active system. Computational Fluid Dynamics (CFD) is also used along with the manikin or/and the thermal model, to evaluate the thermal responses of human body in various applications, such as evaluation of thermal comfort to increase the energy efficiency, prediction of tolerance limits and thermal acceptability exposed to hostile environments, indoor air quality assessment in the car and aerospace industry, and design protective equipment to improve function of the human activities. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

A changing climate: impacts on human exposures to O3 using ...

EPA Pesticide Factsheets

Predicting the impacts of changing climate on human exposure to air pollution requires future scenarios that account for changes in ambient pollutant concentrations, population sizes and distributions, and housing stocks. An integrated methodology to model changes in human exposures due to these impacts was developed by linking climate, air quality, land-use, and human exposure models. This methodology was then applied to characterize changes in predicted human exposures to O3 under multiple future scenarios. Regional climate projections for the U.S. were developed by downscaling global circulation model (GCM) scenarios for three of the Intergovernmental Panel on Climate Change’s (IPCC’s) Representative Concentration Pathways (RCPs) using the Weather Research and Forecasting (WRF) model. The regional climate results were in turn used to generate air quality (concentration) projections using the Community Multiscale Air Quality (CMAQ) model. For each of the climate change scenarios, future U.S. census-tract level population distributions from the Integrated Climate and Land Use Scenarios (ICLUS) model for four future scenarios based on the IPCC’s Special Report on Emissions Scenarios (SRES) storylines were used. These climate, air quality, and population projections were used as inputs to EPA’s Air Pollutants Exposure (APEX) model for 12 U.S. cities. Probability density functions show changes in the population distribution of 8 h maximum daily O3 exposur

Keep it simple - A case study of model development in the context of the Dynamic Stocks and Flows (DSF) task

NASA Astrophysics Data System (ADS)

Halbrügge, Marc

2010-12-01

This paper describes the creation of a cognitive model submitted to the ‘Dynamic Stocks and Flows’ (DSF) modeling challenge. This challenge aims at comparing computational cognitive models for human behavior during an open ended control task. Participants in the modeling competition were provided with a simulation environment and training data for benchmarking their models while the actual specification of the competition task was withheld. To meet this challenge, the cognitive model described here was designed and optimized for generalizability. Only two simple assumptions about human problem solving were used to explain the empirical findings of the training data. In-depth analysis of the data set prior to the development of the model led to the dismissal of correlations or other parametric statistics as goodness-of-fit indicators. A new statistical measurement based on rank orders and sequence matching techniques is being proposed instead. This measurement, when being applied to the human sample, also identifies clusters of subjects that use different strategies for the task. The acceptability of the fits achieved by the model is verified using permutation tests.

Developing a 3-choice serial reaction time task for examining neural and cognitive function in an equine model.

PubMed

Roberts, Kirsty; Hemmings, Andrew J; McBride, Sebastian D; Parker, Matthew O

2017-12-01

Large animal models of human neurological disorders are advantageous compared to rodent models due to their neuroanatomical complexity, longevity and their ability to be maintained in naturalised environments. Some large animal models spontaneously develop behaviours that closely resemble the symptoms of neural and psychiatric disorders. The horse is an example of this; the domestic form of this species consistently develops spontaneous stereotypic behaviours akin to the compulsive and impulsive behaviours observed in human neurological disorders such as Tourette's syndrome. The ability to non-invasively probe normal and abnormal equine brain function through cognitive testing may provide an extremely useful methodological tool to assess brain changes associated with certain human neurological and psychiatric conditions. An automated operant system with the ability to present visual and auditory stimuli as well as dispense salient food reward was developed. To validate the system, ten horses were trained and tested using a standard cognitive task (three choice serial reaction time task (3-CSRTT)). All animals achieved total learning criterion and performed six probe sessions. Learning criterion was met within 16.30±0.79 sessions over a three day period. During six probe sessions, level of performance was maintained at 80.67±0.57% (mean±SEM) accuracy. This is the first mobile fully automated system developed to examine cognitive function in the horse. A fully-automated operant system for mobile cognitive function of a large animal model has been designed and validated. Horses pose an interesting complementary model to rodents for the examination of human neurological dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative Analysis of Human Resource Development between Different Countries under the Vision of Competition

ERIC Educational Resources Information Center

Xie, Jinyu; Huang, Erjia

2010-01-01

Based on a literature review from English language journals related to the field of human resource development (HRD), the conceptual framework for this study was derived from the models developed by American Society for Training and Development (ASTD) for HRD practice. This study compared and analyzed the similarities and differences in HRD roles,…

Protective effect of Korean Red Ginseng against chemotherapeutic drug-induced premature catagen development assessed with human hair follicle organ culture model

