Intergenerational Transmission of Adaptive Functioning: A Test of the Interactionist Model of SES and Human Development

ERIC Educational Resources Information Center

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…

Ecogeography, genetics, and the evolution of human body form.

PubMed

Roseman, Charles C; Auerbach, Benjamin M

2015-01-01

Genetic resemblances among groups are non-randomly distributed in humans. This population structure may influence the correlations between traits and environmental drivers of natural selection thus complicating the interpretation of the fossil record when modern human variation is used as a referential model. In this paper, we examine the effects of population structure and natural selection on postcranial traits that reflect body size and shape with application to the more general issue of how climate - using latitude as a proxy - has influenced hominin morphological variation. We compare models that include terms reflecting population structure, ascertained from globally distributed microsatellite data, and latitude on postcranial phenotypes derived from skeletal dimensions taken from a large global sample of modern humans. We find that models with a population structure term fit better than a model of natural selection along a latitudinal cline in all cases. A model including both latitude and population structure terms is a good fit to distal limb element lengths and bi-iliac breadth, indicating that multiple evolutionary forces shaped these morphologies. In contrast, a model that included only a population structure term best explained femoral head diameter and the crural index. The results demonstrate that population structure is an important part of human postcranial variation, and that clinally distributed natural selection is not sufficient to explain among-group differentiation. The distribution of human body form is strongly influenced by the contingencies of modern human origins, which calls for new ways to approach problems in the evolution of human variation, past and present. Copyright © 2014 Elsevier Ltd. All rights reserved.

Animal Models and Bone Histomorphometry: Translational Research for the Human Research Program

NASA Technical Reports Server (NTRS)

Sibonga, Jean D.

2010-01-01

This slide presentation reviews the use of animal models to research and inform bone morphology, in particular relating to human research in bone loss as a result of low gravity environments. Reasons for use of animal models as tools for human research programs include: time-efficient, cost-effective, invasive measures, and predictability as some model are predictive for drug effects.

Human Pose Estimation from Monocular Images: A Comprehensive Survey

PubMed Central

Gong, Wenjuan; Zhang, Xuena; Gonzàlez, Jordi; Sobral, Andrews; Bouwmans, Thierry; Tu, Changhe; Zahzah, El-hadi

2016-01-01

Human pose estimation refers to the estimation of the location of body parts and how they are connected in an image. Human pose estimation from monocular images has wide applications (e.g., image indexing). Several surveys on human pose estimation can be found in the literature, but they focus on a certain category; for example, model-based approaches or human motion analysis, etc. As far as we know, an overall review of this problem domain has yet to be provided. Furthermore, recent advancements based on deep learning have brought novel algorithms for this problem. In this paper, a comprehensive survey of human pose estimation from monocular images is carried out including milestone works and recent advancements. Based on one standard pipeline for the solution of computer vision problems, this survey splits the problem into several modules: feature extraction and description, human body models, and modeling methods. Problem modeling methods are approached based on two means of categorization in this survey. One way to categorize includes top-down and bottom-up methods, and another way includes generative and discriminative methods. Considering the fact that one direct application of human pose estimation is to provide initialization for automatic video surveillance, there are additional sections for motion-related methods in all modules: motion features, motion models, and motion-based methods. Finally, the paper also collects 26 publicly available data sets for validation and provides error measurement methods that are frequently used. PMID:27898003

A Perspective on Computational Human Performance Models as Design Tools

NASA Technical Reports Server (NTRS)

Jones, Patricia M.

2010-01-01

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

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.

Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering.

PubMed

Maffioletti, Sara Martina; Sarcar, Shilpita; Henderson, Alexander B H; Mannhardt, Ingra; Pinton, Luca; Moyle, Louise Anne; Steele-Stallard, Heather; Cappellari, Ornella; Wells, Kim E; Ferrari, Giulia; Mitchell, Jamie S; Tyzack, Giulia E; Kotiadis, Vassilios N; Khedr, Moustafa; Ragazzi, Martina; Wang, Weixin; Duchen, Michael R; Patani, Rickie; Zammit, Peter S; Wells, Dominic J; Eschenhagen, Thomas; Tedesco, Francesco Saverio

2018-04-17

Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Integrating Human Factors into Crew Exploration Vehicle (CEV) Design

NASA Technical Reports Server (NTRS)

Whitmore, Mihriban; Holden, Kritina; Baggerman, Susan; Campbell, Paul

2007-01-01

The purpose of this design process is to apply Human Engineering (HE) requirements and guidelines to hardware/software and to provide HE design, analysis and evaluation of crew interfaces. The topics include: 1) Background/Purpose; 2) HE Activities; 3) CASE STUDY: Net Habitable Volume (NHV) Study; 4) CASE STUDY: Human Modeling Approach; 5) CASE STUDY: Human Modeling Results; 6) CASE STUDY: Human Modeling Conclusions; 7) CASE STUDY: Human-in-the-Loop Evaluation Approach; 8) CASE STUDY: Unsuited Evaluation Results; 9) CASE STUDY: Suited Evaluation Results; 10) CASE STUDY: Human-in-the-Loop Evaluation Conclusions; 11) Near-Term Plan; and 12) In Conclusion

A Generalized Radiation Model for Human Mobility: Spatial Scale, Searching Direction and Trip Constraint.

PubMed

Kang, Chaogui; Liu, Yu; Guo, Diansheng; Qin, Kun

2015-01-01

We generalized the recently introduced "radiation model", as an analog to the generalization of the classic "gravity model", to consolidate its nature of universality for modeling diverse mobility systems. By imposing the appropriate scaling exponent λ, normalization factor κ and system constraints including searching direction and trip OD constraint, the generalized radiation model accurately captures real human movements in various scenarios and spatial scales, including two different countries and four different cities. Our analytical results also indicated that the generalized radiation model outperformed alternative mobility models in various empirical analyses.

New techniques for the analysis of manual control systems. [mathematical models of human operator behavior

NASA Technical Reports Server (NTRS)

Bekey, G. A.

1971-01-01

Studies are summarized on the application of advanced analytical and computational methods to the development of mathematical models of human controllers in multiaxis manual control systems. Specific accomplishments include the following: (1) The development of analytical and computer methods for the measurement of random parameters in linear models of human operators. (2) Discrete models of human operator behavior in a multiple display situation were developed. (3) Sensitivity techniques were developed which make possible the identification of unknown sampling intervals in linear systems. (4) The adaptive behavior of human operators following particular classes of vehicle failures was studied and a model structure proposed.

Animal models of aging research: implications for human aging and age-related diseases.

PubMed

Mitchell, Sarah J; Scheibye-Knudsen, Morten; Longo, Dan L; de Cabo, Rafael

2015-01-01

Aging is characterized by an increasing morbidity and functional decline that eventually results in the death of an organism. Aging is the largest risk factor for numerous human diseases, and understanding the aging process may thereby facilitate the development of new treatments for age-associated diseases. The use of humans in aging research is complicated by many factors, including ethical issues; environmental and social factors; and perhaps most importantly, their long natural life span. Although cellular models of human disease provide valuable mechanistic information, they are limited in that they may not replicate the in vivo biology. Almost all organisms age, and thus animal models can be useful for studying aging. Herein, we review some of the major models currently used in aging research and discuss their benefits and pitfalls, including interventions known to extend life span and health span. Finally, we conclude by discussing the future of animal models in aging research.

Human tissue models in cancer research: looking beyond the mouse.

PubMed

Jackson, Samuel J; Thomas, Gareth J

2017-08-01

Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of 'non-animal human tissue' models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models. © 2017. Published by The Company of Biologists Ltd.

Humanized mouse models: Application to human diseases.

PubMed

Ito, Ryoji; Takahashi, Takeshi; Ito, Mamoru

2018-05-01

Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft-versus-host disease. © 2017 Wiley Periodicals, Inc.

Synthetic, multi-layer, self-oscillating vocal fold model fabrication.

PubMed

Murray, Preston R; Thomson, Scott L

2011-12-02

Sound for the human voice is produced via flow-induced vocal fold vibration. The vocal folds consist of several layers of tissue, each with differing material properties. Normal voice production relies on healthy tissue and vocal folds, and occurs as a result of complex coupling between aerodynamic, structural dynamic, and acoustic physical phenomena. Voice disorders affect up to 7.5 million annually in the United States alone and often result in significant financial, social, and other quality-of-life difficulties. Understanding the physics of voice production has the potential to significantly benefit voice care, including clinical prevention, diagnosis, and treatment of voice disorders. Existing methods for studying voice production include in vivo experimentation using human and animal subjects, in vitro experimentation using excised larynges and synthetic models, and computational modeling. Owing to hazardous and difficult instrument access, in vivo experiments are severely limited in scope. Excised larynx experiments have the benefit of anatomical and some physiological realism, but parametric studies involving geometric and material property variables are limited. Further, they are typically only able to be vibrated for relatively short periods of time (typically on the order of minutes). Overcoming some of the limitations of excised larynx experiments, synthetic vocal fold models are emerging as a complementary tool for studying voice production. Synthetic models can be fabricated with systematic changes to geometry and material properties, allowing for the study of healthy and unhealthy human phonatory aerodynamics, structural dynamics, and acoustics. For example, they have been used to study left-right vocal fold asymmetry, clinical instrument development, laryngeal aerodynamics, vocal fold contact pressure, and subglottal acoustics (a more comprehensive list can be found in Kniesburges et al.) Existing synthetic vocal fold models, however, have either been homogenous (one-layer models) or have been fabricated using two materials of differing stiffness (two-layer models). This approach does not allow for representation of the actual multi-layer structure of the human vocal folds that plays a central role in governing vocal fold flow-induced vibratory response. Consequently, one- and two-layer synthetic vocal fold models have exhibited disadvantages such as higher onset pressures than what are typical for human phonation (onset pressure is the minimum lung pressure required to initiate vibration), unnaturally large inferior-superior motion, and lack of a "mucosal wave" (a vertically-traveling wave that is characteristic of healthy human vocal fold vibration). In this paper, fabrication of a model with multiple layers of differing material properties is described. The model layers simulate the multi-layer structure of the human vocal folds, including epithelium, superficial lamina propria (SLP), intermediate and deep lamina propria (i.e., ligament; a fiber is included for anterior-posterior stiffness), and muscle (i.e., body) layers. Results are included that show that the model exhibits improved vibratory characteristics over prior one- and two-layer synthetic models, including onset pressure closer to human onset pressure, reduced inferior-superior motion, and evidence of a mucosal wave.

DigitalHuman (DH): An Integrative Mathematical Model ofHuman Physiology

NASA Technical Reports Server (NTRS)

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

2010-01-01

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

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.

Cognitive engineering models in space systems

NASA Technical Reports Server (NTRS)

Mitchell, Christine M.

1992-01-01

NASA space systems, including mission operations on the ground and in space, are complex, dynamic, predominantly automated systems in which the human operator is a supervisory controller. The human operator monitors and fine-tunes computer-based control systems and is responsible for ensuring safe and efficient system operation. In such systems, the potential consequences of human mistakes and errors may be very large, and low probability of such events is likely. Thus, models of cognitive functions in complex systems are needed to describe human performance and form the theoretical basis of operator workstation design, including displays, controls, and decision support aids. The operator function model represents normative operator behavior-expected operator activities given current system state. The extension of the theoretical structure of the operator function model and its application to NASA Johnson mission operations and space station applications is discussed.

Sustainability Indicators for Coupled Human-Earth Systems

NASA Astrophysics Data System (ADS)

Motesharrei, S.; Rivas, J. R.; Kalnay, E.

2014-12-01

Over the last two centuries, the Human System went from having a small impact on the Earth System (including the Climate System) to becoming dominant, because both population and per capita consumption have grown extremely fast, especially since about 1950. We therefore argue that Human System Models must be included into Earth System Models through bidirectional couplings with feedbacks. In particular, population should be modeled endogenously, rather than exogenously as done currently in most Integrated Assessment Models. The growth of the Human System threatens to overwhelm the Carrying Capacity of the Earth System, and may be leading to catastrophic climate change and collapse. We propose a set of Ecological and Economic "Sustainability Indicators" that can employ large data-sets for developing and assessing effective mitigation and adaptation policies. Using the Human and Nature Dynamical Model (HANDY) and Coupled Human-Climate-Water Model (COWA), we carry out experiments with this set of Sustainability Indicators and show that they are applicable to various coupled systems including Population, Climate, Water, Energy, Agriculture, and Economy. Impact of nonrenewable resources and fossil fuels could also be understood using these indicators. We demonstrate interconnections of Ecological and Economic Indicators. Coupled systems often include feedbacks and can thus display counterintuitive dynamics. This makes it difficult for even experts to see coming catastrophes from just the raw data for different variables. Sustainability Indicators boil down the raw data into a set of simple numbers that cross their sustainability thresholds with a large time-lag before variables enter their catastrophic regimes. Therefore, we argue that Sustainability Indicators constitute a powerful but simple set of tools that could be directly used for making policies for sustainability.

[Development of the next generation humanized mouse for drug discovery].

PubMed

Ito, Ryoji

A humanized mouse, which is efficiently engrafted human cells and tissues, is an important tool to mimic human physiology for biomedical researches. Since 2000s, severe combined immunodeficient mouse strains such as NOG, BRG, and NSG mice have been generated. They are great recipients to create humanized mouse models compared to previous other immunodeficient strains due to their multiple dysfunctions of innate and acquired immunity. Especially, the transfer of human hematopoietic stem cells into these immunodeficient mice has been enabled to reconstitute human immune systems, because the mice show high engraftment level of human leukocyte in peripheral blood (～50%), spleen and bone marrow (60～90%) and generate well-differentiated multilineage human immune cells including lymphoid and myeloid lineage cells. Using these mice, several human disease models such as cancer, allergy, graft-versus-host disease (GVHD), and etc. have been established to understand the pathogenic mechanisms of the diseases and to evaluate the efficacy and safety of novel drugs. In this review, I provide an overview of recent advances in the humanized mouse technology, including generation of novel platforms of genetically modified NOG (next generation NOG) mice and some applications of them to create human disease models for drug discovery in preclinical researches.

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.

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

Robotic Billiards: Understanding Humans in Order to Counter Them.

PubMed

Nierhoff, Thomas; Leibrandt, Konrad; Lorenz, Tamara; Hirche, Sandra

2016-08-01

Ongoing technological advances in the areas of computation, sensing, and mechatronics enable robotic-based systems to interact with humans in the real world. To succeed against a human in a competitive scenario, a robot must anticipate the human behavior and include it in its own planning framework. Then it can predict the next human move and counter it accordingly, thus not only achieving overall better performance but also systematically exploiting the opponent's weak spots. Pool is used as a representative scenario to derive a model-based planning and control framework where not only the physics of the environment but also a model of the opponent is considered. By representing the game of pool as a Markov decision process and incorporating a model of the human decision-making based on studies, an optimized policy is derived. This enables the robot to include the opponent's typical game style into its tactical considerations when planning a stroke. The results are validated in simulations and real-life experiments with an anthropomorphic robot playing pool against a human.

Comparison of the Gene Expression Profiles of Human Hematopoietic Stem Cells between Humans and a Humanized Xenograft Model.

PubMed

Matsuzawa, Hideyuki; Matsushita, Hiromichi; Yahata, Takashi; Tanaka, Masayuki; Ando, Kiyoshi

2017-04-20

The aim of this study is to evaluate the feasibility of NOD/Shi-scid-IL2Rγ null (NOG) mice transplanted with human CD34 + /CD38 - /Lin -/low hematopoietic cells from cord blood (CB) as an experimental model of the gene expression in human hematopoiesis. We compared the gene expressions of human CD34 + /CD38 - /Lin -/low cells from human bone marrow (BM) and in xenograft models. The microarray data revealed that 25 KEGG pathways were extracted from the comparison of human CD34 + /CD38 - /Lin -/low HSCs between CB and BM, and that 17 of them--which were mostly related to cellular survival, RNA metabolism and lymphoid development--were shared with the xenograft model. When the probes that were commonly altered in CD34 + /CD38 - /Lin -/low cells from both human and xenograft BM were analyzed, most of them, including the genes related hypoxia, hematopoietic differentiation, epigenetic modification, translation initiation, and RNA degradation, were downregulated. These alterations of gene expression suggest a reduced differentiation capacity and likely include key alterations of gene expression for settlement of CB CD34 + /CD38 - /Lin -/low cells in BM. Our findings demonstrate that the xenograft model of human CB CD34 + /CD38 - /Lin -/low cells using NOG mice was useful, at least in part, for the evaluation of the gene expression profile of human hematopoietic stem cells.

New Rodent Population Models May Inform Human Health Risk Assessment and Identification of Genetic Susceptibility to Environmental Exposures.

PubMed

Harrill, Alison H; McAllister, Kimberly A

2017-08-15

This paper provides an introduction for environmental health scientists to emerging population-based rodent resources. Mouse reference populations provide an opportunity to model environmental exposures and gene-environment interactions in human disease and to inform human health risk assessment. This review will describe several mouse populations for toxicity assessment, including older models such as the Mouse Diversity Panel (MDP), and newer models that include the Collaborative Cross (CC) and Diversity Outbred (DO) models. This review will outline the features of the MDP, CC, and DO mouse models and will discuss published case studies investigating the use of these mouse population resources in each step of the risk assessment paradigm. These unique resources have the potential to be powerful tools for generating hypotheses related to gene-environment interplay in human disease, performing controlled exposure studies to understand the differential responses in humans for susceptibility or resistance to environmental exposures, and identifying gene variants that influence sensitivity to toxicity and disease states. These new resources offer substantial advances to classical toxicity testing paradigms by including genetically sensitive individuals that may inform toxicity risks for sensitive subpopulations. Both in vivo and complementary in vitro resources provide platforms with which to reduce uncertainty by providing population-level data around biological variability. https://doi.org/10.1289/EHP1274.

New Rodent Population Models May Inform Human Health Risk Assessment and Identification of Genetic Susceptibility to Environmental Exposures

PubMed Central

Harrill, Alison H.

2017-01-01

Background: This paper provides an introduction for environmental health scientists to emerging population-based rodent resources. Mouse reference populations provide an opportunity to model environmental exposures and gene–environment interactions in human disease and to inform human health risk assessment. Objectives: This review will describe several mouse populations for toxicity assessment, including older models such as the Mouse Diversity Panel (MDP), and newer models that include the Collaborative Cross (CC) and Diversity Outbred (DO) models. Methods: This review will outline the features of the MDP, CC, and DO mouse models and will discuss published case studies investigating the use of these mouse population resources in each step of the risk assessment paradigm. Discussion: These unique resources have the potential to be powerful tools for generating hypotheses related to gene–environment interplay in human disease, performing controlled exposure studies to understand the differential responses in humans for susceptibility or resistance to environmental exposures, and identifying gene variants that influence sensitivity to toxicity and disease states. Conclusions: These new resources offer substantial advances to classical toxicity testing paradigms by including genetically sensitive individuals that may inform toxicity risks for sensitive subpopulations. Both in vivo and complementary in vitro resources provide platforms with which to reduce uncertainty by providing population-level data around biological variability. https://doi.org/10.1289/EHP1274 PMID:28886592

A stochastic dynamic model for human error analysis in nuclear power plants

NASA Astrophysics Data System (ADS)

Delgado-Loperena, Dharma

Nuclear disasters like Three Mile Island and Chernobyl indicate that human performance is a critical safety issue, sending a clear message about the need to include environmental press and competence aspects in research. This investigation was undertaken to serve as a roadmap for studying human behavior through the formulation of a general solution equation. The theoretical model integrates models from two heretofore-disassociated disciplines (behavior specialists and technical specialists), that historically have independently studied the nature of error and human behavior; including concepts derived from fractal and chaos theory; and suggests re-evaluation of base theory regarding human error. The results of this research were based on comprehensive analysis of patterns of error, with the omnipresent underlying structure of chaotic systems. The study of patterns lead to a dynamic formulation, serving for any other formula used to study human error consequences. The search for literature regarding error yielded insight for the need to include concepts rooted in chaos theory and strange attractors---heretofore unconsidered by mainstream researchers who investigated human error in nuclear power plants or those who employed the ecological model in their work. The study of patterns obtained from the rupture of a steam generator tube (SGTR) event simulation, provided a direct application to aspects of control room operations in nuclear power plant operations. In doing so, the conceptual foundation based in the understanding of the patterns of human error analysis can be gleaned, resulting in reduced and prevent undesirable events.

Humanized Mouse Models for the Study of Human Malaria Parasite Biology, Pathogenesis, and Immunity.

PubMed

Minkah, Nana K; Schafer, Carola; Kappe, Stefan H I

2018-01-01

Malaria parasite infection continues to inflict extensive morbidity and mortality in resource-poor countries. The insufficiently understood parasite biology, continuously evolving drug resistance and the lack of an effective vaccine necessitate intensive research on human malaria parasites that can inform the development of new intervention tools. Humanized mouse models have been greatly improved over the last decade and enable the direct study of human malaria parasites in vivo in the laboratory. Nevertheless, no small animal model developed so far is capable of maintaining the complete life cycle of Plasmodium parasites that infect humans. The ultimate goal is to develop humanized mouse systems in which a Plasmodium infection closely reproduces all stages of a parasite infection in humans, including pre-erythrocytic infection, blood stage infection and its associated pathology, transmission as well as the human immune response to infection. Here, we discuss current humanized mouse models and the future directions that should be taken to develop next-generation models for human malaria parasite research.

Challenges for Preclinical Investigations of Human Biofield Modalities

PubMed Central

Gronowicz, Gloria; Bengston, William

2015-01-01

Preclinical models for studying the effects of the human biofield have great potential to advance our understanding of human biofield modalities, which include external qigong, Johrei, Reiki, therapeutic touch, healing touch, polarity therapy, pranic healing, and other practices. A short history of Western biofield studies using preclinical models is presented and demonstrates numerous and consistent examples of human biofields significantly affecting biological systems both in vitro and in vivo. Methodological issues arising from these studies and practical solutions in experimental design are presented. Important questions still left unanswered with preclinical models include variable reproducibility, dosing, intentionality of the practitioner, best preclinical systems, and mechanisms. Input from the biofield practitioners in the experimental design is critical to improving experimental outcomes; however, the development of standard criteria for uniformity of practice and for inclusion of multiple practitioners is needed. Research in human biofield studies involving preclinical models promises a better understanding of the mechanisms underlying the efficacy of biofield therapies and will be important in guiding clinical protocols and integrating treatments with conventional medical therapies. PMID:26665042

Culture models of human mammary epithelial cell transformation

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

Stampfer, Martha R.; Yaswen, Paul

2000-11-10

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

Development and function of human innate immune cells in a humanized mouse model.

PubMed

Rongvaux, Anthony; Willinger, Tim; Martinek, Jan; Strowig, Till; Gearty, Sofia V; Teichmann, Lino L; Saito, Yasuyuki; Marches, Florentina; Halene, Stephanie; Palucka, A Karolina; Manz, Markus G; Flavell, Richard A

2014-04-01

Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.

Development and function of human innate immune cells in a humanized mouse model

PubMed Central

Rongvaux, Anthony; Willinger, Tim; Martinek, Jan; Strowig, Till; Gearty, Sofia V.; Teichmann, Lino L.; Saito, Yasuyuki; Marches, Florentina; Halene, Stephanie; Palucka, A. Karolina; Manz, Markus G.; Flavell, Richard A.

2014-01-01

Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models are unable to support development of human innate immune cells, including myeloid cells and NK cells. Here we describe a mouse strain, called MI(S)TRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked in to their respective mouse loci. The human cytokines support the development and function of monocytes/macrophages and natural killer cells derived from human fetal liver or adult CD34+ progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MI(S)TRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology. PMID:24633240

Animal and human models to understand ageing.

PubMed

Lees, Hayley; Walters, Hannah; Cox, Lynne S

2016-11-01

Human ageing is the gradual decline in organ and tissue function with increasing chronological time, leading eventually to loss of function and death. To study the processes involved over research-relevant timescales requires the use of accessible model systems that share significant similarities with humans. In this review, we assess the usefulness of various models, including unicellular yeasts, invertebrate worms and flies, mice and primates including humans, and highlight the benefits and possible drawbacks of each model system in its ability to illuminate human ageing mechanisms. We describe the strong evolutionary conservation of molecular pathways that govern cell responses to extracellular and intracellular signals and which are strongly implicated in ageing. Such pathways centre around insulin-like growth factor signalling and integration of stress and nutritional signals through mTOR kinase. The process of cellular senescence is evaluated as a possible underlying cause for many of the frailties and diseases of human ageing. Also considered is ageing arising from systemic changes that cannot be modelled in lower organisms and instead require studies either in small mammals or in primates. We also touch briefly on novel therapeutic options arising from a better understanding of the biology of ageing. Copyright © 2016. Published by Elsevier Ireland Ltd.

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...

A Generalized Radiation Model for Human Mobility: Spatial Scale, Searching Direction and Trip Constraint

PubMed Central

Kang, Chaogui; Liu, Yu; Guo, Diansheng; Qin, Kun

2015-01-01

We generalized the recently introduced “radiation model”, as an analog to the generalization of the classic “gravity model”, to consolidate its nature of universality for modeling diverse mobility systems. By imposing the appropriate scaling exponent λ, normalization factor κ and system constraints including searching direction and trip OD constraint, the generalized radiation model accurately captures real human movements in various scenarios and spatial scales, including two different countries and four different cities. Our analytical results also indicated that the generalized radiation model outperformed alternative mobility models in various empirical analyses. PMID:26600153

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…

Combining Regional- and Local-Scale Air Quality Models with Exposure Models for Use in Environmental Health Studies

EPA Science Inventory

Population-based human exposure models predict the distribution of personal exposures to pollutants of outdoor origin using a variety of inputs, including: air pollution concentrations; human activity patterns, such as the amount of time spent outdoors vs. indoors, commuting, wal...

An improved ultra wideband channel model including the frequency-dependent attenuation for in-body communications.

PubMed

Khaleghi, A; Chávez-Santiago, R; Balasingham, I

2012-01-01

Ultra wideband (UWB) technology has big potential for applications in wireless body area networks (WBANs). The inherent characteristics of UWB signals make them suitable for the wireless interface of medical sensors. In particular, implanted medical wireless sensors for monitoring physiological parameters, automatic drug provision, etc. can benefit greatly from this ultra low power (ULP) interface. As with any other wireless technology, accurate knowledge of the channel is necessary for the proper design of communication systems. Only a few models that describe the radio propagation inside the human body have been published. Moreover, there is no comprehensive UWB in-body propagation model that includes the frequency-dependent attenuation. Hence, this paper extends a statistical model for UWB propagation channels inside the human chest in the 1-6 GHz frequency range by including the frequency-dependent attenuation. This is done by modeling the spectrum shape of distorted pulses at different depths inside the human chest. The distortion of the pulse was obtained through numerical simulations using a voxel representation of the human body. We propose a mathematical expression for the spectrum shape of the distorted pulses that act as a window function to reproduce the effects of frequency-dependent attenuation.

Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line

PubMed Central

Shipley, Mackenzie M.; Mangold, Colleen A.; Szpara, Moriah L.

2016-01-01

Having appropriate in vivo and in vitro systems that provide translational models for human disease is an integral aspect of research in neurobiology and the neurosciences. Traditional in vitro experimental models used in neurobiology include primary neuronal cultures from rats and mice, neuroblastoma cell lines including rat B35 and mouse Neuro-2A cells, rat PC12 cells, and short-term slice cultures. While many researchers rely on these models, they lack a human component and observed experimental effects could be exclusive to the respective species and may not occur identically in humans. Additionally, although these cells are neurons, they may have unstable karyotypes, making their use problematic for studies of gene expression and reproducible studies of cell signaling. It is therefore important to develop more consistent models of human neurological disease. The following procedure describes an easy-to-follow, reproducible method to obtain homogenous and viable human neuronal cultures, by differentiating the chromosomally stable human neuroblastoma cell line, SH-SY5Y. This method integrates several previously described methods1-4 and is based on sequential removal of serum from media. The timeline includes gradual serum-starvation, with introduction of extracellular matrix proteins and neurotrophic factors. This allows neurons to differentiate, while epithelial cells are selected against, resulting in a homogeneous neuronal culture. Representative results demonstrate the successful differentiation of SH-SY5Y neuroblastoma cells from an initial epithelial-like cell phenotype into a more expansive and branched neuronal phenotype. This protocol offers a reliable way to generate homogeneous populations of neuronal cultures that can be used for subsequent biochemical and molecular analyses, which provides researchers with a more accurate translational model of human infection and disease. PMID:26967710

Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line.

PubMed

Shipley, Mackenzie M; Mangold, Colleen A; Szpara, Moriah L

2016-02-17

Having appropriate in vivo and in vitro systems that provide translational models for human disease is an integral aspect of research in neurobiology and the neurosciences. Traditional in vitro experimental models used in neurobiology include primary neuronal cultures from rats and mice, neuroblastoma cell lines including rat B35 and mouse Neuro-2A cells, rat PC12 cells, and short-term slice cultures. While many researchers rely on these models, they lack a human component and observed experimental effects could be exclusive to the respective species and may not occur identically in humans. Additionally, although these cells are neurons, they may have unstable karyotypes, making their use problematic for studies of gene expression and reproducible studies of cell signaling. It is therefore important to develop more consistent models of human neurological disease. The following procedure describes an easy-to-follow, reproducible method to obtain homogenous and viable human neuronal cultures, by differentiating the chromosomally stable human neuroblastoma cell line, SH-SY5Y. This method integrates several previously described methods(1-4) and is based on sequential removal of serum from media. The timeline includes gradual serum-starvation, with introduction of extracellular matrix proteins and neurotrophic factors. This allows neurons to differentiate, while epithelial cells are selected against, resulting in a homogeneous neuronal culture. Representative results demonstrate the successful differentiation of SH-SY5Y neuroblastoma cells from an initial epithelial-like cell phenotype into a more expansive and branched neuronal phenotype. This protocol offers a reliable way to generate homogeneous populations of neuronal cultures that can be used for subsequent biochemical and molecular analyses, which provides researchers with a more accurate translational model of human infection and disease.

Analyzing Human-Landscape Interactions: Tools That Integrate

NASA Astrophysics Data System (ADS)

Zvoleff, Alex; An, Li

2014-01-01

Humans have transformed much of Earth's land surface, giving rise to loss of biodiversity, climate change, and a host of other environmental issues that are affecting human and biophysical systems in unexpected ways. To confront these problems, environmental managers must consider human and landscape systems in integrated ways. This means making use of data obtained from a broad range of methods (e.g., sensors, surveys), while taking into account new findings from the social and biophysical science literatures. New integrative methods (including data fusion, simulation modeling, and participatory approaches) have emerged in recent years to address these challenges, and to allow analysts to provide information that links qualitative and quantitative elements for policymakers. This paper brings attention to these emergent tools while providing an overview of the tools currently in use for analysis of human-landscape interactions. Analysts are now faced with a staggering array of approaches in the human-landscape literature—in an attempt to bring increased clarity to the field, we identify the relative strengths of each tool, and provide guidance to analysts on the areas to which each tool is best applied. We discuss four broad categories of tools: statistical methods (including survival analysis, multi-level modeling, and Bayesian approaches), GIS and spatial analysis methods, simulation approaches (including cellular automata, agent-based modeling, and participatory modeling), and mixed-method techniques (such as alternative futures modeling and integrated assessment). For each tool, we offer an example from the literature of its application in human-landscape research. Among these tools, participatory approaches are gaining prominence for analysts to make the broadest possible array of information available to researchers, environmental managers, and policymakers. Further development of new approaches of data fusion and integration across sites or disciplines pose an important challenge for future work in integrating human and landscape components.

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…

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

Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential

PubMed Central

Tang, Zhao-You; Sun, Fan-Xian; Tian, Jian; Ye, Sheng-Long; Liu, Yin-Kun; Liu, Kang-Da; Xue, Qiong; Chen, Jie; Xia, Jing-Lin; Qin, Lun-Xiu; Sun, Hui-Chuan; Wang, Lu; Zhou, Jian; Li, Yan; Ma, Zeng-Chen; Zhou, Xin-Da; Wu, Zhi-Quan; Lin, Zhi-Ying; Yang, Bing-Hui

2001-01-01

Metastatic human HCC model is needed for the studies on mechanism and interven tion of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient-like metastatic model of hu man HCC in nude mice (LCI-D20) and a low metastatic model of human HCC in nude mice (LCI-D35) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metasta sis to liver, lungs, lymph nodes and peritoneal seeding. Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-1 increased gradually following tumor progression in LCI-D20 model, and correlated with tumor size and AFP level. Phasic expression of tissue intercellular adhesio nmolecule-1 in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including anti-angiogenesis, antisense approach, metallopro teinase inhibitor, differentiation inducer, etc. It is concluded that the establ ishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vivo and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence. PMID:11819839

Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction

PubMed Central

ASAHINA, Makoto; SHIMIZU, Fumi; OHTA, Masayuki; TAKEYAMA, Michiyasu; TOZAWA, Ryuichi

2015-01-01

Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome. PMID:25912321

Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction.

PubMed

Asahina, Makoto; Shimizu, Fumi; Ohta, Masayuki; Takeyama, Michiyasu; Tozawa, Ryuichi

2015-01-01

Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome.

Ergonomic Models of Anthropometry, Human Biomechanics and Operator-Equipment Interfaces

NASA Technical Reports Server (NTRS)

Kroemer, Karl H. E. (Editor); Snook, Stover H. (Editor); Meadows, Susan K. (Editor); Deutsch, Stanley (Editor)

1988-01-01

The Committee on Human Factors was established in October 1980 by the Commission on Behavioral and Social Sciences and Education of the National Research Council. The committee is sponsored by the Office of Naval Research, the Air Force Office of Scientific Research, the Army Research Institute for the Behavioral and Social Sciences, the National Aeronautics and Space Administration, and the National Science Foundation. The workshop discussed the following: anthropometric models; biomechanical models; human-machine interface models; and research recommendations. A 17-page bibliography is included.

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.

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.

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.

Orthotopic mouse models for the preclinical and translational study of targeted therapies against metastatic human thyroid carcinoma with BRAFV600E or wild-type BRAF

PubMed Central

Antonello, ZA; Nucera, C

2015-01-01

Molecular signature of advanced and metastatic thyroid carcinoma involves deregulation of multiple fundamental pathways activated in the tumor microenvironment. They include BRAFV600E and AKT that affect tumor initiation, progression and metastasis. Human thyroid cancer orthotopic mouse models are based on human cell lines that generally harbor genetic alterations found in human thyroid cancers. They can reproduce in vivo and in situ (into the thyroid) many features of aggressive and refractory human advanced thyroid carcinomas, including local invasion and metastasis. Humanized orthotopic mouse models seem to be ideal and commonly used for preclinical and translational studies of compounds and therapies not only because they may mimic key aspects of human diseases (e.g. metastasis), but also for their reproducibility. In addition, they might provide the possibility to evaluate systemic effects of treatments. So far, human thyroid cancer in vivo models were mainly used to test single compounds, non selective and selective. Despite the greater antitumor activity and lower toxicity obtained with different selective drugs in respect to non-selective ones, most of them are only able to delay disease progression, which ultimately could restart with similar aggressive behavior. Aggressive thyroid tumors (for example, anaplastic or poorly differentiated thyroid carcinoma) carry several complex genetic alterations that are likely cooperating to promote disease progression and might confer resistance to single-compound approaches. Orthotopic models of human thyroid cancer also hold the potential to be good models for testing novel combinatorial therapies. In this article, we will summarize results on preclinical testing of selective and nonselective single compounds in orthotopic mouse models based on validated human thyroid cancer cell lines harboring the BRAFV600E mutation or with wild-type BRAF. Furthermore, we will discuss the potential use of this model also for combinatorial approaches, which are expected to take place in the upcoming human thyroid cancer basic and clinical research. PMID:24362526

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

PubMed

Zhu, Zengrong; Huangfu, Danwei

2013-02-01

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

Quantifying human impact on hydrological drought using an Earth System Model

NASA Astrophysics Data System (ADS)

van Huijgevoort, Marjolein; Chaney, Nathaniel; Malyshev, Sergey; Shevliakova, Elena; Milly, Chris

2017-04-01

Predicting the human impact on the present and future hydrological cycle remains a significant scientific challenge. Anthropogenic impact includes water management practices like diverting water for irrigation, abstraction of groundwater, and reservoirs. Hydrological extremes, in particular, are heavily affected by water management practices, due to the existing stress on the system during droughts and floods. Therefore, to prepare adaptation plans for hydrological extremes in the future, it is essential to account for water management and other human influences in Earth System Models. In this study we have implemented water management practices in the state-of-the-art GFDL land model, which includes terrestrial water, energy, and carbon balances. Both irrigation practices and reservoirs have been added in the land surface model component of the model. Irrigation amounts are determined from the soil water balance, the evaporative demand of the vegetation and fractional coverage of croplands. The resulting water demand is fulfilled by abstractions from surface water and groundwater. Reservoir outflow is dynamically coupled to the downstream water demand and available reservoir storage. Retrospective model simulations over the contiguous United States indicate a strong human influence on hydrological drought. A water management attribution analysis shows a significant impact on the water availability, mostly in the Midwest of the United States and California. Implementation of reservoirs alters the flow regime, thereby decreasing the short-term drought impact, however, in the case of multi-year drought, impacts are delayed due to the dependency on the reservoir outflow. Irrigation, on the other hand, decreases the water availability in rivers due to increased evapotranspiration leading to a higher drought impact. The average increase in evapotranspiration amounted up to 2 mm/day for cropland areas in California and Texas. Overall, the results show the importance of including water management in global scale models. This new modelling framework can be used to understand how humans will impact future water availability, water scarcity, and drought. Next steps will include coupled model simulations to investigate the human impact on feedbacks in land-atmosphere interactions.

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.

Animal and in silico models for the study of sarcomeric cardiomyopathies

PubMed Central

Duncker, Dirk J.; Bakkers, Jeroen; Brundel, Bianca J.; Robbins, Jeff; Tardiff, Jil C.; Carrier, Lucie

2015-01-01

Over the past decade, our understanding of cardiomyopathies has improved dramatically, due to improvements in screening and detection of gene defects in the human genome as well as a variety of novel animal models (mouse, zebrafish, and drosophila) and in silico computational models. These novel experimental tools have created a platform that is highly complementary to the naturally occurring cardiomyopathies in cats and dogs that had been available for some time. A fully integrative approach, which incorporates all these modalities, is likely required for significant steps forward in understanding the molecular underpinnings and pathogenesis of cardiomyopathies. Finally, novel technologies, including CRISPR/Cas9, which have already been proved to work in zebrafish, are currently being employed to engineer sarcomeric cardiomyopathy in larger animals, including pigs and non-human primates. In the mouse, the increased speed with which these techniques can be employed to engineer precise ‘knock-in’ models that previously took years to make via multiple rounds of homologous recombination-based gene targeting promises multiple and precise models of human cardiac disease for future study. Such novel genetically engineered animal models recapitulating human sarcomeric protein defects will help bridging the gap to translate therapeutic targets from small animal and in silico models to the human patient with sarcomeric cardiomyopathy. PMID:25600962

Modeling human target acquisition in ground-to-air weapon systems

NASA Technical Reports Server (NTRS)

Phatak, A. V.; Mohr, R. L.; Vikmanis, M.; Wei, K. C.

1982-01-01

The problems associated with formulating and validating mathematical models for describing and predicting human target acquisition response are considered. In particular, the extension of the human observer model to include the acquisition phase as well as the tracking segment is presented. Relationship of the Observer model structure to the more complex Standard Optimal Control model formulation and to the simpler Transfer Function/Noise representation is discussed. Problems pertinent to structural identifiability and the form of the parameterization are elucidated. A systematic approach toward the identification of the observer acquisition model parameters from ensemble tracking error data is presented.

Human ectoparasites and the spread of plague in Europe during the Second Pandemic

PubMed Central

Krauer, Fabienne; Walløe, Lars; Bramanti, Barbara; Stenseth, Nils Chr.; Schmid, Boris V.

2018-01-01

Plague, caused by the bacterium Yersinia pestis, can spread through human populations by multiple transmission pathways. Today, most human plague cases are bubonic, caused by spillover of infected fleas from rodent epizootics, or pneumonic, caused by inhalation of infectious droplets. However, little is known about the historical spread of plague in Europe during the Second Pandemic (14–19th centuries), including the Black Death, which led to high mortality and recurrent epidemics for hundreds of years. Several studies have suggested that human ectoparasite vectors, such as human fleas (Pulex irritans) or body lice (Pediculus humanus humanus), caused the rapidly spreading epidemics. Here, we describe a compartmental model for plague transmission by a human ectoparasite vector. Using Bayesian inference, we found that this model fits mortality curves from nine outbreaks in Europe better than models for pneumonic or rodent transmission. Our results support that human ectoparasites were primary vectors for plague during the Second Pandemic, including the Black Death (1346–1353), ultimately challenging the assumption that plague in Europe was predominantly spread by rats. PMID:29339508

Human ectoparasites and the spread of plague in Europe during the Second Pandemic.

PubMed

Dean, Katharine R; Krauer, Fabienne; Walløe, Lars; Lingjærde, Ole Christian; Bramanti, Barbara; Stenseth, Nils Chr; Schmid, Boris V

2018-02-06

Plague, caused by the bacterium Yersinia pestis , can spread through human populations by multiple transmission pathways. Today, most human plague cases are bubonic, caused by spillover of infected fleas from rodent epizootics, or pneumonic, caused by inhalation of infectious droplets. However, little is known about the historical spread of plague in Europe during the Second Pandemic (14-19th centuries), including the Black Death, which led to high mortality and recurrent epidemics for hundreds of years. Several studies have suggested that human ectoparasite vectors, such as human fleas ( Pulex irritans ) or body lice ( Pediculus humanus humanus ), caused the rapidly spreading epidemics. Here, we describe a compartmental model for plague transmission by a human ectoparasite vector. Using Bayesian inference, we found that this model fits mortality curves from nine outbreaks in Europe better than models for pneumonic or rodent transmission. Our results support that human ectoparasites were primary vectors for plague during the Second Pandemic, including the Black Death (1346-1353), ultimately challenging the assumption that plague in Europe was predominantly spread by rats. Copyright © 2018 the Author(s). Published by PNAS.

A human lung xenograft mouse model of Nipah virus infection.

PubMed

Valbuena, Gustavo; Halliday, Hailey; Borisevich, Viktoriya; Goez, Yenny; Rockx, Barry

2014-04-01

Nipah virus (NiV) is a member of the genus Henipavirus (family Paramyxoviridae) that causes severe and often lethal respiratory illness and encephalitis in humans with high mortality rates (up to 92%). NiV can cause Acute Lung Injury (ALI) in humans, and human-to-human transmission has been observed in recent outbreaks of NiV. While the exact route of transmission to humans is not known, we have previously shown that NiV can efficiently infect human respiratory epithelial cells. The molecular mechanisms of NiV-associated ALI in the human respiratory tract are unknown. Thus, there is an urgent need for models of henipavirus infection of the human respiratory tract to study the pathogenesis and understand the host responses. Here, we describe a novel human lung xenograft model in mice to study the pathogenesis of NiV. Following transplantation, human fetal lung xenografts rapidly graft and develop mature structures of adult lungs including cartilage, vascular vessels, ciliated pseudostratified columnar epithelium, and primitive "air" spaces filled with mucus and lined by cuboidal to flat epithelium. Following infection, NiV grows to high titers (10(7) TCID50/gram lung tissue) as early as 3 days post infection (pi). NiV targets both the endothelium as well as respiratory epithelium in the human lung tissues, and results in syncytia formation. NiV infection in the human lung results in the production of several cytokines and chemokines including IL-6, IP-10, eotaxin, G-CSF and GM-CSF on days 5 and 7 pi. In conclusion, this study demonstrates that NiV can replicate to high titers in a novel in vivo model of the human respiratory tract, resulting in a robust inflammatory response, which is known to be associated with ALI. This model will facilitate progress in the fundamental understanding of henipavirus pathogenesis and virus-host interactions; it will also provide biologically relevant models for other respiratory viruses.

New Integrated Modeling Capabilities: MIDAS' Recent Behavioral Enhancements

NASA Technical Reports Server (NTRS)

Gore, Brian F.; Jarvis, Peter A.

2005-01-01

The Man-machine Integration Design and Analysis System (MIDAS) is an integrated human performance modeling software tool that is based on mechanisms that underlie and cause human behavior. A PC-Windows version of MIDAS has been created that integrates the anthropometric character "Jack (TM)" with MIDAS' validated perceptual and attention mechanisms. MIDAS now models multiple simulated humans engaging in goal-related behaviors. New capabilities include the ability to predict situations in which errors and/or performance decrements are likely due to a variety of factors including concurrent workload and performance influencing factors (PIFs). This paper describes a new model that predicts the effects of microgravity on a mission specialist's performance, and its first application to simulating the task of conducting a Life Sciences experiment in space according to a sequential or parallel schedule of performance.

Human Thermal Model Evaluation Using the JSC Human Thermal Database

NASA Technical Reports Server (NTRS)

Bue, Grant; Makinen, Janice; Cognata, Thomas

2012-01-01

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

Dynamic Simulation of Human Gait Model With Predictive Capability.

PubMed

Sun, Jinming; Wu, Shaoli; Voglewede, Philip A

2018-03-01

In this paper, it is proposed that the central nervous system (CNS) controls human gait using a predictive control approach in conjunction with classical feedback control instead of exclusive classical feedback control theory that controls based on past error. To validate this proposition, a dynamic model of human gait is developed using a novel predictive approach to investigate the principles of the CNS. The model developed includes two parts: a plant model that represents the dynamics of human gait and a controller that represents the CNS. The plant model is a seven-segment, six-joint model that has nine degrees-of-freedom (DOF). The plant model is validated using data collected from able-bodied human subjects. The proposed controller utilizes model predictive control (MPC). MPC uses an internal model to predict the output in advance, compare the predicted output to the reference, and optimize the control input so that the predicted error is minimal. To decrease the complexity of the model, two joints are controlled using a proportional-derivative (PD) controller. The developed predictive human gait model is validated by simulating able-bodied human gait. The simulation results show that the developed model is able to simulate the kinematic output close to experimental data.

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.

Combined Economic and Hydrologic Modeling to Support Collaborative Decision Making Processes

NASA Astrophysics Data System (ADS)

Sheer, D. P.

2008-12-01

For more than a decade, the core concept of the author's efforts in support of collaborative decision making has been a combination of hydrologic simulation and multi-objective optimization. The modeling has generally been used to support collaborative decision making processes. The OASIS model developed by HydroLogics Inc. solves a multi-objective optimization at each time step using a mixed integer linear program (MILP). The MILP can be configured to include any user defined objective, including but not limited too economic objectives. For example, an estimated marginal value for water for crops and M&I use were included in the objective function to drive trades in a model of the lower Rio Grande. The formulation of the MILP, constraints and objectives, in any time step is conditional: it changes based on the value of state variables and dynamic external forcing functions, such as rainfall, hydrology, market prices, arrival of migratory fish, water temperature, etc. It therefore acts as a dynamic short term multi-objective economic optimization for each time step. MILP is capable of solving a general problem that includes a very realistic representation of the physical system characteristics in addition to the normal multi-objective optimization objectives and constraints included in economic models. In all of these models, the short term objective function is a surrogate for achieving long term multi-objective results. The long term performance for any alternative (especially including operating strategies) is evaluated by simulation. An operating rule is the combination of conditions, parameters, constraints and objectives used to determine the formulation of the short term optimization in each time step. Heuristic wrappers for the simulation program have been developed improve the parameters of an operating rule, and are initiating research on a wrapper that will allow us to employ a genetic algorithm to improve the form of the rule (conditions, constraints, and short term objectives) as well. In the models operating rules represent different models of human behavior, and the objective of the modeling is to find rules for human behavior that perform well in terms of long term human objectives. The conceptual model used to represent human behavior incorporates economic multi-objective optimization for surrogate objectives, and rules that set those objectives based on current conditions and accounting for uncertainty, at least implicitly. The author asserts that real world operating rules follow this form and have evolved because they have been perceived as successful in the past. Thus, the modeling efforts focus on human behavior in much the same way that economic models focus on human behavior. This paper illustrates the above concepts with real world examples.

Consolidated Human Activity Database (CHAD) for use in human exposure and health studies and predictive models

EPA Pesticide Factsheets

EPA scientists have compiled detailed data on human behavior from 22 separate exposure and time-use studies into CHAD. The database includes more than 54,000 individual study days of detailed human behavior.

A concentrated parameter model for the human cardiovascular system including heart valve dynamics and atrioventricular interaction.

PubMed

Korakianitis, Theodosios; Shi, Yubing

2006-09-01

Numerical modeling of the human cardiovascular system has always been an active research direction since the 19th century. In the past, various simulation models of different complexities were proposed for different research purposes. In this paper, an improved numerical model to study the dynamic function of the human circulation system is proposed. In the development of the mathematical model, the heart chambers are described with a variable elastance model. The systemic and pulmonary loops are described based on the resistance-compliance-inertia concept by considering local effects of flow friction, elasticity of blood vessels and inertia of blood in different segments of the blood vessels. As an advancement from previous models, heart valve dynamics and atrioventricular interaction, including atrial contraction and motion of the annulus fibrosus, are specifically modeled. With these improvements the developed model can predict several important features that were missing in previous numerical models, including regurgitant flow on heart valve closure, the value of E/A velocity ratio in mitral flow, the motion of the annulus fibrosus (called the KG diaphragm pumping action), etc. These features have important clinical meaning and their changes are often related to cardiovascular diseases. Successful simulation of these features enhances the accuracy of simulations of cardiovascular dynamics, and helps in clinical studies of cardiac function.

Canine mammary tumors as a model for human disease.

PubMed

Abdelmegeed, Somaia M; Mohammed, Sulma

2018-06-01

Animal models for examining human breast cancer (HBC) carcinogenesis have been extensively studied and proposed. With the recent advent of immunotherapy, significant attention has been focused on the dog as a model for human cancer. Dogs develop mammary tumors and other cancer types spontaneously with an intact immune system, which exhibit a number of clinical and molecular similarities to HBC. In addition to the spontaneous tumor presentation, the clinical similarities between human and canine mammary tumors (CMT) include the age at onset, hormonal etiology and course of the diseases. Furthermore, factors that affect the disease outcome, including tumor size, stage and lymph node invasion, are similar in HBC and CMT. Similarly, the molecular characteristics of steroid receptor, epidermal growth factor, proliferation marker, metalloproteinase and cyclooxygenase expression, and the mutation of the p53 tumor suppressor gene in CMT, mimic HBC. Furthermore, ductal carcinomas in situ in human and canine mammary glands are particularly similar in their pathological, molecular and visual characteristics. These CMT characteristics and their similarities to HBC indicate that the dog could be an excellent model for the study of human disease. These similarities are discussed in detail in the present review, and are compared with the in vitro and other in vivo animal models available.

Using an instrumented manikin for Space Station Freedom analysis

NASA Technical Reports Server (NTRS)

Orr, Linda; Hill, Richard

1989-01-01

One of the most intriguing and complex areas of current computer graphics research is animating human figures to behave in a realistic manner. Believable, accurate human models are desirable for many everyday uses including industrial and architectural design, medical applications, and human factors evaluations. For zero-gravity (0-g) spacecraft design and mission planning scenarios, they are particularly valuable since 0-g conditions are difficult to simulate in a one-gravity Earth environment. At NASA/JSC, an in-house human modeling package called PLAID is currently being used to produce animations for human factors evaluation of Space Station Freedom design issues. Presented here is an introductory background discussion of problems encountered in existing techniques for animating human models and how an instrumented manikin can help improve the realism of these models.

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.

42 CFR § 512.730 - Compliance enforcement for FFS-CR participants.

Code of Federal Regulations, 2010 CFR

2017-10-01

... HEALTH AND HUMAN SERVICES (CONTINUED) HEALTH CARE INFRASTRUCTURE AND MODEL PROGRAMS EPISODE PAYMENT MODEL CR Incentive Payment Model for EPM and Medicare Fee-for-Service Participants Provisions for Ffs-Cr... through monitoring by HHS (including CMS and OIG) of the CR incentive payment model, including but not...

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.

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.

Human Centered Hardware Modeling and Collaboration

NASA Technical Reports Server (NTRS)

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

2013-01-01

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

Which experimental systems should we use for human microbiome science?

PubMed

Douglas, Angela E

2018-03-01

Microbiome science is revealing that the phenotype and health of animals, including humans, depend on the sustained function of their resident microorganisms. In this essay, I argue for thoughtful choice of model systems for human microbiome science. A greater variety of experimental systems, including wider use of invertebrate models, would benefit biomedical research, while systems ill-suited to experimental and genetic manipulation can be used to address very limited sets of scientific questions. Microbiome science benefits from the coordinated use of multiple systems, which is facilitated by networks of researchers with expertise in different experimental systems.

Modeling in Big Data Environments

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

Endert, Alexander; Szymczak, Samantha; Gunning, Dave

Human-Centered Big Data Research (HCBDR) is an area of work that focuses on the methodologies and research areas focused on understanding how humans interact with “big data”. In the context of this paper, we refer to “big data” in a holistic sense, including most (if not all) the dimensions defining the term, such as complexity, variety, velocity, veracity, etc. Simply put, big data requires us as researchers of to question and reconsider existing approaches, with the opportunity to illuminate new kinds of insights that were traditionally out of reach to humans. The purpose of this article is to summarize themore » discussions and ideas about the role of models in HCBDR at a recent workshop. Models, within the context of this paper, include both computational and conceptual mental models. As such, the discussions summarized in this article seek to understand the connection between these two categories of models.« less

Application of a PExSim for modeling a POLVAD artificial heart and the human circulatory system with left ventricle assistance

NASA Astrophysics Data System (ADS)

Siewnicka, Alicja; Fajdek, Bartlomiej; Janiszowski, Krzysztof

2010-01-01

This paper presents a model of the human circulatory system with the possible addition of a parallel assist device, which was developed for the purpose of artificial heart monitoring. Information about an identification experiment of an extracorporeal ventricle assist device POLVAD is included. The modelling methods applied and the corresponding functional blocks in a PExSim package are presented. The results of the simulation for physiological conditions, left ventricle failure and pathological conditions with parallel assistance are included.

