Dietary fibers from mushroom Sclerotia: 2. In vitro mineral binding capacity under sequential simulated physiological conditions of the human gastrointestinal tract.

PubMed

Wong, Ka-Hing; Cheung, Peter C K

2005-11-30

The in vitro mineral binding capacity of three novel dietary fibers (DFs) prepared from mushroom sclerotia, namely, Pleurotus tuber-regium, Polyporous rhinocerus, and Wolfiporia cocos, to Ca, Mg, Cu, Fe, and Zn under sequential simulated physiological conditions of the human stomach, small intestine, and colon was investigated and compared. Apart from releasing most of their endogenous Ca (ranged from 96.9 to 97.9% removal) and Mg (ranged from 95.9 to 96.7% removal), simulated physiological conditions of the stomach also attenuated the possible adverse binding effect of the three sclerotial DFs to the exogenous minerals by lowering their cation-exchange capacity (ranged from 20.8 to 32.3%) and removing a substantial amount of their potential mineral chelators including protein (ranged from 16.2 to 37.8%) and phytate (ranged from 58.5 to 64.2%). The in vitro mineral binding capacity of the three sclerotial DF under simulated physiological conditions of small intestine was found to be low, especially for Ca (ranged from 4.79 to 5.91% binding) and Mg (ranged from 3.16 to 4.18% binding), and was highly correlated (r > 0.97) with their residual protein contents. Under simulated physiological conditions of the colon with slightly acidic pH (5.80), only bound Ca was readily released (ranged from 34.2 to 72.3% releasing) from the three sclerotial DFs, and their potential enhancing effect on passive Ca absorption in the human large intestine was also discussed.

Virtual Reality Simulation of the Effects of Microgravity in Gastrointestinal Physiology

NASA Technical Reports Server (NTRS)

Compadre, Cesar M.

1998-01-01

The ultimate goal of this research is to create an anatomically accurate three-dimensional (3D) simulation model of the effects of microgravity in gastrointestinal physiology and to explore the role that such changes may have in the pharmacokinetics of drugs given to the space crews for prevention or therapy. To accomplish this goal the specific aims of this research are: 1) To generate a complete 3-D reconstructions of the human GastroIntestinal (GI) tract of the male and female Visible Humans. 2) To develop and implement time-dependent computer algorithms to simulate the GI motility using the above 3-D reconstruction.

Simulation environment and graphical visualization environment: a COPD use-case.

PubMed

Huertas-Migueláñez, Mercedes; Mora, Daniel; Cano, Isaac; Maier, Dieter; Gomez-Cabrero, David; Lluch-Ariet, Magí; Miralles, Felip

2014-11-28

Today, many different tools are developed to execute and visualize physiological models that represent the human physiology. Most of these tools run models written in very specific programming languages which in turn simplify the communication among models. Nevertheless, not all of these tools are able to run models written in different programming languages. In addition, interoperability between such models remains an unresolved issue. In this paper we present a simulation environment that allows, first, the execution of models developed in different programming languages and second the communication of parameters to interconnect these models. This simulation environment, developed within the Synergy-COPD project, aims at helping and supporting bio-researchers and medical students understand the internal mechanisms of the human body through the use of physiological models. This tool is composed of a graphical visualization environment, which is a web interface through which the user can interact with the models, and a simulation workflow management system composed of a control module and a data warehouse manager. The control module monitors the correct functioning of the whole system. The data warehouse manager is responsible for managing the stored information and supporting its flow among the different modules. It has been proved that the simulation environment presented here allows the user to research and study the internal mechanisms of the human physiology by the use of models via a graphical visualization environment. A new tool for bio-researchers is ready for deployment in various use cases scenarios.

Simulating the decentralized processes of the human immune system in a virtual anatomy model.

PubMed

Sarpe, Vladimir; Jacob, Christian

2013-01-01

Many physiological processes within the human body can be perceived and modeled as large systems of interacting particles or swarming agents. The complex processes of the human immune system prove to be challenging to capture and illustrate without proper reference to the spatial distribution of immune-related organs and systems. Our work focuses on physical aspects of immune system processes, which we implement through swarms of agents. This is our first prototype for integrating different immune processes into one comprehensive virtual physiology simulation. Using agent-based methodology and a 3-dimensional modeling and visualization environment (LINDSAY Composer), we present an agent-based simulation of the decentralized processes in the human immune system. The agents in our model - such as immune cells, viruses and cytokines - interact through simulated physics in two different, compartmentalized and decentralized 3-dimensional environments namely, (1) within the tissue and (2) inside a lymph node. While the two environments are separated and perform their computations asynchronously, an abstract form of communication is allowed in order to replicate the exchange, transportation and interaction of immune system agents between these sites. The distribution of simulated processes, that can communicate across multiple, local CPUs or through a network of machines, provides a starting point to build decentralized systems that replicate larger-scale processes within the human body, thus creating integrated simulations with other physiological systems, such as the circulatory, endocrine, or nervous system. Ultimately, this system integration across scales is our goal for the LINDSAY Virtual Human project. Our current immune system simulations extend our previous work on agent-based simulations by introducing advanced visualizations within the context of a virtual human anatomy model. We also demonstrate how to distribute a collection of connected simulations over a network of computers. As a future endeavour, we plan to use parameter tuning techniques on our model to further enhance its biological credibility. We consider these in silico experiments and their associated modeling and optimization techniques as essential components in further enhancing our capabilities of simulating a whole-body, decentralized immune system, to be used both for medical education and research as well as for virtual studies in immunoinformatics.

Design of a framework for modeling, integration and simulation of physiological models.

PubMed

Erson, E Zeynep; Cavuşoğlu, M Cenk

2012-09-01

Multiscale modeling and integration of physiological models carry challenges due to the complex nature of physiological processes. High coupling within and among scales present a significant challenge in constructing and integrating multiscale physiological models. In order to deal with such challenges in a systematic way, there is a significant need for an information technology framework together with related analytical and computational tools that will facilitate integration of models and simulations of complex biological systems. Physiological Model Simulation, Integration and Modeling Framework (Phy-SIM) is an information technology framework providing the tools to facilitate development, integration and simulation of integrated models of human physiology. Phy-SIM brings software level solutions to the challenges raised by the complex nature of physiological systems. The aim of Phy-SIM, and this paper is to lay some foundation with the new approaches such as information flow and modular representation of the physiological models. The ultimate goal is to enhance the development of both the models and the integration approaches of multiscale physiological processes and thus this paper focuses on the design approaches that would achieve such a goal. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Preventing and Treating Hypoxia: Using a Physiology Simulator to Demonstrate the Value of Pre-Oxygenation and the Futility of Hyperventilation.

PubMed

Lerant, Anna A; Hester, Robert L; Coleman, Thomas G; Phillips, William J; Orledge, Jeffrey D; Murray, W Bosseau

2015-01-01

Insufficient pre-oxygenation before emergency intubation, and hyperventilation after intubation are mistakes that are frequently observed in and outside the operating room, in clinical practice and in simulation exercises. Physiological parameters, as appearing on standard patient monitors, do not alert to the deleterious effects of low oxygen saturation on coronary perfusion, or that of low carbon dioxide concentrations on cerebral perfusion. We suggest the use of HumMod, a computer-based human physiology simulator, to demonstrate beneficial physiological responses to pre-oxygenation and the futility of excessive minute ventilation after intubation. We programmed HumMod, to A.) compare varying times (0-7 minutes) of pre-oxygenation on oxygen saturation (SpO2) during subsequent apnoea; B.) simulate hyperventilation after apnoea. We compared the effect of different minute ventilation rates on SpO2, acid-base status, cerebral perfusion and other haemodynamic parameters. A.) With no pre-oxygenation, starting SpO2 dropped from 98% to 90% in 52 seconds with apnoea. At the other extreme, following full pre-oxygenation with 100% O2 for 3 minutes or more, the SpO2 remained 100% for 7.75 minutes during apnoea, and dropped to 90% after another 75 seconds. B.) Hyperventilation, did not result in more rapid normalization of SpO2, irrespective of the level of minute ventilation. However, hyperventilation did cause significant decreases in cerebral blood flow (CBF). HumMod accurately simulates the physiological responses compared to published human studies of pre-oxygenation and varying post intubation minute ventilations, and it can be used over wider ranges of parameters than available in human studies and therefore available in the literature.

Preventing and Treating Hypoxia: Using a Physiology Simulator to Demonstrate the Value of Pre-Oxygenation and the Futility of Hyperventilation

PubMed Central

Lerant, Anna A.; Hester, Robert L.; Coleman, Thomas G.; Phillips, William J.; Orledge, Jeffrey D.; Murray, W. Bosseau

2015-01-01

Introduction: Insufficient pre-oxygenation before emergency intubation, and hyperventilation after intubation are mistakes that are frequently observed in and outside the operating room, in clinical practice and in simulation exercises. Physiological parameters, as appearing on standard patient monitors, do not alert to the deleterious effects of low oxygen saturation on coronary perfusion, or that of low carbon dioxide concentrations on cerebral perfusion. We suggest the use of HumMod, a computer-based human physiology simulator, to demonstrate beneficial physiological responses to pre-oxygenation and the futility of excessive minute ventilation after intubation. Methods: We programmed HumMod, to A.) compare varying times (0-7 minutes) of pre-oxygenation on oxygen saturation (SpO2) during subsequent apnoea; B.) simulate hyperventilation after apnoea. We compared the effect of different minute ventilation rates on SpO2, acid-base status, cerebral perfusion and other haemodynamic parameters. Results: A.) With no pre-oxygenation, starting SpO2 dropped from 98% to 90% in 52 seconds with apnoea. At the other extreme, following full pre-oxygenation with 100% O2 for 3 minutes or more, the SpO2 remained 100% for 7.75 minutes during apnoea, and dropped to 90% after another 75 seconds. B.) Hyperventilation, did not result in more rapid normalization of SpO2, irrespective of the level of minute ventilation. However, hyperventilation did cause significant decreases in cerebral blood flow (CBF). Conclusions: HumMod accurately simulates the physiological responses compared to published human studies of pre-oxygenation and varying post intubation minute ventilations, and it can be used over wider ranges of parameters than available in human studies and therefore available in the literature. PMID:26283881

Simulated physiological stretch increases expression of extracellular matrix proteins in human bladder smooth muscle cells via integrin α4/αv-FAK-ERK1/2 signaling pathway.

PubMed

Chen, Shulian; Peng, Chuandu; Wei, Xin; Luo, Deyi; Lin, Yifei; Yang, Tongxin; Jin, Xi; Gong, Lina; Li, Hong; Wang, Kunjie

2017-08-01

To investigate the effect of simulated physiological stretch on the expression of extracellular matrix (ECM) proteins and the role of integrin α4/αv, focal adhesion kinase (FAK), extracellular regulated protein kinases 1/2 (ERK1/2) in the stretch-induced ECM protein expression of human bladder smooth muscle cells (HBSMCs). HBSMCs were seeded onto silicone membrane and subjected to simulated physiological stretch at the range of 5, 10, and 15% elongation. Expression of primary ECM proteins in HBSMCs was analyzed by real-time polymerase chain reaction and Western blot. Specificity of the FAK and ERK1/2 was determined by Western blot with FAK inhibitor and ERK1/2 inhibitor (PD98059). Specificity of integrin α4 and integrin αv was determined with small interfering ribonucleic acid (siRNA) transfection. The expression of collagen I (Col1), collagen III (Col3), and fibronectin (Fn) was increased significantly under the simulated physiological stretch of 10 and 15%. Integrin α4 and αv, FAK, ERK1/2 were activated by 10% simulated physiological stretch compared with the static condition. Pretreatment of ERK1/2 inhibitor, FAK inhibitor, integrin α4 siRNA, or integrin αv siRNA reduced the stretch-induced expression of ECM proteins. And FAK inhibitor decreased the stretch-induced ERK1/2 activity and ECM protein expression. Integrin α4 siRNA or integrin αv siRNA inhibited the stretch-induced activity of FAK. Simulated physiological stretch increases the expression of ECM proteins in HBSMCs, and integrin α4/αv-FAK-ERK1/2 signaling pathway partly modulates the mechano-transducing process.

Interpersonal Biocybernetics: Connecting Through Social Psychophysiology

NASA Technical Reports Server (NTRS)

Pope, Alan T.; Stephens, Chad L.

2012-01-01

One embodiment of biocybernetic adaptation is a human-computer interaction system designed such that physiological signals modulate the effect that control of a task by other means, usually manual control, has on performance of the task. Such a modulation system enables a variety of human-human interactions based upon physiological self-regulation performance. These interpersonal interactions may be mixes of competition and cooperation for simulation training and/or videogame entertainment

Simulation of physiological systems in order to evaluate and predict the human condition in a space flight

NASA Technical Reports Server (NTRS)

Verigo, V. V.

1979-01-01

Simulation models were used to study theoretical problems of space biology and medicine. The reaction and adaptation of the main physiological systems to the complex effects of space flight were investigated. Mathematical models were discussed in terms of their significance in the selection of the structure and design of biological life support systems.

Reintrepreting the cardiovascular system as a mechanical model

NASA Astrophysics Data System (ADS)

Lemos, Diogo; Machado, José; Minas, Graça; Soares, Filomena; Barros, Carla; Leão, Celina Pinto

2013-10-01

The simulation of the different physiological systems is very useful as a pedagogical tool, allowing a better understanding of the mechanisms and the functions of the processes. The observation of the physiological phenomena through mechanical simulators represents a great asset. Furthermore, the development of these simulators allows reinterpreting physiological systems, with the advantage of using the same transducers and sensors that are commonly used in diagnostic and therapeutic cardiovascular procedures for the monitoring of system' parameters. The cardiovascular system is one of the most important systems of the human body and has been the target of several biomedical studies. The present work describes a mechanical simulation of the cardiovascular system, in particularly, the systemic circulation, which can be described in terms of its hemodynamic variables. From the mechanical process and parameters, physiological system's behavior was reproduced, as accurately as possible.

Creating Simulated Microgravity Patient Models

NASA Technical Reports Server (NTRS)

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

2004-01-01

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

An Exercise Health Simulation Method Based on Integrated Human Thermophysiological Model

PubMed Central

Chen, Xiaohui; Yu, Liang; Yang, Kaixing

2017-01-01

Research of healthy exercise has garnered a keen research for the past few years. It is known that participation in a regular exercise program can help improve various aspects of cardiovascular function and reduce the risk of suffering from illness. But some exercise accidents like dehydration, exertional heatstroke, and even sudden death need to be brought to attention. If these exercise accidents can be analyzed and predicted before they happened, it will be beneficial to alleviate or avoid disease or mortality. To achieve this objective, an exercise health simulation approach is proposed, in which an integrated human thermophysiological model consisting of human thermal regulation model and a nonlinear heart rate regulation model is reported. The human thermoregulatory mechanism as well as the heart rate response mechanism during exercise can be simulated. On the basis of the simulated physiological indicators, a fuzzy finite state machine is constructed to obtain the possible health transition sequence and predict the exercise health status. The experiment results show that our integrated exercise thermophysiological model can numerically simulate the thermal and physiological processes of the human body during exercise and the predicted exercise health transition sequence from finite state machine can be used in healthcare. PMID:28702074

Long-term regulation in the cardiovascular system - Cornerstone in the development of a composite physiological model

NASA Technical Reports Server (NTRS)

White, R. J.

1974-01-01

The present work discusses a model of the cardiovascular system and related subsystems capable of long-term simulations of the type desired for in-space hypogravic human physiological performance prediction. The discussion centers around the model of Guyton and modifications of it. In order to draw attention to the fluid handling capabilities of the model, one of several transfusion simulations performed is presented, namely, the isotonic saline transfusion simulation.

Human Cadavers vs. Multimedia Simulation: A Study of Student Learning in Anatomy

ERIC Educational Resources Information Center

Saltarelli, Andrew J.; Roseth, Cary J.; Saltarelli, William A.

2014-01-01

Multimedia and simulation programs are increasingly being used for anatomy instruction, yet it remains unclear how learning with these technologies compares with learning with actual human cadavers. Using a multilevel, quasi-experimental-control design, this study compared the effects of "Anatomy and Physiology Revealed" (APR) multimedia…

Simulation environment and graphical visualization environment: a COPD use-case

PubMed Central

2014-01-01

Background Today, many different tools are developed to execute and visualize physiological models that represent the human physiology. Most of these tools run models written in very specific programming languages which in turn simplify the communication among models. Nevertheless, not all of these tools are able to run models written in different programming languages. In addition, interoperability between such models remains an unresolved issue. Results In this paper we present a simulation environment that allows, first, the execution of models developed in different programming languages and second the communication of parameters to interconnect these models. This simulation environment, developed within the Synergy-COPD project, aims at helping and supporting bio-researchers and medical students understand the internal mechanisms of the human body through the use of physiological models. This tool is composed of a graphical visualization environment, which is a web interface through which the user can interact with the models, and a simulation workflow management system composed of a control module and a data warehouse manager. The control module monitors the correct functioning of the whole system. The data warehouse manager is responsible for managing the stored information and supporting its flow among the different modules. This simulation environment has been validated with the integration of three models: two deterministic, i.e. based on linear and differential equations, and one probabilistic, i.e., based on probability theory. These models have been selected based on the disease under study in this project, i.e., chronic obstructive pulmonary disease. Conclusion It has been proved that the simulation environment presented here allows the user to research and study the internal mechanisms of the human physiology by the use of models via a graphical visualization environment. A new tool for bio-researchers is ready for deployment in various use cases scenarios. PMID:25471327

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

Modeling Physiological Systems in the Human Body as Networks of Quasi-1D Fluid Flows

NASA Astrophysics Data System (ADS)

Staples, Anne

2008-11-01

Extensive research has been done on modeling human physiology. Most of this work has been aimed at developing detailed, three-dimensional models of specific components of physiological systems, such as a cell, a vein, a molecule, or a heart valve. While efforts such as these are invaluable to our understanding of human biology, if we were to construct a global model of human physiology with this level of detail, computing even a nanosecond in this computational being's life would certainly be prohibitively expensive. With this in mind, we derive the Pulsed Flow Equations, a set of coupled one-dimensional partial differential equations, specifically designed to capture two-dimensional viscous, transport, and other effects, and aimed at providing accurate and fast-to-compute global models for physiological systems represented as networks of quasi one-dimensional fluid flows. Our goal is to be able to perform faster-than-real time simulations of global processes in the human body on desktop computers.

Bridging the Gap between Physiology and Behavior: Evidence from the sSoTS Model of Human Visual Attention

ERIC Educational Resources Information Center

Mavritsaki, Eirini; Heinke, Dietmar; Allen, Harriet; Deco, Gustavo; Humphreys, Glyn W.

2011-01-01

We present the case for a role of biologically plausible neural network modeling in bridging the gap between physiology and behavior. We argue that spiking-level networks can allow "vertical" translation between physiological properties of neural systems and emergent "whole-system" performance--enabling psychological results to be simulated from…

A human life-stage physiologically based pharmacokinetic and pharmacodynamic model for chlorpyrifos: development and validation.

PubMed

Smith, Jordan Ned; Hinderliter, Paul M; Timchalk, Charles; Bartels, Michael J; Poet, Torka S

2014-08-01

Sensitivity to some chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to predict disposition of chlorpyrifos and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, previously measured age-dependent metabolism of chlorpyrifos and chlorpyrifos-oxon were integrated into age-related descriptions of human anatomy and physiology. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ⩾0.6mg/kg of chlorpyrifos (100- to 1000-fold higher than environmental exposure levels), 6months old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent doses. At lower doses more relevant to environmental exposures, simulations predict that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict chlorpyrifos disposition and biological response over various postnatal life stages. Copyright © 2013 Elsevier Inc. All rights reserved.

Physiologically relevant organs on chips

PubMed Central

Yum, Kyungsuk; Hong, Soon Gweon; Lee, Luke P.

2015-01-01

Recent advances in integrating microengineering and tissue engineering have generated promising microengineered physiological models for experimental medicine and pharmaceutical research. Here we review the recent development of microengineered physiological systems, or organs on chips, that reconstitute the physiologically critical features of specific human tissues and organs and their interactions. This technology uses microengineering approaches to construct organ-specific microenvironments, reconstituting tissue structures, tissue–tissue interactions and interfaces, and dynamic mechanical and biochemical stimuli found in specific organs, to direct cells to assemble into functional tissues. We first discuss microengineering approaches to reproduce the key elements of physiologically important, dynamic mechanical microenvironments, biochemical microenvironments, and microarchitectures of specific tissues and organs in microfluidic cell culture systems. This is followed by examples of microengineered individual organ models that incorporate the key elements of physiological microenvironments into single microfluidic cell culture systems to reproduce organ-level functions. Finally, microengineered multiple organ systems that simulate multiple organ interactions to better represent human physiology, including human responses to drugs, is covered in this review. This emerging organs-on-chips technology has the potential to become an alternative to 2D and 3D cell culture and animal models for experimental medicine, human disease modeling, drug development, and toxicology. PMID:24357624

Predictive neuromechanical simulations indicate why walking performance declines with ageing.

PubMed

Song, Seungmoon; Geyer, Hartmut

2018-04-01

Although the natural decline in walking performance with ageing affects the quality of life of a growing elderly population, its physiological origins remain unknown. By using predictive neuromechanical simulations of human walking with age-related neuro-musculo-skeletal changes, we find evidence that the loss of muscle strength and muscle contraction speed dominantly contribute to the reduced walking economy and speed. The findings imply that focusing on recovering these muscular changes may be the only effective way to improve performance in elderly walking. More generally, the work is of interest for investigating the physiological causes of altered gait due to age, injury and disorders. Healthy elderly people walk slower and energetically less efficiently than young adults. This decline in walking performance lowers the quality of life for a growing ageing population, and understanding its physiological origin is critical for devising interventions that can delay or revert it. However, the origin of the decline in walking performance remains unknown, as ageing produces a range of physiological changes whose individual effects on gait are difficult to separate in experiments with human subjects. Here we use a predictive neuromechanical model to separately address the effects of common age-related changes to the skeletal, muscular and nervous systems. We find in computer simulations of this model that the combined changes produce gait consistent with elderly walking and that mainly the loss of muscle strength and mass reduces energy efficiency. In addition, we find that the slower preferred walking speed of elderly people emerges in the simulations when adapting to muscle fatigue, again mainly caused by muscle-related changes. The results suggest that a focus on recovering these muscular changes may be the only effective way to improve performance in elderly walking. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Functionality of empirical model-based predictive analytics for the early detection of hemodynamic instabilty.

PubMed

Summers, Richard L; Pipke, Matt; Wegerich, Stephan; Conkright, Gary; Isom, Kristen C

2014-01-01

Background. Monitoring cardiovascular hemodynamics in the modern clinical setting is a major challenge. Increasing amounts of physiologic data must be analyzed and interpreted in the context of the individual patient’s pathology and inherent biologic variability. Certain data-driven analytical methods are currently being explored for smart monitoring of data streams from patients as a first tier automated detection system for clinical deterioration. As a prelude to human clinical trials, an empirical multivariate machine learning method called Similarity-Based Modeling (“SBM”), was tested in an In Silico experiment using data generated with the aid of a detailed computer simulator of human physiology (Quantitative Circulatory Physiology or “QCP”) which contains complex control systems with realistic integrated feedback loops. Methods. SBM is a kernel-based, multivariate machine learning method that that uses monitored clinical information to generate an empirical model of a patient’s physiologic state. This platform allows for the use of predictive analytic techniques to identify early changes in a patient’s condition that are indicative of a state of deterioration or instability. The integrity of the technique was tested through an In Silico experiment using QCP in which the output of computer simulations of a slowly evolving cardiac tamponade resulted in progressive state of cardiovascular decompensation. Simulator outputs for the variables under consideration were generated at a 2-min data rate (0.083Hz) with the tamponade introduced at a point 420 minutes into the simulation sequence. The functionality of the SBM predictive analytics methodology to identify clinical deterioration was compared to the thresholds used by conventional monitoring methods. Results. The SBM modeling method was found to closely track the normal physiologic variation as simulated by QCP. With the slow development of the tamponade, the SBM model are seen to disagree while the simulated biosignals in the early stages of physiologic deterioration and while the variables are still within normal ranges. Thus, the SBM system was found to identify pathophysiologic conditions in a timeframe that would not have been detected in a usual clinical monitoring scenario. Conclusion. In this study the functionality of a multivariate machine learning predictive methodology that that incorporates commonly monitored clinical information was tested using a computer model of human physiology. SBM and predictive analytics were able to differentiate a state of decompensation while the monitored variables were still within normal clinical ranges. This finding suggests that the SBM could provide for early identification of a clinical deterioration using predictive analytic techniques. predictive analytics, hemodynamic, monitoring.

Toward the Computational Representation of Individual Cultural, Cognitive, and Physiological State: The Sensor Shooter Simulation

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

RAYBOURN,ELAINE M.; FORSYTHE,JAMES C.

2001-08-01

This report documents an exploratory FY 00 LDRD project that sought to demonstrate the first steps toward a realistic computational representation of the variability encountered in individual human behavior. Realism, as conceptualized in this project, required that the human representation address the underlying psychological, cultural, physiological, and environmental stressors. The present report outlines the researchers' approach to representing cognitive, cultural, and physiological variability of an individual in an ambiguous situation while faced with a high-consequence decision that would greatly impact subsequent events. The present project was framed around a sensor-shooter scenario as a soldier interacts with an unexpected target (twomore » young Iraqi girls). A software model of the ''Sensor Shooter'' scenario from Desert Storm was developed in which the framework consisted of a computational instantiation of Recognition Primed Decision Making in the context of a Naturalistic Decision Making model [1]. Recognition Primed Decision Making was augmented with an underlying foundation based on our current understanding of human neurophysiology and its relationship to human cognitive processes. While the Gulf War scenario that constitutes the framework for the Sensor Shooter prototype is highly specific, the human decision architecture and the subsequent simulation are applicable to other problems similar in concept, intensity, and degree of uncertainty. The goal was to provide initial steps toward a computational representation of human variability in cultural, cognitive, and physiological state in order to attain a better understanding of the full depth of human decision-making processes in the context of ambiguity, novelty, and heightened arousal.« less

Functional modeling of the human auditory brainstem response to broadband stimulationa)

PubMed Central

Verhulst, Sarah; Bharadwaj, Hari M.; Mehraei, Golbarg; Shera, Christopher A.; Shinn-Cunningham, Barbara G.

2015-01-01

Population responses such as the auditory brainstem response (ABR) are commonly used for hearing screening, but the relationship between single-unit physiology and scalp-recorded population responses are not well understood. Computational models that integrate physiologically realistic models of single-unit auditory-nerve (AN), cochlear nucleus (CN) and inferior colliculus (IC) cells with models of broadband peripheral excitation can be used to simulate ABRs and thereby link detailed knowledge of animal physiology to human applications. Existing functional ABR models fail to capture the empirically observed 1.2–2 ms ABR wave-V latency-vs-intensity decrease that is thought to arise from level-dependent changes in cochlear excitation and firing synchrony across different tonotopic sections. This paper proposes an approach where level-dependent cochlear excitation patterns, which reflect human cochlear filter tuning parameters, drive AN fibers to yield realistic level-dependent properties of the ABR wave-V. The number of free model parameters is minimal, producing a model in which various sources of hearing-impairment can easily be simulated on an individualized and frequency-dependent basis. The model fits latency-vs-intensity functions observed in human ABRs and otoacoustic emissions while maintaining rate-level and threshold characteristics of single-unit AN fibers. The simulations help to reveal which tonotopic regions dominate ABR waveform peaks at different stimulus intensities. PMID:26428802

HuPSON: the human physiology simulation ontology.

PubMed

Gündel, Michaela; Younesi, Erfan; Malhotra, Ashutosh; Wang, Jiali; Li, Hui; Zhang, Bijun; de Bono, Bernard; Mevissen, Heinz-Theodor; Hofmann-Apitius, Martin

2013-11-22

Large biomedical simulation initiatives, such as the Virtual Physiological Human (VPH), are substantially dependent on controlled vocabularies to facilitate the exchange of information, of data and of models. Hindering these initiatives is a lack of a comprehensive ontology that covers the essential concepts of the simulation domain. We propose a first version of a newly constructed ontology, HuPSON, as a basis for shared semantics and interoperability of simulations, of models, of algorithms and of other resources in this domain. The ontology is based on the Basic Formal Ontology, and adheres to the MIREOT principles; the constructed ontology has been evaluated via structural features, competency questions and use case scenarios.The ontology is freely available at: http://www.scai.fraunhofer.de/en/business-research-areas/bioinformatics/downloads.html (owl files) and http://bishop.scai.fraunhofer.de/scaiview/ (browser). HuPSON provides a framework for a) annotating simulation experiments, b) retrieving relevant information that are required for modelling, c) enabling interoperability of algorithmic approaches used in biomedical simulation, d) comparing simulation results and e) linking knowledge-based approaches to simulation-based approaches. It is meant to foster a more rapid uptake of semantic technologies in the modelling and simulation domain, with particular focus on the VPH domain.

Comparative Risks of Aldehyde Constituents in Cigarette Smoke Using Transient Computational Fluid Dynamics/Physiologically Based Pharmacokinetic Models of the Rat and Human Respiratory Tracts

PubMed Central

Corley, Richard A.; Kabilan, Senthil; Kuprat, Andrew P.; Carson, James P.; Jacob, Richard E.; Minard, Kevin R.; Teeguarden, Justin G.; Timchalk, Charles; Pipavath, Sudhakar; Glenny, Robb; Einstein, Daniel R.

2015-01-01

Computational fluid dynamics (CFD) modeling is well suited for addressing species-specific anatomy and physiology in calculating respiratory tissue exposures to inhaled materials. In this study, we overcame prior CFD model limitations to demonstrate the importance of realistic, transient breathing patterns for predicting site-specific tissue dose. Specifically, extended airway CFD models of the rat and human were coupled with airway region-specific physiologically based pharmacokinetic (PBPK) tissue models to describe the kinetics of 3 reactive constituents of cigarette smoke: acrolein, acetaldehyde and formaldehyde. Simulations of aldehyde no-observed-adverse-effect levels for nasal toxicity in the rat were conducted until breath-by-breath tissue concentration profiles reached steady state. Human oral breathing simulations were conducted using representative aldehyde yields from cigarette smoke, measured puff ventilation profiles and numbers of cigarettes smoked per day. As with prior steady-state CFD/PBPK simulations, the anterior respiratory nasal epithelial tissues received the greatest initial uptake rates for each aldehyde in the rat. However, integrated time- and tissue depth-dependent area under the curve (AUC) concentrations were typically greater in the anterior dorsal olfactory epithelium using the more realistic transient breathing profiles. For human simulations, oral and laryngeal tissues received the highest local tissue dose with greater penetration to pulmonary tissues than predicted in the rat. Based upon lifetime average daily dose comparisons of tissue hot-spot AUCs (top 2.5% of surface area-normalized AUCs in each region) and numbers of cigarettes smoked/day, the order of concern for human exposures was acrolein > formaldehyde > acetaldehyde even though acetaldehyde yields were 10-fold greater than formaldehyde and acrolein. PMID:25858911

Impacts of Fluid Dynamics Simulation in Study of Nasal Airflow Physiology and Pathophysiology in Realistic Human Three-Dimensional Nose Models

PubMed Central

Lee, Heow Peuh; Gordon, Bruce R.

2012-01-01

During the past decades, numerous computational fluid dynamics (CFD) studies, constructed from CT or MRI images, have simulated human nasal models. As compared to rhinomanometry and acoustic rhinometry, which provide quantitative information only of nasal airflow, resistance, and cross sectional areas, CFD enables additional measurements of airflow passing through the nasal cavity that help visualize the physiologic impact of alterations in intranasal structures. Therefore, it becomes possible to quantitatively measure, and visually appreciate, the airflow pattern (laminar or turbulent), velocity, pressure, wall shear stress, particle deposition, and temperature changes at different flow rates, in different parts of the nasal cavity. The effects of both existing anatomical factors, as well as post-operative changes, can be assessed. With recent improvements in CFD technology and computing power, there is a promising future for CFD to become a useful tool in planning, predicting, and evaluating outcomes of nasal surgery. This review discusses the possibilities and potential impacts, as well as technical limitations, of using CFD simulation to better understand nasal airflow physiology. PMID:23205221

Teaching first-year medical students physiology: does the human patient simulator allow for more effective teaching?

PubMed

Tan, G M; Ti, L K; Suresh, S; Ho, B S; Lee, T L

2002-05-01

Although the Human Patient Simulator (HPS) is an effective teaching tool in many medical fields, literature supporting its use in the teaching of physiology to medical students is lacking. This study investigated the effectiveness of HPS-based teaching of cardiovascular physiology to first-year medical students. Two hundred and ten first-year medical students were scheduled to our HPS laboratory with the purpose of demonstrating "physiology in action". Students were divided into groups of 19-25 each, and attended a lecture followed by a HPS session. Using a theatre-type simulator complete with mannequin, anaesthesia machine and monitors (METI, Sarasota FL), the scenarios of hypovolaemia, sepsis, and cardiac failure were run to demonstrate the physiological changes that occur with changes in preload, afterload, and cardiac contractility. Each student was given a true/false test before, and again after the HPS session, followed by a survey of their learning experience. There was marked improvement in test scores after the HPS session (82.1% vs. 64.6%, P < 0.001). Most of the students felt that HPS was a better teaching tool (94.5%) and raised more questions (76.5%) than lectures. They wanted more topics to be taught this way (96%), as they could apply and re-enforce textbook knowledge, and visualise real-time changes. However, they felt that their experience could have been enhanced with more time and smaller groups. HPS is an excellent teaching tool as it stimulates student curiosity and makes knowledge acquisition and understanding easier. It is highly desirable to be incorporated into the teaching of physiology.

Human habitat positioning system for NASA's space flight environmental simulator

NASA Technical Reports Server (NTRS)

Caldwell, W. F.; Tucker, J.; Keas, P.

1998-01-01

Artificial gravity by centrifugation offers an effective countermeasure to the physiologic deconditioning of chronic exposure to microgravity; however, the system requirements of rotational velocity, radius of rotation, and resultant centrifugal acceleration require thorough investigation to ascertain the ideal human-use centrifuge configuration. NASA's Space Flight Environmental Simulator (SFES), a 16-meter (52-foot) diameter, animal-use centrifuge, was recently modified to accommodate human occupancy. This paper describes the SFES Human Habitat Positioning System, the mechanism that facilitates radius of rotation variability and alignment of the centrifuge occupants with the artificial gravity vector.

Physiologically relevant organs on chips.

PubMed

Yum, Kyungsuk; Hong, Soon Gweon; Healy, Kevin E; Lee, Luke P

2014-01-01

Recent advances in integrating microengineering and tissue engineering have generated promising microengineered physiological models for experimental medicine and pharmaceutical research. Here we review the recent development of microengineered physiological systems, or also known as "ogans-on-chips", that reconstitute the physiologically critical features of specific human tissues and organs and their interactions. This technology uses microengineering approaches to construct organ-specific microenvironments, reconstituting tissue structures, tissue-tissue interactions and interfaces, and dynamic mechanical and biochemical stimuli found in specific organs, to direct cells to assemble into functional tissues. We first discuss microengineering approaches to reproduce the key elements of physiologically important, dynamic mechanical microenvironments, biochemical microenvironments, and microarchitectures of specific tissues and organs in microfluidic cell culture systems. This is followed by examples of microengineered individual organ models that incorporate the key elements of physiological microenvironments into single microfluidic cell culture systems to reproduce organ-level functions. Finally, microengineered multiple organ systems that simulate multiple organ interactions to better represent human physiology, including human responses to drugs, is covered in this review. This emerging organs-on-chips technology has the potential to become an alternative to 2D and 3D cell culture and animal models for experimental medicine, human disease modeling, drug development, and toxicology. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Establishing the Biodynamics Data Resource (BDR): Human Volunteer Impact Acceleration Research Data in the BDR

DTIC Science & Technology

2009-10-01

accelerations (+Z) were applied to HRVs in the supine position to mimic the acceleration of an ejection seat , while runs simulating aircraft crashes were...Naval Biodynamics Laboratory, 1985). The vertical testing provided a more authentic ejection seat simulation than was achievable using axial...impact acceleration exposures with hundreds of human research volunteers. The resulting volumes of kinematic and physiological data serve as a

On the role of numerical simulations in studies of reduced gravity-induced physiological effects in humans. Results from NELME.

NASA Astrophysics Data System (ADS)

Perez-Poch, Antoni

Computer simulations are becoming a promising research line of work, as physiological models become more and more sophisticated and reliable. Technological advances in state-of-the-art hardware technology and software allow nowadays for better and more accurate simulations of complex phenomena, such as the response of the human cardiovascular system to long-term exposure to microgravity. Experimental data for long-term missions are difficult to achieve and reproduce, therefore the predictions of computer simulations are of a major importance in this field. Our approach is based on a previous model developed and implemented in our laboratory (NELME: Numercial Evaluation of Long-term Microgravity Effects). The software simulates the behaviour of the cardiovascular system and different human organs, has a modular archi-tecture, and allows to introduce perturbations such as physical exercise or countermeasures. The implementation is based on a complex electrical-like model of this control system, using inexpensive development frameworks, and has been tested and validated with the available experimental data. The objective of this work is to analyse and simulate long-term effects and gender differences when individuals are exposed to long-term microgravity. Risk probability of a health impairement which may put in jeopardy a long-term mission is also evaluated. . Gender differences have been implemented for this specific work, as an adjustment of a number of parameters that are included in the model. Women versus men physiological differences have been therefore taken into account, based upon estimations from the physiology bibliography. A number of simulations have been carried out for long-term exposure to microgravity. Gravity varying continuosly from Earth-based to zero, and time exposure are the two main variables involved in the construction of results, including responses to patterns of physical aerobic ex-ercise and thermal stress simulating an extra-vehicular activity. Results show that significant differences appear between men and women physiological response after long-term exposure (more than three months) to microgravity. Risk evaluation for every gender, and specific risk thresholds are provided. Different scenarios like a long-term mission to Moon or Mars are evaluated, including countermeasures such as aerobic exercise. Initial results are compatible with the existing data, and provide useful insights regarding different patterns of microgravity exposure. We conclude that computer-based models such us NELME are a promising line of work to predict health risks in long-term missions.

[Development of a basic ration out of commercial foods for nutrition in ground-based simulation experiments].

PubMed

Agureev, A N; Kalandarov, S; Bogatova, R I; Krivitsina, Z A; Vasil'eva, V F

2005-01-01

Food rations composed of canned products were given the physiological and hygienic evaluation in the context of their fitness for human volunteers in experiments with head-down bedrest in isolation and confinement. As a result, the food rations were proven to contain the desired quantities of nutrients. Evaluation of food fitness for human subjects was made based on the data of clinical-physiological and biochemical investigations. The rations met the energy and anabolic metabolism demands of human subjects during extreme chamber experiments and were favorable to maintaining good level of vital processes.

HuPSON: the human physiology simulation ontology

PubMed Central

2013-01-01

Background Large biomedical simulation initiatives, such as the Virtual Physiological Human (VPH), are substantially dependent on controlled vocabularies to facilitate the exchange of information, of data and of models. Hindering these initiatives is a lack of a comprehensive ontology that covers the essential concepts of the simulation domain. Results We propose a first version of a newly constructed ontology, HuPSON, as a basis for shared semantics and interoperability of simulations, of models, of algorithms and of other resources in this domain. The ontology is based on the Basic Formal Ontology, and adheres to the MIREOT principles; the constructed ontology has been evaluated via structural features, competency questions and use case scenarios. The ontology is freely available at: http://www.scai.fraunhofer.de/en/business-research-areas/bioinformatics/downloads.html (owl files) and http://bishop.scai.fraunhofer.de/scaiview/ (browser). Conclusions HuPSON provides a framework for a) annotating simulation experiments, b) retrieving relevant information that are required for modelling, c) enabling interoperability of algorithmic approaches used in biomedical simulation, d) comparing simulation results and e) linking knowledge-based approaches to simulation-based approaches. It is meant to foster a more rapid uptake of semantic technologies in the modelling and simulation domain, with particular focus on the VPH domain. PMID:24267822

Effect of Red Blood Cell Storage on Cardiac Performance. Improved Myocardial Oxygen Delivery and Function during Constant Flow Coronary Perfusion with Low Oxy-Hemoglobin Affinity Human Red Blood Cells in Normothermic and Hypothermic Rabbit Hearts.

DTIC Science & Technology

1983-02-01

with an isovolumic left ven- tricular balloon. Coronary flow was held constant to simulate the physiolog of coronary atherosclerosis and other...erythrocyte DPG content can potentially benefit patients with coronary atherosclerosis , or other states with a limited coronary vasodilator reserve, who...Coronary flow was held constant to simulate the physiology of coronary atherosclerosis and other conditions of limited coronary vasodilator reserve

Construction of a Lower Body Negative Pressure Chamber

ERIC Educational Resources Information Center

Esch, Ben T. A; Scott, Jessica M.; Warburton, Darren E. R.

2007-01-01

Lower body negative pressure (LBNP) is an established and important technique used to physiologically stress the human body, particularly the cardiovascular system. LBNP is most often used to simulate gravitational stress, but it has also been used to simulate hemorrhage, alter preload, and manipulate baroreceptors. During experimentation, the…

Simulator technology as a tool for education in cardiac care.

PubMed

Hravnak, Marilyn; Beach, Michael; Tuite, Patricia

2007-01-01

Assisting nurses in gaining the cognitive and psychomotor skills necessary to safely and effectively care for patients with cardiovascular disease can be challenging for educators. Ideally, nurses would have the opportunity to synthesize and practice these skills in a protected training environment before application in the dynamic clinical setting. Recently, a technology known as high fidelity human simulation was introduced, which permits learners to interact with a simulated patient. The dynamic physiologic parameters and physical assessment capabilities of the simulated patient provide for a realistic learning environment. This article describes the High Fidelity Human Simulation Laboratory at the University of Pittsburgh School of Nursing and presents strategies for using this technology as a tool in teaching complex cardiac nursing care at the basic and advanced practice nursing levels. The advantages and disadvantages of high fidelity human simulation in learning are discussed.

Survival at Isle Royale.

ERIC Educational Resources Information Center

Ballone, Lena M.

2001-01-01

Describes a simulation based on the popular television show "Survivor" in which students work in groups and study physiological needs for human survival. Focuses on communication skills, problem solving, and cooperative learning. (YDS)

Development of an Arm Phantom for Testing Non-Invasive Blood Pressure Monitors

NASA Astrophysics Data System (ADS)

Anderson-Jackson, LaTecia D.

Approximately one in every three adults age 20 older are diagnosed with high blood pressure or hypertension. It is estimated that hypertension affects 78 million people in the United States, is equally prevalent in both men and woman (Crabtree, Stuart-Shor, & McAllister, 2013). In the United States, around 78% of people suffering from hypertension are aware of their condition, with only 68% using hypertensive medications to control their blood pressure (Writing Group et al., 2010). Clinically, blood pressure measurements may lack accuracy, which can be attributed to various factors, including device limitations, cuff mis-sizing and misplacement, white-coat effect, masked hypertension, and lifestyle factors. The development of an arm phantom to simulate physiologic properties of a human arm and arterial BP waveforms may allow us to better assess the accuracy of non-invasive blood pressure (NIBP) monitors. The objective of this study are to: (1) Develop an arm phantom to replicate physiological properties of the human arm, and (2) Incorporate the arm phantom into a mock circulatory flow loop to simulate different physiological blood pressure readings on the bench. A tissue mimicking material, styrene-ethylene-butylene-styrene (SEBS), a co-block polymer was used to develop the arm phantom for in-vitro testing. To determine the optimal mechanical properties for the arm phantom, individual arm components were isolated and tested. A protocol was developed to evaluate various components for optimal arm phantom development. Mechanical testing was conducted on 10%, 15%, and 20% SEBS gel samples for modulus of elasticity measurements in order to simulate physiological properties of the human arm. As a result of the SEBS polymer being a new material for this application, this investigation will contribute to resolving the limitations that occurred during experimentation. In this study, we demonstrated that although SEBS polymer may be an ideal material to use for simulating tissue, further research on the material properties should be conducted.

Prediction of Fetal Darunavir Exposure by Integrating Human Ex-Vivo Placental Transfer and Physiologically Based Pharmacokinetic Modeling.

PubMed

Schalkwijk, Stein; Buaben, Aaron O; Freriksen, Jolien J M; Colbers, Angela P; Burger, David M; Greupink, Rick; Russel, Frans G M

2017-07-25

Fetal antiretroviral exposure is usually derived from the cord-to-maternal concentration ratio. This static parameter does not provide information on the pharmacokinetics in utero, limiting the assessment of a fetal exposure-effect relationship. The aim of this study was to incorporate placental transfer into a pregnancy physiologically based pharmacokinetic model to simulate and evaluate fetal darunavir exposure at term. An existing and validated pregnancy physiologically based pharmacokinetic model of maternal darunavir/ritonavir exposure was extended with a feto-placental unit. To parameterize the model, we determined maternal-to-fetal and fetal-to-maternal darunavir/ritonavir placental clearance with an ex-vivo human cotyledon perfusion model. Simulated maternal and fetal pharmacokinetic profiles were compared with observed clinical data to qualify the model for simulation. Next, population fetal pharmacokinetic profiles were simulated for different maternal darunavir/ritonavir dosing regimens. An average (±standard deviation) maternal-to-fetal cotyledon clearance of 0.91 ± 0.11 mL/min and fetal-to-maternal clearance of 1.6 ± 0.3 mL/min was determined (n = 6 perfusions). Scaled placental transfer was integrated into the pregnancy physiologically based pharmacokinetic model. For darunavir 600/100 mg twice a day, the predicted fetal maximum plasma concentration, trough concentration, time to maximum plasma concentration, and half-life were 1.1, 0.57 mg/L, 3, and 21 h, respectively. This indicates that the fetal population trough concentration is higher or around the half-maximal effective darunavir concentration for a resistant virus (0.55 mg/L). The results indicate that the population fetal exposure after oral maternal darunavir dosing is therapeutic and this may provide benefits to the prevention of mother-to-child transmission of human immunodeficiency virus. Moreover, this integrated approach provides a tool to prevent fetal toxicity or enhance the development of more selectively targeted fetal drug treatments.

Laboratory simulation of the action of weightlessness on the human organism

NASA Technical Reports Server (NTRS)

Genin, A. M.

1977-01-01

A brief history of attemps by the U.S. and the U.S.S.R. to simulate weightlessness in the laboratory is presented. Model for laboratory modeling of weightlessness included the bed regimen, the clinostat, and water immersion. An outline of immediate physiological effects of weightlessness and long term effects is offered.

Simulation-Based Design for Wearable Robotic Systems: An Optimization Framework for Enhancing a Standing Long Jump.

PubMed

Ong, Carmichael F; Hicks, Jennifer L; Delp, Scott L

2016-05-01

Technologies that augment human performance are the focus of intensive research and development, driven by advances in wearable robotic systems. Success has been limited by the challenge of understanding human-robot interaction. To address this challenge, we developed an optimization framework to synthesize a realistic human standing long jump and used the framework to explore how simulated wearable robotic devices might enhance jump performance. A planar, five-segment, seven-degree-of-freedom model with physiological torque actuators, which have variable torque capacity depending on joint position and velocity, was used to represent human musculoskeletal dynamics. An active augmentation device was modeled as a torque actuator that could apply a single pulse of up to 100 Nm of extension torque. A passive design was modeled as rotational springs about each lower limb joint. Dynamic optimization searched for physiological and device actuation patterns to maximize jump distance. Optimization of the nominal case yielded a 2.27 m jump that captured salient kinematic and kinetic features of human jumps. When the active device was added to the ankle, knee, or hip, jump distance increased to between 2.49 and 2.52 m. Active augmentation of all three joints increased the jump distance to 3.10 m. The passive design increased jump distance to 3.32 m by adding torques of 135, 365, and 297 Nm to the ankle, knee, and hip, respectively. Dynamic optimization can be used to simulate a standing long jump and investigate human-robot interaction. Simulation can aid in the design of performance-enhancing technologies.

Mathematical modeling and spectrum analysis of the physiological patello-femoral pulse train produced by slow knee movement.