PubMed Central

Keum, Dong In; Pi, Long-Quan; Hwang, Sungjoo Tommy; Lee, Won-Soo

2015-01-01

Background Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects for patients undergoing chemotherapy. This study evaluated the protective effect of Korean Red Ginseng (KRG) on CIA in a well-established in vitro human hair follicle organ culture model as it occurs in vivo. Methods We examined whether KRG can prevent premature hair follicle dystrophy in a human hair follicle organ culture model during treatment with a key cyclophosphamide metabolite, 4-hydroperoxycyclophosphamide (4-HC). Results 4-HC inhibited human hair growth, induced premature catagen development, and inhibited proliferation and stimulated apoptosis of hair matrix keratinocytes. In addition, 4-HC increased p53 and Bax protein expression and decreased Bcl2 protein expression. Pretreatment with KRG protected against 4-HC-induced hair growth inhibition and premature catagen development. KRG also suppressed 4-HC-induced inhibition of matrix keratinocyte proliferation and stimulation of matrix keratinocyte apoptosis. Moreover, KRG restored 4-HC-induced p53 and Bax/Bcl2 expression. Conclusion Overall, our results indicate that KRG may protect against 4-HC-induced premature catagen development through modulation of p53 and Bax/Bcl2 expression. PMID:27158238

Supervised interpretation of echocardiograms with a psychological model of expert supervision

NASA Astrophysics Data System (ADS)

Revankar, Shriram V.; Sher, David B.; Shalin, Valerie L.; Ramamurthy, Maya

1993-07-01

We have developed a collaborative scheme that facilitates active human supervision of the binary segmentation of an echocardiogram. The scheme complements the reliability of a human expert with the precision of segmentation algorithms. In the developed system, an expert user compares the computer generated segmentation with the original image in a user friendly graphics environment, and interactively indicates the incorrectly classified regions either by pointing or by circling. The precise boundaries of the indicated regions are computed by studying original image properties at that region, and a human visual attention distribution map obtained from the published psychological and psychophysical research. We use the developed system to extract contours of heart chambers from a sequence of two dimensional echocardiograms. We are currently extending this method to incorporate a richer set of inputs from the human supervisor, to facilitate multi-classification of image regions depending on their functionality. We are integrating into our system the knowledge related constraints that cardiologists use, to improve the capabilities of our existing system. This extension involves developing a psychological model of expert reasoning, functional and relational models of typical views in echocardiograms, and corresponding interface modifications to map the suggested actions to image processing algorithms.

Protective effect of Korean Red Ginseng against chemotherapeutic drug-induced premature catagen development assessed with human hair follicle organ culture model.

PubMed

Keum, Dong In; Pi, Long-Quan; Hwang, Sungjoo Tommy; Lee, Won-Soo

2016-04-01

Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects for patients undergoing chemotherapy. This study evaluated the protective effect of Korean Red Ginseng (KRG) on CIA in a well-established in vitro human hair follicle organ culture model as it occurs in vivo. We examined whether KRG can prevent premature hair follicle dystrophy in a human hair follicle organ culture model during treatment with a key cyclophosphamide metabolite, 4-hydroperoxycyclophosphamide (4-HC). 4-HC inhibited human hair growth, induced premature catagen development, and inhibited proliferation and stimulated apoptosis of hair matrix keratinocytes. In addition, 4-HC increased p53 and Bax protein expression and decreased Bcl2 protein expression. Pretreatment with KRG protected against 4-HC-induced hair growth inhibition and premature catagen development. KRG also suppressed 4-HC-induced inhibition of matrix keratinocyte proliferation and stimulation of matrix keratinocyte apoptosis. Moreover, KRG restored 4-HC-induced p53 and Bax/Bcl2 expression. Overall, our results indicate that KRG may protect against 4-HC-induced premature catagen development through modulation of p53 and Bax/Bcl2 expression.

Human IgG subclass cross-species reactivity to mouse and cynomolgus monkey Fcγ receptors.