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.

Integrating human and natural systems in community psychology: an ecological model of stewardship behavior.

PubMed

Moskell, Christine; Allred, Shorna Broussard

2013-03-01

Community psychology (CP) research on the natural environment lacks a theoretical framework for analyzing the complex relationship between human systems and the natural world. We introduce other academic fields concerned with the interactions between humans and the natural environment, including environmental sociology and coupled human and natural systems. To demonstrate how the natural environment can be included within CP's ecological framework, we propose an ecological model of urban forest stewardship action. Although ecological models of behavior in CP have previously modeled health behaviors, we argue that these frameworks are also applicable to actions that positively influence the natural environment. We chose the environmental action of urban forest stewardship because cities across the United States are planting millions of trees and increased citizen participation in urban tree planting and stewardship will be needed to sustain the benefits provided by urban trees. We used the framework of an ecological model of behavior to illustrate multiple levels of factors that may promote or hinder involvement in urban forest stewardship actions. The implications of our model for the development of multi-level ecological interventions to foster stewardship actions are discussed, as well as directions for future research to further test and refine the model.

Tissue and Animal Models of Sudden Cardiac Death

PubMed Central

Sallam, Karim; Li, Yingxin; Sager, Philip T.; Houser, Steven R.; Wu, Joseph C.

2015-01-01

Sudden Cardiac Death (SCD) is a common cause of death in patients with structural heart disease, genetic mutations or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with SCD. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology including ion channel expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell derived Cardiomyocytes (iPSC-CMs) resemble, but are not identical, to adult human cardiomyocytes, and provide a new platform for studying arrhythmic disorders leading to SCD. A variety of platforms exist to phenotype cellular models including conventional and automated patch clamp, multi-electrode array, and computational modeling. iPSC-CMs have been used to study Long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy and other hereditary cardiac disorders. Although iPSC-CMs are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of SCD. PMID:26044252

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.

Human pluripotent stem cells: an emerging model in developmental biology

PubMed Central

Zhu, Zengrong; Huangfu, Danwei

2013-01-01

Developmental biology has long benefited from studies of classic model organisms. Recently, human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, have emerged as a new model system that offers unique advantages for developmental studies. Here, we discuss how studies of hPSCs can complement classic approaches using model organisms, and how hPSCs can be used to recapitulate aspects of human embryonic development ‘in a dish’. We also summarize some of the recently developed genetic tools that greatly facilitate the interrogation of gene function during hPSC differentiation. With the development of high-throughput screening technologies, hPSCs have the potential to revolutionize gene discovery in mammalian development. PMID:23362344

*Combining regional - and local-scale air quality models with exposure models for use in environmental health studies - Title changed from Linking air quality and exposure models for use in environmental health studies

EPA Science Inventory

Population-based human exposure models predict the distribution of personal exposures to pollutants of outdoor origin using a variety of inputs, including air pollution concentrations; human activity patterns, such as the amount of time spent outdoors versus indoors, commuting, w...

Human impact parameterization in global hydrological models improves estimates of monthly discharges and hydrological extremes: a multi-model validation study

NASA Astrophysics Data System (ADS)

Veldkamp, Ted; Ward, Philip; de Moel, Hans; Aerts, Jeroen; Muller Schmied, Hannes; Portmann, Felix; Zhao, Fang; Gerten, Dieter; Masaki, Yoshimitsu; Pokhrel, Yadu; Satoh, Yusuke; Gosling, Simon; Zaherpour, Jamal; Wada, Yoshihide

2017-04-01

Human impacts on freshwater resources and hydrological features form the core of present-day water related hazards, like flooding, droughts, water scarcity, and water quality issues. Driven by the societal and scientific needs to correctly model such water related hazards a fair amount of resources has been invested over the past decades to represent human activities and their interactions with the hydrological cycle in global hydrological models (GHMs). Use of these GHMs - including the human dimension - is widespread, especially in water resources research. Evaluation or comparative assessments of the ability of such GHMs to represent real-world hydrological conditions are, unfortunately, however often limited to (near-)natural river basins. Such studies are, therefore, not able to test the model representation of human activities and its associated impact on estimates of freshwater resources or assessments of hydrological extremes. Studies that did perform a validation exercise - including the human dimension and looking into managed catchments - either focused only on one hydrological model, and/or incorporated only a few data points (i.e. river basins) for validation. To date, a comprehensive comparative analysis that evaluates whether and where incorporating the human dimension actually improves the performance of different GHMs with respect to their representation of real-world hydrological conditions and extremes is missing. The absence of such study limits the potential benchmarking of GHMs and their outcomes in hydrological hazard and risk assessments significantly, potentially hampering incorporation of GHMs and their modelling results in actual policy making and decision support with respect to water resources management. To address this issue, we evaluate in this study the performance of five state-of-the-art GHMs that include anthropogenic activities in their modelling scheme, with respect to their representation of monthly discharges and hydrological extremes. To this end, we compared their monthly discharge simulations under a naturalized and a time-dependent human impact simulation, with monthly GRDC river discharge observations of 2,412 stations over the period 1971-2010. Evaluation metrics that were used to assess the performance of the GHMs included the modified Kling-Gupta Efficiency index, and its individual parameters describing the linear correlation coefficient, the bias ratio, and the variability ratio, as well as indicators for hydrological extremes (Q90, Q10). Our results show that inclusion of anthropogenic activities in the modelling framework generally enhances the overall performance of the GHMs studied, mainly driven by bias-improvements, and to a lesser extent due to changes in modelled hydrological variability. Whilst the inclusion of anthropogenic activities takes mainly effect in the managed catchments, a significant share of the (near-)natural catchments is influenced as well. To get estimates of hydrological extremes right, especially when looking at low-flows, inclusion of human activities is paramount. Whilst high-flow estimates are mainly decreased, impact of human activities on low-flows is ambiguous, i.e. due to the relative importance of the timing of return flows and reservoir operations. Even with inclusion of the human dimension we find, nevertheless, a persistent overestimation of hydrological extremes across all models, which should be accounted for in future assessments.

Predicting the Consequences of Workload Management Strategies with Human Performance Modeling

NASA Technical Reports Server (NTRS)

Mitchell, Diane Kuhl; Samma, Charneta

2011-01-01

Human performance modelers at the US Army Research Laboratory have developed an approach for establishing Soldier high workload that can be used for analyses of proposed system designs. Their technique includes three key components. To implement the approach in an experiment, the researcher would create two experimental conditions: a baseline and a design alternative. Next they would identify a scenario in which the test participants perform all their representative concurrent interactions with the system. This scenario should include any events that would trigger a different set of goals for the human operators. They would collect workload values during both the control and alternative design condition to see if the alternative increased workload and decreased performance. They have successfully implemented this approach for military vehicle. designs using the human performance modeling tool, IMPRINT. Although ARL researches use IMPRINT to implement their approach, it can be applied to any workload analysis. Researchers using other modeling and simulations tools or conducting experiments or field tests can use the same approach.

A 3D human neural cell culture system for modeling Alzheimer’s disease

PubMed Central

Kim, Young Hye; Choi, Se Hoon; D’Avanzo, Carla; Hebisch, Matthias; Sliwinski, Christopher; Bylykbashi, Enjana; Washicosky, Kevin J.; Klee, Justin B.; Brüstle, Oliver; Tanzi, Rudolph E.; Kim, Doo Yeon

2015-01-01

Stem cell technologies have facilitated the development of human cellular disease models that can be used to study pathogenesis and test therapeutic candidates. These models hold promise for complex neurological diseases such as Alzheimer’s disease (AD) because existing animal models have been unable to fully recapitulate all aspects of pathology. We recently reported the characterization of a novel three-dimensional (3D) culture system that exhibits key events in AD pathogenesis, including extracellular aggregation of β-amyloid and accumulation of hyperphosphorylated tau. Here we provide instructions for the generation and analysis of 3D human neural cell cultures, including the production of genetically modified human neural progenitor cells (hNPCs) with familial AD mutations, the differentiation of the hNPCs in a 3D matrix, and the analysis of AD pathogenesis. The 3D culture generation takes 1–2 days. The aggregation of β-amyloid is observed after 6-weeks of differentiation followed by robust tau pathology after 10–14 weeks. PMID:26068894

Radiation Belt and Plasma Model Requirements

NASA Technical Reports Server (NTRS)

Barth, Janet L.

2005-01-01

Contents include the following: Radiation belt and plasma model environment. Environment hazards for systems and humans. Need for new models. How models are used. Model requirements. How can space weather community help?

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.

The Human-Computer Interface and Information Literacy: Some Basics and Beyond.

ERIC Educational Resources Information Center

Church, Gary M.

1999-01-01

Discusses human/computer interaction research, human/computer interface, and their relationships to information literacy. Highlights include communication models; cognitive perspectives; task analysis; theory of action; problem solving; instructional design considerations; and a suggestion that human/information interface may be a more appropriate…

3D Miniaturization of Human Organs for Drug Discovery.

PubMed

Park, Joseph; Wetzel, Isaac; Dréau, Didier; Cho, Hansang

2018-01-01

"Engineered human organs" hold promises for predicting the effectiveness and accuracy of drug responses while reducing cost, time, and failure rates in clinical trials. Multiorgan human models utilize many aspects of currently available technologies including self-organized spherical 3D human organoids, microfabricated 3D human organ chips, and 3D bioprinted human organ constructs to mimic key structural and functional properties of human organs. They enable precise control of multicellular activities, extracellular matrix (ECM) compositions, spatial distributions of cells, architectural organizations of ECM, and environmental cues. Thus, engineered human organs can provide the microstructures and biological functions of target organs and advantageously substitute multiscaled drug-testing platforms including the current in vitro molecular assays, cell platforms, and in vivo models. This review provides an overview of advanced innovative designs based on the three main technologies used for organ construction leading to single and multiorgan systems useable for drug development. Current technological challenges and future perspectives are also discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Excavator Design Validation

NASA Technical Reports Server (NTRS)

Pholsiri, Chalongrath; English, James; Seberino, Charles; Lim, Yi-Je

2010-01-01

The Excavator Design Validation tool verifies excavator designs by automatically generating control systems and modeling their performance in an accurate simulation of their expected environment. Part of this software design includes interfacing with human operations that can be included in simulation-based studies and validation. This is essential for assessing productivity, versatility, and reliability. This software combines automatic control system generation from CAD (computer-aided design) models, rapid validation of complex mechanism designs, and detailed models of the environment including soil, dust, temperature, remote supervision, and communication latency to create a system of high value. Unique algorithms have been created for controlling and simulating complex robotic mechanisms automatically from just a CAD description. These algorithms are implemented as a commercial cross-platform C++ software toolkit that is configurable using the Extensible Markup Language (XML). The algorithms work with virtually any mobile robotic mechanisms using module descriptions that adhere to the XML standard. In addition, high-fidelity, real-time physics-based simulation algorithms have also been developed that include models of internal forces and the forces produced when a mechanism interacts with the outside world. This capability is combined with an innovative organization for simulation algorithms, new regolith simulation methods, and a unique control and study architecture to make powerful tools with the potential to transform the way NASA verifies and compares excavator designs. Energid's Actin software has been leveraged for this design validation. The architecture includes parametric and Monte Carlo studies tailored for validation of excavator designs and their control by remote human operators. It also includes the ability to interface with third-party software and human-input devices. Two types of simulation models have been adapted: high-fidelity discrete element models and fast analytical models. By using the first to establish parameters for the second, a system has been created that can be executed in real time, or faster than real time, on a desktop PC. This allows Monte Carlo simulations to be performed on a computer platform available to all researchers, and it allows human interaction to be included in a real-time simulation process. Metrics on excavator performance are established that work with the simulation architecture. Both static and dynamic metrics are included.

Reconstruction of Tissue-Specific Metabolic Networks Using CORDA

PubMed Central

Schultz, André; Qutub, Amina A.

2016-01-01

Human metabolism involves thousands of reactions and metabolites. To interpret this complexity, computational modeling becomes an essential experimental tool. One of the most popular techniques to study human metabolism as a whole is genome scale modeling. A key challenge to applying genome scale modeling is identifying critical metabolic reactions across diverse human tissues. Here we introduce a novel algorithm called Cost Optimization Reaction Dependency Assessment (CORDA) to build genome scale models in a tissue-specific manner. CORDA performs more efficiently computationally, shows better agreement to experimental data, and displays better model functionality and capacity when compared to previous algorithms. CORDA also returns reaction associations that can greatly assist in any manual curation to be performed following the automated reconstruction process. Using CORDA, we developed a library of 76 healthy and 20 cancer tissue-specific reconstructions. These reconstructions identified which metabolic pathways are shared across diverse human tissues. Moreover, we identified changes in reactions and pathways that are differentially included and present different capacity profiles in cancer compared to healthy tissues, including up-regulation of folate metabolism, the down-regulation of thiamine metabolism, and tight regulation of oxidative phosphorylation. PMID:26942765

The Shigella human challenge model.

PubMed

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

2013-02-01

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

Infection prevention behaviour and infectious disease modelling: a review of the literature and recommendations for the future.

PubMed

Weston, Dale; Hauck, Katharina; Amlôt, Richard

2018-03-09

Given the importance of person to person transmission in the spread of infectious diseases, it is critically important to ensure that human behaviour with respect to infection prevention is appropriately represented within infectious disease models. This paper presents a large scale scoping review regarding the incorporation of infection prevention behaviour in infectious disease models. The outcomes of this review are contextualised within the psychological literature concerning health behaviour and behaviour change, resulting in a series of key recommendations for the incorporation of human behaviour in future infectious disease models. The search strategy focused on terms relating to behaviour, infectious disease and mathematical modelling. The selection criteria were developed iteratively to focus on original research articles that present an infectious disease model with human-human spread, in which individuals' self-protective health behaviour varied endogenously within the model. Data extracted included: the behaviour that is modelled; how this behaviour is modelled; any theoretical background for the modelling of behaviour, and; any behavioural data used to parameterise the models. Forty-two papers from an initial total of 2987 were retained for inclusion in the final review. All of these papers were published between 2002 and 2015. Many of the included papers employed a multiple, linked models to incorporate infection prevention behaviour. Both cognitive constructs (e.g., perceived risk) and, to a lesser extent, social constructs (e.g., social norms) were identified in the included papers. However, only five papers made explicit reference to psychological health behaviour change theories. Finally, just under half of the included papers incorporated behavioural data in their modelling. By contextualising the review outcomes within the psychological literature on health behaviour and behaviour change, three key recommendations for future behavioural modelling are made. First, modellers should consult with the psychological literature on health behaviour/ behaviour change when developing new models. Second, modellers interested in exploring the relationship between behaviour and disease spread should draw on social psychological literature to increase the complexity of the social world represented within infectious disease models. Finally, greater use of context-specific behavioural data (e.g., survey data, observational data) is recommended to parameterise models.

Applications and Limitations of Mouse Models for Understanding Human Atherosclerosis

PubMed Central

von Scheidt, Moritz; Zhao, Yuqi; Kurt, Zeyneb; Pan, Calvin; Zeng, Lingyao; Yang, Xia; Schunkert, Heribert; Lusis, Aldons J.

2017-01-01

Most of the biological understanding of mechanisms underlying coronary artery disease (CAD) derives from studies of mouse models. The identification of multiple CAD loci and strong candidate genes in large human genome-wide association studies (GWAS) presented an opportunity to examine the relevance of mouse models for the human disease. We comprehensively reviewed the mouse literature, including 827 literature-derived genes, and compared it to human data. First, we observed striking concordance of risk factors for atherosclerosis in mice and humans. Second, there was highly significant overlap of mouse genes with human genes identified by GWAS. In particular, of the 46 genes with strong association signals in CAD-GWAS that were studied in mouse models all but one exhibited consistent effects on atherosclerosis-related phenotypes. Third, we compared 178 CAD-associated pathways derived from human GWAS with 263 from mouse studies and observed that over 50% were consistent between both species. PMID:27916529

Modeling the human mental lexicon with self-organizing feature maps

NASA Astrophysics Data System (ADS)

Wittenburg, Peter; Frauenfelder, Uli H.

1992-10-01

Recent efforts to model the remarkable ability of humans to recognize speech and words are described. Different techniques including the use of neural nets for representing phonological similarity between words in the lexicon with self organizing algorithms are discussed. Simulations using the standard Kohonen algorithm are presented to illustrate some problems confronted with this technique in modeling similarity relations of form in the human mental lexicon. Alternative approaches that can potentially deal with some of these limitations are sketched.

Human genome education model project. Ethical, legal, and social implications of the human genome project: Education of interdisciplinary professionals

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

Weiss, J.O.; Lapham, E.V.

1996-12-31

This meeting was held June 10, 1996 at Georgetown University. The purpose of this meeting was to provide a multidisciplinary forum for exchange of state-of-the-art information on the human genome education model. Topics of discussion include the following: psychosocial issues; ethical issues for professionals; legislative issues and update; and education issues.

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

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.

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

PubMed Central

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

2015-01-01

ABSTRACT Human gastrointestinal tract research is limited by the paucity of in vitro intestinal cell models that recapitulate the cellular diversity and complex functions of human physiology and disease pathology. Human intestinal enteroid (HIE) cultures contain multiple intestinal epithelial cell types that comprise the intestinal epithelium (enterocytes and goblet, enteroendocrine, and Paneth cells) and are physiologically active based on responses to agonists. We evaluated these nontransformed, three-dimensional HIE cultures as models for pathogenic infections in the small intestine by examining whether HIEs from different regions of the small intestine from different patients are susceptible to human rotavirus (HRV) infection. Little is known about HRVs, as they generally replicate poorly in transformed cell lines, and host range restriction prevents their replication in many animal models, whereas many animal rotaviruses (ARVs) exhibit a broader host range and replicate in mice. Using HRVs, including the Rotarix RV1 vaccine strain, and ARVs, we evaluated host susceptibility, virus production, and cellular responses of HIEs. HRVs infect at higher rates and grow to higher titers than do ARVs. HRVs infect differentiated enterocytes and enteroendocrine cells, and viroplasms and lipid droplets are induced. Heterogeneity in replication was seen in HIEs from different patients. HRV infection and RV enterotoxin treatment of HIEs caused physiological lumenal expansion detected by time-lapse microscopy, recapitulating one of the hallmarks of rotavirus-induced diarrhea. These results demonstrate that HIEs are a novel pathophysiological model that will allow the study of HRV biology, including host restriction, cell type restriction, and virus-induced fluid secretion. IMPORTANCE Our research establishes HIEs as nontransformed cell culture models to understand human intestinal physiology and pathophysiology and the epithelial response, including host restriction of gastrointestinal infections such as HRV infection. HRVs remain a major worldwide cause of diarrhea-associated morbidity and mortality in children ≤5 years of age. Current in vitro models of rotavirus infection rely primarily on the use of animal rotaviruses because HRV growth is limited in most transformed cell lines and animal models. We demonstrate that HIEs are novel, cellularly diverse, and physiologically relevant epithelial cell cultures that recapitulate in vivo properties of HRV infection. HIEs will allow the study of HRV biology, including human host-pathogen and live, attenuated vaccine interactions; host and cell type restriction; virus-induced fluid secretion; cell-cell communication within the epithelium; and the epithelial response to infection in cultures from genetically diverse individuals. Finally, drug therapies to prevent/treat diarrheal disease can be tested in these physiologically active cultures. PMID:26446608

Gene Expression Profiles of Human Dendritic Cells Interacting with Aspergillus fumigatus in a Bilayer Model of the Alveolar Epithelium/Endothelium Interface

PubMed Central

Morton, Charles Oliver; Fliesser, Mirjam; Dittrich, Marcus; Mueller, Tobias; Bauer, Ruth; Kneitz, Susanne; Hope, William; Rogers, Thomas Richard; Einsele, Hermann; Loeffler, Juergen

2014-01-01

The initial stages of the interaction between the host and Aspergillus fumigatus at the alveolar surface of the human lung are critical in the establishment of aspergillosis. Using an in vitro bilayer model of the alveolus, including both the epithelium (human lung adenocarcinoma epithelial cell line, A549) and endothelium (human pulmonary artery epithelial cells, HPAEC) on transwell membranes, it was possible to closely replicate the in vivo conditions. Two distinct sub-groups of dendritic cells (DC), monocyte-derived DC (moDC) and myeloid DC (mDC), were included in the model to examine immune responses to fungal infection at the alveolar surface. RNA in high quantity and quality was extracted from the cell layers on the transwell membrane to allow gene expression analysis using tailored custom-made microarrays, containing probes for 117 immune-relevant genes. This microarray data indicated minimal induction of immune gene expression in A549 alveolar epithelial cells in response to germ tubes of A. fumigatus. In contrast, the addition of DC to the system greatly increased the number of differentially expressed immune genes. moDC exhibited increased expression of genes including CLEC7A, CD209 and CCL18 in the absence of A. fumigatus compared to mDC. In the presence of A. fumigatus, both DC subgroups exhibited up-regulation of genes identified in previous studies as being associated with the exposure of DC to A. fumigatus and exhibiting chemotactic properties for neutrophils, including CXCL2, CXCL5, CCL20, and IL1B. This model closely approximated the human alveolus allowing for an analysis of the host pathogen interface that complements existing animal models of IA. PMID:24870357

Evaluation of internal noise methods for Hotelling observers

NASA Astrophysics Data System (ADS)

Zhang, Yani; Pham, Binh T.; Eckstein, Miguel P.

2005-04-01

Including internal noise in computer model observers to degrade model observer performance to human levels is a common method to allow for quantitatively comparisons of human and model performance. In this paper, we studied two different types of methods for injecting internal noise to Hotelling model observers. The first method adds internal noise to the output of the individual channels: a) Independent non-uniform channel noise, b) Independent uniform channel noise. The second method adds internal noise to the decision variable arising from the combination of channel responses: a) internal noise standard deviation proportional to decision variable's standard deviation due to the external noise, b) internal noise standard deviation proportional to decision variable's variance caused by the external noise. We tested the square window Hotelling observer (HO), channelized Hotelling observer (CHO), and Laguerre-Gauss Hotelling observer (LGHO). The studied task was detection of a filling defect of varying size/shape in one of four simulated arterial segment locations with real x-ray angiography backgrounds. Results show that the internal noise method that leads to the best prediction of human performance differs across the studied models observers. The CHO model best predicts human observer performance with the channel internal noise. The HO and LGHO best predict human observer performance with the decision variable internal noise. These results might help explain why previous studies have found different results on the ability of each Hotelling model to predict human performance. Finally, the present results might guide researchers with the choice of method to include internal noise into their Hotelling models.

Engineering stromal-epithelial interactions in vitro for ...

EPA Pesticide Factsheets

Background: Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue function. Epithelial-mesenchymal interactions (EMIs) have been examined using mammalian models, ex vivo tissue recombination, and in vitro co-cultures. Although these approaches have elucidated signaling mechanisms underlying morphogenetic processes and adult mammalian epithelial tissue function, they are limited by the availability of human tissue, low throughput, and human developmental or physiological relevance. Objectives: Bioengineering strategies to promote EMIs using human epithelial and mesenchymal cells have enabled the development of human in vitro models of adult epidermal and glandular tissues. In this review, we describe recent bioengineered models of human epithelial tissue and organs that can instruct the design of organotypic models of human developmental processes.Methods: We reviewed current bioengineering literature and here describe how bioengineered EMIs have enabled the development of human in vitro epithelial tissue models.Discussion: Engineered models to promote EMIs have recapitulated the architecture, phenotype, and function of adult human epithelial tissue, and similar engineering principles could be used to develop models of developmental morphogenesis. We describe how bioengineering strategies including bioprinting and spheroid culture could be implemented to

Modeling Analysis of Biomechanical Changes of Middle Ear and Cochlea in Otitis Media

NASA Astrophysics Data System (ADS)

Gan, Rong Z.; Zhang, Xiangming; Guan, Xiying

2011-11-01

A comprehensive finite element (FE) model of the human ear including the ear canal, middle ear, and spiral cochlea was developed using histological sections of human temporal bone. The cochlea was modeled with three chambers separated by the basilar membrane and Reissner's membrane and filled with perilymphatic fluid. The viscoelastic material behavior was applied to middle ear soft tissues based on dynamic measurements of tissues in our lab. The model was validated using the experimental data obtained in human temporal bones and then used to simulate various stages of otitis media (OM) including the changes of morphology, mechanical properties, pressure, and fluid level in the middle ear. Function alterations of the middle ear and cochlea in OM were derived from the model and compared with the measurements from temporal bones. This study indicates that OM can be simulated in the FE model to predict the hearing loss induced by biomechanical changes of the middle ear and cochlea.

Caenorhabditis elegans as a model to study renal development and disease: sexy cilia.

PubMed

Barr, Maureen M

2005-02-01

The nematode Caenorhabditis elegans has no kidney per se, yet "the worm" has proved to be an excellent model to study renal-related issues, including tubulogenesis of the excretory canal, membrane transport and ion channel function, and human genetic diseases including autosomal dominant polycystic kidney disease (ADPKD). The goal of this review is to explain how C. elegans has provided insight into cilia development, cilia function, and human cystic kidney diseases.

Applying Multiagent Simulation to Planetary Surface Operations

NASA Technical Reports Server (NTRS)

Sierhuis, Maarten; Sims, Michael H.; Clancey, William J.; Lee, Pascal; Swanson, Keith (Technical Monitor)

2000-01-01

This paper describes a multiagent modeling and simulation approach for designing cooperative systems. Issues addressed include the use of multiagent modeling and simulation for the design of human and robotic operations, as a theory for human/robot cooperation on planetary surface missions. We describe a design process for cooperative systems centered around the Brahms modeling and simulation environment being developed at NASA Ames.

Tauopathy induced by low level expression of a human brain-derived tau fragment in mice is rescued by phenylbutyrate.

PubMed

Bondulich, Marie K; Guo, Tong; Meehan, Christopher; Manion, John; Rodriguez Martin, Teresa; Mitchell, Jacqueline C; Hortobagyi, Tibor; Yankova, Natalia; Stygelbout, Virginie; Brion, Jean-Pierre; Noble, Wendy; Hanger, Diane P

2016-08-01

Human neurodegenerative tauopathies exhibit pathological tau aggregates in the brain along with diverse clinical features including cognitive and motor dysfunction. Post-translational modifications including phosphorylation, ubiquitination and truncation, are characteristic features of tau present in the brain in human tauopathy. We have previously reported an N-terminally truncated form of tau in human brain that is associated with the development of tauopathy and is highly phosphorylated. We have generated a new mouse model of tauopathy in which this human brain-derived, 35 kDa tau fragment (Tau35) is expressed in the absence of any mutation and under the control of the human tau promoter. Most existing mouse models of tauopathy overexpress mutant tau at levels that do not occur in human neurodegenerative disease, whereas Tau35 transgene expression is equivalent to less than 10% of that of endogenous mouse tau. Tau35 mice recapitulate key features of human tauopathies, including aggregated and abnormally phosphorylated tau, progressive cognitive and motor deficits, autophagic/lysosomal dysfunction, loss of synaptic protein, and reduced life-span. Importantly, we found that sodium 4-phenylbutyrate (Buphenyl®), a drug used to treat urea cycle disorders and currently in clinical trials for a range of neurodegenerative diseases, reverses the observed abnormalities in tau and autophagy, behavioural deficits, and loss of synapsin 1 in Tau35 mice. Our results show for the first time that, unlike other tau transgenic mouse models, minimal expression of a human disease-associated tau fragment in Tau35 mice causes a profound and progressive tauopathy and cognitive changes, which are rescued by pharmacological intervention using a clinically approved drug. These novel Tau35 mice therefore represent a highly disease-relevant animal model in which to investigate molecular mechanisms and to develop novel treatments for human tauopathies. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Tauopathy induced by low level expression of a human brain-derived tau fragment in mice is rescued by phenylbutyrate

PubMed Central

Bondulich, Marie K.; Guo, Tong; Meehan, Christopher; Manion, John; Rodriguez Martin, Teresa; Mitchell, Jacqueline C.; Hortobagyi, Tibor; Yankova, Natalia; Stygelbout, Virginie; Brion, Jean-Pierre; Noble, Wendy

2016-01-01

Abstract Human neurodegenerative tauopathies exhibit pathological tau aggregates in the brain along with diverse clinical features including cognitive and motor dysfunction. Post-translational modifications including phosphorylation, ubiquitination and truncation, are characteristic features of tau present in the brain in human tauopathy. We have previously reported an N-terminally truncated form of tau in human brain that is associated with the development of tauopathy and is highly phosphorylated. We have generated a new mouse model of tauopathy in which this human brain-derived, 35 kDa tau fragment (Tau35) is expressed in the absence of any mutation and under the control of the human tau promoter. Most existing mouse models of tauopathy overexpress mutant tau at levels that do not occur in human neurodegenerative disease, whereas Tau35 transgene expression is equivalent to less than 10% of that of endogenous mouse tau. Tau35 mice recapitulate key features of human tauopathies, including aggregated and abnormally phosphorylated tau, progressive cognitive and motor deficits, autophagic/lysosomal dysfunction, loss of synaptic protein, and reduced life-span. Importantly, we found that sodium 4-phenylbutyrate (Buphenyl®), a drug used to treat urea cycle disorders and currently in clinical trials for a range of neurodegenerative diseases, reverses the observed abnormalities in tau and autophagy, behavioural deficits, and loss of synapsin 1 in Tau35 mice. Our results show for the first time that, unlike other tau transgenic mouse models, minimal expression of a human disease-associated tau fragment in Tau35 mice causes a profound and progressive tauopathy and cognitive changes, which are rescued by pharmacological intervention using a clinically approved drug. These novel Tau35 mice therefore represent a highly disease-relevant animal model in which to investigate molecular mechanisms and to develop novel treatments for human tauopathies. PMID:27297240

Drosophila as a Model for Human Diseases-Focus on Innate Immunity in Barrier Epithelia.

PubMed

Bergman, P; Seyedoleslami Esfahani, S; Engström, Y

2017-01-01

Epithelial immunity protects the host from harmful microbial invaders but also controls the beneficial microbiota on epithelial surfaces. When this delicate balance between pathogen and symbiont is disturbed, clinical disease often occurs, such as in inflammatory bowel disease, cystic fibrosis, or atopic dermatitis, which all can be in part linked to impairment of barrier epithelia. Many innate immune receptors, signaling pathways, and effector molecules are evolutionarily conserved between human and Drosophila. This review describes the current knowledge on Drosophila as a model for human diseases, with a special focus on innate immune-related disorders of the gut, lung, and skin. The discovery of antimicrobial peptides, the crucial role of Toll and Toll-like receptors, and the evolutionary conservation of signaling to the immune systems of both human and Drosophila are described in a historical perspective. Similarities and differences between human and Drosophila are discussed; current knowledge on receptors, signaling pathways, and effectors are reviewed, including antimicrobial peptides, reactive oxygen species, as well as autophagy. We also give examples of human diseases for which Drosophila appears to be a useful model. In addition, the limitations of the Drosophila model are mentioned. Finally, we propose areas for future research, which include using the Drosophila model for drug screening, as a validation tool for novel genetic mutations in humans and for exploratory research of microbiota-host interactions, with relevance for infection, wound healing, and cancer. © 2017 Elsevier Inc. All rights reserved.

Integral Nursing: An Emerging Framework for Engaging the Evolution of the Profession.

ERIC Educational Resources Information Center

Fiandt, Kathryn; Forman, John; Megel, Mary Erickson; Pakieser, Ruth A.; Burge, Stephanie

2003-01-01

Proposes the Integral Nursing framework, which combines Wilber's All-Quadrant/All-Level model, a heuristic device to organize human experience, and the Spiral Dynamics model of human development organized around value memes or cultural units of information. Includes commentary by Beth L. Rodgers. (Contains 17 references.) (JOW)

INTEGRATED PROBABILISTIC AND DETERMINISTIC MODELING TECHNIQUES IN ESTIMATING EXPOSURE TO WATER-BORNE CONTAMINANTS: PART 1 EXPOSURE MODELING

EPA Science Inventory

Exposure to contaminants originating in the domestic water supply is influenced by a number of factors, including human activities, water use behavior, and physical and chemical processes. The key role of human activities is very apparent in exposure related to volatile water-...

Comparison of Chemical-induced Changes in Proliferation and Apoptosis in Human and Mouse Neuroprogenitor Cells.***

EPA Science Inventory

There is a need to develop rapid and efficient models to screen chemicals for their potential to cause developmental neurotoxicity. Use of in vitro neuronal models, including human cells, is one approach that allows for timely, cost-effective toxicity screening. The present study...

COMPARISON OF CHEMICAL-INDUCED CHANGES IN PROLIFERATION AND APOPTOSIS IN HUMAN AND MOUSE NEUROPROGENITOR CELLS.

EPA Science Inventory

There is a need to develop rapid and efficient models for screening chemicals for their potential to cause developmental neurotoxicity. Use of in vitro neuronal models, including human cells, is one approach that allows for timely, cost-effective toxicity screening. The present s...

From bedside to bench and back again: research issues in animal models of human disease.

PubMed

Tkacs, Nancy C; Thompson, Hilaire J

2006-07-01

To improve outcomes for patients with many serious clinical problems, multifactorial research approaches by nurse scientists, including the use of animal models, are necessary. Animal models serve as analogies for clinical problems seen in humans and must meet certain criteria, including validity and reliability, to be useful in moving research efforts forward. This article describes research considerations in the development of rodent models. As the standard of diabetes care evolves to emphasize intensive insulin therapy, rates of severe hypoglycemia are increasing among patients with type 1 and type 2 diabetes mellitus. A consequence of this change in clinical practice is an increase in rates of two hypoglycemia-related diabetes complications: hypoglycemia-associated autonomic failure (HAAF) and resulting hypoglycemia unawareness. Work on an animal model of HAAF is in an early developmental stage, with several labs reporting different approaches to model this complication of type 1 diabetes mellitus. This emerging model serves as an example illustrating how evaluation of validity and reliability is critically important at each stage of developing and testing animal models to support inquiry into human disease.

A visco-hyperelastic constitutive model for human spine ligaments.

PubMed

Jiang, Yugang; Wang, Yu; Peng, Xiongqi

2015-03-01

Human spine ligaments show a highly non-linear, strain rate dependent biomechanical behavior under tensile tests. A visco-hyperelastic fiber-reinforced constitutive model was accordingly developed for human ligaments, in which the energy density function is decomposed into two parts. The first part represents the elastic strain energy stored in the soft tissue, and the second part denotes the energy dissipated due to its inherent viscous characteristics. The model is applied to various human spinal ligaments including the anterior and posterior longitudinal ligaments, ligamentum flavum, capsular ligament, and interspinous ligament. Material parameters for each type of ligament were obtained by curve-fitting with corresponding experimental data available in the literature. The results indicate that the model presented here can properly characterize the visco-hyperelastic biomechanical behavior of human spine ligaments.

Computational Model of Human and System Dynamics in Free Flight: Studies in Distributed Control Technologies

NASA Technical Reports Server (NTRS)

Corker, Kevin M.; Pisanich, Gregory; Lebacqz, J. Victor (Technical Monitor)

1998-01-01

This paper presents a set of studies in full mission simulation and the development of a predictive computational model of human performance in control of complex airspace operations. NASA and the FAA have initiated programs of research and development to provide flight crew, airline operations and air traffic managers with automation aids to increase capacity in en route and terminal area to support the goals of safe, flexible, predictable and efficient operations. In support of these developments, we present a computational model to aid design that includes representation of multiple cognitive agents (both human operators and intelligent aiding systems). The demands of air traffic management require representation of many intelligent agents sharing world-models, coordinating action/intention, and scheduling goals and actions in a potentially unpredictable world of operations. The operator-model structure includes attention functions, action priority, and situation assessment. The cognitive model has been expanded to include working memory operations including retrieval from long-term store, and interference. The operator's activity structures have been developed to provide for anticipation (knowledge of the intention and action of remote operators), and to respond to failures of the system and other operators in the system in situation-specific paradigms. System stability and operator actions can be predicted by using the model. The model's predictive accuracy was verified using the full-mission simulation data of commercial flight deck operations with advanced air traffic management techniques.

Designing automation for human use: empirical studies and quantitative models.

PubMed

Parasuraman, R

2000-07-01

An emerging knowledge base of human performance research can provide guidelines for designing automation that can be used effectively by human operators of complex systems. Which functions should be automated and to what extent in a given system? A model for types and levels of automation that provides a framework and an objective basis for making such choices is described. The human performance consequences of particular types and levels of automation constitute primary evaluative criteria for automation design when using the model. Four human performance areas are considered--mental workload, situation awareness, complacency and skill degradation. Secondary evaluative criteria include such factors as automation reliability, the risks of decision/action consequences and the ease of systems integration. In addition to this qualitative approach, quantitative models can inform design. Several computational and formal models of human interaction with automation that have been proposed by various researchers are reviewed. An important future research need is the integration of qualitative and quantitative approaches. Application of these models provides an objective basis for designing automation for effective human use.

Humanities Curriculum Guide.

ERIC Educational Resources Information Center

Stafford, Mary Ann

Designed as a model for a high school humanities program, this publication outlines a two-course, two-year elective in humanities for high school juniors and seniors. Introductory material includes an overview of the program and its history, credits, goals of the program, and an introduction to humanities. The major portion of the guide contains…

Integrating Economic Models with Biophysical Models in the Willamette Water 2100 Project

NASA Astrophysics Data System (ADS)

Jaeger, W. K.; Plantinga, A.

2013-12-01

This paper highlights the human system modeling components for Willamette Water 2100, a comprehensive, highly integrated study of hydrological, ecological, and human factors affecting water scarcity in the Willamette River Basin (WRB). The project is developing a spatiotemporal simulation model to predict future trajectories of water scarcity, and to evaluate mitigation policies. Economic models of land use and water use are the main human system models in WW2100. Water scarcity depends on both supply and demand for water, and varies greatly across time and space (Jaeger et al., 2013). Thus, the locations of human water use can have enormous influence on where and when water is used, and hence where water scarcity may arise. Modeling the locations of human uses of water (e.g., urban versus agricultural) as well as human values and choices, are the principal quantitative ways that social science can contribute to research of this kind. Our models are empirically-based models of human resource allocation. Each model reflects private behavior (choices by households, farms, firms), institutions (property rights, laws, markets, regulations), public infrastructure (dams, canals, highways), and also 'external drivers' that influence the local economy (migration, population growth, national markets and policies). This paper describes the main model components, emphasizing similarities between human and biophysical components of the overall project, and the model's linkages and feedbacks relevant to our predictions of changes in water scarcity between now and 2100. Results presented include new insights from individual model components as well as available results from the integrated system model. Issues include water scarcity and water quality (temperature) for out-of-stream and instream uses, the impact of urban expansion on water use and potential flood damage. Changes in timing and variability of spring discharge with climate change, as well as changes in human uses of lands in flood-prone areas, will alter the tradeoff for the optimal use of reservoir storage capacity. We emphasize three concepts: i) institutions, ii) scarcity, and iii) the role of social science in projects of this kind. Institutions represent the main instrument or tool that humans use to influence how resources are used, to reduce waste, promote efficiency, and foster predictability. Water scarcity when defined in human normative terms. The concept provides a lens through which to recognize the wide range of ways that water scarcity can arise and persist even in water-abundant settings. We conclude with observations about the role of social science in research on biophysical and human systems. Reference Jaeger, W.K., et al., 2013. Toward a formal definition of water scarcity in natural-human systems. Water Resources Research, Volume 49. Published online: 8 JUL 2013 | DOI: 10.1002/wrcr.20249

Singularity now: using the ventricular assist device as a model for future human-robotic physiology.

PubMed

Martin, Archer K

2016-04-01

In our 21 st century world, human-robotic interactions are far more complicated than Asimov predicted in 1942. The future of human-robotic interactions includes human-robotic machine hybrids with an integrated physiology, working together to achieve an enhanced level of baseline human physiological performance. This achievement can be described as a biological Singularity. I argue that this time of Singularity cannot be met by current biological technologies, and that human-robotic physiology must be integrated for the Singularity to occur. In order to conquer the challenges we face regarding human-robotic physiology, we first need to identify a working model in today's world. Once identified, this model can form the basis for the study, creation, expansion, and optimization of human-robotic hybrid physiology. In this paper, I present and defend the line of argument that currently this kind of model (proposed to be named "IshBot") can best be studied in ventricular assist devices - VAD.

Singularity now: using the ventricular assist device as a model for future human-robotic physiology

PubMed Central

Martin, Archer K.

2016-01-01

In our 21st century world, human-robotic interactions are far more complicated than Asimov predicted in 1942. The future of human-robotic interactions includes human-robotic machine hybrids with an integrated physiology, working together to achieve an enhanced level of baseline human physiological performance. This achievement can be described as a biological Singularity. I argue that this time of Singularity cannot be met by current biological technologies, and that human-robotic physiology must be integrated for the Singularity to occur. In order to conquer the challenges we face regarding human-robotic physiology, we first need to identify a working model in today’s world. Once identified, this model can form the basis for the study, creation, expansion, and optimization of human-robotic hybrid physiology. In this paper, I present and defend the line of argument that currently this kind of model (proposed to be named “IshBot”) can best be studied in ventricular assist devices – VAD. PMID:28913480

On inclusion of water resource management in Earth system models - Part 1: Problem definition and representation of water demand

NASA Astrophysics Data System (ADS)

Nazemi, A.; Wheater, H. S.

2015-01-01

Human activities have caused various changes to the Earth system, and hence the interconnections between human activities and the Earth system should be recognized and reflected in models that simulate Earth system processes. One key anthropogenic activity is water resource management, which determines the dynamics of human-water interactions in time and space and controls human livelihoods and economy, including energy and food production. There are immediate needs to include water resource management in Earth system models. First, the extent of human water requirements is increasing rapidly at the global scale and it is crucial to analyze the possible imbalance between water demands and supply under various scenarios of climate change and across various temporal and spatial scales. Second, recent observations show that human-water interactions, manifested through water resource management, can substantially alter the terrestrial water cycle, affect land-atmospheric feedbacks and may further interact with climate and contribute to sea-level change. Due to the importance of water resource management in determining the future of the global water and climate cycles, the World Climate Research Program's Global Energy and Water Exchanges project (WRCP-GEWEX) has recently identified gaps in describing human-water interactions as one of the grand challenges in Earth system modeling (GEWEX, 2012). Here, we divide water resource management into two interdependent elements, related firstly to water demand and secondly to water supply and allocation. In this paper, we survey the current literature on how various components of water demand have been included in large-scale models, in particular land surface and global hydrological models. Issues of water supply and allocation are addressed in a companion paper. The available algorithms to represent the dominant demands are classified based on the demand type, mode of simulation and underlying modeling assumptions. We discuss the pros and cons of available algorithms, address various sources of uncertainty and highlight limitations in current applications. We conclude that current capability of large-scale models to represent human water demands is rather limited, particularly with respect to future projections and coupled land-atmospheric simulations. To fill these gaps, the available models, algorithms and data for representing various water demands should be systematically tested, intercompared and improved. In particular, human water demands should be considered in conjunction with water supply and allocation, particularly in the face of water scarcity and unknown future climate.

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.

Climate Change: Modeling the Human Response

NASA Astrophysics Data System (ADS)

Oppenheimer, M.; Hsiang, S. M.; Kopp, R. E.

2012-12-01

Integrated assessment models have historically relied on forward modeling including, where possible, process-based representations to project climate change impacts. Some recent impact studies incorporate the effects of human responses to initial physical impacts, such as adaptation in agricultural systems, migration in response to drought, and climate-related changes in worker productivity. Sometimes the human response ameliorates the initial physical impacts, sometimes it aggravates it, and sometimes it displaces it onto others. In these arenas, understanding of underlying socioeconomic mechanisms is extremely limited. Consequently, for some sectors where sufficient data has accumulated, empirically based statistical models of human responses to past climate variability and change have been used to infer response sensitivities which may apply under certain conditions to future impacts, allowing a broad extension of integrated assessment into the realm of human adaptation. We discuss the insights gained from and limitations of such modeling for benefit-cost analysis of climate change.

A physiologically based model for temporal envelope encoding in human primary auditory cortex.

PubMed

Dugué, Pierre; Le Bouquin-Jeannès, Régine; Edeline, Jean-Marc; Faucon, Gérard

2010-09-01

Communication sounds exhibit temporal envelope fluctuations in the low frequency range (<70 Hz) and human speech has prominent 2-16 Hz modulations with a maximum at 3-4 Hz. Here, we propose a new phenomenological model of the human auditory pathway (from cochlea to primary auditory cortex) to simulate responses to amplitude-modulated white noise. To validate the model, performance was estimated by quantifying temporal modulation transfer functions (TMTFs). Previous models considered either the lower stages of the auditory system (up to the inferior colliculus) or only the thalamocortical loop. The present model, divided in two stages, is based on anatomical and physiological findings and includes the entire auditory pathway. The first stage, from the outer ear to the colliculus, incorporates inhibitory interneurons in the cochlear nucleus to increase performance at high stimuli levels. The second stage takes into account the anatomical connections of the thalamocortical system and includes the fast and slow excitatory and inhibitory currents. After optimizing the parameters of the model to reproduce the diversity of TMTFs obtained from human subjects, a patient-specific model was derived and the parameters were optimized to effectively reproduce both spontaneous activity and the oscillatory part of the evoked response. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Modeling Visual, Vestibular and Oculomotor Interactions in Self-Motion Estimation

NASA Technical Reports Server (NTRS)

Perrone, John

1997-01-01

A computational model of human self-motion perception has been developed in collaboration with Dr. Leland S. Stone at NASA Ames Research Center. The research included in the grant proposal sought to extend the utility of this model so that it could be used for explaining and predicting human performance in a greater variety of aerospace applications. This extension has been achieved along with physiological validation of the basic operation of the model.

Finding mouse models of human lymphomas and leukemia's using the Jackson laboratory mouse tumor biology database.

PubMed

Begley, Dale A; Sundberg, John P; Krupke, Debra M; Neuhauser, Steven B; Bult, Carol J; Eppig, Janan T; Morse, Herbert C; Ward, Jerrold M

2015-12-01

Many mouse models have been created to study hematopoietic cancer types. There are over thirty hematopoietic tumor types and subtypes, both human and mouse, with various origins, characteristics and clinical prognoses. Determining the specific type of hematopoietic lesion produced in a mouse model and identifying mouse models that correspond to the human subtypes of these lesions has been a continuing challenge for the scientific community. The Mouse Tumor Biology Database (MTB; http://tumor.informatics.jax.org) is designed to facilitate use of mouse models of human cancer by providing detailed histopathologic and molecular information on lymphoma subtypes, including expertly annotated, on line, whole slide scans, and providing a repository for storing information on and querying these data for specific lymphoma models. Copyright © 2015 Elsevier Inc. All rights reserved.

Overview | Office of Cancer Genomics

Cancer.gov

The Human Cancer Model Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models with associated genomic and clinical data. The HCMI consortium includes the US-National Cancer Institute, part of the National Institutes of Health, Cancer Research UK, foundation Hubrecht Organoid Technology, and Wellcome Sanger Institute. The goal of HCMI is to create up to one thousand cancer models from patient tumors.

Single unit approaches to human vision and memory.

PubMed

Kreiman, Gabriel

2007-08-01

Research on the visual system focuses on using electrophysiology, pharmacology and other invasive tools in animal models. Non-invasive tools such as scalp electroencephalography and imaging allow examining humans but show a much lower spatial and/or temporal resolution. Under special clinical conditions, it is possible to monitor single-unit activity in humans when invasive procedures are required due to particular pathological conditions including epilepsy and Parkinson's disease. We review our knowledge about the visual system and visual memories in the human brain at the single neuron level. The properties of the human brain seem to be broadly compatible with the knowledge derived from animal models. The possibility of examining high-resolution brain activity in conscious human subjects allows investigators to ask novel questions that are challenging to address in animal models.

Roughing in Human Replumbing of the Water Cycle: Challenges, Opportunities, and Progress in Capturing the Influence of Water Management in Regional Models of Hydrology and Climate

NASA Astrophysics Data System (ADS)

Flores, A. N.; Kaiser, K. E.; Steimke, A.; Leonard, A.; FitzGerald, K.; Benner, S. G.; Vache, K. B.; Hillis, V.; Bolte, J.; Han, B.

2017-12-01

Humans exert tremendous influence on the redistribution of water in space and time. Humans have developed substantial infrastructure to provide water in adequate quantity and quality for production of food and energy, while seeking to maintain landscape processes and properties giving rise to ecosystem services on which humans rely (even when and if they are not well understood). Cyber-physical infrastructure includes dams, distributary canal networks, ditches to manage return flow, and networks of sensors to monitor environmental conditions. Social infrastructure includes legal frameworks for water rights, governance networks, and land management policies aimed at maintaining water quality. Changes in regional climate, land use and its intensity, and land cover in source areas exert pressures on this infrastructure, requiring models to characterize system-wide vulnerability and resilience. Here we present a synthesis of several ongoing and completed studies aimed at advancing our fundamental understanding of and ability to numerically model a system in which biophysical and human components cannot be separated. These studies are set within the Boise and Snake River Basin in the US Pacific Northwest and are organized around the aims of: (1) developing improved understanding and models of the ways that humans interact with each other and with biophysical processes at a range of spatiotemporal scales, and (2) using those models to predict how changes in climate and societal drivers, including in-migration and shifts in agricultural practices, will impact regional hydroclimate and associated ecosystem services. Key findings indicate differential pressures on water availability based on water rights seniority within the Lower Boise River basin under historical conditions, the potential for significantly earlier curtailment of water rights in future decades, and potential changes in agricultural practices in anticipation of future climate changes. This ongoing suite of projects illustrate significant improvements in modeling human modification of the timing and partitioning of hydrologic fluxes. Important challenges and opportunities remain, however, particularly in improving modeling the interactions between and among actors that exert controls on the redistribution of water.

Integration of systems biology with organs-on-chips to humanize therapeutic development

NASA Astrophysics Data System (ADS)

Edington, Collin D.; Cirit, Murat; Chen, Wen Li Kelly; Clark, Amanda M.; Wells, Alan; Trumper, David L.; Griffith, Linda G.

2017-02-01

"Mice are not little people" - a refrain becoming louder as the gaps between animal models and human disease become more apparent. At the same time, three emerging approaches are headed toward integration: powerful systems biology analysis of cell-cell and intracellular signaling networks in patient-derived samples; 3D tissue engineered models of human organ systems, often made from stem cells; and micro-fluidic and meso-fluidic devices that enable living systems to be sustained, perturbed and analyzed for weeks in culture. Integration of these rapidly moving fields has the potential to revolutionize development of therapeutics for complex, chronic diseases, including those that have weak genetic bases and substantial contributions from gene-environment interactions. Technical challenges in modeling complex diseases with "organs on chips" approaches include the need for relatively large tissue masses and organ-organ cross talk to capture systemic effects, such that current microfluidic formats often fail to capture the required scale and complexity for interconnected systems. These constraints drive development of new strategies for designing in vitro models, including perfusing organ models, as well as "mesofluidic" pumping and circulation in platforms connecting several organ systems, to achieve the appropriate physiological relevance.

Selection of animal models for pre-clinical strategies in evaluating the fracture healing, bone graft substitutes and bone tissue regeneration and engineering.

PubMed

Bigham-Sadegh, Amin; Oryan, Ahmad

2015-06-01

In vitro assays can be useful in determining biological mechanism and optimizing scaffold parameters, however translation of the in vitro results to clinics is generally hard. Animal experimentation is a better approximation than in vitro tests, and usage of animal models is often essential in extrapolating the experimental results and translating the information in a human clinical setting. In addition, usage of animal models to study fracture healing is useful to answer questions related to the most effective method to treat humans. There are several factors that should be considered when selecting an animal model. These include availability of the animal, cost, ease of handling and care, size of the animal, acceptability to society, resistance to surgery, infection and disease, biological properties analogous to humans, bone structure and composition, as well as bone modeling and remodeling characteristics. Animal experiments on bone healing have been conducted on small and large animals, including mice, rats, rabbits, dogs, pigs, goats and sheep. This review also describes the molecular events during various steps of fracture healing and explains different means of fracture healing evaluation including biomechanical, histopathological and radiological assessments.

Rasmussen's legacy: A paradigm change in engineering for safety.

PubMed

Leveson, Nancy G

2017-03-01

This paper describes three applications of Rasmussen's idea to systems engineering practice. The first is the application of the abstraction hierarchy to engineering specifications, particularly requirements specification. The second is the use of Rasmussen's ideas in safety modeling and analysis to create a new, more powerful type of accident causation model that extends traditional models to better handle human-operated, software-intensive, sociotechnical systems. Because this new model has a formal, mathematical foundation built on systems theory (as was Rasmussen's original model), new modeling and analysis tools become possible. The third application is to engineering hazard analysis. Engineers have traditionally either omitted human from consideration in system hazard analysis or have treated them rather superficially, for example, that they behave randomly. Applying Rasmussen's model of human error to a powerful new hazard analysis technique allows human behavior to be included in engineering hazard analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Model of visual contrast gain control and pattern masking

NASA Technical Reports Server (NTRS)

Watson, A. B.; Solomon, J. A.