PubMed

Zhang, Y T; Frank, C B; Rangayyan, R M; Bell, G D

1992-09-01

Analysis of vibration signals emitted by the knee joint has the potential for the development of a noninvasive procedure for the diagnosis and monitoring of knee pathology. In order to obtain as much information as possible from the power density spectrum of the knee vibration signal, it is necessary to identify the physiological factors (or physiologically relevant parameters) that shape the spectrum. This paper presents a mathematical model for knee vibration signals, in particular the physiological patello-femoral pulse (PFP) train produced by slow knee movement. It demonstrates through the mathematical model that the repetition rate of the physiological PFP train introduces repeated peaks in the power spectrum, and that it affects the spectrum mainly at low frequencies. The theoretical results also show that the spectral peaks at multiples of the PFP repetition rate become more evident when the variance of the interpulse interval (IPI) is small, and that these spectral peaks shift toward higher frequencies with increasing PFP repetition rates. To evaluate the mathematical model, a simulation algorithm was developed, which generates PFP signals with adjustable repetition rate and IPI variance. Signals generated by simulation were seen to possess representative spectral characteristics typically observed in physiological PFP signals. This simulation procedure allows an interactive examination of several factors which affect the PFP train spectrum. Finally, in vivo measurements of physiological PFP signals of normal volunteers are presented. Results of simulations and analysis of signals recorded from human subjects support the mathematical model's prediction that the IPI statistics play a very significant role in determining the low-end power spectrum of the physiological PFP signal.(ABSTRACT TRUNCATED AT 250 WORDS)

Human cadavers Vs. multimedia simulation: A study of student learning in anatomy.

PubMed

Saltarelli, Andrew J; Roseth, Cary J; Saltarelli, William A

2014-01-01

Multimedia and simulation programs are increasingly being used for anatomy instruction, yet it remains unclear how learning with these technologies compares with learning with actual human cadavers. Using a multilevel, quasi-experimental-control design, this study compared the effects of "Anatomy and Physiology Revealed" (APR) multimedia learning system with a traditional undergraduate human cadaver laboratory. APR is a model-based multimedia simulation tool that uses high-resolution pictures to construct a prosected cadaver. APR also provides animations showing the function of specific anatomical structures. Results showed that the human cadaver laboratory offered a significant advantage over the multimedia simulation program on cadaver-based measures of identification and explanatory knowledge. These findings reinforce concerns that incorporating multimedia simulation into anatomy instruction requires careful alignment between learning tasks and performance measures. Findings also imply that additional pedagogical strategies are needed to support transfer from simulated to real-world application of anatomical knowledge. © 2014 American Association of Anatomists.

Zero-gravity movement studies

NASA Technical Reports Server (NTRS)

Badler, N. I.; Fishwick, P.; Taft, N.; Agrawala, M.

1985-01-01

The use of computer graphics to simulate the movement of articulated animals and mechanisms has a number of uses ranging over many fields. Human motion simulation systems can be useful in education, medicine, anatomy, physiology, and dance. In biomechanics, computer displays help to understand and analyze performance. Simulations can be used to help understand the effect of external or internal forces. Similarly, zero-gravity simulation systems should provide a means of designing and exploring the capabilities of hypothetical zero-gravity situations before actually carrying out such actions. The advantage of using a simulation of the motion is that one can experiment with variations of a maneuver before attempting to teach it to an individual. The zero-gravity motion simulation problem can be divided into two broad areas: human movement and behavior in zero-gravity, and simulation of articulated mechanisms.

Measurements, modeling, control and simulation - as applied to the human left ventricle for purposeful physiological monitoring.

NASA Technical Reports Server (NTRS)

Ghista, D. N.; Rasmussen, D. N.; Linebarger, R. N.; Sandler, H.

1971-01-01

Interdisciplinary engineering research effort in studying the intact human left ventricle has been employed to physiologically monitor the heart and to obtain its 'state-of-health' characteristics. The left ventricle was selected for this purpose because it plays a key role in supplying energy to the body cells. The techniques for measurement of the left ventricular geometry are described; the geometry is effectively displayed to bring out the abnormalities in cardiac function. Methods of mathematical modeling, which make it possible to determine the performance of the intact left ventricular muscle, are also described. Finally, features of a control system for the left ventricle for predicting the effect of certain physiological stress situations on the ventricle performance are discussed.

The nature of undergraduates' conceptual understanding of oxygen transport and utilization in humans: Can cardiopulmonary simulation software enhance learning of propositional knowledge and/or diagnose alternative conceptions in novices and intermediates?

NASA Astrophysics Data System (ADS)

Wissing, Dennis Robert

The purpose of the this research was to explore undergraduates' conceptual development for oxygen transport and utilization, as a component of a cardiopulmonary physiology and advanced respiratory care course in the allied health program. This exploration focused on the student's development of knowledge and the presence of alternative conceptions, prior to, during, and after completing cardiopulmonary physiology and advanced respiratory care courses. Using the simulation program, SimBioSysTM (Samsel, 1994), student-participants completed a series of laboratory exercises focusing on cardiopulmonary disease states. This study examined data gathered from: (1) a novice group receiving the simulation program prior to instruction, (2) a novice group that experienced the simulation program following course completion in cardiopulmonary physiology, and (3) an intermediate group who experienced the simulation program following completion of formal education in Respiratory Care. This research was based on the theory of Human Constructivism as described by Mintzes, Wandersee, and Novak (1997). Data-gathering techniques were based on theories supported by Novak (1984), Wandersee (1997), and Chi (1997). Data were generated by exams, interviews, verbal analysis (Chi, 1997), and concept mapping. Results suggest that simulation may be an effective instructional method for assessing conceptual development and diagnosing alternative conceptions in undergraduates enrolled in a cardiopulmonary science program. Use of simulation in conjunction with clinical interview and concept mapping may assist in verifying gaps in learning and conceptual knowledge. This study found only limited evidence to support the use of computer simulation prior to lecture to augment learning. However, it was demonstrated that students' prelecture experience with the computer simulation helped the instructor assess what the learner knew so he or she could be taught accordingly. In addition, use of computer simulation after formal instruction was shown to be useful in aiding students identified by the instructor as needing remediation.

MRI-based three-dimensional thermal physiological characterization of thyroid gland of human body.

PubMed

Jin, Chao; He, Zhi Zhu; Yang, Yang; Liu, Jing

2014-01-01

This article is dedicated to present a MRI (magnetic resonance imaging) based three-dimensional finite element modeling on the thermal manifestations relating to the pathophysiology of thyroid gland. An efficient approach for identifying the metabolic dysfunctions of thyroid has also been demonstrated through tracking the localized non-uniform thermal distribution or enhanced dynamic imaging. The temperature features over the skin surface and thyroid domain have been characterized using the numerical simulation and experimental measurement which will help better interpret the thermal physiological mechanisms of the thyroid under steady-state or water-cooling condition. Further, parametric simulations on the hypermetabolism symptoms of hyperthyroidism and thermal effects within thyroid domain caused by varying breathing airflow in the trachea and blood-flow in artery and vein were performed. It was disclosed that among all the parameters, the airflow volume has the largest effect on the total heat flux of thyroid surface. However, thermal contributions caused by varying the breathing frequency and blood-flow velocity are negligibly small. The present study suggests a generalized way for simulating the close to reality physiological behavior or process of human thyroid, which is of significance for disease diagnosis and treatment planning. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

Knowledge environments representing molecular entities for the virtual physiological human.

PubMed

Hofmann-Apitius, Martin; Fluck, Juliane; Furlong, Laura; Fornes, Oriol; Kolárik, Corinna; Hanser, Susanne; Boeker, Martin; Schulz, Stefan; Sanz, Ferran; Klinger, Roman; Mevissen, Theo; Gattermayer, Tobias; Oliva, Baldo; Friedrich, Christoph M

2008-09-13

In essence, the virtual physiological human (VPH) is a multiscale representation of human physiology spanning from the molecular level via cellular processes and multicellular organization of tissues to complex organ function. The different scales of the VPH deal with different entities, relationships and processes, and in consequence the models used to describe and simulate biological functions vary significantly. Here, we describe methods and strategies to generate knowledge environments representing molecular entities that can be used for modelling the molecular scale of the VPH. Our strategy to generate knowledge environments representing molecular entities is based on the combination of information extraction from scientific text and the integration of information from biomolecular databases. We introduce @neuLink, a first prototype of an automatically generated, disease-specific knowledge environment combining biomolecular, chemical, genetic and medical information. Finally, we provide a perspective for the future implementation and use of knowledge environments representing molecular entities for the VPH.

Human Thiel-Embalmed Cadaveric Aortic Model with Perfusion for Endovascular Intervention Training and Medical Device Evaluation.

PubMed

McLeod, Helen; Cox, Ben F; Robertson, James; Duncan, Robyn; Matthew, Shona; Bhat, Raj; Barclay, Avril; Anwar, J; Wilkinson, Tracey; Melzer, Andreas; Houston, J Graeme

2017-09-01

The purpose of this investigation was to evaluate human Thiel-embalmed cadavers with the addition of extracorporeal driven ante-grade pulsatile flow in the aorta as a model for simulation training in interventional techniques and endovascular device testing. Three human cadavers embalmed according to the method of Thiel were selected. Extracorporeal pulsatile ante-grade flow of 2.5 L per min was delivered directly into the aorta of the cadavers via a surgically placed connection. During perfusion, aortic pressure and temperature were recorded and optimized for physiologically similar parameters. Pre- and post-procedure CT imaging was conducted to plan and follow up thoracic and abdominal endovascular aortic repair as it would be in a clinical scenario. Thoracic endovascular aortic repair (TEVAR) and endovascular abdominal repair (EVAR) procedures were conducted in simulation of a clinical case, under fluoroscopic guidance with a multidisciplinary team present. The Thiel cadaveric aortic perfusion model provided pulsatile ante-grade flow, with pressure and temperature, sufficient to conduct a realistic simulation of TEVAR and EVAR procedures. Fluoroscopic imaging provided guidance during the intervention. Pre- and post-procedure CT imaging facilitated planning and follow-up evaluation of the procedure. The human Thiel-embalmed cadavers with the addition of extracorporeal flow within the aorta offer an anatomically appropriate, physiologically similar robust model to simulate aortic endovascular procedures, with potential applications in interventional radiology training and medical device testing as a pre-clinical model.

Microbial growth and physiology in space - A review

NASA Technical Reports Server (NTRS)

Cioletti, Louis A.; Mishra, S. K.; Pierson, Duane L.

1991-01-01

An overview of microbial behavior in closed environments is given with attention to data related to simulated microgravity and actual space flight. Microbes are described in terms of antibiotic sensitivity, subcellular structure, and physiology, and the combined effects are considered of weightlessness and cosmic radiation on human immunity to such microorganisms. Space flight results report such effects as increased phage induction, accelerated microbial growth rates, and the increased risk of disease communication and microbial exchange aboard confining spacecraft. Ultrastructural changes are also noted in the nuclei, cell membranes, and cytoplasmic streaming, and it appears that antibiotic sensitivity is reduced under both actual and simulated conditions of spaceflight.

Further observations on the relationship of EMG and muscle force

NASA Technical Reports Server (NTRS)

Agarwal, G. C.; Cecchini, L. R.; Gottlieb, G. L.

1972-01-01

Human skeletal muscle may be regarded as an electro-mechanical transducer. Its physiological input is a neural signal originating at the alpha motoneurons in the spinal cord and its output is force and muscle contraction, these both being dependent on the external load. Some experimental data taken during voluntary efforts around the ankle joint and by direct electrical stimulation of the nerve are described. Some of these experiments are simulated by an analog model, the input of which is recorded physiological soleus muscle EMG. The output is simulated foot torque. Limitations of a linear model and effect of some nonlinearities are discussed.

Development of Open Brain Simulator for Human Biomechatronics

NASA Astrophysics Data System (ADS)

Otake, Mihoko; Takagi, Toshihisa; Asama, Hajime

Modeling and simulation based on mechanisms is important in order to design and control mechatronic systems. In particular, in-depth understanding and realistic modeling of biological systems is indispensable for biomechatronics. This paper presents open brain simulator, which estimates the neural state of human through external measurement for the purpose of improving motor and social skills. Macroscopic anatomical nervous systems model was built which can be connected to the musculoskeletal model. Microscopic anatomical and physiological neural models were interfaced to the macroscopic model. Neural activities of somatosensory area and Purkinje cell were calculated from motion capture data. The simulator provides technical infrastructure for human biomechatronics, which is promising for the novel diagnosis of neurological disorders and their treatments through medication and movement therapy, and for motor learning support system supporting acquisition of motor skill considering neural mechanism.

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

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

Kawamoto, Yuko; Matsuyama, Wakoto; Wada, Masahiro

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

A Simple Device for Measuring Static Compliance of Lung-Thorax Combine

ERIC Educational Resources Information Center

Sircar, Sabyasachi

2015-01-01

Explaining the concept of lung compliance remains a challenge to the physiology teacher because it cannot be demonstrated easily in human subjects and all attempts until now have used only simulation models. A simple device is described in the present article to measure the compliance of the "lung-thorax" combine in human subjects with…

Combining Chimeric Mice with Humanized Liver, Mass Spectrometry, and Physiologically-Based Pharmacokinetic Modeling in Toxicology.

PubMed

Yamazaki, Hiroshi; Suemizu, Hiroshi; Mitsui, Marina; Shimizu, Makiko; Guengerich, F Peter

2016-12-19

Species differences exist in terms of drug oxidation activities, which are mediated mainly by cytochrome P450 (P450) enzymes. To overcome the problem of species extrapolation, transchromosomic mice containing a human P450 3A cluster or chimeric mice transplanted with human hepatocytes have been introduced into the human toxicology research area. In this review, drug metabolism and disposition mediated by humanized livers in chimeric mice are summarized in terms of biliary/urinary excretions of phthalate and bisphenol A and plasma clearances of the human cocktail probe drugs caffeine, warfarin, omeprazole, metoprolol, and midazolam. Simulation of human plasma concentrations of the teratogen thalidomide and its human metabolites is possible with a simplified physiologically based pharmacokinetic model based on data obtained in chimeric mice, in accordance with reported clinical thalidomide concentrations. In addition, in vivo nonspecific hepatic protein binding parameters of metabolically activated 14 C-drug candidate and hepatotoxic medicines in humanized liver mice can be analyzed by accelerator mass spectrometry and are useful for predictions in humans.

An integrated physiology model to study regional lung damage effects and the physiologic response

PubMed Central

2014-01-01

Background This work expands upon a previously developed exercise dynamic physiology model (DPM) with the addition of an anatomic pulmonary system in order to quantify the impact of lung damage on oxygen transport and physical performance decrement. Methods A pulmonary model is derived with an anatomic structure based on morphometric measurements, accounting for heterogeneous ventilation and perfusion observed experimentally. The model is incorporated into an existing exercise physiology model; the combined system is validated using human exercise data. Pulmonary damage from blast, blunt trauma, and chemical injury is quantified in the model based on lung fluid infiltration (edema) which reduces oxygen delivery to the blood. The pulmonary damage component is derived and calibrated based on published animal experiments; scaling laws are used to predict the human response to lung injury in terms of physical performance decrement. Results The augmented dynamic physiology model (DPM) accurately predicted the human response to hypoxia, altitude, and exercise observed experimentally. The pulmonary damage parameters (shunt and diffusing capacity reduction) were fit to experimental animal data obtained in blast, blunt trauma, and chemical damage studies which link lung damage to lung weight change; the model is able to predict the reduced oxygen delivery in damage conditions. The model accurately estimates physical performance reduction with pulmonary damage. Conclusions We have developed a physiologically-based mathematical model to predict performance decrement endpoints in the presence of thoracic damage; simulations can be extended to estimate human performance and escape in extreme situations. PMID:25044032

Flight simulator requirements for airline transport pilot training - An evaluation of motion system design alternatives

NASA Technical Reports Server (NTRS)

Lee, A. T.; Bussolari, S. R.

1986-01-01

The effect of motion platform systems on pilot behavior is considered with emphasis placed on civil aviation applications. A dynamic model for human spatial orientation based on the physiological structure and function of the human vestibular system is presented. Motion platform alternatives were evaluated on the basis of the following motion platform conditions: motion with six degrees-of-freedom required for Phase II simulators and two limited motion conditions. Consideration was given to engine flameout, airwork, and approach and landing scenarios.

A new class of methods for functional connectivity estimation

NASA Astrophysics Data System (ADS)

Lin, Wutu

Measuring functional connectivity from neural recordings is important in understanding processing in cortical networks. The covariance-based methods are the current golden standard for functional connectivity estimation. However, the link between the pair-wise correlations and the physiological connections inside the neural network is unclear. Therefore, the power of inferring physiological basis from functional connectivity estimation is limited. To build a stronger tie and better understand the relationship between functional connectivity and physiological neural network, we need (1) a realistic model to simulate different types of neural recordings with known ground truth for benchmarking; (2) a new functional connectivity method that produce estimations closely reflecting the physiological basis. In this thesis, (1) I tune a spiking neural network model to match with human sleep EEG data, (2) introduce a new class of methods for estimating connectivity from different kinds of neural signals and provide theory proof for its superiority, (3) apply it to simulated fMRI data as an application.

Drug-physiology interaction and its influence on the QT prolongation-mechanistic modeling study.

PubMed

Wiśniowska, Barbara; Polak, Sebastian

2018-06-01

The current study is an example of drug-disease interaction modeling where a drug induces a condition which can affect the pharmacodynamics of other concomitantly taken drugs. The electrophysiological effects of hypokaliemia and heart rate changes induced by the antiasthmatic drugs were simulated with the use of the cardiac safety simulator. Biophysically detailed model of the human cardiac physiology-ten Tusscher ventricular cardiomyocyte cell model-was employed to generate pseudo-ECG signals and QTc intervals for 44 patients from four clinical studies. Simulated and observed mean QTc values with standard deviation (SD) for each reported study point were compared and differences were analyzed with Student's t test (α = 0.05). The simulated results reflected the QTc interval changes measured in patients, as well as their clinically observed interindividual variability. The QTc interval changes were highly correlated with the change in plasma potassium both in clinical studies and in the simulations (Pearson's correlation coefficient > 0.55). The results suggest that the modeling and simulation approach could provide valuable quantitative insight into the cardiological effect of the potassium and heart rate changes caused by electrophysiologically inactive, non-cardiological drugs. This allows to simulate and predict the joint effect of several risk factors for QT prolongation, e.g., drug-dependent QT prolongation due to the ion channels inhibition and the current patient physiological conditions.

Virtual Clinical Trial Toward Polytherapy Safety Assessment: Combination of Physiologically Based Pharmacokinetic/Pharmacodynamic-Based Modeling and Simulation Approach With Drug-Drug Interactions Involving Terfenadine as an Example.

PubMed

Wiśniowska, Barbara; Polak, Sebastian

2016-11-01

A Quantitative Systems Pharmacology approach was utilized to predict the cardiac consequences of drug-drug interaction (DDI) at the population level. The Simcyp in vitro-in vivo correlation and physiologically based pharmacokinetic platform was used to predict the pharmacokinetic profile of terfenadine following co-administration of the drug. Electrophysiological effects were simulated using the Cardiac Safety Simulator. The modulation of ion channel activity was dependent on the inhibitory potential of drugs on the main cardiac ion channels and a simulated free heart tissue concentration. ten Tusscher's human ventricular cardiomyocyte model was used to simulate the pseudo-ECG traces and further predict the pharmacodynamic consequences of DDI. Consistent with clinical observations, predicted plasma concentration profiles of terfenadine show considerable intra-subject variability with recorded C max values below 5 ng/mL for most virtual subjects. The pharmacokinetic and pharmacodynamic effects of inhibitors were predicted with reasonable accuracy. In all cases, a combination of the physiologically based pharmacokinetic and physiology-based pharmacodynamic models was able to differentiate between the terfenadine alone and terfenadine + inhibitor scenario. The range of QT prolongation was comparable in the clinical and virtual studies. The results indicate that mechanistic in vitro-in vivo correlation can be applied to predict the clinical effects of DDI even without comprehensive knowledge on all mechanisms contributing to the interaction. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Simulating physiological interactions in a hybrid system of mathematical models.

PubMed

Kretschmer, Jörn; Haunsberger, Thomas; Drost, Erick; Koch, Edmund; Möller, Knut

2014-12-01

Mathematical models can be deployed to simulate physiological processes of the human organism. Exploiting these simulations, reactions of a patient to changes in the therapy regime can be predicted. Based on these predictions, medical decision support systems (MDSS) can help in optimizing medical therapy. An MDSS designed to support mechanical ventilation in critically ill patients should not only consider respiratory mechanics but should also consider other systems of the human organism such as gas exchange or blood circulation. A specially designed framework allows combining three model families (respiratory mechanics, cardiovascular dynamics and gas exchange) to predict the outcome of a therapy setting. Elements of the three model families are dynamically combined to form a complex model system with interacting submodels. Tests revealed that complex model combinations are not computationally feasible. In most patients, cardiovascular physiology could be simulated by simplified models decreasing computational costs. Thus, a simplified cardiovascular model that is able to reproduce basic physiological behavior is introduced. This model purely consists of difference equations and does not require special algorithms to be solved numerically. The model is based on a beat-to-beat model which has been extended to react to intrathoracic pressure levels that are present during mechanical ventilation. The introduced reaction to intrathoracic pressure levels as found during mechanical ventilation has been tuned to mimic the behavior of a complex 19-compartment model. Tests revealed that the model is able to represent general system behavior comparable to the 19-compartment model closely. Blood pressures were calculated with a maximum deviation of 1.8 % in systolic pressure and 3.5 % in diastolic pressure, leading to a simulation error of 0.3 % in cardiac output. The gas exchange submodel being reactive to changes in cardiac output showed a resulting deviation of less than 0.1 %. Therefore, the proposed model is usable in combinations where cardiovascular simulation does not have to be detailed. Computing costs have been decreased dramatically by a factor 186 compared to a model combination employing the 19-compartment model.

Simulating Physiological Response with a Passive Sensor Manikin and an Adaptive Thermal Manikin to Predict Thermal Sensation and Comfort

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

Rugh, John P; Chaney, Larry; Hepokoski, Mark

2015-04-14

Reliable assessment of occupant thermal comfort can be difficult to obtain within automotive environments, especially under transient and asymmetric heating and cooling scenarios. Evaluation of HVAC system performance in terms of comfort commonly requires human subject testing, which may involve multiple repetitions, as well as multiple test subjects. Instrumentation (typically comprised of an array of temperature sensors) is usually only sparsely applied across the human body, significantly reducing the spatial resolution of available test data. Further, since comfort is highly subjective in nature, a single test protocol can yield a wide variation in results which can only be overcome bymore » increasing the number of test replications and subjects. In light of these difficulties, various types of manikins are finding use in automotive testing scenarios. These manikins can act as human surrogates from which local skin and core temperatures can be obtained, which are necessary for accurately predicting local and whole body thermal sensation and comfort using a physiology-based comfort model (e.g., the Berkeley Comfort Model). This paper evaluates two different types of manikins, i) an adaptive sweating thermal manikin, which is coupled with a human thermoregulation model, running in real-time, to obtain realistic skin temperatures; and, ii) a passive sensor manikin, which is used to measure boundary conditions as they would act on a human, from which skin and core temperatures can be predicted using a thermophysiological model. The simulated physiological responses and comfort obtained from both of these manikin-model coupling schemes are compared to those of a human subject within a vehicle cabin compartment transient heat-up scenario.« less

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

PubMed

Kirman, C R; Suh, M; Proctor, D M; Hays, S M

2017-06-15

A physiologically based pharmacokinetic (PBPK) model for hexavalent chromium [Cr(VI)] in mice, rats, and humans developed previously (Kirman et al., 2012, 2013), was updated to reflect an improved understanding of the toxicokinetics of the gastrointestinal tract following oral exposures. Improvements were made to: (1) the reduction model, which describes the pH-dependent reduction of Cr(VI) to Cr(III) in the gastrointestinal tract under both fasted and fed states; (2) drinking water pattern simulations, to better describe dosimetry in rodents under the conditions of the NTP cancer bioassay; and (3) parameterize the model to characterize potentially sensitive human populations. Important species differences, sources of non-linear toxicokinetics, and human variation are identified and discussed within the context of human health risk assessment. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Simulation-Based Design for Wearable Robotic Systems: An Optimization Framework for Enhancing a Standing Long Jump

PubMed Central

Ong, Carmichael F.; Hicks, Jennifer L.; Delp, Scott L.

2017-01-01

Goal Technologies that augment human performance are the focus of intensive research and development, driven by advances in wearable robotic systems. Success has been limited by the challenge of understanding human–robot interaction. To address this challenge, we developed an optimization framework to synthesize a realistic human standing long jump and used the framework to explore how simulated wearable robotic devices might enhance jump performance. Methods A planar, five-segment, seven-degree-of-freedom model with physiological torque actuators, which have variable torque capacity depending on joint position and velocity, was used to represent human musculoskeletal dynamics. An active augmentation device was modeled as a torque actuator that could apply a single pulse of up to 100 Nm of extension torque. A passive design was modeled as rotational springs about each lower limb joint. Dynamic optimization searched for physiological and device actuation patterns to maximize jump distance. Results Optimization of the nominal case yielded a 2.27 m jump that captured salient kinematic and kinetic features of human jumps. When the active device was added to the ankle, knee, or hip, jump distance increased to between 2.49 and 2.52 m. Active augmentation of all three joints increased the jump distance to 3.10 m. The passive design increased jump distance to 3.32 m by adding torques of 135 Nm, 365 Nm, and 297 Nm to the ankle, knee, and hip, respectively. Conclusion Dynamic optimization can be used to simulate a standing long jump and investigate human-robot interaction. Significance Simulation can aid in the design of performance-enhancing technologies. PMID:26258930

Design optimization for accurate flow simulations in 3D printed vascular phantoms derived from computed tomography angiography

NASA Astrophysics Data System (ADS)

Sommer, Kelsey; Izzo, Rick L.; Shepard, Lauren; Podgorsak, Alexander R.; Rudin, Stephen; Siddiqui, Adnan H.; Wilson, Michael F.; Angel, Erin; Said, Zaid; Springer, Michael; Ionita, Ciprian N.

2017-03-01

3D printing has been used to create complex arterial phantoms to advance device testing and physiological condition evaluation. Stereolithographic (STL) files of patient-specific cardiovascular anatomy are acquired to build cardiac vasculature through advanced mesh-manipulation techniques. Management of distal branches in the arterial tree is important to make such phantoms practicable. We investigated methods to manage the distal arterial flow resistance and pressure thus creating physiologically and geometrically accurate phantoms that can be used for simulations of image-guided interventional procedures with new devices. Patient specific CT data were imported into a Vital Imaging workstation, segmented, and exported as STL files. Using a mesh-manipulation program (Meshmixer) we created flow models of the coronary tree. Distal arteries were connected to a compliance chamber. The phantom was then printed using a Stratasys Connex3 multimaterial printer: the vessel in TangoPlus and the fluid flow simulation chamber in Vero. The model was connected to a programmable pump and pressure sensors measured flow characteristics through the phantoms. Physiological flow simulations for patient-specific vasculature were done for six cardiac models (three different vasculatures comparing two new designs). For the coronary phantom we obtained physiologically relevant waves which oscillated between 80 and 120 mmHg and a flow rate of 125 ml/min, within the literature reported values. The pressure wave was similar with those acquired in human patients. Thus we demonstrated that 3D printed phantoms can be used not only to reproduce the correct patient anatomy for device testing in image-guided interventions, but also for physiological simulations. This has great potential to advance treatment assessment and diagnosis.

Applying systems biology methods to the study of human physiology in extreme environments

PubMed Central

2013-01-01

Systems biology is defined in this review as ‘an iterative process of computational model building and experimental model revision with the aim of understanding or simulating complex biological systems’. We propose that, in practice, systems biology rests on three pillars: computation, the omics disciplines and repeated experimental perturbation of the system of interest. The number of ethical and physiologically relevant perturbations that can be used in experiments on healthy humans is extremely limited and principally comprises exercise, nutrition, infusions (e.g. Intralipid), some drugs and altered environment. Thus, we argue that systems biology and environmental physiology are natural symbionts for those interested in a system-level understanding of human biology. However, despite excellent progress in high-altitude genetics and several proteomics studies, systems biology research into human adaptation to extreme environments is in its infancy. A brief description and overview of systems biology in its current guise is given, followed by a mini review of computational methods used for modelling biological systems. Special attention is given to high-altitude research, metabolic network reconstruction and constraint-based modelling. PMID:23849719

The Exercise and Environmental Physiology of Extravehicular Activity

NASA Technical Reports Server (NTRS)

Cowell, S. A.; Stocks, J. M.; Evans, D. G.; Simonson, S. R.; Greenleaf, J. E.; Dalton, Bonnie P. (Technical Monitor)

2000-01-01

Over the history of human expansion into space, extravehicular activity (EVA) has become indispensable for both daily living in weightlessness and for further space exploration. The physiological factors involved in the performance of extensive EVA, necessary for construction and maintenance of the International Space Station and during future human interplanetary missions, require further examination. An understanding of the physiological aspects of exercise and thermoregulation in the EVA environment will help to insure the health, safety, and efficiency of working astronauts. To that end, this review will focus on the interaction of the exercise and environmental aspects of EVA, as well as exercise during spaceflight and ground-based simulations such as bed-rest deconditioning. It will examine inflight exercise thermoregulation, and exercise, muscular strength, supine vs. seated exercise, exercise thermoregulation, and exercise in a hypobaric environment. Due to the paucity of data from controlled human research in this area, it is clear that more scientific studies are needed to insure safe and efficient extravehicular activity.

Applications of physiologically based pharmacokinetic modeling for the optimization of anti-infective therapies.

PubMed

Moss, Darren Michael; Marzolini, Catia; Rajoli, Rajith K R; Siccardi, Marco

2015-01-01

The pharmacokinetic properties of anti-infective drugs are a determinant part of treatment success. Pathogen replication is inhibited if adequate drug levels are achieved in target sites, whereas excessive drug concentrations linked to toxicity are to be avoided. Anti-infective distribution can be predicted by integrating in vitro drug properties and mathematical descriptions of human anatomy in physiologically based pharmacokinetic models. This method reduces the need for animal and human studies and is used increasingly in drug development and simulation of clinical scenario such as, for instance, drug-drug interactions, dose optimization, novel formulations and pharmacokinetics in special populations. We have assessed the relevance of physiologically based pharmacokinetic modeling in the anti-infective research field, giving an overview of mechanisms involved in model design and have suggested strategies for future applications of physiologically based pharmacokinetic models. Physiologically based pharmacokinetic modeling provides a powerful tool in anti-infective optimization, and there is now no doubt that both industry and regulatory bodies have recognized the importance of this technology. It should be acknowledged, however, that major challenges remain to be addressed and that information detailing disease group physiology and anti-infective pharmacodynamics is required if a personalized medicine approach is to be achieved.

Hydroxyl Radical Formation from HULIS and Fe(II) Interactions: Fulvic Acid-Fe(II) Complexes in Simulated and Human Lung Fluids

NASA Astrophysics Data System (ADS)

Gonzalez, D.

2017-12-01

Inhalation of fine particulate matter (PM2.5) has long been associated with adverse health outcomes. However, the causative agents and underlying mechanisms for these health effects have yet to be identified. One hypothesis is that PM2.5 deposited in the alveoli produce an excess of highly reactive radicals, leading to oxidative stress. The OH radical may be the most physiologically damaging, capable of oxidizing of lipids, proteins and DNA. Due to the variability and uncertainty in PM2.5 composition, the components that contribute to OH formation are not well understood. Soluble Fe is a component of PM2.5that produces OH under physiological conditions. Humic-like substances are water soluble organics found in biomass burning and tobacco smoke. Humic-like substances are capable of binding to Fe and enhancing OH formation, but this chemistry is not well understood. In this work, we use soil derived fulvic acid as a surrogate for Humic-like substances and investigate its effect on OH formation from Fe(II) under conditions relevant to the lungs. We use a fluorescent OH trapping probe, chemical kinetics and thermodynamic modeling to investigate OH formation from fulvic acid and Fe(II) dissolved in simulated and human lung fluids. In simulated lung fluid, we find that fulvic acid binds to Fe(II) and enhances the rate of key reactions that form OH. When fulvic acid is added to human lung fluids containing Fe(II), an enhancement of OH formation is observed. In human lung fluid, fulvic acid and metal binding proteins compete for Fe binding. These metal binding proteins are typically not found in simulated lung fluids. Results show that fulvic acid strongly binds Fe(II) and catalyzes key reactions that form OH in both simulated and human lung fluids. These results may help explain the role of Humic-like substances and Fe in oxidative stress and adverse health outcomes. Furthermore, we suggest that future studies employ simulated lung fluids containing metal binding proteins to better reflect human lung fluids.

Simulating Humans as Integral Parts of Spacecraft Missions

NASA Technical Reports Server (NTRS)

Bruins, Anthony C.; Rice, Robert; Nguyen, Lac; Nguyen, Heidi; Saito, Tim; Russell, Elaine

2006-01-01

The Collaborative-Virtual Environment Simulation Tool (C-VEST) software was developed for use in a NASA project entitled "3-D Interactive Digital Virtual Human." The project is oriented toward the use of a comprehensive suite of advanced software tools in computational simulations for the purposes of human-centered design of spacecraft missions and of the spacecraft, space suits, and other equipment to be used on the missions. The C-VEST software affords an unprecedented suite of capabilities for three-dimensional virtual-environment simulations with plug-in interfaces for physiological data, haptic interfaces, plug-and-play software, realtime control, and/or playback control. Mathematical models of the mechanics of the human body and of the aforementioned equipment are implemented in software and integrated to simulate forces exerted on and by astronauts as they work. The computational results can then support the iterative processes of design, building, and testing in applied systems engineering and integration. The results of the simulations provide guidance for devising measures to counteract effects of microgravity on the human body and for the rapid development of virtual (that is, simulated) prototypes of advanced space suits, cockpits, and robots to enhance the productivity, comfort, and safety of astronauts. The unique ability to implement human-in-the-loop immersion also makes the C-VEST software potentially valuable for use in commercial and academic settings beyond the original space-mission setting.

Teaching Real Science with a Microcomputer.

ERIC Educational Resources Information Center

Naiman, Adeline

1983-01-01

Discusses various ways science can be taught using microcomputers, including simulations/games which allow large-scale or historic experiments to be replicated on a manageable scale in a brief time. Examples of several computer programs are also presented, including "Experiments in Human Physiology,""Health Awareness…

Simulation of human plasma concentration-time profiles of the partial glucokinase activator PF-04937319 and its disproportionate N-demethylated metabolite using humanized chimeric mice and semi-physiological pharmacokinetic modeling.

PubMed

Kamimura, Hidetaka; Ito, Satoshi; Chijiwa, Hiroyuki; Okuzono, Takeshi; Ishiguro, Tomohiro; Yamamoto, Yosuke; Nishinoaki, Sho; Ninomiya, Shin-Ichi; Mitsui, Marina; Kalgutkar, Amit S; Yamazaki, Hiroshi; Suemizu, Hiroshi

2017-05-01

1. The partial glucokinase activator N,N-dimethyl-5-((2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide (PF-04937319) is biotransformed in humans to N-methyl-5-((2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide (M1), accounting for ∼65% of total exposure at steady state. 2. As the disproportionately abundant nature of M1 could not be reliably predicted from in vitro metabolism studies, we evaluated a chimeric mouse model with humanized liver on TK-NOG background for its ability to retrospectively predict human disposition of PF-04937319. Since livers of chimeric mice were enlarged by hyperplasia and contained remnant mouse hepatocytes, hepatic intrinsic clearances normalized for liver weight, metabolite formation and liver to plasma concentration ratios were plotted against the replacement index by human hepatocytes and extrapolated to those in the virtual chimeric mouse with 100% humanized liver. 3. Semi-physiological pharmacokinetic analyses using the above parameters revealed that simulated concentration curves of PF-04937319 and M1 were approximately superimposed with the observed clinical data in humans. 4. Finally, qualitative profiling of circulating metabolites in humanized chimeric mice dosed with PF-04937319 or M1 also revealed the presence of a carbinolamide metabolite, identified in the clinical study as a human-specific metabolite. The case study demonstrates that humanized chimeric mice may be potentially useful in preclinical discovery towards studying disproportionate or human-specific metabolism of drug candidates.

Verification and validation of a patient simulator for test and evaluation of a laser doppler vibrometer

NASA Astrophysics Data System (ADS)

Byrd, Kenneth A.; Yauger, Sunny

2012-06-01

In the medical community, patient simulators are used to educate and train nurses, medics and doctors in rendering dierent levels of treatment and care to various patient populations. Students have the opportunity to perform real-world medical procedures without putting any patients at risk. A new thrust for the U.S. Army RDECOM CERDEC Night Vision and Electronic Sensors Directorate (NVESD), is the use of remote sensing technologies to detect human vital signs at stando distances. This capability will provide medics with the ability to diagnose while under re in addition to helping them to prioritize the care and evacuation of battleeld casualties. A potential alternative (or precursor) to human subject testing is the use of patient simulators. This substitution (or augmenting) provides a safe and cost eective means to develop, test, and evaluate sensors without putting any human subjects at risk. In this paper, we present a generalized framework that can be used to accredit patient simulator technologies as human simulants for remote physiological monitoring (RPM). Results indicate that we were successful in using a commercial Laser Doppler Vibrometer (LDV) to exploit pulse and respiration signals from a SimMan 3G patient simulator at stando (8 meters).

Physiologic Mechanisms Underlying the Failure of the Shock Index as a Tool for Accurate Assessment of Patient Status during Progressive Simulated Hemorrhage

DTIC Science & Technology

2013-08-01

in central blood volume similar to hemorrhage in humans. Lower-body negative- pressure (LBNP) is a unique physiologic model that has been adopted to...relatively high tolerance (HT) to reduced blood volume, while 30% to 35% display low toler- ance (LT), with earlier onset of cardiovascular instability (i.e... pressure were recorded by infrared finger photoplethysmography (Finometer Blood Pressure Mon- itor, TNO-TPD Biomedical Instrumentation, Amsterdam

Alcohol-induced physiological displacements and their effects on flight-related functions.

DOT National Transportation Integrated Search

1982-03-01

Tolerances of human subjects for orthostasis and physical work were determined at a simulated altitude of 3,048 m. Orthostasis was induced with a lower body negative pressure (LBNP) device and physical work was done on a pedal ergometer. Altitude was...

Physiological investigation of automobile driver's activation index using simulated monotonous driving.

PubMed

Yamakoshi, T; Yamakoshi, K; Tanaka, S; Nogawa, M; Kusakabe, M; Kusumi, M; Tanida, K

2004-01-01

Monotonous automobile operation in our daily life may cause the lowering of what might be termed an activation state of the human body, resulting in an increased risk of an accident. We therefore propose to create a more suitable environment in-car so as to allow active operation of the vehicle, hopefully thus avoiding potentially dangerous situations during driving. In order to develop such an activation method as a final goal, we have firstly focused on the acquisition of physiological variables, including cardiovascular parameters, during presentation to the driver of a monotonous screen image, simulating autonomous travel of constant-speed on a motorway. Subsequently, we investigated the derivation of a driver's activation index. During the screen image presentation, a momentary electrical stimulation of about 1 second duration was involuntarily applied to a subject's shoulder to obtain a physiological response. We have successfully monitored various physiological variables during the image presentation, and results suggest that a peculiar pattern in the beat-by-beat change of blood pressure in response to the involuntary stimulus may be an appropriate, and feasible, index relevant to activation state.

Dynamic physiological modeling for functional diffuse optical tomography

PubMed Central

Diamond, Solomon Gilbert; Huppert, Theodore J.; Kolehmainen, Ville; Franceschini, Maria Angela; Kaipio, Jari P.; Arridge, Simon R.; Boas, David A.

2009-01-01

Diffuse optical tomography (DOT) is a noninvasive imaging technology that is sensitive to local concentration changes in oxy- and deoxyhemoglobin. When applied to functional neuroimaging, DOT measures hemodynamics in the scalp and brain that reflect competing metabolic demands and cardiovascular dynamics. The diffuse nature of near-infrared photon migration in tissue and the multitude of physiological systems that affect hemodynamics motivate the use of anatomical and physiological models to improve estimates of the functional hemodynamic response. In this paper, we present a linear state-space model for DOT analysis that models the physiological fluctuations present in the data with either static or dynamic estimation. We demonstrate the approach by using auxiliary measurements of blood pressure variability and heart rate variability as inputs to model the background physiology in DOT data. We evaluate the improvements accorded by modeling this physiology on ten human subjects with simulated functional hemodynamic responses added to the baseline physiology. Adding physiological modeling with a static estimator significantly improved estimates of the simulated functional response, and further significant improvements were achieved with a dynamic Kalman filter estimator (paired t tests, n = 10, P < 0.05). These results suggest that physiological modeling can improve DOT analysis. The further improvement with the Kalman filter encourages continued research into dynamic linear modeling of the physiology present in DOT. Cardiovascular dynamics also affect the blood-oxygen-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI). This state-space approach to DOT analysis could be extended to BOLD fMRI analysis, multimodal studies and real-time analysis. PMID:16242967

Entropy generation method to quantify thermal comfort.

PubMed

Boregowda, S C; Tiwari, S N; Chaturvedi, S K

2001-12-01

The present paper presents a thermodynamic approach to assess the quality of human-thermal environment interaction and quantify thermal comfort. The approach involves development of entropy generation term by applying second law of thermodynamics to the combined human-environment system. The entropy generation term combines both human thermal physiological responses and thermal environmental variables to provide an objective measure of thermal comfort. The original concepts and definitions form the basis for establishing the mathematical relationship between thermal comfort and entropy generation term. As a result of logic and deterministic approach, an Objective Thermal Comfort Index (OTCI) is defined and established as a function of entropy generation. In order to verify the entropy-based thermal comfort model, human thermal physiological responses due to changes in ambient conditions are simulated using a well established and validated human thermal model developed at the Institute of Environmental Research of Kansas State University (KSU). The finite element based KSU human thermal computer model is being utilized as a "Computational Environmental Chamber" to conduct series of simulations to examine the human thermal responses to different environmental conditions. The output from the simulation, which include human thermal responses and input data consisting of environmental conditions are fed into the thermal comfort model. Continuous monitoring of thermal comfort in comfortable and extreme environmental conditions is demonstrated. The Objective Thermal Comfort values obtained from the entropy-based model are validated against regression based Predicted Mean Vote (PMV) values. Using the corresponding air temperatures and vapor pressures that were used in the computer simulation in the regression equation generates the PMV values. The preliminary results indicate that the OTCI and PMV values correlate well under ideal conditions. However, an experimental study is needed in the future to fully establish the validity of the OTCI formula and the model. One of the practical applications of this index is that could it be integrated in thermal control systems to develop human-centered environmental control systems for potential use in aircraft, mass transit vehicles, intelligent building systems, and space vehicles.

Entropy generation method to quantify thermal comfort

NASA Technical Reports Server (NTRS)

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

2001-01-01

The present paper presents a thermodynamic approach to assess the quality of human-thermal environment interaction and quantify thermal comfort. The approach involves development of entropy generation term by applying second law of thermodynamics to the combined human-environment system. The entropy generation term combines both human thermal physiological responses and thermal environmental variables to provide an objective measure of thermal comfort. The original concepts and definitions form the basis for establishing the mathematical relationship between thermal comfort and entropy generation term. As a result of logic and deterministic approach, an Objective Thermal Comfort Index (OTCI) is defined and established as a function of entropy generation. In order to verify the entropy-based thermal comfort model, human thermal physiological responses due to changes in ambient conditions are simulated using a well established and validated human thermal model developed at the Institute of Environmental Research of Kansas State University (KSU). The finite element based KSU human thermal computer model is being utilized as a "Computational Environmental Chamber" to conduct series of simulations to examine the human thermal responses to different environmental conditions. The output from the simulation, which include human thermal responses and input data consisting of environmental conditions are fed into the thermal comfort model. Continuous monitoring of thermal comfort in comfortable and extreme environmental conditions is demonstrated. The Objective Thermal Comfort values obtained from the entropy-based model are validated against regression based Predicted Mean Vote (PMV) values. Using the corresponding air temperatures and vapor pressures that were used in the computer simulation in the regression equation generates the PMV values. The preliminary results indicate that the OTCI and PMV values correlate well under ideal conditions. However, an experimental study is needed in the future to fully establish the validity of the OTCI formula and the model. One of the practical applications of this index is that could it be integrated in thermal control systems to develop human-centered environmental control systems for potential use in aircraft, mass transit vehicles, intelligent building systems, and space vehicles.

Challenges in simulating the human gut for understanding the role of the microbiota in obesity.

PubMed

Aguirre, M; Venema, K

2017-02-07

There is an elevated incidence of cases of obesity worldwide. Therefore, the development of strategies to tackle this condition is of vital importance. This review focuses on the necessity of optimising in vitro systems to model human colonic fermentation in obese subjects. This may allow to increase the resolution and the physiological relevance of the information obtained from this type of studies when evaluating the potential role that the human gut microbiota plays in obesity. In light of the parameters that are currently used for the in vitro simulation of the human gut (which are mostly based on information derived from healthy subjects) and the possible difference with an obese condition, we propose to revise and improve specific standard operating procedures.

Numerical Simulation of the Flow in Vascular Grafts for Surgical Applications

NASA Astrophysics Data System (ADS)

McGah, Patrick; Aliseda, Alberto

2009-11-01

Numerical simulation of the human blood vessels, is becoming an important tool in surgical planning and research. Accurate vascular simulations might grant physicians the predictive capability to perform pre-surgical planning. We focus our attention on the implantation of vascular grafts. The high rate of failure of this common vascular interaction is intimately related to the fluid mechanics in the affected region and the subsequent wall tissue remodeling. Here, we will present our current work in developing a methodology for the numerical simulation of vascular grafts which incorporates physiologically realistic geometries and flow boundary conditions. In particular, we seek to correlate the wall shear stress and its spatial (WSSG) and temporal (OSI) variability to wall remodeling as observed in patient specific longitudinal studies. The pulsatility (Remean= 800 , Repeak= 2000, Wo = 2) of the flow gives rise to additional fluid dynamics phenomena such as instability, flow separation, transition, and unsteadiness. Our goal is to describe and evaluate their effect on the wall physiology.

Human-machine interface issues in the use of helmet-mounted displays in short conjugate simulators

NASA Astrophysics Data System (ADS)

Melzer, James E.

2011-06-01

With the introduction of helmet-mounted displays (HMD) into modern aircraft, there is a desire on the part of pilot trainees to achieve a "look and feel" for the simulation environment similar to the real flight hardware. Given this requirement for high fidelity, it may be necessary to configure - or to perhaps re-configure - the HMD for a short conjugate viewing distance and to do so without causing eye strain or other adverse physiological effects. This paper will survey the human factors literature and provide an analysis on the visual construct issues of focus and vergence which - if not properly configured for the short conjugate simulator - could cause adverse effects, which can negatively affect training.

Mathematical modeling of human cardiovascular system for simulation of orthostatic response

NASA Technical Reports Server (NTRS)

Melchior, F. M.; Srinivasan, R. S.; Charles, J. B.

1992-01-01

This paper deals with the short-term response of the human cardiovascular system to orthostatic stresses in the context of developing a mathematical model of the overall system. It discusses the physiological issues involved and how these issues have been handled in published cardiovascular models for simulation of orthostatic response. Most of the models are stimulus specific with no demonstrated capability for simulating the responses to orthostatic stimuli of different types. A comprehensive model incorporating all known phenomena related to cardiovascular regulation would greatly help to interpret the various orthostatic responses of the system in a consistent manner and to understand the interactions among its elements. This paper provides a framework for future efforts in mathematical modeling of the entire cardiovascular system.

A fuzzy logic controller for hormone administration using an implantable pump

NASA Technical Reports Server (NTRS)

Coles, L. Stephen; Wells, George H., Jr.

1994-01-01

This paper describes the requirements for a Fuzzy Logic Controller for the physiologic administration of hormones by means of a FDA-approved surgically implantable infusion pump. Results of a LabVIEW computer simulation for the administration of insulin for diabetic adult patients as well as human growth hormone for pediatric patients are presented. A VHS video tape of the simulation in action has been prepared and is available for viewing.