PubMed

Derebe, Mehabaw G; Nanjunda, Rupesh K; Gilliland, Gary L; Lacy, Eilyn R; Chiu, Mark L

2018-05-01

In therapeutic antibody discovery and early development, mice and cynomolgus monkey are used as animal models to assess toxicity, efficacy and other properties of candidate molecules. As more candidate antibodies are based on human immunoglobulin (IgG) subclasses, many strategies are pursued to simulate the human system in the test animal. However, translation rate from a successful preclinical trial to an approved drug is extremely low. This may partly be due to differences in interaction of human IgG based candidate molecules to endogenous Fcγ receptors of model animals in comparison to those of human Fcγ receptors. In this study, we compare binding characteristics of human IgG subclasses commonly used in drug development (IgG1, IgG2, IgG4) and their respective Fc silent versions (IgG1σ, IgG2σ, IgG4 PAA) to human, mouse, and cynomolgus monkey Fcγ receptors. To control interactions between Fab and Fc domains, the test IgGs all have the same variable region sequences. We found distinct variations of interaction of human IgG subclasses to model animal Fcγ receptors in comparison to their human counterparts. Particularly, cynomolgus monkey Fcγ receptors showed consistently tighter binding to human IgGs than human Fcγ receptors. Moreover, the presumably Fc silent human IgG4 PAA framework bound to cynomolgus monkey FcγRI with nanomolar affinity while only very weak binding was observed for the human FcγRI. Our results highlighted the need for a thorough in vitro affinity characterization of candidate IgGs against model animal Fcγ receptors and careful design of preclinical studies. Copyright © 2018. Published by Elsevier B.V.

Molecular mechanisms of inner ear development.

PubMed

Wu, Doris K; Kelley, Matthew W

2012-08-01

The inner ear is a structurally complex vertebrate organ built to encode sound, motion, and orientation in space. Given its complexity, it is not surprising that inner ear dysfunction is a relatively common consequence of human genetic mutation. Studies in model organisms suggest that many genes currently known to be associated with human hearing impairment are active during embryogenesis. Hence, the study of inner ear development provides a rich context for understanding the functions of genes implicated in hearing loss. This chapter focuses on molecular mechanisms of inner ear development derived from studies of model organisms.

Advances in Swine Biomedical Model Genomics

PubMed Central

Lunney, Joan K.

2007-01-01

This review is a short update on the diversity of swine biomedical models and the importance of genomics in their continued development. The swine has been used as a major mammalian model for human studies because of the similarity in size and physiology, and in organ development and disease progression. The pig model allows for deliberately timed studies, imaging of internal vessels and organs using standard human technologies, and collection of repeated peripheral samples and, at kill, detailed mucosal tissues. The ability to use pigs from the same litter, or cloned or transgenic pigs, facilitates comparative analyses and genetic mapping. The availability of numerous well defined cell lines, representing a broad range of tissues, further facilitates testing of gene expression, drug susceptibility, etc. Thus the pig is an excellent biomedical model for humans. For genomic applications it is an asset that the pig genome has high sequence and chromosome structure homology with humans. With the swine genome sequence now well advanced there are improving genetic and proteomic tools for these comparative analyses. The review will discuss some of the genomic approaches used to probe these models. The review will highlight genomic studies of melanoma and of infectious disease resistance, discussing issues to consider in designing such studies. It will end with a short discussion of the potential for genomic approaches to develop new alternatives for control of the most economically important disease of pigs, porcine reproductive and respiratory syndrome (PRRS), and the potential for applying knowledge gained with this virus for human viral infectious disease studies. PMID:17384736

The role of disturbed blood flow in the development of pulmonary arterial hypertension: lessons from preclinical animal models.

PubMed

Dickinson, Michael G; Bartelds, Beatrijs; Borgdorff, Marinus A J; Berger, Rolf M F

2013-07-01

Pulmonary arterial hypertension (PAH) is a progressive pulmonary vasoproliferative disorder characterized by the development of unique neointimal lesions, including concentric laminar intima fibrosis and plexiform lesions. Although the histomorphology of neointimal lesions is well described, the pathogenesis of PAH and neointimal development is largely unknown. After three decades of PAH pathobiology research the focus has shifted from vasoconstriction towards a mechanism of cancer-like angioproliferation. In this concept the role of disturbed blood flow is seen as an important trigger in the development of vascular remodeling. For instance, in PAH associated with congenital heart disease, increased pulmonary blood flow (i.e., systemic-to-pulmonary shunt) is an essential trigger for the occurrence of neointimal lesions and PAH development. Still, questions remain about the exact role of these blood flow characteristics in disease progression. PAH animal models are important for obtaining insight in new pathobiological processes and therapeutical targets. However, as for any preclinical model the pathophysiological mechanism and clinical course has to be comparable to the human disease that it mimics. This means that animal models mimicking human PAH ideally are characterized by: a hit recognized in human disease (e.g., altered pulmonary blood flow), specific vascular remodeling resembling human neointimal lesions, and disease progression that leads to right ventriclular dysfunction and death. A review that underlines the current knowledge of PAH due to disturbed flow is still lacking. In this review we will summarize the current knowledge obtained from PAH animal models associated with disturbed pulmonary blood flow and address questions for future treatment strategies for PAH.