1997-01-01

We have implemented a model of contrast gain and control in human vision that incorporates a number of key features, including a contrast sensitivity function, multiple oriented bandpass channels, accelerating nonlinearities, and a devisive inhibitory gain control pool. The parameters of this model have been optimized through a fit to the recent data that describe masking of a Gabor function by cosine and Gabor masks [J. M. Foley, "Human luminance pattern mechanisms: masking experiments require a new model," J. Opt. Soc. Am. A 11, 1710 (1994)]. The model achieves a good fit to the data. We also demonstrate how the concept of recruitment may accommodate a variant of this model in which excitatory and inhibitory paths have a common accelerating nonlinearity, but which include multiple channels tuned to different levels of contrast.

Generalized Beer-Lambert model for near-infrared light propagation in thick biological tissues

NASA Astrophysics Data System (ADS)

Bhatt, Manish; Ayyalasomayajula, Kalyan R.; Yalavarthy, Phaneendra K.

2016-07-01

The attenuation of near-infrared (NIR) light intensity as it propagates in a turbid medium like biological tissue is described by modified the Beer-Lambert law (MBLL). The MBLL is generally used to quantify the changes in tissue chromophore concentrations for NIR spectroscopic data analysis. Even though MBLL is effective in terms of providing qualitative comparison, it suffers from its applicability across tissue types and tissue dimensions. In this work, we introduce Lambert-W function-based modeling for light propagation in biological tissues, which is a generalized version of the Beer-Lambert model. The proposed modeling provides parametrization of tissue properties, which includes two attenuation coefficients μ0 and η. We validated our model against the Monte Carlo simulation, which is the gold standard for modeling NIR light propagation in biological tissue. We included numerous human and animal tissues to validate the proposed empirical model, including an inhomogeneous adult human head model. The proposed model, which has a closed form (analytical), is first of its kind in providing accurate modeling of NIR light propagation in biological tissues.

What did the Romans ever do for us? Putting humans in global land models

NASA Astrophysics Data System (ADS)

Bierkens, M. F.; Wada, Y.; Dermody, B.; Van Beek, L. P.

2016-12-01

During the late 1980s and early 1990s, awareness of the shortage of global water resources lead to the first detailed global water resources assessments using regional statistics of water use and observations of meteorological and hydrological variables. Shortly thereafter, the first macroscale hydrological models (MHM) appeared. In these models, blue water (i.e., surface water and renewable groundwater) availability was calculated by accumulating runoff over a stream network and comparing it with population densities or with estimated water demand for agriculture, industry and households. In this talk we review the evolution of human impact modelling in global land models with a focus on global water resources, touching upon developments of the last 15 years: i.e. calculating human water scarcity; estimating groundwater depletion; adding dams and reservoirs; fully integrating water use (abstraction, application, consumption, return flow) in the hydrology; simulating the effects of land use change. We identify four major challenges that hamper the further development of integrated water resources modelling and thus prohibit realistic projections of the future terrestrial water cycle in the Anthropocene. These are: 1) including the ability to model infrastructural changes and measures; 2) projecting future water demand and water use and associated measures; 3) including virtual water trade; 4) including land use change and landscape change. While all these challenges will likely benefit from hydro-economics and the newly developing field of socio-hydrology, we also show that especially for challenges 3 and 4 lessons can be drawn from the (pre)historic past. To make this point we provide two case studies: one modelling the virtual water trade in the Roman Empire and one modelling human-landscape interaction in prehistoric Calabria (Italy).

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.

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.

Air Force Research Laboratory Warfighter Readiness Research Division Participation in the 2008 IITSEC

DTIC Science & Technology

2008-12-15

of the underlying behaviors that led to each element being cited. The AFSC Human Factors Database listed all human factors cited in the Life...situations of increased pressure. Through an understanding of the causal factors of human behavior , and by analysis of one’s own behavioral patterns...JTAC training and overall lessons learned from modeling and simulation of the JTAC environment to include behavior scripting, artillery models

Bone Research and Animal Support of Human Space Exploration: Where do we go from here?

NASA Technical Reports Server (NTRS)

Morey-Holton, Emily R.

2004-01-01

NASA exploration goals include returning humans to the moon by 20 15-2020 as a prelude for human exploration of Mars and beyond. The number of human flight subjects available during this very short time period is insufficient to solve high-risk problems without data from animals. This presentation will focus on three questions: What do we know? What do we need to know? Where do we go from here?: roles for animals in the exploration era. Answers to these questions are based on flight and ground-based models using humans and animals. First, what do we know? Adult humans have spent less than 1% of their lifespan in space while juvenile rats have spent almost 2%. This information suggests that our data are rather meager for projecting to a 30-month mission to Mars. The space platforms for humans have included Skylab, STS/MIR, and STS/ISS and for animals have included the unmanned Bion series and shuttle. The ground-based models include head-down bedrest in humans (BR) and hindlimb unloading in rodents (HU). We know that as gravity decreases, the impact forces generated by the body during locomotion decrease. For example, on Earth, your legs supports approximately 1 body weight (BW) when standing, 1.33BW when walking, and 3BW when jogging. On Mars, the same activity would generate 0.38BW standing, 0.5BW walking, and 1BW when jogging. In space, no impact load is generated, as gravity is minimal.

Development of Four Dimensional Human Model that Enables Deformation of Skin, Organs and Blood Vessel System During Body Movement - Visualizing Movements of the Musculoskeletal System.

PubMed

Suzuki, Naoki; Hattori, Asaki; Hashizume, Makoto

2016-01-01

We constructed a four dimensional human model that is able to visualize the structure of a whole human body, including the inner structures, in real-time to allow us to analyze human dynamic changes in the temporal, spatial and quantitative domains. To verify whether our model was generating changes according to real human body dynamics, we measured a participant's skin expansion and compared it to that of the model conducted under the same body movement. We also made a contribution to the field of orthopedics, as we were able to devise a display method that enables the observer to more easily observe the changes made in the complex skeletal muscle system during body movements, which in the past were difficult to visualize.

What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? Reevaluating the Potential of Mouse Models for the Human Immune System.

PubMed

Jameson, Stephen C; Masopust, David

2018-04-02

Much of what we understand about immunology, including the response to vaccines, come from studies in mice because they provide many practical advantages compared with research in higher mammals and humans. Nevertheless, modalities for preventing or treating disease do not always translate from mouse to humans, which has led to increasing scrutiny of the continued merits of mouse research. Here, we summarize the pros and cons of current laboratory mouse models for immunology research and discuss whether overreliance on nonphysiological, ultra-hygienic animal husbandry approaches has limited the ultimate translation potential of mouse-derived data to humans. Alternative approaches are discussed that may extend the use of the mouse model for preclinical studies. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Digital evaluation of sitting posture comfort in human-vehicle system under Industry 4.0 framework

NASA Astrophysics Data System (ADS)

Tao, Qing; Kang, Jinsheng; Sun, Wenlei; Li, Zhaobo; Huo, Xiao

2016-09-01

Most of the previous studies on the vibration ride comfort of the human-vehicle system were focused only on one or two aspects of the investigation. A hybrid approach which integrates all kinds of investigation methods in real environment and virtual environment is described. The real experimental environment includes the WBV(whole body vibration) test, questionnaires for human subjective sensation and motion capture. The virtual experimental environment includes the theoretical calculation on simplified 5-DOF human body vibration model, the vibration simulation and analysis within ADAMS/VibrationTM module, and the digital human biomechanics and occupational health analysis in Jack software. While the real experimental environment provides realistic and accurate test results, it also serves as core and validation for the virtual experimental environment. The virtual experimental environment takes full advantages of current available vibration simulation and digital human modelling software, and makes it possible to evaluate the sitting posture comfort in a human-vehicle system with various human anthropometric parameters. How this digital evaluation system for car seat comfort design is fitted in the Industry 4.0 framework is also proposed.

Multilayer limb quasi-static electromagnetic modeling with experiments for Galvanic coupling type IBC.

PubMed

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

2010-01-01

Intra-body communication (IBC) is a new, emerging, short-range and human body based communication methodology. It is a technique to network various devices on human body, by utilizing the conducting properties of human tissues. For currently fast developed Body area network(BAN)/Body sensor network(BSN), IBC is believed to have advantages in power consumption, electromagnetic radiation, interference from external electromagnetic noise, security, and restriction in spectrum resource. In this article, the authors propose an improved mathematical model, which includes both electrical properties and proportion of human tissues, for IBC on a human limb. By solving the mathematical model analytically on four-layer system (skin, fat, muscle, and bone) and conducting in-vivo experiment, a comparison has been conducted.

HCMI Research Goals

Cancer.gov

NCI-funded Cancer Model Development Centers (CMDCs) and the Human Cancer Models Initiative (HCMI) consortium members are creating as many as 1000 new cancer models. The models are being derived from many tumor subtypes, including rare and understudied cancers.

Human hepatocytes derived from pluripotent stem cells: a promising cell model for drug hepatotoxicity screening.

PubMed

Gómez-Lechón, María José; Tolosa, Laia

2016-09-01

Drug-induced liver injury (DILI) is a frequent cause of failure in both clinical and post-approval stages of drug development, and poses a key challenge to the pharmaceutical industry. Current animal models offer poor prediction of human DILI. Although several human cell-based models have been proposed for the detection of human DILI, human primary hepatocytes remain the gold standard for preclinical toxicological screening. However, their use is hindered by their limited availability, variability and phenotypic instability. In contrast, pluripotent stem cells, which include embryonic and induced pluripotent stem cells (iPSCs), proliferate extensively in vitro and can be differentiated into hepatocytes by the addition of soluble factors. This provides a stable source of hepatocytes for multiple applications, including early preclinical hepatotoxicity screening. In addition, iPSCs also have the potential to establish genotype-specific cells from different individuals, which would increase the predictivity of toxicity assays allowing more successful clinical trials. Therefore, the generation of human hepatocyte-like cells derived from pluripotent stem cells seems to be promising for overcoming limitations of hepatocyte preparations, and it is expected to have a substantial repercussion in preclinical hepatotoxicity risk assessment in early drug development stages.

Model-based metrics of human-automation function allocation in complex work environments

NASA Astrophysics Data System (ADS)

Kim, So Young

Function allocation is the design decision which assigns work functions to all agents in a team, both human and automated. Efforts to guide function allocation systematically has been studied in many fields such as engineering, human factors, team and organization design, management science, and cognitive systems engineering. Each field focuses on certain aspects of function allocation, but not all; thus, an independent discussion of each does not address all necessary issues with function allocation. Four distinctive perspectives emerged from a review of these fields: technology-centered, human-centered, team-oriented, and work-oriented. Each perspective focuses on different aspects of function allocation: capabilities and characteristics of agents (automation or human), team structure and processes, and work structure and the work environment. Together, these perspectives identify the following eight issues with function allocation: 1) Workload, 2) Incoherency in function allocations, 3) Mismatches between responsibility and authority, 4) Interruptive automation, 5) Automation boundary conditions, 6) Function allocation preventing human adaptation to context, 7) Function allocation destabilizing the humans' work environment, and 8) Mission Performance. Addressing these issues systematically requires formal models and simulations that include all necessary aspects of human-automation function allocation: the work environment, the dynamics inherent to the work, agents, and relationships among them. Also, addressing these issues requires not only a (static) model, but also a (dynamic) simulation that captures temporal aspects of work such as the timing of actions and their impact on the agent's work. Therefore, with properly modeled work as described by the work environment, the dynamics inherent to the work, agents, and relationships among them, a modeling framework developed by this thesis, which includes static work models and dynamic simulation, can capture the issues with function allocation. Then, based on the eight issues, eight types of metrics are established. The purpose of these metrics is to assess the extent to which each issue exists with a given function allocation. Specifically, the eight types of metrics assess workload, coherency of a function allocation, mismatches between responsibility and authority, interruptive automation, automation boundary conditions, human adaptation to context, stability of the human's work environment, and mission performance. Finally, to validate the modeling framework and the metrics, a case study was conducted modeling four different function allocations between a pilot and flight deck automation during the arrival and approach phases of flight. A range of pilot cognitive control modes and maximum human taskload limits were also included in the model. The metrics were assessed for these four function allocations and analyzed to validate capability of the metrics to identify important issues in given function allocations. In addition, the design insights provided by the metrics are highlighted. This thesis concludes with a discussion of mechanisms for further validating the modeling framework and function allocation metrics developed here, and highlights where these developments can be applied in research and in the design of function allocations in complex work environments such as aviation operations.

Effect of clothing material on thermal responses of the human body

NASA Astrophysics Data System (ADS)

Fengzhi, Li; Yi, Li

2005-09-01

The influence of clothing material on thermal responses of the human body are investigated by using an integrated model of a clothed thermoregulatory human body. A modified 25-nodes model considering the sweat accumulation on the skin surface is applied to simulate the human physiological regulatory responses. The heat and moisture coupled transfer mechanisms, including water vapour diffusion, the moisture evaporation/condensation, the moisture sorbtion/desorption by fibres, liquid sweat transfer under capillary pressure, and latent heat absorption/release due to phase change, are considered in the clothing model. On comparing prediction results with the experimental data in the literature, the proposed model seems able to predict dynamic heat and moisture transfer between the human body and the clothing system. The human body's thermal responses and clothing temperature and moisture variations are compared for different clothing materials during transient periods. We concluded that the hygroscopicity of clothing materials influences the human thermoregulation process significantly during environmental transients.

Utility of arterial blood gas, CBC, biochemistry and cardiac hormones as evaluation parameters of cardiovascular disease in nonhuman primates.

PubMed

Nakayama, Shunya; Koie, Hiroshi; Kanayama, Kiichi; Katakai, Yuko; Ito-Fujishiro, Yasuyo; Sankai, Tadashi; Yasutomi, Yasuhiro; Ageyama, Naohide

2018-06-11

Cardiovascular disease (CVD) has a tremendous impact on the quality of life of humans. While experimental animals are valuable to medical research as models of human diseases, cardiac systems differ widely across various animal species. Thus, we examined a CVD model in cynomolgus monkeys. Laboratory primates are precious resources, making it imperative that symptoms of diseases and disorders are detected as early as possible. Thus, in this study we comprehensively examined important indicators of CVD in cynomolgus monkeys, including arterial blood gas, complete blood count (CBC), biochemistry, and cardiac hormones. The control group included 20 healthy macaques showing non-abnormal findings in screening tests, whereas the CVD group included 20 macaques with valvular disease and cardiomyopathy. An increase of red blood cell distribution width was observed in the CBC, indicating chronic inflammation related to CVD. An increase of HCO 3 was attributed to the correction of acidosis. Furthermore, development of the CVD model was supported by significant increases in natriuretic peptides. It is suggested that these results indicated a correlation between human CVD and the model in monkeys. Moreover, blood tests including arterial blood gas are non-invasive and can be performed more easily than other technical tests. CVD affected animals easily change their condition by anesthesia and surgical invasion. Pay attention to arterial blood gas and proper respond to their condition are important for research. This data may facilitate human research and aid in the management and veterinary care of nonhuman primates.

Integrated Earth System Model (iESM)

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

Thornton, Peter Edmond; Mao, Jiafu; Shi, Xiaoying

2016-12-02

The iESM is a simulation code that represents the physical and biological aspects of Earth's climate system, and also includes the macro-economic and demographic properties of human societies. The human aspect of the simulation code is focused in particular on the effects of human activities on land use and land cover change, but also includes aspects such as energy economies. The time frame for predictions with iESM is approximately 1970 through 2100.

Canine and Feline Models of Human Genetic Diseases and Their Contributions to Advancing Clinical Therapies
.

PubMed

Gurda, Brittney L; Bradbury, Allison M; Vite, Charles H

2017-09-01

For many lethal or debilitating genetic disorders in patients there are no satisfactory therapies. Several barriers exist that hinder the developments of effective therapies including the limited availability of clinically relevant animal models that faithfully recapitulate human genetic disease. In 1974, the Referral Center for Animal Models of Human Genetic Disease (RCAM) was established by Dr. Donald F. Patterson and continued by Dr. Mark E. Haskins at the University of Pennsylvania with the mission to discover, understand, treat, and maintain breeding colonies of naturally occurring hereditary disorders in dogs and cats that are orthologous to those found in human patients. Although non-human primates, sheep, and pig models are also available within the medical community, naturally occurring diseases are rarely identified in non-human primates, and the vast behavioral, clinicopathological, physiological, and anatomical knowledge available regarding dogs and cats far surpasses what is available in ovine and porcine species. The canine and feline models that are maintained at RCAM are presented here with a focus on preclinical therapy data. Clinical studies that have been generated from preclinical work in these models are also presented.

Cross-species transmission of CWD prions.

PubMed

Kurt, Timothy D; Sigurdson, Christina J

2016-01-01

Prions cause fatal neurodegenerative diseases in humans and animals and can be transmitted zoonotically. Chronic wasting disease (CWD) is a highly transmissible prion disease of wild deer and elk that affects cervids over extensive regions of the United States and Canada. The risk of cross-species CWD transmission has been experimentally evaluated in a wide array of mammals, including non-human primates and mouse models expressing human cellular prion protein. Here we review the determinants of cross-species CWD transmission, and propose a model that may explain a structural barrier for CWD transmission to humans.

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

M. A. Wasiolek

The purpose of this report is to document the biosphere model, the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), which describes radionuclide transport processes in the biosphere and associated human exposure that may arise as the result of radionuclide release from the geologic repository at Yucca Mountain. The biosphere model is one of the process models that support the Yucca Mountain Project (YMP) Total System Performance Assessment (TSPA) for the license application (LA), the TSPA-LA. The ERMYN model provides the capability of performing human radiation dose assessments. This report documents the biosphere model, which includes: (1) Describing the referencemore » biosphere, human receptor, exposure scenarios, and primary radionuclides for each exposure scenario (Section 6.1); (2) Developing a biosphere conceptual model using site-specific features, events, and processes (FEPs), the reference biosphere, the human receptor, and assumptions (Section 6.2 and Section 6.3); (3) Building a mathematical model using the biosphere conceptual model and published biosphere models (Sections 6.4 and 6.5); (4) Summarizing input parameters for the mathematical model, including the uncertainty associated with input values (Section 6.6); (5) Identifying improvements in the ERMYN model compared with the model used in previous biosphere modeling (Section 6.7); (6) Constructing an ERMYN implementation tool (model) based on the biosphere mathematical model using GoldSim stochastic simulation software (Sections 6.8 and 6.9); (7) Verifying the ERMYN model by comparing output from the software with hand calculations to ensure that the GoldSim implementation is correct (Section 6.10); and (8) Validating the ERMYN model by corroborating it with published biosphere models; comparing conceptual models, mathematical models, and numerical results (Section 7).« less

Simulation-Based Mission Rehearsal as a Human Activity System.

DTIC Science & Technology

1996-09-01

explain this demonstrated importance of the people involved in MR, a human activity system model of simulation-based rehearsal was developed. It provides...Implications of this human activity system view are discussed, including: places in the mission preparation process where simulation can benefit operations

Xenobiotic-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models.

PubMed

Oesch, F; Fabian, E; Guth, K; Landsiedel, R

2014-12-01

The exposure of the skin to medical drugs, skin care products, cosmetics, and other chemicals renders information on xenobiotic-metabolizing enzymes (XME) in the skin highly interesting. Since the use of freshly excised human skin for experimental investigations meets with ethical and practical limitations, information on XME in models comes in the focus including non-human mammalian species and in vitro skin models. This review attempts to summarize the information available in the open scientific literature on XME in the skin of human, rat, mouse, guinea pig, and pig as well as human primary skin cells, human cell lines, and reconstructed human skin models. The most salient outcome is that much more research on cutaneous XME is needed for solid metabolism-dependent efficacy and safety predictions, and the cutaneous metabolism comparisons have to be viewed with caution. Keeping this fully in mind at least with respect to some cutaneous XME, some models may tentatively be considered to approximate reasonable closeness to human skin. For dermal absorption and for skin irritation among many contributing XME, esterase activity is of special importance, which in pig skin, some human cell lines, and reconstructed skin models appears reasonably close to human skin. With respect to genotoxicity and sensitization, activating XME are not yet judgeable, but reactive metabolite-reducing XME in primary human keratinocytes and several reconstructed human skin models appear reasonably close to human skin. For a more detailed delineation and discussion of the severe limitations see the "Overview and Conclusions" section in the end of this review.

Pathogen survival trajectories: an eco-environmental approach to the modeling of human campylobacteriosis ecology.

PubMed Central

Skelly, Chris; Weinstein, Phil

2003-01-01

Campylobacteriosis, like many human diseases, has its own ecology in which the propagation of human infection and disease depends on pathogen survival and finding new hosts in order to replicate and sustain the pathogen population. The complexity of this process, a process common to other enteric pathogens, has hampered control efforts. Many unknowns remain, resulting in a poorly understood disease ecology. To provide structure to these unknowns and help direct further research and intervention, we propose an eco-environmental modeling approach for campylobacteriosis. This modeling approach follows the pathogen population as it moves through the environments that define the physical structure of its ecology. In this paper, we term the ecologic processes and environments through which these populations move "pathogen survival trajectories." Although such a modeling approach could have veterinary applications, our emphasis is on human campylobacteriosis and focuses on human exposures to Campylobacter through feces, food, and aquatic environments. The pathogen survival trajectories that lead to human exposure include ecologic filters that limit population size, e.g., cooking food to kill Campylobacter. Environmental factors that influence the size of the pathogen reservoirs include temperature, nutrient availability, and moisture availability during the period of time the pathogen population is moving through the environment between infected and susceptible hosts. We anticipate that the modeling approach proposed here will work symbiotically with traditional epidemiologic and microbiologic research to help guide and evaluate the acquisition of new knowledge about the ecology, eventual intervention, and control of campylobacteriosis. PMID:12515674

An expanded One Health model: integrating social science and One Health to inform study of the human-animal interface.

PubMed

Woldehanna, Sara; Zimicki, Susan

2015-03-01

Zoonotic disease emergence is not a purely biological process mediated only by ecologic factors; opportunities for transmission of zoonoses from animals to humans also depend on how people interact with animals. While exposure is conditioned by the type of animal and the location in which interactions occur, these in turn are influenced by human activity. The activities people engage in are determined by social as well as contextual factors including gender, age, socio-economic status, occupation, social norms, settlement patterns and livelihood systems, family and community dynamics, as well as national and global influences. This paper proposes an expanded "One Health" conceptual model for human-animal exposure that accounts for social as well as epidemiologic factors. The expanded model informed a new study approach to document the extent of human exposure to animals and explore the interplay of social and environmental factors that influence risk of transmission at the individual and community level. The approach includes a formative phase using qualitative and participatory methods, and a representative, random sample survey to quantify exposure to animals in a variety of settings. The paper discusses the different factors that were considered in developing the approach, including the range of animals asked about and the parameters of exposure that are included, as well as factors to be considered in local adaptation of the generic instruments. Illustrative results from research using this approach in Lao PDR are presented to demonstrate the effect of social factors on how people interact with animals. We believe that the expanded model can be similarly operationalized to explore the interactions of other social and policy-level determinants that may influence transmission of zoonoses. Copyright © 2014 Elsevier Ltd. All rights reserved.

A new approach to modelling schistosomiasis transmission based on stratified worm burden.

PubMed

Gurarie, D; King, C H; Wang, X

2010-11-01

Multiple factors affect schistosomiasis transmission in distributed meta-population systems including age, behaviour, and environment. The traditional approach to modelling macroparasite transmission often exploits the 'mean worm burden' (MWB) formulation for human hosts. However, typical worm distribution in humans is overdispersed, and classic models either ignore this characteristic or make ad hoc assumptions about its pattern (e.g., by assuming a negative binomial distribution). Such oversimplifications can give wrong predictions for the impact of control interventions. We propose a new modelling approach to macro-parasite transmission by stratifying human populations according to worm burden, and replacing MWB dynamics with that of 'population strata'. We developed proper calibration procedures for such multi-component systems, based on typical epidemiological and demographic field data, and implemented them using Wolfram Mathematica. Model programming and calibration proved to be straightforward. Our calibrated system provided good agreement with the individual level field data from the Msambweni region of eastern Kenya. The Stratified Worm Burden (SWB) approach offers many advantages, in that it accounts naturally for overdispersion and accommodates other important factors and measures of human infection and demographics. Future work will apply this model and methodology to evaluate innovative control intervention strategies, including expanded drug treatment programmes proposed by the World Health Organization and its partners.

Finding the rhythm of sudden cardiac death: new opportunities using induced pluripotent stem cell-derived cardiomyocytes.

PubMed

Sallam, Karim; Li, Yingxin; Sager, Philip T; Houser, Steven R; Wu, Joseph C

2015-06-05

Sudden cardiac death is a common cause of death in patients with structural heart disease, genetic mutations, or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with sudden cardiac death. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology, including ion channel expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single-ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell-derived cardiomyocytes resemble, but are not identical, adult human cardiomyocytes and provide a new platform for studying arrhythmic disorders leading to sudden cardiac death. A variety of platforms exist to phenotype cellular models, including conventional and automated patch clamp, multielectrode array, and computational modeling. Induced pluripotent stem cell-derived cardiomyocytes have been used to study long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and other hereditary cardiac disorders. Although induced pluripotent stem cell-derived cardiomyocytes are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of sudden cardiac death. © 2015 American Heart Association, Inc.

Model of human visual-motion sensing

NASA Technical Reports Server (NTRS)

Watson, A. B.; Ahumada, A. J., Jr.

1985-01-01

A model of how humans sense the velocity of moving images is proposed. The model exploits constraints provided by human psychophysics, notably that motion-sensing elements appear tuned for two-dimensional spatial frequency, and by the frequency spectrum of a moving image, namely, that its support lies in the plane in which the temporal frequency equals the dot product of the spatial frequency and the image velocity. The first stage of the model is a set of spatial-frequency-tuned, direction-selective linear sensors. The temporal frequency of the response of each sensor is shown to encode the component of the image velocity in the sensor direction. At the second stage, these components are resolved in order to measure the velocity of image motion at each of a number of spatial locations and spatial frequencies. The model has been applied to several illustrative examples, including apparent motion, coherent gratings, and natural image sequences. The model agrees qualitatively with human perception.

Generation and use of human 3D-CAD models

NASA Astrophysics Data System (ADS)

Grotepass, Juergen; Speyer, Hartmut; Kaiser, Ralf

2002-05-01

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

Recognition of human activity characteristics based on state transitions modeling technique

NASA Astrophysics Data System (ADS)

Elangovan, Vinayak; Shirkhodaie, Amir

2012-06-01

Human Activity Discovery & Recognition (HADR) is a complex, diverse and challenging task but yet an active area of ongoing research in the Department of Defense. By detecting, tracking, and characterizing cohesive Human interactional activity patterns, potential threats can be identified which can significantly improve situation awareness, particularly, in Persistent Surveillance Systems (PSS). Understanding the nature of such dynamic activities, inevitably involves interpretation of a collection of spatiotemporally correlated activities with respect to a known context. In this paper, we present a State Transition model for recognizing the characteristics of human activities with a link to a prior contextbased ontology. Modeling the state transitions between successive evidential events determines the activities' temperament. The proposed state transition model poses six categories of state transitions including: Human state transitions of Object handling, Visibility, Entity-entity relation, Human Postures, Human Kinematics and Distance to Target. The proposed state transition model generates semantic annotations describing the human interactional activities via a technique called Casual Event State Inference (CESI). The proposed approach uses a low cost kinect depth camera for indoor and normal optical camera for outdoor monitoring activities. Experimental results are presented here to demonstrate the effectiveness and efficiency of the proposed technique.

Fast hierarchical knowledge-based approach for human face detection in color images

NASA Astrophysics Data System (ADS)

Jiang, Jun; Gong, Jie; Zhang, Guilin; Hu, Ruolan

2001-09-01

This paper presents a fast hierarchical knowledge-based approach for automatically detecting multi-scale upright faces in still color images. The approach consists of three levels. At the highest level, skin-like regions are determinated by skin model, which is based on the color attributes hue and saturation in HSV color space, as well color attributes red and green in normalized color space. In level 2, a new eye model is devised to select human face candidates in segmented skin-like regions. An important feature of the eye model is that it is independent of the scale of human face. So it is possible for finding human faces in different scale with scanning image only once, and it leads to reduction the computation time of face detection greatly. In level 3, a human face mosaic image model, which is consistent with physical structure features of human face well, is applied to judge whether there are face detects in human face candidate regions. This model includes edge and gray rules. Experiment results show that the approach has high robustness and fast speed. It has wide application perspective at human-computer interactions and visual telephone etc.

A coupled human-water system from a systems dynamics perspective

NASA Astrophysics Data System (ADS)

Kuil, Linda; Blöschl, Günter; Carr, Gemma

2013-04-01

Traditionally, models used in hydrological studies have frequently assumed stationarity. Moreover, human-induced water resources management activities are often included as external forcings in water cycle dynamics. However, considering humans' current impact on the water cycle in terms of a growing population, river basins increasingly being managed and a climate considerably changing, it has recently been questioned whether this is still correct. Furthermore, research directed at the evolution of water resources and society has shown that the components constituting the human-water system are changing interdependently. Goal of this study is therefore to approach water cycle dynamics from an integrated perspective in which humans are considered as endogenous forces to the system. The method used to model a coupled, urban human-water system is system dynamics. In system dynamics, particular emphasis is placed on feedback loops resulting in dynamic behavior. Time delays and non-linearity can relatively easily be included, making the method appropriate for studying complex systems that change over time. The approach of this study is as follows. First, a conceptual model is created incorporating the key components of the urban human-water system. Subsequently, only those components are selected that are both relevant and show causal loop behavior. Lastly, the causal narratives are translated into mathematical relationships. The outcome will be a simple model that shows only those characteristics with which we are able to explore the two-way coupling between the societal behavior and the water system we depend on.

Animal models of female pelvic organ prolapse: lessons learned

PubMed Central

Couri, Bruna M; Lenis, Andrew T; Borazjani, Ali; Paraiso, Marie Fidela R; Damaser, Margot S

2012-01-01

Pelvic organ prolapse is a vaginal protrusion of female pelvic organs. It has high prevalence worldwide and represents a great burden to the economy. The pathophysiology of pelvic organ prolapse is multifactorial and includes genetic predisposition, aberrant connective tissue, obesity, advancing age, vaginal delivery and other risk factors. Owing to the long course prior to patients becoming symptomatic and ethical questions surrounding human studies, animal models are necessary and useful. These models can mimic different human characteristics – histological, anatomical or hormonal, but none present all of the characteristics at the same time. Major animal models include knockout mice, rats, sheep, rabbits and nonhuman primates. In this article we discuss different animal models and their utility for investigating the natural progression of pelvic organ prolapse pathophysiology and novel treatment approaches. PMID:22707980

Swine as a model for influenza A virus infection

USDA-ARS?s Scientific Manuscript database

Influenza A viruses (IAV) infect a variety of hosts, including humans, swine, and various avian species. The annual influenza disease burden in the human population remains significant even with current vaccine usage and much about the pathogenesis and transmission of influenza viruses in human rema...

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.

Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma

PubMed Central

Simpson, R Mark; Bastian, Boris C; Michael, Helen T; Webster, Joshua D; Prasad, Manju L; Conway, Catherine M; Prieto, Victor M; Gary, Joy M; Goldschmidt, Michael H; Esplin, D Glen; Smedley, Rebecca C; Piris, Adriano; Meuten, Donald J; Kiupel, Matti; Lee, Chyi-Chia R; Ward, Jerrold M; Dwyer, Jennifer E; Davis, Barbara J; Anver, Miriam R; Molinolo, Alfredo A; Hoover, Shelley B; Rodriguez-Canales, Jaime; Hewitt, Stephen M

2014-01-01

Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model. PMID:24128326

Using NASA's GRACE and SMAP satellites to measure human impacts on the water cycle

NASA Astrophysics Data System (ADS)

Reager, J. T., II; Castle, S.; Turmon, M.; Famiglietti, J. S.; Fournier, S.

2017-12-01

Two satellite missions, the Gravity Recovery and Climate Experiment (GRACE) mission and the Soil Moisture Active Passive (SMAP) mission are enabling the measurement of the dynamic state of the water cycle globally, offering a unique opportunity for the study of human impacts on terrestrial hydrology and an opportunity to quantify the direct augmentation of natural cycles by human activities. While many model-data fusion studies aim to apply observations to improve model performance, we present recent studies on measuring the multi-scale impacts of human activities by differencing or contrasting model simulations and observations. Results that will be presented include studies on: the measurement of human impacts on evapotranspiration in the Colorado River Basin; the estimation of the human portion of groundwater depletion in the Southwestern U.S.; and the influence of irrigation on runoff generation in the Mississippi River basin. Each of these cases has a unique implications for the sustainable use of natural resources by humans, and indicate the relevant extent and magnitude of human influence on natural processes, suggesting their importance for inclusion in hydrology and land-surface models.

PAL(TM) 2.0 Human Anatomy Software Tool Use in Community College Traditional and Online Anatomy Laboratory Classes: Student-Perceived Learning Benefits

ERIC Educational Resources Information Center

Kuyatt, Brian Lee

2012-01-01

Human anatomy courses, with laboratory, are curricular requirements in graduate medical, undergraduate nursing, and all allied health science programs. Anatomy laboratory courses engage students in hands-on activities, including human cadaver or mammalian dissection, supported by photos from textbooks, detailed plastic models or human anatomical…

Human and feline adipose-derived mesenchymal stem cells have comparable phenotype, immunomodulatory functions, and transcriptome.

PubMed

Clark, Kaitlin C; Fierro, Fernando A; Ko, Emily Mills; Walker, Naomi J; Arzi, Boaz; Tepper, Clifford G; Dahlenburg, Heather; Cicchetto, Andrew; Kol, Amir; Marsh, Lyndsey; Murphy, William J; Fazel, Nasim; Borjesson, Dori L

2017-03-20

Adipose-derived mesenchymal stem cells (ASCs) are a promising cell therapy to treat inflammatory and immune-mediated diseases. Development of appropriate pre-clinical animal models is critical to determine safety and attain early efficacy data for the most promising therapeutic candidates. Naturally occurring diseases in cats already serve as valuable models to inform human clinical trials in oncologic, cardiovascular, and genetic diseases. The objective of this study was to complete a comprehensive side-by-side comparison of human and feline ASCs, with an emphasis on their immunomodulatory capacity and transcriptome. Human and feline ASCs were evaluated for phenotype, immunomodulatory profile, and transcriptome. Additionally, transwells were used to determine the role of cell-cell contact in ASC-mediated inhibition of lymphocyte proliferation in both humans and cats. Similar to human ASCs, feline ASCs were highly proliferative at low passages and fit the minimal criteria of multipotent stem cells including a compatible surface protein phenotype, osteogenic capacity, and normal karyotype. Like ASCs from all species, feline ASCs inhibited mitogen-activated lymphocyte proliferation in vitro, with or without direct ASC-lymphocyte contact. Feline ASCs mimic human ASCs in their mediator secretion pattern, including prostaglandin E2, indoleamine 2,3 dioxygenase, transforming growth factor beta, and interleukin-6, all augmented by interferon gamma secretion by lymphocytes. The transcriptome of three unactivated feline ASC lines were highly similar. Functional analysis of the most highly expressed genes highlighted processes including: 1) the regulation of apoptosis; 2) cell adhesion; 3) response to oxidative stress; and 4) regulation of cell differentiation. Finally, feline ASCs had a similar gene expression profile to noninduced human ASCs. Findings suggest that feline ASCs modulate lymphocyte proliferation using soluble mediators that mirror the human ASC secretion pattern. Uninduced feline ASCs have similar gene expression profiles to uninduced human ASCs, as revealed by transcriptome analysis. These data will help inform clinical trials using cats with naturally occurring diseases as surrogate models for human clinical trials in the regenerative medicine arena.

Modeling and simulation of normal and hemiparetic gait

NASA Astrophysics Data System (ADS)

Luengas, Lely A.; Camargo, Esperanza; Sanchez, Giovanni

2015-09-01

Gait is the collective term for the two types of bipedal locomotion, walking and running. This paper is focused on walking. The analysis of human gait is of interest to many different disciplines, including biomechanics, human-movement science, rehabilitation and medicine in general. Here we present a new model that is capable of reproducing the properties of walking, normal and pathological. The aim of this paper is to establish the biomechanical principles that underlie human walking by using Lagrange method. The constraint forces of Rayleigh dissipation function, through which to consider the effect on the tissues in the gait, are included. Depending on the value of the factor present in the Rayleigh dissipation function, both normal and pathological gait can be simulated. First of all, we apply it in the normal gait and then in the permanent hemiparetic gait. Anthropometric data of adult person are used by simulation, and it is possible to use anthropometric data for children but is necessary to consider existing table of anthropometric data. Validation of these models includes simulations of passive dynamic gait that walk on level ground. The dynamic walking approach provides a new perspective of gait analysis, focusing on the kinematics and kinetics of gait. There have been studies and simulations to show normal human gait, but few of them have focused on abnormal, especially hemiparetic gait. Quantitative comparisons of the model predictions with gait measurements show that the model can reproduce the significant characteristics of normal gait.

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.

Computational modeling of blast wave interaction with a human body and assessment of traumatic brain injury

NASA Astrophysics Data System (ADS)

Tan, X. G.; Przekwas, A. J.; Gupta, R. K.

2017-11-01

The modeling of human body biomechanics resulting from blast exposure poses great challenges because of the complex geometry and the substantial material heterogeneity. We developed a detailed human body finite element model representing both the geometry and the materials realistically. The model includes the detailed head (face, skull, brain and spinal cord), the neck, the skeleton, air cavities (lungs) and the tissues. Hence, it can be used to properly model the stress wave propagation in the human body subjected to blast loading. The blast loading on the human was generated from a simulated C4 explosion. We used the highly scalable solvers in the multi-physics code CoBi for both the blast simulation and the human body biomechanics. The meshes generated for these simulations are of good quality so that relatively large time-step sizes can be used without resorting to artificial time scaling treatments. The coupled gas dynamics and biomechanics solutions were validated against the shock tube test data. The human body models were used to conduct parametric simulations to find the biomechanical response and the brain injury mechanism due to blasts impacting the human body. Under the same blast loading condition, we showed the importance of inclusion of the whole body.

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

Collins, William D.; Craig, Anthony P.; Truesdale, John E.

The integrated Earth System Model (iESM) has been developed as a new tool for pro- jecting 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 in- frastructure. IAMs are the primary tool for describing the human–Earth system, including the sources of global greenhouse gases (GHGs) and short-lived species, land use and land cover change, 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 sin- gle 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 under- standing 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. This paper de- scribes the formulation, requirements, implementation, testing, and resulting functionality of the first version of the iESM released to the global climate community.« less

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

Collins, W. D.; Craig, A. P.; Truesdale, J. E.

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. This paper describes the formulation, requirements, implementation, testing, and resulting functionality of the first version of the iESM released to the global climate community.« less

Cell sources for in vitro human liver cell culture models.

PubMed

Zeilinger, Katrin; Freyer, Nora; Damm, Georg; Seehofer, Daniel; Knöspel, Fanny

2016-09-01

In vitro liver cell culture models are gaining increasing importance in pharmacological and toxicological research. The source of cells used is critical for the relevance and the predictive value of such models. Primary human hepatocytes (PHH) are currently considered to be the gold standard for hepatic in vitro culture models, since they directly reflect the specific metabolism and functionality of the human liver; however, the scarcity and difficult logistics of PHH have driven researchers to explore alternative cell sources, including liver cell lines and pluripotent stem cells. Liver cell lines generated from hepatomas or by genetic manipulation are widely used due to their good availability, but they are generally altered in certain metabolic functions. For the past few years, adult and pluripotent stem cells have been attracting increasing attention, due their ability to proliferate and to differentiate into hepatocyte-like cells in vitro However, controlling the differentiation of these cells is still a challenge. This review gives an overview of the major human cell sources under investigation for in vitro liver cell culture models, including primary human liver cells, liver cell lines, and stem cells. The promises and challenges of different cell types are discussed with a focus on the complex 2D and 3D culture approaches under investigation for improving liver cell functionality in vitro Finally, the specific application options of individual cell sources in pharmacological research or disease modeling are described. © 2016 by the Society for Experimental Biology and Medicine.

Cell sources for in vitro human liver cell culture models

PubMed Central

Freyer, Nora; Damm, Georg; Seehofer, Daniel; Knöspel, Fanny

2016-01-01

In vitro liver cell culture models are gaining increasing importance in pharmacological and toxicological research. The source of cells used is critical for the relevance and the predictive value of such models. Primary human hepatocytes (PHH) are currently considered to be the gold standard for hepatic in vitro culture models, since they directly reflect the specific metabolism and functionality of the human liver; however, the scarcity and difficult logistics of PHH have driven researchers to explore alternative cell sources, including liver cell lines and pluripotent stem cells. Liver cell lines generated from hepatomas or by genetic manipulation are widely used due to their good availability, but they are generally altered in certain metabolic functions. For the past few years, adult and pluripotent stem cells have been attracting increasing attention, due their ability to proliferate and to differentiate into hepatocyte-like cells in vitro. However, controlling the differentiation of these cells is still a challenge. This review gives an overview of the major human cell sources under investigation for in vitro liver cell culture models, including primary human liver cells, liver cell lines, and stem cells. The promises and challenges of different cell types are discussed with a focus on the complex 2D and 3D culture approaches under investigation for improving liver cell functionality in vitro. Finally, the specific application options of individual cell sources in pharmacological research or disease modeling are described. PMID:27385595

An empirical model of human aspiration in low-velocity air using CFD investigations.

PubMed

Anthony, T Renée; Anderson, Kimberly R

2015-01-01

Computational fluid dynamics (CFD) modeling was performed to investigate the aspiration efficiency of the human head in low velocities to examine whether the current inhaled particulate mass (IPM) sampling criterion matches the aspiration efficiency of an inhaling human in airflows common to worker exposures. Data from both mouth and nose inhalation, averaged to assess omnidirectional aspiration efficiencies, were compiled and used to generate a unifying model to relate particle size to aspiration efficiency of the human head. Multiple linear regression was used to generate an empirical model to estimate human aspiration efficiency and included particle size as well as breathing and freestream velocities as dependent variables. A new set of simulated mouth and nose breathing aspiration efficiencies was generated and used to test the fit of empirical models. Further, empirical relationships between test conditions and CFD estimates of aspiration were compared to experimental data from mannequin studies, including both calm-air and ultra-low velocity experiments. While a linear relationship between particle size and aspiration is reported in calm air studies, the CFD simulations identified a more reasonable fit using the square of particle aerodynamic diameter, which better addressed the shape of the efficiency curve's decline toward zero for large particles. The ultimate goal of this work was to develop an empirical model that incorporates real-world variations in critical factors associated with particle aspiration to inform low-velocity modifications to the inhalable particle sampling criterion.

Variable responses of human and non-human primate gut microbiomes to a Western diet.

PubMed

Amato, Katherine R; Yeoman, Carl J; Cerda, Gabriela; Schmitt, Christopher A; Cramer, Jennifer Danzy; Miller, Margret E Berg; Gomez, Andres; Turner, Trudy R; Wilson, Brenda A; Stumpf, Rebecca M; Nelson, Karen E; White, Bryan A; Knight, Rob; Leigh, Steven R

2015-11-16

The human gut microbiota interacts closely with human diet and physiology. To better understand the mechanisms behind this relationship, gut microbiome research relies on complementing human studies with manipulations of animal models, including non-human primates. However, due to unique aspects of human diet and physiology, it is likely that host-gut microbe interactions operate differently in humans and non-human primates. Here, we show that the human microbiome reacts differently to a high-protein, high-fat Western diet than that of a model primate, the African green monkey, or vervet (Chlorocebus aethiops sabaeus). Specifically, humans exhibit increased relative abundance of Firmicutes and reduced relative abundance of Prevotella on a Western diet while vervets show the opposite pattern. Predictive metagenomics demonstrate an increased relative abundance of genes associated with carbohydrate metabolism in the microbiome of only humans consuming a Western diet. These results suggest that the human gut microbiota has unique properties that are a result of changes in human diet and physiology across evolution or that may have contributed to the evolution of human physiology. Therefore, the role of animal models for understanding the relationship between the human gut microbiota and host metabolism must be re-focused.

Combined monitoring, decision and control model for the human operator in a command and control desk

NASA Technical Reports Server (NTRS)

Muralidharan, R.; Baron, S.

1978-01-01

A report is given on the ongoing efforts to mode the human operator in the context of the task during the enroute/return phases in the ground based control of multiple flights of remotely piloted vehicles (RPV). The approach employed here uses models that have their analytical bases in control theory and in statistical estimation and decision theory. In particular, it draws heavily on the modes and the concepts of the optimal control model (OCM) of the human operator. The OCM is being extended into a combined monitoring, decision, and control model (DEMON) of the human operator by infusing decision theoretic notions that make it suitable for application to problems in which human control actions are infrequent and in which monitoring and decision-making are the operator's main activities. Some results obtained with a specialized version of DEMON for the RPV control problem are included.

Formally verifying human–automation interaction as part of a system model: limitations and tradeoffs

PubMed Central

Bass, Ellen J.

2011-01-01

Both the human factors engineering (HFE) and formal methods communities are concerned with improving the design of safety-critical systems. This work discusses a modeling effort that leveraged methods from both fields to perform formal verification of human–automation interaction with a programmable device. This effort utilizes a system architecture composed of independent models of the human mission, human task behavior, human-device interface, device automation, and operational environment. The goals of this architecture were to allow HFE practitioners to perform formal verifications of realistic systems that depend on human–automation interaction in a reasonable amount of time using representative models, intuitive modeling constructs, and decoupled models of system components that could be easily changed to support multiple analyses. This framework was instantiated using a patient controlled analgesia pump in a two phased process where models in each phase were verified using a common set of specifications. The first phase focused on the mission, human-device interface, and device automation; and included a simple, unconstrained human task behavior model. The second phase replaced the unconstrained task model with one representing normative pump programming behavior. Because models produced in the first phase were too large for the model checker to verify, a number of model revisions were undertaken that affected the goals of the effort. While the use of human task behavior models in the second phase helped mitigate model complexity, verification time increased. Additional modeling tools and technological developments are necessary for model checking to become a more usable technique for HFE. PMID:21572930

A model for Huanglongbing spread between citrus plants including delay times and human intervention

NASA Astrophysics Data System (ADS)

Vilamiu, Raphael G. d'A.; Ternes, Sonia; Braga, Guilherme A.; Laranjeira, Francisco F.

2012-09-01

The objective of this work was to present a compartmental deterministic mathematical model for representing the dynamics of HLB disease in a citrus orchard, including delay in the disease's incubation phase in the plants, and a delay period on the nymphal stage of Diaphorina citri, the most important HLB insect vector in Brazil. Numerical simulations were performed to assess the possible impacts of human detection efficiency of symptomatic plants, as well as the influence of a long incubation period of HLB in the plant.

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.

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

Respiratory Syncytial Virus (RSV) Pulmonary Infection in Humanized Mice Induces Human Anti-RSV Immune Responses and Pathology

PubMed Central

Sharma, Anurag; Wu, Wenzhu; Sung, Biin; Huang, Jing; Tsao, Tiffany; Li, Xiangming; Gomi, Rika; Tsuji, Moriya

2016-01-01

ABSTRACT Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease, which causes high rates of morbidity and mortality in infants and the elderly. Models of human RSV pulmonary disease are needed to better understand RSV pathogenesis and to assess the efficacy of RSV vaccines. We assessed the RSV-specific human innate, humoral, and cellular immune responses in humanized mice (mice with a human immune system [HIS mice]) with functional human CD4+ T and B cells. These mice were generated by introduction of HLA class II genes, various human cytokines, and human B cell activation factor into immunodeficient NOD scid gamma (NSG) mice by the use of an adeno-associated virus vector, followed by engraftment of human hematopoietic stem cells. During the first 3 days of infection, HIS mice lost more weight and cleared RSV faster than NSG mice. Human chemokine (C-C motif) ligand 3 (CCL3) and human interleukin-1β (IL-1β) expression was detected in the RSV-infected HIS mice. The pathological features induced by RSV infection in HIS mice included peribronchiolar inflammation, neutrophil predominance in the bronchioalveolar lavage fluid, and enhanced airway mucus production. Human anti-RSV IgG and RSV-neutralizing antibodies were detected in serum and human anti-RSV mucosal IgA was detected in bronchioalveolar lavage fluid for up to 6 weeks. RSV infection induced an RSV-specific human gamma interferon response in HIS mouse splenocytes. These results indicate that human immune cells can induce features of RSV lung disease, including mucus hyperplasia, in murine lungs and that HIS mice can be used to elicit human anti-RSV humoral and cellular immunity. IMPORTANCE Infections with respiratory syncytial virus (RSV) are common and can cause severe lung disease in infants and the elderly. The lack of a suitable animal model with disease features similar to those in humans has hampered efforts to predict the efficacy of novel anti-RSV therapies and vaccines for use in humans. A murine model consisting of mice with a human immune system (HIS mice) could be useful for assessment of RSV disease and anti-RSV responses specific to humans. This study investigates an HIS mouse model to imitate human RSV disease and immune responses. We found that RSV lung infection in HIS mice results in an RSV-specific pathology that mimics RSV disease in humans and induces human anti-RSV immune responses. This model could be useful for better understanding of human RSV disease and for the development of RSV therapies. PMID:26962219

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

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

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

2005-10-01

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

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.

A simple physiologically based pharmacokinetic model evaluating the effect of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans

PubMed Central

Saylor, Kyle; Zhang, Chenming

2017-01-01

Physiologically based pharmacokinetic (PBPK) modeling was applied to investigate the effects of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans. Successful construction of both rat and human models was achieved by fitting model outputs to published nicotine concentration time course data in the blood and in the brain. Key parameters presumed to have the most effect on the ability of these antibodies to prevent nicotine from entering the brain were selected for investigation using the human model. These parameters, which included antibody affinity for nicotine, antibody cross-reactivity with cotinine, and antibody concentration, were broken down into different, clinically-derived in silico treatment levels and fed into the human PBPK model. Model predictions suggested that all three parameters, in addition to smoking status, have a sizable impact on anti-nicotine antibodies’ ability to prevent nicotine from entering the brain and that the antibodies elicited by current human vaccines do not have sufficient binding characteristics to reduce brain nicotine concentrations. If the antibody binding characteristics achieved in animal studies can similarly be achieved in human studies, however, nicotine vaccine efficacy in terms of brain nicotine concentration reduction is predicted to meet threshold values for alleviating nicotine dependence. PMID:27473014

The retention time of inorganic mercury in the brain — A systematic review of the evidence

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

Rooney, James P.K., E-mail: jrooney@rcsi.ie

2014-02-01

Reports from human case studies indicate a half-life for inorganic mercury in the brain in the order of years—contradicting older radioisotope studies that estimated half-lives in the order of weeks to months in duration. This study systematically reviews available evidence on the retention time of inorganic mercury in humans and primates to better understand this conflicting evidence. A broad search strategy was used to capture 16,539 abstracts on the Pubmed database. Abstracts were screened to include only study types containing relevant information. 131 studies of interest were identified. Only 1 primate study made a numeric estimate for the half-life ofmore » inorganic mercury (227–540 days). Eighteen human mercury poisoning cases were followed up long term including autopsy. Brain inorganic mercury concentrations at death were consistent with a half-life of several years or longer. 5 radionucleotide studies were found, one of which estimated head half-life (21 days). This estimate has sometimes been misinterpreted to be equivalent to brain half-life—which ignores several confounding factors including limited radioactive half-life and radioactive decay from surrounding tissues including circulating blood. No autopsy cohort study estimated a half-life for inorganic mercury, although some noted bioaccumulation of brain mercury with age. Modelling studies provided some extreme estimates (69 days vs 22 years). Estimates from modelling studies appear sensitive to model assumptions, however predications based on a long half-life (27.4 years) are consistent with autopsy findings. In summary, shorter estimates of half-life are not supported by evidence from animal studies, human case studies, or modelling studies based on appropriate assumptions. Evidence from such studies point to a half-life of inorganic mercury in human brains of several years to several decades. This finding carries important implications for pharmcokinetic modelling of mercury and potentially for the regulatory toxicology of mercury.« less

Cascading Walks Model for Human Mobility Patterns

PubMed Central

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

2015-01-01

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

Cascading walks model for human mobility patterns.

PubMed

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

2015-01-01

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

Animal models for filovirus infections.

PubMed

Siragam, Vinayakumar; Wong, Gary; Qiu, Xiang-Guo

2018-01-18

The family Filoviridae , which includes the genera Marburgvirus and Ebolavirus , contains some of the most pathogenic viruses in humans and non-human primates (NHPs), causing severe hemorrhagic fevers with high fatality rates. Small animal models against filoviruses using mice, guinea pigs, hamsters, and ferrets have been developed with the goal of screening candidate vaccines and antivirals, before testing in the gold standard NHP models. In this review, we summarize the different animal models used to understand filovirus pathogenesis, and discuss the advantages and disadvantages of each model with respect to filovirus disease research.

Animal models for filovirus infections

PubMed Central

Siragam, Vinayakumar; Wong, Gary; Qiu, Xiang-Guo

2018-01-01

The family Filoviridae, which includes the genera Marburgvirus and Ebolavirus, contains some of the most pathogenic viruses in humans and non-human primates (NHPs), causing severe hemorrhagic fevers with high fatality rates. Small animal models against filoviruses using mice, guinea pigs, hamsters, and ferrets have been developed with the goal of screening candidate vaccines and antivirals, before testing in the gold standard NHP models. In this review, we summarize the different animal models used to understand filovirus pathogenesis, and discuss the advantages and disadvantages of each model with respect to filovirus disease research. PMID:29511141

Human cognition and mobility in aging: a model for berry fruit interventions

USDA-ARS?s Scientific Manuscript database

Changes in motor function in aging, in both animals and humans, include decrements in balance, strength, and coordination, even in the absence of specific movement disorders such as Parkinson’s disease. In humans, these alterations can increase fall risk, often leading to injury and premature nursin...