The electromagnetic response of human skin in the millimetre and submillimetre wave range.

PubMed

Feldman, Yuri; Puzenko, Alexander; Ben Ishai, Paul; Caduff, Andreas; Davidovich, Issak; Sakran, Fadi; Agranat, Aharon J

2009-06-07

Recent studies of the minute morphology of the skin by optical coherence tomography revealed that the sweat ducts in human skin are helically shaped tubes, filled with a conductive aqueous solution. This, together with the fact that the dielectric permittivity of the dermis is higher than that of the epidermis, brings forward the supposition that as electromagnetic entities, the sweat ducts could be regarded as low Q helical antennas. The implications of this statement were further investigated by electromagnetic simulation and experiment of the in vivo reflectivity of the skin of subjects under varying physiological conditions (Feldman et al 2008 Phys. Rev. Lett. 100 128102). The simulation and experimental results are in a good agreement and both demonstrate that sweat ducts in the skin could indeed behave as low Q antennas. Thus, the skin spectral response in the sub-Terahertz region is governed by the level of activity of the perspiration system and shows the minimum of reflectivity at some frequencies in the frequency band of 75-110 GHz. It is also correlated to physiological stress as manifested by the pulse rate and the systolic blood pressure. As such, it has the potential to become the underlying principle for remote sensing of the physiological parameters and the mental state of the examined subject.

Validation of an in vitro digestive system for studying macronutrient decomposition in humans.

PubMed

Kopf-Bolanz, Katrin A; Schwander, Flurina; Gijs, Martin; Vergères, Guy; Portmann, Reto; Egger, Lotti

2012-02-01

The digestive process transforms nutrients and bioactive compounds contained in food to physiologically active compounds. In vitro digestion systems have proven to be powerful tools for understanding and monitoring the complex transformation processes that take place during digestion. Moreover, the investigation of the physiological effects of certain nutrients demands an in vitro digestive process that is close to human physiology. In this study, human digestion was simulated with a 3-step in vitro process that was validated in depth by choosing pasteurized milk as an example of a complex food matrix. The evolution and decomposition of the macronutrients was followed over the entire digestive process to the level of intestinal enterocyte action, using protein and peptide analysis by SDS-PAGE, reversed-phase HPLC, size exclusion HPLC, and liquid chromatography-MS. The mean peptide size after in vitro digestion of pasteurized milk was 5-6 amino acids (AA). Interestingly, mostly essential AA (93.6%) were released during in vitro milk digestion, a significantly different relative distribution compared to the total essential AA concentration of bovine milk (44.5%). All TG were degraded to FFA and monoacylglycerols. Herein, we present a human in vitro digestion model validated for its ability to degrade the macronutrients of dairy products comparable to physiological ranges. It is suited to be used in combination with a human intestinal cell culture system, allowing ex vivo bioavailability measurements and assessment of the bioactive properties of food components.

Analogs of microgravity: head-down tilt and water immersion.

PubMed

Watenpaugh, Donald E

2016-04-15

This article briefly reviews the fidelity of ground-based methods used to simulate human existence in weightlessness (spaceflight). These methods include horizontal bed rest (BR), head-down tilt bed rest (HDT), head-out water immersion (WI), and head-out dry immersion (DI; immersion with an impermeable elastic cloth barrier between subject and water). Among these, HDT has become by far the most commonly used method, especially for longer studies. DI is less common but well accepted for long-duration studies. Very few studies exist that attempt to validate a specific simulation mode against actual microgravity. Many fundamental physical, and thus physiological, differences exist between microgravity and our methods to simulate it, and between the different methods. Also, although weightlessness is the salient feature of spaceflight, several ancillary factors of space travel complicate Earth-based simulation. In spite of these discrepancies and complications, the analogs duplicate many responses to 0 G reasonably well. As we learn more about responses to microgravity and spaceflight, investigators will continue to fine-tune simulation methods to optimize accuracy and applicability. Copyright © 2016 the American Physiological Society.

Dynamic Simulation and Analysis of Human Walking Mechanism

NASA Astrophysics Data System (ADS)

Azahari, Athirah; Siswanto, W. A.; Ngali, M. Z.; Salleh, S. Md.; Yusup, Eliza M.

2017-01-01

Behaviour such as gait or posture may affect a person with the physiological condition during daily activities. The characteristic of human gait cycle phase is one of the important parameter which used to described the human movement whether it is in normal gait or abnormal gait. This research investigates four types of crouch walking (upright, interpolated, crouched and severe) by simulation approach. The assessment are conducting by looking the parameters of hamstring muscle joint, knee joint and ankle joint. The analysis results show that based on gait analysis approach, the crouch walking have a weak pattern of walking and postures. Short hamstring and knee joint is the most influence factor contributing to the crouch walking due to excessive hip flexion that typically accompanies knee flexion.

Numerical simulation of gender differences in a long-term microgravity exposure

NASA Astrophysics Data System (ADS)

Perez-Poch, Antoni

The objective of this work is to analyse and simulate gender differences when individuals are exposed to long-term microgravity. Risk probability of a health impairment which may put in jeopardy a long-term mission is also evaluated. Computer simulations are becoming a promising research line of work, as physiological models become more and more sophisticated and reliable. Technological advances in state-of-the-art hardware technology and software allow nowadays for better and more accurate simulations of complex phenomena, such as the response of the human cardiovascular system to long-term exposure to microgravity. Experimental data for long-term missions are difficult to achieve and reproduce, therefore the predictions of computer simulations are of a major importance in this field. Our approach is based on a previous model developed and implemented in our laboratory (NELME: Numerical Evaluation of Long-term Microgravity Effects). The software simulates the behaviour of the cardiovascular system and different human organs, has a modular architecture, and allows to introduce perturbations such as physical exercise or countermeasures. The implementation is based on a complex electricallike model of this control system, using inexpensive software development frameworks, and has been tested and validated with the available experimental data. Gender differences have been implemented for this specific work, as an adjustment of a number of parameters that are included in the model. Women versus men physiological differences have been therefore taken into account, based upon estimations from the physiology bibliography. A number of simulations have been carried out for long-term exposure to microgravity. Gravity varying from Earth-based to zero, and time exposure are the two main variables involved in the construction of results, including responses to patterns of physical aerobical exercise, and also thermal stress simulating an extra-vehicular activity. Results show that significant differences appear between men and women physiological response after long-term exposure (more than three months) to microgravity. Risk evaluation for every gender, and specific risk thresholds are provided. Initial results are compatible with the existing data, and provide unique information regarding different patterns of microgravity exposure. We conclude that computer-based models such us NELME are a promising line of work to predict health risks in long-term missions. More experimental work is needed to adjust some parameters of the model. This work may be seen as another contribution to a better understanding of the underlying processes involved for both women in man adaptation to long-term microgravity.

Human Behaviour in Long-Term Missions

NASA Technical Reports Server (NTRS)

1997-01-01

In this session, Session WP1, the discussion focuses on the following topics: Psychological Support for International Space Station Mission; Psycho-social Training for Man in Space; Study of the Physiological Adaptation of the Crew During A 135-Day Space Simulation; Interpersonal Relationships in Space Simulation, The Long-Term Bed Rest in Head-Down Tilt Position; Psychological Adaptation in Groups of Varying Sizes and Environments; Deviance Among Expeditioners, Defining the Off-Nominal Act in Space and Polar Field Analogs; Getting Effective Sleep in the Space-Station Environment; Human Sleep and Circadian Rhythms are Altered During Spaceflight; and Methodological Approach to Study of Cosmonauts Errors and Its Instrumental Support.

Novel starch based nano scale enteric coatings from soybean meal for colon-specific delivery

USDA-ARS?s Scientific Manuscript database

Soybean meal was used to isolate resistant starch and produce nanoparticles, which could be potential coating materials for colonic nutrient and drug deliveries. The nanoparticles were in 40 +/- 33.2 nm ranges. These nanoparticles were stable under simulated human physiological conditions. The deg...

A Test Fixture for Simulating Human Limb Physiology and Soft Tissue Biomechanics

DTIC Science & Technology

1989-04-14

Food and Drug Administration (FDA) has not promu!gated performance standards for vital signs monitors that determine blood pressure and heart rate...static char answer[] = "" double f~ttnun~pts, single, doubleit, triple; int single_ -leftover, doubleit I eftover , triple-Leftover; double sin

Mr. Vetro, a Collective Simulation Cyberlearning Infrastructure for Science Education

ERIC Educational Resources Information Center

Ioannidou, Andri; Repenning, Alexander

2010-01-01

The comprehension of interdependent complex systems, which is part of state and national standards, is an enormous challenge for learners. In traditional physiology teaching materials, which structure the human body into decoupled subsystems (e.g., respiratory and cardiovascular) isolated in separate chapters, there is a ubiquitous absence of…

Autonomic physiological data associated with simulator discomfort

NASA Technical Reports Server (NTRS)

Miller, James C.; Sharkey, Thomas J.; Graham, Glenna A.; Mccauley, Michael E.

1993-01-01

The development of a physiological monitoring capability for the Army's advanced helicopter simulator facility is reported. Additionally, preliminary physiological data is presented. Our objective was to demonstrate the sensitivity of physiological measures in this simulator to self-reported simulator sickness. The data suggested that heart period, hypergastria, and skin conductance level were more sensitive to simulator sickness than were vagal tone and normal electrogastric activity.

Anatomically realistic multiscale models of normal and abnormal gastrointestinal electrical activity

PubMed Central

Cheng, Leo K; Komuro, Rie; Austin, Travis M; Buist, Martin L; Pullan, Andrew J

2007-01-01

One of the major aims of the International Union of Physiological Sciences (IUPS) Physiome Project is to develop multiscale mathematical and computer models that can be used to help understand human health. We present here a small facet of this broad plan that applies to the gastrointestinal system. Specifically, we present an anatomically and physiologically based modelling framework that is capable of simulating normal and pathological electrical activity within the stomach and small intestine. The continuum models used within this framework have been created using anatomical information derived from common medical imaging modalities and data from the Visible Human Project. These models explicitly incorporate the various smooth muscle layers and networks of interstitial cells of Cajal (ICC) that are known to exist within the walls of the stomach and small bowel. Electrical activity within individual ICCs and smooth muscle cells is simulated using a previously published simplified representation of the cell level electrical activity. This simulated cell level activity is incorporated into a bidomain representation of the tissue, allowing electrical activity of the entire stomach or intestine to be simulated in the anatomically derived models. This electrical modelling framework successfully replicates many of the qualitative features of the slow wave activity within the stomach and intestine and has also been used to investigate activity associated with functional uncoupling of the stomach. PMID:17457969

A physiologically based pharmacokinetic model for developmental exposure to BDE-47 in rats

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

Emond, Claude, E-mail: claude.emond@umontreal.c; BioSimulation Consulting Inc., Newark, DE 19711; Raymer, James H.

2010-02-01

Polybrominated diphenyl ethers (PBDEs) are used commercially as additive flame retardants and have been shown to transfer into environmental compartments, where they have the potential to bioaccumulate in wildlife and humans. Of the 209 possible PBDEs, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) is usually the dominant congener found in human blood and milk samples. BDE-47 has been shown to have endocrine activity and produce developmental, reproductive, and neurotoxic effects. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for BDE-47 in male and female (pregnant and non-pregnant) adult rats to facilitate investigations of developmental exposure. This model consistsmore » of eight compartments: liver, brain, adipose tissue, kidney, placenta, fetus, blood, and the rest of the body. Concentrations of BDE-47 from the literature and from maternal-fetal pharmacokinetic studies conducted at RTI International were used to parameterize and evaluate the model. The results showed that the model simulated BDE-47 tissue concentrations in adult male, maternal, and fetal compartments within the standard deviations of the experimental data. The model's ability to estimate BDE-47 concentrations in the fetus after maternal exposure will be useful to design in utero exposure/effect studies. This PBPK model is the first one designed for any PBDE pharmaco/toxicokinetic description. The next steps will be to expand this model to simulate BDE-47 pharmacokinetics and distributions across species (mice), and then extrapolate it to humans. After mouse and human model development, additional PBDE congeners will be incorporated into the model and simulated as a mixture.« less

Effects of septum and pericardium on heart-lung interactions in a cardiopulmonary simulation model.

PubMed

Karamolegkos, Nikolaos; Albanese, Antonio; Chbat, Nicolas W

2017-07-01

Mechanical heart-lung interactions are often overlooked in clinical settings. However, their impact on cardiac function can be quite significant. Mechanistic physiology-based models can provide invaluable insights into such cardiorespiratory interactions, which occur not only under external mechanical ventilatory support but in normal physiology as well. In this work, we focus on the cardiac component of a previously developed mathematical model of the human cardiopulmonary system, aiming to improve the model's response to the intrathoracic pressure variations that are associated with the respiratory cycle. Interventricular septum and pericardial membrane are integrated into the existing model. Their effect on the overall cardiac response is explained by means of comparison against simulation results from the original model as well as experimental data from literature.

A Simulator for the Respiratory Tree in Healthy Subjects Derived from Continued Fractions Expansions

NASA Astrophysics Data System (ADS)

Muntean, Ionuţ; Ionescu, Clara; Naşcu, Ioan

2009-04-01

Taking into account the self-similar recurrent geometrical structure of the human respiratory tree, the total respiratory impedance can be represented using an electrical equivalent of a ladder network model. In this paper, the parameters of the respiratory tree are employed in simulation, based on clinical insight and morphology. Once the transfer function of the total input impedance model is calculated, it is further interpreted in its continued fraction expansion form. The purpose is to compare the ladder network structure with the continuous fraction expansion form of the impedance. The results are supporting the theory of fractional-order impedance appearance (also known as constant-phase behaviour) and help understanding the mathematical and morphological basis for constructing a physiology-based simulator of the human lungs.

Development of life sciences equipment for microgravity and hypergravity simulation

NASA Technical Reports Server (NTRS)

Mulenburg, G. M.; Evans, J.; Vasques, M.; Gundo, D. P.; Griffith, J. B.; Harper, J.; Skundberg, T.

1994-01-01

The mission of the Life Science Division at the NASA Ames Research Center is to investigate the effects of gravity on living systems in the spectrum from cells to humans. The range of these investigations is from microgravity, as experienced in space, to Earth's gravity, and hypergravity. Exposure to microgravity causes many physiological changes in humans and other mammals including a headward shift of body fluids, atrophy of muscles - especially the large muscles of the legs - and changes in bone and mineral metabolism. The high cost and limited opportunity for research experiments in space create a need to perform ground based simulation experiments on Earth. Models that simulate microgravity are used to help identify and quantify these changes, to investigate the mechanisms causing these changes and, in some cases, to develop countermeasures.

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

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

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

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

Reproduction in the space environment: Part I. Animal reproductive studies

NASA Technical Reports Server (NTRS)

Santy, P. A.; Jennings, R. T.; Craigie, D.

1990-01-01

Mankind's exploration and colonization of the frontier of space will ultimately depend on men's and women's ability to live, work, and reproduce in the space environment. This paper reviews animal studies, from microorganisms to mammals, done in space or under space-simulated conditions, which identify some of the key areas which might interfere with human reproductive physiology and/or embryonic development. Those space environmental factors which impacted almost all species included: microgravity, artificial gravity, radiation, and closed life support systems. These factors may act independently and in combination to produce their effects. To date, there have been no studies which have looked at the entire process of reproduction in any animal species. This type of investigation will be critical in understanding and preventing the problems which will affect human reproduction. Part II will discuss these problems directly as they relate to human physiology.

Method and Apparatus for Encouraging Physiological Self-Regulation Through Modulation of an Operator's Control Input to a Video Game or Training Simulator

NASA Technical Reports Server (NTRS)

Palsson, Olafur S. (Inventor); Harris, Randall L., Sr. (Inventor); Pope, Alan T. (Inventor)

2002-01-01

Apparatus and methods for modulating the control authority (i.e., control function) of a computer simulation or game input device (e.g., joystick, button control) using physiological information so as to affect the user's ability to impact or control the simulation or game with the input device. One aspect is to use the present invention, along with a computer simulation or game, to affect physiological state or physiological self-regulation according to some programmed criterion (e.g., increase, decrease, or maintain) in order to perform better at the game task. When the affected physiological state or physiological self-regulation is the target of self-regulation or biofeedback training, the simulation or game play reinforces therapeutic changes in the physiological signal(s).

Integrative approaches to computational biomedicine

PubMed Central

Coveney, Peter V.; Diaz-Zuccarini, Vanessa; Graf, Norbert; Hunter, Peter; Kohl, Peter; Tegner, Jesper; Viceconti, Marco

2013-01-01

The new discipline of computational biomedicine is concerned with the application of computer-based techniques and particularly modelling and simulation to human health. Since 2007, this discipline has been synonymous, in Europe, with the name given to the European Union's ambitious investment in integrating these techniques with the eventual aim of modelling the human body as a whole: the virtual physiological human. This programme and its successors are expected, over the next decades, to transform the study and practice of healthcare, moving it towards the priorities known as ‘4P's’: predictive, preventative, personalized and participatory medicine.

Simulation of Plant Physiological Process Using Fuzzy Variables

Treesearch

Daniel L. Schmoldt

1991-01-01

Qualitative modelling can help us understand and project effects of multiple stresses on trees. It is not practical to collect and correlate empirical data for all combinations of plant/environments and human/climate stresses, especially for mature trees in natural settings. Therefore, a mechanistic model was developed to describe ecophysiological processes. This model...

Physiological and behavioural responses of sheep to simulated sea transport motions

USDA-ARS?s Scientific Manuscript database

The motion of ships can cause discomfort and stress in humans, but little is known about the impact on sheep welfare, despite many sheep travelling long distances by ship during live export. We tested whether exposing sheep to roll (side to side movement), heave (up and down movement) and pitch (fro...

Experiments On Flow In A Coronary Artery

NASA Technical Reports Server (NTRS)

Back, Lloyd H.; Kwack, Eug-Yon; Liem, Timothy K.; Crawford, Donald W.

1993-01-01

Report describes experiments on simulated flow of blood in atherosclerotic human coronary artery. Experiments performed on polyurethane cast made from S-shaped coronary artery of cadaver. Sucrose solution with viscosity of blood pumped through cast at physiologically realistic rates, and flow made pulsatile by mechanism alternately compressing and releasing elastic tube just upstream of cast.

Finite element models of the human shoulder complex: a review of their clinical implications and modelling techniques.

PubMed

Zheng, Manxu; Zou, Zhenmin; Bartolo, Paulo Jorge Da Silva; Peach, Chris; Ren, Lei

2017-02-01

The human shoulder is a complicated musculoskeletal structure and is a perfect compromise between mobility and stability. The objective of this paper is to provide a thorough review of previous finite element (FE) studies in biomechanics of the human shoulder complex. Those FE studies to investigate shoulder biomechanics have been reviewed according to the physiological and clinical problems addressed: glenohumeral joint stability, rotator cuff tears, joint capsular and labral defects and shoulder arthroplasty. The major findings, limitations, potential clinical applications and modelling techniques of those FE studies are critically discussed. The main challenges faced in order to accurately represent the realistic physiological functions of the shoulder mechanism in FE simulations involve (1) subject-specific representation of the anisotropic nonhomogeneous material properties of the shoulder tissues in both healthy and pathological conditions; (2) definition of boundary and loading conditions based on individualised physiological data; (3) more comprehensive modelling describing the whole shoulder complex including appropriate three-dimensional (3D) representation of all major shoulder hard tissues and soft tissues and their delicate interactions; (4) rigorous in vivo experimental validation of FE simulation results. Fully validated shoulder FE models would greatly enhance our understanding of the aetiology of shoulder disorders, and hence facilitate the development of more efficient clinical diagnoses, non-surgical and surgical treatments, as well as shoulder orthotics and prosthetics. © 2016 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd. © 2016 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.

Human System Simulation in Support of Human Performance Technical Basis at NPPs

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

David Gertman; Katya Le Blanc; alan mecham

2010-06-01

This paper focuses on strategies and progress toward establishing the Idaho National Laboratory’s (INL’s) Human Systems Simulator Laboratory at the Center for Advanced Energy Studies (CAES), a consortium of Idaho State Universities. The INL is one of the National Laboratories of the US Department of Energy. One of the first planned applications for the Human Systems Simulator Laboratory is implementation of a dynamic nuclear power plant simulation (NPP) where studies of operator workload, situation awareness, performance and preference will be carried out in simulated control rooms including nuclear power plant control rooms. Simulation offers a means by which to reviewmore » operational concepts, improve design practices and provide a technical basis for licensing decisions. In preparation for the next generation power plant and current government and industry efforts in support of light water reactor sustainability, human operators will be attached to a suite of physiological measurement instruments and, in combination with traditional Human Factors Measurement techniques, carry out control room tasks in simulated advanced digital and hybrid analog/digital control rooms. The current focus of the Human Systems Simulator Laboratory is building core competence in quantitative and qualitative measurements of situation awareness and workload. Of particular interest is whether introduction of digital systems including automated procedures has the potential to reduce workload and enhance safety while improving situation awareness or whether workload is merely shifted and situation awareness is modified in yet to be determined ways. Data analysis is carried out by engineers and scientists and includes measures of the physical and neurological correlates of human performance. The current approach supports a user-centered design philosophy (see ISO 13407 “Human Centered Design Process for Interactive Systems, 1999) wherein the context for task performance along with the requirements of the end-user are taken into account during the design process and the validity of design is determined through testing of real end users« less

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

Corley, Richard A.; Kabilan, Senthil; Kuprat, Andrew P.

Coupling computational fluid dynamics (CFD) with physiologically based pharmacokinetic (PBPK) models is 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. Historically, these models were limited to discrete regions of the respiratory system. CFD/PBPK models have now been developed for the rat, monkey, and human that encompass airways from the nose or mouth to the lung. A PBPK model previously developed to describe acrolein uptake in nasal tissues was adapted to the extended airway models as an example application. Model parameters for each anatomicmore » region were obtained from the literature, measured directly, or estimated from published data. Airflow and site-specific acrolein uptake patterns were determined under steadystate inhalation conditions to provide direct comparisons with prior data and nasalonly simulations. Results confirmed that regional uptake was dependent upon airflow rates and acrolein concentrations with nasal extraction efficiencies predicted to be greatest in the rat, followed by the monkey, then the human. For human oral-breathing simulations, acrolein uptake rates in oropharyngeal and laryngeal tissues were comparable to nasal tissues following nasal breathing under the same exposure conditions. For both breathing modes, higher uptake rates were predicted for lower tracheo-bronchial tissues of humans than either the rat or monkey. These extended airway models provide a unique foundation for comparing dosimetry across a significantly more extensive range of conducting airways in the rat, monkey, and human than prior CFD models.« less

Human physiological adaptation to extended Space Flight and its implications for Space Station

NASA Technical Reports Server (NTRS)

Kutyna, F. A.; Shumate, W. H.

1985-01-01

Current work evaluating short-term space flight physiological data on the homeostatic changes due to weightlessness is presented as a means of anticipating Space Station long-term effects. An integrated systems analysis of current data shows a vestibulo-sensory adaptation within days; a loss of body mass, fluids, and electrolytes, stabilizing in a month; and a loss in red cell mass over a month. But bone demineralization which did not level off is seen as the biggest concern. Computer algorithms have been developed to simulate the human adaptation to weightlessness. So far these paradigms have been backed up by flight data and it is hoped that they will provide valuable information for future Space Station design. A series of explanatory schematics is attached.

Contribution of blood oxygen and carbon dioxide sensing to the energetic optimization of human walking.

PubMed

Wong, Jeremy D; O'Connor, Shawn M; Selinger, Jessica C; Donelan, J Maxwell

2017-08-01

People can adapt their gait to minimize energetic cost, indicating that walking's neural control has access to ongoing measurements of the body's energy use. In this study we tested the hypothesis that an important source of energetic cost measurements arises from blood gas receptors that are sensitive to O 2 and CO 2 concentrations. These receptors are known to play a role in regulating other physiological processes related to energy consumption, such as ventilation rate. Given the role of O 2 and CO 2 in oxidative metabolism, sensing their levels can provide an accurate estimate of the body's total energy use. To test our hypothesis, we simulated an added energetic cost for blood gas receptors that depended on a subject's step frequency and determined if subjects changed their behavior in response to this simulated cost. These energetic costs were simulated by controlling inspired gas concentrations to decrease the circulating levels of O 2 and increase CO 2 We found this blood gas control to be effective at shifting the step frequency that minimized the ventilation rate and perceived exertion away from the normally preferred frequency, indicating that these receptors provide the nervous system with strong physiological and psychological signals. However, rather than adapt their preferred step frequency toward these lower simulated costs, subjects persevered at their normally preferred frequency even after extensive experience with the new simulated costs. These results suggest that blood gas receptors play a negligible role in sensing energetic cost for the purpose of optimizing gait. NEW & NOTEWORTHY Human gait adaptation implies that the nervous system senses energetic cost, yet this signal is unknown. We tested the hypothesis that the blood gas receptors sense cost for gait optimization by controlling blood O 2 and CO 2 with step frequency as people walked. At the simulated energetic minimum, ventilation and perceived exertion were lowest, yet subjects preferred walking at their original frequency. This suggests that blood gas receptors are not critical for sensing cost during gait. Copyright © 2017 the American Physiological Society.

On-Line Analysis of Physiologic and Neurobehavioral Variables During Long-Duration Space Missions

NASA Technical Reports Server (NTRS)

Brown, Emery N.

1999-01-01

The goal of this project is to develop reliable statistical algorithms for on-line analysis of physiologic and neurobehavioral variables monitored during long-duration space missions. Maintenance of physiologic and neurobehavioral homeostasis during long-duration space missions is crucial for ensuring optimal crew performance. If countermeasures are not applied, alterations in homeostasis will occur in nearly all-physiologic systems. During such missions data from most of these systems will be either continually and/or continuously monitored. Therefore, if these data can be analyzed as they are acquired and the status of these systems can be continually assessed, then once alterations are detected, appropriate countermeasures can be applied to correct them. One of the most important physiologic systems in which to maintain homeostasis during long-duration missions is the circadian system. To detect and treat alterations in circadian physiology during long duration space missions requires development of: 1) a ground-based protocol to assess the status of the circadian system under the light-dark environment in which crews in space will typically work; and 2) appropriate statistical methods to make this assessment. The protocol in Project 1, Circadian Entrainment, Sleep-Wake Regulation and Neurobehavioral will study human volunteers under the simulated light-dark environment of long-duration space missions. Therefore, we propose to develop statistical models to characterize in near real time circadian and neurobehavioral physiology under these conditions. The specific aims of this project are to test the hypotheses that: 1) Dynamic statistical methods based on the Kronauer model of the human circadian system can be developed to estimate circadian phase, period, amplitude from core-temperature data collected under simulated light- dark conditions of long-duration space missions. 2) Analytic formulae and numerical algorithms can be developed to compute the error in the estimates of circadian phase, period and amplitude determined from the data in Specific Aim 1. 3) Statistical models can detect reliably in near real- time (daily) significant alternations in the circadian physiology of individual subjects by analyzing the circadian and neurobehavioral data collected in Project 1. 4) Criteria can be developed using the Kronauer model and the recently developed Jewett model of cognitive -performance and subjective alertness to define altered circadian and neurobehavioral physiology and to set conditions for immediate administration of countermeasures.

Identification of intestinal loss of a drug through physiologically based pharmacokinetic simulation of plasma concentration-time profiles.

PubMed

Peters, Sheila Annie

2008-01-01

Despite recent advances in understanding of the role of the gut as a metabolizing organ, recognition of gut wall metabolism and/or other factors contributing to intestinal loss of a compound has been a challenging task due to the lack of well characterized methods to distinguish it from first-pass hepatic extraction. The implications of identifying intestinal loss of a compound in drug discovery and development can be enormous. Physiologically based pharmacokinetic (PBPK) simulations of pharmacokinetic profiles provide a simple, reliable and cost-effective way to understand the mechanisms underlying pharmacokinetic processes. The purpose of this article is to demonstrate the application of PBPK simulations in bringing to light intestinal loss of orally administered drugs, using two example compounds: verapamil and an in-house compound that is no longer in development (referred to as compound A in this article). A generic PBPK model, built in-house using MATLAB software and incorporating absorption, metabolism, distribution, biliary and renal elimination models, was employed for simulation of concentration-time profiles. Modulation of intrinsic hepatic clearance and tissue distribution parameters in the generic PBPK model was done to achieve a good fit to the observed intravenous pharmacokinetic profiles of the compounds studied. These optimized clearance and distribution parameters are expected to be invariant across different routes of administration, as long as the kinetics are linear, and were therefore employed to simulate the oral profiles of the compounds. For compounds with reasonably good solubility and permeability, an area under the concentration-time curve for the simulated oral profile that far exceeded the observed would indicate some kind of loss in the intestine. PBPK simulations applied to compound A showed substantial loss of the compound in the gastrointestinal tract in humans but not in rats. This accounted for the lower bioavailability of the compound in humans than in rats. PBPK simulations of verapamil identified gut wall metabolism, well established in the literature, and showed large interspecies differences with respect to both gut wall metabolism and drug-induced delays in gastric emptying. Mechanistic insights provided by PBPK simulations can be very valuable in answering vital questions in drug discovery and development. However, such applications of PBPK models are limited by the lack of accurate inputs for clearance and distribution. This article demonstrates a successful application of PBPK simulations to identify and quantify intestinal loss of two model compounds in rats and humans. The limitation of inaccurate inputs for the clearance and distribution parameters was overcome by optimizing these parameters through fitting intravenous profiles. The study also demonstrated that the large interspecies differences associated with gut wall metabolism and gastric emptying, evident for the compounds studied, make animal model extrapolations to humans unreliable. It is therefore important to do PBPK simulations of human pharmacokinetic profiles to understand the relevance of intestinal loss of a compound in humans.

Generating Pedestrian Trajectories Consistent with the Fundamental Diagram Based on Physiological and Psychological Factors

PubMed Central

Narang, Sahil; Best, Andrew; Curtis, Sean; Manocha, Dinesh

2015-01-01

Pedestrian crowds often have been modeled as many-particle system including microscopic multi-agent simulators. One of the key challenges is to unearth governing principles that can model pedestrian movement, and use them to reproduce paths and behaviors that are frequently observed in human crowds. To that effect, we present a novel crowd simulation algorithm that generates pedestrian trajectories that exhibit the speed-density relationships expressed by the Fundamental Diagram. Our approach is based on biomechanical principles and psychological factors. The overall formulation results in better utilization of free space by the pedestrians and can be easily combined with well-known multi-agent simulation techniques with little computational overhead. We are able to generate human-like dense crowd behaviors in large indoor and outdoor environments and validate the results with captured real-world crowd trajectories. PMID:25875932

Animal research in microgravity and flight environment: lessons from the past for the future.

PubMed

Demaria-Pesce, V H

1995-01-01

The use of animals, and more particularly the use of non-human primates, takes on importance when studying the physiological responses involved in the adaptation to changes in gravitational loading. The "Rhesus project", now canceled, was a joint program between CNES and NASA designed to carry out simultaneous experiments of various physiological disciplines using the Rhesus monkey as a human surrogate. The choice of this species was supported by several strong arguments such as the possibility of studying several physiological systems without over-instrumenting, as well as the morphological and phylogenetical closeness with man. Within this framework, building the inflight animal facilities necessary to achieve the ambitious scientific program that was established, required state of art design and technology. Spacelab flight simulations were conducted with the goal both to obtain baseline data and to evaluate the impact of the cabin environment on the circadian timekeeping system which is involved in the regulation of almost all physiological functions and behavior. Even if this project would never fly, the results from these experiments have been a source of thoughts and lessons for the future animal research in microgravity.

XCAT/DRASIM: a realistic CT/human-model simulation package

NASA Astrophysics Data System (ADS)

Fung, George S. K.; Stierstorfer, Karl; Segars, W. Paul; Taguchi, Katsuyuki; Flohr, Thomas G.; Tsui, Benjamin M. W.

2011-03-01

The aim of this research is to develop a complete CT/human-model simulation package by integrating the 4D eXtended CArdiac-Torso (XCAT) phantom, a computer generated NURBS surface based phantom that provides a realistic model of human anatomy and respiratory and cardiac motions, and the DRASIM (Siemens Healthcare) CT-data simulation program. Unlike other CT simulation tools which are based on simple mathematical primitives or voxelized phantoms, this new simulation package has the advantages of utilizing a realistic model of human anatomy and physiological motions without voxelization and with accurate modeling of the characteristics of clinical Siemens CT systems. First, we incorporated the 4D XCAT anatomy and motion models into DRASIM by implementing a new library which consists of functions to read-in the NURBS surfaces of anatomical objects and their overlapping order and material properties in the XCAT phantom. Second, we incorporated an efficient ray-tracing algorithm for line integral calculation in DRASIM by computing the intersection points of the rays cast from the x-ray source to the detector elements through the NURBS surfaces of the multiple XCAT anatomical objects along the ray paths. Third, we evaluated the integrated simulation package by performing a number of sample simulations of multiple x-ray projections from different views followed by image reconstruction. The initial simulation results were found to be promising by qualitative evaluation. In conclusion, we have developed a unique CT/human-model simulation package which has great potential as a tool in the design and optimization of CT scanners, and the development of scanning protocols and image reconstruction methods for improving CT image quality and reducing radiation dose.

A review: Functional near infrared spectroscopy evaluation in muscle tissues using Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Halim, A. A. A.; Laili, M. H.; Salikin, M. S.; Rusop, M.

2018-05-01

Monte Carlo Simulation has advanced their quantification based on number of the photon counting to solve the propagation of light inside the tissues including the absorption, scattering coefficient and act as preliminary study for functional near infrared application. The goal of this paper is to identify the optical properties using Monte Carlo simulation for non-invasive functional near infrared spectroscopy (fNIRS) evaluation of penetration depth in human muscle. This paper will describe the NIRS principle and the basis for its proposed used in Monte Carlo simulation which focused on several important parameters include ATP, ADP and relate with blow flow and oxygen content at certain exercise intensity. This will cover the advantages and limitation of such application upon this simulation. This result may help us to prove that our human muscle is transparent to this near infrared region and could deliver a lot of information regarding to the oxygenation level in human muscle. Thus, this might be useful for non-invasive technique for detecting oxygen status in muscle from living people either athletes or working people and allowing a lots of investigation muscle physiology in future.

Development and Validation of a Bioreactor System for Dynamic Loading and Mechanical Characterization of Whole Human Intervertebral Discs in Organ Culture

PubMed Central

Walter, BA; Illien-Junger, S; Nasser, P; Hecht, AC; Iatridis, JC

2014-01-01

Intervertebral disc (IVD) degeneration is a common cause of back pain, and attempts to develop therapies are frustrated by lack of model systems that mimic the human condition. Human IVD organ culture models can address this gap, yet current models are limited since vertebral endplates are removed to maintain cell viability, physiological loading is not applied, and mechanical behaviors are not measured. This study aimed to (i) establish a method for isolating human IVDs from autopsy with intact vertebral endplates, and (ii) develop and validate an organ culture loading system for human or bovine IVDs. Human IVDs with intact endplates were isolated from cadavers within 48 hours of death and cultured for up to 21 days. IVDs remained viable with ~80% cell viability in nucleus and annulus regions. A dynamic loading system was designed and built with the capacity to culture 9 bovine or 6 human IVDs simultaneously while applying simulated physiologic loads (maximum force: 4kN) and measuring IVD mechanical behaviors. The loading system accurately applied dynamic loading regimes (RMS error <2.5N and total harmonic distortion <2.45%), and precisely evaluated mechanical behavior of rubber and bovine IVDs. Bovine IVDs maintained their mechanical behavior and retained >85% viable cells throughout the 3 week culture period. This organ culture loading system can closely mimic physiological conditions and be used to investigate response of living human and bovine IVDs to mechanical and chemical challenges and to screen therapeutic repair techniques. PMID:24725441

Absolute electrical impedance tomography (aEIT) guided ventilation therapy in critical care patients: simulations and future trends.

PubMed

Denaï, Mouloud A; Mahfouf, Mahdi; Mohamad-Samuri, Suzani; Panoutsos, George; Brown, Brian H; Mills, Gary H

2010-05-01

Thoracic electrical impedance tomography (EIT) is a noninvasive, radiation-free monitoring technique whose aim is to reconstruct a cross-sectional image of the internal spatial distribution of conductivity from electrical measurements made by injecting small alternating currents via an electrode array placed on the surface of the thorax. The purpose of this paper is to discuss the fundamentals of EIT and demonstrate the principles of mechanical ventilation, lung recruitment, and EIT imaging on a comprehensive physiological model, which combines a model of respiratory mechanics, a model of the human lung absolute resistivity as a function of air content, and a 2-D finite-element mesh of the thorax to simulate EIT image reconstruction during mechanical ventilation. The overall model gives a good understanding of respiratory physiology and EIT monitoring techniques in mechanically ventilated patients. The model proposed here was able to reproduce consistent images of ventilation distribution in simulated acutely injured and collapsed lung conditions. A new advisory system architecture integrating a previously developed data-driven physiological model for continuous and noninvasive predictions of blood gas parameters with the regional lung function data/information generated from absolute EIT (aEIT) is proposed for monitoring and ventilator therapy management of critical care patients.

Bone-Like Hydroxyapatite Formation in Human Blood

ERIC Educational Resources Information Center

Titov, Anatoly T.; Larionov, Peter M.; Ivanova, Alexandra S.; Zaikovskii, Vladimir I.; Chernyavskiy, Mikhail A.

2016-01-01

The purpose of this study was to prove the mechanism of mineralization, when hydroxyapatite (HAP) is formed in blood plasma. These observations were substantiated by in vitro simulation of HAP crystallization in the plasma of healthy adults in a controllable quasi-physiological environment (T = 37°C, pH = 7.4) and at concentrations of dissolved Ca…

A Physiological Signal Transmission Model to be Used for Specific Diagnosis of Cochlear Impairments

NASA Astrophysics Data System (ADS)

Saremi, Amin; Stenfelt, Stefan

2011-11-01

Many of the sophisticated characteristics of human auditory system are attributed to cochlea. Also, most of patients with a hearing loss suffer from impairments that originate from cochlea (sensorineural). Despite this, today's clinical diagnosis methods do not probe the specific origins of such cochlear lesions. The aim of this research is to introduce a physiological signal transmission model to be clinically used as a tool for diagnosis of cochlear losses. This model enables simulation of different bio-mechano-electrical processes which occur in the auditory organ of Corti inside the cochlea. What makes this model different from many available computational models is its loyalty to physiology since the ultimate goal is to model each single physiological phenomenon. This includes passive BM vibration, outer hair cells' performances such as nonlinear mechanoelectrical transduction (MET), active amplifications by somatic motor, as well as vibration to neural conversion at the inner hair cells.

Mathematical modeling of human brain physiological data

NASA Astrophysics Data System (ADS)

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

2013-12-01

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

Real-time human-robot interaction underlying neurorobotic trust and intent recognition.

PubMed

Bray, Laurence C Jayet; Anumandla, Sridhar R; Thibeault, Corey M; Hoang, Roger V; Goodman, Philip H; Dascalu, Sergiu M; Bryant, Bobby D; Harris, Frederick C

2012-08-01

In the past three decades, the interest in trust has grown significantly due to its important role in our modern society. Everyday social experience involves "confidence" among people, which can be interpreted at the neurological level of a human brain. Recent studies suggest that oxytocin is a centrally-acting neurotransmitter important in the development and alteration of trust. Its administration in humans seems to increase trust and reduce fear, in part by directly inhibiting the amygdala. However, the cerebral microcircuitry underlying this mechanism is still unknown. We propose the first biologically realistic model for trust, simulating spiking neurons in the cortex in a real-time human-robot interaction simulation. At the physiological level, oxytocin cells were modeled with triple apical dendrites characteristic of their structure in the paraventricular nucleus of the hypothalamus. As trust was established in the simulation, this architecture had a direct inhibitory effect on the amygdala tonic firing, which resulted in a willingness to exchange an object from the trustor (virtual neurorobot) to the trustee (human actor). Our software and hardware enhancements allowed the simulation of almost 100,000 neurons in real time and the incorporation of a sophisticated Gabor mechanism as a visual filter. Our brain was functional and our robotic system was robust in that it trusted or distrusted a human actor based on movement imitation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Using a simulation model to assess risk of false negative point-of-care urinary human chorionic gonadotropin device results due to high-dose hook interference.

PubMed

Milhorn, Denise; Korpi-Steiner, Nichole

2015-02-01

It is unclear if the point-of-care (POC) Clinitest hCG device is subject to high-dose hook interference from physiological concentrations of intact human chorionic gonadotropin (hCG), β-core fragment of hCG (hCGβcf), and hCG free β-subunit (hCGβ) found in urine during pregnancy. We used a simulation model to address this question and related our findings to our institution's pregnant population in order to assess risk for potential false-negative hCG results. The expected distribution of days relative to ovulation during routine POC hCG testing was estimated from 182 patients. Clinitest-Clinitek Status hCG device susceptibility to high-dose hook interference from hCG variants and potential risk of false-negative results as it relates to this population were evaluated by testing increasing concentrations of hCG, hCGβcf, hCGβ as well as urine simulating physiological hCG, hCGβcf and hCGβ concentrations expected during early pregnancy (≤44 days post-ovulation). The Clinitest-Clinitek Status hCG device exhibited high-dose hook interference from hCGβcf alone, but not from hCG, hCGβ, or simulated physiological urinary concentrations of combined hCG, hCGβcf and hCGβ expected during early pregnancy. The majority of our patient population had urinary hCG testing conducted during early pregnancy. The Clinitest-Clinitek Status hCG device is unlikely to exhibit false-negative urinary hCG results due to high-dose hook interference for women in early healthy pregnancy, although additional studies are necessary to determine potential risk in other patient populations. Visual interpretation of POC urinary hCG device results is an important failure mode to consider in risk analyses for erroneous urinary hCG device results. Published by Elsevier Inc.

A new flexible plug and play scheme for modeling, simulating, and predicting gastric emptying

PubMed Central

2014-01-01

Background In-silico models that attempt to capture and describe the physiological behavior of biological organisms, including humans, are intrinsically complex and time consuming to build and simulate in a computing environment. The level of detail of description incorporated in the model depends on the knowledge of the system’s behavior at that level. This knowledge is gathered from the literature and/or improved by knowledge obtained from new experiments. Thus model development is an iterative developmental procedure. The objective of this paper is to describe a new plug and play scheme that offers increased flexibility and ease-of-use for modeling and simulating physiological behavior of biological organisms. Methods This scheme requires the modeler (user) first to supply the structure of the interacting components and experimental data in a tabular format. The behavior of the components described in a mathematical form, also provided by the modeler, is externally linked during simulation. The advantage of the plug and play scheme for modeling is that it requires less programming effort and can be quickly adapted to newer modeling requirements while also paving the way for dynamic model building. Results As an illustration, the paper models the dynamics of gastric emptying behavior experienced by humans. The flexibility to adapt the model to predict the gastric emptying behavior under varying types of nutrient infusion in the intestine (ileum) is demonstrated. The predictions were verified with a human intervention study. The error in predicting the half emptying time was found to be less than 6%. Conclusions A new plug-and-play scheme for biological systems modeling was developed that allows changes to the modeled structure and behavior with reduced programming effort, by abstracting the biological system into a network of smaller sub-systems with independent behavior. In the new scheme, the modeling and simulation becomes an automatic machine readable and executable task. PMID:24917054

Semi-physiologic model validation and bioequivalence trials simulation to select the best analyte for acetylsalicylic acid.

PubMed

Cuesta-Gragera, Ana; Navarro-Fontestad, Carmen; Mangas-Sanjuan, Victor; González-Álvarez, Isabel; García-Arieta, Alfredo; Trocóniz, Iñaki F; Casabó, Vicente G; Bermejo, Marival

2015-07-10

The objective of this paper is to apply a previously developed semi-physiologic pharmacokinetic model implemented in NONMEM to simulate bioequivalence trials (BE) of acetyl salicylic acid (ASA) in order to validate the model performance against ASA human experimental data. ASA is a drug with first-pass hepatic and intestinal metabolism following Michaelis-Menten kinetics that leads to the formation of two main metabolites in two generations (first and second generation metabolites). The first aim was to adapt the semi-physiological model for ASA in NOMMEN using ASA pharmacokinetic parameters from literature, showing its sequential metabolism. The second aim was to validate this model by comparing the results obtained in NONMEM simulations with published experimental data at a dose of 1000 mg. The validated model was used to simulate bioequivalence trials at 3 dose schemes (100, 1000 and 3000 mg) and with 6 test formulations with decreasing in vivo dissolution rate constants versus the reference formulation (kD 8-0.25 h (-1)). Finally, the third aim was to determine which analyte (parent drug, first generation or second generation metabolite) was more sensitive to changes in formulation performance. The validation results showed that the concentration-time curves obtained with the simulations reproduced closely the published experimental data, confirming model performance. The parent drug (ASA) was the analyte that showed to be more sensitive to the decrease in pharmaceutical quality, with the highest decrease in Cmax and AUC ratio between test and reference formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

Innovative model to simulate exhalation phase in human respiratory system.

PubMed

Sbrana, Tommaso; Landi, Alberto; Catapano, Giosuè Angelo

2011-11-01

In this paper, we present a mathematical model, which mimics the bronchial resistances of human's lung in an expiratory act. The model is implemented in Matlab. The inputs that are used in this model derive from spirometry test. This model is able to study a physiologic condition, a pathologic one and the patient's follow up after drug treatment. We split our study into two parts. The first one focuses the analysis on the gas fluido dynamic inside of the respiratory pathways. The second part takes care of the pressure equilibrium in the exchange zone. We use the outputs that derive from the second subsystem to solve the Bernoulli's equation of the first part. The model was validated with data provided from "Clinical Physiology Institute" of CNR and G. Monasterio Foundation of Pisa. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Virtual Interactive Musculoskeletal System (VIMS) in orthopaedic research, education and clinical patient care.

PubMed

Chao, Edmund Y S; Armiger, Robert S; Yoshida, Hiroaki; Lim, Jonathan; Haraguchi, Naoki

2007-03-08

The ability to combine physiology and engineering analyses with computer sciences has opened the door to the possibility of creating the "Virtual Human" reality. This paper presents a broad foundation for a full-featured biomechanical simulator for the human musculoskeletal system physiology. This simulation technology unites the expertise in biomechanical analysis and graphic modeling to investigate joint and connective tissue mechanics at the structural level and to visualize the results in both static and animated forms together with the model. Adaptable anatomical models including prosthetic implants and fracture fixation devices and a robust computational infrastructure for static, kinematic, kinetic, and stress analyses under varying boundary and loading conditions are incorporated on a common platform, the VIMS (Virtual Interactive Musculoskeletal System). Within this software system, a manageable database containing long bone dimensions, connective tissue material properties and a library of skeletal joint system functional activities and loading conditions are also available and they can easily be modified, updated and expanded. Application software is also available to allow end-users to perform biomechanical analyses interactively. Examples using these models and the computational algorithms in a virtual laboratory environment are used to demonstrate the utility of these unique database and simulation technology. This integrated system, model library and database will impact on orthopaedic education, basic research, device development and application, and clinical patient care related to musculoskeletal joint system reconstruction, trauma management, and rehabilitation.

Virtual interactive musculoskeletal system (VIMS) in orthopaedic research, education and clinical patient care

PubMed Central

Chao, Edmund YS; Armiger, Robert S; Yoshida, Hiroaki; Lim, Jonathan; Haraguchi, Naoki

2007-01-01

The ability to combine physiology and engineering analyses with computer sciences has opened the door to the possibility of creating the "Virtual Human" reality. This paper presents a broad foundation for a full-featured biomechanical simulator for the human musculoskeletal system physiology. This simulation technology unites the expertise in biomechanical analysis and graphic modeling to investigate joint and connective tissue mechanics at the structural level and to visualize the results in both static and animated forms together with the model. Adaptable anatomical models including prosthetic implants and fracture fixation devices and a robust computational infrastructure for static, kinematic, kinetic, and stress analyses under varying boundary and loading conditions are incorporated on a common platform, the VIMS (Virtual Interactive Musculoskeletal System). Within this software system, a manageable database containing long bone dimensions, connective tissue material properties and a library of skeletal joint system functional activities and loading conditions are also available and they can easily be modified, updated and expanded. Application software is also available to allow end-users to perform biomechanical analyses interactively. Examples using these models and the computational algorithms in a virtual laboratory environment are used to demonstrate the utility of these unique database and simulation technology. This integrated system, model library and database will impact on orthopaedic education, basic research, device development and application, and clinical patient care related to musculoskeletal joint system reconstruction, trauma management, and rehabilitation. PMID:17343764

A physiologically-based model for simulation of color vision deficiency.

PubMed

Machado, Gustavo M; Oliveira, Manuel M; Fernandes, Leandro A F

2009-01-01

Color vision deficiency (CVD) affects approximately 200 million people worldwide, compromising the ability of these individuals to effectively perform color and visualization-related tasks. This has a significant impact on their private and professional lives. We present a physiologically-based model for simulating color vision. Our model is based on the stage theory of human color vision and is derived from data reported in electrophysiological studies. It is the first model to consistently handle normal color vision, anomalous trichromacy, and dichromacy in a unified way. We have validated the proposed model through an experimental evaluation involving groups of color vision deficient individuals and normal color vision ones. Our model can provide insights and feedback on how to improve visualization experiences for individuals with CVD. It also provides a framework for testing hypotheses about some aspects of the retinal photoreceptors in color vision deficient individuals.

Atrial Model Development and Prototype Simulations: CRADA Final Report on Tasks 3 and 4

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

O'Hara, T.; Zhang, X.; Villongco, C.

2016-10-28

The goal of this CRADA was to develop essential tools needed to simulate human atrial electrophysiology in 3-dimensions using an anatomical image-based anatomy and physiologically detailed human cellular model. The atria were modeled as anisotropic, representing the preferentially longitudinal electrical coupling between myocytes. Across the entire anatomy, cellular electrophysiology was heterogeneous, with left and right atrial myocytes defined differently. Left and right cell types for the “control” case of sinus rhythm (SR) was compared with remodeled electrophysiology and calcium cycling characteristics of chronic atrial fibrillation (cAF). The effects of Isoproterenol (ISO), a beta-adrenergic agonist that represents the functional consequences ofmore » PKA phosphorylation of various ion channels and transporters, was also simulated in SR and cAF to represent atrial activity under physical or emotional stress. Results and findings from Tasks 3 & 4 are described. Tasks 3 and 4 are, respectively: Input parameters prepared for a Cardioid simulation; Report including recommendations for additional scenario development and post-processing analytic strategy.« less

The analysis of thermal comfort requirements through the simulation of an occupied building.

PubMed

Thellier, F; Cordier, A; Monchoux, F

1994-05-01

Building simulation usually focuses on the study of physical indoor parameters, but we must not forget the main aim of a house: to provide comfort to the occupants. This study was undertaken in order to build a complete tool to model thermal behaviour that will enable the prediction of thermal sensations of humans in a real environment. A human thermoregulation model was added to TRNSYS, a building simulation program. For our purposes, improvements had to be made to the original physiological model, by refining the calculation of all heat exchanges with the environment and adding a representation of clothes. This paper briefly describes the program, its modifications, and compares its results with experimental ones. An example of potential use is given, which points out the usefulness of such models in seeking the best solutions to reach optimal environmental conditions for global, and specially local comfort, of building occupants.

Studying permethrin exposure in flight attendants using a physiologically based pharmacokinetic model

PubMed Central

Wei, Binnian; Isukapalli, Sastry S.; Weisel, Clifford P.

2014-01-01

Assessment of potential health risks to flight attendants from exposure to pyrethroid insecticides, used for aircraft disinsection, is limited because of (a) lack of information on exposures to these insecticides, and (b) lack of tools for linking these exposures to biomarker data. We developed and evaluated a physiologically based pharmacokinetic (PBPK) model to assess the exposure of flight attendants to the pyrethroid insecticide permethrin attributable to aircraft disinsection. The permethrin PBPK model was developed by adapting previous models for pyrethroids, and was parameterized using currently available metabolic parameters for permethrin. The human permethrin model was first evaluated with data from published human studies. Then, it was used to estimate urinary metabolite concentrations of permethrin in flight attendants who worked in aircrafts, which underwent residual and pre-flight spray treatments. The human model was also applied to analyze the toxicokinetics following permethrin exposures attributable to other aircraft disinsection scenarios. Predicted levels of urinary 3-phenoxybenzoic acid (3-PBA), a metabolite of permethrin, following residual disinsection treatment were comparable to the measurements made for flight attendants. Simulations showed that the median contributions of the dermal, oral and inhalation routes to permethrin exposure in flight attendants were 83.5%, 16.1% and 0.4% under residual treatment scenario, respectively, and were 5.3%, 5.0% and 89.7% under pre-flight spray scenario, respectively. The PBPK model provides the capability to simulate the toxicokinetic profiles of permethrin, and can be used in the studies on human exposure to permethrin. PMID:23462847

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

PubMed

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

2016-04-01

Several cardiovascular and pulmonary models have been proposed in the last few decades. However, very few have addressed the interactions between these two systems. Our group has developed an integrated cardiopulmonary model (CP Model) that mathematically describes the interactions between the cardiovascular and respiratory systems, along with their main short-term control mechanisms. The model has been compared with human and animal data taken from published literature. Due to the volume of the work, the paper is divided in two parts. The present paper is on model development and normophysiology, whereas the second is on the model's validation on hypoxic and hypercapnic conditions. The CP Model incorporates cardiovascular circulation, respiratory mechanics, tissue and alveolar gas exchange, as well as short-term neural control mechanisms acting on both the cardiovascular and the respiratory functions. The model is able to simulate physiological variables typically observed in adult humans under normal and pathological conditions and to explain the underlying mechanisms and dynamics. Copyright © 2016 the American Physiological Society.

The Value of Biomedical Simulation Environments to Future Human Space Flight Missions

NASA Technical Reports Server (NTRS)

Mulugeta, Lealem; Myers, Jerry G.; Skytland, Nicholas G.; Platts, Steven H.

2010-01-01

With the ambitious goals to send manned missions to asteroids and onto Mars, substantial work will be required to ensure the well being of the men and women who will undertake these difficult missions. Unlike current International Space Station or Shuttle missions, astronauts will be required to endure long-term exposure to higher levels of radiation, isolation and reduced gravity. These new operation conditions will pose health risks that are currently not well understood and perhaps unanticipated. Therefore, it is essential to develop and apply advanced tools to predict, assess and mitigate potential hazards to astronaut health. NASA s Digital Astronaut Project (DAP) is working to develop and apply computational models of physiologic response to space flight operation conditions over various time periods and environmental circumstances. The collective application and integration of well vetted models assessing the physiology, biomechanics and anatomy is referred to as the Digital Astronaut. The Digital Astronaut simulation environment will serve as a practical working tool for use by NASA in operational activities such as the prediction of biomedical risks and functional capabilities of astronauts. In additional to space flight operation conditions, DAP s work has direct applicability to terrestrial biomedical research by providing virtual environments for hypothesis testing, experiment design, and to reduce animal/human testing. A practical application of the DA to assess pre and post flight responses to exercise is illustrated and the difficulty in matching true physiological responses is discussed.

The concept of comparative information yield curves and its application to risk-based site characterization

NASA Astrophysics Data System (ADS)

de Barros, Felipe P. J.; Rubin, Yoram; Maxwell, Reed M.

2009-06-01

Defining rational and effective hydrogeological data acquisition strategies is of crucial importance as such efforts are always resource limited. Usually, strategies are developed with the goal of reducing uncertainty, but less often they are developed in the context of their impacts on uncertainty. This paper presents an approach for determining site characterization needs on the basis of human health risk. The main challenge is in striking a balance between reduction in uncertainty in hydrogeological, behavioral, and physiological parameters. Striking this balance can provide clear guidance on setting priorities for data acquisition and for better estimating adverse health effects in humans. This paper addresses this challenge through theoretical developments and numerical simulation. A wide range of factors that affect site characterization needs are investigated, including the dimensions of the contaminant plume and additional length scales that characterize the transport problem, as well as the model of human health risk. The concept of comparative information yield curves is used for investigating the relative impact of hydrogeological and physiological parameters in risk. Results show that characterization needs are dependent on the ratios between flow and transport scales within a risk-driven approach. Additionally, the results indicate that human health risk becomes less sensitive to hydrogeological measurements for large plumes. This indicates that under near-ergodic conditions, uncertainty reduction in human health risk may benefit from better understanding of the physiological component as opposed to a more detailed hydrogeological characterization.

Spontaneous quaternary and tertiary T-R transitions of human hemoglobin in molecular dynamics simulation.

PubMed

Hub, Jochen S; Kubitzki, Marcus B; de Groot, Bert L

2010-05-06

We present molecular dynamics simulations of unliganded human hemoglobin (Hb) A under physiological conditions, starting from the R, R2, and T state. The simulations were carried out with protonated and deprotonated HC3 histidines His(beta)146, and they sum up to a total length of 5.6 micros. We observe spontaneous and reproducible T-->R quaternary transitions of the Hb tetramer and tertiary transitions of the alpha and beta subunits, as detected from principal component projections, from an RMSD measure, and from rigid body rotation analysis. The simulations reveal a marked asymmetry between the alpha and beta subunits. Using the mutual information as correlation measure, we find that the beta subunits are substantially more strongly linked to the quaternary transition than the alpha subunits. In addition, the tertiary populations of the alpha and beta subunits differ substantially, with the beta subunits showing a tendency towards R, and the alpha subunits showing a tendency towards T. Based on the simulation results, we present a transition pathway for coupled quaternary and tertiary transitions between the R and T conformations of Hb.

Spontaneous Quaternary and Tertiary T-R Transitions of Human Hemoglobin in Molecular Dynamics Simulation

PubMed Central

de Groot, Bert L.

2010-01-01

We present molecular dynamics simulations of unliganded human hemoglobin (Hb) A under physiological conditions, starting from the R, R2, and T state. The simulations were carried out with protonated and deprotonated HC3 histidines His(β)146, and they sum up to a total length of 5.6µs. We observe spontaneous and reproducible T→R quaternary transitions of the Hb tetramer and tertiary transitions of the α and β subunits, as detected from principal component projections, from an RMSD measure, and from rigid body rotation analysis. The simulations reveal a marked asymmetry between the α and β subunits. Using the mutual information as correlation measure, we find that the β subunits are substantially more strongly linked to the quaternary transition than the α subunits. In addition, the tertiary populations of the α and β subunits differ substantially, with the β subunits showing a tendency towards R, and the α subunits showing a tendency towards T. Based on the simulation results, we present a transition pathway for coupled quaternary and tertiary transitions between the R and T conformations of Hb. PMID:20463873

Virtual Reality as a Distraction Technique in Chronic Pain Patients

PubMed Central

Gao, Kenneth; Sulea, Camelia; Wiederhold, Mark D.

2014-01-01

Abstract We explored the use of virtual reality distraction techniques for use as adjunctive therapy to treat chronic pain. Virtual environments were specifically created to provide pleasant and engaging experiences where patients navigated on their own through rich and varied simulated worlds. Real-time physiological monitoring was used as a guide to determine the effectiveness and sustainability of this intervention. Human factors studies showed that virtual navigation is a safe and effective method for use with chronic pain patients. Chronic pain patients demonstrated significant relief in subjective ratings of pain that corresponded to objective measurements in peripheral, noninvasive physiological measures. PMID:24892196

Biomarkers of human cardiopulmonary response after short-term exposures to medical laser generated particulate matter from simulated procedures: a pilot study

PubMed Central

Lopez, Ramon; Farber, Mark O.; Wong, Vincent; Lacey, Steven E.

2016-01-01

Objective We conducted an exposure chamber study in humans using a simulated clinical procedure lasing porcine tissue to demonstrate evidence of effects of exposure to laser generated particulate matter (LGPM). Methods We measured pre- and post-exposure changes in exhaled nitric oxide (eNO), spirometry, heart rate variability (HRV), and blood markers of inflammation in five volunteers. Results Change in pre- and post-exposure measurements of eNO and spirometry were unremarkable. Neutrophil and lymphocyte counts increased and fibrinogen levels decreased in four of the five subjects. Measures of HRV showed decreases in the standard deviation of normal between beat intervals and sequential five-minute intervals. Conclusion These data represent the first evidence of human physiologic response to LGPM exposure. Further exploration of coagulation effects and HRV are warranted. PMID:27465102

Metabolic profiles of pomalidomide in human plasma simulated with pharmacokinetic data in control and humanized-liver mice.

PubMed

Shimizu, Makiko; Suemizu, Hiroshi; Mitsui, Marina; Shibata, Norio; Guengerich, F Peter; Yamazaki, Hiroshi

2017-10-01

1. Pomalidomide has been shown to be potentially teratogenic in thalidomide-sensitive animal species such as rabbits. Screening for thalidomide analogs devoid of teratogenicity/toxicity - attributable to metabolites formed by cytochrome P450 enzymes - but having immunomodulatory properties is a strategic pathway towards development of new anticancer drugs. 2. In this study, plasma concentrations of pomalidomide, its primary 5-hydroxylated metabolite, and its glucuronide conjugate(s) were investigated in control and humanized-liver mice. Following oral administration of pomalidomide (100 mg/kg), plasma concentrations of 7-hydroxypomalidomide and 5-hydroxypomalidomide glucuronide were slightly higher in humanized-liver mice than in control mice. 3. Simulations of human plasma concentrations of pomalidomide were achieved with simplified physiologically-based pharmacokinetic models in both groups of mice in accordance with reported pomalidomide concentrations after low dose administration in humans. 4. The results indicate that pharmacokinetic profiles of pomalidomide were roughly similar between control mice and humanized-liver mice and that control and humanized-liver mice mediated pomalidomide 5-hydroxylation in vivo. Introducing one aromatic amino group into thalidomide resulted in less species differences in in vivo pharmacokinetics in control and humanized-liver mice.

Animal models and their importance to human physiological responses in microgravity

NASA Technical Reports Server (NTRS)

Tipton, C. M.

1996-01-01

Two prominent theories to explain the physiological effects of microgravity relate to the cascade of changes associated with the cephalic shifts of fluids and the absence of tissue deformation forces. One-g experiments for humans used bed rest and the head-down tilt (HDT) method, while animal experiments have been conducted using the tail-suspended, head-down, and hindlimbs non-weightbearing model. Because of the success of the HDT approach with rats to simulate the gravitational effects on the musculoskeletal system exhibited by humans, the same model has been used to study the effects of gravity on the cardiopulmonary systems of humans and other vertebrates. Results to date indicate the model is effective in producing comparable changes associated with blood volume, erythropoiesis, cardiac mass, baroreceptor responsiveness, carbohydrate metabolism, post-flight VO2max, and post-flight cardiac output during exercise. Inherent with these results is the potential of the model to be useful in investigating responsible mechanisms. The suspension model has promise in understanding the capillary blood PO2 changes in space as well as the arterial PO2 changes in subjects participating in a HDT experiment. However, whether the model can provide insights on the up-or-down regulation of adrenoreceptors remains to be determined, and many investigators believe the HDT approach should not be followed to study gravitational influences on pulmonary function in either humans or animals. It was concluded that the tail-suspended animal model had sufficient merit to study in-flight and post-flight human physiological responses and mechanisms.

Coupling of the Models of Human Physiology and Thermal Comfort

NASA Astrophysics Data System (ADS)

Pokorny, J.; Jicha, M.

2013-04-01

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

Artificial gravity as a countermeasure for mitigating physiological deconditioning during long-duration space missions.

PubMed

Clément, Gilles R; Bukley, Angelia P; Paloski, William H

2015-01-01

In spite of the experience gained in human space flight since Yuri Gagarin's historical flight in 1961, there has yet to be identified a completely effective countermeasure for mitigating the effects of weightlessness on humans. Were astronauts to embark upon a journey to Mars today, the 6-month exposure to weightlessness en route would leave them considerably debilitated, even with the implementation of the suite of piece-meal countermeasures currently employed. Continuous or intermittent exposure to simulated gravitational states on board the spacecraft while traveling to and from Mars, also known as artificial gravity, has the potential for enhancing adaptation to Mars gravity and re-adaptation to Earth gravity. Many physiological functions are adversely affected by the weightless environment of spaceflight because they are calibrated for normal, Earth's gravity. Hence, the concept of artificial gravity is to provide a broad-spectrum replacement for the gravitational forces that naturally occur on the Earth's surface, thereby avoiding the physiological deconditioning that takes place in weightlessness. Because researchers have long been concerned by the adverse sensorimotor effects that occur in weightlessness as well as in rotating environments, additional study of the complex interactions among sensorimotor and other physiological systems in rotating environments must be undertaken both on Earth and in space before artificial gravity can be implemented.

Noninvasive spectral imaging of skin chromophores based on multiple regression analysis aided by Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Nishidate, Izumi; Wiswadarma, Aditya; Hase, Yota; Tanaka, Noriyuki; Maeda, Takaaki; Niizeki, Kyuichi; Aizu, Yoshihisa

2011-08-01

In order to visualize melanin and blood concentrations and oxygen saturation in human skin tissue, a simple imaging technique based on multispectral diffuse reflectance images acquired at six wavelengths (500, 520, 540, 560, 580 and 600nm) was developed. The technique utilizes multiple regression analysis aided by Monte Carlo simulation for diffuse reflectance spectra. Using the absorbance spectrum as a response variable and the extinction coefficients of melanin, oxygenated hemoglobin, and deoxygenated hemoglobin as predictor variables, multiple regression analysis provides regression coefficients. Concentrations of melanin and total blood are then determined from the regression coefficients using conversion vectors that are deduced numerically in advance, while oxygen saturation is obtained directly from the regression coefficients. Experiments with a tissue-like agar gel phantom validated the method. In vivo experiments with human skin of the human hand during upper limb occlusion and of the inner forearm exposed to UV irradiation demonstrated the ability of the method to evaluate physiological reactions of human skin tissue.

Advanced research to qualify man for long term weightlessness.

NASA Technical Reports Server (NTRS)

Jones, W. L.

1972-01-01

NASA is in the process of conducting a broad program of research and development of technology to qualify, support, and permit the successful use of man in long-term space flight. The technological tasks include human engineering, extravehicular engineering, life support, and human research to assess the effect of space stresses on human physiology and psychology. Various testing techniques that are being used may have future relevance to world health. These include a biocybernetic approach to the study of cardiovascular stresses, measurement of blood flow by means of the Doppler effect, and a device for simulating radiation dosages similar to those produced in solar flares. The planned program includes a study of both humans and animals.

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.

A systems approach to the physiology of weightlessness

NASA Technical Reports Server (NTRS)

White, Ronald J.; Leonard, Joel I.; Rummel, John A.; Leach, Carolyn S.

1991-01-01

A general systems approach to conducting and analyzing research on the human adaptation to weightlessness is presented. The research is aimed at clarifying the role that each of the major components of the human system plays following the transition to and from space. The approach utilizes a variety of mathematical models in order to pose and test alternative hypotheses concerned with the adaptation process. Certain aspects of the problem of fluid and electrolyte shifts in weightlessnes are considered, and an integrated hypothesis based on numerical simulation studies and experimental data is presented.

Objects Mental Rotation under 7 Days Simulated Weightlessness Condition: An ERP Study.

PubMed

Wang, Hui; Duan, Jiaobo; Liao, Yang; Wang, Chuang; Li, Hongzheng; Liu, Xufeng

2017-01-01

During the spaceflight under weightlessness condition, human's brain function may be affected by the changes of physiological effects along with the distribution of blood and body fluids to the head. This variation of brain function will influence the performance of astronauts and therefore create possible harm to flight safety. This study employs 20 male subjects in a 7-day-6° head-down tilted (HDT) bed rest model to simulate physiological effects under weightlessness condition, and use behavioral, electrophysiological techniques to compare the changes of mental rotation ability (MR ability) before and after short-term simulated weightlessness state. Behavioral results suggested that significant linear relationship existed between the rotation angle of stimuli and the reaction time, which means mental rotation process do happen during the MR task in simulated weightlessness state. In the first 3 days, the P300 component induced by object mental rotation followed the "down-up-down" pattern. In the following 4 days it changed randomly. On HDT D2, the mean of the amplitude of the P300 was the lowest, while increased gently on HDT D3. There was no obvious changing pattern of the amplitude of P300 observed after 3 days of HDT. Simulated weightlessness doesn't change the basic process of mental rotation. The effect of simulated weightlessness is neural mechanism of self-adaptation. MR ability didn't bounce back to the original level after HDT test.

Optimizing Muscle Parameters in Musculoskeletal Modeling Using Monte Carlo Simulations

NASA Technical Reports Server (NTRS)

Hanson, Andrea; Reed, Erik; Cavanagh, Peter

2011-01-01

Astronauts assigned to long-duration missions experience bone and muscle atrophy in the lower limbs. The use of musculoskeletal simulation software has become a useful tool for modeling joint and muscle forces during human activity in reduced gravity as access to direct experimentation is limited. Knowledge of muscle and joint loads can better inform the design of exercise protocols and exercise countermeasure equipment. In this study, the LifeModeler(TM) (San Clemente, CA) biomechanics simulation software was used to model a squat exercise. The initial model using default parameters yielded physiologically reasonable hip-joint forces. However, no activation was predicted in some large muscles such as rectus femoris, which have been shown to be active in 1-g performance of the activity. Parametric testing was conducted using Monte Carlo methods and combinatorial reduction to find a muscle parameter set that more closely matched physiologically observed activation patterns during the squat exercise. Peak hip joint force using the default parameters was 2.96 times body weight (BW) and increased to 3.21 BW in an optimized, feature-selected test case. The rectus femoris was predicted to peak at 60.1% activation following muscle recruitment optimization, compared to 19.2% activation with default parameters. These results indicate the critical role that muscle parameters play in joint force estimation and the need for exploration of the solution space to achieve physiologically realistic muscle activation.

An ultrasonic methodology for muscle cross section measurement of support space flight

NASA Astrophysics Data System (ADS)

Hatfield, Thomas R.; Klaus, David M.; Simske, Steven J.

2004-09-01

The number one priority for any manned space mission is the health and safety of its crew. The study of the short and long term physiological effects on humans is paramount to ensuring crew health and mission success. One of the challenges associated in studying the physiological effects of space flight on humans, such as loss of bone and muscle mass, has been that of readily attaining the data needed to characterize the changes. The small sampling size of astronauts, together with the fact that most physiological data collection tends to be rather tedious, continues to hinder elucidation of the underlying mechanisms responsible for the observed changes that occur in space. Better characterization of the muscle loss experienced by astronauts requires that new technologies be implemented. To this end, we have begun to validate a 360° ultrasonic scanning methodology for muscle measurements and have performed empirical sampling of a limb surrogate for comparison. Ultrasonic wave propagation was simulated using 144 stations of rotated arm and calf MRI images. These simulations were intended to provide a preliminary check of the scanning methodology and data analysis before its implementation with hardware. Pulse-echo waveforms were processed for each rotation station to characterize fat, muscle, bone, and limb boundary interfaces. The percentage error between MRI reference values and calculated muscle areas, as determined from reflection points for calf and arm cross sections, was -2.179% and +2.129%, respectively. These successful simulations suggest that ultrasound pulse scanning can be used to effectively determine limb cross-sectional areas. Cross-sectional images of a limb surrogate were then used to simulate signal measurements at several rotation angles, with ultrasonic pulse-echo sampling performed experimentally at the same stations on the actual limb surrogate to corroborate the results. The objective of the surrogate sampling was to compare the signal output of the simulation tool used as a methodology validation for actual tissue signals. The disturbance patterns of the simulated and sampled waveforms were consistent. Although only discussed as a small part of the work presented, the sampling portion also helped identify important considerations such as tissue compression and transducer positioning for future work involving tissue scanning with this methodology.

In vivo nuclear magnetic resonance imaging

NASA Technical Reports Server (NTRS)

Leblanc, A.; Evans, H.; Bryan, R. N.; Johnson, P.; Schonfeld, E.; Jhingran, S. G.

1984-01-01

A number of physiological changes have been demonstrated in bone, muscle and blood after exposure of humans and animals to microgravity. Determining mechanisms and the development of effective countermeasures for long duration space missions is an important NASA goal. The advent of tomographic nuclear magnetic resonance imaging (NMR or MRI) gives NASA a way to greatly extend early studies of this phenomena in ways not previously possible; NMR is also noninvasive and safe. NMR provides both superb anatomical images for volume assessments of individual organs and quantification of chemical/physical changes induced in the examined tissues. The feasibility of NMR as a tool for human physiological research as it is affected by microgravity is demonstrated. The animal studies employed the rear limb suspended rat as a model of mucle atrophy that results from microgravity. And bedrest of normal male subjects was used to simulate the effects of microgravity on bone and muscle.

Modeling liver physiology: combining fractals, imaging and animation.

PubMed

Lin, Debbie W; Johnson, Scott; Hunt, C Anthony

2004-01-01

Physiological modeling of vascular and microvascular networks in several key human organ systems is critical for a deeper understanding of pharmacology and the effect of pharmacotherapies on disease. Like the lung and the kidney, the morphology of its vascular and microvascular system plays a major role in its functional capability. To understand liver function in absorption and metabolism of food and drugs, one must examine the morphology and physiology at both higher and lower level liver function. We have developed validated virtualized dynamic three dimensional (3D) models of liver secondary units and primary units by combining a number of different methods: three-dimensional rendering, fractals, and animation. We have simulated particle dynamics in the liver secondary unit. The resulting models are suitable for use in helping researchers easily visualize and gain intuition on results of in silico liver experiments.

Investigation into the interaction of losartan with human serum albumin and glycated human serum albumin by spectroscopic and molecular dynamics simulation techniques: A comparison study.

PubMed

Moeinpour, Farid; Mohseni-Shahri, Fatemeh S; Malaekeh-Nikouei, Bizhan; Nassirli, Hooriyeh

2016-09-25

The interaction between losartan and human serum albumin (HSA), as well as its glycated form (gHSA) was studied by multiple spectroscopic techniques and molecular dynamics simulation under physiological conditions. The binding information, including the binding constants, effective quenching constant and number of binding sites showed that the binding partiality of losartan to HSA was higher than to gHSA. The findings of three-dimensional fluorescence spectra demonstrated that the binding of losartan to HSA and gHSA would alter the protein conformation. The distances between Trp residue and the binding sites of the drug were evaluated on the basis of the Förster theory, and it was indicated that non-radiative energy transfer from HSA and gHSA to the losartan happened with a high possibility. According to molecular dynamics simulation, the protein secondary and tertiary structure changes were compared in HSA and gHSA for clarifying the obtained results. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Resolving Low-Density Lipoprotein (LDL) on the Human Aortic Surface Using Large Eddy Simulation

NASA Astrophysics Data System (ADS)

Lantz, Jonas; Karlsson, Matts

2011-11-01

The prediction and understanding of the genesis of vascular diseases is one of the grand challenges in biofluid engineering. The progression of atherosclerosis is correlated to the build- up of LDL on the arterial surface, which is affected by the blood flow. A multi-physics simulation of LDL mass transport in the blood and through the arterial wall of a subject specific human aorta was performed, employing a LES turbulence model to resolve the turbulent flow. Geometry and velocity measurements from magnetic resonance imaging (MRI) were incorporated to assure physiological relevance of the simulation. Due to the turbulent nature of the flow, consecutive cardiac cycles are not identical, neither in vivo nor in the simulations. A phase average based on a large number of cardiac cycles is therefore computed, which is the proper way to get reliable statistical results from a LES simulation. In total, 50 cardiac cycles were simulated, yielding over 2.5 Billion data points to be post-processed. An inverse relation between LDL and WSS was found; LDL accumulated on locations where WSS was low and vice-versa. Large temporal differences were present, with the concentration level decreasing during systolic acceleration and increasing during the deceleration phase. This method makes it possible to resolve the localization of LDL accumulation in the normal human aorta with its complex transitional flow.

Influence of a fat layer on the near infrared spectra of human muscle: quantitative analysis based on two-layered Monte Carlo simulations and phantom experiments

NASA Technical Reports Server (NTRS)

Yang, Ye; Soyemi, Olusola O.; Landry, Michelle R.; Soller, Babs R.

2005-01-01

The influence of fat thickness on the diffuse reflectance spectra of muscle in the near infrared (NIR) region is studied by Monte Carlo simulations of a two-layer structure and with phantom experiments. A polynomial relationship was established between the fat thickness and the detected diffuse reflectance. The influence of a range of optical coefficients (absorption and reduced scattering) for fat and muscle over the known range of human physiological values was also investigated. Subject-to-subject variation in the fat optical coefficients and thickness can be ignored if the fat thickness is less than 5 mm. A method was proposed to correct the fat thickness influence. c2005 Optical Society of America.

Biological Effects of Protracted Exposure to Ionizing Radiation: Review, Analysis, and Model Development

DTIC Science & Technology

1991-11-01

dynamics, physiological changes, morphologi- cal changes, cell/tissue damage and recovery mechanisms, and existing radiobiological injury and recovery...humans and the ferret. The gut injury model (GIM) is a three-compartment hierarchial- type tissue model to simulate radiation-induced changes in the...Prodromal Symptoms Diarrhea Gastrointestinal Symptoms Dose Rate Cell Survival Intestinal Injury Fatigability Cell Damage Cell Repair Cell Proliferation

Reference Models for Multi-Layer Tissue Structures

DTIC Science & Technology

2016-09-01

simulation,  finite   element  analysis 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC...Physiologically realistic, fully specimen-specific, nonlinear reference models. Tasks. Finite element analysis of non-linear mechanics of cadaver...models. Tasks. Finite element analysis of non-linear mechanics of multi-layer tissue regions of human subjects. Deliverables. Partially subject- and

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.

The Integrated Impact of Diet On Human Immune Response, the Gut Microbiota, and Nutritional Status During Adaptation to a Spaceflight Analog

NASA Technical Reports Server (NTRS)

Douglas, G. L.; Zwart, S. R.; Young, M.; Kloeris, V.; Crucian, B.; Smith, S. M.; Lorenzi, H.

2017-01-01

Spaceflight impacts human physiology, including well documented immune system dysregulation. Diet, immune function, and the microbiome are interlinked, but diet is the only one of these factors that we have the ability to easily, and significantly, alter on Earth or during flight. As we understand dietary impacts on physiology more thoroughly, we may then improve the spaceflight diet to improve crew health and potentially reduce flight-associated physiological alterations. It is expected that increasing the consumption of fruits and vegetables and bioactive compounds (e.g.,omega-3 fatty acids, lycopene, flavonoids) and therefore enhancing overall nutritional intake from the nominal shelf-stable, fully-processed space food system could serve as a countermeasure to improve human immunological profiles, the taxonomic profile of the gut microbiota, and nutritional status, especially where currently dysregulated during spaceflight. This interdisciplinary study will determine the effect of the current shelf-stable spaceflight diet compared to an "enhanced" shelf-stable spaceflight diet (25% more foods rich in omega-3 fatty acids, lycopene, flavonoids, fruits, and vegetables). The NASA Human Exploration Research Analog (HERA) 2017 missions, consisting of closed chamber confinement, realistic mission simulation, in a high-fidelity mock space vehicle, will serve as a platform to replicate mission stressors and the dysregulated physiology observed in astronauts. Biosampling of crew members will occur at selected intervals, with complete dietary tracking. Outcome measures will include immune markers (e.g., peripheral leukocyte distribution, inflammatory cytokine profiles, T cell function), the taxonomic and metatranscriptomic profile of the gut microbiome, and nutritional status biomarkers and metabolites. Data collection will also include complete dietary tracking. Statistical evaluations will determine physiological and biochemical shifts in relation to nutrient in take and study phase. Beneficial improvements will provide evidence of the impact of diet on crew health and adaptation to this spaceflight analog, and will aid in the design and development of more-efficient targeted dietary interventions.

The temporal representation of speech in a nonlinear model of the guinea pig cochlea

NASA Astrophysics Data System (ADS)

Holmes, Stephen D.; Sumner, Christian J.; O'Mard, Lowel P.; Meddis, Ray

2004-12-01

The temporal representation of speechlike stimuli in the auditory-nerve output of a guinea pig cochlea model is described. The model consists of a bank of dual resonance nonlinear filters that simulate the vibratory response of the basilar membrane followed by a model of the inner hair cell/auditory nerve complex. The model is evaluated by comparing its output with published physiological auditory nerve data in response to single and double vowels. The evaluation includes analyses of individual fibers, as well as ensemble responses over a wide range of best frequencies. In all cases the model response closely follows the patterns in the physiological data, particularly the tendency for the temporal firing pattern of each fiber to represent the frequency of a nearby formant of the speech sound. In the model this behavior is largely a consequence of filter shapes; nonlinear filtering has only a small contribution at low frequencies. The guinea pig cochlear model produces a useful simulation of the measured physiological response to simple speech sounds and is therefore suitable for use in more advanced applications including attempts to generalize these principles to the response of human auditory system, both normal and impaired. .

Human spaceflight and space adaptations: Computational simulation of gravitational unloading on the spine

NASA Astrophysics Data System (ADS)

Townsend, Molly T.; Sarigul-Klijn, Nesrin

2018-04-01

Living in reduced gravitational environments for a prolonged duration such, as a fly by mission to Mars or an extended stay at the international space station, affects the human body - in particular, the spine. As the spine adapts to spaceflight, morphological and physiological changes cause the mechanical integrity of the spinal column to be compromised, potentially endangering internal organs, nervous health, and human body mechanical function. Therefore, a high fidelity computational model and simulation of the whole human spine was created and validated for the purpose of investigating the mechanical integrity of the spine in crew members during exploratory space missions. A spaceflight exposed spine has been developed through the adaptation of a three-dimensional nonlinear finite element model with the updated Lagrangian formulation of a healthy ground-based human spine in vivo. Simulation of the porohyperelastic response of the intervertebral disc to mechanical unloading resulted in a model capable of accurately predicting spinal swelling/lengthening, spinal motion, and internal stress distribution. The curvature of this space adaptation exposed spine model was compared to a control terrestrial-based finite element model, indicating how the shape changed. Finally, the potential of injury sites to crew members are predicted for a typical 9 day mission.

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

PubMed

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

2017-05-01

This paper aims to integrate a human thermoregulatory model with a clothing model to predict core and skin temperatures. The human thermoregulatory model, consisting of an active system and a passive system, was used to determine the thermoregulation and heat exchanges within the body. The clothing model simulated heat and moisture transfer from the human skin to the environment through the microenvironment and fabric. In this clothing model, the air gap between skin and clothing, as well as clothing properties such as thickness, thermal conductivity, density, porosity, and tortuosity were taken into consideration. The simulated core and mean skin temperatures were compared to the published experimental results of subject tests at three levels of ambient temperatures of 20 °C, 30 °C, and 40 °C. Although lower signal-to-noise-ratio was observed, the developed model demonstrated positive performance at predicting core temperatures with a maximum difference between the simulations and measurements of no more than 0.43 °C. Generally, the current model predicted the mean skin temperatures with reasonable accuracy. It could be applied to predict human physiological responses and assess thermal comfort and heat stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects on Task Performance and Psychophysiological Measures of Performance During Normobaric Hypoxia Exposure

NASA Technical Reports Server (NTRS)

Stephens, Chad; Kennedy, Kellie; Napoli, Nicholas; Demas, Matthew; Barnes, Laura; Crook, Brenda; Williams, Ralph; Last, Mary Carolyn; Schutte, Paul

2017-01-01

Human-autonomous systems have the potential to mitigate pilot cognitive impairment and improve aviation safety. A research team at NASA Langley conducted an experiment to study the impact of mild normobaric hypoxia induction on aircraft pilot performance and psychophysiological state. A within-subjects design involved non-hypoxic and hypoxic exposures while performing three 10-minute tasks. Results indicated the effect of 15,000 feet simulated altitude did not induce significant performance decrement but did produce increase in perceived workload. Analyses of psychophysiological responses evince the potential of biomarkers for hypoxia onset. This study represents on-going work at NASA intending to add to the current knowledge of psychophysiologically-based input to automation to increase aviation safety. Analyses involving coupling across physiological systems and wavelet transforms of cortical activity revealed patterns that can discern between the simulated altitude conditions. Specifically, multivariate entropy of ECG/Respiration components were found to be significant predictors (p< 0.02) of hypoxia. Furthermore, in EEG, there was a significant decrease in mid-level beta (15.19-18.37Hz) during the hypoxic condition in thirteen of sixteen sites across the scalp. Task performance was not appreciably impacted by the effect of 15,000 feet simulated altitude. Analyses of psychophysiological responses evince the potential of biomarkers for mild hypoxia onset.The potential for identifying shifts in underlying cortical and physiological systems could serve as a means to identify the onset of deteriorated cognitive state. Enabling such assessment in future flightdecks could permit increasingly autonomous systems-supported operations. Augmenting human operator through assessment of cognitive impairment has the potential to further improve operator performance and mitigate human error in safety critical contexts. This study represents ongoing work at NASA intending to add to the current knowledge of psychophysiologically-based input to automation to increase aviation safety.

Implementation and validation of the extended Hill-type muscle model with robust routing capabilities in LS-DYNA for active human body models.

PubMed

Kleinbach, Christian; Martynenko, Oleksandr; Promies, Janik; Haeufle, Daniel F B; Fehr, Jörg; Schmitt, Syn

2017-09-02

In the state of the art finite element AHBMs for car crash analysis in the LS-DYNA software material named *MAT_MUSCLE (*MAT_156) is used for active muscles modeling. It has three elements in parallel configuration, which has several major drawbacks: restraint approximation of the physical reality, complicated parameterization and absence of the integrated activation dynamics. This study presents implementation of the extended four element Hill-type muscle model with serial damping and eccentric force-velocity relation including [Formula: see text] dependent activation dynamics and internal method for physiological muscle routing. Proposed model was implemented into the general-purpose finite element (FE) simulation software LSDYNA as a user material for truss elements. This material model is verified and validated with three different sets of mammalian experimental data, taken from the literature. It is compared to the *MAT_MUSCLE (*MAT_156) Hill-type muscle model already existing in LS-DYNA, which is currently used in finite element human body models (HBMs). An application example with an arm model extracted from the FE ViVA OpenHBM is given, taking into account physiological muscle paths. The simulation results show better material model accuracy, calculation robustness and improved muscle routing capability compared to *MAT_156. The FORTRAN source code for the user material subroutine dyn21.f and the muscle parameters for all simulations, conducted in the study, are given at https://zenodo.org/record/826209 under an open source license. This enables a quick application of the proposed material model in LS-DYNA, especially in active human body models (AHBMs) for applications in automotive safety.

Physiology informed virtual surgical planning: a case study with a virtual airway surgical planner and BioGears

NASA Astrophysics Data System (ADS)

Potter, Lucas; Arikatla, Sreekanth; Bray, Aaron; Webb, Jeff; Enquobahrie, Andinet

2017-03-01

Stenosis of the upper airway affects approximately 1 in 200,000 adults per year1 , and occurs in neonates as well2 . Its treatment is often dictated by institutional factors and clinicians' experience or preferences 3 . Objective and quantitative methods of evaluating treatment options hold the potential to improve care in stenosis patients. Virtual surgical planning software tools are critically important for this. The Virtual Pediatric Airway Workbench (VPAW) is a software platform designed and evaluated for upper airway stenosis treatment planning. It incorporates CFD simulation and geometric authoring with objective metrics from both that help in informed evaluation and planning. However, this planner currently lacks physiological information which could impact the surgical planning outcomes. In this work, we integrated a lumped parameter, model based human physiological engine called BioGears with VPAW. We demonstrated the use of physiology informed virtual surgical planning platform for patient-specific stenosis treatment planning. The preliminary results show that incorporating patient-specific physiology in the pretreatment plan would play important role in patient-specific surgical trainers and planners in airway surgery and other types of surgery that are significantly impacted by physiological conditions during surgery.

Graphic-based musculoskeletal model for biomechanical analyses and animation.

PubMed

Chao, Edmund Y S

2003-04-01

The ability to combine physiology and engineering analyses with computer sciences has opened the door to the possibility of creating the 'Virtual Human' reality. This paper presents a broad foundation for a full-featured biomechanical simulator for the human musculoskeletal system physiology. This simulation technology unites the expertise in biomechanical analysis and graphic modeling to investigate joint and connective tissue mechanics at the structural level and to visualize the results in both static and animated forms together with the model. Adaptable anatomical models including prosthetic implants and fracture fixation devices and a robust computational infrastructure for static, kinematic, kinetic, and stress analyses under varying boundary and loading conditions are incorporated on a common platform, the VIMS (Virtual Interactive Musculoskeletal System). Within this software system, a manageable database containing long bone dimensions, connective tissue material properties and a library of skeletal joint system functional activities and loading conditions are also available and they can easily be modified, updated and expanded. Application software is also available to allow end-users to perform biomechanical analyses interactively. This paper details the design, capabilities, and features of the VIMS development at Johns Hopkins University, an effort possible only through academic and commercial collaborations. Examples using these models and the computational algorithms in a virtual laboratory environment are used to demonstrate the utility of this unique database and simulation technology. This integrated system will impact on medical education, basic research, device development and application, and clinical patient care related to musculoskeletal diseases, trauma, and rehabilitation.

[Scientific significance and prospective application of digitized virtual human].

PubMed

Zhong, Shi-zhen

2003-03-01

As a cutting-edge research project, digitization of human anatomical information combines conventional medicine with information technology, computer technology, and virtual reality technology. Recent years have seen the establishment of, or the ongoing effort to establish various virtual human models in many countries, on the basis of continuous sections of human body that are digitized by means of computational medicine incorporating information technology to quantitatively simulate human physiological and pathological conditions, and to provide wide prospective applications in the fields of medicine and other disciplines. This article addresses 4 issues concerning the progress in virtual human model researches as the following: (1) Worldwide survey of sectioning and modeling of visible human. American visible human database was completed in 1994, which contains both a male and a female datasets, and has found wide application internationally. South Korea also finished the data collection for a male visible Korean human dataset in 2000. (2) Application of the dataset of Visible Human Project (VHP). This dataset has yielded plentiful fruits in medical education and clinical research, and further plans are proposed and practiced to construct a Physical Human and Physiological Human . (3) Scientific significance and prospect of virtual human studies. Digitized human dataset may eventually contribute to the development of many new high-tech industries. (4) Progress of virtual Chinese human project. The 174th session of Xiangshang Science Conferences held in 2001 marked the initiation of digitized virtual human project in China, and some key techniques have been explored. By now the data-collection process for 4 Chinese virtual human datasets have been successfully completed.

Development and validation of simulated virtual patients to impart early clinical exposure in endocrine physiology.

PubMed

Gupta, Akriti; Singh, Satendra; Khaliq, Farah; Dhaliwal, Upreet; Madhu, S V

2018-03-01

In the country presently, preclinical medical students are not routinely exposed to real patients. Thus, when they start clinical postings, they are found to have poor clinical reasoning skills. Simulated virtual patients (SVPs) can improve clinical skills without endangering real patients. This pilot study describes the development of two SVPs in endocrine physiology and their validation in terms of acquisition of clinical knowledge and student engagement. Two SVPs, Nandini Sharma (unintentional weight gain) and Sunil Yadav (polyuria), were created and published on the i-Human Patients platform through an iterative, interdisciplinary, and transdisciplinary collaborative process using the conceptual framework of Kim et al. (Kim S, Phillips WR, Pinsky L, Brock D, Phillips K, Keary J. Med Educ 40: 867-876, 2006). After internal and external peer validation, the SVPs were piloted on 40 students (20 students per virtual patient) over 2 wk. A cognitive pretest was conducted before exposure, and a posttest soon after. Faculty and student feedback were collected. Faculty found SVPs authentic, helpful as teaching-learning tools, and useful for giving feedback and for assessment. Students found SVPs more engaging than paper cases and helpful in developing clinical reasoning and in imparting clinical exposure. Pretest and posttest scores indicated knowledge gain ( P < 0.01). Although challenging to create, SVPs created on the i-Human Patients platform improved learning in endocrine physiology and were well accepted by students and faculty as a means to provide early clinical exposure. More SVPs can be developed through collaboration between stakeholder departments and integrated into the curriculum for greater benefit.

Monte Carlo study for physiological interference reduction in near-infrared spectroscopy based on empirical mode decomposition

NASA Astrophysics Data System (ADS)

Zhang, Yan; Sun, JinWei; Rolfe, Peter

2010-12-01

Near-infrared spectroscopy (NIRS) can be used as the basis of non-invasive neuroimaging that may allow the measurement of haemodynamic changes in the human brain evoked by applied stimuli. Since this technique is very sensitive, physiological interference arising from the cardiac cycle and breathing can significantly affect the signal quality. Such interference is difficult to remove by conventional techniques because it occurs not only in the extracerebral layer but also in the brain tissue itself. Previous work on this problem employing temporal filtering, spatial filtering, and adaptive filtering have exhibited good performance for recovering brain activity data in evoked response studies. However, in this study, we present a time-frequency adaptive method for physiological interference reduction based on the combination of empirical mode decomposition (EMD) and Hilbert spectral analysis (HSA). Monte Carlo simulations based on a five-layered slab model of a human adult head were implemented to evaluate our methodology. We applied an EMD algorithm to decompose the NIRS time series derived from Monte Carlo simulations into a series of intrinsic mode functions (IMFs). In order to identify the IMFs associated with symmetric interference, the extracted components were then Hilbert transformed from which the instantaneous frequencies could be acquired. By reconstructing the NIRS signal by properly selecting IMFs, we determined that the evoked brain response is effectively filtered out with even higher signal-to-noise ratio (SNR). The results obtained demonstrated that EMD, combined with HSA, can effectively separate, identify and remove the contamination from the evoked brain response obtained with NIRS using a simple single source-detector pair.

Cardiovascular Deconditioning in Humans: Alteration in Cardiovascular Regulation and Function During Simulated Microgravity

NASA Technical Reports Server (NTRS)

Cohen, Richard

1999-01-01

Alterations in cardiovascular regulation and function that occur during and after space flight have been reported. These alterations are manifested, for example, by reduced orthostatic tolerance upon reentry to the earth's gravity from space. However, the precise physiologic mechanisms responsible for these alterations remain to be fully elucidated. Perhaps, as a result, effective countermeasures have yet to be developed. In this project we apply a powerful, new method - cardiovascular system identification (CSI) - for the study of the effects of space flight on the cardiovascular system so that effective countermeasures can be developed. CSI involves the mathematical analysis of second-to-second fluctuations in non-invasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV - respiratory activity) in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of all the physiologic mechanisms coupling these signals, CSI provides a model of the closed-loop cardiovascular regulatory state in an individual subject. The model includes quantitative descriptions of the heart rate baroreflex, autonomic function, as well as other important physiologic mechanisms. We are in the process of incorporating beat-to-beat fluctuations of stroke volume into the CSI technique in order to quantify additional physiologic mechanisms such as those involved in control of peripheral vascular resistance and alterations in cardiac contractility. We apply CSI in conjunction with the two general protocols of the Human Studies Core project. The first protocol involves ground-based, human head down tilt bed rest to simulate microgravity and acute stressors - upright tilt, standing and bicycle exercise - to provide orthostatic and exercise challenges. The second protocol is intended to be the same as the first but with the addition of sleep deprivation to determine whether this contributes to cardiovascular alterations. In these studies, we focus on the basic physiologic mechanisms responsible for the alterations in cardiovascular regulation and function during the simulated microgravity in order to formulate hypotheses regarding what countermeasures are likely to be most effective. Compared to our original proposal, the protocol we are using has been slightly modified to lengthen the bed rest period to 16 days and streamline the data collection. These modifications provide us data on a longer bed rest period and have enabled us to increase our subject throughput. Based on review of our preliminary data we have decided to test a countermeasure which is applied the very end of the bed rest period. We will use the same bed rest protocol to test this countermeasure. We anticipate completing the baseline data collection in our first protocol plus testing of the countermeasure in an additional eight subjects, at which time we plan to initiate the second protocol which includes sleep deprivation. In future studies, we plan to apply CSI to test other potential countermeasures in conjunction with the same bed rest, sleep deprivation and acute stressor models. We also anticipate applying CSI for studying astronauts before and after space flight and ultimately, during space flight. The application of CSI is providing information relevant to the development and evaluation of effective countermeasures allowing humans to adapt appropriately upon re-exposure to a gravity field, and to live and work for longer periods of time in microgravity.