Zoonotic Transmission of Waterborne Disease: A Mathematical Model.

PubMed

Waters, Edward K; Hamilton, Andrew J; Sidhu, Harvinder S; Sidhu, Leesa A; Dunbar, Michelle

2016-01-01

Waterborne parasites that infect both humans and animals are common causes of diarrhoeal illness, but the relative importance of transmission between humans and animals and vice versa remains poorly understood. Transmission of infection from animals to humans via environmental reservoirs, such as water sources, has attracted attention as a potential source of endemic and epidemic infections, but existing mathematical models of waterborne disease transmission have limitations for studying this phenomenon, as they only consider contamination of environmental reservoirs by humans. This paper develops a mathematical model that represents the transmission of waterborne parasites within and between both animal and human populations. It also improves upon existing models by including animal contamination of water sources explicitly. Linear stability analysis and simulation results, using realistic parameter values to describe Giardia transmission in rural Australia, show that endemic infection of an animal host with zoonotic protozoa can result in endemic infection in human hosts, even in the absence of person-to-person transmission. These results imply that zoonotic transmission via environmental reservoirs is important.

From Network Analysis to Functional Metabolic Modeling of the Human Gut Microbiota.

PubMed

Bauer, Eugen; Thiele, Ines

2018-01-01

An important hallmark of the human gut microbiota is its species diversity and complexity. Various diseases have been associated with a decreased diversity leading to reduced metabolic functionalities. Common approaches to investigate the human microbiota include high-throughput sequencing with subsequent correlative analyses. However, to understand the ecology of the human gut microbiota and consequently design novel treatments for diseases, it is important to represent the different interactions between microbes with their associated metabolites. Computational systems biology approaches can give further mechanistic insights by constructing data- or knowledge-driven networks that represent microbe interactions. In this minireview, we will discuss current approaches in systems biology to analyze the human gut microbiota, with a particular focus on constraint-based modeling. We will discuss various community modeling techniques with their advantages and differences, as well as their application to predict the metabolic mechanisms of intestinal microbial communities. Finally, we will discuss future perspectives and current challenges of simulating realistic and comprehensive models of the human gut microbiota.

TALEN-based generation of a cynomolgus monkey disease model for human microcephaly

PubMed Central

Ke, Qiong; Li, Weiqiang; Lai, Xingqiang; Chen, Hong; Huang, Lihua; Kang, Zhuang; Li, Kai; Ren, Jie; Lin, Xiaofeng; Zheng, Haiqing; Huang, Weijun; Ma, Yunhan; Xu, Dongdong; Chen, Zheng; Song, Xinming; Lin, Xinyi; Zhuang, Min; Wang, Tao; Zhuang, Fengfeng; Xi, Jianzhong; Mao, Frank Fuxiang; Xia, Huimin; Lahn, Bruce T; Zhou, Qi; Yang, Shihua; Xiang, Andy Peng

2016-01-01

Gene editing in non-human primates may lead to valuable models for exploring the etiologies and therapeutic strategies of genetically based neurological disorders in humans. However, a monkey model of neurological disorders that closely mimics pathological and behavioral deficits in humans has not yet been successfully generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic MCPH1 mutations using transcription activator-like effector nucleases. The monkey recapitulated most of the important clinical features observed in patients, including marked reductions in head circumference, premature chromosome condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity. Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC syndrome. This monkey model may help us elucidate the role of MCPH1 in the pathogenesis of human microcephaly and better understand the function of this protein in the evolution of primate brain size. PMID:27502025

Human-centric predictive model of task difficulty for human-in-the-loop control tasks

PubMed Central

Majewicz Fey, Ann

2018-01-01

Quantitatively measuring the difficulty of a manipulation task in human-in-the-loop control systems is ill-defined. Currently, systems are typically evaluated through task-specific performance measures and post-experiment user surveys; however, these methods do not capture the real-time experience of human users. In this study, we propose to analyze and predict the difficulty of a bivariate pointing task, with a haptic device interface, using human-centric measurement data in terms of cognition, physical effort, and motion kinematics. Noninvasive sensors were used to record the multimodal response of human user for 14 subjects performing the task. A data-driven approach for predicting task difficulty was implemented based on several task-independent metrics. We compare four possible models for predicting task difficulty to evaluated the roles of the various types of metrics, including: (I) a movement time model, (II) a fusion model using both physiological and kinematic metrics, (III) a model only with kinematic metrics, and (IV) a model only with physiological metrics. The results show significant correlation between task difficulty and the user sensorimotor response. The fusion model, integrating user physiology and motion kinematics, provided the best estimate of task difficulty (R2 = 0.927), followed by a model using only kinematic metrics (R2 = 0.921). Both models were better predictors of task difficulty than the movement time model (R2 = 0.847), derived from Fitt’s law, a well studied difficulty model for human psychomotor control. PMID:29621301

Computational modeling of the human auditory periphery: Auditory-nerve responses, evoked potentials and hearing loss.

PubMed

Verhulst, Sarah; Altoè, Alessandro; Vasilkov, Viacheslav

2018-03-01

Models of the human auditory periphery range from very basic functional descriptions of auditory filtering to detailed computational models of cochlear mechanics, inner-hair cell (IHC), auditory-nerve (AN) and brainstem signal processing. It is challenging to include detailed physiological descriptions of cellular components into human auditory models because single-cell data stems from invasive animal recordings while human reference data only exists in the form of population responses (e.g., otoacoustic emissions, auditory evoked potentials). To embed physiological models within a comprehensive human auditory periphery framework, it is important to capitalize on the success of basic functional models of hearing and render their descriptions more biophysical where possible. At the same time, comprehensive models should capture a variety of key auditory features, rather than fitting their parameters to a single reference dataset. In this study, we review and improve existing models of the IHC-AN complex by updating their equations and expressing their fitting parameters into biophysical quantities. The quality of the model framework for human auditory processing is evaluated using recorded auditory brainstem response (ABR) and envelope-following response (EFR) reference data from normal and hearing-impaired listeners. We present a model with 12 fitting parameters from the cochlea to the brainstem that can be rendered hearing impaired to simulate how cochlear gain loss and synaptopathy affect human population responses. The model description forms a compromise between capturing well-described single-unit IHC and AN properties and human population response features. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Multiplex CRISPR/Cas9-Based Genome Editing in Human Hematopoietic Stem Cells Models Clonal Hematopoiesis and Myeloid Neoplasia.

PubMed

Tothova, Zuzana; Krill-Burger, John M; Popova, Katerina D; Landers, Catherine C; Sievers, Quinlan L; Yudovich, David; Belizaire, Roger; Aster, Jon C; Morgan, Elizabeth A; Tsherniak, Aviad; Ebert, Benjamin L

2017-10-05

Hematologic malignancies are driven by combinations of genetic lesions that have been difficult to model in human cells. We used CRISPR/Cas9 genome engineering of primary adult and umbilical cord blood CD34 + human hematopoietic stem and progenitor cells (HSPCs), the cells of origin for myeloid pre-malignant and malignant diseases, followed by transplantation into immunodeficient mice to generate genetic models of clonal hematopoiesis and neoplasia. Human hematopoietic cells bearing mutations in combinations of genes, including cohesin complex genes, observed in myeloid malignancies generated immunophenotypically defined neoplastic clones capable of long-term, multi-lineage reconstitution and serial transplantation. Employing these models to investigate therapeutic efficacy, we found that TET2 and cohesin-mutated hematopoietic cells were sensitive to azacitidine treatment. These findings demonstrate the potential for generating genetically defined models of human myeloid diseases, and they are suitable for examining the biological consequences of somatic mutations and the testing of therapeutic agents. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of a computerized aid for creating human behavioral representations of human-computer interaction.

PubMed

Williams, Kent E; Voigt, Jeffrey R

2004-01-01

The research reported herein presents the results of an empirical evaluation that focused on the accuracy and reliability of cognitive models created using a computerized tool: the cognitive analysis tool for human-computer interaction (CAT-HCI). A sample of participants, expert in interacting with a newly developed tactical display for the U.S. Army's Bradley Fighting Vehicle, individually modeled their knowledge of 4 specific tasks employing the CAT-HCI tool. Measures of the accuracy and consistency of task models created by these task domain experts using the tool were compared with task models created by a double expert. The findings indicated a high degree of consistency and accuracy between the different "single experts" in the task domain in terms of the resultant models generated using the tool. Actual or potential applications of this research include assessing human-computer interaction complexity, determining the productivity of human-computer interfaces, and analyzing an interface design to determine whether methods can be automated.

The integrated Earth system model version 1: formulation and functionality

DOE PAGES

Collins, W. D.; Craig, A. P.; Truesdale, J. E.; ...

2015-07-23

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. This paper describes the formulation, requirements, implementation, testing, and resulting functionality of the first version of the iESM released to the global climate community.« less

Recent technology products from Space Human Factors research

NASA Technical Reports Server (NTRS)

Jenkins, James P.

1991-01-01

The goals of the NASA Space Human Factors program and the research carried out concerning human factors are discussed with emphasis given to the development of human performance models, data, and tools. The major products from this program are described, which include the Laser Anthropometric Mapping System; a model of the human body for evaluating the kinematics and dynamics of human motion and strength in microgravity environment; an operational experience data base for verifying and validating the data repository of manned space flights; the Operational Experience Database Taxonomy; and a human-computer interaction laboratory whose products are the display softaware and requirements and the guideline documents and standards for applications on human-computer interaction. Special attention is given to the 'Convoltron', a prototype version of a signal processor for synthesizing the head-related transfer functions.

A simple physiologically based pharmacokinetic model evaluating the effect of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans

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

Saylor, Kyle, E-mail: saylor@vt.edu; Zhang, Chenmi

Physiologically based pharmacokinetic (PBPK) modeling was applied to investigate the effects of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans. Successful construction of both rat and human models was achieved by fitting model outputs to published nicotine concentration time course data in the blood and in the brain. Key parameters presumed to have the most effect on the ability of these antibodies to prevent nicotine from entering the brain were selected for investigation using the human model. These parameters, which included antibody affinity for nicotine, antibody cross-reactivity with cotinine, and antibody concentration, were broken down intomore » different, clinically-derived in silico treatment levels and fed into the human PBPK model. Model predictions suggested that all three parameters, in addition to smoking status, have a sizable impact on anti-nicotine antibodies' ability to prevent nicotine from entering the brain and that the antibodies elicited by current human vaccines do not have sufficient binding characteristics to reduce brain nicotine concentrations. If the antibody binding characteristics achieved in animal studies can similarly be achieved in human studies, however, nicotine vaccine efficacy in terms of brain nicotine concentration reduction is predicted to meet threshold values for alleviating nicotine dependence. - Highlights: • Modelling of nicotine disposition in the presence of anti-nicotine antibodies • Key vaccine efficacy factors are evaluated in silico in rats and in humans. • Model predicts insufficient antibody binding in past human nicotine vaccines. • Improving immunogenicity and antibody specificity may lead to vaccine success.« less

Human effects on the hydrologic system of the Verde Valley, central Arizona, 1910–2005 and 2005–2110, using a regional groundwater flow model

USGS Publications Warehouse

Garner, Bradley D.; Pool, D.R.; Tillman, Fred D.; Forbes, Brandon T.

2013-01-01

Water budgets were developed for the Verde Valley of central Arizona in order to evaluate the degree to which human stresses have affected the hydrologic system and might affect it in the future. The Verde Valley is a portion of central Arizona wherein concerns have been raised about water availability, particularly perennial base flow of the Verde River. The Northern Arizona Regional Groundwater Flow Model (NARGFM) was used to generate the water budgets and was run in several configurations for the 1910–2005 and 2005–2110 time periods. The resultant water budgets were subtracted from one another in order to quantify the relative changes that were attributable solely to human stresses; human stresses included groundwater withdrawals and incidental and artificial recharge but did not include, for example, human effects on the global climate. Three hypothetical and varied conditions of human stresses were developed and applied to the model for the 2005–2110 period. On the basis of this analysis, human stresses during 1910–2005 were found to have already affected the hydrologic system of the Verde Valley, and human stresses will continue to affect the hydrologic system during 2005–2110. Riparian evapotranspiration decreased and underflow into the Verde Valley increased because of human stresses, and net groundwater discharge to the Verde River in the Verde Valley decreased for the 1910–2005 model runs. The model also showed that base flow at the upstream end of the study area, as of 2005, was about 4,900 acre-feet per year less than it would have been in the absence of human stresses. At the downstream end of the Verde Valley, base flow had been reduced by about 10,000 acre-feet per year by the year 2005 because of human stresses. For the 2005–2110 period, the model showed that base flow at the downstream end of the Verde Valley may decrease by an additional 5,400 to 8,600 acre-feet per year because of past, ongoing, and hypothetical future human stresses. The process known as capture (or streamflow depletion caused by the pumping of groundwater) was the reason for these human-stress-induced changes in water-budget components.

Correlation between human observer performance and model observer performance in differential phase contrast CT

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

Li, Ke; Garrett, John; Chen, Guang-Hong

2013-11-15

Purpose: With the recently expanding interest and developments in x-ray differential phase contrast CT (DPC-CT), the evaluation of its task-specific detection performance and comparison with the corresponding absorption CT under a given radiation dose constraint become increasingly important. Mathematical model observers are often used to quantify the performance of imaging systems, but their correlations with actual human observers need to be confirmed for each new imaging method. This work is an investigation of the effects of stochastic DPC-CT noise on the correlation of detection performance between model and human observers with signal-known-exactly (SKE) detection tasks.Methods: The detectabilities of different objectsmore » (five disks with different diameters and two breast lesion masses) embedded in an experimental DPC-CT noise background were assessed using both model and human observers. The detectability of the disk and lesion signals was then measured using five types of model observers including the prewhitening ideal observer, the nonprewhitening (NPW) observer, the nonprewhitening observer with eye filter and internal noise (NPWEi), the prewhitening observer with eye filter and internal noise (PWEi), and the channelized Hotelling observer (CHO). The same objects were also evaluated by four human observers using the two-alternative forced choice method. The results from the model observer experiment were quantitatively compared to the human observer results to assess the correlation between the two techniques.Results: The contrast-to-detail (CD) curve generated by the human observers for the disk-detection experiments shows that the required contrast to detect a disk is inversely proportional to the square root of the disk size. Based on the CD curves, the ideal and NPW observers tend to systematically overestimate the performance of the human observers. The NPWEi and PWEi observers did not predict human performance well either, as the slopes of their CD curves tended to be steeper. The CHO generated the best quantitative agreement with human observers with its CD curve overlapping with that of human observer. Statistical equivalence between CHO and humans can be claimed within 11% of the human observer results, including both the disk and lesion detection experiments.Conclusions: The model observer method can be used to accurately represent human observer performance with the stochastic DPC-CT noise for SKE tasks with sizes ranging from 8 to 128 pixels. The incorporation of the anatomical noise remains to be studied.« less

Dual-loop model of the human controller

NASA Technical Reports Server (NTRS)

Hess, R. A.

1978-01-01

A dual-loop model of the human controller in single-axis compensatory tracking tasks is introduced. This model possesses an inner-loop closure that involves feeding back that portion of controlled element output rate that is due to control activity. A novel feature of the model is the explicit appearance of the human's internal representation of the manipulator-controlled element dynamics in the inner loop. The sensor inputs to the human controller are assumed to be system error and control force. The former can be sensed via visual, aural, or tactile displays, whereas the latter is assumed to be sensed in kinesthetic fashion. A set of general adaptive characteristics for the model is hypothesized, including a method for selecting simplified internal models of the manipulator-controlled element dynamics. It is demonstrated that the model can produce controller describing functions that closely approximate those measured in four laboratory tracking tasks in which the controlled element dynamics vary considerably in terms of ease of control. An empirically derived expression for the normalized injected error remnant spectrum is introduced.

How Genetically Engineered Mouse Tumor Models Provide Insights Into Human Cancers

PubMed Central

Politi, Katerina; Pao, William

2011-01-01

Genetically engineered mouse models (GEMMs) of human cancer were first created nearly 30 years ago. These early transgenic models demonstrated that mouse cells could be transformed in vivo by expression of an oncogene. A new field emerged, dedicated to generating and using mouse models of human cancer to address a wide variety of questions in cancer biology. The aim of this review is to highlight the contributions of mouse models to the diagnosis and treatment of human cancers. Because of the breadth of the topic, we have selected representative examples of how GEMMs are clinically relevant rather than provided an exhaustive list of experiments. Today, as detailed here, sophisticated mouse models are being created to study many aspects of cancer biology, including but not limited to mechanisms of sensitivity and resistance to drug treatment, oncogene cooperation, early detection, and metastasis. Alternatives to GEMMs, such as chemically induced or spontaneous tumor models, are not discussed in this review. PMID:21263096

In vitro experimental investigation of voice production

PubMed Central

Horáčcek, Jaromír; Brücker, Christoph; Becker, Stefan

2012-01-01

The process of human phonation involves a complex interaction between the physical domains of structural dynamics, fluid flow, and acoustic sound production and radiation. Given the high degree of nonlinearity of these processes, even small anatomical or physiological disturbances can significantly affect the voice signal. In the worst cases, patients can lose their voice and hence the normal mode of speech communication. To improve medical therapies and surgical techniques it is very important to understand better the physics of the human phonation process. Due to the limited experimental access to the human larynx, alternative strategies, including artificial vocal folds, have been developed. The following review gives an overview of experimental investigations of artificial vocal folds within the last 30 years. The models are sorted into three groups: static models, externally driven models, and self-oscillating models. The focus is on the different models of the human vocal folds and on the ways in which they have been applied. PMID:23181007

Non-animal methodologies within biomedical research and toxicity testing.

PubMed

Knight, Andrew

2008-01-01

Laboratory animal models are limited by scientific constraints on human applicability, and increasing regulatory restrictions, driven by social concerns. Reliance on laboratory animals also incurs marked - and in some cases, prohibitive - logistical challenges, within high-throughput chemical testing programmes, such as those currently underway within Europe and the US. However, a range of non-animal methodologies is available within biomedical research and toxicity testing. These include: mechanisms to enhance the sharing and assessment of existing data prior to conducting further studies, and physicochemical evaluation and computerised modelling, including the use of structure-activity relationships and expert systems. Minimally-sentient animals from lower phylogenetic orders or early developmental vertebral stages may be used, as well as microorganisms and higher plants. A variety of tissue cultures, including immortalised cell lines, embryonic and adult stem cells, and organotypic cultures, are also available. In vitro assays utilising bacterial, yeast, protozoal, mammalian or human cell cultures exist for a wide range of toxic and other endpoints. These may be static or perfused, and may be used individually, or combined within test batteries. Human hepatocyte cultures and metabolic activation systems offer potential assessment of metabolite activity and organ-organ interaction. Microarray technology may allow genetic expression profiling, increasing the speed of toxin detection, well prior to more invasive endpoints. Enhanced human clinical trials utilising micro- dosing, staggered dosing, and more representative study populations and durations, as well as surrogate human tissues, advanced imaging modalities and human epidemiological, sociological and psycho- logical studies, may increase our understanding of illness aetiology and pathogenesis, and facilitate the development of safe and effective pharmacologic interventions. Particularly when human tissues are used, non-animal models may generate faster, cheaper results, more reliably predictive for humans, whilst yielding greater insights into human biochemical processes. Greater commitment to their development and implementation is necessary, however, to efficiently meet the needs of high-throughput chemical testing programmes, important emerging testing needs, and the ongoing development of human clinical interventions.

A human rights framework for midwifery care.

PubMed

Thompson, Joyce Beebe

2004-01-01

This article presents a rights-based model for midwifery care of women and childbearing families. Salient features include discussion of the influence of values on how women are viewed within cultures and societies, universal ethical principles applicable to health care services, and human rights based on the view of women as persons rather than as objects or chattel. Examples of the health impact on women of persistent violation of basic human rights are used to support the need for using a human rights framework for midwifery care--a model supported by codes of ethics, the midwifery philosophy of care, and standards of practice.

Designing a Curriculum Model to Include Sexuality and a Procedure for its Administration. Human Sexuality-Nursing 50383.

ERIC Educational Resources Information Center

Hoffman, Elise; And Others

In order to design and implement a plan to integrate human sexuality into the curriculum for associate degree nursing students at Alvin Community College (Texas), levels of knowledge, attitudes and skills necessary in promoting sexual health were defined. Of the four levels in the Mims and Swenson Sexual Health Model (life experiences, basic,…

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

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

Use of Physiologically Based Pharmacokinetic (PBPK) Models ...

EPA Pesticide Factsheets

EPA announced the availability of the final report, Use of Physiologically Based Pharmacokinetic (PBPK) Models to Quantify the Impact of Human Age and Interindividual Differences in Physiology and Biochemistry Pertinent to Risk Final Report for Cooperative Agreement. This report describes and demonstrates techniques necessary to extrapolate and incorporate in vitro derived metabolic rate constants in PBPK models. It also includes two case study examples designed to demonstrate the applicability of such data for health risk assessment and addresses the quantification, extrapolation and interpretation of advanced biochemical information on human interindividual variability of chemical metabolism for risk assessment application. It comprises five chapters; topics and results covered in the first four chapters have been published in the peer reviewed scientific literature. Topics covered include: Data Quality ObjectivesExperimental FrameworkRequired DataTwo example case studies that develop and incorporate in vitro metabolic rate constants in PBPK models designed to quantify human interindividual variability to better direct the choice of uncertainty factors for health risk assessment. This report is intended to serve as a reference document for risk assors to use when quantifying, extrapolating, and interpretating advanced biochemical information about human interindividual variability of chemical metabolism.

The Companion Dog as a Model for the Longevity Dividend

PubMed Central

Creevy, Kate E.; Austad, Steven N.; Hoffman, Jessica M.; O’Neill, Dan G.; Promislow, Daniel E.L.

2016-01-01

The companion dog is the most phenotypically diverse species on the planet. This enormous variability between breeds extends not only to morphology and behavior but also to longevity and the disorders that affect dogs. There are remarkable overlaps and similarities between the human and canine species. Dogs closely share our human environment, including its many risk factors, and the veterinary infrastructure to manage health in dogs is second only to the medical infrastructure for humans. Distinct breed-based health profiles, along with their well-developed health record system and high overlap with the human environment, make the companion dog an exceptional model to improve understanding of the physiological, social, and economic impacts of the longevity dividend (LD). In this review, we describe what is already known about age-specific patterns of morbidity and mortality in companion dogs, and then explore whether this existing evidence supports the LD. We also discuss some potential limitations to using dogs as models of aging, including the fact that many dogs are euthanized before they have lived out their natural life span. Overall, we conclude that the companion dog offers high potential as a model system that will enable deeper research into the LD than is otherwise possible. PMID:26729759

Dynamic motion planning of 3D human locomotion using gradient-based optimization.

PubMed

Kim, Hyung Joo; Wang, Qian; Rahmatalla, Salam; Swan, Colby C; Arora, Jasbir S; Abdel-Malek, Karim; Assouline, Jose G

2008-06-01

Since humans can walk with an infinite variety of postures and limb movements, there is no unique solution to the modeling problem to predict human gait motions. Accordingly, we test herein the hypothesis that the redundancy of human walking mechanisms makes solving for human joint profiles and force time histories an indeterminate problem best solved by inverse dynamics and optimization methods. A new optimization-based human-modeling framework is thus described for predicting three-dimensional human gait motions on level and inclined planes. The basic unknowns in the framework are the joint motion time histories of a 25-degree-of-freedom human model and its six global degrees of freedom. The joint motion histories are calculated by minimizing an objective function such as deviation of the trunk from upright posture that relates to the human model's performance. A variety of important constraints are imposed on the optimization problem, including (1) satisfaction of dynamic equilibrium equations by requiring the model's zero moment point (ZMP) to lie within the instantaneous geometrical base of support, (2) foot collision avoidance, (3) limits on ground-foot friction, and (4) vanishing yawing moment. Analytical forms of objective and constraint functions are presented and discussed for the proposed human-modeling framework in which the resulting optimization problems are solved using gradient-based mathematical programming techniques. When the framework is applied to the modeling of bipedal locomotion on level and inclined planes, acyclic human walking motions that are smooth and realistic as opposed to less natural robotic motions are obtained. The aspects of the modeling framework requiring further investigation and refinement, as well as potential applications of the framework in biomechanics, are discussed.

Toward a Model of Human Information Processing for Decision-Making and Skill Acquisition in Laparoscopic Colorectal Surgery.

PubMed

White, Eoin J; McMahon, Muireann; Walsh, Michael T; Coffey, J Calvin; O Sullivan, Leonard

To create a human information-processing model for laparoscopic surgery based on already established literature and primary research to enhance laparoscopic surgical education in this context. We reviewed the literature for information-processing models most relevant to laparoscopic surgery. Our review highlighted the necessity for a model that accounts for dynamic environments, perception, allocation of attention resources between the actions of both hands of an operator, and skill acquisition and retention. The results of the literature review were augmented through intraoperative observations of 7 colorectal surgical procedures, supported by laparoscopic video analysis of 12 colorectal procedures. The Wickens human information-processing model was selected as the most relevant theoretical model to which we make adaptions for this specific application. We expanded the perception subsystem of the model to involve all aspects of perception during laparoscopic surgery. We extended the decision-making system to include dynamic decision-making to account for case/patient-specific and surgeon-specific deviations. The response subsystem now includes dual-task performance and nontechnical skills, such as intraoperative communication. The memory subsystem is expanded to include skill acquisition and retention. Surgical decision-making during laparoscopic surgery is the result of a highly complex series of processes influenced not only by the operator's knowledge, but also patient anatomy and interaction with the surgical team. Newer developments in simulation-based education must focus on the theoretically supported elements and events that underpin skill acquisition and affect the cognitive abilities of novice surgeons. The proposed human information-processing model builds on established literature regarding information processing, accounting for a dynamic environment of laparoscopic surgery. This revised model may be used as a foundation for a model describing robotic surgery. Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

An advanced computational bioheat transfer model for a human body with an embedded systemic circulation.

PubMed

Coccarelli, Alberto; Boileau, Etienne; Parthimos, Dimitris; Nithiarasu, Perumal

2016-10-01

In the present work, an elaborate one-dimensional thermofluid model for a human body is presented. By contrast to the existing pure conduction-/perfusion-based models, the proposed methodology couples the arterial fluid dynamics of a human body with a multi-segmental bioheat model of surrounding solid tissues. In the present configuration, arterial flow is included through a network of elastic vessels. More than a dozen solid segments are employed to represent the heat conduction in the surrounding tissues, and each segment is constituted by a multilayered circular cylinder. Such multi-layers allow flexible delineation of the geometry and incorporation of properties of different tissue types. The coupling of solid tissue and fluid models requires subdivision of the arterial circulation into large and small arteries. The heat exchange between tissues and arterial wall occurs by convection in large vessels and by perfusion in small arteries. The core region, including the heart, provides the inlet conditions for the fluid equations. In the proposed model, shivering, sweating, and perfusion changes constitute the basis of the thermoregulatory system. The equations governing flow and heat transfer in the circulatory system are solved using a locally conservative Galerkin approach, and the heat conduction in the surrounding tissues is solved using a standard implicit backward Euler method. To investigate the effectiveness of the proposed model, temperature field evolutions are monitored at different points of the arterial tree and in the surrounding tissue layers. To study the differences due to flow-induced convection effects on thermal balance, the results of the current model are compared against those of the widely used modelling methodologies. The results show that the convection significantly influences the temperature distribution of the solid tissues in the vicinity of the arteries. Thus, the inner convection has a more predominant role in the human body heat balance than previously thought. To demonstrate its capabilities, the proposed new model is used to study different scenarios, including thermoregulation inactivity and variation in surrounding atmospheric conditions.

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.

Numerical evaluation of implantable hearing devices using a finite element model of human ear considering viscoelastic properties.

PubMed

Zhang, Jing; Tian, Jiabin; Ta, Na; Huang, Xinsheng; Rao, Zhushi

2016-08-01

Finite element method was employed in this study to analyze the change in performance of implantable hearing devices due to the consideration of soft tissues' viscoelasticity. An integrated finite element model of human ear including the external ear, middle ear and inner ear was first developed via reverse engineering and analyzed by acoustic-structure-fluid coupling. Viscoelastic properties of soft tissues in the middle ear were taken into consideration in this model. The model-derived dynamic responses including middle ear and cochlea functions showed a better agreement with experimental data at high frequencies above 3000 Hz than the Rayleigh-type damping. On this basis, a coupled finite element model consisting of the human ear and a piezoelectric actuator attached to the long process of incus was further constructed. Based on the electromechanical coupling analysis, equivalent sound pressure and power consumption of the actuator corresponding to viscoelasticity and Rayleigh damping were calculated using this model. The analytical results showed that the implant performance of the actuator evaluated using a finite element model considering viscoelastic properties gives a lower output above about 3 kHz than does Rayleigh damping model. Finite element model considering viscoelastic properties was more accurate to numerically evaluate implantable hearing devices. © IMechE 2016.

An Integrated Self-Aware Cognitive Architecture

DTIC Science & Technology

2008-03-01

human-like cognitive growth. Our approach is inspired by studies of the human brain -mind: in particular, by theoretical models of representations of...agency in the higher associative human brain areas. This feature (a theory of mind including representations of one’s self) allows the system to...self-aware cognition that we believe is necessary for human-like cognitive growth. Our approach is inspired by studies of the human brain -mind: in

Molecular Hydrogen as an Emerging Therapeutic Medical Gas for Neurodegenerative and Other Diseases

PubMed Central

Ohno, Kinji; Ito, Mikako; Ichihara, Masatoshi; Ito, Masafumi

2012-01-01

Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Most studies have been performed on rodents including two models of Parkinson's disease and three models of Alzheimer's disease. Prominent effects are observed especially in oxidative stress-mediated diseases including neonatal cerebral hypoxia; Parkinson's disease; ischemia/reperfusion of spinal cord, heart, lung, liver, kidney, and intestine; transplantation of lung, heart, kidney, and intestine. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects. Two enigmas, however, remain to be solved. First, no dose-response effect is observed. Rodents and humans are able to take a small amount of hydrogen by drinking hydrogen-rich water, but marked effects are observed. Second, intestinal bacteria in humans and rodents produce a large amount of hydrogen, but an addition of a small amount of hydrogen exhibits marked effects. Further studies are required to elucidate molecular bases of prominent hydrogen effects and to determine the optimal frequency, amount, and method of hydrogen administration for each human disease. PMID:22720117

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

Air pollution exposure prediction approaches used in air pollution epidemiology studies.

PubMed

Özkaynak, Halûk; Baxter, Lisa K; Dionisio, Kathie L; Burke, Janet

2013-01-01

Epidemiological studies of the health effects of outdoor air pollution have traditionally relied upon surrogates of personal exposures, most commonly ambient concentration measurements from central-site monitors. However, this approach may introduce exposure prediction errors and misclassification of exposures for pollutants that are spatially heterogeneous, such as those associated with traffic emissions (e.g., carbon monoxide, elemental carbon, nitrogen oxides, and particulate matter). We review alternative air quality and human exposure metrics applied in recent air pollution health effect studies discussed during the International Society of Exposure Science 2011 conference in Baltimore, MD. Symposium presenters considered various alternative exposure metrics, including: central site or interpolated monitoring data, regional pollution levels predicted using the national scale Community Multiscale Air Quality model or from measurements combined with local-scale (AERMOD) air quality models, hybrid models that include satellite data, statistically blended modeling and measurement data, concentrations adjusted by home infiltration rates, and population-based human exposure model (Stochastic Human Exposure and Dose Simulation, and Air Pollutants Exposure models) predictions. These alternative exposure metrics were applied in epidemiological applications to health outcomes, including daily mortality and respiratory hospital admissions, daily hospital emergency department visits, daily myocardial infarctions, and daily adverse birth outcomes. This paper summarizes the research projects presented during the symposium, with full details of the work presented in individual papers in this journal issue.

Computational Model for Oxygen Transport and Consumption in Human Vitreous

PubMed Central

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

2013-01-01

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

Computational model for oxygen transport and consumption in human vitreous.

PubMed

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

2013-10-15

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

On modeling human reliability in space flights - Redundancy and recovery operations

NASA Astrophysics Data System (ADS)

Aarset, M.; Wright, J. F.

The reliability of humans is of paramount importance to the safety of space flight systems. This paper describes why 'back-up' operators might not be the best solution, and in some cases, might even degrade system reliability. The problem associated with human redundancy calls for special treatment in reliability analyses. The concept of Standby Redundancy is adopted, and psychological and mathematical models are introduced to improve the way such problems can be estimated and handled. In the past, human reliability has practically been neglected in most reliability analyses, and, when included, the humans have been modeled as a component and treated numerically the way technical components are. This approach is not wrong in itself, but it may lead to systematic errors if too simple analogies from the technical domain are used in the modeling of human behavior. In this paper redundancy in a man-machine system will be addressed. It will be shown how simplification from the technical domain, when applied to human components of a system, may give non-conservative estimates of system reliability.

Canine and Feline Models of Human Genetic Diseases and Their Contributions to Advancing Clinical Therapies


PubMed Central

Gurda, Brittney L.; Bradbury, Allison M.; Vite, Charles H.

2017-01-01

For many lethal or debilitating genetic disorders in patients there are no satisfactory therapies. Several barriers exist that hinder the developments of effective therapies including the limited availability of clinically relevant animal models that faithfully recapitulate human genetic disease. In 1974, the Referral Center for Animal Models of Human Genetic Disease (RCAM) was established by Dr. Donald F. Patterson and continued by Dr. Mark E. Haskins at the University of Pennsylvania with the mission to discover, understand, treat, and maintain breeding colonies of naturally occurring hereditary disorders in dogs and cats that are orthologous to those found in human patients. Although non-human primates, sheep, and pig models are also available within the medical community, naturally occurring diseases are rarely identified in non-human primates, and the vast behavioral, clinicopathological, physiological, and anatomical knowledge available regarding dogs and cats far surpasses what is available in ovine and porcine species. The canine and feline models that are maintained at RCAM are presented here with a focus on preclinical therapy data. Clinical studies that have been generated from preclinical work in these models are also presented. PMID:28955181

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.

Using surveillance and monitoring data of different origins in a Salmonella source attribution model: a European Union example with challenges and proposed solutions.

PubMed

DE Knegt, L V; Pires, S M; Hald, T

2015-04-01

Microbial subtyping approaches are commonly used for source attribution of human salmonellosis. Such methods require data on Salmonella in animals and humans, outbreaks, infection abroad and amounts of food available for consumption. A source attribution model was applied to 24 European countries, requiring special data management to produce a standardized dataset. Salmonellosis data on animals and humans were obtained from datasets provided by the European Food Safety Authority. The amount of food available for consumption was calculated based on production and trade data. Limitations included different types of underreporting, non-participation in prevalence studies, and non-availability of trade data. Cases without travel information were assumed to be domestic; non-subtyped human or animal records were re-identified according to proportions observed in reference datasets; missing trade information was estimated based on previous years. The resulting dataset included data on 24 serovars in humans, broilers, laying hens, pigs and turkeys in 24 countries.

Human pluripotent stem cells: Prospects and challenges as a source of cardiomyocytes for in vitro modeling and cell-based cardiac repair.

PubMed

Hartman, Matthew E; Dai, Dao-Fu; Laflamme, Michael A

2016-01-15

Human pluripotent stem cells (PSCs) represent an attractive source of cardiomyocytes with potential applications including disease modeling, drug discovery and safety screening, and novel cell-based cardiac therapies. Insights from embryology have contributed to the development of efficient, reliable methods capable of generating large quantities of human PSC-cardiomyocytes with cardiac purities ranging up to 90%. However, for human PSCs to meet their full potential, the field must identify methods to generate cardiomyocyte populations that are uniform in subtype (e.g. homogeneous ventricular cardiomyocytes) and have more mature structural and functional properties. For in vivo applications, cardiomyocyte production must be highly scalable and clinical grade, and we will need to overcome challenges including graft cell death, immune rejection, arrhythmogenesis, and tumorigenic potential. Here we discuss the types of human PSCs, commonly used methods to guide their differentiation into cardiomyocytes, the phenotype of the resultant cardiomyocytes, and the remaining obstacles to their successful translation. Copyright © 2015 Elsevier B.V. All rights reserved.

Understanding human dynamics in microblog posting activities

NASA Astrophysics Data System (ADS)

Jiang, Zhihong; Zhang, Yubao; Wang, Hui; Li, Pei

2013-02-01

Human activity patterns are an important issue in behavior dynamics research. Empirical evidence indicates that human activity patterns can be characterized by a heavy-tailed inter-event time distribution. However, most researchers give an understanding by only modeling the power-law feature of the inter-event time distribution, and those overlooked non-power-law features are likely to be nontrivial. In this work, we propose a behavior dynamics model, called the finite memory model, in which humans adaptively change their activity rates based on a finite memory of recent activities, which is driven by inherent individual interest. Theoretical analysis shows a finite memory model can properly explain various heavy-tailed inter-event time distributions, including a regular power law and some non-power-law deviations. To validate the model, we carry out an empirical study based on microblogging activity from thousands of microbloggers in the Celebrity Hall of the Sina microblog. The results show further that the model is reasonably effective. We conclude that finite memory is an effective dynamics element to describe the heavy-tailed human activity pattern.

Mouse Tumor Biology (MTB): a database of mouse models for human cancer.

PubMed

Bult, Carol J; Krupke, Debra M; Begley, Dale A; Richardson, Joel E; Neuhauser, Steven B; Sundberg, John P; Eppig, Janan T

2015-01-01

The Mouse Tumor Biology (MTB; http://tumor.informatics.jax.org) database is a unique online compendium of mouse models for human cancer. MTB provides online access to expertly curated information on diverse mouse models for human cancer and interfaces for searching and visualizing data associated with these models. The information in MTB is designed to facilitate the selection of strains for cancer research and is a platform for mining data on tumor development and patterns of metastases. MTB curators acquire data through manual curation of peer-reviewed scientific literature and from direct submissions by researchers. Data in MTB are also obtained from other bioinformatics resources including PathBase, the Gene Expression Omnibus and ArrayExpress. Recent enhancements to MTB improve the association between mouse models and human genes commonly mutated in a variety of cancers as identified in large-scale cancer genomics studies, provide new interfaces for exploring regions of the mouse genome associated with cancer phenotypes and incorporate data and information related to Patient-Derived Xenograft models of human cancers. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Dog Models of Naturally Occurring Cancer

PubMed Central

Rowell, Jennie L.; McCarthy, Donna O.; Alvarez, Carlos E.

2011-01-01

Studies using dogs provide an ideal solution to the gap in animal models of natural disease and translational medicine. This is evidenced by approximately 400 inherited disorders being characterized in domesticated dogs, most of which are relevant to humans. There are several hundred isolated populations of dogs (breeds) and each has vastly reduced genetic variation compared to humans; this simplifies disease mapping and pharmacogenomics. Dogs age five to eight-fold faster than humans, share environments with their owners, are usually kept until old age, and receive a high level of health care. Farseeing investigators recognized this potential and, over the last decade, developed the necessary tools and infrastructure to utilize this powerful model of human disease, including the sequencing of the dog genome in 2005. Here we review the nascent convergence of genetic and translational canine models of spontaneous disease, focusing on cancer. PMID:21439907

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.

Application of the human needs conceptual model of dental hygiene to the role of the clinician : part II.

PubMed

Walsh, M M; Darby, M

1993-01-01

In summary, the theories of Maslow and of Yura and Walsh have been highlighted as background for understanding the human needs conceptual model of dental hygiene. In addition, 11 human needs have been identified and defined as being especially related to dental hygiene care, and a sample evaluation tool for their clinical assessment and a dental hygiene care plan have been presented. The four concepts of client, environment, health/oral health, and dental hygiene actions explained in terms of human need theory, and the 11 human needs related to dental hygiene care constitute the human needs conceptual model of dental hygiene. Within the framework of the human needs conceptual model of dental hygiene, the dental hygiene process is a systematic approach to dental hygiene care that involves assessment of the 11 human needs related to dental hygiene care; analysis of deficits in these needs; determination of the dental hygiene care plan based on identified deficits; implementation of dental hygiene interventions stated in the care plan; and evaluation of the effectiveness of dental hygiene interventions in achieving specific goals, including subsequent reassessment and revision of the dental hygiene care plan. This human needs conceptual model for dental hygiene provides a guide for comprehensive and humanistic client care. This model allows the dental hygienist to view each client (whether an individual or a group) holistically to prevent oral disease and to promote health and wellness. Dental hygiene theorists are encouraged to expand this model or to develop additional conceptual models based on dental hygiene's paradigm.

FlyBase portals to human disease research using Drosophila models

PubMed Central

Millburn, Gillian H.; Crosby, Madeline A.; Gramates, L. Sian; Tweedie, Susan

2016-01-01

ABSTRACT The use of Drosophila melanogaster as a model for studying human disease is well established, reflected by the steady increase in both the number and proportion of fly papers describing human disease models in recent years. In this article, we highlight recent efforts to improve the availability and accessibility of the disease model information in FlyBase (http://flybase.org), the model organism database for Drosophila. FlyBase has recently introduced Human Disease Model Reports, each of which presents background information on a specific disease, a tabulation of related disease subtypes, and summaries of experimental data and results using fruit flies. Integrated presentations of relevant data and reagents described in other sections of FlyBase are incorporated into these reports, which are specifically designed to be accessible to non-fly researchers in order to promote collaboration across model organism communities working in translational science. Another key component of disease model information in FlyBase is that data are collected in a consistent format ­­– using the evolving Disease Ontology (an open-source standardized ontology for human-disease-associated biomedical data) – to allow robust and intuitive searches. To facilitate this, FlyBase has developed a dedicated tool for querying and navigating relevant data, which include mutations that model a disease and any associated interacting modifiers. In this article, we describe how data related to fly models of human disease are presented in individual Gene Reports and in the Human Disease Model Reports. Finally, we discuss search strategies and new query tools that are available to access the disease model data in FlyBase. PMID:26935103

Modeling human behaviors and reactions under dangerous environment.

PubMed

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

2005-01-01

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

Beyond Study Abroad: A Human Rights Delegation to Teach Policy Advocacy

ERIC Educational Resources Information Center

Gammonley, Denise; Rotabi, Karen Smith; Forte, Janett; Martin, Amanda

2013-01-01

Advancement of human rights is a core competency in the social work curriculum. Presented is a model to teach policy practice from a human rights perspective based on a violence-against-women delegation visit to Guatemala. Postdelegation policy advocacy responses included White House and State Department briefings on the problems, including…

Effects of chemicals and pathway inhibitors on a human in vitro model of secondary palatal fusion.

EPA Science Inventory

The mechanisms of tissue and organ formation during embryonic development are unique, but many tissues like the iris, urethra, heart, neural tube, and palate rely upon common cellular and tissue events including tissue fusion. Few human in vitro assays exist to study human embryo...

Using Human Induced Pluripotent Stem Cells to Model Skeletal Diseases.

PubMed

Barruet, Emilie; Hsiao, Edward C

2016-01-01

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

A fully humanized transgenic mouse model of Huntington disease

PubMed Central

Southwell, Amber L.; Warby, Simon C.; Carroll, Jeffrey B.; Doty, Crystal N.; Skotte, Niels H.; Zhang, Weining; Villanueva, Erika B.; Kovalik, Vlad; Xie, Yuanyun; Pouladi, Mahmoud A.; Collins, Jennifer A.; Yang, X. William; Franciosi, Sonia; Hayden, Michael R.

2013-01-01

Silencing the mutant huntingtin gene (muHTT) is a direct and simple therapeutic strategy for the treatment of Huntington disease (HD) in principle. However, targeting the HD mutation presents challenges because it is an expansion of a common genetic element (a CAG tract) that is found throughout the genome. Moreover, the HTT protein is important for neuronal health throughout life, and silencing strategies that also reduce the wild-type HTT allele may not be well tolerated during the long-term treatment of HD. Several HTT silencing strategies are in development that target genetic sites in HTT that are outside of the CAG expansion, including HD mutation-linked single-nucleotide polymorphisms and the HTT promoter. Preclinical testing of these genetic therapies has required the development of a new mouse model of HD that carries these human-specific genetic targets. To generate a fully humanized mouse model of HD, we have cross-bred BACHD and YAC18 on the Hdh−/− background. The resulting line, Hu97/18, is the first murine model of HD that fully genetically recapitulates human HD having two human HTT genes, no mouse Hdh genes and heterozygosity of the HD mutation. We find that Hu97/18 mice display many of the behavioral changes associated with HD including motor, psychiatric and cognitive deficits, as well as canonical neuropathological abnormalities. This mouse line will be useful for gaining additional insights into the disease mechanisms of HD as well as for testing genetic therapies targeting human HTT. PMID:23001568

A preliminary regional PBPK model of lung metabolism for improving species dependent descriptions of 1,3-butadiene and its metabolites.

PubMed

Campbell, Jerry; Van Landingham, Cynthia; Crowell, Susan; Gentry, Robinan; Kaden, Debra; Fiebelkorn, Stacy; Loccisano, Anne; Clewell, Harvey

2015-08-05

1,3-Butadiene (BD), a volatile organic chemical (VOC), is used in synthetic rubber production and other industrial processes. It is detectable at low levels in ambient air as well as in tobacco smoke and gasoline vapors. Inhalation exposures to high concentrations of BD have been associated with lung cancer in both humans and experimental animals, although differences in species sensitivity have been observed. Metabolically active lung cells such as Pulmonary Type I and Type II epithelial cells and club cells (Clara cells)(1) are potential targets of BD metabolite-induced toxicity. Metabolic capacities of these cells, their regional densities, and distributions vary throughout the respiratory tract as well as between species and cell types. Here we present a physiologically based pharmacokinetic (PBPK) model for BD that includes a regional model of lung metabolism, based on a previous model for styrene, to provide species-dependent descriptions of BD metabolism in the mouse, rat, and human. Since there are no in vivo data on BD pharmacokinetics in the human, the rat and mouse models were parameterized to the extent possible on the basis of in vitro metabolic data. Where it was necessary to use in vivo data, extrapolation from rat to mouse was performed to evaluate the level of uncertainty in the human model. A kidney compartment and description of downstream metabolism were also included in the model to allow for eventual use of available urinary and blood biomarker data in animals and humans to calibrate the model for estimation of BD exposures and internal metabolite levels. Results from simulated inhalation exposures to BD indicate that incorporation of differential lung region metabolism is important in describing species differences in pulmonary response and that these differences may have implications for risk assessments of human exposures to BD. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

A preliminary regional PBPK model of lung metabolism for improving species dependent descriptions of 1,3-butadiene and its metabolites

DOE PAGES

Campbell, Jerry; Van Landingham, Cynthia; Crowell, Susan; ...

2015-06-12

1,3-Butadiene (BD), a volatile organic chemical (VOC), is used in synthetic rubber production and other industrial processes. It is detectable at low levels in ambient air as well as in tobacco smoke and gasoline vapors. Inhalation exposures to high concentrations of BD have been associated with lung cancer in both humans and experimental animals, although differences in species sensitivity have been observed. Metabolically active lung cells such as Pulmonary Type I and Type II epithelial cells and club cells (Clara cells) 1 are potential targets of BD metabolite-induced toxicity. Metabolic capacities of these cells, their regional densities, and distributions varymore » throughout the respiratory tract as well as between species and cell types. Here we present a physiologically based pharmacokinetic (PBPK) model for BD that includes a regional model of lung metabolism, based on a previous model for styrene, to provide species-dependent descriptions of BD metabolism in the mouse, rat, and human. Since there are no in vivo data on BD pharmacokinetics in the human, the rat and mouse models were parameterized to the extent possible on the basis of in vitro metabolic data. Where it was necessary to use in vivo data, extrapolation from rat to mouse was performed to evaluate the level of uncertainty in the human model. A kidney compartment and description of downstream metabolism were also included in the model to allow for eventual use of available urinary and blood biomarker data in animals and humans to calibrate the model for estimation of BD exposures and internal metabolite levels. Results from simulated inhalation exposures to BD indicate that incorporation of differential lung region metabolism is important in describing species differences in pulmonary response and that these differences may have implications for risk assessments of human exposures to BD.« less

A preliminary regional PBPK model of lung metabolism for improving species dependent descriptions of 1,3-butadiene and its metabolites

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

Campbell, Jerry; Van Landingham, Cynthia; Crowell, Susan

1,3-Butadiene (BD), a volatile organic chemical (VOC), is used in synthetic rubber production and other industrial processes. It is detectable at low levels in ambient air as well as in tobacco smoke and gasoline vapors. Inhalation exposures to high concentrations of BD have been associated with lung cancer in both humans and experimental animals, although differences in species sensitivity have been observed. Metabolically active lung cells such as Pulmonary Type I and Type II epithelial cells and club cells (Clara cells) 1 are potential targets of BD metabolite-induced toxicity. Metabolic capacities of these cells, their regional densities, and distributions varymore » throughout the respiratory tract as well as between species and cell types. Here we present a physiologically based pharmacokinetic (PBPK) model for BD that includes a regional model of lung metabolism, based on a previous model for styrene, to provide species-dependent descriptions of BD metabolism in the mouse, rat, and human. Since there are no in vivo data on BD pharmacokinetics in the human, the rat and mouse models were parameterized to the extent possible on the basis of in vitro metabolic data. Where it was necessary to use in vivo data, extrapolation from rat to mouse was performed to evaluate the level of uncertainty in the human model. A kidney compartment and description of downstream metabolism were also included in the model to allow for eventual use of available urinary and blood biomarker data in animals and humans to calibrate the model for estimation of BD exposures and internal metabolite levels. Results from simulated inhalation exposures to BD indicate that incorporation of differential lung region metabolism is important in describing species differences in pulmonary response and that these differences may have implications for risk assessments of human exposures to BD.« less

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

Safety Analysis of FMS/CTAS Interactions During Aircraft Arrivals

NASA Technical Reports Server (NTRS)

Leveson, Nancy G.

1998-01-01

This grant funded research on human-computer interaction design and analysis techniques, using future ATC environments as a testbed. The basic approach was to model the nominal behavior of both the automated and human procedures and then to apply safety analysis techniques to these models. Our previous modeling language, RSML, had been used to specify the system requirements for TCAS II for the FAA. Using the lessons learned from this experience, we designed a new modeling language that (among other things) incorporates features to assist in designing less error-prone human-computer interactions and interfaces and in detecting potential HCI problems, such as mode confusion. The new language, SpecTRM-RL, uses "intent" abstractions, based on Rasmussen's abstraction hierarchy, and includes both informal (English and graphical) specifications and formal, executable models for specifying various aspects of the system. One of the goals for our language was to highlight the system modes and mode changes to assist in identifying the potential for mode confusion. Three published papers resulted from this research. The first builds on the work of Degani on mode confusion to identify aspects of the system design that could lead to potential hazards. We defined and modeled modes differently than Degani and also defined design criteria for SpecTRM-RL models. Our design criteria include the Degani criteria but extend them to include more potential problems. In a second paper, Leveson and Palmer showed how the criteria for indirect mode transitions could be applied to a mode confusion problem found in several ASRS reports for the MD-88. In addition, we defined a visual task modeling language that can be used by system designers to model human-computer interaction. The visual models can be translated into SpecTRM-RL models, and then the SpecTRM-RL suite of analysis tools can be used to perform formal and informal safety analyses on the task model in isolation or integrated with the rest of the modeled system. We had hoped to be able to apply these modeling languages and analysis tools to a TAP air/ground trajectory negotiation scenario, but the development of the tools took more time than we anticipated.

Cognition and procedure representational requirements for predictive human performance models

NASA Technical Reports Server (NTRS)

Corker, K.

1992-01-01

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

High Resolution Spatial Mapping of Human Footprint across Antarctica and Its Implications for the Strategic Conservation of Avifauna

PubMed Central

Hughes, Kevin A.; Vega, Greta C.; Olalla-Tárraga, Miguel Á.

2017-01-01

Human footprint models allow visualization of human spatial pressure across the globe. Up until now, Antarctica has been omitted from global footprint models, due possibly to the lack of a permanent human population and poor accessibility to necessary datasets. Yet Antarctic ecosystems face increasing cumulative impacts from the expanding tourism industry and national Antarctic operator activities, the management of which could be improved with footprint assessment tools. Moreover, Antarctic ecosystem dynamics could be modelled to incorporate human drivers. Here we present the first model of estimated human footprint across predominantly ice-free areas of Antarctica. To facilitate integration into global models, the Antarctic model was created using methodologies applied elsewhere with land use, density and accessibility features incorporated. Results showed that human pressure is clustered predominantly in the Antarctic Peninsula, southern Victoria Land and several areas of East Antarctica. To demonstrate the practical application of the footprint model, it was used to investigate the potential threat to Antarctica’s avifauna by local human activities. Relative footprint values were recorded for all 204 of Antarctica’s Important Bird Areas (IBAs) identified by BirdLife International and the Scientific Committee on Antarctic Research (SCAR). Results indicated that formal protection of avifauna under the Antarctic Treaty System has been unsystematic and is lacking for penguin and flying bird species in some of the IBAs most vulnerable to human activity and impact. More generally, it is hoped that use of this human footprint model may help Antarctic Treaty Consultative Meeting policy makers in their decision making concerning avifauna protection and other issues including cumulative impacts, environmental monitoring, non-native species and terrestrial area protection. PMID:28085889

High Resolution Spatial Mapping of Human Footprint across Antarctica and Its Implications for the Strategic Conservation of Avifauna.

PubMed

Pertierra, Luis R; Hughes, Kevin A; Vega, Greta C; Olalla-Tárraga, Miguel Á

2017-01-01

Human footprint models allow visualization of human spatial pressure across the globe. Up until now, Antarctica has been omitted from global footprint models, due possibly to the lack of a permanent human population and poor accessibility to necessary datasets. Yet Antarctic ecosystems face increasing cumulative impacts from the expanding tourism industry and national Antarctic operator activities, the management of which could be improved with footprint assessment tools. Moreover, Antarctic ecosystem dynamics could be modelled to incorporate human drivers. Here we present the first model of estimated human footprint across predominantly ice-free areas of Antarctica. To facilitate integration into global models, the Antarctic model was created using methodologies applied elsewhere with land use, density and accessibility features incorporated. Results showed that human pressure is clustered predominantly in the Antarctic Peninsula, southern Victoria Land and several areas of East Antarctica. To demonstrate the practical application of the footprint model, it was used to investigate the potential threat to Antarctica's avifauna by local human activities. Relative footprint values were recorded for all 204 of Antarctica's Important Bird Areas (IBAs) identified by BirdLife International and the Scientific Committee on Antarctic Research (SCAR). Results indicated that formal protection of avifauna under the Antarctic Treaty System has been unsystematic and is lacking for penguin and flying bird species in some of the IBAs most vulnerable to human activity and impact. More generally, it is hoped that use of this human footprint model may help Antarctic Treaty Consultative Meeting policy makers in their decision making concerning avifauna protection and other issues including cumulative impacts, environmental monitoring, non-native species and terrestrial area protection.

Anatomy of large animal spines and its comparison to the human spine: a systematic review.

PubMed

Sheng, Sun-Ren; Wang, Xiang-Yang; Xu, Hua-Zi; Zhu, Guo-Qing; Zhou, Yi-Fei

2010-01-01

Animal models have been commonly used for in vivo and in vitro spinal research. However, the extent to which animal models resemble the human spine has not been well known. We conducted a systematic review to compare the morphometric features of vertebrae between human and animal species, so as to give some suggestions on how to choose an appropriate animal model in spine research. A literature search of all English language peer-reviewed publications was conducted using PubMed, OVID, Springer and Elsevier (Science Direct) for the years 1980-2008. Two reviewers extracted data on the anatomy of large animal spines from the identified articles. Each anatomical study of animals had to include at least three vertebral levels. The anatomical data from all animal studies were compared with the existing data of the human spine in the literature. Of the papers retrieved, seven were included in the review. The animals in the studies involved baboon, sheep, porcine, calf and deer. Distinct anatomical differences of vertebrae were found between the human and each large animal spine. In cervical region, spines of the baboon and human are more similar as compared to other animals. In thoracic and lumbar regions, the mean pedicle height of all animals was greater than the human pedicles. There was similar mean pedicle width between animal and the human specimens, except in thoracic segments of sheep. The human spinal canal was wider and deeper in the anteroposterior plane than any of the animals. The mean human vertebral body width and depth were greater than that of the animals except in upper thoracic segments of the deer. However, the mean vertebral body height was lower than that of all animals. This paper provides a comprehensive review to compare vertebrae geometries of experimental animal models to the human vertebrae, and will help for choosing animal model in vivo and in vitro spine research. When the animal selected for spine research, the structural similarities and differences found in the animal studies must be kept in mind.

Kalman filter estimation of human pilot-model parameters

NASA Technical Reports Server (NTRS)

Schiess, J. R.; Roland, V. R.

1975-01-01

The parameters of a human pilot-model transfer function are estimated by applying the extended Kalman filter to the corresponding retarded differential-difference equations in the time domain. Use of computer-generated data indicates that most of the parameters, including the implicit time delay, may be reasonably estimated in this way. When applied to two sets of experimental data obtained from a closed-loop tracking task performed by a human, the Kalman filter generated diverging residuals for one of the measurement types, apparently because of model assumption errors. Application of a modified adaptive technique was found to overcome the divergence and to produce reasonable estimates of most of the parameters.

Human Capital Investment and the Gender Division of Labor in a Brawn-Based Economy

PubMed Central

Pitt, Mark M.; Rosenzweig, Mark R.; Hassan, Nazmul

2013-01-01

We use a model of human capital investment and activity choice to explain facts describing gender differentials in the levels and returns to human capital investments. These include the higher return to and level of schooling, the small effect of healthiness on wages, and the large effect of healthiness on schooling for females relative to males. The model incorporates gender differences in the level and responsiveness of brawn to nutrition in a Roy-economy setting in which activities reward skill and brawn differentially. Empirical evidence from rural Bangladesh provides support for the model and the importance of the distribution of brawn. PMID:25152536

Modeling human decision making behavior in supervisory control

NASA Technical Reports Server (NTRS)

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

1977-01-01

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

Animal Models for Periodontal Disease

PubMed Central

Oz, Helieh S.; Puleo, David A.

2011-01-01

Animal models and cell cultures have contributed new knowledge in biological sciences, including periodontology. Although cultured cells can be used to study physiological processes that occur during the pathogenesis of periodontitis, the complex host response fundamentally responsible for this disease cannot be reproduced in vitro. Among the animal kingdom, rodents, rabbits, pigs, dogs, and nonhuman primates have been used to model human periodontitis, each with advantages and disadvantages. Periodontitis commonly has been induced by placing a bacterial plaque retentive ligature in the gingival sulcus around the molar teeth. In addition, alveolar bone loss has been induced by inoculation or injection of human oral bacteria (e.g., Porphyromonas gingivalis) in different animal models. While animal models have provided a wide range of important data, it is sometimes difficult to determine whether the findings are applicable to humans. In addition, variability in host responses to bacterial infection among individuals contributes significantly to the expression of periodontal diseases. A practical and highly reproducible model that truly mimics the natural pathogenesis of human periodontal disease has yet to be developed. PMID:21331345

The normative dimensions of extending the human lifespan by age-related biomedical innovations.

PubMed

Ehni, Hans-Joerg; Marckmann, Georg

2008-10-01

The current normative debate on age-related biomedical innovations and the extension of the human lifespan has important shortcomings. Mainly, the complexity of the different normative dimensions relevant for ethical and/or juridicial norms is not fully developed and the normative quality of teleological and deontological arguments is not properly distinguished. This article addresses some of these shortcomings and develops the outline of a more comprehensive normative framework covering all relevant dimensions. Such a frame necessarily has to include conceptions of a good life on the individual and societal levels. Furthermore, as a third dimension, a model for the access to and the just distribution of age-related biomedical innovations and technologies extending the human lifespan will be developed. It is argued that such a model has to include the different levels of the general philosophical theories of distributive justice, including social rights and theories of just health care. Furthermore, it has to show how these theories can be applied to the problem area of aging and extending the human lifespan.

HUMAN--A Comprehensive Physiological Model.

ERIC Educational Resources Information Center

Coleman, Thomas G.; Randall, James E.

1983-01-01

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

Human Factors in the Design and Evaluation of Air Traffic Control Systems

DTIC Science & Technology

1995-04-01

the controller must filter through and decipher. Fortunately, some of this is done without the need for conscious attention ; fcr example, a clear...components of an information-processing model ? ...................... 166 5.3 ATTENTION ......................................... 172 0 5.3.1 What is...processing? support of our performance of daily activities, including our (,) job tasks. Two models of attention currently in use assume that human infor

Modeling and analysis of passive dynamic bipedal walking with segmented feet and compliant joints

NASA Astrophysics Data System (ADS)

Huang, Yan; Wang, Qi-Ning; Gao, Yue; Xie, Guang-Ming

2012-10-01

Passive dynamic walking has been developed as a possible explanation for the efficiency of the human gait. This paper presents a passive dynamic walking model with segmented feet, which makes the bipedal walking gait more close to natural human-like gait. The proposed model extends the simplest walking model with the addition of flat feet and torsional spring based compliance on ankle joints and toe joints, to achieve stable walking on a slope driven by gravity. The push-off phase includes foot rotations around the toe joint and around the toe tip, which shows a great resemblance to human normal walking. This paper investigates the effects of the segmented foot structure on bipedal walking in simulations. The model achieves satisfactory walking results on even or uneven slopes.

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.

Development of a mathematical model of the human cardiovascular system: An educational perspective

NASA Astrophysics Data System (ADS)

Johnson, Bruce Allen

A mathematical model of the human cardiovascular system will be a useful educational tool in biological sciences and bioengineering classrooms. The goal of this project is to develop a mathematical model of the human cardiovascular system that responds appropriately to variations of significant physical variables. Model development is based on standard fluid statics and dynamics principles, pressure-volume characteristics of the cardiac cycle, and compliant behavior of blood vessels. Cardiac cycle phases provide the physical and logical model structure, and Boolean algebra links model sections. The model is implemented using VisSim, a highly intuitive and easily learned block diagram modeling software package. Comparisons of model predictions of key variables to published values suggest that the model reasonably approximates expected behavior of those variables. The model responds plausibly to variations of independent variables. Projected usefulness of the model as an educational tool is threefold: independent variables which determine heart function may be easily varied to observe cause and effect; the model is used in an interactive setting; and the relationship of governing equations to model behavior is readily viewable and intuitive. Future use of this model in classrooms may give a more reasonable indication of its value as an educational tool.* *This dissertation includes a CD that is multimedia (contains text and other applications that are not available in a printed format). The CD requires the following applications: CorelPhotoHouse, CorelWordPerfect, VisSinViewer (included on CD), Internet access.

Modeling the human body/seat system in a vibration environment.

PubMed

Rosen, Jacob; Arcan, Mircea

2003-04-01

The vibration environment is a common man-made artificial surrounding with which humans have a limited tolerance to cope due to their body dynamics. This research studied the dynamic characteristics of a seated human body/seat system in a vibration environment. The main result is a multi degrees of freedom lumped parameter model that synthesizes two basic dynamics: (i) global human dynamics, the apparent mass phenomenon, including a systematic set of the model parameters for simulating various conditions like body posture, backrest, footrest, muscle tension, and vibration directions, and (ii) the local human dynamics, represented by the human pelvis/vibrating seat contact, using a cushioning interface. The model and its selected parameters successfully described the main effects of the apparent mass phenomenon compared to experimental data documented in the literature. The model provided an analytical tool for human body dynamics research. It also enabled a primary tool for seat and cushioning design. The model was further used to develop design guidelines for a composite cushion using the principle of quasi-uniform body/seat contact force distribution. In terms of evenly distributing the contact forces, the best result for the different materials and cushion geometries simulated in the current study was achieved using a two layer shaped geometry cushion built from three materials. Combining the geometry and the mechanical characteristics of a structure under large deformation into a lumped parameter model enables successful analysis of the human/seat interface system and provides practical results for body protection in dynamic environment.

Concordant but Varied Phenotypes among Duchenne Muscular Dystrophy Patient-Specific Myoblasts Derived using a Human iPSC-Based Model.

PubMed

Choi, In Young; Lim, HoTae; Estrellas, Kenneth; Mula, Jyothi; Cohen, Tatiana V; Zhang, Yuanfan; Donnelly, Christopher J; Richard, Jean-Philippe; Kim, Yong Jun; Kim, Hyesoo; Kazuki, Yasuhiro; Oshimura, Mitsuo; Li, Hongmei Lisa; Hotta, Akitsu; Rothstein, Jeffrey; Maragakis, Nicholas; Wagner, Kathryn R; Lee, Gabsang

2016-06-07

Duchenne muscular dystrophy (DMD) remains an intractable genetic disease. Althogh there are several animal models of DMD, there is no human cell model that carries patient-specific DYSTROPHIN mutations. Here, we present a human DMD model using human induced pluripotent stem cells (hiPSCs). Our model reveals concordant disease-related phenotypes with patient-dependent variation, which are partially reversed by genetic and pharmacological approaches. Our "chemical-compound-based" strategy successfully directs hiPSCs into expandable myoblasts, which exhibit a myogenic transcriptional program, forming striated contractile myofibers and participating in muscle regeneration in vivo. DMD-hiPSC-derived myoblasts show disease-related phenotypes with patient-to-patient variability, including aberrant expression of inflammation or immune-response genes and collagens, increased BMP/TGFβ signaling, and reduced fusion competence. Furthermore, by genetic correction and pharmacological "dual-SMAD" inhibition, the DMD-hiPSC-derived myoblasts and genetically corrected isogenic myoblasts form "rescued" multi-nucleated myotubes. In conclusion, our findings demonstrate the feasibility of establishing a human "DMD-in-a-dish" model using hiPSC-based disease modeling. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

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

DTIC Science & Technology

2015-10-01

xenograft models . 12-36 Dr. Engelman Subtask 3: Analyze CTCs for P-4EBP1, P-S6, BIM , Bcl-2, Bcl-xL, and Mcl-1 using ISH and IHC We propose...Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells PRINCIPAL INVESTIGATOR: Jeffrey Engelman MD PhD CONTRACTING...reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions

Biology of obesity: lessons from animal models of obesity.

PubMed

Kanasaki, Keizo; Koya, Daisuke

2011-01-01

Obesity is an epidemic problem in the world and is associated with several health problems, including diabetes, cardiovascular disease, respiratory failure, muscle weakness, and cancer. The precise molecular mechanisms by which obesity induces these health problems are not yet clear. To better understand the pathomechanisms of human disease, good animal models are essential. In this paper, we will analyze animal models of obesity and their use in the research of obesity-associated human health conditions and diseases such as diabetes, cancer, and obstructive sleep apnea syndrome.

Fractional poisson--a simple dose-response model for human norovirus.

PubMed

Messner, Michael J; Berger, Philip; Nappier, Sharon P

2014-10-01

This study utilizes old and new Norovirus (NoV) human challenge data to model the dose-response relationship for human NoV infection. The combined data set is used to update estimates from a previously published beta-Poisson dose-response model that includes parameters for virus aggregation and for a beta-distribution that describes variable susceptibility among hosts. The quality of the beta-Poisson model is examined and a simpler model is proposed. The new model (fractional Poisson) characterizes hosts as either perfectly susceptible or perfectly immune, requiring a single parameter (the fraction of perfectly susceptible hosts) in place of the two-parameter beta-distribution. A second parameter is included to account for virus aggregation in the same fashion as it is added to the beta-Poisson model. Infection probability is simply the product of the probability of nonzero exposure (at least one virus or aggregate is ingested) and the fraction of susceptible hosts. The model is computationally simple and appears to be well suited to the data from the NoV human challenge studies. The model's deviance is similar to that of the beta-Poisson, but with one parameter, rather than two. As a result, the Akaike information criterion favors the fractional Poisson over the beta-Poisson model. At low, environmentally relevant exposure levels (<100), estimation error is small for the fractional Poisson model; however, caution is advised because no subjects were challenged at such a low dose. New low-dose data would be of great value to further clarify the NoV dose-response relationship and to support improved risk assessment for environmentally relevant exposures. © 2014 Society for Risk Analysis Published 2014. This article is a U.S. Government work and is in the public domain for the U.S.A.

Using the Past in the Class: Learning from Historical Models of Cell Membranes.

ERIC Educational Resources Information Center

Johnson, Cameron; Luft, Julie A.

2001-01-01

Including historical events and cultural contexts to enrich science teaching helps students understand the human aspect of science. Describes a sample lesson that includes the historical milestones that led to our current understanding of the structure of cell membranes. Examines the development and use of scientific models within the historical…

Confronting human papilloma virus/oropharyngeal cancer: a model for interprofessional collaboration.

PubMed

Fried, Jacquelyn L

2014-06-01

A collaborative practice model related to Human Papilloma Virus (HPV) associated oropharyngeal cancer highlights the role of the dental hygienist in addressing this condition. The incidence of HPV associated head and neck cancer is rising. Multiple professionals including the dental hygienist can work collaboratively to confront this growing public health concern. A critical review applies the growth and utilization of interprofessional education (IPE) and interprofessional collaboration (IPC) to multi-disciplinary models addressing the human papilloma virus and oropharyngeal cancers. A model related to HPV associated oropharyngeal cancer addresses an oral systemic condition that supports the inclusion of a dental hygienist on collaborative teams addressing prevention, detection, treatment and cure of OPC. Copyright © 2014 Elsevier Inc. All rights reserved.

Advances in mechanisms of allergy.

PubMed

Bochner, Bruce S; Busse, William W

2004-05-01

This review summarizes selected Mechanisms of Allergy articles appearing between 2002 and 2003 in the Journal of Allergy and Clinical Immunology. Articles chosen include those dealing with human airways disease pathophysiology, pharmacology, cell biology, cell recruitment, and genetics, as well as information from allergen challenge models in both human and nonhuman systems. When appropriate, articles from other journals have been included to supplement the topics being presented.

Understanding the Osteosarcoma Pathobiology: A Comparative Oncology Approach

PubMed Central

Varshney, Jyotika; Scott, Milcah C.; Largaespada, David A.; Subramanian, Subbaya

2016-01-01

Osteosarcoma is an aggressive primary bone tumor in humans and is among the most common cancer afflicting dogs. Despite surgical advancements and intensification of chemo- and targeted therapies, the survival outcome for osteosarcoma patients is, as of yet, suboptimal. The presence of metastatic disease at diagnosis or its recurrence after initial therapy is a major factor for the poor outcomes. It is thought that most human and canine patients have at least microscopic metastatic lesions at diagnosis. Osteosarcoma in dogs occurs naturally with greater frequency and shares many biological and clinical similarities with osteosarcoma in humans. From a genetic perspective, osteosarcoma in both humans and dogs is characterized by complex karyotypes with highly variable structural and numerical chromosomal aberrations. Similar molecular abnormalities have been observed in human and canine osteosarcoma. For instance, loss of TP53 and RB regulated pathways are common. While there are several oncogenes that are commonly amplified in both humans and dogs, such as MYC and RAS, no commonly activated proto-oncogene has been identified that could form the basis for targeted therapies. It remains possible that recurrent aberrant gene expression changes due to gene amplification or epigenetic alterations could be uncovered and these could be used for developing new, targeted therapies. However, the remarkably high genomic complexity of osteosarcoma has precluded their definitive identification. Several advantageous murine models of osteosarcoma have been generated. These include spontaneous and genetically engineered mouse models, including a model based on forward genetics and transposon mutagenesis allowing new genes and genetic pathways to be implicated in osteosarcoma development. The proposition of this review is that careful comparative genomic studies between human, canine and mouse models of osteosarcoma may help identify commonly affected and targetable pathways for alternative therapies for osteosarcoma patients. Translational research may be found through a path that begins in mouse models, and then moves through canine patients, and then human patients. PMID:29056713

One-Health Simulation Modelling: A Case Study of Influenza Spread between Human and Swine Populations using NAADSM.

PubMed

Dorjee, S; Revie, C W; Poljak, Z; McNab, W B; Sanchez, J

2016-02-01

The circulation of zoonotic influenza A viruses including pH1N1 2009 and H5N1 continue to present a constant threat to animal and human populations. Recently, an H3N2 variant spread from pigs to humans and between humans in limited numbers. Accordingly, this research investigated a range of scenarios of the transmission dynamics of pH1N1 2009 virus at the swine-human interface while accounting for different percentages of swine workers initially immune. Furthermore, the feasibility of using NAADSM (North American Animal Disease Spread Model) applied as a one-health simulation model was assessed. The study population included 488 swine herds and 29, 707 households of people within a county in Ontario, Canada. Households were categorized as follows: (i) rural households with swine workers, (ii) rural households without swine workers, and (iii) urban households without swine workers. Forty-eight scenarios were investigated, based on the combination of six scenarios around the transmissibility of the virus at the interface and four vaccination coverage levels of swine workers (0-60%), all under two settings of either swine or human origin of the virus. Outcomes were assessed in terms of stochastic 'die-out' fraction, size and time to peak epidemic day, overall size and duration of the outbreaks. The modelled outcomes indicated that minimizing influenza transmissibility at the interface and targeted vaccination of swine workers had significant beneficial effects. Our results indicate that NAADSM can be used as a framework to model the spread and control of contagious zoonotic diseases among animal and human populations, under certain simplifying assumptions. Further evaluation of the model is required. In addition to these specific findings, this study serves as a benchmark that can provide useful input to a future one-health influenza modelling studies. Some pertinent information gaps were also identified. Enhanced surveillance and the collection of high-quality information for more accurate parameterization of such models are encouraged. © 2014 Blackwell Verlag GmbH.

Genetics of SLE: evidence from mouse models.

PubMed

Morel, Laurence

2010-06-01

Great progress has been made in the field of lupus genetics in the past few years, notably with the publication of genome-wide association studies in humans and the identification of susceptibility genes (including Fcgr2b, Ly108, Kallikrein genes and Coronin-1A) in mouse models of spontaneous lupus. This influx of new information has revealed an ever-increasing interdependence between the mouse and human systems for unraveling the genetic basis of lupus susceptibility. Studies in the 1980s and 1990s established that mice prone to spontaneous lupus constitute excellent models of the genetic architecture of human systemic lupus erythematosus (SLE). This notion has been greatly strengthened by the convergence of the functional pathways that are defective in both human and murine lupus. Within these pathways, variants in a number of genes have now been shown to be directly associated with lupus in both species. Consequently, mouse models will continue to serve a pre-eminent role in lupus genetics research, with an increased emphasis on mechanistic and molecular studies of human susceptibility alleles.

Common ecology quantifies human insurgency.

PubMed

Bohorquez, Juan Camilo; Gourley, Sean; Dixon, Alexander R; Spagat, Michael; Johnson, Neil F

2009-12-17

Many collective human activities, including violence, have been shown to exhibit universal patterns. The size distributions of casualties both in whole wars from 1816 to 1980 and terrorist attacks have separately been shown to follow approximate power-law distributions. However, the possibility of universal patterns ranging across wars in the size distribution or timing of within-conflict events has barely been explored. Here we show that the sizes and timing of violent events within different insurgent conflicts exhibit remarkable similarities. We propose a unified model of human insurgency that reproduces these commonalities, and explains conflict-specific variations quantitatively in terms of underlying rules of engagement. Our model treats each insurgent population as an ecology of dynamically evolving, self-organized groups following common decision-making processes. Our model is consistent with several recent hypotheses about modern insurgency, is robust to many generalizations, and establishes a quantitative connection between human insurgency, global terrorism and ecology. Its similarity to financial market models provides a surprising link between violent and non-violent forms of human behaviour.

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

PubMed

Szabó, Viktor; Halász, Gábor

2017-07-01

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

A mathematical model of Chagas disease transmission

NASA Astrophysics Data System (ADS)

Hidayat, Dayat; Nugraha, Edwin Setiawan; Nuraini, Nuning

2018-03-01

Chagas disease is a parasitic infection caused by protozoan Trypanosoma cruzi which is transmitted to human by insects of the subfamily Triatominae, including Rhodnius prolixus. This disease is a major problem in several countries of Latin America. A mathematical model of Chagas disease with separate vector reservoir and a neighboring human resident is constructed. The basic reproductive ratio is obtained and stability analysis of the equilibria is shown. We also performed sensitivity populations dynamics of infected humans and infected insects based on migration rate, carrying capacity, and infection rate parameters. Our findings showed that the dynamics of the infected human and insect is mostly affected by carrying capacity insect in the settlement.

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.

Development of a Finite Element Model of the Human Shoulder to Investigate the Mechanical Responses and Injuries in Side Impact

NASA Astrophysics Data System (ADS)

Iwamoto, Masami; Miki, Kazuo; Yang, King H.

Previous studies in both fields of automotive safety and orthopedic surgery have hypothesized that immobilization of the shoulder caused by the shoulder injury could be related to multiple rib fractures, which are frequently life threatening. Therefore, for more effective occupant protection, it is important to understand the relationship between shoulder injury and multiple rib fractures in side impact. The purpose of this study is to develop a finite element model of the human shoulder in order to understand this relationship. The shoulder model included three bones (the humerus, scapula and clavicle) and major ligaments and muscles around the shoulder. The model also included approaches to represent bone fractures and joint dislocations. The relationships between shoulder injury and immobilization of the shoulder are discussed using model responses for lateral shoulder impact. It is also discussed how the injury can be related to multiple rib fractures.

Beyond the Ego: Toward Transpersonal Models of the Person and Psychotherapy.

ERIC Educational Resources Information Center

Walsh, Roger N.; Vaughan, Frances

1980-01-01

Discusses a transpersonal model which, like a humanistic model, focuses on the human potential for growth, health, and well-being. It goes beyond existing models to include self-transcendence and emphasizes the centrality of consciousness in shaping experience and enhancing well-being. (Author)

Translation: screening for novel therapeutics with disease-relevant cell types derived from human stem cell models.

PubMed

Haggarty, Stephen J; Perlis, Roy H

2014-06-15

The advent of somatic cell reprogramming technologies-which enables the generation of patient-specific, induced pluripotent stem cell and other trans-differentiated human neuronal cell models-provides new means of gaining insight into the molecular mechanisms and neural substrates of psychiatric disorders. By allowing a more precise understanding of genotype-phenotype relationship in disease-relevant human cell types, the use of reprogramming technologies in tandem with emerging genome engineering approaches provides a previously "missing link" between basic research and translational efforts. In this review, we summarize advances in applying human pluripotent stem cell and reprogramming technologies to generate specific neural subtypes with a focus on the use of these in vitro systems for the discovery of small molecule-probes and novel therapeutics. Examples are given where human cell models of psychiatric disorders have begun to reveal new mechanistic insight into pathophysiology and simultaneously have provided the foundation for developing disease-relevant, phenotypic assays suitable for both functional genomic and chemical screens. A number of areas for future research are discussed, including the need to develop robust methodology for the reproducible, large-scale production of disease-relevant neural cell types in formats compatible with high-throughput screening modalities, including high-content imaging, multidimensional, signature-based screening, and in vitro network with multielectrode arrays. Limitations, including the challenges in recapitulating neurocircuits and non-cell autonomous phenotypes are discussed. Although these technologies are still in active development, we conclude that, as our understanding of how to efficiently generate and probe the plasticity of patient-specific stem models improves, their utility is likely to advance rapidly. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Growing evidence for human health benefits of boron

USDA-ARS?s Scientific Manuscript database

Growing evidence from numerous laboratories using a variety of experimental models shows that boron is a bioactive beneficial, perhaps essential, element for humans. Reported beneficial actions of boron include arthritis alleviation or risk reduction; bone growth and maintenance; central nervous sys...

Mutant mice: experimental organisms as materialised models in biomedicine.

PubMed

Huber, Lara; Keuck, Lara K

2013-09-01

Animal models have received particular attention as key examples of material models. In this paper, we argue that the specificities of establishing animal models-acknowledging their status as living beings and as epistemological tools-necessitate a more complex account of animal models as materialised models. This becomes particularly evident in animal-based models of diseases that only occur in humans: in these cases, the representational relation between animal model and human patient needs to be generated and validated. The first part of this paper presents an account of how disease-specific animal models are established by drawing on the example of transgenic mice models for Alzheimer's disease. We will introduce an account of validation that involves a three-fold process including (1) from human being to experimental organism; (2) from experimental organism to animal model; and (3) from animal model to human patient. This process draws upon clinical relevance as much as scientific practices and results in disease-specific, yet incomplete, animal models. The second part of this paper argues that the incompleteness of models can be described in terms of multi-level abstractions. We qualify this notion by pointing to different experimental techniques and targets of modelling, which give rise to a plurality of models for a specific disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Construction and evaluation of thoracic injury risk curves for a finite element human body model in frontal car crashes.

PubMed

Mendoza-Vazquez, Manuel; Davidsson, Johan; Brolin, Karin

2015-12-01

There is a need to improve the protection to the thorax of occupants in frontal car crashes. Finite element human body models are a more detailed representation of humans than anthropomorphic test devices (ATDs). On the other hand, there is no clear consensus on the injury criteria and the thresholds to use with finite element human body models to predict rib fractures. The objective of this study was to establish a set of injury risk curves to predict rib fractures using a modified Total HUman Model for Safety (THUMS). Injury criteria at the global, structural and material levels were computed with a modified THUMS in matched Post Mortem Human Subjects (PMHSs) tests. Finally, the quality of each injury risk curve was determined. For the included PMHS tests and the modified THUMS, DcTHOR and shear stress were the criteria at the global and material levels that reached an acceptable quality. The injury risk curves at the structural level did not reach an acceptable quality. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Multiple hypotheses testing of fish incidence patterns in an urbanized ecosystem

USGS Publications Warehouse

Chizinski, C.J.; Higgins, C.L.; Shavlik, C.E.; Pope, K.L.

2006-01-01

Ecological and evolutionary theories have focused traditionally on natural processes with little attempt to incorporate anthropogenic influences despite the fact that humans are such an integral part of virtually all ecosystems. A series of alternate models that incorporated anthropogenic factors and traditional ecological mechanisms of invasion to account for fish incidence patterns in urban lakes was tested. The models were based on fish biology, human intervention, and habitat characteristics. However, the only models to account for empirical patterns were those that included fish invasiveness, which incorporated species-specific information about overall tolerance and fecundity. This suggests that species-specific characteristics are more important in general distributional patterns than human-mediated dispersal. Better information of illegal stocking activities is needed to improve human-mediated models, and more insight into basic life history of ubiquitous species is needed to truly understand underlying mechanisms of biotic homogenization. ?? Springer 2005.

Active site similarity between human and Plasmodium falciparum phosphodiesterases: considerations for antimalarial drug design

NASA Astrophysics Data System (ADS)

Howard, Brittany L.; Thompson, Philip E.; Manallack, David T.

2011-08-01

The similarity between Plasmodium falciparum phosphodiesterase enzymes ( PfPDEs) and their human counterparts have been examined and human PDE9A was found to be a suitable template for the construction of homology models for each of the four PfPDE isoforms. In contrast, the architecture of the active sites of each model was most similar to human PDE1. Molecular docking was able to model cyclic guanosine monophosphate (cGMP) substrate binding in each case but a docking mode supporting cyclic adenosine monophosphate (cAMP) binding could not be found. Anticipating the potential of PfPDE inhibitors as anti-malarial drugs, a range of reported PDE inhibitors including zaprinast and sildenafil were docked into the model of PfPDEα. The results were consistent with their reported biological activities, and the potential of PDE1/9 inhibitor analogues was also supported by docking.

Use of animal models for space flight physiology studies, with special focus on the immune system

NASA Technical Reports Server (NTRS)

Sonnenfeld, Gerald

2005-01-01

Animal models have been used to study the effects of space flight on physiological systems. The animal models have been used because of the limited availability of human subjects for studies to be carried out in space as well as because of the need to carry out experiments requiring samples and experimental conditions that cannot be performed using humans. Experiments have been carried out in space using a variety of species, and included developmental biology studies. These species included rats, mice, non-human primates, fish, invertebrates, amphibians and insects. The species were chosen because they best fit the experimental conditions required for the experiments. Experiments with animals have also been carried out utilizing ground-based models that simulate some of the effects of exposure to space flight conditions. Most of the animal studies have generated results that parallel the effects of space flight on human physiological systems. Systems studied have included the neurovestibular system, the musculoskeletal system, the immune system, the neurological system, the hematological system, and the cardiovascular system. Hindlimb unloading, a ground-based model of some of the effects of space flight on the immune system, has been used to study the effects of space flight conditions on physiological parameters. For the immune system, exposure to hindlimb unloading has been shown to results in alterations of the immune system similar to those observed after space flight. This has permitted the development of experiments that demonstrated compromised resistance to infection in rodents maintained in the hindlimb unloading model as well as the beginning of studies to develop countermeasures to ameliorate or prevent such occurrences. Although there are limitations to the use of animal models for the effects of space flight on physiological systems, the animal models should prove very valuable in designing countermeasures for exploration class missions of the future.

New equivalent-electrical circuit model and a practical measurement method for human body impedance.

PubMed

Chinen, Koyu; Kinjo, Ichiko; Zamami, Aki; Irei, Kotoyo; Nagayama, Kanako

2015-01-01

Human body impedance analysis is an effective tool to extract electrical information from tissues in the human body. This paper presents a new measurement method of impedance using armpit electrode and a new equivalent circuit model for the human body. The lowest impedance was measured by using an LCR meter and six electrodes including armpit electrodes. The electrical equivalent circuit model for the cell consists of resistance R and capacitance C. The R represents electrical resistance of the liquid of the inside and outside of the cell, and the C represents high frequency conductance of the cell membrane. We propose an equivalent circuit model which consists of five parallel high frequency-passing CR circuits. The proposed equivalent circuit represents alpha distribution in the impedance measured at a lower frequency range due to ion current of the outside of the cell, and beta distribution at a high frequency range due to the cell membrane and the liquid inside cell. The calculated values by using the proposed equivalent circuit model were consistent with the measured values for the human body impedance.

Operator dynamics for stability condition in haptic and teleoperation system: A survey.

PubMed

Li, Hongbing; Zhang, Lei; Kawashima, Kenji

2018-04-01

Currently, haptic systems ignore the varying impedance of the human hand with its countless configurations and thus cannot recreate the complex haptic interactions. The literature does not reveal a comprehensive survey on the methods proposed and this study is an attempt to bridge this gap. The paper includes an extensive review of human arm impedance modeling and control deployed to address inherent stability and transparency issues in haptic interaction and teleoperation systems. Detailed classification and comparative study of various contributions in human arm modeling are presented and summarized in tables and diagrams. The main challenges in modeling human arm impedance for haptic robotic applications are identified. The possible future research directions are outlined based on the gaps identified in the survey. Copyright © 2018 John Wiley & Sons, Ltd.

Hierarchical graphical-based human pose estimation via local multi-resolution convolutional neural network

NASA Astrophysics Data System (ADS)

Zhu, Aichun; Wang, Tian; Snoussi, Hichem

2018-03-01

This paper addresses the problems of the graphical-based human pose estimation in still images, including the diversity of appearances and confounding background clutter. We present a new architecture for estimating human pose using a Convolutional Neural Network (CNN). Firstly, a Relative Mixture Deformable Model (RMDM) is defined by each pair of connected parts to compute the relative spatial information in the graphical model. Secondly, a Local Multi-Resolution Convolutional Neural Network (LMR-CNN) is proposed to train and learn the multi-scale representation of each body parts by combining different levels of part context. Thirdly, a LMR-CNN based hierarchical model is defined to explore the context information of limb parts. Finally, the experimental results demonstrate the effectiveness of the proposed deep learning approach for human pose estimation.

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 Systems Integration (HSI) Tradeoff Model

DTIC Science & Technology

2014-03-01

Distribution A: Approved for public release; distribution is unlimited. AIR FORCE RESEARCH LABORATORY 711TH HUMAN PERFORMANCE WING HUMAN SYSTEMS...This report was cleared for public release by the 88th Air Base Wing Public Affairs Office and is available to the general public , including...BEEN REVIEWED AND IS APPROVED FOR PUBLICATION IN ACCORDANCE WITH ASSIGNED DISTRIBUTION STATEMENT. //SIGNATURE// ANTHONY P

A Model Human Sexuality--HIV/AIDS Prevention and Intervention Service-Learning Program

ERIC Educational Resources Information Center

Stewart, Clarence, M., Jr.

2005-01-01

This article deals with a service-learning program focused on human sexuality and HIV/AIDS prevention and intervention at the Howard University Department of Health, Human Performance and Leisure Studies. Topics discussed include how this program was created, an overview of peer education, HIV/AIDS peer education training, and services provided to…

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.

Plasmodium vivax: modern strategies to study a persistent parasite's life cycle.

PubMed

Galinski, Mary R; Meyer, Esmeralda V S; Barnwell, John W

2013-01-01

Plasmodium vivax has unique attributes to support its survival in varying ecologies and climates. These include hypnozoite forms in the liver, an invasion preference for reticulocytes, caveola-vesicle complex structures in the infected erythrocyte membrane and rapidly forming and circulating gametocytes. These characteristics make this species very different from P. falciparum. Plasmodium cynomolgi and other related simian species have identical biology and can serve as informative models of P. vivax infections. Plasmodium vivax and its model parasites can be grown in non-human primates (NHP), and in short-term ex vivo cultures. For P. vivax, in the absence of in vitro culture systems, these models remain highly relevant side by side with human clinical studies. While post-genomic technologies allow for greater exploration of P. vivax-infected blood samples from humans, these come with restrictions. Two advantages of NHP models are that infections can be experimentally tailored to address hypotheses, including genetic manipulation. Also, systems biology approaches can capitalise on computational biology combined with set experimental infection periods and protocols, which may include multiple sampling times, different types of samples, and the broad use of "omics" technologies. Opportunities for research on vivax malaria are increasing with the use of existing and new methodological strategies in combination with modern technologies. Copyright © 2013 Elsevier Ltd. All rights reserved.

A three-dimensional human neural cell culture model of Alzheimer's disease.

PubMed

Choi, Se Hoon; Kim, Young Hye; Hebisch, Matthias; Sliwinski, Christopher; Lee, Seungkyu; D'Avanzo, Carla; Chen, Hechao; Hooli, Basavaraj; Asselin, Caroline; Muffat, Julien; Klee, Justin B; Zhang, Can; Wainger, Brian J; Peitz, Michael; Kovacs, Dora M; Woolf, Clifford J; Wagner, Steven L; Tanzi, Rudolph E; Kim, Doo Yeon

2014-11-13

Alzheimer's disease is the most common form of dementia, characterized by two pathological hallmarks: amyloid-β plaques and neurofibrillary tangles. The amyloid hypothesis of Alzheimer's disease posits that the excessive accumulation of amyloid-β peptide leads to neurofibrillary tangles composed of aggregated hyperphosphorylated tau. However, to date, no single disease model has serially linked these two pathological events using human neuronal cells. Mouse models with familial Alzheimer's disease (FAD) mutations exhibit amyloid-β-induced synaptic and memory deficits but they do not fully recapitulate other key pathological events of Alzheimer's disease, including distinct neurofibrillary tangle pathology. Human neurons derived from Alzheimer's disease patients have shown elevated levels of toxic amyloid-β species and phosphorylated tau but did not demonstrate amyloid-β plaques or neurofibrillary tangles. Here we report that FAD mutations in β-amyloid precursor protein and presenilin 1 are able to induce robust extracellular deposition of amyloid-β, including amyloid-β plaques, in a human neural stem-cell-derived three-dimensional (3D) culture system. More importantly, the 3D-differentiated neuronal cells expressing FAD mutations exhibited high levels of detergent-resistant, silver-positive aggregates of phosphorylated tau in the soma and neurites, as well as filamentous tau, as detected by immunoelectron microscopy. Inhibition of amyloid-β generation with β- or γ-secretase inhibitors not only decreased amyloid-β pathology, but also attenuated tauopathy. We also found that glycogen synthase kinase 3 (GSK3) regulated amyloid-β-mediated tau phosphorylation. We have successfully recapitulated amyloid-β and tau pathology in a single 3D human neural cell culture system. Our unique strategy for recapitulating Alzheimer's disease pathology in a 3D neural cell culture model should also serve to facilitate the development of more precise human neural cell models of other neurodegenerative disorders.

Host-pathogen interactions between the human innate immune system and Candida albicans—understanding and modeling defense and evasion strategies

PubMed Central

Dühring, Sybille; Germerodt, Sebastian; Skerka, Christine; Zipfel, Peter F.; Dandekar, Thomas; Schuster, Stefan

2015-01-01

The diploid, polymorphic yeast Candida albicans is one of the most important human pathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within the human host for a long time. However, alterations in the host environment can render C. albicans virulent. In this review, we describe the immunological cross-talk between C. albicans and the human innate immune system. We give an overview in form of pairs of human defense strategies including immunological mechanisms as well as general stressors such as nutrient limitation, pH, fever etc. and the corresponding fungal response and evasion mechanisms. Furthermore, Computational Systems Biology approaches to model and investigate these complex interactions are highlighted with a special focus on game-theoretical methods and agent-based models. An outlook on interesting questions to be tackled by Systems Biology regarding entangled defense and evasion mechanisms is given. PMID:26175718

Avian Models for Human Cognitive Neuroscience: A Proposal.

PubMed

Clayton, Nicola S; Emery, Nathan J

2015-06-17

Research on avian cognitive neuroscience over the past two decades has revealed the avian brain to be a better model for understanding human cognition than previously thought, despite differences in the neuroarchitecture of avian and mammalian brains. The brain, behavior, and cognition of songbirds have provided an excellent model of human cognition in one domain, namely learning human language and the production of speech. There are other important behavioral candidates of avian cognition, however, notably the capacity of corvids to remember the past and plan for the future, as well as their ability to think about another's perspective, and physical reasoning. We review this work and assess the evidence that the corvid brain can support such a cognitive architecture. We propose potential applications of these behavioral paradigms for cognitive neuroscience, including recent work on single-cell recordings and neuroimaging in corvids. Finally, we discuss their impact on understanding human developmental cognition. Copyright © 2015 Elsevier Inc. All rights reserved.

Reproduction of Epstein-Barr Virus Infection and Pathogenesis in Humanized Mice

PubMed Central

2014-01-01

Epstein-Barr virus (EBV) is etiologically associated with a variety of diseases including lymphoproliferative diseases, lymphomas, carcinomas, and autoimmune diseases. Humans are the only natural host of EBV and limited species of new-world monkeys can be infected with the virus in experimental conditions. Small animal models of EBV infection, required for evaluation of novel therapies and vaccines for EBV-associated diseases, have not been available. Recently the development of severely immunodeficient mouse strains enabled production of humanized mice in which human immune system components are reconstituted and express their normal functions. Humanized mice can serve as infection models for human-specific viruses such as EBV that target cells of the immune system. This review summarizes recent studies by the author's group addressing reproduction of EBV infection and pathogenesis in humanized mice. PMID:24605074

FlyBase portals to human disease research using Drosophila models.

PubMed

Millburn, Gillian H; Crosby, Madeline A; Gramates, L Sian; Tweedie, Susan

2016-03-01

The use of Drosophila melanogaster as a model for studying human disease is well established, reflected by the steady increase in both the number and proportion of fly papers describing human disease models in recent years. In this article, we highlight recent efforts to improve the availability and accessibility of the disease model information in FlyBase (http://flybase.org), the model organism database for Drosophila. FlyBase has recently introduced Human Disease Model Reports, each of which presents background information on a specific disease, a tabulation of related disease subtypes, and summaries of experimental data and results using fruit flies. Integrated presentations of relevant data and reagents described in other sections of FlyBase are incorporated into these reports, which are specifically designed to be accessible to non-fly researchers in order to promote collaboration across model organism communities working in translational science. Another key component of disease model information in FlyBase is that data are collected in a consistent format --- using the evolving Disease Ontology (an open-source standardized ontology for human-disease-associated biomedical data) - to allow robust and intuitive searches. To facilitate this, FlyBase has developed a dedicated tool for querying and navigating relevant data, which include mutations that model a disease and any associated interacting modifiers. In this article, we describe how data related to fly models of human disease are presented in individual Gene Reports and in the Human Disease Model Reports. Finally, we discuss search strategies and new query tools that are available to access the disease model data in FlyBase. © 2016. Published by The Company of Biologists Ltd.

Modeling asthma: Pitfalls, promises, and the road ahead.

PubMed

Rosenberg, Helene F; Druey, Kirk M

2018-02-16

Asthma is a chronic, heterogeneous, and recurring inflammatory disease of the lower airways, with exacerbations that feature airway inflammation and bronchial hyperresponsiveness. Asthma has been modeled extensively via disease induction in both wild-type and genetically manipulated laboratory mice (Mus musculus). Antigen sensitization and challenge strategies have reproduced numerous important features of airway inflammation characteristic of human asthma, notably the critical roles of type 2 T helper cell cytokines. Recent models of disease induction have advanced to include physiologic aeroallergens with prolonged respiratory challenge without systemic sensitization; others incorporate tobacco, respiratory viruses, or bacteria as exacerbants. Nonetheless, differences in lung size, structure, and physiologic responses limit the degree to which airway dynamics measured in mice can be compared to human subjects. Other rodent allergic airways models, including those featuring the guinea pig (Cavia porcellus) might be considered for lung function studies. Finally, domestic cats (Feline catus) and horses (Equus caballus) develop spontaneous obstructive airway disorders with clinical and pathologic features that parallel human asthma. Information on pathogenesis and treatment of these disorders is an important resource. ©2018 Society for Leukocyte Biology.

Myeloproliferative Neoplasm Animal Models

PubMed Central

Mullally, Ann; Lane, Steven W.; Brumme, Kristina; Ebert, Benjamin L.

2012-01-01

Synopsis Myeloproliferative neoplasm (MPN) animal models accurately re-capitulate human disease in mice and have been an important tool for the study of MPN biology and therapy. Transplantation of BCR-ABL transduced bone marrow cells into irradiated syngeneic mice established the field of MPN animal modeling and the retroviral bone marrow transplantation (BMT) assay has been used extensively since. Genetically engineered MPN animal models have enabled detailed characterization of the effects of specific MPN associated genetic abnormalities on the hematopoietic stem and progenitor cell (HSPC) compartment and xenograft models have allowed the study of primary human MPN-propagating cells in vivo. All models have facilitated the pre-clinical development of MPN therapies. JAK2V617F, the most common molecular abnormality in BCR-ABL negative MPN, has been extensively studied using retroviral, transgenic, knock-in and xenograft models. MPN animal models have also been used to investigate additional genetic lesions found in human MPN and to evaluate the bone marrow microenvironment in these diseases. Finally, several genetic lesions, although not common, somatically mutated drivers of MPN in humans induce a MPN phenotype in mice. Future uses for MPN animal models will include modeling compound genetic lesions in MPN and studying myelofibrotic transformation. PMID:23009938

A Biologically Constrained, Mathematical Model of Cortical Wave Propagation Preceding Seizure Termination

PubMed Central

González-Ramírez, Laura R.; Ahmed, Omar J.; Cash, Sydney S.; Wayne, C. Eugene; Kramer, Mark A.

2015-01-01

Epilepsy—the condition of recurrent, unprovoked seizures—manifests in brain voltage activity with characteristic spatiotemporal patterns. These patterns include stereotyped semi-rhythmic activity produced by aggregate neuronal populations, and organized spatiotemporal phenomena, including waves. To assess these spatiotemporal patterns, we develop a mathematical model consistent with the observed neuronal population activity and determine analytically the parameter configurations that support traveling wave solutions. We then utilize high-density local field potential data recorded in vivo from human cortex preceding seizure termination from three patients to constrain the model parameters, and propose basic mechanisms that contribute to the observed traveling waves. We conclude that a relatively simple and abstract mathematical model consisting of localized interactions between excitatory cells with slow adaptation captures the quantitative features of wave propagation observed in the human local field potential preceding seizure termination. PMID:25689136

Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs.

PubMed

Fulkerson, Christopher M; Dhawan, Deepika; Ratliff, Timothy L; Hahn, Noah M; Knapp, Deborah W

2017-01-01

Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs

PubMed Central

Fulkerson, Christopher M.; Ratliff, Timothy L.; Hahn, Noah M.

2017-01-01

Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed. PMID:28487862

Preclinical Mouse Models of Neurofibromatosis

DTIC Science & Technology

2005-11-01

and NF2-deficient human cells and in cells from Nf1 and Nf2 mutant mice. Genetic analysis of human and murine tumors has provided compelling...lethal myeloproliferative disorder (MPD) characterized by over-production of infiltrative myeloid cells (13). JMML has been modeled in mice by...tumor development for 18 months after exposure. Pathologic analysis was performed on 91% of the Shannon, K.M. 11 study cohort, including 95 of 104

Severe Life Stress and Oxidative Stress in the Brain: From Animal Models to Human Pathology

PubMed Central

Jaquet, Vincent; Trabace, Luigia; Krause, Karl-Heinz

2013-01-01

Abstract Significance: Severe life stress (SLS), as opposed to trivial everyday stress, is defined as a serious psychosocial event with the potential of causing an impacting psychological traumatism. Recent Advances: Numerous studies have attempted to understand how the central nervous system (CNS) responds to SLS. This response includes a variety of morphological and neurochemical modifications; among them, oxidative stress is almost invariably observed. Oxidative stress is defined as disequilibrium between oxidant generation and the antioxidant response. Critical Issues: In this review, we discuss how SLS leads to oxidative stress in the CNS, and how the latter impacts pathophysiological outcomes. We also critically discuss experimental methods that measure oxidative stress in the CNS. The review covers animal models and human observations. Animal models of SLS include sleep deprivation, maternal separation, and social isolation in rodents, and the establishment of hierarchy in non-human primates. In humans, SLS, which is caused by traumatic events such as child abuse, war, and divorce, is also accompanied by oxidative stress in the CNS. Future Directions: The outcome of SLS in humans ranges from resilience, over post-traumatic stress disorder, to development of chronic mental disorders. Defining the sources of oxidative stress in SLS might in the long run provide new therapeutic avenues. Antioxid. Redox Signal. 18, 1475–1490. PMID:22746161

Mice with chimeric livers are an improved model for human lipoprotein metabolism.

PubMed

Ellis, Ewa C S; Naugler, Willscott Edward; Nauglers, Scott; Parini, Paolo; Mörk, Lisa-Mari; Jorns, Carl; Zemack, Helen; Sandblom, Anita Lövgren; Björkhem, Ingemar; Ericzon, Bo-Göran; Wilson, Elizabeth M; Strom, Stephen C; Grompe, Markus

2013-01-01

Rodents are poor model for human hyperlipidemias because total cholesterol and low density lipoprotein levels are very low on a normal diet. Lipoprotein metabolism is primarily regulated by hepatocytes and we therefore assessed whether chimeric mice extensively repopulated with human cells can model human lipid and bile acid metabolism. FRG [ F ah(-/-) R ag2(-/-)Il2r g (-/-)]) mice were repopulated with primary human hepatocytes. Serum lipoprotein lipid composition and distribution (VLDL, LDL, and HDL) was analyzed by size exclusion chromatography. Bile was analyzed by LC-MS or by GC-MS. RNA expression levels were measured by quantitative RT-PCR. Chimeric mice displayed increased LDL and VLDL fractions and a lower HDL fraction compared to wild type, thus significantly shifting the ratio of LDL/HDL towards a human profile. Bile acid analysis revealed a human-like pattern with high amounts of cholic acid and deoxycholic acid (DCA). Control mice had only taurine-conjugated bile acids as expcted, but highly repopulated mice had glycine-conjugated cholic acid as found in human bile. RNA levels of human genes involved in bile acid synthesis including CYP7A1, and CYP27A1 were significantly upregulated as compared to human control liver. However, administration of recombinant hFGF19 restored human CYP7A1 levels to normal. Humanized-liver mice showed a typical human lipoprotein profile with LDL as the predominant lipoprotein fraction even on a normal diet. The bile acid profile confirmed presence of an intact enterohepatic circulation. Although bile acid synthesis was deregulated in this model, this could be fully normalized by FGF19 administration. Taken together these data indicate that chimeric FRG-mice are a useful new model for human lipoprotein and bile-acid metabolism.

Human performance across decision making, selective attention, and working memory tasks: Experimental data and computer simulations.

PubMed

Stocco, Andrea; Yamasaki, Brianna L; Prat, Chantel S

2018-04-01

This article describes the data analyzed in the paper "Individual differences in the Simon effect are underpinned by differences in the competitive dynamics in the basal ganglia: An experimental verification and a computational model" (Stocco et al., 2017) [1]. The data includes behavioral results from participants performing three cognitive tasks (Probabilistic Stimulus Selection (Frank et al., 2004) [2], Simon task (Craft and Simon, 1970) [3], and Automated Operation Span (Unsworth et al., 2005) [4]), as well as simulationed traces generated by a computational neurocognitive model that accounts for individual variations in human performance across the tasks. The experimental data encompasses individual data files (in both preprocessed and native output format) as well as group-level summary files. The simulation data includes the entire model code, the results of a full-grid search of the model's parameter space, and the code used to partition the model space and parallelize the simulations. Finally, the repository includes the R scripts used to carry out the statistical analyses reported in the original paper.

42 CFR § 512.735 - Enforcement authority for FFS-CR participants.

Code of Federal Regulations, 2010 CFR

2017-10-01

... HEALTH AND HUMAN SERVICES (CONTINUED) HEALTH CARE INFRASTRUCTURE AND MODEL PROGRAMS EPISODE PAYMENT MODEL CR Incentive Payment Model for EPM and Medicare Fee-for-Service Participants Provisions for Ffs-Cr... limited or restricted by the provisions of the CR incentive payment model, including the authority to...

AVAILABLE MICRO-ACTIVITY DATA AND THEIR APPLICABILITY TO AGGREGATE EXPOSURE MODELING

EPA Science Inventory

Several human exposure models have been developed in recent years to address children's aggregate and cumulative exposures to pesticides under the Food Quality Protection Act of 1996. These models estimate children's exposures via all significant routes and pathways including ...

The Emergence of Modern Humans.

ERIC Educational Resources Information Center

Stringer, Christopher B.

1990-01-01

Presented are the three main theories that describe the pattern of evolution of geographic variants of H. sapiens--the multiregional model, the out-of-Africa model, and the gene-flow or hybridization model. The contributions of geneticists, paleoanthropologists, and the history of fossils are included. (KR)

SEIPS 2.0: a human factors framework for studying and improving the work of healthcare professionals and patients.

PubMed

Holden, Richard J; Carayon, Pascale; Gurses, Ayse P; Hoonakker, Peter; Hundt, Ann Schoofs; Ozok, A Ant; Rivera-Rodriguez, A Joy

2013-01-01

Healthcare practitioners, patient safety leaders, educators and researchers increasingly recognise the value of human factors/ergonomics and make use of the discipline's person-centred models of sociotechnical systems. This paper first reviews one of the most widely used healthcare human factors systems models, the Systems Engineering Initiative for Patient Safety (SEIPS) model, and then introduces an extended model, 'SEIPS 2.0'. SEIPS 2.0 incorporates three novel concepts into the original model: configuration, engagement and adaptation. The concept of configuration highlights the dynamic, hierarchical and interactive properties of sociotechnical systems, making it possible to depict how health-related performance is shaped at 'a moment in time'. Engagement conveys that various individuals and teams can perform health-related activities separately and collaboratively. Engaged individuals often include patients, family caregivers and other non-professionals. Adaptation is introduced as a feedback mechanism that explains how dynamic systems evolve in planned and unplanned ways. Key implications and future directions for human factors research in healthcare are discussed.