Physiological Indicators of Workload in a Remotely Piloted Aircraft Simulation

DTIC Science & Technology

2015-10-01

Aviation Psychology, 21(2), 105-122. Deci , E. L., & Ryan , R. M. (1991). Intrinsic motivation and self - determination in human behavior. In R. Steers...rankings (Martens, 1975). Furthermore, individuals have a tendency to challenge themselves in an effort to develop competence and prove self - determination ... Deci & Ryan , 1991). So, when presented with performance feedback, people are motivated to continuously improve their own performance, and beat the

Altered Gravity Simulated by Parabolic Flight and Water Immersion Leads to Decreased Trunk Motion

PubMed Central

Tian, Yu; Li, Fan; Zhang, Shaoyao; Zhang, Lin; Guo, Yaoyu; Liu, Weibo; Wang, Chunhui; Chen, Shanguang; Guo, Jinhu

2015-01-01

Gravity is one of the important environmental factors that influence the physiologies and behaviors of animals and humans, and changes in gravity elicit a variety of physiological and behavioral alterations that include impaired movement coordination, vertigo, spatial disorientation, and perceptual illusions. To elucidate the effects of gravity on human physiology and behavior, we examined changes in wrist and trunk activities and heart rate during parabolic flight and the activity of wrist and trunk in water immersion experiments. Data from 195 person-time parabolas performed by eight subjects revealed that the trunk motion counts decreased by approximately half during ascending legs (hypergravity), relative to the data acquired before the parabolic flights. In contrast, the wrist activity remained unchanged. The results from the water immersion experiments demonstrated that in the underwater condition, both the wrist and trunk activities were significantly decreased but the latter decreased to a much lower level. Together, these data suggest that gravitational alterations can result in differential influences on the motions of the wrist and the trunk. These findings might be important for understanding the degeneration of skeleton and muscular system and performance of astronauts in microgravity. PMID:26208253

Intestinal biomechanics simulator for robotic capsule endoscope validation.

PubMed

Slawinski, Piotr R; Oleynikov, Dmitry; Terry, Benjamin S

2015-01-01

This work describes the development and validation of a novel device which simulates important forces experienced by Robotic Capsule Endoscopes (RCE) in vivo in the small intestine. The purpose of the device is to expedite and lower the cost of RCE development. Currently, there is no accurate in vitro test method nor apparatus to validate new RCE designs; therefore, RCEs are tested in vivo at a cost of ∼$1400 per swine test. The authors have developed an in vitro RCE testing device which generates two peristaltic waves to accurately simulate the two biomechanical actions of the human small intestine that are most relevant to RCE locomotion: traction force and contact force. The device was successfully calibrated to match human physiological ranges for traction force (4-40 gf), contact force (80-500 gf) and peristaltic wave propagation speed (0.08-2 cm s(-1)) for a common RCE capsule geometry of 3.5 cm length and 1.5 cm diameter.

Some physiological aspects of artificial gravity. [gravitational effects on human orthostatic tolerance and physical fitness

NASA Technical Reports Server (NTRS)

Cramer, D. B.; Graybiel, A.

1973-01-01

The effects of increasing artificial gravity exposure on four aspects of physiological fitness are examined in four young men who, prior to exposure, were deconditioned with bed rest and water immersion. The four aspects of physiological fitness are orthostatic tolerance, exercise tolerance, forearm endurance, and maximum strength. Orthostatic tolerance was sharply reduced by deconditioning and was substantially improved by walking in simulated lunar gravity (1/6 g) for 2.5 hours daily for 7 days or by walking in 1/2 g and 1 g for 1 hour daily for 3 days. Exercise tolerance was also sharply reduced by deconditioning but did not significantly improve with increasing g-exposure. Walking in 1 g for 1 hour daily for 3 days raised exercise tolerance only a little above the low produced by deconditioning. Forearm endurance and maximum strength were relatively unaffected by deconditioning and subsequent g-exposure.

Non-contact physiological signal detection using continuous wave Doppler radar.

PubMed

Qiao, Dengyu; He, Tan; Hu, Boping; Li, Ye

2014-01-01

The aim of this work is to show non-contact physiological signal monitoring system based on continuous-wave (CW) Doppler radar, which is becoming highly attractive in the field of health care monitoring of elderly people. Two radar signal processing methods were introduced in this paper: one to extract respiration and heart rates of a single person and the other to separate mixed respiration signals. To verify the validity of the methods, physiological signal is obtained from stationary human subjects using a CW Doppler radar unit. The sensor operating at 24 GHz is located 0.5 meter away from the subject. The simulation results show that the respiration and heart rates are clearly extracted, and the mixed respiration signals are successfully separated. Finally, reference respiration and heart rate signals are measured by an ECG monitor and compared with the results tracked by the CW Doppler radar monitoring system.

Biological and medical applications of a brain-on-a-chip

PubMed Central

2016-01-01

The desire to develop and evaluate drugs as potential countermeasures for biological and chemical threats requires test systems that can also substitute for the clinical trials normally crucial for drug development. Current animal models have limited predictivity for drug efficacy in humans as the large majority of drugs fails in clinical trials. We have limited understanding of the function of the central nervous system and the complexity of the brain, especially during development and neuronal plasticity. Simple in vitro systems do not represent physiology and function of the brain. Moreover, the difficulty of studying interactions between human genetics and environmental factors leads to lack of knowledge about the events that induce neurological diseases. Microphysiological systems (MPS) promise to generate more complex in vitro human models that better simulate the organ’s biology and function. MPS combine different cell types in a specific three-dimensional (3D) configuration to simulate organs with a concrete function. The final aim of these MPS is to combine different “organoids” to generate a human-on-a-chip, an approach that would allow studies of complex physiological organ interactions. The recent discovery of induced pluripotent stem cells (iPSCs) gives a range of possibilities allowing cellular studies of individuals with different genetic backgrounds (e.g., human disease models). Application of iPSCs from different donors in MPS gives the opportunity to better understand mechanisms of the disease and can be a novel tool in drug development, toxicology, and medicine. In order to generate a brain-on-a-chip, we have established a 3D model from human iPSCs based on our experience with a 3D rat primary aggregating brain model. After four weeks of differentiation, human 3D aggregates stain positive for different neuronal markers and show higher gene expression of various neuronal differentiation markers compared to 2D cultures. Here we present the applications and challenges of this emerging technology. PMID:24912505

Application of muscadine grape (Vitis rotundifolia Michx.) pomace extract to reduce carcinogenic acrylamide.

PubMed

Xu, Changmou; Yagiz, Yavuz; Marshall, Sara; Li, Zheng; Simonne, Amarat; Lu, Jiang; Marshall, Maurice R

2015-09-01

Acrylamide is a byproduct of the Maillard reaction and is formed in a variety of heat-treated commercial starchy foods. It is known to be toxic and potentially carcinogenic to humans. Muscadine grape polyphenols and standard phenolic compounds were examined on the reduction of acrylamide in an equimolar asparagine/glucose chemical model, a potato chip model, and a simulated physiological system. Polyphenols were found to significantly reduce acrylamide in the chemical model, with reduced rates higher than 90% at 100 μg/ml. In the potato chip model, grape polyphenols reduced the acrylamide level by 60.3% as concentration was increased to 0.1%. However, polyphenols exhibited no acrylamide reduction in the simulated physiological system. Results also indicated no significant correlation between the antioxidant activities of polyphenols and their acrylamide inhibition. This study demonstrated muscadine grape extract can mitigate acrylamide formation in the Maillard reaction, which provides a new value-added application for winery pomace waste. Copyright © 2015 Elsevier Ltd. All rights reserved.

A first step towards a consensus static in vitro model for simulating full-term infant digestion.

PubMed

Ménard, O; Bourlieu, C; De Oliveira, S C; Dellarosa, N; Laghi, L; Carrière, F; Capozzi, F; Dupont, D; Deglaire, A

2018-02-01

In vitro alternatives to clinical trials are used for studying human food digestion. For simulating infant digestion, only a few models, lacking physiological relevance, are available. Thanks to an extensive literature review of the in vivo infant digestive conditions, a gastrointestinal static in vitro model was developed for infants born at term and aged 28days. The model was applied to the digestion of a commercial infant formula. Kinetics of digestion, as well as the structural evolution, were compared with those obtained while submitting the same formula to the adult international consensus protocol of in vitro static digestion. The kinetics of proteolysis and lipolysis differed according to the physiological stage resulting mainly from the reduced level of enzymes and bile salts, as well as the higher gastric pH in the infant model. This in vitro static model of infant digestion is of interest for scientists, food or pharmaceutical manufacturers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of simulated microgravity on growth and production of exopolymeric substances of Micrococcus luteus space and earth isolates.

PubMed

Mauclaire, Laurie; Egli, Marcel

2010-08-01

Microorganisms tend to form biofilms on surfaces, thereby causing deterioration of the underlaying material. In addition, biofilm is a potential health risk to humans. Therefore, microorganism growth is not only an issue on Earth but also in manned space habitats like the International Space Station (ISS). The aim of the study was to identify physiological processes relevant for Micrococcus luteus attachment under microgravity conditions. The results demonstrate that simulated microgravity influences physiological processes which trigger bacterial attachment and biofilm formation. The ISS strains produced larger amounts of exopolymeric substances (EPS) compared with a reference strain from Earth. In contrast, M. luteus strains were growing faster, and Earth as well as ISS isolates produced a higher yield of biomass under microgravity conditions than under normal gravity. Furthermore, microgravity caused a reduction of the colloidal EPS production of ISS isolates in comparison with normal gravity, which probably influences biofilm thickness and stability as well.

Objects Mental Rotation under 7 Days Simulated Weightlessness Condition: An ERP Study

PubMed Central

Wang, Hui; Duan, Jiaobo; Liao, Yang; Wang, Chuang; Li, Hongzheng; Liu, Xufeng

2017-01-01

During the spaceflight under weightlessness condition, human's brain function may be affected by the changes of physiological effects along with the distribution of blood and body fluids to the head. This variation of brain function will influence the performance of astronauts and therefore create possible harm to flight safety. This study employs 20 male subjects in a 7-day−6° head-down tilted (HDT) bed rest model to simulate physiological effects under weightlessness condition, and use behavioral, electrophysiological techniques to compare the changes of mental rotation ability (MR ability) before and after short-term simulated weightlessness state. Behavioral results suggested that significant linear relationship existed between the rotation angle of stimuli and the reaction time, which means mental rotation process do happen during the MR task in simulated weightlessness state. In the first 3 days, the P300 component induced by object mental rotation followed the “down-up-down” pattern. In the following 4 days it changed randomly. On HDT D2, the mean of the amplitude of the P300 was the lowest, while increased gently on HDT D3. There was no obvious changing pattern of the amplitude of P300 observed after 3 days of HDT. Simulated weightlessness doesn't change the basic process of mental rotation. The effect of simulated weightlessness is neural mechanism of self-adaptation. MR ability didn't bounce back to the original level after HDT test. PMID:29270115

Artificial gravity as a countermeasure for mitigating physiological deconditioning during long-duration space missions

PubMed Central

Clément, Gilles R.; Bukley, Angelia P.; Paloski, William H.

2015-01-01

In spite of the experience gained in human space flight since Yuri Gagarin’s historical flight in 1961, there has yet to be identified a completely effective countermeasure for mitigating the effects of weightlessness on humans. Were astronauts to embark upon a journey to Mars today, the 6-month exposure to weightlessness en route would leave them considerably debilitated, even with the implementation of the suite of piece-meal countermeasures currently employed. Continuous or intermittent exposure to simulated gravitational states on board the spacecraft while traveling to and from Mars, also known as artificial gravity, has the potential for enhancing adaptation to Mars gravity and re-adaptation to Earth gravity. Many physiological functions are adversely affected by the weightless environment of spaceflight because they are calibrated for normal, Earth’s gravity. Hence, the concept of artificial gravity is to provide a broad-spectrum replacement for the gravitational forces that naturally occur on the Earth’s surface, thereby avoiding the physiological deconditioning that takes place in weightlessness. Because researchers have long been concerned by the adverse sensorimotor effects that occur in weightlessness as well as in rotating environments, additional study of the complex interactions among sensorimotor and other physiological systems in rotating environments must be undertaken both on Earth and in space before artificial gravity can be implemented. PMID:26136665

The use of physiological solutions or media in calcium phosphate synthesis and processing.

PubMed

Tas, A Cuneyt

2014-05-01

This review examined the literature to spot uses, if any, of physiological solutions/media for the in situ synthesis of calcium phosphates (CaP) under processing conditions (i.e. temperature, pH, concentration of inorganic ions present in media) mimicking those prevalent in the human hard tissue environments. There happens to be a variety of aqueous solutions or media developed for different purposes; sometimes they have been named as physiological saline, isotonic solution, cell culture solution, metastable CaP solution, supersaturated calcification solution, simulated body fluid or even dialysate solution (for dialysis patients). Most of the time such solutions were not used as the aqueous medium to perform the biomimetic synthesis of calcium phosphates, and their use was usually limited to the in vitro testing of synthetic biomaterials. This review illustrates that only a limited number of research studies used physiological solutions or media such as Earle's balanced salt solution, Bachra et al. solutions or Tris-buffered simulated body fluid solution containing 27mM HCO3(-) for synthesizing CaP, and these studies have consistently reported the formation of X-ray-amorphous CaP nanopowders instead of Ap-CaP or stoichiometric hydroxyapatite (HA, Ca10(PO4)6(OH)2) at 37°C and pH 7.4. By relying on the published articles, this review highlights the significance of the use of aqueous solutions containing 0.8-1.5 mMMg(2+), 22-27mM HCO3(-), 142-145mM Na(+), 5-5.8mM K(+), 103-133mM Cl(-), 1.8-3.75mM Ca(2+), and 0.8-1.67mM HPO4(2-), which essentially mimic the composition and the overall ionic strength of the human extracellular fluid (ECF), in forming the nanospheres of X-ray-amorphous CaP. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Multiwaveband simulation-based signature analysis of camouflaged human dismounts in cluttered environments with TAIThermIR and MuSES

NASA Astrophysics Data System (ADS)

Packard, Corey D.; Klein, Mark D.; Viola, Timothy S.; Hepokoski, Mark A.

2016-10-01

The ability to predict electro-optical (EO) signatures of diverse targets against cluttered backgrounds is paramount for signature evaluation and/or management. Knowledge of target and background signatures is essential for a variety of defense-related applications. While there is no substitute for measured target and background signatures to determine contrast and detection probability, the capability to simulate any mission scenario with desired environmental conditions is a tremendous asset for defense agencies. In this paper, a systematic process for the thermal and visible-through-infrared simulation of camouflaged human dismounts in cluttered outdoor environments is presented. This process, utilizing the thermal and EO/IR radiance simulation tool TAIThermIR (and MuSES), provides a repeatable and accurate approach for analyzing contrast, signature and detectability of humans in multiple wavebands. The engineering workflow required to combine natural weather boundary conditions and the human thermoregulatory module developed by ThermoAnalytics is summarized. The procedure includes human geometry creation, human segmental physiology description and transient physical temperature prediction using environmental boundary conditions and active thermoregulation. Radiance renderings, which use Sandford-Robertson BRDF optical surface property descriptions and are coupled with MODTRAN for the calculation of atmospheric effects, are demonstrated. Sensor effects such as optical blurring and photon noise can be optionally included, increasing the accuracy of detection probability outputs that accompany each rendering. This virtual evaluation procedure has been extensively validated and provides a flexible evaluation process that minimizes the difficulties inherent in human-subject field testing. Defense applications such as detection probability assessment, camouflage pattern evaluation, conspicuity tests and automatic target recognition are discussed.

Reconstruction of Exposure to m-Xylene from Human Biomonitoring Data Using PBPK Modelling, Bayesian Inference, and Markov Chain Monte Carlo Simulation

PubMed Central

McNally, Kevin; Cotton, Richard; Cocker, John; Jones, Kate; Bartels, Mike; Rick, David; Price, Paul; Loizou, George

2012-01-01

There are numerous biomonitoring programs, both recent and ongoing, to evaluate environmental exposure of humans to chemicals. Due to the lack of exposure and kinetic data, the correlation of biomarker levels with exposure concentrations leads to difficulty in utilizing biomonitoring data for biological guidance values. Exposure reconstruction or reverse dosimetry is the retrospective interpretation of external exposure consistent with biomonitoring data. We investigated the integration of physiologically based pharmacokinetic modelling, global sensitivity analysis, Bayesian inference, and Markov chain Monte Carlo simulation to obtain a population estimate of inhalation exposure to m-xylene. We used exhaled breath and venous blood m-xylene and urinary 3-methylhippuric acid measurements from a controlled human volunteer study in order to evaluate the ability of our computational framework to predict known inhalation exposures. We also investigated the importance of model structure and dimensionality with respect to its ability to reconstruct exposure. PMID:22719759

Use of Multiple GPUs to Speedup the Execution of a Three-Dimensional Computational Model of the Innate Immune System

NASA Astrophysics Data System (ADS)

Xavier, M. P.; do Nascimento, T. M.; dos Santos, R. W.; Lobosco, M.

2014-03-01

The development of computational systems that mimics the physiological response of organs or even the entire body is a complex task. One of the issues that makes this task extremely complex is the huge computational resources needed to execute the simulations. For this reason, the use of parallel computing is mandatory. In this work, we focus on the simulation of temporal and spatial behaviour of some human innate immune system cells and molecules in a small three-dimensional section of a tissue. To perform this simulation, we use multiple Graphics Processing Units (GPUs) in a shared-memory environment. Despite of high initialization and communication costs imposed by the use of GPUs, the techniques used to implement the HIS simulator have shown to be very effective to achieve this purpose.

The role of ecosystem-atmosphere interactions in simulated Amazonian precipitation decrease and forest dieback under global climate warming

NASA Astrophysics Data System (ADS)

Betts, R. A.; Cox, P. M.; Collins, M.; Harris, P. P.; Huntingford, C.; Jones, C. D.

A suite of simulations with the HadCM3LC coupled climate-carbon cycle model is used to examine the various forcings and feedbacks involved in the simulated precipitation decrease and forest dieback. Rising atmospheric CO2 is found to contribute 20% to the precipitation reduction through the physiological forcing of stomatal closure, with 80% of the reduction being seen when stomatal closure was excluded and only radiative forcing by CO2 was included. The forest dieback exerts two positive feedbacks on the precipitation reduction; a biogeophysical feedback through reduced forest cover suppressing local evaporative water recycling, and a biogeochemical feedback through the release of CO2 contributing to an accelerated global warming. The precipitation reduction is enhanced by 20% by the biogeophysical feedback, and 5% by the carbon cycle feedback from the forest dieback. This analysis helps to explain why the Amazonian precipitation reduction simulated by HadCM3LC is more extreme than that simulated in other GCMs; in the fully-coupled, climate-carbon cycle simulation, approximately half of the precipitation reduction in Amazonia is attributable to a combination of physiological forcing and biogeophysical and global carbon cycle feedbacks, which are generally not included in other GCM simulations of future climate change. The analysis also demonstrates the potential contribution of regional-scale climate and ecosystem change to uncertainties in global CO2 and climate change projections. Moreover, the importance of feedbacks suggests that a human-induced increase in forest vulnerability to climate change may have implications for regional and global scale climate sensitivity.

Virtual tissues in toxicology.

PubMed

Shah, Imran; Wambaugh, John

2010-02-01

New approaches are vital for efficiently evaluating human health risk of thousands of chemicals in commerce. In vitro models offer a high-throughput approach for assaying chemical-induced molecular and cellular changes; however, bridging these perturbations to in vivo effects across chemicals, dose, time, and species remains challenging. Technological advances in multiresolution imaging and multiscale simulation are making it feasible to reconstruct tissues in silico. In toxicology, these "virtual" tissues (VT) aim to predict histopathological outcomes from alterations of cellular phenotypes that are controlled by chemical-induced perturbations in molecular pathways. The behaviors of thousands of heterogeneous cells in tissues are simulated discretely using agent-based modeling (ABM), in which computational "agents" mimic cell interactions and cellular responses to the microenvironment. The behavior of agents is constrained by physical laws and biological rules derived from experimental evidence. VT extend compartmental physiologic models to simulate both acute insults as well as the chronic effects of low-dose exposure. Furthermore, agent behavior can encode the logic of signaling and genetic regulatory networks to evaluate the role of different pathways in chemical-induced injury. To extrapolate toxicity across species, chemicals, and doses, VT require four main components: (a) organization of prior knowledge on physiologic events to define the mechanistic rules for agent behavior, (b) knowledge on key chemical-induced molecular effects, including activation of stress sensors and changes in molecular pathways that alter the cellular phenotype, (c) multiresolution quantitative and qualitative analysis of histologic data to characterize and measure chemical-, dose-, and time-dependent physiologic events, and (d) multiscale, spatiotemporal simulation frameworks to effectively calibrate and evaluate VT using experimental data. This investigation presents the motivation, implementation, and application of VT with examples from hepatotoxicity and carcinogenesis.

Results and Lessons Learned from Performance Testing of Humans in Spacesuits in Simulated Reduced Gravity

NASA Technical Reports Server (NTRS)

Chappell, Steven P.; Norcross, Jason R.; Gernhardt, Michael L.

2010-01-01

The Apollo lunar EVA experience revealed challenges with suit stability and control-likely a combination of mass, mobility, and center of gravity (CG) factors. The EVA Physiology, Systems and Performence (EPSP) Project is systematically working with other NASA projects, labs, and facilities to lead a series of studies to understand the role of suit mass, weight, CG, and other parameters on astronaut performance in partial gravity environments.

In vitro method for assessing the biomechanics of the patellofemoral joint following total knee arthroplasty.

PubMed

Coles, L G; Gheduzzi, S; Miles, A W

2014-12-01

The patellofemoral joint is a common site of pain and failure following total knee arthroplasty. A contributory factor may be adverse patellofemoral biomechanics. Cadaveric investigations are commonly used to assess the biomechanics of the joint, but are associated with high inter-specimen variability and often cannot be carried out at physiological levels of loading. This study aimed to evaluate the suitability of a novel knee simulator for investigating patellofemoral joint biomechanics. This simulator specifically facilitated the extended assessment of patellofemoral joint biomechanics under physiological levels of loading. The simulator allowed the knee to move in 6 degrees of freedom under quadriceps actuation and included a simulation of the action of the hamstrings. Prostheses were implanted on synthetic bones and key soft tissues were modelled with a synthetic analogue. In order to evaluate the physiological relevance and repeatability of the simulator, measurements were made of the quadriceps force and the force, contact area and pressure within the patellofemoral joint using load cells, pressure-sensitive film, and a flexible pressure sensor. The results were in agreement with those previously reported in the literature, confirming that the simulator is able to provide a realistic physiological loading situation. Under physiological loading, average standard deviations of force and area measurements were substantially lower and comparable to those reported in previous cadaveric studies, respectively. The simulator replicates the physiological environment and has been demonstrated to allow the initial investigation of factors affecting patellofemoral biomechanics following total knee arthroplasty. © IMechE 2014.

Successful Implementation of Inquiry-Based Physiology Laboratories in Undergraduate Major and Nonmajor Courses

ERIC Educational Resources Information Center

Casotti, G.; Rieser-Danner, L.; Knabb, M. T.

2008-01-01

Recent evidence has demonstrated that inquiry-based physiology laboratories improve students' critical- and analytical-thinking skills. We implemented inquiry-based learning into three physiology courses: Comparative Vertebrate Physiology (majors), Human Physiology (majors), and Human Anatomy and Physiology (nonmajors). The aims of our curricular…

Prediction of human pharmacokinetics using physiologically based modeling: a retrospective analysis of 26 clinically tested drugs.

PubMed

De Buck, Stefan S; Sinha, Vikash K; Fenu, Luca A; Nijsen, Marjoleen J; Mackie, Claire E; Gilissen, Ron A H J

2007-10-01

The aim of this study was to evaluate different physiologically based modeling strategies for the prediction of human pharmacokinetics. Plasma profiles after intravenous and oral dosing were simulated for 26 clinically tested drugs. Two mechanism-based predictions of human tissue-to-plasma partitioning (P(tp)) from physicochemical input (method Vd1) were evaluated for their ability to describe human volume of distribution at steady state (V(ss)). This method was compared with a strategy that combined predicted and experimentally determined in vivo rat P(tp) data (method Vd2). Best V(ss) predictions were obtained using method Vd2, providing that rat P(tp) input was corrected for interspecies differences in plasma protein binding (84% within 2-fold). V(ss) predictions from physicochemical input alone were poor (32% within 2-fold). Total body clearance (CL) was predicted as the sum of scaled rat renal clearance and hepatic clearance projected from in vitro metabolism data. Best CL predictions were obtained by disregarding both blood and microsomal or hepatocyte binding (method CL2, 74% within 2-fold), whereas strong bias was seen using both blood and microsomal or hepatocyte binding (method CL1, 53% within 2-fold). The physiologically based pharmacokinetics (PBPK) model, which combined methods Vd2 and CL2 yielded the most accurate predictions of in vivo terminal half-life (69% within 2-fold). The Gastroplus advanced compartmental absorption and transit model was used to construct an absorption-disposition model and provided accurate predictions of area under the plasma concentration-time profile, oral apparent volume of distribution, and maximum plasma concentration after oral dosing, with 74%, 70%, and 65% within 2-fold, respectively. This evaluation demonstrates that PBPK models can lead to reasonable predictions of human pharmacokinetics.

Virtual physiological human: training challenges.

PubMed

Lawford, Patricia V; Narracott, Andrew V; McCormack, Keith; Bisbal, Jesus; Martin, Carlos; Bijnens, Bart; Brook, Bindi; Zachariou, Margarita; Freixa, Jordi Villà I; Kohl, Peter; Fletcher, Katherine; Diaz-Zuccarini, Vanessa

2010-06-28

The virtual physiological human (VPH) initiative encompasses a wide range of activities, including structural and functional imaging, data mining, knowledge discovery tool and database development, biomedical modelling, simulation and visualization. The VPH community is developing from a multitude of relatively focused, but disparate, research endeavours into an integrated effort to bring together, develop and translate emerging technologies for application, from academia to industry and medicine. This process initially builds on the evolution of multi-disciplinary interactions and abilities, but addressing the challenges associated with the implementation of the VPH will require, in the very near future, a translation of quantitative changes into a new quality of highly trained multi-disciplinary personnel. Current strategies for undergraduate and on-the-job training may soon prove insufficient for this. The European Commission seventh framework VPH network of excellence is exploring this emerging need, and is developing a framework of novel training initiatives to address the predicted shortfall in suitably skilled VPH-aware professionals. This paper reports first steps in the implementation of a coherent VPH training portfolio.

Bayesian inference of physiologically meaningful parameters from body sway measurements.

PubMed

Tietäväinen, A; Gutmann, M U; Keski-Vakkuri, E; Corander, J; Hæggström, E

2017-06-19

The control of the human body sway by the central nervous system, muscles, and conscious brain is of interest since body sway carries information about the physiological status of a person. Several models have been proposed to describe body sway in an upright standing position, however, due to the statistical intractability of the more realistic models, no formal parameter inference has previously been conducted and the expressive power of such models for real human subjects remains unknown. Using the latest advances in Bayesian statistical inference for intractable models, we fitted a nonlinear control model to posturographic measurements, and we showed that it can accurately predict the sway characteristics of both simulated and real subjects. Our method provides a full statistical characterization of the uncertainty related to all model parameters as quantified by posterior probability density functions, which is useful for comparisons across subjects and test settings. The ability to infer intractable control models from sensor data opens new possibilities for monitoring and predicting body status in health applications.

Effects of restraint and cabin environment on skin temperature, sleep-wake, feeding and drinking circadian rhythms in Macaca mulatta during spacelab flight simulation.

PubMed

Demaria-Pesce, V H; Balzamo, E

1994-05-01

Exposure to a weightless environment such as in spaceflight, leads to a number of physiological responses to assure the survival of an organism in this new environment. However, the real effect of microgravity itself has not been clearly established yet. Considering the environmental and operational characteristics of a spaceflight, and as it has been shown in previous flights, the use of animals, and more particularly the non-human primates, takes on importance in understanding the mechanisms and factors involved in the adaptation to changes in gravitational loading. The SLS-3 flight of the American shuttle, scheduled for launch in early 1996, will be the first flight of the Rhesus project, a joint program of C.N.E.S. and N.A.S.A. which will carry out experiments in various physiological disciplines using the Rhesus monkey as a human surrogate. This 16 day orbital flight will be the longest flight accomplished by the shuttle to date. A number of feasibility studies have already been conducted on Macaca mulatta in order to simulate flight conditions to obtain ground data and to test the technical characteristics of the Rhesus Research Facility which have been described elsewhere. Microgravity might be the main factor inducing the physiological changes observed during spaceflights. However, these responses could also be influenced by other factors related to the spaceflight environment such as the life support systems of the spacecraft. Thus, the main purpose of the present study was to determine the impact of specific restraint and cabin environment on the circadian rhythms of body temperature, feeding, drinking, and sleep-waking in order to separate them from the real impact of microgravity.

Frontiers in the Teaching of Physiology. Computer Literacy and Simulation.

ERIC Educational Resources Information Center

Tidball, Charles S., Ed.; Shelesnyak, M. C., Ed.

Provided is a collection of papers on computer literacy and simulation originally published in The Physiology Teacher, supplemented by additional papers and a glossary of terms relevant to the field. The 12 papers are presented in five sections. An affirmation of conventional physiology laboratory exercises, coping with computer terminology, and…

Identifying populations sensitive to environmental chemicals by simulating toxicokinetic variability.

PubMed

Ring, Caroline L; Pearce, Robert G; Setzer, R Woodrow; Wetmore, Barbara A; Wambaugh, John F

2017-09-01

The thousands of chemicals present in the environment (USGAO, 2013) must be triaged to identify priority chemicals for human health risk research. Most chemicals have little of the toxicokinetic (TK) data that are necessary for relating exposures to tissue concentrations that are believed to be toxic. Ongoing efforts have collected limited, in vitro TK data for a few hundred chemicals. These data have been combined with biomonitoring data to estimate an approximate margin between potential hazard and exposure. The most "at risk" 95th percentile of adults have been identified from simulated populations that are generated either using standard "average" adult human parameters or very specific cohorts such as Northern Europeans. To better reflect the modern U.S. population, we developed a population simulation using physiologies based on distributions of demographic and anthropometric quantities from the most recent U.S. Centers for Disease Control and Prevention National Health and Nutrition Examination Survey (NHANES) data. This allowed incorporation of inter-individual variability, including variability across relevant demographic subgroups. Variability was analyzed with a Monte Carlo approach that accounted for the correlation structure in physiological parameters. To identify portions of the U.S. population that are more at risk for specific chemicals, physiologic variability was incorporated within an open-source high-throughput (HT) TK modeling framework. We prioritized 50 chemicals based on estimates of both potential hazard and exposure. Potential hazard was estimated from in vitro HT screening assays (i.e., the Tox21 and ToxCast programs). Bioactive in vitro concentrations were extrapolated to doses that produce equivalent concentrations in body tissues using a reverse dosimetry approach in which generic TK models are parameterized with: 1) chemical-specific parameters derived from in vitro measurements and predicted from chemical structure; and 2) with physiological parameters for a virtual population. For risk-based prioritization of chemicals, predicted bioactive equivalent doses were compared to demographic-specific inferences of exposure rates that were based on NHANES urinary analyte biomonitoring data. The inclusion of NHANES-derived inter-individual variability decreased predicted bioactive equivalent doses by 12% on average for the total population when compared to previous methods. However, for some combinations of chemical and demographic groups the margin was reduced by as much as three quarters. This TK modeling framework allows targeted risk prioritization of chemicals for demographic groups of interest, including potentially sensitive life stages and subpopulations. Published by Elsevier Ltd.

Lab-on-a-brane: A novel physiologically relevant planar arterial model to study transendothelial transport

NASA Astrophysics Data System (ADS)

Budhwani, Karim Ismail

The tremendous quality of life impact notwithstanding, cardiovascular diseases and Cancer add up to over US$ 700bn each year in financial costs alone. Aging and population growth are expected to further expand the problem space while drug research and development remain expensive. However, preclinical costs can be substantially mitigated by substituting animal models with in vitro devices that accurately model human cardiovascular transport. Here we present a novel physiologically relevant lab-on-a-brane that simulates in vivo pressure, flow, strain, and shear waveforms associated with normal and pathological conditions in large and small blood vessels for studying molecular transport across the endothelial monolayer. The device builds upon previously demonstrated integrated microfluidic loop design by: (a) introducing nanoscale pores in the substrate membrane to enable transmembrane molecular transport, (b) transforming the substrate membrane into a nanofibrous matrix for 3D smooth muscle cell (SMC) tissue culture, (c) integrating electrospinning fabrication methods, (d) engineering an invertible sandwich cell culture device architecture, and (e) devising a healthy co-culture mechanism for human arterial endothelial cell (HAEC) monolayer and multiple layers of human smooth muscle cells (HSMC) to accurately mimic arterial anatomy. Structural and mechanical characterization was conducted using confocal microscopy, SEM, stress/strain analysis, and infrared spectroscopy. Transport was characterized using FITC-Dextran hydraulic permeability protocol. Structure and transport characterization successfully demonstrate device viability as a physiologically relevant arterial mimic for testing transendothelial transport. Thus, our lab-on-a-brane provides a highly effective and efficient, yet considerably inexpensive, physiologically relevant alternative for pharmacokinetic evaluation; possibly reducing animals used in pre-clinical testing, clinical trials cost from false starts, and time-to-market. Furthermore, this platform can be easily configured for testing targeted therapeutic delivery and in multiple simultaneous arrays for personalized and precision medicine applications.

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

Human Milk Warming Temperatures Using a Simulation of Currently Available Storage and Warming Methods

PubMed Central

Bransburg-Zabary, Sharron; Virozub, Alexander; Mimouni, Francis B.

2015-01-01

Human milk handling guidelines are very demanding, based upon solid scientific evidence that handling methods can make a real difference in infant health and nutrition. Indeed, properly stored milk maintains many of its unique qualities and continues to be the second and third best infant feeding alternatives, much superior to artificial feeding. Container type and shape, mode of steering, amount of air exposure and storage temperature may adversely affect milk stability and composition. Heating above physiological temperatures significantly impacts nutritional and immunological properties of milk. In spite of this knowledge, there are no strict guidelines regarding milk warming. Human milk is often heated in electrical-based bottle warmers that can exceed 80°C, a temperature at which many beneficial human milk properties disappear. High temperatures can also induce fat profile variations as compared with fresh human milk. In this manuscript we estimate the amount of damage due to overheating during warming using a heat flow simulation of a regular water based bottle warmer. To do so, we carried out a series of warming simulations which provided us with dynamic temperature fields within bottled milk. We simulated the use of a hot water-bath at 80°C to heat bottled refrigerated milk (60ml and 178 ml) to demonstrate that large milk portions are overheated (above 40°C). It seems that the contemporary storage method (upright feeding tool, i.e. bottle) and bottle warming device, are not optimize to preserve the unique properties of human milk. Health workers and parents should be aware of this problem especially when it relates to sick neonates and preemies that cannot be directly fed at the breast. PMID:26061694

Physics, chemistry and pulmonary sequelae of thermodegradation events in long-mission space flight

NASA Technical Reports Server (NTRS)

Todd, Paul; Sklar, Michael; Ramirez, W. Fred; Smith, Gerald J.; Morgenthaler, George W.; Oberdoerster, Guenter

1993-01-01

An event in which electronic insulation consisting of polytetrafluoroethylene undergoes thermodegradation on the Space Station Freedom is considered experimentally and theoretically from the initial chemistry and convective transport through pulmonary deposition in humans. The low-gravity enviroment impacts various stages of event simulation. Vapor-phase and particulate thermodegradation products were considered as potential spacecraft contaminants. A potential pathway for the production of ultrafine particles was identified. Different approaches to the simulation and prediction of contaminant transport were studied and used to predict the distribution of generic vapor-phase products in a Space Station model. A lung transport model was used to assess the pulmonary distribution of inhaled particles, and, finally, the impact of adaptation to low gravity on the human response to this inhalation risk was explored on the basis of known physiological modifications of the immune, endocrine, musculoskeletal and pulmonary systems that accompany space flight.

Predicting the oral pharmacokinetic profiles of multiple-unit (pellet) dosage forms using a modeling and simulation approach coupled with biorelevant dissolution testing: case example diclofenac sodium.

PubMed

Kambayashi, Atsushi; Blume, Henning; Dressman, Jennifer B

2014-07-01

The objective of this research was to characterize the dissolution profile of a poorly soluble drug, diclofenac, from a commercially available multiple-unit enteric coated dosage form, Diclo-Puren® capsules, and to develop a predictive model for its oral pharmacokinetic profile. The paddle method was used to obtain the dissolution profiles of this dosage form in biorelevant media, with the exposure to simulated gastric conditions being varied in order to simulate the gastric emptying behavior of pellets. A modified Noyes-Whitney theory was subsequently fitted to the dissolution data. A physiologically-based pharmacokinetic (PBPK) model for multiple-unit dosage forms was designed using STELLA® software and coupled with the biorelevant dissolution profiles in order to simulate the plasma concentration profiles of diclofenac from Diclo-Puren® capsule in both the fasted and fed state in humans. Gastric emptying kinetics relevant to multiple-units pellets were incorporated into the PBPK model by setting up a virtual patient population to account for physiological variations in emptying kinetics. Using in vitro biorelevant dissolution coupled with in silico PBPK modeling and simulation it was possible to predict the plasma profile of this multiple-unit formulation of diclofenac after oral administration in both the fasted and fed state. This approach might be useful to predict variability in the plasma profiles for other drugs housed in multiple-unit dosage forms. Copyright © 2014 Elsevier B.V. All rights reserved.

The Effects of Filter Cutoff Frequency on Musculoskeletal Simulations of High-Impact Movements.

PubMed

Tomescu, Sebastian; Bakker, Ryan; Beach, Tyson A C; Chandrashekar, Naveen

2018-02-12

Estimation of muscle forces through musculoskeletal simulation is important in understanding human movement and injury. Unmatched filter frequencies used to low-pass filter marker and force platform data can create artifacts during inverse dynamics analysis, but their effects on muscle force calculations are unknown. The objective of this study was to determine the effects of filter cutoff frequency on simulation parameters and magnitudes of lower extremity muscle and resultant joint contact forces during a high-impact maneuver. Eight participants performed a single leg jump-landing. Kinematics were captured with a 3D motion capture system and ground reaction forces were recorded with a force platform. The marker and force platform data were filtered using two matched filter frequencies (10-10Hz, 15-15Hz) and two unmatched frequencies (10-50Hz, 15-50Hz). Musculoskeletal simulations using Computed Muscle Control were performed in OpenSim. The results revealed significantly higher peak quadriceps (13%), hamstrings (48%), and gastrocnemius forces (69%) in the unmatched (10-50Hz, 15-50Hz) conditions than in the matched (10-10Hz, 15-15Hz) conditions (p<0.05). Resultant joint contact forces and reserve (non-physiologic) moments were similarly larger in the unmatched filter categories (p<0.05). This study demonstrated that artifacts created from filtering with unmatched filter cutoffs result in altered muscle forces and dynamics which are not physiologic.

A Case for Hypogravity Studies Aboard ISS

NASA Technical Reports Server (NTRS)

Paloski, William H.

2014-01-01

Future human space exploration missions being contemplated by NASA and other spacefaring nations include some that would require long stays upon bodies having gravity levels much lower than that of Earth. While we have been able to quantify the physiological effects of sustained exposure to microgravity during various spaceflight programs over the past half-century, there has been no opportunity to study the physiological adaptations to gravity levels between zero-g and one-g. We know now that the microgravity environment of spaceflight drives adaptive responses of the bone, muscle, cardiovascular, and sensorimotor systems, causing bone demineralization, muscle atrophy, reduced aerobic capacity, motion sickness, and malcoordination. All of these outcomes can affect crew health and performance, particularly after return to a one-g environment. An important question for physicians, scientists, and mission designers planning human exploration missions to Mars (3/8 g), the Moon (1/6 g), or asteroids (likely negligible g) is: What protection can be expected from gravitational levels between zero-g and one-g? Will crewmembers deconditioned by six months of microgravity exposure on their way to Mars experience continued deconditioning on the Martian surface? Or, will the 3/8 g be sufficient to arrest or even reverse these adaptive changes? The implications for countermeasure deployment, habitat accommodations, and mission design warrant further investigation into the physiological responses to hypogravity. It is not possible to fully simulate hypogravity exposure on Earth for other than transient episodes (e.g., parabolic flight). However, it would be possible to do so in low Earth orbit (LEO) using the centrifugal forces produced in a live-aboard centrifuge. As we're not likely to launch a rotating human spacecraft into LEO anytime in the near future, we could take advantage of rodent subjects aboard the ISS if we had a centrifuge that could accommodate the rodent subjects for extended periods (weeks to months) at various hypogravity levels. Experiments aboard such a centrifuge could provide important insight into human exploration questions and simultaneously answer fundamental questions in gravitational physiology.

Teaching cardiovascular physiology with equivalent electronic circuits in a practically oriented teaching module.

PubMed

Ribaric, Samo; Kordas, Marjan

2011-06-01

Here, we report on a new tool for teaching cardiovascular physiology and pathophysiology that promotes qualitative as well as quantitative thinking about time-dependent physiological phenomena. Quantification of steady and presteady-state (transient) cardiovascular phenomena is traditionally done by differential equations, but this is time consuming and unsuitable for most undergraduate medical students. As a result, quantitative thinking about time-dependent physiological phenomena is often not extensively dealt with in an undergraduate physiological course. However, basic concepts of steady and presteady state can be explained with relative simplicity, without the introduction of differential equation, with equivalent electronic circuits (EECs). We introduced undergraduate medical students to the concept of simulating cardiovascular phenomena with EECs. EEC simulations facilitate the understanding of simple or complex time-dependent cardiovascular physiological phenomena by stressing the analogies between EECs and physiological processes. Student perceptions on using EEC to simulate, study, and understand cardiovascular phenomena were documented over a 9-yr period, and the impact of the course on the students' knowledge of selected basic facts and concepts in cardiovascular physiology was evaluated over a 3-yr period. We conclude that EECs are a valuable tool for teaching cardiovascular physiology concepts and that EECs promote active learning.

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

Structural alterations by five disease-causing mutations in the low-pH conformation of human dihydrolipoamide dehydrogenase (hLADH) analyzed by molecular dynamics - Implications in functional loss and modulation of reactive oxygen species generation by pathogenic hLADH forms.

PubMed

Ambrus, Attila; Mizsei, Reka; Adam-Vizi, Vera

2015-07-01

Human dihydrolipoamide dehydrogenase (hLADH) is a flavoenzyme component (E3) of the human alpha-ketoglutarate dehydrogenase complex (α-KGDHc) and few other dehydrogenase complexes. Pathogenic mutations of hLADH cause severe metabolic diseases (atypical forms of E3 deficiency) that often escalate to cardiological or neurological presentations and even premature death; the pathologies are generally accompanied by lactic acidosis. hLADH presents a distinct conformation under acidosis (pH 5.5-6.8) with lower physiological activity and the capacity of generating reactive oxygen species (ROS). It has been shown by our laboratory that selected pathogenic mutations, besides lowering the physiological activity of hLADH, significantly stimulate ROS generation by hLADH, especially at lower pH, which might play a role in the pathogenesis of E3-deficiency in respective cases. Previously, we generated by molecular dynamics (MD) simulation the low-pH hLADH structure and analyzed the structural changes induced in this structure by eight of the pathogenic mutations of hLADH. In the absence of high resolution mutant structures these pieces of information are crucial for the mechanistic investigation of the molecular pathogeneses of the hLADH protein. In the present work we analyzed by molecular dynamics simulation the structural changes induced in the low-pH conformation of hLADH by five pathogenic mutations of hLADH; the structures of these disease-causing mutants of hLADH have never been examined before.

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.

Investigation of clinical pharmacokinetic variability of an opioid antagonist through physiologically based absorption modeling.

PubMed

Ding, Xuan; He, Minxia; Kulkarni, Rajesh; Patel, Nita; Zhang, Xiaoyu

2013-08-01

Identifying the source of inter- and/or intrasubject variability in pharmacokinetics (PK) provides fundamental information in understanding the pharmacokinetics-pharmacodynamics relationship of a drug and project its efficacy and safety in clinical populations. This identification process can be challenging given that a large number of potential causes could lead to PK variability. Here we present an integrated approach of physiologically based absorption modeling to investigate the root cause of unexpectedly high PK variability of a Phase I clinical trial drug. LY2196044 exhibited high intersubject variability in the absorption phase of plasma concentration-time profiles in humans. This could not be explained by in vitro measurements of drug properties and excellent bioavailability with low variability observed in preclinical species. GastroPlus™ modeling suggested that the compound's optimal solubility and permeability characteristics would enable rapid and complete absorption in preclinical species and in humans. However, simulations of human plasma concentration-time profiles indicated that despite sufficient solubility and rapid dissolution of LY2196044 in humans, permeability and/or transit in the gastrointestinal (GI) tract may have been negatively affected. It was concluded that clinical PK variability was potentially due to the drug's antagonism on opioid receptors that affected its transit and absorption in the GI tract. Copyright © 2013 Wiley Periodicals, Inc.

Simulation of fluorescent measurements in the human skin

NASA Astrophysics Data System (ADS)

Meglinski, Igor V.; Sinichkin, Yurii P.; Utz, Sergei R.; Pilipenko, Helena A.

1995-05-01

Reflectance and fluorescence spectroscopy are successfully used for skin disease diagnostics. Human skin optical parameters are defined by its turbid, scattering properties with nonuniform absorption and fluorescence chromophores distribution, its multilayered structure, and variability under different physiological and pathological conditions. Theoretical modeling of light propagation in skin could improve the understanding of these condition and may be useful in the interpretation of in vivo reflectance and autofluorescence (AF) spectra. Laser application in medical optical tomography, tissue spectroscopy, and phototherapy stimulates the development of optical and mathematical light-tissue interaction models allowing to account the specific features of laser beam and tissue inhomogeneities. This paper presents the version of a Monte Carlo method for simulating of optical radiation propagation in biotissue and highly scattering media, allowing for 3D geometry of a medium. The simulation is based on use of Green's function of medium response to single external pulse. The process of radiation propagation is studied in the area with given boundary conditions, taking into account the processes of reflection and refraction at the boundaries of layers inside the medium under study. Results of Monte Carlo simulation were compared with experimental investigations and demonstrated good agreement.

Behavioral and Physiological Responses of Horses to Simulated Aircraft Noise

DTIC Science & Technology

1991-01-01

AL-TR-1991-0123 A R M BEHAVIORAL AND PHYSIOLOGICAL S RESPONSES OF HORSES TO SIMULATED T AIRCRAFT NOISE R 0 N G Michelle M. LeBlanc Christoph Lombard...COVERED • 10 January 1991 IFinal Report Dec 89 to Jan 91 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Behavioral and Physiological Responses of Horses to...NUMBER OF PAGES Aircraft, Noise, Domestic Animals, Horses , 70 Disturbance, Physiological Effects 16. PRICE CODE 17. SECURITY CLASSIFICATION 18. SECURITY

A Physiologically Based Pharmacokinetic Model for the Oxime TMB-4: Simulation of Rodent and Human Data

DTIC Science & Technology

2013-01-13

concentration gradient–driven diffusion across the membranes, but also on the permeability area (PA) cross product for the tissue, which slows the pene...or slowly (mus- cle, skin, bone) perfused tissues. Diffusion limitation con- stants (permeability area cross products or PAs), metabolism and...al. 1991; Worek et al. 2005). A PBPK model has the advan- tage of interspecies and cross -route extrapolation. This PBPK model was initially developed

Sociological aspects of permanent manned occupancy of space.

PubMed

Bluth, B J

1981-01-01

The author examines human experiences with isolation and confined groups to determine the sociological aspects of social isolation in space. Precedent experiences include Antarctic stations, oceanographic research vessels, submarines, undersea laboratories, and space simulators. The Soviet experience with multiple-person crews on the Salyut 6 space station is explored. Sociological aspects of isolation and confinement aboard a space station include physiological stress, social and psychological stress, group size and composition, group organization, architectural programming, privacy, and work/rest scheduling.