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.

Spatiotemporal Patterns of Urban Human Mobility

NASA Astrophysics Data System (ADS)

Hasan, Samiul; Schneider, Christian M.; Ukkusuri, Satish V.; González, Marta C.

2013-04-01

The modeling of human mobility is adopting new directions due to the increasing availability of big data sources from human activity. These sources enclose digital information about daily visited locations of a large number of individuals. Examples of these data include: mobile phone calls, credit card transactions, bank notes dispersal, check-ins in internet applications, among several others. In this study, we consider the data obtained from smart subway fare card transactions to characterize and model urban mobility patterns. We present a simple mobility model for predicting peoples' visited locations using the popularity of places in the city as an interaction parameter between different individuals. This ingredient is sufficient to reproduce several characteristics of the observed travel behavior such as: the number of trips between different locations in the city, the exploration of new places and the frequency of individual visits of a particular location. Moreover, we indicate the limitations of the proposed model and discuss open questions in the current state of the art statistical models of human mobility.

Cultural selection drives the evolution of human communication systems

PubMed Central

Tamariz, Monica; Ellison, T. Mark; Barr, Dale J.; Fay, Nicolas

2014-01-01

Human communication systems evolve culturally, but the evolutionary mechanisms that drive this evolution are not well understood. Against a baseline that communication variants spread in a population following neutral evolutionary dynamics (also known as drift models), we tested the role of two cultural selection models: coordination- and content-biased. We constructed a parametrized mixed probabilistic model of the spread of communicative variants in four 8-person laboratory micro-societies engaged in a simple communication game. We found that selectionist models, working in combination, explain the majority of the empirical data. The best-fitting parameter setting includes an egocentric bias and a content bias, suggesting that participants retained their own previously used communicative variants unless they encountered a superior (content-biased) variant, in which case it was adopted. This novel pattern of results suggests that (i) a theory of the cultural evolution of human communication systems must integrate selectionist models and (ii) human communication systems are functionally adaptive complex systems. PMID:24966310

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

Cultural selection drives the evolution of human communication systems.

PubMed

Tamariz, Monica; Ellison, T Mark; Barr, Dale J; Fay, Nicolas

2014-08-07

Human communication systems evolve culturally, but the evolutionary mechanisms that drive this evolution are not well understood. Against a baseline that communication variants spread in a population following neutral evolutionary dynamics (also known as drift models), we tested the role of two cultural selection models: coordination- and content-biased. We constructed a parametrized mixed probabilistic model of the spread of communicative variants in four 8-person laboratory micro-societies engaged in a simple communication game. We found that selectionist models, working in combination, explain the majority of the empirical data. The best-fitting parameter setting includes an egocentric bias and a content bias, suggesting that participants retained their own previously used communicative variants unless they encountered a superior (content-biased) variant, in which case it was adopted. This novel pattern of results suggests that (i) a theory of the cultural evolution of human communication systems must integrate selectionist models and (ii) human communication systems are functionally adaptive complex systems.

Project management tool

NASA Technical Reports Server (NTRS)

Maluf, David A. (Inventor); Bell, David G. (Inventor); Gurram, Mohana M. (Inventor); Gawdiak, Yuri O. (Inventor)

2009-01-01

A system for managing a project that includes multiple tasks and a plurality of workers. Input information includes characterizations based upon a human model, a team model and a product model. Periodic reports, such as a monthly report, a task plan report, a budget report and a risk management report, are generated and made available for display or further analysis. An extensible database allows searching for information based upon context and upon content.

A model of the human supervisor

NASA Technical Reports Server (NTRS)

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

1977-01-01

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

Overview of past, ongoing and future efforts of the integrated modeling of global change for Northern Eurasia

NASA Astrophysics Data System (ADS)

Monier, Erwan; Kicklighter, David; Sokolov, Andrei; Zhuang, Qianlai; Melillo, Jerry; Reilly, John

2016-04-01

Northern Eurasia is both a major player in the global carbon budget (it includes roughly 70% of the Earth's boreal forest and more than two-thirds of the Earth's permafrost) and a region that has experienced dramatic climate change (increase in temperature, growing season length, floods and droughts) over the past century. Northern Eurasia has also undergone significant land-use change, both driven by human activity (including deforestation, expansion of agricultural lands and urbanization) and natural disturbances (such as wildfires and insect outbreaks). These large environmental and socioeconomic impacts have major implications for the carbon cycle in the region. Northern Eurasia is made up of a diverse set of ecosystems that range from tundra to forests, with significant areas of croplands and pastures as well as deserts, with major urban areas. As such, it represents a complex system with substantial challenges for the modeling community. In this presentation, we provide an overview of past, ongoing and possible future efforts of the integrated modeling of global change for Northern Eurasia. We review the variety of existing modeling approaches to investigate specific components of Earth system dynamics in the region. While there are a limited number of studies that try to integrate various aspects of the Earth system (through scale, teleconnections or processes), we point out that there are few systematic analyses of the various feedbacks within the Earth system (between components, regions or scale). As a result, there is a lack of knowledge of the relative importance of such feedbacks, and it is unclear how policy relevant current studies are that fail to account for these feedbacks. We review the role of Earth system models, and their advantages/limitations compared to detailed single component models. We further introduce the human activity system (global trade, economic models, demographic model and so on), the need for coupled human/earth system models and Integrated Assessment Models (IAMs), a suite of models that couple human activity models to Earth System Models. Finally, we conclude the presentation with examples of emerging issues that require a representation of the coupled human/earth system models.

Persistence: A Key Factor in Human Performance at Work.

ERIC Educational Resources Information Center

Blair, Daniel V.; Price, Donna J.

1998-01-01

Reviews the construct of persistence as it relates to achievement motivation at work. Topics include foundational concepts of persistence; achievement motivation theory; a human motivation model; goal-setting theory; self-efficacy theory; expectancy theory; task assignments; confidence; and perceived value. (LRW)

Insights from Modeling the Integrated Climate, Biogeochemical Cycles, Human Activities and Their Interactions in the ACME Earth System Model

NASA Astrophysics Data System (ADS)

Leung, L. R.; Thornton, P. E.; Riley, W. J.; Calvin, K. V.

2017-12-01

Towards the goal of understanding the contributions from natural and managed systems to current and future greenhouse gas fluxes and carbon-climate and carbon-CO2 feedbacks, efforts have been underway to improve representations of the terrestrial, river, and human components of the ACME earth system model. Broadly, our efforts include implementation and comparison of approaches to represent the nutrient cycles and nutrient limitations on ecosystem production, extending the river transport model to represent sediment and riverine biogeochemistry, and coupling of human systems such as irrigation, reservoir operations, and energy and land use with the ACME land and river components. Numerical experiments have been designed to understand how terrestrial carbon, nitrogen, and phosphorus cycles regulate climate system feedbacks and the sensitivity of the feedbacks to different model treatments, examine key processes governing sediment and biogeochemistry in the rivers and their role in the carbon cycle, and exploring the impacts of human systems in perturbing the hydrological and carbon cycles and their interactions. This presentation will briefly introduce the ACME modeling approaches and discuss preliminary results and insights from numerical experiments that lay the foundation for improving understanding of the integrated climate-biogeochemistry-human system.

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

Modeling recent human evolution in mice by expression of a selected EDAR variant

PubMed Central

Kamberov, Yana G.; Wang, Sijia; Tan, Jingze; Gerbault, Pascale; Wark, Abigail; Tan, Longzhi; Yang, Yajun; Li, Shilin; Tang, Kun; Chen, Hua; Powell, Adam; Itan, Yuval; Fuller, Dorian; Lohmueller, Jason; Mao, Junhao; Schachar, Asa; Paymer, Madeline; Hostetter, Elizabeth; Byrne, Elizabeth; Burnett, Melissa; McMahon, Andrew P.; Thomas, Mark G.; Lieberman, Daniel E.; Jin, Li; Tabin, Clifford J.; Morgan, Bruce A.; Sabeti, Pardis C.

2013-01-01

Summary An adaptive variant of the human Ectodysplasin receptor, EDARV370A, is one of the strongest candidates of recent positive selection from genome-wide scans. We have modeled EDAR370A in mice and characterized its phenotype and evolutionary origins in humans. Our computational analysis suggests the allele arose in Central China approximately 30,000 years ago. Although EDAR370A has been associated with increased scalp hair thickness and changed tooth morphology in humans, its direct biological significance and potential adaptive role remain unclear. We generated a knock-in mouse model and find that, as in humans, hair thickness is increased in EDAR370A mice. We identify novel biological targets affected by the mutation, including mammary and eccrine glands. Building on these results, we find that EDAR370A is associated with an increased number of active eccrine glands in the Han Chinese. This interdisciplinary approach yields unique insight into the generation of adaptive variation among modern humans. PMID:23415220

The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering

NASA Astrophysics Data System (ADS)

Moreno-Jiménez, Inés; Hulsart-Billstrom, Gry; Lanham, Stuart A.; Janeczek, Agnieszka A.; Kontouli, Nasia; Kanczler, Janos M.; Evans, Nicholas D.; Oreffo, Richard Oc

2016-08-01

Biomaterial development for tissue engineering applications is rapidly increasing but necessitates efficacy and safety testing prior to clinical application. Current in vitro and in vivo models hold a number of limitations, including expense, lack of correlation between animal models and human outcomes and the need to perform invasive procedures on animals; hence requiring new predictive screening methods. In the present study we tested the hypothesis that the chick embryo chorioallantoic membrane (CAM) can be used as a bioreactor to culture and study the regeneration of human living bone. We extracted bone cylinders from human femoral heads, simulated an injury using a drill-hole defect, and implanted the bone on CAM or in vitro control-culture. Micro-computed tomography (μCT) was used to quantify the magnitude and location of bone volume changes followed by histological analyses to assess bone repair. CAM blood vessels were observed to infiltrate the human bone cylinder and maintain human cell viability. Histological evaluation revealed extensive extracellular matrix deposition in proximity to endochondral condensations (Sox9+) on the CAM-implanted bone cylinders, correlating with a significant increase in bone volume by μCT analysis (p < 0.01). This human-avian system offers a simple refinement model for animal research and a step towards a humanized in vivo model for tissue engineering.

Socio-hydrologic Modeling to Understand and Mediate the Competition for Water between Humans and Ecosystems: Murrumbidgee River Basin, Australia (Invited)

NASA Astrophysics Data System (ADS)

Sivapalan, M.

2013-12-01

Competition for water between humans and ecosystems is set to become a flash point in coming decades in all parts of the world. An entirely new and comprehensive quantitative framework is needed to establish a holistic understanding of that competition, thereby enabling development of effective mediation strategies. This paper presents a case study centered on the Murrumbidgee river basin in eastern Australia that illustrates the dynamics of the balance between water extraction and use for food production and efforts to mitigate and reverse consequent degradation of the riparian environment. Interactions between patterns of water management and climate driven hydrological variability within the prevailing socio-economic environment have contributed to the emergence of new whole system dynamics over the last 100 years. In particular, data analysis reveals a pendulum swing between an exclusive focus on agricultural development and food production in the initial stages of water resource development and its attendant socio-economic benefits, followed by the gradual realization of the adverse environmental impacts, efforts to mitigate these with the use of remedial measures, and ultimately concerted efforts and externally imposed solutions to restore environmental health and ecosystem services. A quasi-distributed coupled socio-hydrologic system model that explicitly includes the two-way coupling between human and hydrological systems, including evolution of human values/norms relating to water and the environment, is able to mimic broad features of this pendulum swing. The model consists of coupled nonlinear differential equations that include four state variables describing the co-evolution of storage capacity, irrigated area, human population, and ecosystem health. The model is used to generate insights into the dominant controls of the trajectory of co-evolution of the coupled human-water system, to serve as the theoretical framework for more detailed analysis of the system, and to generate organizing principles that may be transferable to other systems in different climatic and socio-economic settings.

Retinal image contrast obtained by a model eye with combined correction of chromatic and spherical aberrations

PubMed Central

Ohnuma, Kazuhiko; Kayanuma, Hiroyuki; Lawu, Tjundewo; Negishi, Kazuno; Yamaguchi, Takefumi; Noda, Toru

2011-01-01

Correcting spherical and chromatic aberrations in vitro in human eyes provides substantial visual acuity and contrast sensitivity improvements. We found the same improvement in the retinal images using a model eye with/without correction of longitudinal chromatic aberrations (LCAs) and spherical aberrations (SAs). The model eye included an intraocular lens (IOL) and artificial cornea with human ocular LCAs and average human SAs. The optotypes were illuminated using a D65 light source, and the images were obtained using two-dimensional luminance colorimeter. The contrast improvement from the SA correction was higher than the LCA correction, indicating the benefit of an aspheric achromatic IOL. PMID:21698008

Glycogen storage disease type Ia in canines: a model for human metabolic and genetic liver disease.

PubMed

Specht, Andrew; Fiske, Laurie; Erger, Kirsten; Cossette, Travis; Verstegen, John; Campbell-Thompson, Martha; Struck, Maggie B; Lee, Young Mok; Chou, Janice Y; Byrne, Barry J; Correia, Catherine E; Mah, Cathryn S; Weinstein, David A; Conlon, Thomas J

2011-01-01

A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including "lactic acidosis", larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.

An assessment of a conical horn waveguide to represent the human eardrum

NASA Astrophysics Data System (ADS)

Fields, Taylor N.; Schnetzer, Lucia; Brister, Eileen; Yates, Charles W.; Withnell, Robert H.

2018-05-01

This study examined a model of the acoustic input impedance of the ear that includes a waveguide model of the eardrum. The eardrum was modeled as a lossless conical-horn with rigid walls. The ear canal was modeled as a one-dimensional lossy transmission line. The output impedance of the eardrum, the middle ear, and the cochlea, was modeled as a circuit analog. The model was fit to acoustic input impedance data from human ears using a nonlinear least-squares fit. The impact of a conical-horn shape for the eardrum was quantified by comparison with the eardrum modeled as a near-flat surface. The model provided a good match to the data over the frequency range examined. A conical-horn model of the human eardrum provided gain at high frequencies, most notably above 1–2 kHz, with a broader middle-ear frequency response. This finding may suggest that eardrum shape plays an important role in sound transmission to the cochlea.

Using model order tests to determine sensory inputs in a motion study

NASA Technical Reports Server (NTRS)

Repperger, D. W.; Junker, A. M.

1977-01-01

In the study of motion effects on tracking performance, a problem of interest is the determination of what sensory inputs a human uses in controlling his tracking task. In the approach presented here a simple canonical model (FID or a proportional, integral, derivative structure) is used to model the human's input-output time series. A study of significant changes in reduction of the output error loss functional is conducted as different permutations of parameters are considered. Since this canonical model includes parameters which are related to inputs to the human (such as the error signal, its derivatives and integration), the study of model order is equivalent to the study of which sensory inputs are being used by the tracker. The parameters are obtained which have the greatest effect on reducing the loss function significantly. In this manner the identification procedure converts the problem of testing for model order into the problem of determining sensory inputs.

An Empirical Human Controller Model for Preview Tracking Tasks.

PubMed

van der El, Kasper; Pool, Daan M; Damveld, Herman J; van Paassen, Marinus Rene M; Mulder, Max

2016-11-01

Real-life tracking tasks often show preview information to the human controller about the future track to follow. The effect of preview on manual control behavior is still relatively unknown. This paper proposes a generic operator model for preview tracking, empirically derived from experimental measurements. Conditions included pursuit tracking, i.e., without preview information, and tracking with 1 s of preview. Controlled element dynamics varied between gain, single integrator, and double integrator. The model is derived in the frequency domain, after application of a black-box system identification method based on Fourier coefficients. Parameter estimates are obtained to assess the validity of the model in both the time domain and frequency domain. Measured behavior in all evaluated conditions can be captured with the commonly used quasi-linear operator model for compensatory tracking, extended with two viewpoints of the previewed target. The derived model provides new insights into how human operators use preview information in tracking tasks.

Importance of Past Human and Natural Disturbance in Present-Day Net Ecosystem Productivity

NASA Astrophysics Data System (ADS)

Felzer, B. S.; Phelps, P.

2014-12-01

Gridded datasets of Net Ecosystem Exchange derived from eddy covariance and remote sensing measurements provide a means of validating Net Ecosystem Productivity (NEP, opposite of NEE) from terrestrial ecosystem models. While most forested regions in the U.S. are observed to be moderate to strong carbon sinks, models not including human or natural disturbances will tend to be more carbon neutral, which is expected of mature ecosystems. We have developed the Terrestrial Ecosystems Model Hydro version (TEM-Hydro) to include both human and natural disturbances to compare against gridded NEP datasets. Human disturbances are based on the Hurtt et al. (2006) land use transition dataset and include transient agricultural (crops and pasture) conversion and abandonment and timber harvest. We include natural disturbances of storms and fires based on stochastic return intervals. Tropical storms and hurricane return intervals are based on Zheng et al. (2009) and occur only along the U.S. Atlantic and Gulf coasts. Fire return intervals are based on LANDFIRE Rapid Assessment Vegetation Models and vegetation types from the Hurtt dataset. We are running three experiments with TEM-Hydro from 1700-2011 for the conterminous U.S.: potential vegetation (POT), human disturbance only (agriculture and timber harvest, LULC), and human plus natural disturbance (agriculture, timber harvest, storms, and fire, DISTURB). The goal is to compare our NEP values to those obtained by FLUXNET-MTE (Jung et al. 2009) from 1982-2008 and ECMOD (Xiao et al., 2008) from 2000-2006 for different plant functional types (PFTs) within the conterminous U.S. Preliminary results show that, for the entire U.S., potential vegetation yields an NEP of 10.8 gCm-2yr-1 vs 128.1 gCm-2yr-1 for LULC and 89.8 gCm-2yr-1 for DISTURB from 1982-2008. The effect of regrowth following agricultural and timber harvest disturbance therefore contributes substantially to the present-day carbon sink, while stochastic storms and fires have a negative effect on NEP. Even though the current NEP reflects the carbon uptake from regrowth, a full carbon accounting would also include the carbon released to the atmosphere during disturbance or carbon lost to decomposition of agricultural or timber products

The contribution of human/non-human animal chimeras to stem cell research.

PubMed

Levine, Sonya; Grabel, Laura

2017-10-01

Chimeric animals are made up of cells from two separate zygotes. Human/non-human animal chimeras have been used for a number of research purposes, including human disease modeling. Pluripotent stem cell (PSC) research has relied upon the chimera approach to examine the developmental potential of stem cells, to determine the efficacy of cell replacement therapies, and to establish a means of producing human organs. Based on ethical issues, this work has faced pushback from various sources including funding agencies. We discuss here the essential role these studies have played, from gaining a better understanding of human biology to providing a stepping stone to human disease treatments. We also consider the major ethical issues, as well as the current status of support for this work in the United States. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Evidence in Support of the Independent Channel Model Describing the Sensorimotor Control of Human Stance Using a Humanoid Robot

PubMed Central

Pasma, Jantsje H.; Assländer, Lorenz; van Kordelaar, Joost; de Kam, Digna; Mergner, Thomas; Schouten, Alfred C.

2018-01-01

The Independent Channel (IC) model is a commonly used linear balance control model in the frequency domain to analyze human balance control using system identification and parameter estimation. The IC model is a rudimentary and noise-free description of balance behavior in the frequency domain, where a stable model representation is not guaranteed. In this study, we conducted firstly time-domain simulations with added noise, and secondly robot experiments by implementing the IC model in a real-world robot (PostuRob II) to test the validity and stability of the model in the time domain and for real world situations. Balance behavior of seven healthy participants was measured during upright stance by applying pseudorandom continuous support surface rotations. System identification and parameter estimation were used to describe the balance behavior with the IC model in the frequency domain. The IC model with the estimated parameters from human experiments was implemented in Simulink for computer simulations including noise in the time domain and robot experiments using the humanoid robot PostuRob II. Again, system identification and parameter estimation were used to describe the simulated balance behavior. Time series, Frequency Response Functions, and estimated parameters from human experiments, computer simulations, and robot experiments were compared with each other. The computer simulations showed similar balance behavior and estimated control parameters compared to the human experiments, in the time and frequency domain. Also, the IC model was able to control the humanoid robot by keeping it upright, but showed small differences compared to the human experiments in the time and frequency domain, especially at high frequencies. We conclude that the IC model, a descriptive model in the frequency domain, can imitate human balance behavior also in the time domain, both in computer simulations with added noise and real world situations with a humanoid robot. This provides further evidence that the IC model is a valid description of human balance control. PMID:29615886

Evidence in Support of the Independent Channel Model Describing the Sensorimotor Control of Human Stance Using a Humanoid Robot.

PubMed

Pasma, Jantsje H; Assländer, Lorenz; van Kordelaar, Joost; de Kam, Digna; Mergner, Thomas; Schouten, Alfred C

2018-01-01

The Independent Channel (IC) model is a commonly used linear balance control model in the frequency domain to analyze human balance control using system identification and parameter estimation. The IC model is a rudimentary and noise-free description of balance behavior in the frequency domain, where a stable model representation is not guaranteed. In this study, we conducted firstly time-domain simulations with added noise, and secondly robot experiments by implementing the IC model in a real-world robot (PostuRob II) to test the validity and stability of the model in the time domain and for real world situations. Balance behavior of seven healthy participants was measured during upright stance by applying pseudorandom continuous support surface rotations. System identification and parameter estimation were used to describe the balance behavior with the IC model in the frequency domain. The IC model with the estimated parameters from human experiments was implemented in Simulink for computer simulations including noise in the time domain and robot experiments using the humanoid robot PostuRob II. Again, system identification and parameter estimation were used to describe the simulated balance behavior. Time series, Frequency Response Functions, and estimated parameters from human experiments, computer simulations, and robot experiments were compared with each other. The computer simulations showed similar balance behavior and estimated control parameters compared to the human experiments, in the time and frequency domain. Also, the IC model was able to control the humanoid robot by keeping it upright, but showed small differences compared to the human experiments in the time and frequency domain, especially at high frequencies. We conclude that the IC model, a descriptive model in the frequency domain, can imitate human balance behavior also in the time domain, both in computer simulations with added noise and real world situations with a humanoid robot. This provides further evidence that the IC model is a valid description of human balance control.

The utility of the new generation of humanized mice to study HIV-1 infection: transmission, prevention, pathogenesis, and treatment

PubMed Central

2011-01-01

Substantial improvements have been made in recent years in the ability to engraft human cells and tissues into immunodeficient mice. The use of human hematopoietic stem cells (HSCs) leads to multi-lineage human hematopoiesis accompanied by production of a variety of human immune cell types. Population of murine primary and secondary lymphoid organs with human cells occurs, and long-term engraftment has been achieved. Engrafted cells are capable of producing human innate and adaptive immune responses, making these models the most physiologically relevant humanized animal models to date. New models have been successfully infected by a variety of strains of Human Immunodeficiency Virus Type 1 (HIV-1), accompanied by virus replication in lymphoid and non-lymphoid organs, including the gut-associated lymphoid tissue, the male and female reproductive tracts, and the brain. Multiple forms of virus-induced pathogenesis are present, and human T cell and antibody responses to HIV-1 are detected. These humanized mice are susceptible to a high rate of rectal and vaginal transmission of HIV-1 across an intact epithelium, indicating the potential to study vaccines and microbicides. Antiviral drugs, siRNAs, and hematopoietic stem cell gene therapy strategies have all been shown to be effective at reducing viral load and preventing or reversing helper T cell loss in humanized mice, indicating that they will serve as an important preclinical model to study new therapeutic modalities. HIV-1 has also been shown to evolve in response to selective pressures in humanized mice, thus showing that the model will be useful to study and/or predict viral evolution in response to drug or immune pressures. The purpose of this review is to summarize the findings reported to date on all new humanized mouse models (those transplanted with human HSCs) in regards to HIV-1 sexual transmission, pathogenesis, anti-HIV-1 immune responses, viral evolution, pre- and post-exposure prophylaxis, and gene therapeutic strategies. PMID:21835012

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.

To generate a finite element model of human thorax using the VCH dataset

NASA Astrophysics Data System (ADS)

Shi, Hui; Liu, Qian

2009-10-01

Purpose: To generate a three-dimensional (3D) finite element (FE) model of human thorax which may provide the basis of biomechanics simulation for the study of design effect and mechanism of safety belt when vehicle collision. Methods: Using manually or semi-manually segmented method, the interested area can be segmented from the VCH (Visible Chinese Human) dataset. The 3D surface model of thorax is visualized by using VTK (Visualization Toolkit) and further translated into (Stereo Lithography) STL format, which approximates the geometry of solid model by representing the boundaries with triangular facets. The data in STL format need to be normalized into NURBS surfaces and IGES format using software such as Geomagic Studio to provide archetype for reverse engineering. The 3D FE model was established using Ansys software. Results: The generated 3D FE model was an integrated thorax model which could reproduce human's complicated structure morphology including clavicle, ribs, spine and sternum. It was consisted of 1 044 179 elements in total. Conclusions: Compared with the previous thorax model, this FE model enhanced the authenticity and precision of results analysis obviously, which can provide a sound basis for analysis of human thorax biomechanical research. Furthermore, using the method above, we can also establish 3D FE models of some other organizes and tissues utilizing the VCH dataset.

A Budyko-type Model for Human Water Consumption

NASA Astrophysics Data System (ADS)

Lei, X.; Zhao, J.; Wang, D.; Sivapalan, M.

2017-12-01

With the expansion of human water footprint, water crisis is no longer only a conflict or competition for water between different economic sectors, but also increasingly between human and the environment. In order to describe the emergent dynamics and patterns of the interaction, a theoretical framework that encapsulates the physical and societal controls impacting human water consumption is needed. In traditional hydrology, Budyko-type models are simple but efficient descriptions of vegetation-mediated hydrologic cycle in catchments, i.e., the partitioning of mean annual precipitation into runoff and evapotranspiration. Plant water consumption plays a crucial role in the process. Hypothesized similarities between human-water and vegetation-water interactions, including water demand, constraints and system functioning, give the idea of corresponding Budyko-type framework for human water consumption at the catchment scale. Analogous to variables of Budyko-type models for hydrologic cycle, water demand, water consumption, environmental water use and available water are corresponding to potential evaporation, actual evaporation, runoff and precipitation respectively. Human water consumption data, economic and hydro-meteorological data for 51 human-impacted catchments and 10 major river basins in China are assembled to look for the existence of a Budyko-type relationship for human water consumption, and to seek explanations for the spread in the observed relationship. Guided by this, a Budyko-type analytical model is derived based on application of an optimality principle, that of maximum water benefit. The model derived has the same functional form and mathematical features as those that apply for the original Budyko model. Parameters of the new Budyko-type model for human consumption are linked to economic and social factors. The results of this paper suggest that the functioning of both social and hydrologic subsystems within catchment systems can be explored within a common conceptual framework, thus providing a unified socio-hydrologic basis for the study of coupled human-water systems. The exploration of the theoretical connections between the two subsystems pushes the water system modeling from a problem-solving orientation to puzzle-solving orientation.

Principles of establishing material cycling with a high degree of closure in the experimental model of a BTLSS intended for a rated "fraction of a human"

NASA Astrophysics Data System (ADS)

Tikhomirov, Alexander A.; Ushakova, Sofya; Velichko, Vladimir; Tikhomirova, Natalia; Shikhov, Valentin; Trifonov, Sergey V.

2016-07-01

A promising way to develop future biotechnical life support systems (BTLSS) is to construct experimental models and establish the cycling intended for a fraction of a human. Being of relatively low cost, such models provide an opportunity to test effectively closed process that could be further transferred to the real BTLSS with humans. Researchers of the IBP SB RAS are developing an adequate BTLSS model with the loops closed to a high degree. To attain high closure of mass exchange processes, plants in the phototrophic compartment are cultivated under intensive lighting conditions, created by using modern LED irradiators of enhanced power, equipped with lens optics. The higher plant compartment has been renewed and broadened by including soybean plants, which improve the vegetable part of the human diet and make it more diverse. It is very important that the operation of the physicochemical installation for waste mineralization fully matches the composition of the atmosphere of plant growth chambers: the purified gaseous components of this installation enter the common atmosphere of the system, without causing any deviations from the norm in the gaseous composition. This proves the eco-friendliness of the developed physicochemical method of waste mineralization and shows that the gaseous components resulting from waste mineralization can be included in the system mass exchange. A system for including human respiration into the gas exchange of the BTLSS has been developed and tested; the associated gas exchange and water exchange dynamics have been analyzed. Results of the functioning of the experimental model of the BTLSS for several months are proposed for discussion in order to get insight into the formation of dynamic characteristics of cycling processes and factors determining them. The study was supported by the grant of the Russian Science Foundation (Project 14-14-00599) and carried out at the IBP SB RAS.

Human Language Technology: Opportunities and Challenges

DTIC Science & Technology

2005-01-01

because of the connections to and reliance on signal processing. Audio diarization critically includes indexing of speakers [12], since speaker ...to reduce inter- speaker variability in training. Standard techniques include vocal-tract length normalization, adaptation of acoustic models using...maximum likelihood linear regression (MLLR), and speaker -adaptive training based on MLLR. The acoustic models are mixtures of Gaussians, typically with

GIANT API: an application programming interface for functional genomics

PubMed Central

Roberts, Andrew M.; Wong, Aaron K.; Fisk, Ian; Troyanskaya, Olga G.

2016-01-01

GIANT API provides biomedical researchers programmatic access to tissue-specific and global networks in humans and model organisms, and associated tools, which includes functional re-prioritization of existing genome-wide association study (GWAS) data. Using tissue-specific interaction networks, researchers are able to predict relationships between genes specific to a tissue or cell lineage, identify the changing roles of genes across tissues and uncover disease-gene associations. Additionally, GIANT API enables computational tools like NetWAS, which leverages tissue-specific networks for re-prioritization of GWAS results. The web services covered by the API include 144 tissue-specific functional gene networks in human, global functional networks for human and six common model organisms and the NetWAS method. GIANT API conforms to the REST architecture, which makes it stateless, cacheable and highly scalable. It can be used by a diverse range of clients including web browsers, command terminals, programming languages and standalone apps for data analysis and visualization. The API is freely available for use at http://giant-api.princeton.edu. PMID:27098035

Advanced Life Support Research and Technology Development

NASA Technical Reports Server (NTRS)

Kliss, Mark

2001-01-01

A videograph outlining life support research. The Human Exploration and Development of Space (HEDS) Enterprise's goals are to provide life support self-sufficiency for human beings to carry out research and exploration productively in space, to open the door for planetary exploration, and for benefits on Earth. Topics presented include the role of NASA Ames, funding, and technical monitoring. The focused research areas discussed include air regeneration, carbon dioxide removal, Mars Life Support, water recovery, Vapor Phase Catalytic Ammonia Removal (VPCAR), solid waste treatment, and Supercritical Water Oxidation (SCWC). Focus is placed on the utilization of Systems Integration, Modeling and Analysis (SIMA) and Dynamic Systems Modeling in this research.

Optimal race strategy for a 200-m flying sprint in a human-powered vehicle: A case study of a world-record attempt.

PubMed

de Koning, Jos J; van der Zweep, Cees-Jan; Cornelissen, Jesper; Kuiper, Bouke

2013-03-01

Optimal pacing strategy was determined for breaking the world speed record on a human-powered vehicle (HPV) using an energy-flow model in which the rider's physical capacities, the vehicle's properties, and the environmental conditions were included. Power data from world-record attempts were compared with data from the model, and race protocols were adjusted to the results from the model. HPV performance can be improved by using an energy-flow model for optimizing race strategy. A biphased in-run followed by a sprint gave best results.

The "GeneTrustee": a universal identification system that ensures privacy and confidentiality for human genetic databases.

PubMed

Burnett, Leslie; Barlow-Stewart, Kris; Proos, Anné L; Aizenberg, Harry

2003-05-01

This article describes a generic model for access to samples and information in human genetic databases. The model utilises a "GeneTrustee", a third-party intermediary independent of the subjects and of the investigators or database custodians. The GeneTrustee model has been implemented successfully in various community genetics screening programs and has facilitated research access to genetic databases while protecting the privacy and confidentiality of research subjects. The GeneTrustee model could also be applied to various types of non-conventional genetic databases, including neonatal screening Guthrie card collections, and to forensic DNA samples.

Optimal Configuration of Human Motion Tracking Systems: A Systems Engineering Approach

NASA Technical Reports Server (NTRS)

Henderson, Steve

2005-01-01

Human motion tracking systems represent a crucial technology in the area of modeling and simulation. These systems, which allow engineers to capture human motion for study or replication in virtual environments, have broad applications in several research disciplines including human engineering, robotics, and psychology. These systems are based on several sensing paradigms, including electro-magnetic, infrared, and visual recognition. Each of these paradigms requires specialized environments and hardware configurations to optimize performance of the human motion tracking system. Ideally, these systems are used in a laboratory or other facility that was designed to accommodate the particular sensing technology. For example, electromagnetic systems are highly vulnerable to interference from metallic objects, and should be used in a specialized lab free of metal components.

Human-computer interaction in multitask situations

NASA Technical Reports Server (NTRS)

Rouse, W. B.

1977-01-01

Human-computer interaction in multitask decisionmaking situations is considered, and it is proposed that humans and computers have overlapping responsibilities. Queueing theory is employed to model this dynamic approach to the allocation of responsibility between human and computer. Results of simulation experiments are used to illustrate the effects of several system variables including number of tasks, mean time between arrivals of action-evoking events, human-computer speed mismatch, probability of computer error, probability of human error, and the level of feedback between human and computer. Current experimental efforts are discussed and the practical issues involved in designing human-computer systems for multitask situations are considered.

New insights into epididymal biology and function.

PubMed

Cornwall, Gail A

2009-01-01

The epididymis performs an important role in the maturation of spermatozoa including their acquisition of progressive motility and fertilizing ability. However, the molecular mechanisms that govern these maturational events are still poorly defined. This review focuses on recent progress in our understanding of epididymal function including its development, role of the luminal microenvironment in sperm maturation, regulation and novel mechanisms the epididymis utilizes to carry out some of its functions. A systematic search of Pubmed was carried out using the search term 'epididymis'. Articles that were published in the English language until the end of August 2008 and that focused on the specific topics described above were included. Additional papers cited in the primary reference were also included. While the majority of these findings were the result of studies in animal models, recent studies in the human epididymis are also presented including gene profiling studies to examine regionalized expression in normal epididymides as well as in those from vasectomized patients. Significant progress has been made in our understanding of epididymal function providing new insights that ultimately could improve human health. The data also indicate that the human epididymis plays an important role in sperm maturation but has unique properties compared with animal models.

Non-animal models of wound healing in cutaneous repair: In silico, in vitro, ex vivo, and in vivo models of wounds and scars in human skin.

PubMed

Ud-Din, Sara; Bayat, Ardeshir

2017-04-01

Tissue repair models are essential to explore the pathogenesis of wound healing and scar formation, identify new drug targets/biomarkers and to test new therapeutics. However, no animal model is an exact replicate of the clinical situation in man as in addition to differences in the healing of animal skin; the response to novel therapeutics can be variable when compared to human skin. The aim of this review is to evaluate currently available non-animal wound repair models in human skin, including: in silico, in vitro, ex vivo, and in vivo. The appropriate use of these models is extremely relevant to wound-healing research as it enables improved understanding of the basic mechanisms present in the wound healing cascade and aid in discovering better means to regulate them for enhanced healing or prevention of abnormal scarring. The advantage of in silico models is that they can be used as a first in virtue screening tool to predict the effect of a drug/stimulus on cells/tissues and help plan experimental research/clinical trial studies but remain theoretical until validated. In vitro models allow direct quantitative examination of an effect on specific cell types alone without incorporating other tissue-matrix components, which limits their utility. Ex vivo models enable immediate and short-term evaluation of a particular effect on cells and its surrounding tissue components compared with in vivo models that provide direct analysis of a stimulus in the living human subject before/during/after exposure to a stimulus. Despite clear advantages, there remains a lack of standardisation in design, evaluation and follow-up, for acute/chronic wounds and scars in all models. In conclusion, ideal models of wound healing research are desirable and should mimic not only the structure but also the cellular and molecular interactions, of wound types in human skin. Future models may also include organ/skin-on-a-chip with potential application in wound healing research. © 2017 by the Wound Healing Society.

Real-time stylistic prediction for whole-body human motions.

PubMed

Matsubara, Takamitsu; Hyon, Sang-Ho; Morimoto, Jun

2012-01-01

The ability to predict human motion is crucial in several contexts such as human tracking by computer vision and the synthesis of human-like computer graphics. Previous work has focused on off-line processes with well-segmented data; however, many applications such as robotics require real-time control with efficient computation. In this paper, we propose a novel approach called real-time stylistic prediction for whole-body human motions to satisfy these requirements. This approach uses a novel generative model to represent a whole-body human motion including rhythmic motion (e.g., walking) and discrete motion (e.g., jumping). The generative model is composed of a low-dimensional state (phase) dynamics and a two-factor observation model, allowing it to capture the diversity of motion styles in humans. A real-time adaptation algorithm was derived to estimate both state variables and style parameter of the model from non-stationary unlabeled sequential observations. Moreover, with a simple modification, the algorithm allows real-time adaptation even from incomplete (partial) observations. Based on the estimated state and style, a future motion sequence can be accurately predicted. In our implementation, it takes less than 15 ms for both adaptation and prediction at each observation. Our real-time stylistic prediction was evaluated for human walking, running, and jumping behaviors. Copyright © 2011 Elsevier Ltd. All rights reserved.

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…

Orthology for comparative genomics in the mouse genome database.

PubMed

Dolan, Mary E; Baldarelli, Richard M; Bello, Susan M; Ni, Li; McAndrews, Monica S; Bult, Carol J; Kadin, James A; Richardson, Joel E; Ringwald, Martin; Eppig, Janan T; Blake, Judith A

2015-08-01

The mouse genome database (MGD) is the model organism database component of the mouse genome informatics system at The Jackson Laboratory. MGD is the international data resource for the laboratory mouse and facilitates the use of mice in the study of human health and disease. Since its beginnings, MGD has included comparative genomics data with a particular focus on human-mouse orthology, an essential component of the use of mouse as a model organism. Over the past 25 years, novel algorithms and addition of orthologs from other model organisms have enriched comparative genomics in MGD data, extending the use of orthology data to support the laboratory mouse as a model of human biology. Here, we describe current comparative data in MGD and review the history and refinement of orthology representation in this resource.

Differentiation and Characterization of Myeloid Cells

PubMed Central

Gupta, Dipti; Shah, Hetavi Parag; Malu, Krishnakumar; Berliner, Nancy; Gaines, Peter

2015-01-01

Recent molecular studies of myeloid differentiation have utilized several in vitro models of myelopoiesis, generated from either ex vivo differentiated bone marrow progenitors or induced immortalized myeloid cell lines. Ex vivo differentiation begins with an enriched population of bone marrow-derived hematopoietic stem cells generated by lineage depletion and/or positive selection for CD34+ antigen (human) or Sca-1+ (mouse) cells, which are then expanded and subsequently induced in vitro in a process that recapitulates normal myeloid development. Myeloid cell lines include two human leukemic cell lines, NB-4 and HL-60, which have been demonstrated to undergo retinoic acid–induced myeloid development, however, both cell lines exhibit defects in the upregulation of late-expressed neutrophil-specific genes. Multiple murine factor–dependent cell models of myelopoiesis are also available that express the full range of neutrophil maturation markers, including: 32Dcl3 cells, which undergo G-CSF-induced myeloid maturation, EML/EPRO cells, which develop into mature neutrophils in response to cytokines and retinoic acid, and ER-Hoxb8 cells, which undergo myeloid maturation upon removal of estradial in the maintenance medium. In this unit, the induction of myeloid maturation in each of these model systems is described, including their differentiation to either neutrophils or macrophages, if applicable. Commonly used techniques to test for myeloid characteristics of developing cells are also described, including flow cytometry and real time RT-PCR. Together, these assays provide a solid foundation for in vitro investigations of myeloid development with either human or mouse models. PMID:24510620

Development of a parametric kinematic model of the human hand and a novel robotic exoskeleton.

PubMed

Burton, T M W; Vaidyanathan, R; Burgess, S C; Turton, A J; Melhuish, C

2011-01-01

This paper reports the integration of a kinematic model of the human hand during cylindrical grasping, with specific focus on the accurate mapping of thumb movement during grasping motions, and a novel, multi-degree-of-freedom assistive exoskeleton mechanism based on this model. The model includes thumb maximum hyper-extension for grasping large objects (~> 50 mm). The exoskeleton includes a novel four-bar mechanism designed to reproduce natural thumb opposition and a novel synchro-motion pulley mechanism for coordinated finger motion. A computer aided design environment is used to allow the exoskeleton to be rapidly customized to the hand dimensions of a specific patient. Trials comparing the kinematic model to observed data of hand movement show the model to be capable of mapping thumb and finger joint flexion angles during grasping motions. Simulations show the exoskeleton to be capable of reproducing the complex motion of the thumb to oppose the fingers during cylindrical and pinch grip motions. © 2011 IEEE

Optimized Assistive Human-Robot Interaction Using Reinforcement Learning.

PubMed

Modares, Hamidreza; Ranatunga, Isura; Lewis, Frank L; Popa, Dan O

2016-03-01

An intelligent human-robot interaction (HRI) system with adjustable robot behavior is presented. The proposed HRI system assists the human operator to perform a given task with minimum workload demands and optimizes the overall human-robot system performance. Motivated by human factor studies, the presented control structure consists of two control loops. First, a robot-specific neuro-adaptive controller is designed in the inner loop to make the unknown nonlinear robot behave like a prescribed robot impedance model as perceived by a human operator. In contrast to existing neural network and adaptive impedance-based control methods, no information of the task performance or the prescribed robot impedance model parameters is required in the inner loop. Then, a task-specific outer-loop controller is designed to find the optimal parameters of the prescribed robot impedance model to adjust the robot's dynamics to the operator skills and minimize the tracking error. The outer loop includes the human operator, the robot, and the task performance details. The problem of finding the optimal parameters of the prescribed robot impedance model is transformed into a linear quadratic regulator (LQR) problem which minimizes the human effort and optimizes the closed-loop behavior of the HRI system for a given task. To obviate the requirement of the knowledge of the human model, integral reinforcement learning is used to solve the given LQR problem. Simulation results on an x - y table and a robot arm, and experimental implementation results on a PR2 robot confirm the suitability of the proposed method.

The importance of shared mental models and shared situation awareness for transforming robots from tools to teammates

NASA Astrophysics Data System (ADS)

Ososky, Scott; Schuster, David; Jentsch, Florian; Fiore, Stephen; Shumaker, Randall; Lebiere, Christian; Kurup, Unmesh; Oh, Jean; Stentz, Anthony

2012-06-01

Current ground robots are largely employed via tele-operation and provide their operators with useful tools to extend reach, improve sensing, and avoid dangers. To move from robots that are useful as tools to truly synergistic human-robot teaming, however, will require not only greater technical capabilities among robots, but also a better understanding of the ways in which the principles of teamwork can be applied from exclusively human teams to mixed teams of humans and robots. In this respect, a core characteristic that enables successful human teams to coordinate shared tasks is their ability to create, maintain, and act on a shared understanding of the world and the roles of the team and its members in it. The team performance literature clearly points towards two important cornerstones for shared understanding of team members: mental models and situation awareness. These constructs have been investigated as products of teams as well; amongst teams, they are shared mental models and shared situation awareness. Consequently, we are studying how these two constructs can be measured and instantiated in human-robot teams. In this paper, we report results from three related efforts that are investigating process and performance outcomes for human robot teams. Our investigations include: (a) how human mental models of tasks and teams change whether a teammate is human, a service animal, or an advanced automated system; (b) how computer modeling can lead to mental models being instantiated and used in robots; (c) how we can simulate the interactions between human and future robotic teammates on the basis of changes in shared mental models and situation assessment.

FLOW SIMULATION IN THE HUMAN UPPER RESPIRATORY TRACT

EPA Science Inventory

ABSTRACT

Computer simulations of airflow patterns within the human upper respiratory tract (URT) are presented. The URT model includes airways of the head (nasal and oral), throat (pharyngeal and laryngeal), and lungs (trachea and main bronchi). The head and throat mor...

Large Vocabulary Audio-Visual Speech Recognition

DTIC Science & Technology

2002-06-12

www.is.cs.cmu.edu Email: waibel(a)cs.cmu~edu Inttractive Systenms Labs ttoctis Ssstms Labs Meeting Browser - -- Interpreting Human Communication "Why did...Speech Interacti Stams Labs t-cive Systms Focus of Attention Tracking Conclusion - Complete Model of Human Communication is Needed - Include all

Engineering adolescence: maturation of human pluripotent stem cell-derived cardiomyocytes.

PubMed

Yang, Xiulan; Pabon, Lil; Murry, Charles E

2014-01-31

The discovery of human pluripotent stem cells (hPSCs), including both human embryonic stem cells and human-induced pluripotent stem cells, has opened up novel paths for a wide range of scientific studies. The capability to direct the differentiation of hPSCs into functional cardiomyocytes has provided a platform for regenerative medicine, development, tissue engineering, disease modeling, and drug toxicity testing. Despite exciting progress, achieving the optimal benefits has been hampered by the immature nature of these cardiomyocytes. Cardiac maturation has long been studied in vivo using animal models; however, finding ways to mature hPSC cardiomyocytes is only in its initial stages. In this review, we discuss progress in promoting the maturation of the hPSC cardiomyocytes, in the context of our current knowledge of developmental cardiac maturation and in relation to in vitro model systems such as rodent ventricular myocytes. Promising approaches that have begun to be examined in hPSC cardiomyocytes include long-term culturing, 3-dimensional tissue engineering, mechanical loading, electric stimulation, modulation of substrate stiffness, and treatment with neurohormonal factors. Future studies will benefit from the combinatorial use of different approaches that more closely mimic nature's diverse cues, which may result in broader changes in structure, function, and therapeutic applicability.

A Subjective Assessment of Alternative Mission Architecture Operations Concepts for the Human Exploration of Mars at NASA Using a Three-Dimensional Multi-Criteria Decision Making Model

NASA Technical Reports Server (NTRS)

Tavana, Madjid

2003-01-01

The primary driver for developing missions to send humans to other planets is to generate significant scientific return. NASA plans human planetary explorations with an acceptable level of risk consistent with other manned operations. Space exploration risks can not be completely eliminated. Therefore, an acceptable level of cost, technical, safety, schedule, and political risks and benefits must be established for exploratory missions. This study uses a three-dimensional multi-criteria decision making model to identify the risks and benefits associated with three alternative mission architecture operations concepts for the human exploration of Mars identified by the Mission Operations Directorate at Johnson Space Center. The three alternatives considered in this study include split, combo lander, and dual scenarios. The model considers the seven phases of the mission including: 1) Earth Vicinity/Departure; 2) Mars Transfer; 3) Mars Arrival; 4) Planetary Surface; 5) Mars Vicinity/Departure; 6) Earth Transfer; and 7) Earth Arrival. Analytic Hierarchy Process (AHP) and subjective probability estimation are used to captures the experts belief concerning the risks and benefits of the three alternative scenarios through a series of sequential, rational, and analytical processes.

Probabilistic risk assessment for a loss of coolant accident in McMaster Nuclear Reactor and application of reliability physics model for modeling human reliability

NASA Astrophysics Data System (ADS)

Ha, Taesung

A probabilistic risk assessment (PRA) was conducted for a loss of coolant accident, (LOCA) in the McMaster Nuclear Reactor (MNR). A level 1 PRA was completed including event sequence modeling, system modeling, and quantification. To support the quantification of the accident sequence identified, data analysis using the Bayesian method and human reliability analysis (HRA) using the accident sequence evaluation procedure (ASEP) approach were performed. Since human performance in research reactors is significantly different from that in power reactors, a time-oriented HRA model (reliability physics model) was applied for the human error probability (HEP) estimation of the core relocation. This model is based on two competing random variables: phenomenological time and performance time. The response surface and direct Monte Carlo simulation with Latin Hypercube sampling were applied for estimating the phenomenological time, whereas the performance time was obtained from interviews with operators. An appropriate probability distribution for the phenomenological time was assigned by statistical goodness-of-fit tests. The human error probability (HEP) for the core relocation was estimated from these two competing quantities: phenomenological time and operators' performance time. The sensitivity of each probability distribution in human reliability estimation was investigated. In order to quantify the uncertainty in the predicted HEPs, a Bayesian approach was selected due to its capability of incorporating uncertainties in model itself and the parameters in that model. The HEP from the current time-oriented model was compared with that from the ASEP approach. Both results were used to evaluate the sensitivity of alternative huinan reliability modeling for the manual core relocation in the LOCA risk model. This exercise demonstrated the applicability of a reliability physics model supplemented with a. Bayesian approach for modeling human reliability and its potential usefulness of quantifying model uncertainty as sensitivity analysis in the PRA model.

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

Models of wound healing: an emphasis on clinical studies.

PubMed

Wilhelm, K-P; Wilhelm, D; Bielfeldt, S

2017-02-01

The healing of wounds has always provided challenges for the medical community whether chronic or acute. Understanding the processes which enable wounds to heal is primarily carried out by the use of models, in vitro, animal and human. It is generally accepted that the use of human models offers the best opportunity to understand the factors that influence wound healing as well as to evaluate efficacy of treatments applied to wounds. The objective of this article is to provide an overview of the different methodologies that are currently used to experimentally induce wounds of various depths in human volunteers and examines the information that may be gained from them. There is a number of human volunteer healing models available varying in their invasiveness to reflect the different possible depth levels of wounds. Currently available wound healing models include sequential tape stripping, suction blister, abrasion, laser, dermatome, and biopsy techniques. The various techniques can be utilized to induce wounds of variable depth, from removing solely the stratum corneum barrier, the epidermis to even split-thickness or full thickness wounds. Depending on the study objective, a number of models exist to study wound healing in humans. These models provide efficient and reliable results to evaluate treatment modalities. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Modeling the integration of bacterial rRNA fragments into the human cancer genome.

PubMed

Sieber, Karsten B; Gajer, Pawel; Dunning Hotopp, Julie C

2016-03-21

Cancer is a disease driven by the accumulation of genomic alterations, including the integration of exogenous DNA into the human somatic genome. We previously identified in silico evidence of DNA fragments from a Pseudomonas-like bacteria integrating into the 5'-UTR of four proto-oncogenes in stomach cancer sequencing data. The functional and biological consequences of these bacterial DNA integrations remain unknown. Modeling of these integrations suggests that the previously identified sequences cover most of the sequence flanking the junction between the bacterial and human DNA. Further examination of these reads reveals that these integrations are rich in guanine nucleotides and the integrated bacterial DNA may have complex transcript secondary structures. The models presented here lay the foundation for future experiments to test if bacterial DNA integrations alter the transcription of the human genes.

Non-invasive quantification of hemodynamics in human choriocapillaries

NASA Astrophysics Data System (ADS)

Yu, Huidan (Whitney); Chen, Rou; An, Senyou; McDonough, James; Gelfand, Bradley; Yao, Jun

2016-11-01

The development of retinal disease is inextricably linked to defects in the choroidal blood supply. However, to date a description of the hemodynamics in the human choroidal circulation is lacking. Through high resolution choroidal vascular network mapped from immunofluorescent labeling and confocal microscopy of human cadaver donor eyes. We noninvasively quantify hemodynamics including velocity, pressure, and wall-shear stress (WSS) in choriocapillaries through mesoscale modeling and GPU-accelerated fast computation. This is the first-ever map of hemodynamic parameters (WSS, pressure, and velocity) in anatomically accurate human choroidal vasculature in health and disease. The pore scale simulation results are used to evaluate porous media models with the same porosity and boundary conditions. School of Medicine, Indiana University.

Spatiotemporal property and predictability of large-scale human mobility

NASA Astrophysics Data System (ADS)

Zhang, Hai-Tao; Zhu, Tao; Fu, Dongfei; Xu, Bowen; Han, Xiao-Pu; Chen, Duxin

2018-04-01

Spatiotemporal characteristics of human mobility emerging from complexity on individual scale have been extensively studied due to the application potential on human behavior prediction and recommendation, and control of epidemic spreading. We collect and investigate a comprehensive data set of human activities on large geographical scales, including both websites browse and mobile towers visit. Numerical results show that the degree of activity decays as a power law, indicating that human behaviors are reminiscent of scale-free random walks known as Lévy flight. More significantly, this study suggests that human activities on large geographical scales have specific non-Markovian characteristics, such as a two-segment power-law distribution of dwelling time and a high possibility for prediction. Furthermore, a scale-free featured mobility model with two essential ingredients, i.e., preferential return and exploration, and a Gaussian distribution assumption on the exploration tendency parameter is proposed, which outperforms existing human mobility models under scenarios of large geographical scales.

The Design and Use of Animal Models for Translational Research in Bone Tissue Engineering and Regenerative Medicine

DTIC Science & Technology

2010-01-07

many domains: mechanical load bearing and force transmission, immunogologic function (leukogenesis and lymphogenesis), mass transport (erythrogenesis...models including NHPs) does not reproduce upright posture of bipedal humans with respect to axial compression and rotational loading in the human lumbar...Schell, M. Mehta, M. A. Schuetz, G. N. Duda, D. W. Hutmacher. 2012. A Tissue Engineering Solution for Segmental Defect Regeneration in Load - Bearing

Functional Analysis of Human NF1 in Drosophila

DTIC Science & Technology

2008-12-01

also have learning problem. Such learning phenotypes have been recapitulated in animal models, including in mouse and Drosophila mutants. This proposal...by examining the phenotypes of mutated human genes expressed in Drosophila NF1 null mutants. We also propose that Gsα/NF1 activated AC pathway...in both Drosophila and mouse NF1 models. Our previous work has shown that defective cAMP signaling leads to the learning phenotype in Drosophila Nf1

Using a Hybrid Model to Forecast the Prevalence of Schistosomiasis in Humans.