Virtually-augmented interfaces for tactical aircraft.

PubMed

Haas, M W

1995-05-01

The term Fusion Interface is defined as a class of interface which integrally incorporates both virtual and non-virtual concepts and devices across the visual, auditory and haptic sensory modalities. A fusion interface is a multi-sensory virtually-augmented synthetic environment. A new facility has been developed within the Human Engineering Division of the Armstrong Laboratory dedicated to exploratory development of fusion-interface concepts. One of the virtual concepts to be investigated in the Fusion Interfaces for Tactical Environments facility (FITE) is the application of EEG and other physiological measures for virtual control of functions within the flight environment. FITE is a specialized flight simulator which allows efficient concept development through the use of rapid prototyping followed by direct experience of new fusion concepts. The FITE facility also supports evaluation of fusion concepts by operational fighter pilots in a high fidelity simulated air combat environment. The facility was utilized by a multi-disciplinary team composed of operational pilots, human-factors engineers, electronics engineers, computer scientists, and experimental psychologists to prototype and evaluate the first multi-sensory, virtually-augmented cockpit. The cockpit employed LCD-based head-down displays, a helmet-mounted display, three-dimensionally localized audio displays, and a haptic display. This paper will endeavor to describe the FITE facility architecture, some of the characteristics of the FITE virtual display and control devices, and the potential application of EEG and other physiological measures within the FITE facility.

The design and development of a triaxial wear-testing joint simulator.

PubMed

Green, A S; O'Connell, M K; Lyons, A S; James, S P

1999-01-01

Most of the existing wear testers created to wear test total hip replacements, specifically the acetabular component, are designed to exert only an axial force and provide rotation in a close approximation of the actual femoral movement. The Rocky Mountain Joint Simulator was designed to exert three orthogonal forces and provide rotations about the X-, Y- and Z-axes to more closely simulate the physiological forces and motions found in the human gait cycle. The RMJS was also designed with adaptability for other joints, such as knees or canine hips, through the use of hydraulics and a computer-programmable control system. Such adaptability and functionality allows the researcher to more closely model a gait cycle, thereby obtaining wear patterns that resemble those found in retrieved implants more closely than existing simulators. Research is ongoing into the tuning and evaluation of the machine and preliminary acetabular component wear test results will be presented at the conference.

Integrating Medical Simulation Into the Physician Assistant Physiology Curriculum.

PubMed

Li, Lixin; Lopes, John; Zhou, Joseph Yi; Xu, Biao

2016-12-01

Medical simulation has recently been used in medical education, and evidence indicates that it is a valuable tool for teaching and evaluation. Very few studies have evaluated the integration of medical simulation in medical physiology education, particularly in PA programs. This study was designed to assess the value of integrating medical simulation into the PA physiology curriculum. Seventy-five students from the PA program at Central Michigan University participated in this study. Mannequin-based simulation was used to simulate a patient with hemorrhagic shock and congestive heart failure to demonstrate the Frank-Starling force and cardiac function curve. Before and after the medical simulation, students completed a questionnaire as a self-assessment. A knowledge test was also delivered after the simulation. Our study demonstrated a significant improvement in student confidence in understanding congestive heart failure, hemorrhagic shock, and the Frank-Starling curve after the simulation. Medical simulation may be an effective way to enhance basic science learning experiences for students and an ideal supplement to traditional, lecture-based teaching in PA education.

Bioglass implant-coating interactions in synthetic physiological fluids with varying degrees of biomimicry

PubMed Central

Popa, AC; Stan, GE; Husanu, MA; Mercioniu, I; Santos, LF; Fernandes, HR; Ferreira, JMF

2017-01-01

Synthetic physiological fluids are currently used as a first in vitro bioactivity assessment for bone grafts. Our understanding about the interactions taking place at the fluid–implant interface has evolved remarkably during the last decade, and does not comply with the traditional International Organization for Standardization/final draft International Standard 23317 protocol in purely inorganic simulated body fluid. The advances in our knowledge point to the need of a true paradigm shift toward testing physiological fluids with enhanced biomimicry and a better understanding of the materials’ structure-dissolution behavior. This will contribute to “upgrade” our vision of entire cascades of events taking place at the implant surfaces upon immersion in the testing media or after implantation. Starting from an osteoinductive bioglass composition with the ability to alleviate the oxidative stress, thin bioglass films with different degrees of polymerization were deposited onto titanium substrates. Their biomineralization activity in simulated body fluid and in a series of new inorganic–organic media with increasing biomimicry that more closely simulated the human intercellular environment was compared. A comprehensive range of advanced characterization tools (scanning electron microscopy; grazing-incidence X-ray diffraction; Fourier-transform infrared, micro-Raman, energy-dispersive, X-ray photoelectron, and surface-enhanced laser desorption/ionization time-of-flight mass spectroscopies; and cytocompatibility assays using mesenchymal stem cells) were used. The information gathered is very useful to biologists, biophysicists, clinicians, and material scientists with special interest in teaching and research. By combining all the analyses, we propose herein a step forward toward establishing an improved unified protocol for testing the bioactivity of implant materials. PMID:28176941

Bioglass implant-coating interactions in synthetic physiological fluids with varying degrees of biomimicry.

PubMed

Popa, A C; Stan, G E; Husanu, M A; Mercioniu, I; Santos, L F; Fernandes, H R; Ferreira, Jmf

2017-01-01

Synthetic physiological fluids are currently used as a first in vitro bioactivity assessment for bone grafts. Our understanding about the interactions taking place at the fluid-implant interface has evolved remarkably during the last decade, and does not comply with the traditional International Organization for Standardization/final draft International Standard 23317 protocol in purely inorganic simulated body fluid. The advances in our knowledge point to the need of a true paradigm shift toward testing physiological fluids with enhanced biomimicry and a better understanding of the materials' structure-dissolution behavior. This will contribute to "upgrade" our vision of entire cascades of events taking place at the implant surfaces upon immersion in the testing media or after implantation. Starting from an osteoinductive bioglass composition with the ability to alleviate the oxidative stress, thin bioglass films with different degrees of polymerization were deposited onto titanium substrates. Their biomineralization activity in simulated body fluid and in a series of new inorganic-organic media with increasing biomimicry that more closely simulated the human intercellular environment was compared. A comprehensive range of advanced characterization tools (scanning electron microscopy; grazing-incidence X-ray diffraction; Fourier-transform infrared, micro-Raman, energy-dispersive, X-ray photoelectron, and surface-enhanced laser desorption/ionization time-of-flight mass spectroscopies; and cytocompatibility assays using mesenchymal stem cells) were used. The information gathered is very useful to biologists, biophysicists, clinicians, and material scientists with special interest in teaching and research. By combining all the analyses, we propose herein a step forward toward establishing an improved unified protocol for testing the bioactivity of implant materials.

Drugs in space: Pharmacokinetics and pharmacodynamics in astronauts.

PubMed

Kast, Johannes; Yu, Yichao; Seubert, Christoph N; Wotring, Virginia E; Derendorf, Hartmut

2017-11-15

Space agencies are working intensely to push the current boundaries of human spaceflight by sending astronauts deeper into space than ever before, including missions to Mars and asteroids. Spaceflight alters human physiology due to fluid shifts, muscle and bone loss, immune system dysregulation, and changes in the gastrointestinal tract and metabolic enzymes. These alterations may change the pharmacokinetics and/or pharmacodynamics of medications used by astronauts and subsequently might impact drug efficacy and safety. Most commonly, medications are administered during space missions to treat sleep disturbances, allergies, space motion sickness, pain, and sinus congestion. These medications are administered under the assumption that they act in a similar way as on Earth, an assumption that has not been investigated systematically yet. Few inflight pharmacokinetic data have been published, and pharmacodynamic and pharmacokinetic/pharmacodynamic studies during spaceflight are also lacking. Therefore, bed-rest models are often used to simulate physiological changes observed during microgravity. In addition to pharmacokinetic/pharmacodynamic changes, decreased drug and formulation stability in space could also influence efficacy and safety of medications. These alterations along with physiological changes and their resulting pharmacokinetic and pharmacodynamic effects must to be considered to determine their ultimate impact on medication efficacy and safety during spaceflight. Copyright © 2017 Elsevier B.V. All rights reserved.

Underwater Electrical Safety Practices

DTIC Science & Technology

1976-01-01

under water. While advances continue in developing new and more effective underwater electrical equipment, the Navy is concerned that its underwater...levels passing through human tissue is known to alter, temporarily, the physiological function of cells. The long-term effects , if any, are unknown. Much...of the system--human physiology, equipment, procedures, and training. Human Physiology Present knowledge of the physiological effects of electrical

Numerical Simulation of cardiovascular deconditioning in different reduced gravity exposure scenarios. Parabolic flight validation.

NASA Astrophysics Data System (ADS)

Perez-Poch, Antoni; Gonzalez, Daniel

Numerical models and simulations are an emerging area of research in human physiology. As complex numerical models are available, along with high-speed computing technologies, it is possible to produce more accurate predictions of the long-term effects of reduced gravity on the human body. NELME (Numerical Emulation of Long-Term Microgravity Effects) has been developed as an electrical-like control system model of the pysiological changes that may arise when gravity changes are applied to the cardiovascular system. Validation of the model has been carried out in parabolic flights at UPC BarcelonaTech Platform. A number of parabolas of up to 8 seconds were performed at Sabadell Airport with an aerobatic single-engine CAP10B plane capable of performing such maneuvres. Heart rate, arterial pressure, and gravity data was collected and compared to the output obtained from the model in order to optimize its parameters. The model is then able to perform simulations for long-term periods of exposure to microgravity, and then the risk for a major malfunction is evaluated. Vascular resistance is known to be impaired during a long-term mission. This effects are not fully understood, and the model is capable of providing a continuous thread of simulated scenarios, while varying gravity in a nearly-continuous way. Aerobic exercise as countermeasure has been simulated as a periodic perturbation into the simulated physiological system. Results are discussed in terms of the validaty and reliability of the outcomes from the model, that have been found compatible with the available data in the literature. Different gender sensitivities to microgravity exposure are discussed. Also thermal stress along with exercise, as it happens in the case of Extravehicular activity is smulated. Results show that vascular resistance is significantly impared (p<0,05) at gravity levels less than 0,4g, when exposed for a period of time longer than 16 days. This degree of impairement is comparable with that resulting from a microgravity exposure. These results suggest that long-term activities on the surface of Mars may have a greater impact on the cardiovascular health than previously thought.

Appropriate Mechanochemical Conditions for Corrosion-Fatigue Testing of Magnesium Alloys for Temporary Bioimplant Applications

NASA Astrophysics Data System (ADS)

Harandi, Shervin Eslami; Singh Raman, R. K.

2015-05-01

Magnesium (Mg) alloys possess great potential as bioimplants. A temporary implant employed as support for the repair of a fractured bone must possess sufficient strength to maintain their mechanical integrity for the required duration of healing. However, Mg alloys are susceptible to sudden cracking or fracture under the simultaneous action of cyclic loading and the corrosive physiological environment, i.e., corrosion fatigue (CF). Investigations of such fracture should be performed under appropriate mechanochemical conditions that appropriately simulate the actual human body conditions. This article reviews the existing knowledge on CF of Mg alloys in simulated body fluid and describes a relatively more accurate testing procedure developed in the authors' laboratory.

Digestibility of fucosylated glycosaminoglycan from sea cucumber and its effects on digestive enzymes under simulated salivary and gastrointestinal conditions.

PubMed

Zhao, Longyan; Qin, Yujing; Guan, Ruowei; Zheng, Wenqi; Liu, Jikai; Zhao, Jinhua

2018-04-15

The digestibility of fucosylated glycosaminoglycan (FG) and its effects on digestive enzymes were investigated using an in vitro digestion model. Results showed that the molecular weight and the reducing sugar content of FG were not significantly changed, and no free monosaccharides released from FG were detected after the salivary, gastric and intestinal digestion, indicating that both the backbone and the sulfated fucose branches of FG are resistant to be cleaved in the saliva and gastrointestinal tract environments. Furthermore, FG can dose-dependently inhibit digestive enzymes such as α-amylase, pepsin and pancreatic lipase in different degrees under the simulated digestion conditions due to the sulfate and carboxyl groups. These physiological effects of FG may help control the postprandial glucose concentration and have the potential in the prevention or treatment of reflux disease and obesity. The findings may provide information on the digestibility and beneficial physiological effects of FG as a potential natural product to promote human health. Copyright © 2018 Elsevier Ltd. All rights reserved.

Analysis of the Federal Cataloging System and COSATI (Committee on Scientific and Technical Information) Cataloging,

DTIC Science & Technology

1985-06-21

etc. Animal anatomy, physiology, and pathology. Care and breeding of labora- tory animals. For human anatomy and physiology, see 06 16 Physiology...sensation, etc. Human anatomy . For animal anatomy and physiology, see 06 03 Biology. For physiological psychology, see 05 10 Psychology. See also 06 19

Human Physiology and the Environment in Health and Disease: Readings from Scientific American.

ERIC Educational Resources Information Center

1976

This anthology of articles is designed to supplement standard texts for courses in human physiology, environmental physiology, anatomy and physiology, pathobiology, general biology, and environmental medicine. It focuses on the influences of the external environment on the body, the physiological responses to environmental challenges, and the ways…

Parameterization using Fourier series expansion of the diffuse reflectance of human skin to vary the concentration of the melanocytes

NASA Astrophysics Data System (ADS)

Narea, J. Freddy; Muñoz, Aarón A.; Castro, Jorge; Muñoz, Rafael A.; Villalba, Caroleny E.; Martinez, María. F.; Bravo, Kelly D.

2013-11-01

Human skin has been studied in numerous investigations, given the interest in knowing information about physiology, morphology and chemical composition. These parameters can be determined using non invasively optical techniques in vivo, such as the diffuse reflectance spectroscopy. The human skin color is determined by many factors, but primarily by the amount and distribution of the pigment melanin. The melanin is produced by the melanocytes in the basal layer of the epidermis. This research characterize the spectral response of the human skin using the coefficients of Fourier series expansion. Simulating the radiative transfer equation for the Monte Carlo method to vary the concentration of the melanocytes (fme) in a simplified model of human skin. It fits relating the Fourier series coefficient a0 with fme. Therefore it is possible to recover the skin biophysical parameter.

Evolutionary Medicine: The Ongoing Evolution of Human Physiology and Metabolism.

PubMed

Rühli, Frank; van Schaik, Katherine; Henneberg, Maciej

2016-11-01

The field of evolutionary medicine uses evolutionary principles to understand changes in human anatomy and physiology that have occurred over time in response to environmental changes. Through this evolutionary-based approach, we can understand disease as a consequence of anatomical and physiological "trade-offs" that develop to facilitate survival and reproduction. We demonstrate how diachronic study of human anatomy and physiology is fundamental for an increased understanding of human health and disease. ©2016 Int. Union Physiol. Sci./Am. Physiol. Soc.

Method and System for Physiologically Modulating Videogames and Simulations which Use Gesture and Body Image Sensing Control Input Devices

NASA Technical Reports Server (NTRS)

Pope, Alan T. (Inventor); Stephens, Chad L. (Inventor); Habowski, Tyler (Inventor)

2017-01-01

Method for physiologically modulating videogames and simulations includes utilizing input from a motion-sensing video game system and input from a physiological signal acquisition device. The inputs from the physiological signal sensors are utilized to change the response of a user's avatar to inputs from the motion-sensing sensors. The motion-sensing system comprises a 3D sensor system having full-body 3D motion capture of a user's body. This arrangement encourages health-enhancing physiological self-regulation skills or therapeutic amplification of healthful physiological characteristics. The system provides increased motivation for users to utilize biofeedback as may be desired for treatment of various conditions.

The effects of bed rest on crew performance during simulated shuttle reentry. Volume 1: Study overview and physiological results

NASA Technical Reports Server (NTRS)

Chambers, A.; Vykukal, H. C.

1974-01-01

A centrifuge study was carried out to measure physiological stress and control task performance during simulated space shuttle orbiter reentry. Jet pilots were tested with, and without, anti-g-suit protection. The pilots were exposed to simulated space shuttle reentry acceleration profiles before, and after, ten days of complete bed rest, which produced physiological deconditioning similar to that resulting from prolonged exposure to orbital zero g. Pilot performance in selected control tasks was determined during simulated reentry, and before and after each simulation. Physiological stress during reentry was determined by monitoring heart rate, blood pressure, and respiration rate. Study results indicate: (1) heart rate increased during the simulated reentry when no g protection was given, and remained at or below pre-bed rest values when g-suits were used; (2) pilots preferred the use of g-suits to muscular contraction for control of vision tunneling and grayout during reentry; (3) prolonged bed rest did not alter blood pressure or respiration rate during reentry, but the peak reentry acceleration level did; and (4) pilot performance was not affected by prolonged bed rest or simulated reentry.

Use of an iPad App to simulate pressure-volume loops and cardiovascular physiology.

PubMed

Leisman, Staci; Burkhoff, Daniel

2017-09-01

The purpose of this laboratory exercise is to model the changes in preload, afterload, and contractility on a simulated pressure-volume loop and to correlate those findings with common measurements of clinical cardiovascular physiology. Once students have modeled these changes on a healthy heart, the students are asked to look at a simulated case of cardiogenic shock. Effects on preload, contractility, and afterload are explored, as well as the hemodynamic effects of a number of student-suggested treatment strategies. Copyright © 2017 the American Physiological Society.

Development of simulation interfaces for evaluation task with the use of physiological data and virtual reality applied to a vehicle simulator

NASA Astrophysics Data System (ADS)

Miranda, Mateus R.; Costa, Henrik; Oliveira, Luiz; Bernardes, Thiago; Aguiar, Carla; Miosso, Cristiano; Oliveira, Alessandro B. S.; Diniz, Alberto C. G. C.; Domingues, Diana Maria G.

2015-03-01

This paper aims at describing an experimental platform used to evaluate the performance of individuals at training immersive physiological games. The platform proposed is embedded in an immersive environment in a CAVE of Virtual Reality and consists on a base frame with actuators with three degrees of freedom, sensor array interface and physiological sensors. Physiological data of breathing, galvanic skin resistance (GSR) and pressure on the hand of the user and a subjective questionnaire were collected during the experiments. The theoretical background used in a project focused on Software Engineering, Biomedical Engineering in the field of Ergonomics and Creative Technologies in order to presents this case study, related of an evaluation of a vehicular simulator located inside the CAVE. The analysis of the simulator uses physiological data of the drivers obtained in a period of rest and after the experience, with and without movements at the simulator. Also images from the screen are captured through time at the embedded experience and data collected through physiological data visualization (average frequency and RMS graphics). They are empowered by the subjective questionnaire as strong lived experience provided by the technological apparatus. The performed immersion experience inside the CAVE allows to replicate behaviors from physical spaces inside data space enhanced by physiological properties. In this context, the biocybrid condition is expanded beyond art and entertainment, as it is applied to automotive engineering and biomedical engineering. In fact, the kinesthetic sensations amplified by synesthesia replicates the sensation of displacement in the interior of an automobile, as well as the sensations of vibration and vertical movements typical of a vehicle, different speeds, collisions, etc. The contribution of this work is the possibility to tracing a stress analysis protocol for drivers while operating a vehicle getting affective behaviors coming from physiological data, mixed to embedded simulation in Mixed Reality.

The development of a whole-body algorithm

NASA Technical Reports Server (NTRS)

Kay, F. J.

1973-01-01

The whole-body algorithm is envisioned as a mathematical model that utilizes human physiology to simulate the behavior of vital body systems. The objective of this model is to determine the response of selected body parameters within these systems to various input perturbations, or stresses. Perturbations of interest are exercise, chemical unbalances, gravitational changes and other abnormal environmental conditions. This model provides for a study of man's physiological response in various space applications, underwater applications, normal and abnormal workloads and environments, and the functioning of the system with physical impairments or decay of functioning components. Many methods or approaches to the development of a whole-body algorithm are considered. Of foremost concern is the determination of the subsystems to be included, the detail of the subsystems and the interaction between the subsystems.

Both Predator and Prey

PubMed Central

Löw, Andreas; Lang, Peter J.; Smith, J. Carson; Bradley, Margaret M.

2013-01-01

This research examined the psychophysiology of emotional arousal anticipatory to potentially aversive and highly pleasant outcomes. Human brain reactions (event-related potentials) and body reactions (heart rate, skin conductance, the probe startle reflex) were assessed along motivational gradients determined by apparent distance from sites of potential punishment or reward. A predator-prey survival context was simulated using cues that signaled possible money rewards or possible losses; the cues appeared to loom progressively closer to the viewer, until a final step when a rapid key response could ensure reward or avoid a punishing loss. The observed anticipatory response patterns of heightened vigilance and physiological mobilization are consistent with the view that the physiology of emotion is founded on action dispositions that evolved in mammals to facilitate survival by dealing with threats or capturing life-sustaining rewards. PMID:18947351

Physiological adaptations and countermeasures associated with long-duration spaceflights.

PubMed

Tipton, C M; Hargens, A

1996-08-01

Since 1961, there have been more than 165 flights involving several hundred individuals who have remained in a space environment from 15 min to more than a year. In addition, plans exist for humans to explore, colonize, and remain in microgravity for 1000 d or more. This symposium will address the current state of knowledge in select aspects associated with the cardiovascular, fluid and electrolytes, musculoskeletal, and the neuroendocrine and immune systems. The authors will focus on responses, mechanisms, and the appropriate countermeasures to minimize or prevent the physiological and biochemical consequences of a microgravity environment. Since exercise is frequently cited as a generic countermeasure, this topic will be covered in greater detail. Models for simulated microgravity conditions will be discussed in subsequent manuscripts, as will future directions for ground-based research.

Physiological adaptations and countermeasures associated with long-duration spaceflights

NASA Technical Reports Server (NTRS)

Tipton, C. M.; Hargens, A.

1996-01-01

Since 1961, there have been more than 165 flights involving several hundred individuals who have remained in a space environment from 15 min to more than a year. In addition, plans exist for humans to explore, colonize, and remain in microgravity for 1000 d or more. This symposium will address the current state of knowledge in select aspects associated with the cardiovascular, fluid and electrolytes, musculoskeletal, and the neuroendocrine and immune systems. The authors will focus on responses, mechanisms, and the appropriate countermeasures to minimize or prevent the physiological and biochemical consequences of a microgravity environment. Since exercise is frequently cited as a generic countermeasure, this topic will be covered in greater detail. Models for simulated microgravity conditions will be discussed in subsequent manuscripts, as will future directions for ground-based research.

Human Health Countermeasures - Partial-Gravity Analogs Workshop

NASA Technical Reports Server (NTRS)

Barr, Yael; Clement, Gilles; Norsk, Peter

2016-01-01

The experimental conditions that were deemed the most interesting by the HHC Element lead scientists are those permitting studies of the long-term effects of exposure to (a) chronic rotation when supine or in head down tilt (ground-based); and (b) long-radius centrifugation (space based). It is interesting to note that chronic ground based slow rotation room studies have not been performed since the 1960's, when the USA and USSR were investigating the potential use of AG for long-duration space missions. On the other hand, the other partial gravity analogs, i.e., parabolic flight, HUT, suspension, and short-radius centrifugation, have been regularly used in the last three decades (see review in Clément et al. 2015). Based on the workshop evaluations and the scores by the HHC scientific disciplines indicated in tables 3 and 4, simulation of partial G between 0 and 1 should be prioritized as follows: Priority 1. Chronic space-based partial-G analogs: a. Chronic space-based long-radius centrifugation. The ideal scenario would be chronic long-radius centrifugation of cells, animals and humans in a translational research approach - ideally beyond low earth orbit under deep space environmental effects and at various rotations - to obtain different G-effects. In this scenario, all physiological systems could be evaluated and the relationship between physiological response and G level established. This would be the most integrative way of defining, for the first time ever, G-thresholds for each physiological system. b. Chronic space-based centrifugation of animals. Chronic centrifugation of rodents at various G levels in space would allow for determination of AG thresholds of protection for each physiological system. In this case, all physiological systems will be of interest. Intermittent centrifugation will be of secondary interest. c. Chronic space-based centrifugation of cell cultures (RWV). Bioreactor studies of cells and cell cultures of various tissues at various G levels would allow for intracellular investigations of the effects of partial-G. Priority 2. Acute, intermittent space based partial-G analogs: a. Acute, intermittent space-based short radius human centrifugation. Intermittent centrifugation of humans would allow determination of thresholds of AG for protection of astronaut health in space. Priority 3. Chronic ground-based partial-G analogs: a. Chronic centrifugation of supine or head-down tilted humans. b. Chronic head-up tilt in humans. c. Chronic head-out graded dry immersion in humans. d. Chronic partial suspension of rodents e. Chronic rotating bioreactor cell culture studies (RWV) Priority 4. Acute ground based partial-G analogs. a. Parabolic flights. Very acute and short term effects of G levels between 0 and 1 in humans for fast responding systems like cardiovascular and sensorimotor as well as for acute responses in cell cultures and animals. b. Other acute models as indicated in table 3.

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.

Journal of Gravitational Physiology, Volume 13, No. 1

NASA Technical Reports Server (NTRS)

Fuller, Charles A. (Editor); Cogoli, Augusto (Editor); Hargens, Alan R. (Editor); Smith, Arthur H. (Editor)

2006-01-01

At the outset, the Journal published one issue in 1994. The first number comprised the Proceedings of the 15th Annual International Gravitational Physiology Meeting, held in Barcelona, Spain in October 1993. The Proceedings of the previous 14 Annual Meetings appeared as supplements to The Physiologist from 1979 to 1993. Each year, one issue of the Journal is devoted to the Annual Meeting Proceedings, and up to four more issues are comprised of full-length research papers. Additionally, Supplement Issues are considered by the Editorial Board as they are submitted. The Journal is published for the International Society for Gravitational Physiology by the Galileo Foundation, a 501(c)(3) nonprofit public benefit corporation. This issue, the first number of 2006, comprises the Proceedings of the joint meeting of the International Society for Gravitational Physiology s 27th Annual International Gravitational Physiology Meeting, held in Osaka, Japan 23- 28 April, 2006. The Journal of Gravitational Physiology invites the submission of original experimental or observational papers on subjects in the field of gravitational physiology. Review articles, theoretical papers and historical or biographical articles will also be solicited by the Editor for publication. The wide scientific span of the Journal rests on physiology as its keystone. Gravitational physiology is considered to include the effects of changes in the magnitude and directions of the gravitational force environment on cells and physiological systems and behavior of humans, animals and plants. The effects of weightlessness during space flight, high sustained G forces and chronic acceleration, vibration, impact and the various forms of simulated weightlessness are also included, as well as is consideration of the evolutionary consequences of gravity and the role of gravity in the manifestation of scale effects in animals and plants.

Program Code Generator for Cardiac Electrophysiology Simulation with Automatic PDE Boundary Condition Handling

PubMed Central

Punzalan, Florencio Rusty; Kunieda, Yoshitoshi; Amano, Akira

2015-01-01

Clinical and experimental studies involving human hearts can have certain limitations. Methods such as computer simulations can be an important alternative or supplemental tool. Physiological simulation at the tissue or organ level typically involves the handling of partial differential equations (PDEs). Boundary conditions and distributed parameters, such as those used in pharmacokinetics simulation, add to the complexity of the PDE solution. These factors can tailor PDE solutions and their corresponding program code to specific problems. Boundary condition and parameter changes in the customized code are usually prone to errors and time-consuming. We propose a general approach for handling PDEs and boundary conditions in computational models using a replacement scheme for discretization. This study is an extension of a program generator that we introduced in a previous publication. The program generator can generate code for multi-cell simulations of cardiac electrophysiology. Improvements to the system allow it to handle simultaneous equations in the biological function model as well as implicit PDE numerical schemes. The replacement scheme involves substituting all partial differential terms with numerical solution equations. Once the model and boundary equations are discretized with the numerical solution scheme, instances of the equations are generated to undergo dependency analysis. The result of the dependency analysis is then used to generate the program code. The resulting program code are in Java or C programming language. To validate the automatic handling of boundary conditions in the program code generator, we generated simulation code using the FHN, Luo-Rudy 1, and Hund-Rudy cell models and run cell-to-cell coupling and action potential propagation simulations. One of the simulations is based on a published experiment and simulation results are compared with the experimental data. We conclude that the proposed program code generator can be used to generate code for physiological simulations and provides a tool for studying cardiac electrophysiology. PMID:26356082

Three-dimensional fuse deposition modeling of tissue-simulating phantom for biomedical optical imaging

NASA Astrophysics Data System (ADS)

Dong, Erbao; Zhao, Zuhua; Wang, Minjie; Xie, Yanjun; Li, Shidi; Shao, Pengfei; Cheng, Liuquan; Xu, Ronald X.

2015-12-01

Biomedical optical devices are widely used for clinical detection of various tissue anomalies. However, optical measurements have limited accuracy and traceability, partially owing to the lack of effective calibration methods that simulate the actual tissue conditions. To facilitate standardized calibration and performance evaluation of medical optical devices, we develop a three-dimensional fuse deposition modeling (FDM) technique for freeform fabrication of tissue-simulating phantoms. The FDM system uses transparent gel wax as the base material, titanium dioxide (TiO2) powder as the scattering ingredient, and graphite powder as the absorption ingredient. The ingredients are preheated, mixed, and deposited at the designated ratios layer-by-layer to simulate tissue structural and optical heterogeneities. By printing the sections of human brain model based on magnetic resonance images, we demonstrate the capability for simulating tissue structural heterogeneities. By measuring optical properties of multilayered phantoms and comparing with numerical simulation, we demonstrate the feasibility for simulating tissue optical properties. By creating a rat head phantom with embedded vasculature, we demonstrate the potential for mimicking physiologic processes of a living system.

Modeling and simulating the neuromuscular mechanisms regulating ankle and knee joint stiffness during human locomotion.

PubMed

Sartori, Massimo; Maculan, Marco; Pizzolato, Claudio; Reggiani, Monica; Farina, Dario

2015-10-01

This work presents an electrophysiologically and dynamically consistent musculoskeletal model to predict stiffness in the human ankle and knee joints as derived from the joints constituent biological tissues (i.e., the spanning musculotendon units). The modeling method we propose uses electromyography (EMG) recordings from 13 muscle groups to drive forward dynamic simulations of the human leg in five healthy subjects during overground walking and running. The EMG-driven musculoskeletal model estimates musculotendon and resulting joint stiffness that is consistent with experimental EMG data as well as with the experimental joint moments. This provides a framework that allows for the first time observing 1) the elastic interplay between the knee and ankle joints, 2) the individual muscle contribution to joint stiffness, and 3) the underlying co-contraction strategies. It provides a theoretical description of how stiffness modulates as a function of muscle activation, fiber contraction, and interacting tendon dynamics. Furthermore, it describes how this differs from currently available stiffness definitions, including quasi-stiffness and short-range stiffness. This work offers a theoretical and computational basis for describing and investigating the neuromuscular mechanisms underlying human locomotion. Copyright © 2015 the American Physiological Society.

Human-induced greening of the northern extratropical land surface

NASA Astrophysics Data System (ADS)

Mao, J.; Ribes, A.; Yan, B.; Shi, X.; Thornton, P. E.; Seferian, R.; Ciais, P.; Myneni, R. B.; Douville, H.; Piao, S.; Zhu, Z.; Dickinson, R. E.; Dai, Y. J.; Ricciuto, D. M.; Jin, M.; Hoffman, F. M.; Wang, B.; Huang, M.; Lian, X.

2016-12-01

Significant land greening in the northern extratropical latitudes (NEL) has been documented through satellite observations during the past three decades. This enhanced vegetation growth has broad implications for surface energy, water and carbon budgets, and ecosystem services across multiple scales. Discernible human impacts on the Earth's climate system have been revealed by using statistical frameworks of detection-attribution. These impacts, however, were not previously identified on the NEL greening signal, owing to the lack of long-term observational records, possible bias of satellite data, different algorithms used to calculate vegetation greenness, and the lack of suitable simulations from coupled Earth system models (ESMs). Here we have overcome these challenges to attribute recent changes in NEL vegetation activity. We used two 30-year-long remote-sensing-based leaf area index (LAI) data sets, simulations from 19 coupled ESMs with interactive vegetation, and a formal detection and attribution algorithm. Our findings reveal that the observed greening record is consistent with an assumption of anthropogenic forcings, where greenhouse gases play a dominant role, but is not consistent with simulations that include only natural forcings and internal climate variability. These results provide the first clear evidence of a discernible human fingerprint on physiological vegetation changes other than phenology and range shifts.

Human-induced greening of the northern extratropical land surface

NASA Astrophysics Data System (ADS)

Mao, Jiafu; Ribes, Aurélien; Yan, Binyan; Shi, Xiaoying; Thornton, Peter E.; Séférian, Roland; Ciais, Philippe; Myneni, Ranga B.; Douville, Hervé; Piao, Shilong; Zhu, Zaichun; Dickinson, Robert E.; Dai, Yongjiu; Ricciuto, Daniel M.; Jin, Mingzhou; Hoffman, Forrest M.; Wang, Bin; Huang, Mengtian; Lian, Xu

2016-10-01

Significant land greening in the northern extratropical latitudes (NEL) has been documented through satellite observations during the past three decades. This enhanced vegetation growth has broad implications for surface energy, water and carbon budgets, and ecosystem services across multiple scales. Discernible human impacts on the Earth's climate system have been revealed by using statistical frameworks of detection-attribution. These impacts, however, were not previously identified on the NEL greening signal, owing to the lack of long-term observational records, possible bias of satellite data, different algorithms used to calculate vegetation greenness, and the lack of suitable simulations from coupled Earth system models (ESMs). Here we have overcome these challenges to attribute recent changes in NEL vegetation activity. We used two 30-year-long remote-sensing-based leaf area index (LAI) data sets, simulations from 19 coupled ESMs with interactive vegetation, and a formal detection and attribution algorithm. Our findings reveal that the observed greening record is consistent with an assumption of anthropogenic forcings, where greenhouse gases play a dominant role, but is not consistent with simulations that include only natural forcings and internal climate variability. These results provide the first clear evidence of a discernible human fingerprint on physiological vegetation changes other than phenology and range shifts.

Human-induced greening of the northern extratropical land surface

DOE PAGES

Mao, Jiafu; Ribes, Aurélien; Yan, Binyan; ...

2016-06-27

Significant land greening in the northern extratropical latitudes (NEL) has been documented from satellite observations during the past three decades. This enhanced vegetation growth has broad implications for surface energy, water and carbon budgets, and ecosystem services across multiple scales. Discernible human impacts on the Earth’s climate system have been revealed by using statistical frameworks of detection–attribution. These impacts, however, were not previously identified on the NEL greening signal, owing to the lack of long-term observational records, possible bias of satellite data, different algorithms used to calculate vegetation greenness, and the lack of suitable simulations from coupled Earth system modelsmore » (ESMs). Here we have overcome these challenges to attribute recent changes in NEL vegetation activity. We have used two 30-year-long remote-sensing-based leaf area index (LAI) data sets, simulations from 19 coupled ESMs with interactive vegetation, and a formal detection and attribution algorithm. Our findings reveal that the observed greening record is consistent with an assumption of anthropogenic forcings, where greenhouse gases play a dominant role, but is not consistent with simulations that include only natural forcings and internal climate variability. These results provide the first clear evidence of a discernible human fingerprint on physiological vegetation changes other than phenology and range shifts.« less

APPLICATION OF EYE TRACKING FOR MEASUREMENT AND EVALUATION IN HUMAN FACTORS STUDIES IN CONTROL ROOM MODERNIZATION

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

Kovesdi, C.; Spielman, Z.; LeBlanc, K.

An important element of human factors engineering (HFE) pertains to measurement and evaluation (M&E). The role of HFE-M&E should be integrated throughout the entire control room modernization (CRM) process and be used for human-system performance evaluation and diagnostic purposes with resolving potential human engineering deficiencies (HEDs) and other human machine interface (HMI) design issues. NUREG-0711 describes how HFE in CRM should employ a hierarchical set of measures, particularly during integrated system validation (ISV), including plant performance, personnel task performance, situation awareness, cognitive workload, and anthropometric/ physiological factors. Historically, subjective measures have been primarily used since they are easier to collectmore » and do not require specialized equipment. However, there are pitfalls with relying solely on subjective measures in M&E such that negatively impact reliability, sensitivity, and objectivity. As part of comprehensively capturing a diverse set of measures that strengthen findings and inferences made of the benefits from emerging technologies like advanced displays, this paper discusses the value of using eye tracking as an objective method that can be used in M&E. A brief description of eye tracking technology and relevant eye tracking measures is provided. Additionally, technical considerations and the unique challenges with using eye tracking in full-scaled simulations are addressed. Finally, this paper shares preliminary findings regarding the use of a wearable eye tracking system in a full-scale simulator study. These findings should help guide future full-scale simulator studies using eye tracking as a methodology to evaluate human-system performance.« less

Space flight nutrition research: platforms and analogs

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Uchakin, Peter N.; Tobin, Brian W.

2002-01-01

Conducting research during actual or simulated weightlessness is a challenging endeavor, where even the simplest activities may present significant challenges. This article reviews some of the potential obstacles associated with performing research during space flight and offers brief descriptions of current and previous space research platforms and ground-based analogs, including those for human, animal, and cell-based research. This review is intended to highlight the main issues of space flight research analogs and leave the specifics for each physiologic system for the other papers in this section.

Kinetics and thermodynamics of DNA polymerases with exonuclease proofreading

NASA Astrophysics Data System (ADS)

Gaspard, Pierre

2016-04-01

Kinetic theory and thermodynamics are applied to DNA polymerases with exonuclease activity, taking into account the dependence of the rates on the previously incorporated nucleotide. The replication fidelity is shown to increase significantly thanks to this dependence at the basis of the mechanism of exonuclease proofreading. In particular, this dependence can provide up to a 100-fold lowering of the error probability under physiological conditions. Theory is compared with numerical simulations for the DNA polymerases of T7 viruses and human mitochondria.

Human cardiovascular response to sympathomimetic agents during head-down bed rest: the effect of dietary sodium

NASA Technical Reports Server (NTRS)

Williams, W. J.; Stuart, C. A.; Fortney, S. M.; Pietrzyk, R. A.; Chen, Y. M.; Whitson, P. A.

1994-01-01

Changes in sympathoadrenal function and cardiovascular deconditioning have long been recognized as a feature of the physiological adaptation to microgravity. The deconditioning process, coupled with altered hydration status, is thought to significantly contribute to orthostatic intolerance upon return to Earth gravity. The cardiovascular response to stimulation by sympathomimetic agents before, during, and after exposure to simulated microgravity was determined in healthy volunteers equilibrated on normal or high sodium diets in order to further the understanding of the deconditioning process.

Human plasma metabolic profiles of benzydamine, a flavin-containing monooxygenase probe substrate, simulated with pharmacokinetic data from control and humanized-liver mice.

PubMed

Yamazaki-Nishioka, Miho; Shimizu, Makiko; Suemizu, Hiroshi; Nishiwaki, Megumi; Mitsui, Marina; Yamazaki, Hiroshi

2018-02-01

1. Benzydamine is used clinically as a nonsteroidal anti-inflammatory drug in oral rinses and is employed in preclinical research as a flavin-containing monooxygenase (FMO) probe substrate. In this study, plasma concentrations of benzydamine and its primary N-oxide and N-demethylated metabolites were investigated in control TK-NOG mice, in humanized-liver mice, and in mice whose liver cells had been ablated with ganciclovir. 2. Following oral administration of benzydamine (10 mg/kg) in humanized-liver TK-NOG mice, plasma concentrations of benzydamine N-oxide were slightly higher than those of demethyl benzydamine. In contrast, in control and ganciclovir-treated TK-NOG mice, concentrations of demethyl benzydamine were slightly higher than those of benzydamine N-oxide. 3. Simulations of human plasma concentrations of benzydamine and its N-oxide were achieved using simplified physiologically based pharmacokinetic models based on data from control TK-NOG mice and from reported benzydamine concentrations after low-dose administration in humans. Estimated clearance rates based on data from humanized-liver and ganciclovir-treated TK-NOG mice were two orders magnitude high. 4. The pharmacokinetic profiles of benzydamine were different for control and humanized-liver TK-NOG mice. Humanized-liver mice are generally accepted human models; however, drug oxidation in mouse kidney might need to be considered when probe substrates undergo FMO-dependent drug oxidation in mouse liver and kidney.

An integrative approach to space-flight physiology using systems analysis and mathematical simulation

NASA Technical Reports Server (NTRS)

Leonard, J. I.; White, R. J.; Rummel, J. A.

1980-01-01

An approach was developed to aid in the integration of many of the biomedical findings of space flight, using systems analysis. The mathematical tools used in accomplishing this task include an automated data base, a biostatistical and data analysis system, and a wide variety of mathematical simulation models of physiological systems. A keystone of this effort was the evaluation of physiological hypotheses using the simulation models and the prediction of the consequences of these hypotheses on many physiological quantities, some of which were not amenable to direct measurement. This approach led to improvements in the model, refinements of the hypotheses, a tentative integrated hypothesis for adaptation to weightlessness, and specific recommendations for new flight experiments.

Development of a Physiologically Based Pharmacokinetic Model for Sinogliatin, a First-in-Class Glucokinase Activator, by Integrating Allometric Scaling, In Vitro to In Vivo Exploration and Steady-State Concentration-Mean Residence Time Methods: Mechanistic Understanding of its Pharmacokinetics.

PubMed

Song, Ling; Zhang, Yi; Jiang, Ji; Ren, Shuang; Chen, Li; Liu, Dongyang; Chen, Xijing; Hu, Pei

2018-04-06

The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for sinogliatin (HMS-5552, dorzagliatin) by integrating allometric scaling (AS), in vitro to in vivo exploration (IVIVE), and steady-state concentration-mean residence time (C ss -MRT) methods and to provide mechanistic insight into its pharmacokinetic properties in humans. Human major pharmacokinetic parameters were analyzed using AS, IVIVE, and C ss -MRT methods with available preclinical in vitro and in vivo data to understand sinogliatin drug metabolism and pharmacokinetic (DMPK) characteristics and underlying mechanisms. On this basis, an initial mechanistic PBPK model of sinogliatin was developed. The initial PBPK model was verified using observed data from a single ascending dose (SAD) study and further optimized with various strategies. The final model was validated by simulating sinogliatin pharmacokinetics under a fed condition. The validated model was applied to support a clinical drug-drug interaction (DDI) study design and to evaluate the effects of intrinsic (hepatic cirrhosis, genetic) factors on drug exposure. The two-species scaling method using rat and dog data (TS- rat,dog ) was the best AS method in predicting human systemic clearance in the central compartment (CL). The IVIVE method confirmed that sinogliatin was predominantly metabolized by cytochrome P450 (CYP) 3A4. The C ss -MRT method suggested dog pharmacokinetic profiles were more similar to human pharmacokinetic profiles. The estimated CL using the AS and IVIVE approaches was within 1.5-fold of that observed. The C ss -MRT method in dogs also provided acceptable prediction of human pharmacokinetic characteristics. For the PBPK approach, the 90% confidence intervals (CIs) of the simulated maximum concentration (C max ), CL, and area under the plasma concentration-time curve (AUC) of sinogliatin were within those observed and the 90% CI of simulated time to C max (t max ) was closed to that observed for a dose range of 5-50 mg in the SAD study. The final PBPK model was validated by simulating sinogliatin pharmacokinetics with food. The 90% CIs of the simulated C max , CL, and AUC values for sinogliatin were within those observed and the 90% CI of the simulated t max was partially within that observed for the dose range of 25-200 mg in the multiple ascending dose (MAD) study. This PBPK model selected a final clinical DDI study design with itraconazole from four potential designs and also evaluated the effects of intrinsic (hepatic cirrhosis, genetic) factors on drug exposure. Sinogliatin pharmacokinetic properties were mechanistically understood by integrating all four methods and a mechanistic PBPK model was successfully developed and validated using clinical data. This PBPK model was applied to support the development of sinogliatin.

Enhancing Learning through Optimal Sequencing of Web-Based and Manikin Simulators to Teach Shock Physiology in the Medical Curriculum

ERIC Educational Resources Information Center

Cendan, Juan C.; Johnson, Teresa R.

2011-01-01

The Association of American Medical Colleges has encouraged educators to investigate proper linkage of simulation experiences with medical curricula. The authors aimed to determine if student knowledge and satisfaction differ between participation in web-based and manikin simulations for learning shock physiology and treatment and to determine if…

Millimeter spatial resolution in vivo sodium MRI of the human eye at 7 T using a dedicated radiofrequency transceiver array.

PubMed

Wenz, Daniel; Kuehne, Andre; Huelnhagen, Till; Nagel, Armin M; Waiczies, Helmar; Weinberger, Oliver; Oezerdem, Celal; Stachs, Oliver; Langner, Soenke; Seeliger, Erdmann; Flemming, Bert; Hodge, Russell; Niendorf, Thoralf

2018-08-01

The aim of this study was to achieve millimeter spatial resolution sodium in vivo MRI of the human eye at 7 T using a dedicated six-channel transceiver array. We present a detailed description of the radiofrequency coil design, along with electromagnetic field and specific absorption ratio simulations, data validation, and in vivo application. Electromagnetic field and specific absorption ratio simulations were performed. Transmit field uniformity was optimized by using a multi-objective genetic algorithm. Transmit field mapping was conducted using a phase-sensitive method. An in vivo feasibility study was carried out with 3-dimensional density-adapted projection reconstruction imaging technique. Measured transmit field distribution agrees well with the one obtained from simulations. The specific absorption ratio simulations confirm that the radiofrequency coil is safe for clinical use. Our radiofrequency coil is light and conforms to an average human head. High spatial resolution (nominal 1.4 and 1.0 mm isotropic) sodium in vivo images of the human eye were acquired within scan times suitable for clinical applications (∼ 10 min). Three most important eye compartments in the context of sodium physiology were clearly delineated in all of the images: the vitreous humor, the aqueous humor, and the lens. Our results provide encouragement for further clinical studies. The implications for research into eye diseases including ocular melanoma, cataract, and glaucoma are discussed. Magn Reson Med 80:672-684, 2018. © 2018 International Society for Magnetic Resonance in Medicine. © 2018 International Society for Magnetic Resonance in Medicine.

A hip joint simulator study using simplified loading and motion cycles generating physiological wear paths and rates.

PubMed

Barbour, P S; Stone, M H; Fisher, J

1999-01-01

In some designs of hip joint simulator the cost of building a highly complex machine has been offset with the requirement for a large number of test stations. The application of the wear results generated by these machines depends on their ability to reproduce physiological wear rates and processes. In this study a hip joint simulator has been shown to reproduce physiological wear using only one load vector and two degrees of motion with simplified input cycles. The actual path of points on the femoral head relative to the acetabular cup were calculated and compared for physiological and simplified input cycles. The in vitro wear rates were found to be highly dependent on the shape of these paths and similarities could be drawn between the shape of the physiological paths and the simplified elliptical paths.

Modelling radiation fluxes in simple and complex environments: basics of the RayMan model.

PubMed

Matzarakis, Andreas; Rutz, Frank; Mayer, Helmut

2010-03-01

Short- and long-wave radiation flux densities absorbed by people have a significant influence on their energy balance. The heat effect of the absorbed radiation flux densities is parameterised by the mean radiant temperature. This paper presents the physical basis of the RayMan model, which simulates the short- and long-wave radiation flux densities from the three-dimensional surroundings in simple and complex environments. RayMan has the character of a freely available radiation and human-bioclimate model. The aim of the RayMan model is to calculate radiation flux densities, sunshine duration, shadow spaces and thermo-physiologically relevant assessment indices using only a limited number of meteorological and other input data. A comparison between measured and simulated values for global radiation and mean radiant temperature shows that the simulated data closely resemble measured data.

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.

Metabolism and physiologically based pharmacokinetic modeling of flumioxazin in pregnant animals

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

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

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

Comprehensive Modeling and Visualization of Cardiac Anatomy and Physiology from CT Imaging and Computer Simulations

PubMed Central

Sun, Peng; Zhou, Haoyin; Ha, Seongmin; Hartaigh, Bríain ó; Truong, Quynh A.; Min, James K.

2016-01-01

In clinical cardiology, both anatomy and physiology are needed to diagnose cardiac pathologies. CT imaging and computer simulations provide valuable and complementary data for this purpose. However, it remains challenging to gain useful information from the large amount of high-dimensional diverse data. The current tools are not adequately integrated to visualize anatomic and physiologic data from a complete yet focused perspective. We introduce a new computer-aided diagnosis framework, which allows for comprehensive modeling and visualization of cardiac anatomy and physiology from CT imaging data and computer simulations, with a primary focus on ischemic heart disease. The following visual information is presented: (1) Anatomy from CT imaging: geometric modeling and visualization of cardiac anatomy, including four heart chambers, left and right ventricular outflow tracts, and coronary arteries; (2) Function from CT imaging: motion modeling, strain calculation, and visualization of four heart chambers; (3) Physiology from CT imaging: quantification and visualization of myocardial perfusion and contextual integration with coronary artery anatomy; (4) Physiology from computer simulation: computation and visualization of hemodynamics (e.g., coronary blood velocity, pressure, shear stress, and fluid forces on the vessel wall). Substantially, feedback from cardiologists have confirmed the practical utility of integrating these features for the purpose of computer-aided diagnosis of ischemic heart disease. PMID:26863663

EXPOSURES AND INTERNAL DOSES OF ...

EPA Pesticide Factsheets

The National Center for Environmental Assessment (NCEA) has released a final report that presents and applies a method to estimate distributions of internal concentrations of trihalomethanes (THMs) in humans resulting from a residential drinking water exposure. The report presents simulations of oral, dermal and inhalation exposures and demonstrates the feasibility of linking the US EPA’s information Collection Rule database with other databases on external exposure factors and physiologically based pharmacokinetic modeling to refine population-based estimates of exposure. Review Draft - by 2010, develop scientifically sound data and approaches to assess and manage risks to human health posed by exposure to specific regulated waterborne pathogens and chemicals, including those addressed by the Arsenic, M/DBP and Six-Year Review Rules.

Organ-On-A-Chip Platforms: A Convergence of Advanced Materials, Cells, and Microscale Technologies.

PubMed

Ahadian, Samad; Civitarese, Robert; Bannerman, Dawn; Mohammadi, Mohammad Hossein; Lu, Rick; Wang, Erika; Davenport-Huyer, Locke; Lai, Ben; Zhang, Boyang; Zhao, Yimu; Mandla, Serena; Korolj, Anastasia; Radisic, Milica

2018-01-01

Significant advances in biomaterials, stem cell biology, and microscale technologies have enabled the fabrication of biologically relevant tissues and organs. Such tissues and organs, referred to as organ-on-a-chip (OOC) platforms, have emerged as a powerful tool in tissue analysis and disease modeling for biological and pharmacological applications. A variety of biomaterials are used in tissue fabrication providing multiple biological, structural, and mechanical cues in the regulation of cell behavior and tissue morphogenesis. Cells derived from humans enable the fabrication of personalized OOC platforms. Microscale technologies are specifically helpful in providing physiological microenvironments for tissues and organs. In this review, biomaterials, cells, and microscale technologies are described as essential components to construct OOC platforms. The latest developments in OOC platforms (e.g., liver, skeletal muscle, cardiac, cancer, lung, skin, bone, and brain) are then discussed as functional tools in simulating human physiology and metabolism. Future perspectives and major challenges in the development of OOC platforms toward accelerating clinical studies of drug discovery are finally highlighted. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterization and inhibitive study of gel-grown hydroxyapatite crystals at physiological temperature

NASA Astrophysics Data System (ADS)

Parekh, Bharat; Joshi, Mihir; Vaidya, Ashok

2008-04-01

Hydroxyapatite is very useful for various biomedical applications, due to its chemical similarity with mineralized bone of human. Hydroxyapatite is also responsible for arthropathy (joint disease). In the present study, the growth of hydroxyapatite crystals was carried out by using single-diffusion gel growth technique in silica hydro gel media, at physiological temperature. The growth of hydroxyapatite crystals under slow and controlled environment in gel medium can be simulated in a simple manner to the growth in human body. The crystals, formed in the Liesegang rings, were characterized by powder XRD, FTIR and dielectric study. The diffusion study is also carried out for the hydroxyapatite crystals using the moving boundary model. The inhibitive influence of various Ayurvedic medicinal plant extracts such as Boswellia serrata gum resin , Tribulus terrestris fruits, Rotula aquatica roots, Boerhaavia diffusa roots and Commiphora wightii, on the growth of hydroxyapatite was studied. Roots of R. aquatica and B. diffusa show some inhibition of the hydroxyapatite crystals in vitro. This preclinical study will be helpful to design the therapy for prevention of hydroxyapatite-based ailments.

The Physical Price of a Ticket into Space

NASA Astrophysics Data System (ADS)

Hawkey, A.

As a direct consequence of exposure to microgravity astronauts experience a number of physiological changes, which can have serious medical implications when they return to Earth. Most immediate and significant are the head-ward shift of body fluids and the removal of gravitational loading from bone and muscles, which lead to progressive changes in the cardiovascular and musculoskeletal systems. Cardiovascular adaptations result in an increased incidence of orthostatic intolerance (fainting) post-flight, decreased cardiac output and reduced exercise capacity. Changes in the musculoskeletal system contribute significantly to the impaired functions experienced in the post-flight period. The underlying factor producing these changes is the absence of gravity. Countermeasures, therefore, are designed primarily to simulate Earth-like movements, stresses and system interactions. Exercise is one approach that has received wide operational use and acceptance in both the US and Russian space programmes, and has enabled humans to stay relatively healthy in space for well over a year. Although it remains the most effective countermeasure currently available, significant physiological degrada- tion still occurs. The development of other countermeasures will therefore be necessary for longer duration missions, such as the human exploration of Mars.

Physiologically based pharmacokinetic model for quinocetone in pigs and extrapolation to mequindox.

PubMed

Zhu, Xudong; Huang, Lingli; Xu, Yamei; Xie, Shuyu; Pan, Yuanhu; Chen, Dongmei; Liu, Zhenli; Yuan, Zonghui

2017-02-01

Physiologically based pharmacokinetic (PBPK) models are scientific methods used to predict veterinary drug residues that may occur in food-producing animals, and which have powerful extrapolation ability. Quinocetone (QCT) and mequindox (MEQ) are widely used in China for the prevention of bacterial infections and promoting animal growth, but their abuse causes a potential threat to human health. In this study, a flow-limited PBPK model was developed to simulate simultaneously residue depletion of QCT and its marker residue dideoxyquinocetone (DQCT) in pigs. The model included compartments for blood, liver, kidney, muscle and fat and an extra compartment representing the other tissues. Physiological parameters were obtained from the literature. Plasma protein binding rates, renal clearances and tissue/plasma partition coefficients were determined by in vitro and in vivo experiments. The model was calibrated and validated with several pharmacokinetic and residue-depletion datasets from the literature. Sensitivity analysis and Monte Carlo simulations were incorporated into the PBPK model to estimate individual variation of residual concentrations. The PBPK model for MEQ, the congener compound of QCT, was built through cross-compound extrapolation based on the model for QCT. The QCT model accurately predicted the concentrations of QCT and DQCT in various tissues at most time points, especially the later time points. Correlation coefficients between predicted and measured values for all tissues were greater than 0.9. Monte Carlo simulations showed excellent consistency between estimated concentration distributions and measured data points. The extrapolation model also showed good predictive power. The present models contribute to improve the residue monitoring systems of QCT and MEQ, and provide evidence of the usefulness of PBPK model extrapolation for the same kinds of compounds.

A Simulator-Assisted Workshop for Teaching Chemostat Cultivation in Academic Classes on Microbial Physiology.

PubMed

Hakkaart, Xavier D V; Pronk, Jack T; van Maris, Antonius J A

2017-01-01

Understanding microbial growth and metabolism is a key learning objective of microbiology and biotechnology courses, essential for understanding microbial ecology, microbial biotechnology and medical microbiology. Chemostat cultivation, a key research tool in microbial physiology that enables quantitative analysis of growth and metabolism under tightly defined conditions, provides a powerful platform to teach key features of microbial growth and metabolism. Substrate-limited chemostat cultivation can be mathematically described by four equations. These encompass mass balances for biomass and substrate, an empirical relation that describes distribution of consumed substrate over growth and maintenance energy requirements (Pirt equation), and a Monod-type equation that describes the relation between substrate concentration and substrate-consumption rate. The authors felt that the abstract nature of these mathematical equations and a lack of visualization contributed to a suboptimal operative understanding of quantitative microbial physiology among students who followed their Microbial Physiology B.Sc. courses. The studio-classroom workshop presented here was developed to improve student understanding of quantitative physiology by a set of question-guided simulations. Simulations are run on Chemostatus, a specially developed MATLAB-based program, which visualizes key parameters of simulated chemostat cultures as they proceed from dynamic growth conditions to steady state. In practice, the workshop stimulated active discussion between students and with their teachers. Moreover, its introduction coincided with increased average exam scores for questions on quantitative microbial physiology. The workshop can be easily implemented in formal microbial physiology courses or used by individuals seeking to test and improve their understanding of quantitative microbial physiology and/or chemostat cultivation.

Female anthropometric variability and their effects on predicted thermoregulatory responses to work in the heat

NASA Astrophysics Data System (ADS)

Yokota, Miyo; Berglund, Larry G.; Bathalon, Gaston P.

2012-03-01

The use of thermoregulatory models for assessing physiological responses of workers in thermally stressful situations has been increasing because of the risks and costs related to human studies. In a previous study (Yokota et al. Eur J Appl Physiol 104:297-302, 2008), the effects of anthropometric variability on predicted physiological responses to heat stress in U.S. Army male soldiers were evaluated. Five somatotypes were identified in U.S. Army male multivariate anthropometric distribution. The simulated heat responses, using a thermoregulatory model, were different between somatotypes. The present study further extends this line of research to female soldiers. Anthropometric somatotypes were identified using multivariate analysis [height, weight, percent body fat (%BF)] and the predicted physiological responses to simulated exercise and heat stress using a thermoregulatory model were evaluated. The simulated conditions included walking at ~3 mph (4.8 km/h) for 300 min and wearing battle dress uniform and body armor in a 30°C, 25% relative humidity (RH) environment without solar radiation. Five major somatotypes (tall-fat, tall-lean, average, short-lean, and short-fat), identified through multivariate analysis of anthropometric distributions, showed different tolerance levels to simulated heat stress: lean women were predicted to maintain their core temperatures (Tc) lower than short-fat or tall-fat women. The measured Tc of female subjects obtained from two heat studies (data1: 30°C, 32% RH, protective garments, ~225 w·m-2 walk for 90 min; data2: 32°C, 75% RH, hot weather battle dress uniform, ~378 ± 32 w·m-2 for 30 min walk/30 min rest cycles for 120 min) were utilized for validation. Validation results agreed with the findings in this study: fat subjects tended to have higher core temperatures than medium individuals (data2) and lean subjects maintained lower core temperatures than medium subjects (data1).

Female anthropometric variability and their effects on predicted thermoregulatory responses to work in the heat.

PubMed

Yokota, Miyo; Berglund, Larry G; Bathalon, Gaston P

2012-03-01

The use of thermoregulatory models for assessing physiological responses of workers in thermally stressful situations has been increasing because of the risks and costs related to human studies. In a previous study (Yokota et al. Eur J Appl Physiol 104:297-302, 2008), the effects of anthropometric variability on predicted physiological responses to heat stress in U.S. Army male soldiers were evaluated. Five somatotypes were identified in U.S. Army male multivariate anthropometric distribution. The simulated heat responses, using a thermoregulatory model, were different between somatotypes. The present study further extends this line of research to female soldiers. Anthropometric somatotypes were identified using multivariate analysis [height, weight, percent body fat (%BF)] and the predicted physiological responses to simulated exercise and heat stress using a thermoregulatory model were evaluated. The simulated conditions included walking at ~3 mph (4.8 km/h) for 300 min and wearing battle dress uniform and body armor in a 30°C, 25% relative humidity (RH) environment without solar radiation. Five major somatotypes (tall-fat, tall-lean, average, short-lean, and short-fat), identified through multivariate analysis of anthropometric distributions, showed different tolerance levels to simulated heat stress: lean women were predicted to maintain their core temperatures (T(c)) lower than short-fat or tall-fat women. The measured T(c) of female subjects obtained from two heat studies (data1: 30°C, 32% RH, protective garments, ~225 w·m(-2) walk for 90 min; data2: 32°C, 75% RH, hot weather battle dress uniform, ~378 ± 32 w·m(-2) for 30 min walk/30 min rest cycles for 120 min) were utilized for validation. Validation results agreed with the findings in this study: fat subjects tended to have higher core temperatures than medium individuals (data2) and lean subjects maintained lower core temperatures than medium subjects (data1).

The effect of physiological conditions on the surface structure of proteins: Setting the scene for human digestion of emulsions

NASA Astrophysics Data System (ADS)

Maldonado-Valderrama, J.; Gunning, A. P.; Ridout, M. J.; Wilde, P. J.; Morris, V. J.

2009-10-01

Understanding and manipulating the interfacial mechanisms that control human digestion of food emulsions is a crucial step towards improved control of dietary intake. This article reports initial studies on the effects of the physiological conditions within the stomach on the properties of the film formed by the milk protein ( β -lactoglobulin) at the air-water interface. Atomic force microscopy (AFM), surface tension and surface rheology techniques were used to visualize and examine the effect of gastric conditions on the network structure. The effects of changes in temperature, pH and ionic strength on a pre-formed interfacial structure were characterized in order to simulate the actual digestion process. Changes in ionic strength had little effect on the surface properties. In isolation, acidification reduced both the dilatational and the surface shear modulus, mainly due to strong repulsive electrostatic interactions within the surface layer and raising the temperature to body temperature accelerated the rearrangements within the surface layer, resulting in a decrease of the dilatational response and an increase of surface pressure. Together pH and temperature display an unexpected synergism, independent of the ionic strength. Thus, exposure of a pre-formed interfacial β -lactoglobulin film to simulated gastric conditions reduced the surface dilatational modulus and surface shear moduli. This is attributed to a weakening of the surface network in which the surface rearrangements of the protein prior to exposure to gastric conditions might play a crucial role.

Interactions of poly(amidoamine) dendrimers with human serum albumin: binding constants and mechanisms.

PubMed

Giri, Jyotsnendu; Diallo, Mamadou S; Simpson, André J; Liu, Yi; Goddard, William A; Kumar, Rajeev; Woods, Gwen C

2011-05-24

The interactions of nanomaterials with plasma proteins have a significant impact on their in vivo transport and fate in biological fluids. This article discusses the binding of human serum albumin (HSA) to poly(amidoamine) [PAMAM] dendrimers. We use protein-coated silica particles to measure the HSA binding constants (K(b)) of a homologous series of 19 PAMAM dendrimers in aqueous solutions at physiological pH (7.4) as a function of dendrimer generation, terminal group, and core chemistry. To gain insight into the mechanisms of HSA binding to PAMAM dendrimers, we combined (1)H NMR, saturation transfer difference (STD) NMR, and NMR diffusion ordered spectroscopy (DOSY) of dendrimer-HSA complexes with atomistic molecular dynamics (MD) simulations of dendrimer conformation in aqueous solutions. The binding measurements show that the HSA binding constants (K(b)) of PAMAM dendrimers depend on dendrimer size and terminal group chemistry. The NMR (1)H and DOSY experiments indicate that the interactions between HSA and PAMAM dendrimers are relatively weak. The (1)H NMR STD experiments and MD simulations suggest that the inner shell protons of the dendrimers groups interact more strongly with HSA proteins. These interactions, which are consistently observed for different dendrimer generations (G0-NH(2)vs G4-NH(2)) and terminal groups (G4-NH(2)vs G4-OH with amidoethanol groups), suggest that PAMAM dendrimers adopt backfolded configurations as they form weak complexes with HSA proteins in aqueous solutions at physiological pH (7.4).

Extracorporeal Membrane Oxygenation for End-Stage Interstitial Lung Disease With Secondary Pulmonary Hypertension at Rest and Exercise: Insights From Simulation Modeling.

PubMed

Chicotka, Scott; Burkhoff, Daniel; Dickstein, Marc L; Bacchetta, Matthew

Interstitial lung disease (ILD) represents a collection of lung disorders with a lethal trajectory with few therapeutic options with the exception of lung transplantation. Various extracorporeal membrane oxygenation (ECMO) configurations have been used for bridge to transplant (BTT), yet no optimal configuration has been clearly demonstrated. Using a cardiopulmonary simulation, we assessed different ECMO configurations for patients with end-stage ILD to assess the physiologic deficits and help guide the development of new long-term pulmonary support devices. A cardiopulmonary ECMO simulation was created, and changes in hemodynamics and blood gases were compared for different inflow and outflow anatomic locations and for different sweep gas and blood pump flow rates. The system simulated the physiologic response of patients with severe ILD at rest and during exercise with central ECMO, peripheral ECMO, and with no ECMO. The output parameters were total cardiac output (CO), mixed venous oxygen (O2) saturation, arterial pH, and O2 delivery (DO2)/O2 utilization (VO2) at different levels of exercise. The model described the physiologic state of progressive ILD and showed the relative effects of using various ECMO configurations to support them. It elucidated the optimal device configurations and required physiologic pump performance and provided insight into the physiologic demands of exercise in ILD patients. The simulation program was able to model the pathophysiologic state of progressive ILD with PH and demonstrate how mechanical support devices can be implemented to improve cardiopulmonary function at rest and during exercise. The information generated from simulation can be used to optimize ECMO configuration selection for BTT patients and provide design guidance for new devices to better meet the physiologic demands of exercise associated with normal activities of daily living.

Motion cue effects on human pilot dynamics in manual control

NASA Technical Reports Server (NTRS)

Washizu, K.; Tanaka, K.; Endo, S.; Itoko, T.

1977-01-01

Two experiments were conducted to study the motion cue effects on human pilots during tracking tasks. The moving-base simulator of National Aerospace Laboratory was employed as the motion cue device, and the attitude director indicator or the projected visual field was employed as the visual cue device. The chosen controlled elements were second-order unstable systems. It was confirmed that with the aid of motion cues the pilot workload was lessened and consequently the human controllability limits were enlarged. In order to clarify the mechanism of these effects, the describing functions of the human pilots were identified by making use of the spectral and the time domain analyses. The results of these analyses suggest that the sensory system of the motion cues can yield the differential informations of the signal effectively, which coincides with the existing knowledges in the physiological area.

Spectroscopic and molecular modeling studies of the interaction between cytidine and human serum albumin and its analytical application.

PubMed

Cui, Fengling; Wang, Junli; Yao, Xiaojun; Wang, Li; Zhang, Qiangzhai; Qu, Guirong

In this study, the interaction between cytidine and human serum albumin (HSA) was investigated for the first time by fluorescence spectroscopy in combination with UV absorption spectrum and molecular modeling under simulative physiological conditions. Experimental results indicated that cytidine had a strong ability to quench the intrinsic fluorescence of human serum albumin. The binding constants (K) at different temperatures, thermodynamic parameter enthalpy changes (DeltaH) and entropy changes (DeltaS) of HSA-cytidine had been calculated according to the relevant fluorescence data, which indicated that the hydrophobic and electrostatic interactions played a major role, which was in agreement with the results of molecular modeling study. In addition, the effects of other ions on the binding constants were also studied. Furthermore, synchronous fluorescence technology was successfully applied to the determination of human serum albumin added into the cytidine solution.

Epidermis Microstructure Inspired Graphene Pressure Sensor with Random Distributed Spinosum for High Sensitivity and Large Linearity.

PubMed

Pang, Yu; Zhang, Kunning; Yang, Zhen; Jiang, Song; Ju, Zhenyi; Li, Yuxing; Wang, Xuefeng; Wang, Danyang; Jian, Muqiang; Zhang, Yingying; Liang, Renrong; Tian, He; Yang, Yi; Ren, Tian-Ling

2018-03-27

Recently, wearable pressure sensors have attracted tremendous attention because of their potential applications in monitoring physiological signals for human healthcare. Sensitivity and linearity are the two most essential parameters for pressure sensors. Although various designed micro/nanostructure morphologies have been introduced, the trade-off between sensitivity and linearity has not been well balanced. Human skin, which contains force receptors in a reticular layer, has a high sensitivity even for large external stimuli. Herein, inspired by the skin epidermis with high-performance force sensing, we have proposed a special surface morphology with spinosum microstructure of random distribution via the combination of an abrasive paper template and reduced graphene oxide. The sensitivity of the graphene pressure sensor with random distribution spinosum (RDS) microstructure is as high as 25.1 kPa -1 in a wide linearity range of 0-2.6 kPa. Our pressure sensor exhibits superior comprehensive properties compared with previous surface-modified pressure sensors. According to simulation and mechanism analyses, the spinosum microstructure and random distribution contribute to the high sensitivity and large linearity range, respectively. In addition, the pressure sensor shows promising potential in detecting human physiological signals, such as heartbeat, respiration, phonation, and human motions of a pushup, arm bending, and walking. The wearable pressure sensor array was further used to detect gait states of supination, neutral, and pronation. The RDS microstructure provides an alternative strategy to improve the performance of pressure sensors and extend their potential applications in monitoring human activities.

Meeting review: Bioinformatics and Medicine - from molecules to humans, virtual and real.

PubMed

Russell, Roslin

2002-01-01

The Industrialization Workshop Series aims to promote and discuss integration, automation, simulation, quality, availability and standards in the high-throughput life sciences. The main issues addressed being the transformation of bioinformatics and bioinformaticsbased drug design into a robust discipline in industry, the government, research institutes and academia. The latest workshop emphasized the influence of the post-genomic era on medicine and healthcare with reference to advanced biological systems modeling and simulation, protein structure research, protein-protein interactions, metabolism and physiology. Speakers included Michael Ashburner, Kenneth Buetow, Francois Cambien, Cyrus Chothia, Jean Garnier, Francois Iris, Matthias Mann, Maya Natarajan, Peter Murray-Rust, Richard Mushlin, Barry Robson, David Rubin, Kosta Steliou, John Todd, Janet Thornton, Pim van der Eijk, Michael Vieth and Richard Ward.

Fabrication of a co-culture micro-bioreactor device for efficient hepatic differentiation of human induced pluripotent stem cells (hiPSCs).

PubMed

Kehtari, Mousa; Zeynali, Bahman; Soleimani, Masoud; Kabiri, Mahboubeh; Seyedjafari, Ehsan

2018-04-27

Primary hepatocytes, as the gold standard cell type for in vitro models, lose their characteristic morphology and functions after few days. There is an urgent need to develop physiologically relevant models that recapitulate liver microenvironment to obtain mature hepatocyte from stem cells. We designed and fabricated a micro-bioreactor device mimicking the physiological shear stress and cell-cell interaction in liver sinusoid microenvironment. Induced pluripotent stem cells (iPSCs) were co-cultured with human umbilical vein endothelial cells (HUVECs) in the micro-bioreactor device with continuous perfusion of hepatic differentiation medium (100 μL/h). Simulation results showed that flow field inside our perfusion device was uniform and shear stress was adjusted to physiological condition (<2 dyne/cm 2 ). IPSCs-derived hepatocytes (iPSCs-Heps) that were cultured in micro-bioreactor device showed a higher level of hepatic markers compared to those in static condition. Flow cytometry and immunocytochemistry analysis revealed iPSCs cultured in the device sequentially acquired characteristics of definitive endodermal cells (SOX17 positive), hepatoblasts (AFP positive) and mature hepatocyte (ALB positive). Moreover, the albumin and urea secretion were significantly higher in micro-bioreactor device than those cultured in culture dishes during experiment. Thus, based on our results, we propose our micro-bioreactor as a beneficial device to generate mature hepatocytes for drug screening and basic research.

Robotics-based synthesis of human motion.

PubMed

Khatib, O; Demircan, E; De Sapio, V; Sentis, L; Besier, T; Delp, S

2009-01-01

The synthesis of human motion is a complex procedure that involves accurate reconstruction of movement sequences, modeling of musculoskeletal kinematics, dynamics and actuation, and characterization of reliable performance criteria. Many of these processes have much in common with the problems found in robotics research. Task-based methods used in robotics may be leveraged to provide novel musculoskeletal modeling methods and physiologically accurate performance predictions. In this paper, we present (i) a new method for the real-time reconstruction of human motion trajectories using direct marker tracking, (ii) a task-driven muscular effort minimization criterion and (iii) new human performance metrics for dynamic characterization of athletic skills. Dynamic motion reconstruction is achieved through the control of a simulated human model to follow the captured marker trajectories in real-time. The operational space control and real-time simulation provide human dynamics at any configuration of the performance. A new criteria of muscular effort minimization has been introduced to analyze human static postures. Extensive motion capture experiments were conducted to validate the new minimization criterion. Finally, new human performance metrics were introduced to study in details an athletic skill. These metrics include the effort expenditure and the feasible set of operational space accelerations during the performance of the skill. The dynamic characterization takes into account skeletal kinematics as well as muscle routing kinematics and force generating capacities. The developments draw upon an advanced musculoskeletal modeling platform and a task-oriented framework for the effective integration of biomechanics and robotics methods.

Rimonabant effects on anxiety induced by simulated public speaking in healthy humans: a preliminary report.

PubMed

Bergamaschi, Mateus M; Queiroz, Regina H C; Chagas, Marcos H N; Linares, Ila M P; Arrais, Kátia C; de Oliveira, Danielle C G; Queiroz, Maria E; Nardi, Antonio E; Huestis, Marilyn A; Hallak, Jaime E C; Zuardi, Antonio W; Moreira, Fabrício A; Crippa, José A S

2014-01-01

We investigated the hypothesis that rimonabant, a cannabinoid antagonist/inverse agonist, would increase anxiety in healthy subjects during a simulation of the public speaking test. Participants were randomly allocated to receive oral placebo or 90 mg rimonabant in a double-blind design. Subjective effects were measured by Visual Analogue Mood Scale. Physiological parameters, namely arterial blood pressure and heart rate, also were monitored. Twelve participants received oral placebo and 12 received 90 mg rimonabant. Rimonabant increased self-reported anxiety levels during the anticipatory speech and performance phase compared with placebo. Interestingly, rimonabant did not modulate anxiety prestress and was not associated with sedation, cognitive impairment, discomfort, or blood pressure changes. Cannabinoid-1 antagonism magnifies the responses to an anxiogenic stimulus without interfering with the prestress phase. These data suggest that the endocannabinoid system may work on-demand to counteract the consequences of anxiogenic stimuli in healthy humans. Copyright © 2013 John Wiley & Sons, Ltd.

Rimonabant effects on anxiety induced by simulated public speaking in healthy humans: a preliminary report

PubMed Central

Bergamaschi, Mateus M.; Queiroz, Regina H. C.; Chagas, Marcos H. N.; Linares, Ila M. P.; Arrais, Kátia C.; de Oliveira, Danielle C. G.; Queiroz, Maria E.; Nardi, Antonio E.; Huestis, Marilyn A.; Hallak, Jaime E. C.; Zuardi, Antonio W.; Moreira, Fabrício A.; Crippa, José A. S.

2015-01-01

Objective We investigated the hypothesis that rimonabant, a cannabinoid antagonist/inverse agonist, would increase anxiety in healthy subjects during a simulation of the public speaking test. Methods Participants were randomly allocated to receive oral placebo or 90 mg rimonabant in a double-blind design. Subjective effects were measured by Visual Analogue Mood Scale. Physiological parameters, namely arterial blood pressure and heart rate, also were monitored. Results Twelve participants received oral placebo and 12 received 90 mg rimonabant. Rimonabant increased self-reported anxiety levels during the anticipatory speech and performance phase compared with placebo. Interestingly, rimonabant did not modulate anxiety prestress and was not associated with sedation, cognitive impairment, discomfort, or blood pressure changes. Conclusions Cannabinoid-1 antagonism magnifies the responses to an anxiogenic stimulus without interfering with the prestress phase. These data suggest that the endocannabinoid system may work on-demand to counteract the consequences of anxiogenic stimuli in healthy humans. PMID:24424711

An Advanced In Vitro Technology Platform to Study the Mechanism of Action of Prebiotics and Probiotics in the Gastrointestinal Tract.

PubMed

Marzorati, Massimo; Van de Wiele, Tom

The gastrointestinal tract (GIT) hosts the most complex microbial community in the human body. Given the extensive metabolic potential which is present in this community, this additional organ is of key importance to maintain a healthy status and several diseases are frequently correlated with an alteration of the composition/functionality of the gut microbiota. Consequently, there is a great interest in identifying potential approaches that could modulate the microbiota and its metabolism to bring about a positive health effect. A classical approach to reach this goal is the use of prebiotics and/or probiotics. How to study the potential effect of new prebiotics/probiotics and how to localize this effect along the full GIT? Human intervention trials are the golden standard to validate functional properties of food products. Yet, most studies on gut microbiota are based on the analysis of fecal samples because they are easily collected in a non-invasive manner. A complementary option is represented by well-designed in vitro simulation technologies. Among all the available systems, the Simulator of Human Intestinal Microbial Ecosystem has already been shown to be a useful model for nutrition studies in terms of analysis of the intestinal microbial community composition and activity. The Simulator of Human Intestinal Microbial Ecosystem is a scientifically validated platform representing the physiology and microbiology of the adult human GIT. Furthermore, recent advances in in vitro modelling also allow to combine the study of bacteria-host interactions, such as mucosal adhesion and interaction with the immune system, thereby further increasing the value of the scientific output.

Thermal comfort of pedestrians in an urban street canyon is affected by increasing albedo of building walls

NASA Astrophysics Data System (ADS)

Lee, Hyunjung; Mayer, Helmut

2018-03-01

Numerical simulations based on the ENVI-met model were carried out for an E-W street canyon in the city of Stuttgart (Southwest Germany) to analyse the effect of increased albedo of building walls on outdoor human thermal comfort. It was quantified by air temperature (T a ), mean radiant temperature (T mrt ) and physiologically equivalent temperature (PET). The simulations were conducted on 4 August 2003 as a heat wave day that represents a typical scenario for future summer weather in Central Europe. The simulation results presented for 13 CET and averaged over the period 10-16 CET are focused on pedestrians on both sidewalks. For the initial situation, i.e. albedo of 0.2, human heat stress indicated by mean PET is by 26% lower on the N-facing than on the S-facing sidewalk, while this reduction amounts to 42% for mean T mrt . Mean T a does not show any spatial differentiation. The systematic albedo increment by 0.2 from 0.2 to 0.8 leads to a linear increase of outdoor human heat stress in terms of T mrt and PET. For both variables, this increase is more pronounced on the N-facing than on the S-facing sidewalk. Mean relative T a shows the tendency of a minimal increase with rising albedo. The results were achieved for the usual standardised human-biometeorological reference person. Its substitution by two other types of male and female pedestrians, respectively, which are statistically characteristic of human conditions in Germany, does not reveal any significant change in the results.

Thermal comfort of pedestrians in an urban street canyon is affected by increasing albedo of building walls.

PubMed

Lee, Hyunjung; Mayer, Helmut

2018-03-12

Numerical simulations based on the ENVI-met model were carried out for an E-W street canyon in the city of Stuttgart (Southwest Germany) to analyse the effect of increased albedo of building walls on outdoor human thermal comfort. It was quantified by air temperature (T a ), mean radiant temperature (T mrt ) and physiologically equivalent temperature (PET). The simulations were conducted on 4 August 2003 as a heat wave day that represents a typical scenario for future summer weather in Central Europe. The simulation results presented for 13 CET and averaged over the period 10-16 CET are focused on pedestrians on both sidewalks. For the initial situation, i.e. albedo of 0.2, human heat stress indicated by mean PET is by 26% lower on the N-facing than on the S-facing sidewalk, while this reduction amounts to 42% for mean T mrt . Mean T a does not show any spatial differentiation. The systematic albedo increment by 0.2 from 0.2 to 0.8 leads to a linear increase of outdoor human heat stress in terms of T mrt and PET. For both variables, this increase is more pronounced on the N-facing than on the S-facing sidewalk. Mean relative T a shows the tendency of a minimal increase with rising albedo. The results were achieved for the usual standardised human-biometeorological reference person. Its substitution by two other types of male and female pedestrians, respectively, which are statistically characteristic of human conditions in Germany, does not reveal any significant change in the results.

Design Projects in Human Anatomy & Physiology

ERIC Educational Resources Information Center

Polizzotto, Kristin; Ortiz, Mary T.

2008-01-01

Very often, some type of writing assignment is required in college entry-level Human Anatomy and Physiology courses. This assignment can be anything from an essay to a research paper on the literature, focusing on a faculty-approved topic of interest to the student. As educators who teach Human Anatomy and Physiology at an urban community college,…

Cardiovascular Deconditioning in Humans: Human Studies Core

NASA Technical Reports Server (NTRS)

Williams, Gordon

1999-01-01

Major cardiovascular problems, secondary to cardiovascular deconditioning, may occur on extended space missions. While it is generally assumed that the microgravity state is the primary cause of cardiovascular deconditioning, sleep deprivation and disruption of diurnal rhythms may also play an important role. Factors that could be modified by either or both of these perturbations include: autonomic function and short-term cardiovascular reflexes, vasoreactivity, circadian rhythm of cardiovascular hormones (specifically the renin-angiotensin system) and renal sodium handling and hormonal influences on that process, venous compliance, cardiac mass, and cardiac conduction processes. The purpose of the Human Studies Core is to provide the infrastructure to conduct human experiments which will allow for the assessment of the likely role of such factors in the space travel associated cardiovascular deconditioning process and to develop appropriate countermeasures. The Core takes advantage of a newly-created Intensive Physiologic Monitoring (IPM) Unit at the Brigham and Women's Hospital, Boston, MA, to perform these studies. The Core includes two general experimental protocols. The first protocol involves a head down tilt bed-rest study to simulate microgravity. The second protocol includes the addition of a disruption of circadian rhythms to the simulated microgravity environment. Before and after each of these environmental manipulations, the subjects will undergo acute stressors simulating changes in volume and/or stress, which could occur in space and on return to Earth. The subjects are maintained in a rigidly controlled environment with fixed light/dark cycles, activity pattern, and dietary intake of nutrients, fluids, ions and calories.

Physiologically based pharmacokinetic toolkit to evaluate environmental exposures: Applications of the dioxin model to study real life exposures.

PubMed

Emond, Claude; Ruiz, Patricia; Mumtaz, Moiz

2017-01-15

Chlorinated dibenzo-p-dioxins (CDDs) are a series of mono- to octa-chlorinated homologous chemicals commonly referred to as polychlorinated dioxins. One of the most potent, well-known, and persistent member of this family is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). As part of translational research to make computerized models accessible to health risk assessors, we present a Berkeley Madonna recoded version of the human physiologically based pharmacokinetic (PBPK) model used by the U.S. Environmental Protection Agency (EPA) in the recent dioxin assessment. This model incorporates CYP1A2 induction, which is an important metabolic vector that drives dioxin distribution in the human body, and it uses a variable elimination half-life that is body burden dependent. To evaluate the model accuracy, the recoded model predictions were compared with those of the original published model. The simulations performed with the recoded model matched well with those of the original model. The recoded model was then applied to available data sets of real life exposure studies. The recoded model can describe acute and chronic exposures and can be useful for interpreting human biomonitoring data as part of an overall dioxin and/or dioxin-like compounds risk assessment. Copyright © 2016. Published by Elsevier Inc.

Characteristics of hyperthermia-induced hyperventilation in humans

PubMed Central

Tsuji, Bun; Hayashi, Keiji; Kondo, Narihiko; Nishiyasu, Takeshi

2016-01-01

ABSTRACT In humans, hyperthermia leads to activation of a set of thermoregulatory responses that includes cutaneous vasodilation and sweating. Hyperthermia also increases ventilation in humans, as is observed in panting dogs, but the physiological significance and characteristics of the hyperventilatory response in humans remain unclear. The relative contribution of respiratory heat loss to total heat loss in a hot environment in humans is small, and this hyperventilation causes a concomitant reduction in arterial CO2 pressure (hypocapnia), which can cause cerebral hypoperfusion. Consequently, hyperventilation in humans may not contribute to the maintenance of physiological homeostasis (i.e., thermoregulation). To gain some insight into the physiological significance of hyperthermia-induced hyperventilation in humans, in this review, we discuss 1) the mechanisms underlying hyperthermia-induced hyperventilation, 2) the factors modulating this response, and 3) the physiological consequences of the response. PMID:27227102

Next Steps Toward Understanding Human Habitation of Space: Environmental Impacts and Mechanisms

NASA Technical Reports Server (NTRS)

Globus, Ruth

2016-01-01

Entry into low earth orbit and beyond causes profound shifts in environmental conditions that have the potential to influence human productivity, long term health, and even survival. We now have evidence that microgravity, radiation and/or confinement in space can lead to demonstrably detrimental changes in the cardiovascular (e.g. vessel function, orthostatic intolerance), musculoskeletal (muscle atrophy, bone loss) and nervous (eye, neurovestibular) systems of astronauts. Because of both the limited number of astronauts who have flown (especially females) and the high degree of individual variability in the human population, important unanswered questions about responses to the space environment remain: What are the sex differences with respect to specific physiological systems? Are the responses age-dependent and/or reversible after return to Earth? Do observed detrimental changes that resemble accelerated aging progress continuously over time or plateau? What are the mechanisms of the biological responses? Answering these important questions certainly demands a multi-pronged approach, and the study of multicellular model organisms (such as rodents and flies) already has provided opportunities for exploring those questions in some detail. Recent long duration spaceflight experiments with rodents show that mice in space provide a mammalian model that uniquely combines the influence of reduced gravitational loading with increased physical activity. In addition, multiple investigators have shown that ground-based models that simulate aspects of spaceflight (including rodent hind limb unloading to mimic weightlessness and exposure to ionizing radiation), cause various transient and persistent detrimental consequences in multiple physiological systems. In general, we have found that adverse skeletal effects of simulated weightlessness and space radiation when combined, can be quantitatively, if not qualitatively, different from the influence of each environmental factor alone implying at least some shared underlying mechanisms. Thus, both ground based and spaceflight research utilizing model organisms provide the opportunity to better understand environmental factors and biological mechanisms that contribute to human health and survival in space.

The thermal environment of the human being on the global scale.

PubMed

Jendritzky, Gerd; Tinz, Birger

2009-11-11

The close relationship between human health, performance, well-being and the thermal environment is obvious. Nevertheless, most studies of climate and climate change impacts show amazing shortcomings in the assessment of the environment. Populations living in different climates have different susceptibilities, due to socio-economic reasons, and different customary behavioural adaptations. The global distribution of risks of hazardous thermal exposure has not been analysed before. To produce maps of the baseline and future bioclimate that allows a direct comparison of the differences in the vulnerability of populations to thermal stress across the world. The required climatological data fields are obtained from climate simulations with the global General Circulation Model ECHAM4 in T106-resolution. For the thermo-physiologically relevant assessment of these climate data a complete heat budget model of the human being, the 'Perceived Temperature' procedure has been applied which already comprises adaptation by clothing to a certain degree. Short-term physiological acclimatisation is considered via Health Related Assessment of the Thermal Environment. The global maps 1971-1980 (control run, assumed as baseline climate) show a pattern of thermal stress intensities as frequencies of heat. The heat load for people living in warm-humid climates is the highest. Climate change will lead to clear differences in health-related thermal stress between baseline climate and the future bioclimate 2041-2050 based on the 'business-as-usual' greenhouse gas scenario IS92a. The majority of the world's population will be faced with more frequent and more intense heat strain in spite of an assumed level of acclimatisation. Further adaptation measures are crucial in order to reduce the vulnerability of the populations. This bioclimatology analysis provides a tool for various questions in climate and climate change impact research. Considerations of regional or local scale require climate simulations with higher resolution. As adaptation is the key term in understanding the role of climate/climate change for human health, performance and well-being, further research in this field is crucial.

A graphical simulation software for instruction in cardiovascular mechanics physiology.

PubMed

Wildhaber, Reto A; Verrey, François; Wenger, Roland H

2011-01-25

Computer supported, interactive e-learning systems are widely used in the teaching of physiology. However, the currently available complimentary software tools in the field of the physiology of cardiovascular mechanics have not yet been adapted to the latest systems software. Therefore, a simple-to-use replacement for undergraduate and graduate students' education was needed, including an up-to-date graphical software that is validated and field-tested. Software compatible to Windows, based on modified versions of existing mathematical algorithms, has been newly developed. Testing was performed during a full term of physiological lecturing to medical and biology students. The newly developed CLabUZH software models a reduced human cardiovascular loop containing all basic compartments: an isolated heart including an artificial electrical stimulator, main vessels and the peripheral resistive components. Students can alter several physiological parameters interactively. The resulting output variables are printed in x-y diagrams and in addition shown in an animated, graphical model. CLabUZH offers insight into the relations of volume, pressure and time dependency in the circulation and their correlation to the electrocardiogram (ECG). Established mechanisms such as the Frank-Starling Law or the Windkessel Effect are considered in this model. The CLabUZH software is self-contained with no extra installation required and runs on most of today's personal computer systems. CLabUZH is a user-friendly interactive computer programme that has proved to be useful in teaching the basic physiological principles of heart mechanics.

Multiscale simulation of red blood cell aggregation

NASA Astrophysics Data System (ADS)

Bagchi, P.; Popel, A. S.

2004-11-01

In humans and other mammals, aggregation of red blood cells (RBC) is a major determinant to blood viscosity in microcirculation under physiological and pathological conditions. Elevated levels of aggregation are often related to cardiovascular diseases, bacterial infection, diabetes, and obesity. Aggregation is a multiscale phenomenon that is governed by the molecular bond formation between adjacent cells, morphological and rheological properties of the cells, and the motion of the extra-cellular fluid in which the cells circulate. We have developed a simulation technique using front tracking methods for multiple fluids that includes the multiscale characteristics of aggregation. We will report the first-ever direct computer simulation of aggregation of deformable cells in shear flows. We will present results on the effect of shear rate, strength of the cross-bridging bonds, and the cell rheological properties on the rolling motion, deformation and subsequent breakage of an aggregate.

Helicobacter pylori colonization critically depends on postprandial gastric conditions

PubMed Central

Bücker, Roland; Azevedo-Vethacke, Marina; Groll, Claudia; Garten, Désirée; Josenhans, Christine; Suerbaum, Sebastian; Schreiber, Sören

2012-01-01

The risk of Helicobacter pylori infection is highest in childhood, but the colonization process of the stomach mucosa is poorly understood. We used anesthetized Mongolian gerbils to study the initial stages of H. pylori colonization. Prandial and postprandial gastric conditions characteristic of humans of different ages were simulated. The fraction of bacteria that reached the deep mucus layer varied strongly with the modelled postprandial conditions. Colonization success was weak with fast gastric reacidification typical of adults. The efficiency of deep mucus entry was also low with a slow pH decrease as seen in pH profiles simulating the situation in babies. Initial colonization was most efficient under conditions simulating the postprandial reacidification and pepsin activation profiles in young children. In conclusion, initial H. pylori colonization depends on age-related gastric physiology, providing evidence from an in vivo infection model that suggests an explanation why the bacterium is predominantly acquired in early childhood. PMID:23251780

Wall Shear Stress Distribution in a Patient-Specific Cerebral Aneurysm Model using Reduced Order Modeling

NASA Astrophysics Data System (ADS)

Han, Suyue; Chang, Gary Han; Schirmer, Clemens; Modarres-Sadeghi, Yahya

2016-11-01

We construct a reduced-order model (ROM) to study the Wall Shear Stress (WSS) distributions in image-based patient-specific aneurysms models. The magnitude of WSS has been shown to be a critical factor in growth and rupture of human aneurysms. We start the process by running a training case using Computational Fluid Dynamics (CFD) simulation with time-varying flow parameters, such that these parameters cover the range of parameters of interest. The method of snapshot Proper Orthogonal Decomposition (POD) is utilized to construct the reduced-order bases using the training CFD simulation. The resulting ROM enables us to study the flow patterns and the WSS distributions over a range of system parameters computationally very efficiently with a relatively small number of modes. This enables comprehensive analysis of the model system across a range of physiological conditions without the need to re-compute the simulation for small changes in the system parameters.

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

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)

EPA Science Inventory

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. Th...

Placenta-on-a-chip: a novel platform to study the biology of the human placenta.

PubMed

Lee, Ji Soo; Romero, Roberto; Han, Yu Mi; Kim, Hee Chan; Kim, Chong Jai; Hong, Joon-Seok; Huh, Dongeun

2016-01-01

Studying the biology of the human placenta represents a major experimental challenge. Although conventional cell culture techniques have been used to study different types of placenta-derived cells, current in vitro models have limitations in recapitulating organ-specific structure and key physiological functions of the placenta. Here we demonstrate that it is possible to leverage microfluidic and microfabrication technologies to develop a microengineered biomimetic model that replicates the architecture and function of the placenta. A "Placenta-on-a-Chip" microdevice was created by using a set of soft elastomer-based microfabrication techniques known as soft lithography. This microsystem consisted of two polydimethylsiloxane (PDMS) microfluidic channels separated by a thin extracellular matrix (ECM) membrane. To reproduce the placental barrier in this model, human trophoblasts (JEG-3) and human umbilical vein endothelial cells (HUVECs) were seeded onto the opposite sides of the ECM membrane and cultured under dynamic flow conditions to form confluent epithelial and endothelial layers in close apposition. We tested the physiological function of the microengineered placental barrier by measuring glucose transport across the trophoblast-endothelial interface over time. The permeability of the barrier study was analyzed and compared to that obtained from acellular devices and additional control groups that contained epithelial or endothelial layers alone. Our microfluidic cell culture system provided a tightly controlled fluidic environment conducive to the proliferation and maintenance of JEG-3 trophoblasts and HUVECs on the ECM scaffold. Prolonged culture in this model produced confluent cellular monolayers on the intervening membrane that together formed the placental barrier. This in vivo-like microarchitecture was also critical for creating a physiologically relevant effective barrier to glucose transport. Quantitative investigation of barrier function was conducted by calculating permeability coefficients and metabolic rates in varying conditions of barrier structure. The rates of glucose transport and metabolism were consistent with previously reported in vivo observations. The "Placenta-on-a-Chip" microdevice described herein provides new opportunities to simulate and analyze critical physiological responses of the placental barrier. This system may be used to address the major limitations of existing placenta model systems and serve to enable research platforms for reproductive biology and medicine.

Testing Crew Responses to Varied Higher Plant Presentations in the MARS-500 Day Mission Simulation

NASA Astrophysics Data System (ADS)

Marquit, J. D.; Bates, S. C.; Gushin, V. I.; Synchev, V. N.; Levinskikh, M. A.; Podolsky, I. G.; Marchant, C. C.; Bingham, G. E.

2008-06-01

Maintaining psychological and behavioral health of humans during long-duration space missions is of great importance for the future success of space exploration as the hostile space environment adversely impacts the psychological, social, and physiological well-being of humans in space. Growing and tending plants has been proposed as a countermeasures for the negative impacts of long-duration space missions[3] as interactions with plant life on earth have been found to be beneficial to humans in other settings. Preliminary results from a pilot 14-day chamber study appear to support the notion that interactions with plant life may act as a countermeasure for the negative impacts of life in space. Additional data will be collected during the Mars 500-day Chamber Study at Institute of Biomedical Problems (IMBP).

Absolute quantification methods in tissue near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Matcher, Steven J.; Kirkpatrick, Peter J.; Nahid, K.; Cope, Mark; Delpy, David T.

1995-05-01

Recent work aimed at providing an absolute measurement of tissue haemoglobin saturation and a new instrument development, the spatially resolved spectrometer (SRS), are discussed. The theoretical basis of operation of this device and its hardware implementation are described and the results of validation studies on tissue simulating phantoms are presented as are preliminary measurements on human volunteers and observations on patients undergoing neurosurgery. In its present form the instrument appears to produce absolute haemoglobin saturation values for resting human skeletal muscle and the normally perfused human head which are rather low based on physiological expectations. However, we obtained a tight correlation between the saturation values measured by the SRS instrument and those obtained from blood-gas analysis of samples drawn from a jugular bulb catheter in one neurosurgery subject during clamping of the right carotid arteries.

Human experimental anxiety: actual public speaking induces more intense physiological responses than simulated public speaking.