PubMed

Zhou, Lingling; Xia, Jing; Yu, Lijing; Wang, Ying; Shi, Yun; Cai, Shunxiang; Nie, Shaofa

2016-03-23

We previously proposed a hybrid model combining both the autoregressive integrated moving average (ARIMA) and the nonlinear autoregressive neural network (NARNN) models in forecasting schistosomiasis. Our purpose in the current study was to forecast the annual prevalence of human schistosomiasis in Yangxin County, using our ARIMA-NARNN model, thereby further certifying the reliability of our hybrid model. We used the ARIMA, NARNN and ARIMA-NARNN models to fit and forecast the annual prevalence of schistosomiasis. The modeling time range included was the annual prevalence from 1956 to 2008 while the testing time range included was from 2009 to 2012. The mean square error (MSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) were used to measure the model performance. We reconstructed the hybrid model to forecast the annual prevalence from 2013 to 2016. The modeling and testing errors generated by the ARIMA-NARNN model were lower than those obtained from either the single ARIMA or NARNN models. The predicted annual prevalence from 2013 to 2016 demonstrated an initial decreasing trend, followed by an increase. The ARIMA-NARNN model can be well applied to analyze surveillance data for early warning systems for the control and elimination of schistosomiasis.

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.

Objective Model Selection for Identifying the Human Feedforward Response in Manual Control.

PubMed

Drop, Frank M; Pool, Daan M; van Paassen, Marinus Rene M; Mulder, Max; Bulthoff, Heinrich H

2018-01-01

Realistic manual control tasks typically involve predictable target signals and random disturbances. The human controller (HC) is hypothesized to use a feedforward control strategy for target-following, in addition to feedback control for disturbance-rejection. Little is known about human feedforward control, partly because common system identification methods have difficulty in identifying whether, and (if so) how, the HC applies a feedforward strategy. In this paper, an identification procedure is presented that aims at an objective model selection for identifying the human feedforward response, using linear time-invariant autoregressive with exogenous input models. A new model selection criterion is proposed to decide on the model order (number of parameters) and the presence of feedforward in addition to feedback. For a range of typical control tasks, it is shown by means of Monte Carlo computer simulations that the classical Bayesian information criterion (BIC) leads to selecting models that contain a feedforward path from data generated by a pure feedback model: "false-positive" feedforward detection. To eliminate these false-positives, the modified BIC includes an additional penalty on model complexity. The appropriate weighting is found through computer simulations with a hypothesized HC model prior to performing a tracking experiment. Experimental human-in-the-loop data will be considered in future work. With appropriate weighting, the method correctly identifies the HC dynamics in a wide range of control tasks, without false-positive results.

[The methods of assessment of health risk from exposure to radon and radon daughters].

PubMed

Demin, V F; Zhukovskiy, M V; Kiselev, S M

2014-01-01

The critical analysis of existing models of the relationship dose-effect (RDE) for radon exposure on human health has been performed. Conclusion about the necessity and possibility of improving these models has been made. A new improved version ofthe RDE has been developed. A technique for assessing the human health risk of exposure to radon, including the method for estimating of exposure doses of radon, an improved model of RDE, proper methodology risk assessment has been described. Methodology is proposed for the use in the territory of Russia.

Nutraceuticals in rodent models as potential treatments for human Inflammatory Bowel Disease.

PubMed

Ghattamaneni, Naga K R; Panchal, Sunil K; Brown, Lindsay

2018-04-20

Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation of all or part of the digestive tract. Nutraceuticals include bioactive compounds such as polyphenols with anti-inflammatory activities, thus these products have the potential to treat chronic inflammatory diseases. We have emphasized the role of nutraceuticals in ameliorating the symptoms of IBD in rodent models of human IBD through modulation of key pathogenic mechanisms including dysbiosis, oxidative stress, increased inflammatory cytokines, immune system dysregulation, and inflammatory cell signaling pathways. Nutraceuticals have an important role in IBD patients as a preventive approach to extend remission phases and as a therapeutic intervention to suppress active IBD. Further clinical trials on nutraceuticals with positive results in rodent models are warranted. Copyright © 2018. Published by Elsevier Ltd.

Thermal Indices and Thermophysiological Modeling for Heat Stress.

PubMed

Havenith, George; Fiala, Dusan

2015-12-15

The assessment of the risk of human exposure to heat is a topic as relevant today as a century ago. The introduction and use of heat stress indices and models to predict and quantify heat stress and heat strain has helped to reduce morbidity and mortality in industrial, military, sports, and leisure activities dramatically. Models used range from simple instruments that attempt to mimic the human-environment heat exchange to complex thermophysiological models that simulate both internal and external heat and mass transfer, including related processes through (protective) clothing. This article discusses the most commonly used indices and models and looks at how these are deployed in the different contexts of industrial, military, and biometeorological applications, with focus on use to predict related thermal sensations, acute risk of heat illness, and epidemiological analysis of morbidity and mortality. A critical assessment is made of tendencies to use simple indices such as WBGT in more complex conditions (e.g., while wearing protective clothing), or when employed in conjunction with inappropriate sensors. Regarding the more complex thermophysiological models, the article discusses more recent developments including model individualization approaches and advanced systems that combine simulation models with (body worn) sensors to provide real-time risk assessment. The models discussed in the article range from historical indices to recent developments in using thermophysiological models in (bio) meteorological applications as an indicator of the combined effect of outdoor weather settings on humans. Copyright © 2015 John Wiley & Sons, Inc.

The bovine model for elucidating the role of γδ T cells in controlling infectious diseases of importance to cattle and humans.

PubMed

Baldwin, Cynthia L; Telfer, Janice C

2015-07-01

There are several instances of co-investigation and related discoveries and achievements in bovine and human immunology; perhaps most interesting is the development of the BCG vaccine, the tuberculin skin test and the more recent interferon-gamma test that were developed first in cattle to prevent and diagnosis bovine tuberculosis and then applied to humans. There are also a number of immune-physiological traits that ruminant share with humans including the development of their immune systems in utero which increases the utility of cattle as a model for human immunology. These are reviewed here with a particular focus on the use of cattle to unravel γδ T cell biology. Based on the sheer number of γδ T cells in this γδ T cell high species, it is reasonable to expect γδ T cells to play an important role in protective immune responses. For that reason alone cattle may provide good models for elucidating at least some of the roles γδ T cells play in protective immunity in all species. This includes fundamental research on γδ T cells as well as the responses of ruminant γδ T cells to a variety of infectious disease situations including to protozoan and bacterial pathogens. The role that pattern recognition receptors (PRR) play in the activation of γδ T cells may be unique relative to αβ T cells. Here we focus on that of the γδ T cell specific family of molecules known as WC1 or T19 in ruminants, which are part of the CD163 scavenger receptor cysteine rich (SRCR) family that includes SCART1 and SCART2 expressed on murine γδ T cells. We review the evidence for WC1 being a PRR as well as an activating co-receptor and the role that γδ T cells bearing these receptors play in immunity to leptospirosis and tuberculosis. This includes the generation of memory responses to vaccines, thereby continuing the tradition of co-discovery between cattle and humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

Assessing the Risk of Crew Injury Due to Dynamic Loads During Spaceflight

NASA Technical Reports Server (NTRS)

Somers, J. T.; Gernhardt, M.; Newby, N.

2014-01-01

Spaceflight requires tremendous amounts of energy to achieve Earth orbit and to attain escape velocity for interplanetary missions. Although the majority of the energy is managed in such a way as to limit the accelerations on the crew, several mission phases may result in crew exposure to dynamic loads. In the automotive industry, risk of serious injury can be tolerated because the probability of a crash is remote each time a person enters a vehicle, resulting in a low total risk of injury. For spaceflight, the level of acceptable injury risk must be lower to achieve a low total risk of injury because the dynamic loads are expected on each flight. To mitigate the risk of injury due to dynamic loads, the NASA Human Research Program has developed a research plan to inform the knowledge gaps and develop relevant tools for assessing injury risk. The risk of injury due to dynamic loads can be further subdivided into extrinsic and intrinsic risk factors. Extrinsic risk factors include the vehicle dynamic profile, seat and restraint design, and spacesuit design. Human tolerance to loads varies considerably depending on the direction, amplitude, and rise-time of acceleration therefore the orientation of the body to the dynamic vector is critical to determining crew risk of injury. Although a particular vehicle dynamic profile may be safe for a particular design, the seat, restraint, and suit designs can affect the risk of injury due to localized effects. In addition, characteristics intrinsic to the crewmember may also contribute to the risk of injury, such as crewmember sex, age, anthropometry, and deconditioning due to spaceflight, and each astronaut may have a different risk profile because of these factors. The purpose of the research plan is to address any knowledge gaps in the risk factors to mitigate injury risk. Methods for assessing injury risk have been well documented in other analogous industries and include human volunteer testing, human exposure to dynamic environments, post-mortem human subject (PMHS) testing, animal testing, anthropomorphic test devices (ATD), dynamic models of the human, numerical models of ATDs, and numerical models of the human. Each has inherent strengths and limitations. For example, human volunteer testing is advantageous because a population can be selected that is similar to the astronaut corps; however, because of the inherent ethical limitations, only sub-injurious conditions can be tested. PMHSs can be tested in a variety of conditions including injurious levels, but the responses are not completely analogous to living human subjects. In addition, it is exceedingly difficult to select a PMHS population that is similar to the astronaut corps. ATDs are currently widely used in the automotive industry and military because they are highly repeatable and durable. Unfortunately, because they are mechanical models of the human body, the biofidelity of the responses are limited to dynamic conditions used to validate the ATD. Numerical models of the ATD, in addition to the strengths and limitations for ATDs, are easy to use for a variety of designs before a design is fabricated, but also have additional limitations for ATDs, are easy to use for a variety of designs before a design is fabricated, but also have additional uncertainty. Dynamic models are simple and easy to use, but do not account for localized effects of the seat and suit. Finally, numerical models of the human have the potential to have the most advantages; however, the current models are not validated for the conditions expected during spaceflight. To properly assess spaceflight conditions with numerical human models, human data would be needed to optimize the model responses for those conditions. Using the appropriate assessment method with the knowledge gained for each risk factor, an appropriate approach for mitigating the risk of injury due to dynamic loads can be developed ensuring crew safety in future NASA vehicles.

Incorporating Anthropogenic Influences into Fire Probability Models: Effects of Human Activity and Climate Change on Fire Activity in California.

PubMed

Mann, Michael L; Batllori, Enric; Moritz, Max A; Waller, Eric K; Berck, Peter; Flint, Alan L; Flint, Lorraine E; Dolfi, Emmalee

2016-01-01

The costly interactions between humans and wildfires throughout California demonstrate the need to understand the relationships between them, especially in the face of a changing climate and expanding human communities. Although a number of statistical and process-based wildfire models exist for California, there is enormous uncertainty about the location and number of future fires, with previously published estimates of increases ranging from nine to fifty-three percent by the end of the century. Our goal is to assess the role of climate and anthropogenic influences on the state's fire regimes from 1975 to 2050. We develop an empirical model that integrates estimates of biophysical indicators relevant to plant communities and anthropogenic influences at each forecast time step. Historically, we find that anthropogenic influences account for up to fifty percent of explanatory power in the model. We also find that the total area burned is likely to increase, with burned area expected to increase by 2.2 and 5.0 percent by 2050 under climatic bookends (PCM and GFDL climate models, respectively). Our two climate models show considerable agreement, but due to potential shifts in rainfall patterns, substantial uncertainty remains for the semiarid inland deserts and coastal areas of the south. Given the strength of human-related variables in some regions, however, it is clear that comprehensive projections of future fire activity should include both anthropogenic and biophysical influences. Previous findings of substantially increased numbers of fires and burned area for California may be tied to omitted variable bias from the exclusion of human influences. The omission of anthropogenic variables in our model would overstate the importance of climatic ones by at least 24%. As such, the failure to include anthropogenic effects in many models likely overstates the response of wildfire to climatic change.

CystiSim – An Agent-Based Model for Taenia solium Transmission and Control

PubMed Central

Gabriël, Sarah; Dorny, Pierre; Speybroeck, Niko; Magnussen, Pascal; Torgerson, Paul; Johansen, Maria Vang

2016-01-01

Taenia solium taeniosis/cysticercosis was declared eradicable by the International Task Force for Disease Eradication in 1993, but remains a neglected zoonosis. To assist in the attempt to regionally eliminate this parasite, we developed cystiSim, an agent-based model for T. solium transmission and control. The model was developed in R and available as an R package (http://cran.r-project.org/package=cystiSim). cystiSim was adapted to an observed setting using field data from Tanzania, but adaptable to other settings if necessary. The model description adheres to the Overview, Design concepts, and Details (ODD) protocol and consists of two entities—pigs and humans. Pigs acquire cysticercosis through the environment or by direct contact with a tapeworm carrier's faeces. Humans acquire taeniosis from slaughtered pigs proportional to their infection intensity. The model allows for evaluation of three interventions measures or combinations hereof: treatment of humans, treatment of pigs, and pig vaccination, and allows for customary coverage and efficacy settings. cystiSim is the first agent-based transmission model for T. solium and suggests that control using a strategy consisting of an intervention only targeting the porcine host is possible, but that coverage and efficacy must be high if elimination is the ultimate goal. Good coverage of the intervention is important, but can be compensated for by including an additional intervention targeting the human host. cystiSim shows that the scenarios combining interventions in both hosts, mass drug administration to humans, and vaccination and treatment of pigs, have a high probability of success if coverage of 75% can be maintained over at least a four year period. In comparison with an existing mathematical model for T. solium transmission, cystiSim also includes parasite maturation, host immunity, and environmental contamination. Adding these biological parameters to the model resulted in new insights in the potential effect of intervention measures. PMID:27984581

CystiSim - An Agent-Based Model for Taenia solium Transmission and Control.

PubMed

Braae, Uffe Christian; Devleesschauwer, Brecht; Gabriël, Sarah; Dorny, Pierre; Speybroeck, Niko; Magnussen, Pascal; Torgerson, Paul; Johansen, Maria Vang

2016-12-01

Taenia solium taeniosis/cysticercosis was declared eradicable by the International Task Force for Disease Eradication in 1993, but remains a neglected zoonosis. To assist in the attempt to regionally eliminate this parasite, we developed cystiSim, an agent-based model for T. solium transmission and control. The model was developed in R and available as an R package (http://cran.r-project.org/package=cystiSim). cystiSim was adapted to an observed setting using field data from Tanzania, but adaptable to other settings if necessary. The model description adheres to the Overview, Design concepts, and Details (ODD) protocol and consists of two entities-pigs and humans. Pigs acquire cysticercosis through the environment or by direct contact with a tapeworm carrier's faeces. Humans acquire taeniosis from slaughtered pigs proportional to their infection intensity. The model allows for evaluation of three interventions measures or combinations hereof: treatment of humans, treatment of pigs, and pig vaccination, and allows for customary coverage and efficacy settings. cystiSim is the first agent-based transmission model for T. solium and suggests that control using a strategy consisting of an intervention only targeting the porcine host is possible, but that coverage and efficacy must be high if elimination is the ultimate goal. Good coverage of the intervention is important, but can be compensated for by including an additional intervention targeting the human host. cystiSim shows that the scenarios combining interventions in both hosts, mass drug administration to humans, and vaccination and treatment of pigs, have a high probability of success if coverage of 75% can be maintained over at least a four year period. In comparison with an existing mathematical model for T. solium transmission, cystiSim also includes parasite maturation, host immunity, and environmental contamination. Adding these biological parameters to the model resulted in new insights in the potential effect of intervention measures.

Incorporating Anthropogenic Influences into Fire Probability Models: Effects of Human Activity and Climate Change on Fire Activity in California

PubMed Central

Batllori, Enric; Moritz, Max A.; Waller, Eric K.; Berck, Peter; Flint, Alan L.; Flint, Lorraine E.; Dolfi, Emmalee

2016-01-01

The costly interactions between humans and wildfires throughout California demonstrate the need to understand the relationships between them, especially in the face of a changing climate and expanding human communities. Although a number of statistical and process-based wildfire models exist for California, there is enormous uncertainty about the location and number of future fires, with previously published estimates of increases ranging from nine to fifty-three percent by the end of the century. Our goal is to assess the role of climate and anthropogenic influences on the state’s fire regimes from 1975 to 2050. We develop an empirical model that integrates estimates of biophysical indicators relevant to plant communities and anthropogenic influences at each forecast time step. Historically, we find that anthropogenic influences account for up to fifty percent of explanatory power in the model. We also find that the total area burned is likely to increase, with burned area expected to increase by 2.2 and 5.0 percent by 2050 under climatic bookends (PCM and GFDL climate models, respectively). Our two climate models show considerable agreement, but due to potential shifts in rainfall patterns, substantial uncertainty remains for the semiarid inland deserts and coastal areas of the south. Given the strength of human-related variables in some regions, however, it is clear that comprehensive projections of future fire activity should include both anthropogenic and biophysical influences. Previous findings of substantially increased numbers of fires and burned area for California may be tied to omitted variable bias from the exclusion of human influences. The omission of anthropogenic variables in our model would overstate the importance of climatic ones by at least 24%. As such, the failure to include anthropogenic effects in many models likely overstates the response of wildfire to climatic change. PMID:27124597

Information processing. [in human performance

NASA Technical Reports Server (NTRS)

Wickens, Christopher D.; Flach, John M.

1988-01-01

Theoretical models of sensory-information processing by the human brain are reviewed from a human-factors perspective, with a focus on their implications for aircraft and avionics design. The topics addressed include perception (signal detection and selection), linguistic factors in perception (context provision, logical reversals, absence of cues, and order reversals), mental models, and working and long-term memory. Particular attention is given to decision-making problems such as situation assessment, decision formulation, decision quality, selection of action, the speed-accuracy tradeoff, stimulus-response compatibility, stimulus sequencing, dual-task performance, task difficulty and structure, and factors affecting multiple task performance (processing modalities, codes, and stages).

Socio-hydrologic Modeling to Understand and Mediate the Competition for Water between Humans and Ecosystems: Murrumbidgee River Basin, Australia

NASA Astrophysics Data System (ADS)

van Emmerik, Tim; Sivapalan, Murugesu; Li, Zheng; Pande, Saket; Savenije, Hubert

2014-05-01

Around the world the demand for water resources is growing in order to satisfy rapidly increasing human populations, leading to competition for water between humans and ecosystems. An entirely new and comprehensive quantitative framework is needed to establish a holistic understanding of that competition, thereby enabling development and evaluation of effective mediation strategies. We present a case study centered on the Murrumbidgee river basin in eastern Australia that illustrates the dynamics of the balance between water extraction and use for food production and efforts to mitigate and reverse consequent degradation of the riparian environment. Interactions between patterns of water resources management and climate driven hydrological variability within the prevailing socio-economic environment have contributed to the emergence of new whole system dynamics over the last 100 years. In particular, data analysis reveals a pendulum swing between an exclusive focus on agricultural development and food production in the initial stages of water resources development and its attendant socio-economic benefits, followed by the gradual realization of the adverse environmental impacts, efforts to mitigate these with the use of remedial measures, and ultimately concerted efforts and externally imposed solutions to restore environmental health and ecosystem services. A quasi-distributed coupled socio-hydrologic system model that explicitly includes the two-way coupling between human and hydrological systems, including evolution of human values/norms relating to water and the environment, is able to mimic broad features of this pendulum swing. The model consists of coupled nonlinear differential equations that include four state variables describing the co-evolution of storage capacity, irrigated area, human population, and ecosystem health, which are all connected by feedback mechanisms. The model is used to generate insights into the dominant controls of the trajectory of co-evolution of the coupled human-water system, to serve as the theoretical framework for more detailed analysis of the system, and to generate organizing principles that may be transferable to other systems in different climatic and socio-economic settings.

Biological and statistical approaches to predicting human lung cancer risk from silica.

PubMed

Kuempel, E D; Tran, C L; Bailer, A J; Porter, D W; Hubbs, A F; Castranova, V

2001-01-01

Chronic inflammation is a key step in the pathogenesis of particle-elicited fibrosis and lung cancer in rats, and possibly in humans. In this study, we compute the excess risk estimates for lung cancer in humans with occupational exposure to crystalline silica, using both rat and human data, and using both a threshold approach and linear models. From a toxicokinetic/dynamic model fit to lung burden and pulmonary response data from a subchronic inhalation study in rats, we estimated the minimum critical quartz lung burden (Mcrit) associated with reduced pulmonary clearance and increased neutrophilic inflammation. A chronic study in rats was also used to predict the human excess risk of lung cancer at various quartz burdens, including mean Mcrit (0.39 mg/g lung). We used a human kinetic lung model to link the equivalent lung burdens to external exposures in humans. We then computed the excess risk of lung cancer at these external exposures, using data of workers exposed to respirable crystalline silica and using Poisson regression and lifetable analyses. Finally, we compared the lung cancer excess risks estimated from male rat and human data. We found that the rat-based linear model estimates were approximately three times higher than those based on human data (e.g., 2.8% in rats vs. 0.9-1% in humans, at mean Mcrit lung burden or associated mean working lifetime exposure of 0.036 mg/m3). Accounting for variability and uncertainty resulted in 100-1000 times lower estimates of human critical lung burden and airborne exposure. This study illustrates that assumptions about the relevant biological mechanism, animal model, and statistical approach can all influence the magnitude of lung cancer risk estimates in humans exposed to crystalline silica.

Genetics and recent human evolution.

PubMed

Templeton, Alan R

2007-07-01

Starting with "mitochondrial Eve" in 1987, genetics has played an increasingly important role in studies of the last two million years of human evolution. It initially appeared that genetic data resolved the basic models of recent human evolution in favor of the "out-of-Africa replacement" hypothesis in which anatomically modern humans evolved in Africa about 150,000 years ago, started to spread throughout the world about 100,000 years ago, and subsequently drove to complete genetic extinction (replacement) all other human populations in Eurasia. Unfortunately, many of the genetic studies on recent human evolution have suffered from scientific flaws, including misrepresenting the models of recent human evolution, focusing upon hypothesis compatibility rather than hypothesis testing, committing the ecological fallacy, and failing to consider a broader array of alternative hypotheses. Once these flaws are corrected, there is actually little genetic support for the out-of-Africa replacement hypothesis. Indeed, when genetic data are used in a hypothesis-testing framework, the out-of-Africa replacement hypothesis is strongly rejected. The model of recent human evolution that emerges from a statistical hypothesis-testing framework does not correspond to any of the traditional models of human evolution, but it is compatible with fossil and archaeological data. These studies also reveal that any one gene or DNA region captures only a small part of human evolutionary history, so multilocus studies are essential. As more and more loci became available, genetics will undoubtedly offer additional insights and resolutions of human evolution.

How Human and Natural Disturbance Affects the U.S. Carbon Sink

NASA Astrophysics Data System (ADS)

Felzer, B. S.

2015-12-01

Gridded datasets of Net Ecosystem Exchange derived from eddy covariance and remote sensing measurements (EC-MOD and FLUXNET-MTE) provide a means of validating Net Ecosystem Productivity (NEP, opposite of NEE) from terrestrial ecosystem models. While most forested regions in the U.S. are observed to be moderate to strong carbon sinks, models not including human or natural disturbances will tend to be more carbon neutral, which is expected of mature ecosystems. I have developed the Terrestrial Ecosystems Model Hydro version (TEM-Hydro) to include both human and natural disturbances to compare against gridded NEP datasets. Human disturbances are based on the Hurtt et al. land use transition dataset and include transient agricultural (crops and pasture) conversion and abandonment and timber harvest. Natural disturbances include tropical storms and hurricane and fires based on stochastic return intervals. Model results indicate that forests are the largest carbon sink, seconded by croplands and pastures, if not accounting for decomposition of agricultural products and animal respiration. Grasslands and shrublands are both small sinks or carbon neutral. The NEP of forests in EC-MOD from 2001-2006 is 240 gCm2yr-1 and for FLUXNET-MTE from 1982-2007 is 375 gCm-2yr-1. With potential vegetation, the respective forest sinks for those two time periods are 54 and 62 gCm-2yr-1, respectively. Including the effects of human disturbance increases the sinks to 154 and 147 gCm-2yr-1. The effect of stochastic fire and storms is to reduce the NEP to 114 and 108 gCm-2yr-1. While the positive carbon sink today is the result of past land use disturbance, net carbon sequestration, including product decomposition, conversion fluxes, and animal respiration, has not yet returned to predisturbance levels as seen in the potential vegetation. Differences in response to disturbance have to do with the type, frequency, and intensity of disturbance. Fire, in particular, is seen to have a net negative effect on carbon storage in forests due to decomposition of coarse woody debris and the fact that some nitrogen is lost during volatilization. Croplands become a carbon source if assuming product decomposition occurs where the crops are grown, and pasturelands become carbon neutral if accounting for animal respiration.

Investigating the state of physiologically based kinetic modelling practices and challenges associated with gaining regulatory acceptance of model applications

EPA Science Inventory

Physiologically based kinetic (PBK) models are used widely throughout a number of working sectors, including academia and industry, to provide insight into the dosimetry related to observed adverse health effects in humans and other species. Use of these models has increased over...

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

Statistical Models for Predicting Automobile Driving Postures for Men and Women Including Effects of Age.

PubMed

Park, Jangwoon; Ebert, Sheila M; Reed, Matthew P; Hallman, Jason J

2016-03-01

Previously published statistical models of driving posture have been effective for vehicle design but have not taken into account the effects of age. The present study developed new statistical models for predicting driving posture. Driving postures of 90 U.S. drivers with a wide range of age and body size were measured in laboratory mockup in nine package conditions. Posture-prediction models for female and male drivers were separately developed by employing a stepwise regression technique using age, body dimensions, vehicle package conditions, and two-way interactions, among other variables. Driving posture was significantly associated with age, and the effects of other variables depended on age. A set of posture-prediction models is presented for women and men. The results are compared with a previously developed model. The present study is the first study of driver posture to include a large cohort of older drivers and the first to report a significant effect of age. The posture-prediction models can be used to position computational human models or crash-test dummies for vehicle design and assessment. © 2015, Human Factors and Ergonomics Society.

Ballistics and anatomical modelling - A review.

PubMed

Humphrey, Caitlin; Kumaratilake, Jaliya

2016-11-01

Ballistics is the study of a projectiles motion and can be broken down into four stages: internal, intermediate, external and terminal ballistics. The study of the effects a projectile has on a living tissue is referred to as wound ballistics and falls within terminal ballistics. To understand the effects a projectile has on living tissues the mechanisms of wounding need to be understood. These include the permanent and temporary cavities, energy, yawing, tumbling and fragmenting. Much ballistics research has been conducted including using cadavers, animal models and simulants such as ballistics ordnance gelatine. Further research is being conducted into developing anatomical, 3D, experimental and computational models. However, these models need to accurately represent the human body and its heterogeneous nature which involves understanding the biomechanical properties of the different tissues and organs. Further research is needed to accurately represent the human tissues with simulants and is slowly being conducted. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Health economics of screening for gynaecological cancers.

PubMed

Kulasingam, Shalini; Havrilesky, Laura

2012-04-01

In this chapter, we summarise findings from recent cost-effectiveness analyses of screening for cervical cancer and ovarian cancer. We begin with a brief summary of key issues that affect the cost-effectiveness of screening, including disease burden, and availability and type of screening tests. For cervical cancer, we discuss the potential effect of human papilloma virus vaccines on screening. Outstanding epidemiological and cost-effectiveness issues are included. For cervical cancer, this includes incorporating the long-term effect of treatment (including adverse birth outcomes in treated women who are of reproductive age) into cost-effectiveness models using newly available trial data to identify the best strategy for incorporating human papilloma virus tests. A second issue is the need for additional data on human papilloma virus vaccines, such as effectiveness of reduced cancer incidence and mortality, effectiveness in previously exposed women and coverage. Definitive data on these parameters will allow us to update model-based analyses to include more realistic estimates, and also potentially dramatically alter our approach to screening. For ovarian cancer, outstanding issues include confirming within the context of a trial that screening is effective for reducing mortality and incorporating tests with high specificity into screening into screening algorithms for ovarian cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

77 FR 56581 - Airworthiness Directives; Sikorsky Aircraft Corporation Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-13

... HEC, in this model helicopter that now meets the Category A performance standard. DATES: We must... airworthiness directive (AD) for the Sikorsky Aircraft Corporation (Sikorsky) Model S-92A helicopter, which... external load operations, including human external cargo (HEC), because this model helicopter was not...

Rodent Models of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis

PubMed Central

Imajo, Kento; Yoneda, Masato; Kessoku, Takaomi; Ogawa, Yuji; Maeda, Shin; Sumida, Yoshio; Hyogo, Hideyuki; Eguchi, Yuichiro; Wada, Koichiro; Nakajima, Atsushi

2013-01-01

Research in nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), has been limited by the availability of suitable models for this disease. A number of rodent models have been described in which the relevant liver pathology develops in an appropriate metabolic context. These models are promising tools for researchers investigating one of the key issues of NASH: not so much why steatosis occurs, but what causes the transition from simple steatosis to the inflammatory, progressive fibrosing condition of steatohepatitis. The different rodent models can be classified into two large groups. The first includes models in which the disease is acquired after dietary or pharmacological manipulation, and the second, genetically modified models in which liver disease develops spontaneously. To date, no single rodent model has encompassed the full spectrum of human disease progression, but individual models can imitate particular characteristics of human disease. Therefore, it is important that researchers choose the appropriate rodent models. The purpose of the present review is to discuss the metabolic abnormalities present in the currently available rodent models of NAFLD, summarizing the strengths and weaknesses of the established models and the key findings that have furthered our understanding of the disease’s pathogenesis. PMID:24192824

Human tracking over camera networks: a review

NASA Astrophysics Data System (ADS)

Hou, Li; Wan, Wanggen; Hwang, Jenq-Neng; Muhammad, Rizwan; Yang, Mingyang; Han, Kang

2017-12-01

In recent years, automated human tracking over camera networks is getting essential for video surveillance. The tasks of tracking human over camera networks are not only inherently challenging due to changing human appearance, but also have enormous potentials for a wide range of practical applications, ranging from security surveillance to retail and health care. This review paper surveys the most widely used techniques and recent advances for human tracking over camera networks. Two important functional modules for the human tracking over camera networks are addressed, including human tracking within a camera and human tracking across non-overlapping cameras. The core techniques of human tracking within a camera are discussed based on two aspects, i.e., generative trackers and discriminative trackers. The core techniques of human tracking across non-overlapping cameras are then discussed based on the aspects of human re-identification, camera-link model-based tracking and graph model-based tracking. Our survey aims to address existing problems, challenges, and future research directions based on the analyses of the current progress made toward human tracking techniques over camera networks.

Human impact on wildfires varies between regions and with vegetation productivity

NASA Astrophysics Data System (ADS)

Lasslop, Gitta; Kloster, Silvia

2017-11-01

We assess the influence of humans on burned area simulated with a dynamic global vegetation model. The human impact in the model is based on population density and cropland fraction, which were identified as important drivers of burned area in analyses of global datasets, and are commonly used in global models. After an evaluation of the sensitivity to these two variables we extend the model by including an additional effect of the cropland fraction on the fire duration. The general pattern of human influence is similar in both model versions: the strongest human impact is found in regions with intermediate productivity, where fire occurrence is not limited by fuel load or climatic conditions. Human effects in the model increases burned area in the tropics, while in temperate regions burned area is reduced. While the population density is similar on average for the tropical and temperate regions, the cropland fraction is higher in temperate regions, and leads to a strong suppression of fire. The model shows a low human impact in the boreal region, where both population density and cropland fraction is very low and the climatic conditions, as well as the vegetation productivity limit fire. Previous studies attributed a decrease in fire activity found in global charcoal datasets to human activity. This is confirmed by our simulations, which only show a decrease in burned area when the human influence on fire is accounted for, and not with only natural effects on fires. We assess how the vegetation-fire feedback influences the results, by comparing simulations with dynamic vegetation biogeography to simulations with prescribed vegetation. The vegetation-fire feedback increases the human impact on burned area by 10% for present day conditions. These results emphasize that projections of burned area need to account for the interactions between fire, climate, vegetation and humans.

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

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.

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.

Genetic evidence and the modern human origins debate.

PubMed

Relethford, J H

2008-06-01

A continued debate in anthropology concerns the evolutionary origin of 'anatomically modern humans' (Homo sapiens sapiens). Different models have been proposed to examine the related questions of (1) where and when anatomically modern humans first appeared and (2) the genetic and evolutionary relationship between modern humans and earlier human populations. Genetic data have been increasingly used to address these questions. Genetic data on living human populations have been used to reconstruct the evolutionary history of the human species by considering how global patterns of human variation could be produced given different evolutionary scenarios. Of particular interest are gene trees that reconstruct the time and place of the most recent common ancestor of humanity for a given haplotype and the analysis of regional differences in genetic diversity. Ancient DNA has also allowed a direct assessment of genetic variation in European Neandertals. Together with the fossil record, genetic data provide insight into the origin of modern humans. The evidence points to an African origin of modern humans dating back to 200,000 years followed by later expansions of moderns out of Africa across the Old World. What is less clear is what happened when these early modern humans met preexisting 'archaic human' populations outside of Africa. At present, it is difficult to distinguish between a model of total genetic replacement and a model that includes some degree of genetic mixture.

Prototype Biology-Based Radiation Risk Module Project

NASA Technical Reports Server (NTRS)

Terrier, Douglas; Clayton, Ronald G.; Patel, Zarana; Hu, Shaowen; Huff, Janice

2015-01-01

Biological effects of space radiation and risk mitigation are strategic knowledge gaps for the Evolvable Mars Campaign. The current epidemiology-based NASA Space Cancer Risk (NSCR) model contains large uncertainties (HAT #6.5a) due to lack of information on the radiobiology of galactic cosmic rays (GCR) and lack of human data. The use of experimental models that most accurately replicate the response of human tissues is critical for precision in risk projections. Our proposed study will compare DNA damage, histological, and cell kinetic parameters after irradiation in normal 2D human cells versus 3D tissue models, and it will use a multi-scale computational model (CHASTE) to investigate various biological processes that may contribute to carcinogenesis, including radiation-induced cellular signaling pathways. This cross-disciplinary work, with biological validation of an evolvable mathematical computational model, will help reduce uncertainties within NSCR and aid risk mitigation for radiation-induced carcinogenesis.

Silkworm: A Promising Model Organism in Life Science.

PubMed

Meng, Xu; Zhu, Feifei; Chen, Keping

2017-09-01

As an important economic insect, silkworm Bombyx mori (L.) (Lepidoptera: Bombycidae) has numerous advantages in life science, such as low breeding cost, large progeny size, short generation time, and clear genetic background. Additionally, there are rich genetic resources associated with silkworms. The completion of the silkworm genome has further accelerated it to be a modern model organism in life science. Genomic studies showed that some silkworm genes are highly homologous to certain genes related to human hereditary disease and, therefore, are a candidate model for studying human disease. In this article, we provided a review of silkworm as an important model in various research areas, including human disease, screening of antimicrobial agents, environmental safety monitoring, and antitumor studies. In addition, the application potentiality of silkworm model in life sciences was discussed. © The Author 2017. Published by Oxford University Press on behalf of Entomological Society of America.

Alzheimer’s in 3D culture: Challenges and perspectives

PubMed Central

D'Avanzo, Carla; Aronson, Jenna; Kim, Young Hye; Choi, Se Hoon; Tanzi, Rudolph E.; Kim, Doo Yeon

2015-01-01

Summary Alzheimer’s disease (AD) is the most common cause of dementia, and there is currently no cure. The “β-amyloid cascade hypothesis” of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three-dimensional (3D) cell culture system. These cells were able to recapitulate key events of AD pathology including β-amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery. PMID:26252541

Integrating Household Risk Mitigation Behavior in Flood Risk Analysis: An Agent-Based Model Approach.

PubMed

Haer, Toon; Botzen, W J Wouter; de Moel, Hans; Aerts, Jeroen C J H

2017-10-01

Recent studies showed that climate change and socioeconomic trends are expected to increase flood risks in many regions. However, in these studies, human behavior is commonly assumed to be constant, which neglects interaction and feedback loops between human and environmental systems. This neglect of human adaptation leads to a misrepresentation of flood risk. This article presents an agent-based model that incorporates human decision making in flood risk analysis. In particular, household investments in loss-reducing measures are examined under three economic decision models: (1) expected utility theory, which is the traditional economic model of rational agents; (2) prospect theory, which takes account of bounded rationality; and (3) a prospect theory model, which accounts for changing risk perceptions and social interactions through a process of Bayesian updating. We show that neglecting human behavior in flood risk assessment studies can result in a considerable misestimation of future flood risk, which is in our case study an overestimation of a factor two. Furthermore, we show how behavior models can support flood risk analysis under different behavioral assumptions, illustrating the need to include the dynamic adaptive human behavior of, for instance, households, insurers, and governments. The method presented here provides a solid basis for exploring human behavior and the resulting flood risk with respect to low-probability/high-impact risks. © 2016 The Authors Risk Analysis published by Wiley Periodicals, Inc. on behalf of Society for Risk Analysis.

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

Universal predictability of mobility patterns in cities

PubMed Central

Yan, Xiao-Yong; Zhao, Chen; Fan, Ying; Di, Zengru; Wang, Wen-Xu

2014-01-01

Despite the long history of modelling human mobility, we continue to lack a highly accurate approach with low data requirements for predicting mobility patterns in cities. Here, we present a population-weighted opportunities model without any adjustable parameters to capture the underlying driving force accounting for human mobility patterns at the city scale. We use various mobility data collected from a number of cities with different characteristics to demonstrate the predictive power of our model. We find that insofar as the spatial distribution of population is available, our model offers universal prediction of mobility patterns in good agreement with real observations, including distance distribution, destination travel constraints and flux. By contrast, the models that succeed in modelling mobility patterns in countries are not applicable in cities, which suggests that there is a diversity of human mobility at different spatial scales. Our model has potential applications in many fields relevant to mobility behaviour in cities, without relying on previous mobility measurements. PMID:25232053

Predicting lung dosimetry of inhaled particleborne benzo[a]pyrene using physiologically based pharmacokinetic modeling

PubMed Central

Campbell, Jerry; Franzen, Allison; Van Landingham, Cynthia; Lumpkin, Michael; Crowell, Susan; Meredith, Clive; Loccisano, Anne; Gentry, Robinan; Clewell, Harvey

2016-01-01

Abstract Benzo[a]pyrene (BaP) is a by-product of incomplete combustion of fossil fuels and plant/wood products, including tobacco. A physiologically based pharmacokinetic (PBPK) model for BaP for the rat was extended to simulate inhalation exposures to BaP in rats and humans including particle deposition and dissolution of absorbed BaP and renal elimination of 3-hydroxy benzo[a]pyrene (3-OH BaP) in humans. The clearance of particle-associated BaP from lung based on existing data in rats and dogs suggest that the process is bi-phasic. An initial rapid clearance was represented by BaP released from particles followed by a slower first-order clearance that follows particle kinetics. Parameter values for BaP-particle dissociation were estimated using inhalation data from isolated/ventilated/perfused rat lungs and optimized in the extended inhalation model using available rat data. Simulations of acute inhalation exposures in rats identified specific data needs including systemic elimination of BaP metabolites, diffusion-limited transfer rates of BaP from lung tissue to blood and the quantitative role of macrophage-mediated and ciliated clearance mechanisms. The updated BaP model provides very good prediction of the urinary 3-OH BaP concentrations and the relative difference between measured 3-OH BaP in nonsmokers versus smokers. This PBPK model for inhaled BaP is a preliminary tool for quantifying lung BaP dosimetry in rat and humans and was used to prioritize data needs that would provide significant model refinement and robust internal dosimetry capabilities. PMID:27569524

The Importance of Human Reliability Analysis in Human Space Flight: Understanding the Risks

NASA Technical Reports Server (NTRS)

Hamlin, Teri L.

2010-01-01

HRA is a method used to describe, qualitatively and quantitatively, the occurrence of human failures in the operation of complex systems that affect availability and reliability. Modeling human actions with their corresponding failure in a PRA (Probabilistic Risk Assessment) provides a more complete picture of the risk and risk contributions. A high quality HRA can provide valuable information on potential areas for improvement, including training, procedural, equipment design and need for automation.

Peer-to-Peer Human-Robot Interaction for Space Exploration

NASA Technical Reports Server (NTRS)

Fong, Terrence; Nourbakhsh, Illah

2004-01-01

NASA has embarked on a long-term program to develop human-robot systems for sustained, affordable space exploration. To support this mission, we are working to improve human-robot interaction and performance on planetary surfaces. Rather than building robots that function as glorified tools, our focus is to enable humans and robots to work as partners and peers. In this paper. we describe our approach, which includes contextual dialogue, cognitive modeling, and metrics-based field testing.

Parallel Computing for Brain Simulation.

PubMed

Pastur-Romay, L A; Porto-Pazos, A B; Cedron, F; Pazos, A

2017-01-01

The human brain is the most complex system in the known universe, it is therefore one of the greatest mysteries. It provides human beings with extraordinary abilities. However, until now it has not been understood yet how and why most of these abilities are produced. For decades, researchers have been trying to make computers reproduce these abilities, focusing on both understanding the nervous system and, on processing data in a more efficient way than before. Their aim is to make computers process information similarly to the brain. Important technological developments and vast multidisciplinary projects have allowed creating the first simulation with a number of neurons similar to that of a human brain. This paper presents an up-to-date review about the main research projects that are trying to simulate and/or emulate the human brain. They employ different types of computational models using parallel computing: digital models, analog models and hybrid models. This review includes the current applications of these works, as well as future trends. It is focused on various works that look for advanced progress in Neuroscience and still others which seek new discoveries in Computer Science (neuromorphic hardware, machine learning techniques). Their most outstanding characteristics are summarized and the latest advances and future plans are presented. In addition, this review points out the importance of considering not only neurons: Computational models of the brain should also include glial cells, given the proven importance of astrocytes in information processing. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cognitive Phenotype of Velocardiofacial Syndrome: A Review

ERIC Educational Resources Information Center

Furniss, Frederick; Biswas, Asit B.; Gumber, Rohit; Singh, Niraj

2011-01-01

The behavioural phenotype of velocardiofacial syndrome (VCFS), one of the most common human multiple anomaly syndromes, includes developmental disabilities, frequently including intellectual disability (ID) and high risk of diagnosis of psychotic disorders including schizophrenia. VCFS may offer a model of the relationship between ID and risk of…

[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.

Predicting detection performance with model observers: Fourier domain or spatial domain?

PubMed

Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia

2016-02-27

The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images.

Predicting detection performance with model observers: Fourier domain or spatial domain?

PubMed Central

Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia

2016-01-01

The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images. PMID:27239086

ADDRESSING ENVIRONMENTAL ENGINEERING CHALLENGES WITH COMPUTATIONAL FLUID DYNAMICS

EPA Science Inventory

In the field of environmental engineering, modeling tools are playing an ever larger role in addressing air quality issues, including source pollutant emissions, atmospheric dispersion and human exposure risks. More detailed modeling of environmental flows requires tools for c...

An Engineered Organoid Culture Model That Incorporates Human Mesenchymal and Epithelial Cells to Model Palatal Fusion.

EPA Science Inventory

During embryonic development, fusion events are critical to morphogenesis of organs and tissues, including the iris, urethra, heart, neural tube, and secondary palate. Modeling this process in vitro is challenging as the interactions of mesenchymal and epithelial cells can be cr...

Drosophila melanogaster as a model system for the evaluation of anti-aging compounds.

PubMed

Jafari, Mahtab

2010-01-01

Understanding the causes of aging is a complex problem due to the multiple factors that influence aging, which include genetics, environment, metabolism and reproduction, among others. These multiple factors create logistical difficulties in the evaluation of anti-aging agents. There is a need for good model systems to evaluate potential anti-aging compounds. The model systems used should represent the complexities of aging in humans, so that the findings may be extrapolated to human studies, but they should also present an opportunity to minimize the variables so that the experimental results can be accurately interpreted. In addition to positively affecting lifespan, the impact of the compound on the physiologic confounders of aging, including fecundity and the health span--the period of life where an organism is generally healthy and free from serious or chronic illness--of the model organism needs to be evaluated. Fecundity is considered a major confounder of aging in fruit flies. It is well established that female flies that are exposed to toxic substances typically reduce their dietary intake and their reproductive output and display an artifactual lifespan extension. As a result, drugs that achieve longevity benefits by reducing fecundity as a result of diminished food intake are probably not useful candidates for eventual treatment of aging in humans and should be eliminated during the screening process. Drosophila melanogaster provides a suitable model system for the screening of anti-aging compounds as D. melanogaster and humans have many conserved physiological and biological pathways. In this paper, I propose an algorithm to screen anti-aging compounds using Drosophila melanogaster as a model system.

Tissue engineering a human phalanx.

PubMed

Landis, W J; Chubinskaya, S; Tokui, T; Wada, Y; Isogai, N; Jacquet, R

2017-08-01

A principal purpose of tissue engineering is the augmentation, repair or replacement of diseased or injured human tissue. This study was undertaken to determine whether human biopsies as a cell source could be utilized for successful engineering of human phalanges consisting of both bone and cartilage. This paper reports the use of cadaveric human chondrocytes and periosteum as a model for the development of phalanx constructs. Two factors, osteogenic protein-1 [OP-1/bone morphogenetic protein-7 (BMP7)], alone or combined with insulin-like growth factor (IGF-1), were examined for their potential enhancement of chondrocytes and their secreted extracellular matrices. Design of the study included culture of chondrocytes and periosteum on biodegradable polyglycolic acid (PGA) and poly-l-lactic acid (PLLA)-poly-ε-caprolactone (PCL) scaffolds and subsequent implantation in athymic nu/nu (nude) mice for 5, 20, 40 and 60 weeks. Engineered constructs retrieved from mice were characterized with regard to genotype and phenotype as a function of developmental (implantation) time. Assessments included gross observation, X-ray radiography or microcomputed tomography, histology and gene expression. The resulting data showed that human cell-scaffold constructs could be successfully developed over 60 weeks, despite variability in donor age. Cartilage formation of the distal phalanx models enhanced with both OP-1 and IGF-1 yielded more cells and extracellular matrix (collagen and proteoglycans) than control chondrocytes without added factors. Summary data demonstrated that human distal phalanx models utilizing cadaveric chondrocytes and periosteum were successfully fabricated and OP-1 and OP-1/IGF-1 accelerated construct development and mineralization. The results suggest that similar engineering and transplantation of human autologous tissues in patients are clinically feasible. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Novel mouse model recapitulates genome and transcriptome alterations in human colorectal carcinomas.

PubMed

McNeil, Nicole E; Padilla-Nash, Hesed M; Buishand, Floryne O; Hue, Yue; Ried, Thomas

2017-03-01

Human colorectal carcinomas are defined by a nonrandom distribution of genomic imbalances that are characteristic for this disease. Often, these imbalances affect entire chromosomes. Understanding the role of these aneuploidies for carcinogenesis is of utmost importance. Currently, established transgenic mice do not recapitulate the pathognonomic genome aberration profile of human colorectal carcinomas. We have developed a novel model based on the spontaneous transformation of murine colon epithelial cells. During this process, cells progress through stages of pre-immortalization, immortalization and, finally, transformation, and result in tumors when injected into immunocompromised mice. We analyzed our model for genome and transcriptome alterations using ArrayCGH, spectral karyotyping (SKY), and array based gene expression profiling. ArrayCGH revealed a recurrent pattern of genomic imbalances. These results were confirmed by SKY. Comparing these imbalances with orthologous maps of human chromosomes revealed a remarkable overlap. We observed focal deletions of the tumor suppressor genes Trp53 and Cdkn2a/p16. High-level focal genomic amplification included the locus harboring the oncogene Mdm2, which was confirmed by FISH in the form of double minute chromosomes. Array-based global gene expression revealed distinct differences between the sequential steps of spontaneous transformation. Gene expression changes showed significant similarities with human colorectal carcinomas. Pathways most prominently affected included genes involved in chromosomal instability and in epithelial to mesenchymal transition. Our novel mouse model therefore recapitulates the most prominent genome and transcriptome alterations in human colorectal cancer, and might serve as a valuable tool for understanding the dynamic process of tumorigenesis, and for preclinical drug testing. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

Three-Dimensional Reconstruction of Thoracic Structures: Based on Chinese Visible Human

PubMed Central

Luo, Na; Tan, Liwen; Fang, Binji; Li, Ying; Xie, Bing; Liu, Kaijun; Chu, Chun; Li, Min

2013-01-01

We managed to establish three-dimensional digitized visible model of human thoracic structures and to provide morphological data for imaging diagnosis and thoracic and cardiovascular surgery. With Photoshop software, the contour line of lungs and mediastinal structures including heart, aorta and its ramus, azygos vein, superior vena cava, inferior vena cava, thymus, esophagus, diaphragm, phrenic nerve, vagus nerve, sympathetic trunk, thoracic vertebrae, sternum, thoracic duct, and so forth were segmented from the Chinese Visible Human (CVH)-1 data set. The contour data set of segmented thoracic structures was imported to Amira software and 3D thorax models were reconstructed via surface rendering and volume rendering. With Amira software, surface rendering reconstructed model of thoracic organs and its volume rendering reconstructed model were 3D reconstructed and can be displayed together clearly and accurately. It provides a learning tool of interpreting human thoracic anatomy and virtual thoracic and cardiovascular surgery for medical students and junior surgeons. PMID:24369489

The effect of sun-dried raisins (Vitis vinifera L.) on the in vitro composition of the gut microbiota.

PubMed

Mandalari, Giuseppina; Chessa, Simona; Bisignano, Carlo; Chan, Luisa; Carughi, Arianna

2016-09-14

Modulation of the human gut microbiota has proven to have beneficial effects on host health. The aim of this work was to evaluate the effect of sun-dried raisins (SR) on the composition of the human gut microbiota. A full model of the gastrointestinal tract, which includes simulated mastication, a dynamic gastric model, a duodenal model and a colonic model of the human large intestine, was used. An increase in the numbers of bifidobacteria and lactobacilli was observed by plate-counting in response to the addition of either SR or FOS after 8 and 24 h fermentation. A significant decrease in Firmicutes and Bacteroidetes was observed in SR samples after 8 and 24 h fermentation. FOS resulted in the greatest production of short chain fatty acids. Sun-dried raisins demonstrated considerable potential to promote the colonization and proliferation of beneficial bacteria in the human large intestine and to stimulate the production of organic acids.

Opportunities and constraints of presently used thermal manikins for thermo-physiological simulation of the human body.

PubMed

Psikuta, Agnes; Kuklane, Kalev; Bogdan, Anna; Havenith, George; Annaheim, Simon; Rossi, René M

2016-03-01

Combining the strengths of an advanced mathematical model of human physiology and a thermal manikin is a new paradigm for simulating thermal behaviour of humans. However, the forerunners of such adaptive manikins showed some substantial limitations. This project aimed to determine the opportunities and constraints of the existing thermal manikins when dynamically controlled by a mathematical model of human thermal physiology. Four thermal manikins were selected and evaluated for their heat flux measurement uncertainty including lateral heat flows between manikin body parts and the response of each sector to the frequent change of the set-point temperature typical when using a physiological model for control. In general, all evaluated manikins are suitable for coupling with a physiological model with some recommendations for further improvement of manikin dynamic performance. The proposed methodology is useful to improve the performance of the adaptive manikins and help to provide a reliable and versatile tool for the broad research and development domain of clothing, automotive and building engineering.

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.

Measuring and Modeling Behavioral Decision Dynamics in Collective Evacuation

PubMed Central

Carlson, Jean M.; Alderson, David L.; Stromberg, Sean P.; Bassett, Danielle S.; Craparo, Emily M.; Guiterrez-Villarreal, Francisco; Otani, Thomas

2014-01-01

Identifying and quantifying factors influencing human decision making remains an outstanding challenge, impacting the performance and predictability of social and technological systems. In many cases, system failures are traced to human factors including congestion, overload, miscommunication, and delays. Here we report results of a behavioral network science experiment, targeting decision making in a natural disaster. In a controlled laboratory setting, our results quantify several key factors influencing individual evacuation decision making in a controlled laboratory setting. The experiment includes tensions between broadcast and peer-to-peer information, and contrasts the effects of temporal urgency associated with the imminence of the disaster and the effects of limited shelter capacity for evacuees. Based on empirical measurements of the cumulative rate of evacuations as a function of the instantaneous disaster likelihood, we develop a quantitative model for decision making that captures remarkably well the main features of observed collective behavior across many different scenarios. Moreover, this model captures the sensitivity of individual- and population-level decision behaviors to external pressures, and systematic deviations from the model provide meaningful estimates of variability in the collective response. Identification of robust methods for quantifying human decisions in the face of risk has implications for policy in disasters and other threat scenarios, specifically the development and testing of robust strategies for training and control of evacuations that account for human behavior and network topologies. PMID:24520331

Finite element micro-modelling of a human ankle bone reveals the importance of the trabecular network to mechanical performance: new methods for the generation and comparison of 3D models.

PubMed

Parr, W C H; Chamoli, U; Jones, A; Walsh, W R; Wroe, S

2013-01-04

Most modelling of whole bones does not incorporate trabecular geometry and treats bone as a solid non-porous structure. Some studies have modelled trabecular networks in isolation. One study has modelled the performance of whole human bones incorporating trabeculae, although this required considerable computer resources and purpose-written code. The difference between mechanical behaviour in models that incorporate trabecular geometry and non-porous models has not been explored. The ability to easily model trabecular networks may shed light on the mechanical consequences of bone loss in osteoporosis and remodelling after implant insertion. Here we present a Finite Element Analysis (FEA) of a human ankle bone that includes trabecular network geometry. We compare results from this model with results from non-porous models and introduce protocols achievable on desktop computers using widely available softwares. Our findings show that models including trabecular geometry are considerably stiffer than non-porous whole bone models wherein the non-cortical component has the same mass as the trabecular network, suggesting inclusion of trabecular geometry is desirable. We further present new methods for the construction and analysis of 3D models permitting: (1) construction of multi-property, non-porous models wherein cortical layer thickness can be manipulated; (2) maintenance of the same triangle network for the outer cortical bone surface in both 3D reconstruction and non-porous models allowing exact replication of load and restraint cases; and (3) creation of an internal landmark point grid allowing direct comparison between 3D FE Models (FEMs). Copyright © 2012 Elsevier Ltd. All rights reserved.

The Cool and Belkin Faceted Classification of Information Interactions Revisited

ERIC Educational Resources Information Center

Huvila, Isto

2010-01-01

Introduction: The complexity of human information activity is a challenge for both practice and research in information sciences and information management. Literature presents a wealth of approaches to analytically structure and make sense of human information activity including a faceted classification model of information interactions published…

Ultraviolet Radiation: Human Exposure and Health Risks.

ERIC Educational Resources Information Center

Tenkate, Thomas D.

1998-01-01

Provides an overview of human exposure to ultraviolet radiation and associated health effects as well as risk estimates for acute and chronic conditions resulting from such exposure. Demonstrates substantial reductions in health risk that can be achieved through preventive actions. Also includes a risk assessment model for skin cancer. Contains 36…

Undergraduate Research in the Human Sciences: Three Models

ERIC Educational Resources Information Center

Collins, Nina; Mitstifer, Dorothy I.; Nelson Goff, Briana S.; Hymon-Parker, Shirley

2009-01-01

Undergraduate research in the sciences has been shown by numerous studies to enhance the educational experience. The Undergraduate Research Community (URC) founded in 2001 supports several initiatives that promote research in human sciences/family and consumer sciences including an online peer-reviewed journal specifically for undergraduate work,…

Young Children Proactively Remedy Unnoticed Accidents

ERIC Educational Resources Information Center

Warneken, Felix

2013-01-01

Human adults will sometimes help without being asked to help, including in situations in which the helpee is oblivious to the problem and thus provides no communicative or behavioral cues that intervention is necessary. Some theoretical models argue that these acts of "proactive helping" are an important and possibly human-specific form of…

Human Resource Development and Manpower Training. Paper Presentations: Session B.

ERIC Educational Resources Information Center

2000

This document contains 18 papers from the human resource development and manpower training section of an international conference on vocational education and training (VET) for lifelong learning in the information era. The following papers are included: "Use of Social and Economic Modeling to Plan Vocational Education and Training"…

Characterization of lipopolysaccharide-stimulated cytokine expression in macrophages and monocytes

USDA-ARS?s Scientific Manuscript database

Inflammation plays a pivotal role in several chronic human conditions and diseases including atherosclerosis, ischemic heart disease, cancer, obesity, diabetes, and autoimmune diseases. In vitro cell culture models such as exposure of mouse macrophage J774A.1 and human monocyte THP-1 cells to bacter...

HRD Issues in Asia.

ERIC Educational Resources Information Center

1998

This document contains four papers from a symposium on human resource development (HRD) issues in Asia. "The Japanese Human Resource Development System" (Kiyoe Harada) provides a comprehensive model of the Japanese HRD system based on the current state of the art, including management practices and issues and trends in Japanese HRD.…

Time series modeling of human operator dynamics in manual control tasks

NASA Technical Reports Server (NTRS)

Biezad, D. J.; Schmidt, D. K.

1984-01-01

A time-series technique is presented for identifying the dynamic characteristics of the human operator in manual control tasks from relatively short records of experimental data. Control of system excitation signals used in the identification is not required. The approach is a multi-channel identification technique for modeling multi-input/multi-output situations. The method presented includes statistical tests for validity, is designed for digital computation, and yields estimates for the frequency responses of the human operator. A comprehensive relative power analysis may also be performed for validated models. This method is applied to several sets of experimental data; the results are discussed and shown to compare favorably with previous research findings. New results are also presented for a multi-input task that has not been previously modeled to demonstrate the strengths of the method.

Time Series Modeling of Human Operator Dynamics in Manual Control Tasks

NASA Technical Reports Server (NTRS)

Biezad, D. J.; Schmidt, D. K.

1984-01-01

A time-series technique is presented for identifying the dynamic characteristics of the human operator in manual control tasks from relatively short records of experimental data. Control of system excitation signals used in the identification is not required. The approach is a multi-channel identification technique for modeling multi-input/multi-output situations. The method presented includes statistical tests for validity, is designed for digital computation, and yields estimates for the frequency response of the human operator. A comprehensive relative power analysis may also be performed for validated models. This method is applied to several sets of experimental data; the results are discussed and shown to compare favorably with previous research findings. New results are also presented for a multi-input task that was previously modeled to demonstrate the strengths of the method.

Quantitative comparison of ligament formulation and pre-strain in finite element analysis of the human lumbar spine.

PubMed

Hortin, Mitchell S; Bowden, Anton E

2016-11-01

Data has been published that quantifies the nonlinear, anisotropic material behaviour and pre-strain behaviour of the anterior longitudinal, supraspinous (SSL), and interspinous ligaments of the human lumbar spine. Additionally, data has been published on localized material properties of the SSL. These results have been incrementally incorporated into a previously validated finite element model of the human lumbar spine. Results suggest that the effects of increased ligament model fidelity on bone strain energy were moderate and the effects on disc pressure were slight, and do not justify a change in modelling strategy for most clinical applications. There were significant effects on the ligament stresses of the ligaments that were directly modified, suggesting that these phenomena should be included in FE models where ligament stresses are the desired metric.

Radiation transport modeling and assessment to better predict radiation exposure, dose, and toxicological effects to human organs on long duration space flights.

PubMed

Denkins, P; Badhwar, G; Obot, V; Wilson, B; Jejelewo, O

2001-01-01

NASA is very interested in improving its ability to monitor and forecast the radiation levels that pose a health risk to space-walking astronauts as they construct the International Space Station and astronauts that will participate in long-term and deep-space missions. Human exploratory missions to the moon and Mars within the next quarter century, will expose crews to transient radiation from solar particle events which include high-energy galactic cosmic rays and high-energy protons. Because the radiation levels in space are high and solar activity is presently unpredictable, adequate shielding is needed to minimize the deleterious health effects of exposure to radiation. Today, numerous models have been developed and used to predict radiation exposure. Such a model is the Space Environment Information Systems (SPENVIS) modeling program, developed by the Belgian Institute for Space Aeronautics. SPENVIS, which has been assessed to be an excellent tool in characterizing the radiation environment for microelectronics and investigating orbital debris, is being evaluated for its usefulness with determining the dose and dose-equivalent for human exposure. Thus far. the calculations for dose-depth relations under varying shielding conditions have been in agreement with calculations done using HZETRN and PDOSE, which are well-known and widely used models for characterizing the environments for human exploratory missions. There is disagreement when assessing the impact of secondary radiation particles since SPENVIS does a crude estimation of the secondary radiation particles when calculating LET versus Flux. SPENVIS was used to model dose-depth relations for the blood-forming organs. Radiation sickness and cancer are life-threatening consequences resulting from radiation exposure. In space. exposure to radiation generally includes all of the critical organs. Biological and toxicological impacts have been included for discussion along with alternative risk mitigation methods--shielding and anti-carcinogens. c 2001. Elsevier Science Ltd. All rights reserved.

Radiation transport modeling and assessment to better predict radiation exposure, dose, and toxicological effects to human organs on long duration space flights

NASA Technical Reports Server (NTRS)

Denkins, P.; Badhwar, G.; Obot, V.; Wilson, B.; Jejelewo, O.

2001-01-01

NASA is very interested in improving its ability to monitor and forecast the radiation levels that pose a health risk to space-walking astronauts as they construct the International Space Station and astronauts that will participate in long-term and deep-space missions. Human exploratory missions to the moon and Mars within the next quarter century, will expose crews to transient radiation from solar particle events which include high-energy galactic cosmic rays and high-energy protons. Because the radiation levels in space are high and solar activity is presently unpredictable, adequate shielding is needed to minimize the deleterious health effects of exposure to radiation. Today, numerous models have been developed and used to predict radiation exposure. Such a model is the Space Environment Information Systems (SPENVIS) modeling program, developed by the Belgian Institute for Space Aeronautics. SPENVIS, which has been assessed to be an excellent tool in characterizing the radiation environment for microelectronics and investigating orbital debris, is being evaluated for its usefulness with determining the dose and dose-equivalent for human exposure. Thus far. the calculations for dose-depth relations under varying shielding conditions have been in agreement with calculations done using HZETRN and PDOSE, which are well-known and widely used models for characterizing the environments for human exploratory missions. There is disagreement when assessing the impact of secondary radiation particles since SPENVIS does a crude estimation of the secondary radiation particles when calculating LET versus Flux. SPENVIS was used to model dose-depth relations for the blood-forming organs. Radiation sickness and cancer are life-threatening consequences resulting from radiation exposure. In space. exposure to radiation generally includes all of the critical organs. Biological and toxicological impacts have been included for discussion along with alternative risk mitigation methods--shielding and anti-carcinogens. c 2001. Elsevier Science Ltd. All rights reserved.

Radiation transport modeling and assessment to better predict radiation exposure, dose, and toxicological effects to human organs on long duration space flights

NASA Astrophysics Data System (ADS)

Denkins, Pamela; Badhwar, Gautam; Obot, Victor; Wilson, Bobby; Jejelewo, Olufisayo

2001-08-01

NASA is very interested in improving its ability to monitor and forecast the radiation levels that pose a health risk to space-walking astronauts as they construct the International Space Station and astronauts that will participate in long-term and deep-space missions. Human exploratory missions to the moon and Mars within the next quarter century, will expose crews to transient radiation from solar particle events which include high-energy galactic cosmic rays and high-energy protons. Because the radiation levels in space are high and solar activity is presently unpredictable, adequate shielding is needed to minimize the deleterious health effects of exposure to radiation. Today, numerous models have been developed and used to predict radiation exposure. Such a model is the Space Environment Information Systems (SPENVIS) modeling program, developed by the Belgian Institute for Space Aeronautics. SPENVIS, which has been assessed to be an excellent tool in characterizing the radiation environment for microelectronics and investigating orbital debris, is being evaluated for its usefulness with determining the dose and dose-equivalent for human exposure. Thus far, the calculations for dose-depth relations under varying shielding conditions have been in agreement with calculations done using HZETRN and PDOSE, which are well-known and widely used models for characterizing the environments for human exploratory missions. There is disagreement when assessing the impact of secondary radiation particles since SPENVIS does a crude estimation of the secondary radiation particles when calculating LET versus Flux. SPENVIS was used to model dose-depth relations for the blood-forming organs. Radiation sickness and cancer are life-threatening consequences resulting from radiation exposure. In space, exposure to radiation generally includes all of the critical organs. Biological and toxicological impacts have been included for discussion along with alternative risk mitigation methods — shielding and anti-carcinogens.

Advances in the Study of Heart Development and Disease Using Zebrafish

PubMed Central

Brown, Daniel R.; Samsa, Leigh Ann; Qian, Li; Liu, Jiandong

2016-01-01

Animal models of cardiovascular disease are key players in the translational medicine pipeline used to define the conserved genetic and molecular basis of disease. Congenital heart diseases (CHDs) are the most common type of human birth defect and feature structural abnormalities that arise during cardiac development and maturation. The zebrafish, Danio rerio, is a valuable vertebrate model organism, offering advantages over traditional mammalian models. These advantages include the rapid, stereotyped and external development of transparent embryos produced in large numbers from inexpensively housed adults, vast capacity for genetic manipulation, and amenability to high-throughput screening. With the help of modern genetics and a sequenced genome, zebrafish have led to insights in cardiovascular diseases ranging from CHDs to arrhythmia and cardiomyopathy. Here, we discuss the utility of zebrafish as a model system and summarize zebrafish cardiac morphogenesis with emphasis on parallels to human heart diseases. Additionally, we discuss the specific tools and experimental platforms utilized in the zebrafish model including forward screens, functional characterization of candidate genes, and high throughput applications. PMID:27335817

Case Study: Organotypic human in vitro models of embryonic ...

EPA Pesticide Factsheets

Morphogenetic fusion of tissues is a common event in embryonic development and disruption of fusion is associated with birth defects of the eye, heart, neural tube, phallus, palate, and other organ systems. Embryonic tissue fusion requires precise regulation of cell-cell and cell-matrix interactions that drive proliferation, differentiation, and morphogenesis. Chemical low-dose exposures can disrupt morphogenesis across space and time by interfering with key embryonic fusion events. The Morphogenetic Fusion Task uses computer and in vitro models to elucidate consequences of developmental exposures. The Morphogenetic Fusion Task integrates multiple approaches to model responses to chemicals that leaad to birth defects, including integrative mining on ToxCast DB, ToxRefDB, and chemical structures, advanced computer agent-based models, and human cell-based cultures that model disruption of cellular and molecular behaviors including mechanisms predicted from integrative data mining and agent-based models. The purpose of the poster is to indicate progress on the CSS 17.02 Virtual Tissue Models Morphogenesis Task 1 products for the Board of Scientific Counselors meeting on Nov 16-17.

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

Re-Design and Beat Testing of the Man-Machine Integration Design and Analysis System: MIDAS

NASA Technical Reports Server (NTRS)

Shively, R. Jay; Rutkowski, Michael (Technical Monitor)

1999-01-01

The Man-machine Design and Analysis System (MIDAS) is a human factors design and analysis system that combines human cognitive models with 3D CAD models and rapid prototyping and simulation techniques. MIDAS allows designers to ask 'what if' types of questions early in concept exploration and development prior to actual hardware development. The system outputs predictions of operator workload, situational awareness and system performance as well as graphical visualization of the cockpit designs interacting with models of the human in a mission scenario. Recently, MIDAS was re-designed to enhance functionality and usability. The goals driving the redesign include more efficient processing, GUI interface, advances in the memory structures, implementation of external vision models and audition. These changes were detailed in an earlier paper. Two Beta test sites with diverse applications have been chosen. One Beta test site is investigating the development of a new airframe and its interaction with the air traffic management system. The second Beta test effort will investigate 3D auditory cueing in conjunction with traditional visual cueing strategies including panel-mounted and heads-up displays. The progress and lessons learned on each of these projects will be discussed.

Early life stress paradigms in rodents: potential animal models of depression?

PubMed

Schmidt, Mathias V; Wang, Xiao-Dong; Meijer, Onno C

2011-03-01

While human depressive illness is indeed uniquely human, many of its symptoms may be modeled in rodents. Based on human etiology, the assumption has been made that depression-like behavior in rats and mice can be modulated by some of the powerful early life programming effects that are known to occur after manipulations in the first weeks of life. Here we review the evidence that is available in literature for early life manipulation as risk factors for the development of depression-like symptoms such as anhedonia, passive coping strategies, and neuroendocrine changes. Early life paradigms that were evaluated include early handling, separation, and deprivation protocols, as well as enriched and impoverished environments. We have also included a small number of stress-related pharmacological models. We find that for most early life paradigms per se, the actual validity for depression is limited. A number of models have not been tested with respect to classical depression-like behaviors, while in many cases, the outcome of such experiments is variable and depends on strain and additional factors. Because programming effects confer vulnerability rather than disease, a number of paradigms hold promise for usefulness in depression research, in combination with the proper genetic background and adult life challenges.

A cortically-inspired model for inverse kinematics computation of a humanoid finger with mechanically coupled joints.

PubMed

Gentili, Rodolphe J; Oh, Hyuk; Kregling, Alissa V; Reggia, James A

2016-05-19

The human hand's versatility allows for robust and flexible grasping. To obtain such efficiency, many robotic hands include human biomechanical features such as fingers having their two last joints mechanically coupled. Although such coupling enables human-like grasping, controlling the inverse kinematics of such mechanical systems is challenging. Here we propose a cortical model for fine motor control of a humanoid finger, having its two last joints coupled, that learns the inverse kinematics of the effector. This neural model functionally mimics the population vector coding as well as sensorimotor prediction processes of the brain's motor/premotor and parietal regions, respectively. After learning, this neural architecture could both overtly (actual execution) and covertly (mental execution or motor imagery) perform accurate, robust and flexible finger movements while reproducing the main human finger kinematic states. This work contributes to developing neuro-mimetic controllers for dexterous humanoid robotic/prosthetic upper-extremities, and has the potential to promote human-robot interactions.

Priming nanoparticle-guided diagnostics and therapeutics towards human organs-on-chips microphysiological system

NASA Astrophysics Data System (ADS)

Choi, Jin-Ha; Lee, Jaewon; Shin, Woojung; Choi, Jeong-Woo; Kim, Hyun Jung

2016-10-01

Nanotechnology and bioengineering have converged over the past decades, by which the application of multi-functional nanoparticles (NPs) has been emerged in clinical and biomedical fields. The NPs primed to detect disease-specific biomarkers or to deliver biopharmaceutical compounds have beena validated in conventional in vitro culture models including two dimensional (2D) cell cultures or 3D organoid models. However, a lack of experimental models that have strong human physiological relevance has hampered accurate validation of the safety and functionality of NPs. Alternatively, biomimetic human "Organs-on-Chips" microphysiological systems have recapitulated the mechanically dynamic 3D tissue interface of human organ microenvironment, in which the transport, cytotoxicity, biocompatibility, and therapeutic efficacy of NPs and their conjugates may be more accurately validated. Finally, integration of NP-guided diagnostic detection and targeted nanotherapeutics in conjunction with human organs-on-chips can provide a novel avenue to accelerate the NP-based drug development process as well as the rapid detection of cellular secretomes associated with pathophysiological processes.

Environmental assessment model for shallow land disposal of low-level radioactive wastes

NASA Astrophysics Data System (ADS)

Little, C. A.; Fields, D. E.; Emerson, C. J.; Hiromoto, G.

1981-09-01

The PRESTO (Prediction of Radiation Effects from Shallow Trench Operations) computer code developed to evaluate health effects from shallow land burial trenches is described. This generic model assesses radionuclide transport, ensuing exposure, and health impact to a static local population for a 1000 y period following the end of burial operations. Human exposure scenarios considered include normal releases (including leaching and operational spillage), human intrusion, and site farming or reclamation. Pathways and processes of transit from the trench to an individual or population includes ground water transport overland flow, erosion, surface water dilution, resuspension, atmospheric transport, deposition, inhalation, and ingestion of contaminated beef, milk, crops, and water. Both population doses and individual doses are calculated as well as doses to the intruder and farmer. Cumulative health effects in terms of deaths from cancer are calculated for the population over the 1000 y period using a life table approach. Data bases for three shallow land burial sites (Barnwell, South Carolina, Beatty, Nevada, and West Valley, New York) are under development. The interim model, includes coding for environmental transport through air, surface water, and ground water.

Using Zebrafish Models of Human Influenza A Virus Infections to Screen Antiviral Drugs and Characterize Host Immune Cell Responses.

PubMed

Sullivan, Con; Jurcyzszak, Denise; Goody, Michelle F; Gabor, Kristin A; Longfellow, Jacob R; Millard, Paul J; Kim, Carol H

2017-01-20

Each year, seasonal influenza outbreaks profoundly affect societies worldwide. In spite of global efforts, influenza remains an intractable healthcare burden. The principle strategy to curtail infections is yearly vaccination. In individuals who have contracted influenza, antiviral drugs can mitigate symptoms. There is a clear and unmet need to develop alternative strategies to combat influenza. Several animal models have been created to model host-influenza interactions. Here, protocols for generating zebrafish models for systemic and localized human influenza A virus (IAV) infection are described. Using a systemic IAV infection model, small molecules with potential antiviral activity can be screened. As a proof-of-principle, a protocol that demonstrates the efficacy of the antiviral drug Zanamivir in IAV-infected zebrafish is described. It shows how disease phenotypes can be quantified to score the relative efficacy of potential antivirals in IAV-infected zebrafish. In recent years, there has been increased appreciation for the critical role neutrophils play in the human host response to influenza infection. The zebrafish has proven to be an indispensable model for the study of neutrophil biology, with direct impacts on human medicine. A protocol to generate a localized IAV infection in the Tg(mpx:mCherry) zebrafish line to study neutrophil biology in the context of a localized viral infection is described. Neutrophil recruitment to localized infection sites provides an additional quantifiable phenotype for assessing experimental manipulations that may have therapeutic applications. Both zebrafish protocols described faithfully recapitulate aspects of human IAV infection. The zebrafish model possesses numerous inherent advantages, including high fecundity, optical clarity, amenability to drug screening, and availability of transgenic lines, including those in which immune cells such as neutrophils are labeled with fluorescent proteins. The protocols detailed here exploit these advantages and have the potential to reveal critical insights into host-IAV interactions that may ultimately translate into the clinic.

Comparison of a Conceptual Groundwater Model and Physically Based Groundwater Mode

NASA Astrophysics Data System (ADS)

Yang, J.; Zammit, C.; Griffiths, J.; Moore, C.; Woods, R. A.

2017-12-01

Groundwater is a vital resource for human activities including agricultural practice and urban water demand. Hydrologic modelling is an important way to study groundwater recharge, movement and discharge, and its response to both human activity and climate change. To understand the groundwater hydrologic processes nationally in New Zealand, we have developed a conceptually based groundwater flow model, which is fully integrated into a national surface-water model (TopNet), and able to simulate groundwater recharge, movement, and interaction with surface water. To demonstrate the capability of this groundwater model (TopNet-GW), we applied the model to an irrigated area with water shortage and pollution problems in the upper Ruamahanga catchment in Great Wellington Region, New Zealand, and compared its performance with a physically-based groundwater model (MODFLOW). The comparison includes river flow at flow gauging sites, and interaction between groundwater and river. Results showed that the TopNet-GW produced similar flow and groundwater interaction patterns as the MODFLOW model, but took less computation time. This shows the conceptually-based groundwater model has the potential to simulate national groundwater process, and could be used as a surrogate for the more physically based model.

Mammalian Models for the Study of H7 Virus Pathogenesis and Transmission

PubMed Central

Belser, Jessica A.; Tumpey, Terrence M.

2018-01-01

Mammalian models, most notably the mouse and ferret, have been instrumental in the assessment of avian influenza virus pathogenicity and transmissibility, and have been used widely to characterize the molecular determinants that confer H5N1 virulence in mammals. However, while H7 influenza viruses have typically been associated with conjunctivitis and/or mild respiratory disease in humans, severe disease and death is also possible, as underscored by the recent emergence of H7N9 viruses in China. Despite the public health need to understand the pandemic potential of this virus subtype, H7 virus pathogenesis and transmission has not been as extensively studied. In this review, we discuss the heterogeneity of H7 subtype viruses isolated from humans, and the characterization of mammalian models to study the virulence of H7 subtype viruses associated with human infection, including viruses of both high and low pathogenicity and following multiple inoculation routes. The use of the ferret transmission model to assess the influence of receptor binding preference among contemporary H7 influenza viruses is described. These models have enabled the study of preventative and therapeutic agents, including vaccines and antivirals, to reduce disease burden, and have permitted a greater appreciation that not all highly pathogenic influenza viruses are created equal. PMID:24996862

Perception of mind and dehumanization: Human, animal, or machine?

PubMed

Morera, María D; Quiles, María N; Correa, Ana D; Delgado, Naira; Leyens, Jacques-Philippe

2016-08-02

Dehumanization is reached through several approaches, including the attribute-based model of mind perception and the metaphor-based model of dehumanization. We performed two studies to find different (de)humanized images for three targets: Professional people, Evil people, and Lowest of the low. In Study 1, we examined dimensions of mind, expecting the last two categories to be dehumanized through denial of agency (Lowest of the low) or experience (Evil people), compared with humanized targets (Professional people). Study 2 aimed to distinguish these targets using metaphors. We predicted that Evil and Lowest of the low targets would suffer mechanistic and animalistic dehumanization, respectively; our predictions were confirmed, but the metaphor-based model nuanced these results: animalistic and mechanistic dehumanization were shown as overlapping rather than independent. Evil persons were perceived as "killing machines" and "predators." Finally, Lowest of the low were not animalized but considered human beings. We discuss possible interpretations. © 2016 International Union of Psychological Science.

Tooth enamel oxygen "isoscapes" show a high degree of human mobility in prehistoric Britain.

PubMed

Pellegrini, Maura; Pouncett, John; Jay, Mandy; Pearson, Mike Parker; Richards, Michael P

2016-10-07

A geostatistical model to predict human skeletal oxygen isotope values (δ 18 O p ) in Britain is presented here based on a new dataset of Chalcolithic and Early Bronze Age human teeth. The spatial statistics which underpin this model allow the identification of individuals interpreted as 'non-local' to the areas where they were buried (spatial outliers). A marked variation in δ 18 O p is observed in several areas, including the Stonehenge region, the Peak District, and the Yorkshire Wolds, suggesting a high degree of human mobility. These areas, rich in funerary and ceremonial monuments, may have formed focal points for people, some of whom would have travelled long distances, ultimately being buried there. The dataset and model represent a baseline for future archaeological studies, avoiding the complex conversions from skeletal to water δ 18 O values-a process known to be problematic.

Tooth enamel oxygen “isoscapes” show a high degree of human mobility in prehistoric Britain

PubMed Central

Pellegrini, Maura; Pouncett, John; Jay, Mandy; Pearson, Mike Parker; Richards, Michael P.

2016-01-01

A geostatistical model to predict human skeletal oxygen isotope values (δ18Op) in Britain is presented here based on a new dataset of Chalcolithic and Early Bronze Age human teeth. The spatial statistics which underpin this model allow the identification of individuals interpreted as ‘non-local’ to the areas where they were buried (spatial outliers). A marked variation in δ18Op is observed in several areas, including the Stonehenge region, the Peak District, and the Yorkshire Wolds, suggesting a high degree of human mobility. These areas, rich in funerary and ceremonial monuments, may have formed focal points for people, some of whom would have travelled long distances, ultimately being buried there. The dataset and model represent a baseline for future archaeological studies, avoiding the complex conversions from skeletal to water δ18O values–a process known to be problematic. PMID:27713538

Tooth enamel oxygen “isoscapes” show a high degree of human mobility in prehistoric Britain

NASA Astrophysics Data System (ADS)

Pellegrini, Maura; Pouncett, John; Jay, Mandy; Pearson, Mike Parker; Richards, Michael P.

2016-10-01

A geostatistical model to predict human skeletal oxygen isotope values (δ18Op) in Britain is presented here based on a new dataset of Chalcolithic and Early Bronze Age human teeth. The spatial statistics which underpin this model allow the identification of individuals interpreted as ‘non-local’ to the areas where they were buried (spatial outliers). A marked variation in δ18Op is observed in several areas, including the Stonehenge region, the Peak District, and the Yorkshire Wolds, suggesting a high degree of human mobility. These areas, rich in funerary and ceremonial monuments, may have formed focal points for people, some of whom would have travelled long distances, ultimately being buried there. The dataset and model represent a baseline for future archaeological studies, avoiding the complex conversions from skeletal to water δ18O values-a process known to be problematic.

Establishment of an evaluation model for human milk fat substitutes.

PubMed

Wang, Yong-Hua; Mai, Qing-Yun; Qin, Xiao-Li; Yang, Bo; Wang, Zi-Lian; Chen, Hai-Tian

2010-01-13

Fatty acid composition and distribution of human milk fat (HMF), from mothers over different lactating periods in Guangzhou, China, were analyzed. The universal characteristics were consistent with previously reported results although the fatty acid content was within a different range and dependent on the local population (low saturated fatty acid and high oleic acid for Guangdong mothers' milk fat). Based on the composition of the total and sn-2 fatty acids of mature milk fat, an efficient evaluation model was innovatively established by adopting the "deducting score" principle. The model showed good agreement between the scores and the degree of similarity by assessing 15 samples from different sources including four samples of HMF, eight samples of human milk fat substitutes (HMFSs) and infant formulas, and three samples of fats and oils. This study would allow for the devolvement of individual human milk fat substitutes with different and specific fatty acid compositions for local infants.

Efficacy and safety of herbal medicines in treating gastric ulcer: a review.

PubMed

Bi, Wei-Ping; Man, Hui-Bin; Man, Mao-Qiang

2014-12-07

Gastric ulcer is a common disorder of the digestive system. Current therapeutic regimens largely rely on Western medicine. However, numerous studies have demonstrated that herbal medicines can effectively treat gastric ulcer in humans and various animal models via divergent mechanisms. This review updates the efficacy and safety of herbal medicines in treating gastric ulcer, and the mechanisms of their action in humans and animal models. Studies have demonstrated that the efficacy of herbal medicines is comparable or superior to that of drugs such as omeprazole or cimetidine in humans and animal models, and herbal medicines display fewer adverse effects. The mechanisms by which herbal medicines benefit gastric ulcer include stimulation of mucous cell proliferation, anti-oxidation, and inhibition of gastric acid secretion and H(+)/K(+)-ATPase activity. Some herbal medicines also exhibit antimicrobial properties. Utilization of herbal medicines could be a valuable alternative to treat gastric ulcer in humans effectively, with few adverse effects.

Mathematical Modeling for Scrub Typhus and Its Implications for Disease Control.

PubMed

Min, Kyung Duk; Cho, Sung Il

2018-03-19

The incidence rate of scrub typhus has been increasing in the Republic of Korea. Previous studies have suggested that this trend may have resulted from the effects of climate change on the transmission dynamics among vectors and hosts, but a clear explanation of the process is still lacking. In this study, we applied mathematical models to explore the potential factors that influence the epidemiology of tsutsugamushi disease. We developed mathematical models of ordinary differential equations including human, rodent and mite groups. Two models, including simple and complex models, were developed, and all parameters employed in the models were adopted from previous articles that represent epidemiological situations in the Republic of Korea. The simulation results showed that the force of infection at the equilibrium state under the simple model was 0.236 (per 100,000 person-months), and that in the complex model was 26.796 (per 100,000 person-months). Sensitivity analyses indicated that the most influential parameters were rodent and mite populations and contact rate between them for the simple model, and trans-ovarian transmission for the complex model. In both models, contact rate between humans and mites is more influential than morality rate of rodent and mite group. The results indicate that the effect of controlling either rodents or mites could be limited, and reducing the contact rate between humans and mites is more practical and effective strategy. However, the current level of control would be insufficient relative to the growing mite population. © 2018 The Korean Academy of Medical Sciences.

Engineered cell and tissue models of pulmonary fibrosis.

PubMed

Sundarakrishnan, Aswin; Chen, Ying; Black, Lauren D; Aldridge, Bree B; Kaplan, David L

2018-04-01

Pulmonary fibrosis includes several lung disorders characterized by scar formation and Idiopathic Pulmonary Fibrosis (IPF) is a particularly severe form of pulmonary fibrosis of unknown etiology with a mean life expectancy of 3years' post-diagnosis. Treatments for IPF are limited to two FDA approved drugs, pirfenidone and nintedanib. Most lead candidate drugs that are identified in pre-clinical animal studies fail in human clinical trials. Thus, there is a need for advanced humanized in vitro models of the lung to improve candidate treatments prior to moving to human clinical trials. The development of 3D tissue models has created systems capable of emulating human lung structure, function, and cell and matrix interactions. The specific models accomplish these features and preliminary studies conducted using some of these systems have shown potential for in vitro anti-fibrotic drug testing. Further characterization and improvements will enable these tissue models to extend their utility for in vitro drug testing, to help identify signaling pathways and mechanisms for new drug targets, and potentially reduce animal models as standard pre-clinical models of study. In the current review, we contrast different in vitro models based on increasing dimensionality (2D, 2.5D and 3D), with added focus on contemporary 3D pulmonary models of fibrosis. Copyright © 2017. Published by Elsevier B.V.

A journey of a thousand miles begins with one small step - human agency, hydrological processes and time in socio-hydrology

NASA Astrophysics Data System (ADS)

Ertsen, M. W.; Murphy, J. T.; Purdue, L. E.; Zhu, T.

2013-11-01

When simulating social action in modeling efforts, as in socio-hydrology, an issue of obvious importance is how to ensure that social action by human agents is well-represented in the analysis and the model. Generally, human decision-making is either modeled on a yearly basis or lumped together as collective social structures. Both responses are problematic, as human decision making is more complex and organizations are the result of human agency and cannot be used as explanatory forces. A way out of the dilemma how to include human agency is to go to the largest societal and environmental clustering possible: society itself and climate, with time steps of years or decades. In the paper, the other way out is developed: to face human agency squarely, and direct the modeling approach to the human agency of individuals and couple this with the lowest appropriate hydrological level and time step. This approach is supported theoretically by the work of Bruno Latour, the French sociologist and philosopher. We discuss irrigation archaeology, as it is in this discipline that the issues of scale and explanatory force are well discussed. The issue is not just what scale to use: it is what scale matters. We argue that understanding the arrangements that permitted the management of irrigation over centuries, requires modeling and understanding the small-scale, day-to-day operations and personal interactions upon which they were built. This effort, however, must be informed by the longer-term dynamics as these provide the context within which human agency, is acted out.

Data Sets from Major NCI Initiaves

Cancer.gov

The NCI Data Catalog includes links to data collections produced by major NCI initiatives and other widely used data sets, including animal models, human tumor cell lines, epidemiology data sets, genomics data sets from TCGA, TARGET, COSMIC, GSK, NCI60.

SEIPS 2.0: A human factors framework for studying and improving the work of healthcare professionals and patients

PubMed Central

Holden, Richard J.; Carayon, Pascale; Gurses, Ayse P.; Hoonakker, Peter; Hundt, Ann Schoofs; Ozok, A. Ant; Rivera-Rodriguez, A. Joy

2013-01-01

Healthcare practitioners, patient safety leaders, educators, and researchers increasingly recognize the value of human factors/ergonomics and make use of the discipline’s person-centered models of sociotechnical systems. This paper first reviews one of the most widely used healthcare human factors systems models, the Systems Engineering Initiative for Patient Safety (SEIPS) model, and then introduces an extended model, “SEIPS 2.0.” SEIPS 2.0 incorporates three novel concepts into the original model: configuration, engagement, and adaptation. The concept of configuration highlights the dynamic, hierarchical, and interactive properties of sociotechnical systems, making it possible to depict how health-related performance is shaped at “a moment in time.” Engagement conveys that various individuals and teams can perform health-related activities separately and collaboratively. Engaged individuals often include patients, family caregivers, and other non-professionals. Adaptation is introduced as a feedback mechanism that explains how dynamic systems evolve in planned and unplanned ways. Key implications and future directions for human factors research in healthcare are discussed. PMID:24088063

Preclinical models for obesity research

PubMed Central

Barrett, Perry; Morgan, Peter J.

2016-01-01

ABSTRACT A multi-dimensional strategy to tackle the global obesity epidemic requires an in-depth understanding of the mechanisms that underlie this complex condition. Much of the current mechanistic knowledge has arisen from preclinical research performed mostly, but not exclusively, in laboratory mouse and rat strains. These experimental models mimic certain aspects of the human condition and its root causes, particularly the over-consumption of calories and unbalanced diets. As with human obesity, obesity in rodents is the result of complex gene–environment interactions. Here, we review the traditional monogenic models of obesity, their contemporary optogenetic and chemogenetic successors, and the use of dietary manipulations and meal-feeding regimes to recapitulate the complexity of human obesity. We critically appraise the strengths and weaknesses of these different models to explore the underlying mechanisms, including the neural circuits that drive behaviours such as appetite control. We also discuss the use of these models for testing and screening anti-obesity drugs, beneficial bio-actives, and nutritional strategies, with the goal of ultimately translating these findings for the treatment of human obesity. PMID:27821603

Scaling Pharmacodynamics from In Vitro and Preclinical Animal Studies to Humans

PubMed Central

Mager, Donald E.; Woo, Sukyung; Jusko, William J.

2013-01-01

Summary An important feature of mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) models is the identification of drug- and system-specific factors that determine the intensity and time-course of pharmacological effects. This provides an opportunity to integrate information obtained from in vitro bioassays and preclinical pharmacological studies in animals to anticipate the clinical and adverse responses to drugs in humans. The fact that contemporary PK/PD modeling continues to evolve and seeks to emulate systems level properties should provide enhanced capabilities to scale-up pharmacodynamic data. Critical steps in drug discovery and development, such as lead compound and first in human dose selection, may become more efficient with the implementation and further refinement of translational PK/PD modeling. In this review, we highlight fundamental principles in pharmacodynamics and the basic expectations for in vitro bioassays and traditional allometric scaling in PK/PD modeling. Discussion of PK/PD modeling efforts for recombinant human erythropoietin is also included as a case study showing the potential for advanced systems analysis to facilitate extrapolations and improve understanding of inter-species differences in drug responses. PMID:19252333

The Global Food System as a Transport Pathway for Hazardous Chemicals: The Missing Link between Emissions and Exposure.

PubMed

Ng, Carla A; von Goetz, Natalie

2017-01-01

Food is a major pathway for human exposure to hazardous chemicals. The modern food system is becoming increasingly complex and globalized, but models for food-borne exposure typically assume locally derived diets or use concentrations directly measured in foods without accounting for food origin. Such approaches may not reflect actual chemical intakes because concentrations depend on food origin, and representative analysis is seldom available. Processing, packaging, storage, and transportation also impart different chemicals to food and are not yet adequately addressed. Thus, the link between environmental emissions and realistic human exposure is effectively broken. We discuss the need for a fully integrated treatment of the modern industrialized food system, and we propose strategies for using existing models and relevant supporting data sources to track chemicals during production, processing, packaging, storage, and transport. Fate and bioaccumulation models describe how chemicals distribute in the environment and accumulate through local food webs. Human exposure models can use concentrations in food to determine body burdens based on individual or population characteristics. New models now include the impacts of processing and packaging but are far from comprehensive. We propose to close the gap between emissions and exposure by utilizing a wider variety of models and data sources, including global food trade data, processing, and packaging models. A comprehensive approach that takes into account the complexity of the modern global food system is essential to enable better prediction of human exposure to chemicals in food, sound risk assessments, and more focused risk abatement strategies. Citation: Ng CA, von Goetz N. 2017. The global food system as a transport pathway for hazardous chemicals: the missing link between emissions and exposure. Environ Health Perspect 125:1-7; http://dx.doi.org/10.1289/EHP168.

Socio-Hydrologic Modeling: Characterizing the Dynamics of Coupled Human-Water Systems Using Natural Science Methods

NASA Astrophysics Data System (ADS)

Sivapalan, M.; Elshafei, Y.; Srinivasan, V.

2014-12-01

A challenging research puzzle in the research on sustainable water management in the Anthropocene is why some societies successfully recover from "ecological destruction" to transition to "successful adaptation" over decadal timescales, while others fail. We present a conceptual modeling framework to understand and characterize these transitions. In this way, we aim to capture the potential drivers of the desired shift towards achieving sustainability of socio-hydrological systems. This is done through a synthesis of detailed socio-hydrological analyses of four river basins in three continents, carried out using different quantitative socio-hydrologic models: Murrumbidgee River Basin in eastern Australia, Lake Toolibin Catchment in Western Australia, Tarim River Basin in Western China and Kissimmee River Basin, in south-east United States. The case studies are analysed using either place-based models designed specifically to mimic observed long-term socio-hydrologic trends, or generic conceptual models with foundations in diverse strands of literature including sustainability science and resilience theory. A comparative analysis of the four case studies reveals a commonality in the building blocks employed to model these socio-hydrologic systems; including water balance, economic, environmental and human-feedback components. Each model reveals varying interpretations of a common organising principle that could explain the shift between productive (socio-economic) and restorative (environmental) forces that was evident in each of these systems observed over a long time frame. The emergent principle is related to the essential drivers of the human feedback component and rests with a general formulation of human well-being, as reflected by both their economic and environmental well-being. It is envisaged that the understanding of the system drivers gained from such a comparative study would enable more targeted water management strategies that can be administered in developing basins to achieve overall sustainability.

From animal models to human disease: a genetic approach for personalized medicine in ALS.

PubMed

Picher-Martel, Vincent; Valdmanis, Paul N; Gould, Peter V; Julien, Jean-Pierre; Dupré, Nicolas

2016-07-11

Amyotrophic Lateral Sclerosis (ALS) is the most frequent motor neuron disease in adults. Classical ALS is characterized by the death of upper and lower motor neurons leading to progressive paralysis. Approximately 10 % of ALS patients have familial form of the disease. Numerous different gene mutations have been found in familial cases of ALS, such as mutations in superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43), fused in sarcoma (FUS), C9ORF72, ubiquilin-2 (UBQLN2), optineurin (OPTN) and others. Multiple animal models were generated to mimic the disease and to test future treatments. However, no animal model fully replicates the spectrum of phenotypes in the human disease and it is difficult to assess how a therapeutic effect in disease models can predict efficacy in humans. Importantly, the genetic and phenotypic heterogeneity of ALS leads to a variety of responses to similar treatment regimens. From this has emerged the concept of personalized medicine (PM), which is a medical scheme that combines study of genetic, environmental and clinical diagnostic testing, including biomarkers, to individualized patient care. In this perspective, we used subgroups of specific ALS-linked gene mutations to go through existing animal models and to provide a comprehensive profile of the differences and similarities between animal models of disease and human disease. Finally, we reviewed application of biomarkers and gene therapies relevant in personalized medicine approach. For instance, this includes viral delivering of antisense oligonucleotide and small interfering RNA in SOD1, TDP-43 and C9orf72 mice models. Promising gene therapies raised possibilities for treating differently the major mutations in familial ALS cases.

Predictors of immune function in space flight

NASA Astrophysics Data System (ADS)

Shearer, William T.; Zhang, Shaojie; Reuben, James M.; Lee, Bang-Ning; Butel, Janet S.

2007-02-01

Of all of the environmental conditions of space flight that might have an adverse effect upon human immunity and the incidence of infection, space radiation stands out as the single-most important threat. As important as this would be on humans engaged in long and deep space flight, it obviously is not possible to plan Earth-bound radiation and infection studies in humans. Therefore, we propose to develop a murine model that could predict the adverse effects of space flight radiation and reactivation of latent virus infection for humans. Recent observations on the effects of gamma and latent virus infection demonstrate latent virus reactivation and loss of T cell mediated immune responses in a murine model. We conclude that using this small animal method of quantitating the amounts of radiation and latent virus infection and resulting alterations in immune responses, it may be possible to predict the degree of immunosuppression in interplanetary space travel for humans. Moreover, this model could be extended to include other space flight conditions, such as microgravity, sleep deprivation, and isolation, to obtain a more complete assessment of space flight risks for humans.

Modeling the transmission dynamics and control of rabies in China.

PubMed

Ruan, Shigui

2017-04-01

Human rabies was first recorded in ancient China in about 556 BC and is still one of the major public-health problems in China. From 1950 to 2015, 130,494 human rabies cases were reported in Mainland China with an average of 1977 cases per year. It is estimated that 95% of these human rabies cases are due to dog bites. The purpose of this article is to provide a review about the models, results, and simulations that we have obtained recently on studying the transmission of rabies in China. We first construct a basic susceptible, exposed, infectious, and recovered (SEIR) type model for the spread of rabies virus among dogs and from dogs to humans and use the model to simulate the human rabies data in China from 1996 to 2010. Then we modify the basic model by including both domestic and stray dogs and apply the model to simulate the human rabies data from Guangdong Province, China. To study the seasonality of rabies, in Section 4 we further propose a SEIR model with periodic transmission rates and employ the model to simulate the monthly data of human rabies cases reported by the Chinese Ministry of Health from January 2004 to December 2010. To understand the spatial spread of rabies, in Section 5 we add diffusion to the dog population in the basic SEIR model to obtain a reaction-diffusion equation model and determine the minimum wave speed connecting the disease-free equilibrium to the endemic equilibrium. Finally, in order to investigate how the movement of dogs affects the geographically inter-provincial spread of rabies in Mainland China, in Section 6 we propose a multi-patch model to describe the transmission dynamics of rabies between dogs and humans and use the two-patch submodel to investigate the rabies virus clades lineages and to simulate the human rabies data from Guizhou and Guangxi, Hebei and Fujian, and Sichuan and Shaanxi, respectively. Some discussions are provided in Section 7. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of Modeling Methods to Determine Liver-to-blood Inocula and Parasite Multiplication Rates During Controlled Human Malaria Infection

PubMed Central

Douglas, Alexander D.; Edwards, Nick J.; Duncan, Christopher J. A.; Thompson, Fiona M.; Sheehy, Susanne H.; O'Hara, Geraldine A.; Anagnostou, Nicholas; Walther, Michael; Webster, Daniel P.; Dunachie, Susanna J.; Porter, David W.; Andrews, Laura; Gilbert, Sarah C.; Draper, Simon J.; Hill, Adrian V. S.; Bejon, Philip

2013-01-01

Controlled human malaria infection is used to measure efficacy of candidate malaria vaccines before field studies are undertaken. Mathematical modeling using data from quantitative polymerase chain reaction (qPCR) parasitemia monitoring can discriminate between vaccine effects on the parasite's liver and blood stages. Uncertainty regarding the most appropriate modeling method hinders interpretation of such trials. We used qPCR data from 267 Plasmodium falciparum infections to compare linear, sine-wave, and normal-cumulative-density-function models. We find that the parameters estimated by these models are closely correlated, and their predictive accuracy for omitted data points was similar. We propose that future studies include the linear model. PMID:23570846

FDA-approved drugs that are spermatotoxic in animals and the utility of animal testing for human risk prediction.

PubMed

Rayburn, Elizabeth R; Gao, Liang; Ding, Jiayi; Ding, Hongxia; Shao, Jun; Li, Haibo

2018-02-01

This study reviews FDA-approved drugs that negatively impact spermatozoa in animals, as well as how these findings reflect on observations in human male gametes. The FDA drug warning labels included in the DailyMed database and the peer-reviewed literature in the PubMed database were searched for information to identify single-ingredient, FDA-approved prescription drugs with spermatotoxic effects. A total of 235 unique, single-ingredient, FDA-approved drugs reported to be spermatotoxic in animals were identified in the drug labels. Forty-nine of these had documented negative effects on humans in either the drug label or literature, while 31 had no effect or a positive impact on human sperm. For the other 155 drugs that were spermatotoxic in animals, no human data was available. The current animal models are not very effective for predicting human spermatotoxicity, and there is limited information available about the impact of many drugs on human spermatozoa. New approaches should be designed that more accurately reflect the findings in men, including more studies on human sperm in vitro and studies using other systems (ex vivo tissue culture, xenograft models, in silico studies, etc.). In addition, the present data is often incomplete or reported in a manner that prevents interpretation of their clinical relevance. Changes should be made to the requirements for pre-clinical testing, drug surveillance, and the warning labels of drugs to ensure that the potential risks to human fertility are clearly indicated.

Alzheimer’s Disease: Experimental Models and Reality

PubMed Central

Drummond, Eleanor

2017-01-01

Experimental models of Alzheimer’s disease (AD) are critical to gaining a better understanding of pathogenesis and to assess the potential of novel therapeutic approaches. The most commonly used experimental animal models are transgenic mice that overexpress human genes associated with familial AD (FAD) that result in the formation of amyloid plaques. However, AD is defined by the presence and interplay of both amyloid plaques and neurofibrillary tangle pathology. The track record of success in AD clinical trials thus far has been very poor. In part, this high failure rate has been related to the premature translation of highly successful results in animal models that mirror only limited aspects of AD pathology to humans. A greater understanding of the strengths and weakness of each of the various models and the use of more than one model to evaluate potential therapies would help enhance the success of therapy translation from preclinical studies to patients. In this review we summarize the pathological features and limitations of the major experimental models of AD including transgenic mice, transgenic rats, various physiological models of sporadic AD and in vitro human cell culture models. PMID:28025715

Mouse models for the study of colon carcinogenesis

PubMed Central

Rosenberg, Daniel W.; Giardina, Charles; Tanaka, Takuji

2009-01-01

The study of experimental colon carcinogenesis in rodents has a long history, dating back almost 80 years. There are many advantages to studying the pathogenesis of carcinogen-induced colon cancer in mouse models, including rapid and reproducible tumor induction and the recapitulation of the adenoma–carcinoma sequence that occurs in humans. The availability of recombinant inbred mouse panels and the existence of transgenic, knock-out and knock-in genetic models further increase the value of these studies. In this review, we discuss the general mechanisms of tumor initiation elicited by commonly used chemical carcinogens and how genetic background influences the extent of disease. We will also describe the general features of lesions formed in response to carcinogen treatment, including the underlying molecular aberrations and how these changes may relate to the pathogenesis of human colorectal cancer. PMID:19037092

The integrated manual and automatic control of complex flight systems

NASA Technical Reports Server (NTRS)

Schmidt, David K.

1991-01-01

Research dealt with the general area of optimal flight control synthesis for manned flight vehicles. The work was generic; no specific vehicle was the focus of study. However, the class of vehicles generally considered were those for which high authority, multivariable control systems might be considered, for the purpose of stabilization and the achievement of optimal handling characteristics. Within this scope, the topics of study included several optimal control synthesis techniques, control-theoretic modeling of the human operator in flight control tasks, and the development of possible handling qualities metrics and/or measures of merit. Basic contributions were made in all these topics, including human operator (pilot) models for multi-loop tasks, optimal output feedback flight control synthesis techniques; experimental validations of the methods developed, and fundamental modeling studies of the air-to-air tracking and flared landing tasks.

The virtual morphology and the main movements of the human neck simulations used for car crash studies

NASA Astrophysics Data System (ADS)

Ciunel, St.; Tica, B.

2016-08-01

The paper presents the studies made on a similar biomechanical system composed by neck, head and thorax bones. The models were defined in a CAD environment which includes Adams algorithm for dynamic simulations. The virtual models and the entire morphology were obtained starting with CT images made on a living human subject. The main movements analyzed were: axial rotation (left-right), lateral bending (left-right) and flexion- extension movement. After simulation was obtained the entire biomechanical behavior based on data tables or diagrams. That virtual model composed by neck and head can be included in complex system (as a car system) and supposed to several impact simulations (virtual crash tests). Also, our research team built main components of a testing device for dummy car crash neck-head system using anatomical data.

Natural language processing in an intelligent writing strategy tutoring system.

PubMed

McNamara, Danielle S; Crossley, Scott A; Roscoe, Rod

2013-06-01

The Writing Pal is an intelligent tutoring system that provides writing strategy training. A large part of its artificial intelligence resides in the natural language processing algorithms to assess essay quality and guide feedback to students. Because writing is often highly nuanced and subjective, the development of these algorithms must consider a broad array of linguistic, rhetorical, and contextual features. This study assesses the potential for computational indices to predict human ratings of essay quality. Past studies have demonstrated that linguistic indices related to lexical diversity, word frequency, and syntactic complexity are significant predictors of human judgments of essay quality but that indices of cohesion are not. The present study extends prior work by including a larger data sample and an expanded set of indices to assess new lexical, syntactic, cohesion, rhetorical, and reading ease indices. Three models were assessed. The model reported by McNamara, Crossley, and McCarthy (Written Communication 27:57-86, 2010) including three indices of lexical diversity, word frequency, and syntactic complexity accounted for only 6% of the variance in the larger data set. A regression model including the full set of indices examined in prior studies of writing predicted 38% of the variance in human scores of essay quality with 91% adjacent accuracy (i.e., within 1 point). A regression model that also included new indices related to rhetoric and cohesion predicted 44% of the variance with 94% adjacent accuracy. The new indices increased accuracy but, more importantly, afford the means to provide more meaningful feedback in the context of a writing tutoring system.

Revenue Prediction of a Local Event Using the Mathematical Model of Hit Phenomena

NASA Astrophysics Data System (ADS)

Ishii, A.; Matsumoto, T.; Miki, S.

We propose a theoretical approach to investigate human-humaninteraction in the society, which uses a many-body theory that incorporates human-human interaction. We treat advertisement as an external force, and include the word of mouth (WOM) effect as a two-body interaction between humans and the rumor effect as a three-body interaction among humans. The parameters to define the strength of human interactions are assumed to be constant values. The calculated result explained well the two local events ``Mizuki-Shigeru Road in Sakaiminato" and ``the sculpture festival at Tottori" in Japan.

A Drainage Model: A One-Week Project.

ERIC Educational Resources Information Center

Lennert, James W.

1981-01-01

Describes a one-week unit in Earth science for the elementary science classroom. The concepts included are land formation, erosion, the water cycle, and human impact on the Earth's surface through planning and building a massive outdoor drainage model. (Author/DS)

A PROBABILISTIC MODELING FRAMEWORK FOR PREDICTING POPULATION EXPOSURES TO BENZENE

EPA Science Inventory

The US Environmental Protection Agency (EPA) is modifying their probabilistic Stochastic Human Exposure Dose Simulation (SHEDS) model to assess aggregate exposures to air toxics. Air toxics include urban Hazardous Air Pollutants (HAPS) such as benzene from mobile sources, part...

On a basic model of circulatory, fluid, and electrolyte regulation in the human system based upon the model of Guyton

NASA Technical Reports Server (NTRS)

White, R. J.

1973-01-01

A detailed description of Guyton's model and modifications are provided. Also included are descriptions of several typical experiments which the model can simulate to illustrate the model's general utility. A discussion of the problems associated with the interfacing of the model to other models such as respiratory and thermal regulation models which is prime importance since these stimuli are not present in the current model is also included. A user's guide for the operation of the model on the Xerox Sigma 3 computer is provided and two programs are described. A verification plan and procedure for performing experiments is also presented.