PubMed

Zuardi, Antonio Waldo; Crippa, José Alexandre de Souza; Hallak, Jaime Eduardo Cecílio; Gorayeb, Ricardo

2013-01-01

a) To perform a systematic and meta-analytic review to verify whether the Simulated Public Speaking Task (SPST) leads to a greater increase in self-rated anxiety than in physiological correlates of anxiety; and b) to compare the results obtained with the SPST with an actual public speaking task involving healthy volunteers. a) The PubMed and ISI Web of Knowledge databases were searched for studies involving the SPST prior to 2012. Eleven publications were eligible and provided data from 143 healthy volunteers for meta-analysis; b) 48 university students without somatic or psychiatric disorders were divided into three experimental groups of 16 subjects to undergo one of the following: SPST, real-world public speaking task (real-world), and control situation (control). The meta-analysis showed that the SPST induced a significant increase in the Visual Analogue Mood Scale (VAMS) anxiety factor, but no significant increases in systolic blood pressure or heart rate. The empirical study showed that the real-world public speaking task increased heart rate, systolic blood pressure and diastolic blood pressure significantly more than the control and SPST conditions. These results suggest that real public speaking might be better than SPST in inducing experimental anxiety.

The Structural Basis of IKs Ion-Channel Activation: Mechanistic Insights from Molecular Simulations.

PubMed

Ramasubramanian, Smiruthi; Rudy, Yoram

2018-06-05

Relating ion channel (iCh) structural dynamics to physiological function remains a challenge. Current experimental and computational techniques have limited ability to explore this relationship in atomistic detail over physiological timescales. A framework associating iCh structure to function is necessary for elucidating normal and disease mechanisms. We formulated a modeling schema that overcomes the limitations of current methods through applications of artificial intelligence machine learning. Using this approach, we studied molecular processes that underlie human IKs voltage-mediated gating. IKs malfunction underlies many debilitating and life-threatening diseases. Molecular components of IKs that underlie its electrophysiological function include KCNQ1 (a pore-forming tetramer) and KCNE1 (an auxiliary subunit). Simulations, using the IKs structure-function model, reproduced experimentally recorded saturation of gating-charge displacement at positive membrane voltages, two-step voltage sensor (VS) movement shown by fluorescence, iCh gating statistics, and current-voltage relationship. Mechanistic insights include the following: 1) pore energy profile determines iCh subconductance; 2) the entire protein structure, not limited to the pore, contributes to pore energy and channel subconductance; 3) interactions with KCNE1 result in two distinct VS movements, causing gating-charge saturation at positive membrane voltages and current activation delay; and 4) flexible coupling between VS and pore permits pore opening at lower VS positions, resulting in sequential gating. The new modeling approach is applicable to atomistic scale studies of other proteins on timescales of physiological function. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The paranasal sinuses: the last frontier in craniofacial biology.

PubMed

Márquez, Samuel

2008-11-01

This special issue of the Anatomical Record explores the presence and diversity of paranasal sinuses in distinct vertebrate groups. The following topics are addressed in particular: dinosaur physiology; development; physiology; adaptation; imaging; and primate systematics. A variety of approaches and techniques are used to examine and characterize the diversity of paranasal sinus pneumatization in a wide spectrum of vertebrates. These range from dissection to histology, from plain X-rays to computer tomography, from comparative anatomy to natural experimental settings, from mathematical computation to computer model simulation, and 2D to 3D reconstructions. The articles in this issue are a combination of literature review and new, hypothesis-driven anatomical research that highlights the complexities of paranasal sinus growth and development; ontogenetic and disease processes; physiology; paleontology; primate systematics; and human evolution. The issue incorporates a wide variety of vertebrates, encompassing a period of over 65 million years, in an effort to offer insight into the diversity of the paranasal sinus complexes through time and space, and thereby providing a greater understanding and appreciation of these special spaces within the cranium. Copyright 2008 Wiley-Liss, Inc.

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.

The Effect of Center of Gravity and Anthropometrics on Human Performance in Simulated Lunar Gravity

NASA Technical Reports Server (NTRS)

Mulugeta, Lealem; Chappell, Steven P.; Skytland, Nicholas G.

2009-01-01

NASA EVA Physiology, Systems and Performance (EPSP) Project at JSC has been investigating the effects of Center of Gravity and other factors on astronaut performance in reduced gravity. A subset of the studies have been performed with the water immersion technique. Study results show correlation between Center of Gravity location and performance. However, data variability observed between subjects for prescribed Center of Gravity configurations. The hypothesis is that Anthropometric differences between test subjects could be a source of the performance variability.

Aerospace Medicine and Biology: A Continuing Bibliography. Supplement 483

NASA Technical Reports Server (NTRS)

1999-01-01

Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

Stress-oriented driver assistance system for electric vehicles.

PubMed

Athanasiou, Georgia; Tsotoulidis, Savvas; Mitronikas, Epaminondas; Lymberopoulos, Dimitrios

2014-01-01

Stress is physiological and physical reaction that appears in highly demanding situations and affects human's perception and reaction capability. Occurrence of stress events within highly dynamic road environment could lead to life-threatening situation. With the perspective of safety and comfort driving provision to anxious drivers, in this paper a stress-oriented Driver Assistance System (DAS) is proposed. The DAS deployed on Electric Vehicle. This novel DAS customizes driving command signal in respect to road context, when stress is detected. The effectiveness of this novel DAS is verified by simulation in MATLAB/SIMULINK environment.

Physiological pattern changes in response to a simulated competition in elite women artistic gymnasts.

PubMed

Isacco, Laurie; Ennequin, Gaël; Cassirame, Johan; Tordi, Nicolas

2017-08-04

The outstanding progress in women's artistic gymnastics in recent decades has led to increased technical and physiological demands. The aim of this study was to investigate i) the physiological demands of elite French gymnasts and ii) the impact of a competitive routine on physiological pattern changes. Fourteen French elite female gymnasts performed anthropometric measurements, physical fitness tests and a simulated four event competition. Heart rate (HR) was continuously recorded throughout the duration of the simulated competition. Blood lactate concentrations were assessed at rest, before the beginning and at 2, 4 and 10 min after completion of the routine on each apparatus. Isometric handgrip strength and anaerobic endurance and power were assessed during the simulated competition. The highest values of HR and blood lactate concentrations were reached during the floor and uneven bar exercises. Blood lactate concentrations and HR kinetics were apparatus dependent and values remained significantly increased at 10 min of recovery compared with resting data. Anaerobic endurance and power decreased significantly as the competition progressed (P <0.001). The present results show specifically cardiorespiratory and anaerobic apparatus- dependent responses throughout a simulated competition. Recovery approaches appear relevant to prevent and/or minimize fatigue and optimize performance in these athletes.

Adverse Effects of Simulated Hyper- and Hypo-Phosphatemia on Endothelial Cell Function and Viability

PubMed Central

Zeng, Caihong; Rakheja, Dinesh; Zhu, Jiankun; Ye, Ting; Hutcheson, Jack; Vaziri, Nosratola D.; Liu, Zhihong; Mohan, Chandra; Zhou, Xin J.

2011-01-01

Background Dysregulaiton of phosphate homeostasis as occurs in chronic kidney disease is associated with cardiovascular complications. It has been suggested that both hyperphosphatemia and hypophosphatemia can cause cardiovascular disease. The molecular mechanisms by which high or low serum phosphate levels adversely affect cardiovascular function are poorly understood. The purpose of this study was to explore the mechanisms of endothelial dysfunction in the presence of non-physiologic phosphate levels. Methodology/Principal Findings We studied the effects of simulated hyper- and hypophosphatemia in human umbilical vein endothelial cells in vitro. We found both simulated hyperphosphatemia and hypophosphatemia decrease eNOS expression and NO production. This was associated with reduced intracellular calcium, increased protein kinase C β2 (PKCβ2), reduced cell viability, and increased apoptosis. While simulated hyperphosphatemia was associated with decreased Akt/p-Akt, Bcl-xl/Bax ratios, NFkB-p65 and p-Erk abundance, simulated hypophosphatemia was associated with increased Akt/p-Akt and Bcl-xl/Bax ratios and p-Mek, p38, and p-p38 abundance. Conclusions/Significance This is the first demonstration of endothelial dysfunction with hypophosphatemia. Our data suggests that both hyperphosphatemia and hypophosphatemia decrease eNOS activity via reduced intracellular calcium and increased PKCβ2. Hyperphosphatemia also appears to reduce eNOS transcription via reduced signaling through PI3K/Akt/NF-kB and MAPK/NF-kB pathways. On the other hand, hypophosphatemia appears to activate these pathways. Our data provides the basis for further studies to elucidate the relationship between altered phosphate homeostasis and cardiovascular disease. As a corollary, our data suggests that the level of phosphate in the culture media, if not in the physiologic range, may inadvertently affect experimental results. PMID:21858050

Advancements in remote physiological measurement and applications in human-computer interaction

NASA Astrophysics Data System (ADS)

McDuff, Daniel

2017-04-01

Physiological signals are important for tracking health and emotional states. Imaging photoplethysmography (iPPG) is a set of techniques for remotely recovering cardio-pulmonary signals from video of the human body. Advances in iPPG methods over the past decade combined with the ubiquity of digital cameras presents the possibility for many new, lowcost applications of physiological monitoring. This talk will highlight methods for recovering physiological signals, work characterizing the impact of video parameters and hardware on these measurements, and applications of this technology in human-computer interfaces.

Novel use of a noninvasive hemodynamic monitor in a personalized, active learning simulation.

PubMed

Zoller, Jonathan K; He, Jianghua; Ballew, Angela T; Orr, Walter N; Flynn, Brigid C

2017-06-01

The present study furthered the concept of simulation-based medical education by applying a personalized active learning component. We tested this novel approach utilizing a noninvasive hemodynamic monitor with the capability to measure and display in real time numerous hemodynamic parameters in the exercising participant. Changes in medical knowledge concerning physiology were examined with a pre-and posttest. Simply by observation of one's own hemodynamic variables, the understanding of complex physiological concepts was significantly enhanced. Copyright © 2017 the American Physiological Society.

Bovine lactoferrin digested with human gastrointestinal enzymes inhibits replication of human echovirus 5 in cell culture.

PubMed

Furlund, Camilla B; Kristoffersen, Anja B; Devold, Tove G; Vegarud, Gerd E; Jonassen, Christine M

2012-07-01

Many infant formulas are enriched with lactoferrin (Lf) because of its claimed beneficial effects on health. Native bovine Lf (bLf) is known to inhibit in vitro replication of human enteroviruses, a group of pathogenic viruses that replicate in the gut as their primary infection site. On the basis of a model digestion and human gastrointestinal enzymes, we hypothesized that bLf could retain its antiviral properties against enterovirus in the gastrointestinal tract, either as an intact protein or through bioactive peptide fragments released by digestive enzymes. To test our hypothesis, bLf was digested with human gastric juice and duodenal juice in a 2-step in vitro digestion model. Two gastric pH levels and reduction conditions were used to simulate physiological conditions in adults and infants. The antiviral activity of native bLf and of the digested fractions was studied on echovirus 5 in vitro, using various assay conditions, addressing several mechanisms for replication inhibition. Both native and digested bLf fractions revealed a significant inhibitory effect, when added before or simultaneously with the virus onto the cells. Furthermore, a significant stronger sustained antiviral effect was observed when bLf was fully digested in the gastric phase with fast pH reduction to 2.5, compared with native bLf, suggesting the release of antiviral peptides from bLf during the human digestion process. In conclusion, this study demonstrates that bLf may have a role in the prevention of human gastrointestinal virus infection under physiological conditions and that food containing bLf may protect against infection in vivo. Copyright © 2012 Elsevier Inc. All rights reserved.

Impedances of the ear estimated with intracochlear pressures in normal human temporal bones

NASA Astrophysics Data System (ADS)

Frear, Darcy; Guan, Xiying; Stieger, Christof; Nakajima, Hideko Heidi

2018-05-01

We have measured intracochlear pressures and velocities of stapes and round window (RW) evoked by air conduction (AC) stimulation in many fresh human cadaveric specimens. Our techniques have improved through the years to ensure reliable pressure sensor measurements in the scala vestibuli and scala tympani. Using these measurements, we have calculated impedances of the middle and inner ear (cochlear partition, RW, and physiological leakage impedance in scala vestibuli) to create a lumped element model. Our model simulates our data and allows us to understand the mechanisms involved in air-conducted sound transmission. In the future this model will be used as a tool to understand transmission mechanisms of various stimuli and to help create more sophisticated models of the ear.

Estimation of the bioaccessibility and bioavailability of Fe, Mn, Cu, and Zn in Chinese vegetables using the in vitro digestion/Caco-2 cell model: the influence of gut microbiota.

PubMed

Cai, Xiaolin; Chen, Xiaochen; Yin, Naiyi; Du, Huili; Sun, Guoxin; Wang, Lihong; Xu, Yudong; Chen, Yuqing; Cui, Yanshan

2017-12-13

The influence of the human gut microbiota on the bioaccessibility and bioavailability of trace elements in vegetables has barely been studied. An in vitro digestion model combining the physiologically based extraction test (PBET) and the Simulator of Human Intestinal Microbial Ecosystem (SHIME) was applied. Results showed that the gut microbiota increased the bioaccessibility of iron (Fe) in ten test vegetables by 1.3-1.8 times, but reduced the bioaccessibility of manganese (Mn), copper (Cu), and zinc (Zn) in vegetables in the colon phase by 3.7% to 89.6%, 24.8% to 100.0%, and 59.9% to 100.0%, respectively. Using the Caco-2 cell model to simulate the human absorption process, the bioavailable contents and the bioavailability of the trace elements were further determined. Swamp cabbage was the best source of Fe and Cu; spinach and lettuce provided the highest amounts of bioavailable Mn and Zn, respectively. Referring to the daily reference intakes of trace elements, the obtained data provide a scientific basis for both reasonable ingestion of vegetables in diets and diversification of diets.

Design of a cost-effective, hemodynamically adjustable model for resuscitative endovascular balloon occlusion of the aorta (REBOA) simulation.

PubMed

Keller, Benjamin A; Salcedo, Edgardo S; Williams, Timothy K; Neff, Lucas P; Carden, Anthony J; Li, Yiran; Gotlib, Oren; Tran, Nam K; Galante, Joseph M

2016-09-01

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct technique for salvaging patients with noncompressible torso hemorrhage. Current REBOA training paradigms require large animals, virtual reality simulators, or human cadavers for acquisition of skills. These training strategies are expensive and resource intensive, which may prevent widespread dissemination of REBOA. We have developed a low-cost, near-physiologic, pulsatile REBOA simulator by connecting an anatomic vascular circuit constructed out of latex and polyvinyl chloride tubing to a commercially available pump. This pulsatile simulator is capable of generating cardiac outputs ranging from 1.7 to 6.8 L/min with corresponding arterial blood pressures of 54 to 226/14 to 121 mmHg. The simulator accommodates a 12 French introducer sheath and a CODA balloon catheter. Upon balloon inflation, the arterial waveform distal to the occlusion flattens, distal pulsation within the simulator is lost, and systolic blood pressures proximal to the balloon catheter increase by up to 62 mmHg. Further development and validation of this simulator will allow for refinement, reduction, and replacement of large animal models, costly virtual reality simulators, and perfused cadavers for training purposes. This will ultimately facilitate the low-cost, high-fidelity REBOA simulation needed for the widespread dissemination of this life-saving technique.

Simulation of urinary excretion of 1-hydroxypyrene in various scenarios of exposure to polycyclic aromatic hydrocarbons with a generic, cross-chemical predictive PBTK-model.

PubMed

Jongeneelen, Frans; ten Berge, Wil

2012-08-01

A physiologically based toxicokinetic (PBTK) model can predict blood and urine concentrations, given a certain exposure scenario of inhalation, dermal and/or oral exposure. The recently developed PBTK-model IndusChemFate is a unified model that mimics the uptake, distribution, metabolism and elimination of a chemical in a reference human of 70 kg. Prediction of the uptake by inhalation is governed by pulmonary exchange to blood. Oral uptake is simulated as a bolus dose that is taken up at a first-order rate. Dermal uptake is estimated by the use of a novel dermal physiologically based module that considers dermal deposition rate and duration of deposition. Moreover, evaporation during skin contact is fully accounted for and related to the volatility of the substance. Partitioning of the chemical and metabolite(s) over blood and tissues is estimated by a Quantitative Structure-Property Relationship (QSPR) algorithm. The aim of this study was to test the generic PBTK-model by comparing measured urinary levels of 1-hydroxypyrene in various inhalation and dermal exposure scenarios with the result of model simulations. In the last three decades, numerous biomonitoring studies of PAH-exposed humans were published that used the bioindicator 1-hydroxypyrene (1-OH-pyrene) in urine. Longitudinal studies that encompass both dosimetry and biomonitoring with repeated sampling in time were selected to test the accuracy of the PBTK-model by comparing the reported concentrations of 1-OHP in urine with the model-predicted values. Two controlled human volunteer studies and three field studies of workers exposed to polycyclic aromatic hydrocarbons (PAH) were included. The urinary pyrene-metabolite levels of a controlled human inhalation study, a transdermal uptake study of bitumen fume, efficacy of respirator use in electrode paste workers, cokery workers in shale oil industry and a longitudinal study of five coke liquefaction workers were compared to the PBTK-predicted values. The simulations showed that the model-predicted concentrations of urinary pyrene and metabolites over time, as well as peak-concentrations and total excreted amount in different exposure scenarios of inhalation and transdermal exposure were in all comparisons within an order of magnitude. The model predicts that only a very small fraction is excreted in urine as parent pyrene and as free 1-OH-pyrene. The predominant urinary metabolite is 1-OH-pyrene-glucuronide. Enterohepatic circulation of 1-OH-pyrene-glucuronide seems the reason of the delayed release from the body. It appeared that urinary excretion of pyrene and pyrene-metabolites in humans is predictable with the PBTK-model. The model outcomes have a satisfying accuracy for early testing, in so-called 1st tier simulations and in range finding. This newly developed generic PBTK-model IndusChemFate is a tool that can be used to do early explorations of the significance of uptake of pyrene in the human body following industrial or environmental exposure scenarios. And it can be used to optimize the sampling time and urine sampling frequency of a biomonitoring program.

Human Adaptation to Space: Space Physiology and Countermeasures

NASA Technical Reports Server (NTRS)

Fogarty, Jennifer

2009-01-01

This viewgraph presentation reviews human physiological responses to spaceflight, and the countermeasures taken to prevent adverse effects of manned space flight. The topics include: 1) Human Spaceflight Experience; 2) Human Response to Spaceflight; 3) ISS Expeditions 1-16; 4) Countermeasure; and 5) Biomedical Data;

Enhancing learning through optimal sequencing of web-based and manikin simulators to teach shock physiology in the medical curriculum.

PubMed

Cendan, Juan C; Johnson, Teresa R

2011-12-01

The Association of American Medical Colleges has encouraged educators to investigate proper linkage of simulation experiences with medical curricula. The authors aimed to determine if student knowledge and satisfaction differ between participation in web-based and manikin simulations for learning shock physiology and treatment and to determine if a specific training sequencing had a differential effect on learning. All 40 second-year medical students participated in a randomized, counterbalanced study with two interventions: group 1 (n = 20) participated in a web-based simulation followed by a manikin simulation and group 2 (n = 20) participated in reverse order. Knowledge and attitudes were documented. Mixed-model ANOVA indicated a significant main effect of time (F(1,38) = 18.6, P < 0.001, η(p)(2) = 0.33). Group 1 scored significantly higher on quiz 2 (81.5%) than on quiz 1 (74.3%, t(19) = 3.9, P = 0.001), for an observed difference of 7.2% (95% confidence interval: 3.3, 11.0). Mean quiz scores of group 2 did not differ significantly (quiz 1: 77.0% and quiz 2: 79.7%). There was no significant main effect of group or a group by time interaction effect. Students rated the simulations as equally effective in teaching shock physiology (P = 0.88); however, the manikin simulation was regarded as more effective in teaching shock treatment (P < 0.001). Most students (73.7%) preferred the manikin simulation. The two simulations may be of similar efficacy for educating students on the physiology of shock; however, the data suggest improved learning when web-based simulation precedes manikin use. This finding warrants further study.

Anterior Cruciate Ligament Biomechanics During Robotic and Mechanical Simulations of Physiologic and Clinical Motion Tasks: A Systematic Review and Meta-Analysis

PubMed Central

Bates, Nathaniel A.; Myer, Gregory D.; Shearn, Jason T.; Hewett, Timothy E.

2014-01-01

Investigators use in vitro joint simulations to invasively study the biomechanical behaviors of the anterior cruciate ligament. The aims of these simulations are to replicate physiologic conditions, but multiple mechanisms can be used to drive in vitro motions, which may influence biomechanical outcomes. The objective of this review was to examine, summarize, and compare biomechanical evidence related to anterior cruciate ligament function from in vitro simulations of knee motion. A systematic review was conducted (2004 to 2013) in Scopus, PubMed/Medline, and SPORTDiscus to identify peer-reviewed studies that reported kinematic and kinetic outcomes from in vitro simulations of physiologic or clinical tasks at the knee. Inclusion criteria for relevant studies were articles published in English that reported on whole-ligament anterior cruciate ligament mechanics during the in vitro simulation of physiologic or clinical motions on cadaveric knees that were unaltered outside of the anterior-cruciate-ligament-intact, -deficient, and -reconstructed conditions. A meta-analysis was performed to synthesize biomechanical differences between the anterior-cruciate-ligament-intact and reconstructed conditions. 77 studies met our inclusion/exclusion criteria and were reviewed. Combined joint rotations have the greatest impact on anterior cruciate ligament loads, but the magnitude by which individual kinematic degrees of freedom contribute to ligament loading during in vitro simulations is technique-dependent. Biomechanical data collected in prospective, longitudinal studies corresponds better with robotic-manipulator simulations than mechanical-impact simulations. Robotic simulation indicated that the ability to restore intact anterior cruciate ligament mechanics with anterior cruciate ligament reconstructions was dependent on loading condition and degree of freedom examined. PMID:25547070

R-warfarin clearances from plasma associated with polymorphic cytochrome P450 2C19 and simulated by individual physiologically based pharmacokinetic models for 11 cynomolgus monkeys.

PubMed

Utoh, Masahiro; Kusama, Takashi; Miura, Tomonori; Mitsui, Marina; Kawano, Mirai; Hirano, Takahiro; Shimizu, Makiko; Uno, Yasuhiro; Yamazaki, Hiroshi

2018-02-01

1. Cynomolgus monkey cytochrome P450 2C19 (formerly known as P450 2C75), homologous to human P450 2C19, has been identified as R-warfarin 7-hydroxylase. In this study, simulations of R-warfarin clearance in individual cynomolgus monkeys genotyped for P450 2C19 p.[(Phe100Asn; Ala103Val; Ile112Leu)] were performed using individual simplified physiologically based pharmacokinetic (PBPK) modeling. 2. Pharmacokinetic parameters and absorption rate constants, volumes of the systemic circulation, and hepatic intrinsic clearances for individual PBPK models were estimated for eleven cynomolgus monkeys. 3. One-way ANOVA revealed significant effects of the genotype (p < 0.01) on the observed elimination half-lives and areas under the curves of R-warfarin among the homozygous mutant, heterozygous mutant, and wild-type groups. R-Warfarin clearances in individual cynomolgus monkeys genotyped for P450 2C19 were simulated by simplified PBPK modeling. The modeled hepatic intrinsic clearances were significantly associated with the P450 2C19 genotypes. The liver microsomal elimination rates of R-warfarin for individual animals after in vivo administration showed significant reductions associated with the genotype (p < 0.01). 4. This study provides important information to help simulate clearances of R-warfarin and related medicines associated with polymorphic P450 2C19 in individual cynomolgus monkeys, thereby facilitating calculation of the fraction of hepatic clearance.

Magnesium alloys as body implants: fracture mechanism under dynamic and static loadings in a physiological environment.

PubMed

Choudhary, Lokesh; Raman, R K Singh

2012-02-01

It is essential that a metallic implant material possesses adequate resistance to cracking/fracture under the synergistic action of a corrosive physiological environment and mechanical loading (i.e. stress corrosion cracking (SCC)), before the implant can be put to actual use. This paper presents a critique of the fundamental issues with an assessment of SCC of a rapidly corroding material such as magnesium alloys, and describes an investigation into the mechanism of SCC of a magnesium alloy in a physiological environment. The SCC susceptibility of the alloy in a simulated human body fluid was established by slow strain rate tensile (SSRT) testing using smooth specimens under different electrochemical conditions for understanding the mechanism of SCC. However, to assess the life of the implant devices that often possess fine micro-cracks, SCC susceptibility of notched specimens was investigated by circumferential notch tensile (CNT) testing. CNT tests also produced important design data, i.e. threshold stress intensity for SCC (KISCC) and SCC crack growth rate. Fractographic features of SCC were examined using scanning electron microscopy. The SSRT and CNT results, together with fractographic evidence, confirmed the SCC susceptibility of both smooth and notched specimens of a magnesium alloy in the physiological environment. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Rain influences the physiological and metabolic responses to exercise in hot conditions.

PubMed

Ito, Ryo; Yamashita, Naoyuki; Suzuki, Eiko; Matsumoto, Takaaki

2015-01-01

Outdoor exercise often proceeds in rainy conditions. However, the cooling effects of rain on human physiological responses have not been systematically studied in hot conditions. The present study determined physiological and metabolic responses using a climatic chamber that can precisely simulate hot, rainy conditions. Eleven healthy men ran on a treadmill at an intensity of 70% VO2max for 30 min in the climatic chamber at an ambient temperature of 33°C in the presence (RAIN) or absence (CON) of 30 mm · h(-1) of precipitation and a headwind equal to the running velocity of 3.15 ± 0.19 m · s(-1). Oesophageal temperature, mean skin temperature, heart rate, rating of perceived exertion, blood parameters, volume of expired air and sweat loss were measured. Oesophageal and mean skin temperatures were significantly lower from 5 to 30 min, and heart rate was significantly lower from 20 to 30 min in RAIN than in CON (P < 0.05 for all). Plasma lactate and epinephrine concentrations (30 min) and sweat loss were significantly lower (P < 0.05) in RAIN compared with CON. Rain appears to influence physiological and metabolic responses to exercise in heat such that heat-induced strain might be reduced.

A Digital Computer Simulation of Cardiovascular and Renal Physiology.

ERIC Educational Resources Information Center

Tidball, Charles S.

1979-01-01

Presents the physiological MACPEE, one of a family of digital computer simulations used in Canada and Great Britain. A general description of the model is provided, along with a sample of computer output format, options for making interventions, advanced capabilities, an evaluation, and technical information for running a MAC model. (MA)

Physiological role of somatostatin-mediated autofeedback regulation for growth hormone: importance of growth hormone in triggering somatostatin release during a trough period of pulsatile growth hormone release in conscious male rats.

PubMed

Sato, M; Chihara, K; Kita, T; Kashio, Y; Okimura, Y; Kitajima, N; Fujita, T

1989-08-01

In mammals including human, it is generally accepted that growth hormone (GH) can regulate its own secretion through an autofeedback mechanism in which somatostatin (SRIF) may be involved. To explore a physiological role of SRIF-mediated GH autoregulation, the effect of exogenous human GH administration on plasma rat GH response to [D-Ala2, Nle27]-human GH-releasing hormone-(1-28)-agmatine (hGHRH-analog), which does not crossreact with anti-rat GH-releasing hormone gamma-globulin (GHRH-Ab), was examined in conscious male rats treated with GHRH-Ab in the absence and presence of anti-SRIF gamma-globulin (SRIF-Ab). Enhanced SRIF release during a trough period of natural pulsatile GH secretion, suggested by the blunted GH response to exogenous hGHRH-analog, no longer occurred when major GH secretory bursts were abolished by GHRH-Ab treatment. On the other hand, when hGH was administered in GHRH-Ab-treated rats so as to simulate the quantity and dynamic change of GH in hypophysial portal circulation in rats exhibiting pulsatile GH secretion, hGHRH-analog-induced GH rises were significantly suppressed during the period corresponding to a GH trough. This suppression was completely prevented by simultaneous treatment with SRIF-Ab. Furthermore, administration of bovine GH, but not ovine prolactin, resulted in significant suppression of hGHRH-analog-provoked GH rises. These findings suggest that enhanced SRIF release during a trough period of spontaneous GH secretory rhythm is induced by the preceding GH secretory burst, and also suggest a possible role for SRIF-mediated GH autoregulation in a physiological state.

Physiological modeling for detecting degree of perception of a color-deficient person.

PubMed

Rajalakshmi, T; Prince, Shanthi

2017-04-01

Physiological modeling of retina plays a vital role in the development of high-performance image processing methods to produce better visual perception. People with normal vision have an ability to discern different colors. The situation is different in the case of people with color blindness. The aim of this work is to develop a human visual system model for detecting the level of perception of people with red, green and blue deficiency by considering properties like luminance, spatial and temporal frequencies. Simulation results show that in the photoreceptor, outer plexiform and inner plexiform layers, the energy and intensity level of the red, green and blue component for a normal person is proved to be significantly higher than for dichromats. The proposed method explains with appropriate results that red and blue color blindness people could not perceive red and blue color completely.

French research program on the physiological problems caused by weightlessness. Use of the primate model

NASA Astrophysics Data System (ADS)

Pesquies, P. C.; Milhaud, C.; Nogues, C.; Klein, M.; Cailler, B.; Bost, R.

The need to acquire a better knowledge of the main biological problems induced by microgravity implies—in addition to human experimentation—the use of animal models, and primates seem to be particularly well adapted to this type of research. The major areas of investigation to be considered are the phospho-calcium metabolism and the metabolism of supporting tissues, the hydroelectrolytic metabolism, the cardiovascular function, awakeness, sleep-awakeness cycles, the physiology of equilibrium and the pathophysiology of space sickness. Considering this program, the Centre d'Etudes et de Recherches de Medecine Aerospatiale, under the sponsorship of the Centre National d'Etudes Spatiales, developed both a program of research on restrained primates for the French-U.S. space cooperation (Spacelab program) and for the French-Soviet space cooperation (Bio-cosmos program), and simulation of the effects of microgravity by head-down bedrest. Its major characteristics are discussed in the study.

Investigating gender differences under conditions of fatigue in a simulated high G aerial combat environment.

PubMed

Chelette, T L

1997-06-01

Advances in technology have equipped high-performance combat aircraft with the capability of delivering higher and higher sustained acceleration or G-forces on the pilots flying them. While the physiological effects of increased g-forces on the human body continue to be investigated, studies examining the effects of acceleration on the cognitive abilities of high-performance aircraft pilots remain sparse. Additionally, as higher technology is making its way into the cockpit, so are female pilots. With even fewer studies investigating women's physiological and cognitive tolerances to the stressors in the high-performance cockpit and flight environment, Dr. Chelette's study aimed to investigate these issues. Examining pilot workload, flight task abilities, and the effects of sleeplessness on both male and female pilots, Dr. Chelette's results revealed findings that will make their way into the high-performance cockpit of the future.

Characterization of interaction between doxycycline and human serum albumin by capillary electrophoresis-frontal analysis.

PubMed

Sun, Hanwen; He, Pan

2009-06-01

The binding of doxycycline to HSA under simulated physiological conditions (pH 7.4, 67 mM phosphate, I=0.17, drug concentration 100 microM, HSA concentration up to 475 microM, 36.5 degrees C) was studied by CE-frontal analysis. The number of primary binding sites, binding constant and physiological protein-binding percentage were 1.9, 1.51 x 10(3) M(-1) and 59.80%, respectively. In addition, the thermodynamic parameters including enthalpy change (DeltaH), entropy change (DeltaS) and free energy change (DeltaG) of the reaction were obtained in order to characterize the acting forces between doxycycline and HSA. Furthermore, to better understand the nature of doxycycline-HSA binding and to get information about potential interaction with other drugs, displacement experiments were performed. The results showed that doxycycline binds at site II of HSA.

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

PubMed

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

2009-09-01

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

Research on human physiological parameters intelligent clothing based on distributed Fiber Bragg Grating

NASA Astrophysics Data System (ADS)

Miao, Changyun; Shi, Boya; Li, Hongqiang

2008-12-01

A human physiological parameters intelligent clothing is researched with FBG sensor technology. In this paper, the principles and methods of measuring human physiological parameters including body temperature and heart rate in intelligent clothing with distributed FBG are studied, the mathematical models of human physiological parameters measurement are built; the processing method of body temperature and heart rate detection signals is presented; human physiological parameters detection module is designed, the interference signals are filtered out, and the measurement accuracy is improved; the integration of the intelligent clothing is given. The intelligent clothing can implement real-time measurement, processing, storage and output of body temperature and heart rate. It has accurate measurement, portability, low cost, real-time monitoring, and other advantages. The intelligent clothing can realize the non-contact monitoring between doctors and patients, timely find the diseases such as cancer and infectious diseases, and make patients get timely treatment. It has great significance and value for ensuring the health of the elders and the children with language dysfunction.

Validation of the Cat as a Model for the Human Lumbar Spine During Simulated High-Velocity, Low-Amplitude Spinal Manipulation

PubMed Central

Pickar, Joel G.; Khalsa, Partap S.

2012-01-01

High-velocity, low-amplitude spinal manipulation (HVLA-SM) is an efficacious treatment for low back pain, although the physiological mechanisms underlying its effects remain elusive. The lumbar facet joint capsule (FJC) is innervated with mechanically sensitive neurons and it has been theorized that the neurophysiological benefits of HVLA-SM are partially induced by stimulation of FJC neurons. Biomechanical aspects of this theory have been investigated in humans while neurophysiological aspects have been investigated using cat models. The purpose of this study was to determine the relationship between human and cat lumbar spines during HVLA-SM. Cat lumbar spine specimens were mechanically tested, using a displacement-controlled apparatus, during simulated HVLA-SM applied at L5, L6, and L7 that produced preload forces of ~25% bodyweight for 0.5 s and peak forces that rose to 50–100% bodyweight within ~125 ms, similar to that delivered clinically. Joint kinematics and FJC strain were measured optically. Human FJC strain and kinematics data were taken from a prior study. Regression models were established for FJC strain magnitudes as functions of factors species, manipulation site, and interactions thereof. During simulated HVLA-SM, joint kinematics in cat spines were greater in magnitude compared with humans. Similar to human spines, site-specific HVLA-SM produced regional cat FJC strains at distant motion segments. Joint motions and FJC strain magnitudes for cat spines were larger than those for human spine specimens. Regression relationships demonstrated that species, HVLA-SM site, and interactions thereof were significantly and moderately well correlated for HVLA-SM that generated tensile strain in the FJC. The relationships established in the current study can be used in future neurophysiological studies conducted in cats to extrapolate how human FJC afferents might respond to HVLA-SM. The data from the current study warrant further investigation into the clinical relevance of site targeted HVLA-SM. PMID:20590286

Development of In Vitro-In Vivo Correlation/Relationship Modeling Approaches for Immediate Release Formulations Using Compartmental Dynamic Dissolution Data from “Golem”: A Novel Apparatus

PubMed Central

Tuszyński, Paweł K.; Polak, Sebastian; Jachowicz, Renata; Mendyk, Aleksander; Dohnal, Jiří

2015-01-01

Different batches of atorvastatin, represented by two immediate release formulation designs, were studied using a novel dynamic dissolution apparatus, simulating stomach and small intestine. A universal dissolution method was employed which simulated the physiology of human gastrointestinal tract, including the precise chyme transit behavior and biorelevant conditions. The multicompartmental dissolution data allowed direct observation and qualitative discrimination of the differences resulting from highly pH dependent dissolution behavior of the tested batches. Further evaluation of results was performed using IVIVC/IVIVR development. While satisfactory correlation could not be achieved using a conventional deconvolution based-model, promising results were obtained through the use of a nonconventional approach exploiting the complex compartmental dissolution data. PMID:26120580

A time dependent anatomically detailed model of cardiac conduction

NASA Technical Reports Server (NTRS)

Saxberg, B. E.; Grumbach, M. P.; Cohen, R. J.

1985-01-01

In order to understand the determinants of transitions in cardiac electrical activity from normal patterns to dysrhythmias such as ventricular fibrillation, we are constructing an anatomically and physiologically detailed finite element simulation of myocardial electrical propagation. A healthy human heart embedded in paraffin was sectioned to provide a detailed anatomical substrate for model calculations. The simulation of propagation includes anisotropy in conduction velocity due to fiber orientation as well as gradients in conduction velocities, absolute and relative refractory periods, action potential duration and electrotonic influence of nearest neighbors. The model also includes changes in the behaviour of myocardial tissue as a function of the past local activity. With this model, we can examine the significance of fiber orientation and time dependence of local propagation parameters on dysrhythmogenesis.

Joint independent component analysis for simultaneous EEG-fMRI: principle and simulation.

PubMed

Moosmann, Matthias; Eichele, Tom; Nordby, Helge; Hugdahl, Kenneth; Calhoun, Vince D

2008-03-01

An optimized scheme for the fusion of electroencephalography and event related potentials with functional magnetic resonance imaging (BOLD-fMRI) data should simultaneously assess all available electrophysiologic and hemodynamic information in a common data space. In doing so, it should be possible to identify features of latent neural sources whose trial-to-trial dynamics are jointly reflected in both modalities. We present a joint independent component analysis (jICA) model for analysis of simultaneous single trial EEG-fMRI measurements from multiple subjects. We outline the general idea underlying the jICA approach and present results from simulated data under realistic noise conditions. Our results indicate that this approach is a feasible and physiologically plausible data-driven way to achieve spatiotemporal mapping of event related responses in the human brain.

A multi-tissue type genome-scale metabolic network for analysis of whole-body systems physiology

PubMed Central

2011-01-01

Background Genome-scale metabolic reconstructions provide a biologically meaningful mechanistic basis for the genotype-phenotype relationship. The global human metabolic network, termed Recon 1, has recently been reconstructed allowing the systems analysis of human metabolic physiology and pathology. Utilizing high-throughput data, Recon 1 has recently been tailored to different cells and tissues, including the liver, kidney, brain, and alveolar macrophage. These models have shown utility in the study of systems medicine. However, no integrated analysis between human tissues has been done. Results To describe tissue-specific functions, Recon 1 was tailored to describe metabolism in three human cells: adipocytes, hepatocytes, and myocytes. These cell-specific networks were manually curated and validated based on known cellular metabolic functions. To study intercellular interactions, a novel multi-tissue type modeling approach was developed to integrate the metabolic functions for the three cell types, and subsequently used to simulate known integrated metabolic cycles. In addition, the multi-tissue model was used to study diabetes: a pathology with systemic properties. High-throughput data was integrated with the network to determine differential metabolic activity between obese and type II obese gastric bypass patients in a whole-body context. Conclusion The multi-tissue type modeling approach presented provides a platform to study integrated metabolic states. As more cell and tissue-specific models are released, it is critical to develop a framework in which to study their interdependencies. PMID:22041191

Development and application of a multiroute physiologically based pharmacokinetic model for oxytetracycline in dogs and humans.

PubMed

Lin, Zhoumeng; Li, Mengjie; Gehring, Ronette; Riviere, Jim E

2015-01-01

Oxytetracycline (OTC) is a commonly used tetracycline antibiotic in veterinary and human medicine. To establish a quantitative model for predicting OTC plasma and tissue exposure, a permeability-limited multiroute physiologically based pharmacokinetic model was developed in dogs. The model was calibrated with plasma pharmacokinetic data in beagle dogs following single intravenous (5 mg/kg), oral (100 mg/kg), and intramuscular (20 mg/kg) administrations. The model predicted other available dog data well, including drug concentrations in the liver, kidney, and muscle after repeated exposure, and data in the mixed-breed dog. The model was extrapolated to humans and the human model adequately simulated measured plasma OTC concentrations after intravenous (7.14 mg/kg) and oral exposures (6.67 mg/kg). The dog model was applied to predict 24-h OTC area-under-the-curve after three therapeutic treatments. Results were 27.75, 51.76, and 64.17 μg/mL*h in the plasma, and 120.93, 225.64, and 279.67 μg/mL*h in the kidney for oral (100 mg/kg), intravenous (10 mg/kg), and intramuscular (20 mg/kg) administrations, respectively. This model can be used to predict plasma and tissue concentrations to aid in designing optimal therapeutic regimens with OTC in veterinary, and potentially, human medicine; and as a foundation for scaling to other tetracycline antibiotics and to other animal species. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:233-243, 2015. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Incorporating neurophysiological concepts in mathematical thermoregulation models

NASA Astrophysics Data System (ADS)

Kingma, Boris R. M.; Vosselman, M. J.; Frijns, A. J. H.; van Steenhoven, A. A.; van Marken Lichtenbelt, W. D.

2014-01-01

Skin blood flow (SBF) is a key player in human thermoregulation during mild thermal challenges. Various numerical models of SBF regulation exist. However, none explicitly incorporates the neurophysiology of thermal reception. This study tested a new SBF model that is in line with experimental data on thermal reception and the neurophysiological pathways involved in thermoregulatory SBF control. Additionally, a numerical thermoregulation model was used as a platform to test the function of the neurophysiological SBF model for skin temperature simulation. The prediction-error of the SBF-model was quantified by root-mean-squared-residual (RMSR) between simulations and experimental measurement data. Measurement data consisted of SBF (abdomen, forearm, hand), core and skin temperature recordings of young males during three transient thermal challenges (1 development and 2 validation). Additionally, ThermoSEM, a thermoregulation model, was used to simulate body temperatures using the new neurophysiological SBF-model. The RMSR between simulated and measured mean skin temperature was used to validate the model. The neurophysiological model predicted SBF with an accuracy of RMSR < 0.27. Tskin simulation results were within 0.37 °C of the measured mean skin temperature. This study shows that (1) thermal reception and neurophysiological pathways involved in thermoregulatory SBF control can be captured in a mathematical model, and (2) human thermoregulation models can be equipped with SBF control functions that are based on neurophysiology without loss of performance. The neurophysiological approach in modelling thermoregulation is favourable over engineering approaches because it is more in line with the underlying physiology.

Locally enhanced sampling molecular dynamics study of the dioxygen transport in human cytoglobin.

PubMed

Orlowski, Slawomir; Nowak, Wieslaw

2007-07-01

Cytoglobin (Cyg)--a new member of the vertebrate heme globin family--is expressed in many tissues of the human body but its physiological role is still unclear. It may deliver oxygen under hypoxia, serve as a scavenger of reactive species or be involved in collagen synthesis. This protein is usually six-coordinated and binds oxygen by a displacement of the distal HisE7 imidazole. In this paper, the results of 60 ns molecular dynamics (MD) simulations of dioxygen diffusion inside Cyg matrix are discussed. In addition to a classical MD trajectory, an approximate Locally Enhanced Sampling (LES) method has been employed. Classical diffusion paths were carefully analyzed, five cavities in dynamical structures were determined and at least four distinct ligand exit paths were identified. The most probable exit/entry path is connected with a large tunnel present in Cyg. Several residues that are perhaps critical for kinetics of small gaseous diffusion were discovered. A comparison of gaseous ligand transport in Cyg and in the most studied heme protein myoglobin is presented. Implications of efficient oxygen transport found in Cyg to its possible physiological role are discussed.

Operational Issues: What Science in Available?

NASA Technical Reports Server (NTRS)

Rosekind, Mark R.; Neri, David F.

1997-01-01

Flight/duty/rest considerations involve two highly complex factors: the diverse demands of aviation operations and human physiology (especially sleep and circadian rhythms). Several core operational issues related to fatigue have been identified, such as minimum rest requirements, duty length, flight time considerations, crossing multiple time zones, and night flying. Operations also can involve on-call reserve status and callout, delays due to unforeseen circumstances (e.g., weather, mechanical), and on-demand flights. Over 40 years of scientific research is now available to apply to these complex issues of flight/duty/rest requirements. This research involves controlled 'laboratory studies, simulations, and data collected during regular flight operations. When flight/duty/rest requirements are determined they are typically based on a variety of considerations, such as operational demand, safety, economic, etc. Rarely has the available, state-of-the-art science been a consideration along with these other factors when determining flight/duty/rest requirements. While the complexity of the operational demand and human physiology precludes an absolute solution, there is an opportunity to take full advantage of the current scientific data. Incorporating these data in a rational operational manner into flight/duty/rest requirements can improve flight crew performance, alertness, and ultimately, aviation safety.

Decompression to altitude: assumptions, experimental evidence, and future directions.

PubMed

Foster, Philip P; Butler, Bruce D

2009-02-01

Although differences exist, hypobaric and hyperbaric exposures share common physiological, biochemical, and clinical features, and their comparison may provide further insight into the mechanisms of decompression stress. Although altitude decompression illness (DCI) has been experienced by high-altitude Air Force pilots and is common in ground-based experiments simulating decompression profiles of extravehicular activities (EVAs) or astronauts' space walks, no case has been reported during actual EVAs in the non-weight-bearing microgravity environment of orbital space missions. We are uncertain whether gravity influences decompression outcomes via nitrogen tissue washout or via alterations related to skeletal muscle activity. However, robust experimental evidence demonstrated the role of skeletal muscle exercise, activities, and/or movement in bubble formation and DCI occurrence. Dualism of effects of exercise, positive or negative, on bubble formation and DCI is a striking feature in hypobaric exposure. Therefore, the discussion and the structure of this review are centered on those highlighted unresolved topics about the relationship between muscle activity, decompression, and microgravity. This article also provides, in the context of altitude decompression, an overview of the role of denitrogenation, metabolic gases, gas micronuclei, stabilization of bubbles, biochemical pathways activated by bubbles, nitric oxide, oxygen, anthropometric or physiological variables, Doppler-detectable bubbles, and potential arterialization of bubbles. These findings and uncertainties will produce further physiological challenges to solve in order to line up for the programmed human return to the Moon, the preparation for human exploration of Mars, and the EVAs implementation in a non-zero gravity environment.

Heat shock protein 70 as a biomarker of heat stress in a simulated hot cockpit.

PubMed

Kumar, Yadunanda; Chawla, Anuj; Tatu, Utpal

2003-07-01

Fighter pilots are frequently exposed to high temperatures during high-speed low-level flight. Heat strain can result in temporary impairment of cognitive functions and when severe, loss of consciousness and consequent loss of life and equipment. Induction of stress proteins is a highly conserved stress response mechanism from bacteria to humans. Induced stress protein levels are known to be cytoprotective and have been correlated with stress tolerance. Although many studies on the heat shock response mechanisms have been performed in cell culture and animal model systems, there is very limited information on stress protein induction in human subjects. Heat shock proteins (Hsp), especially Hsp70, may be induced in human subjects exposed to high temperatures in a hot cockpit designed to simulate heat stress experienced in low flying sorties. Six healthy volunteers were subjected to heat stress at 55 degrees C in a high temperature cockpit simulator for a period of 1 h at 30% humidity. Physiological parameters such as oral and skin temperatures, heart rate, and sweat rate were monitored regularly during this time. The level of Hsp70 in leukocytes was examined before and after the heat exposure in each subject. Hsp70 was found to be significantly induced in all the six subjects exposed to heat stress. The level of induced Hsp70 appears to correlate with other strain indicators such as accumulative circulatory strain and Craig's modified index. The usefulness of Hsp70 as a molecular marker of heat stress in humans is discussed.

The Graphical Representation of the Digital Astronaut Physiology Backbone

NASA Technical Reports Server (NTRS)

Briers, Demarcus

2010-01-01

This report summarizes my internship project with the NASA Digital Astronaut Project to analyze the Digital Astronaut (DA) physiology backbone model. The Digital Astronaut Project (DAP) applies integrated physiology models to support space biomedical operations, and to assist NASA researchers in closing knowledge gaps related to human physiologic responses to space flight. The DA physiology backbone is a set of integrated physiological equations and functions that model the interacting systems of the human body. The current release of the model is HumMod (Human Model) version 1.5 and was developed over forty years at the University of Mississippi Medical Center (UMMC). The physiology equations and functions are scripted in an XML schema specifically designed for physiology modeling by Dr. Thomas G. Coleman at UMMC. Currently it is difficult to examine the physiology backbone without being knowledgeable of the XML schema. While investigating and documenting the tags and algorithms used in the XML schema, I proposed a standard methodology for a graphical representation. This standard methodology may be used to transcribe graphical representations from the DA physiology backbone. In turn, the graphical representations can allow examination of the physiological functions and equations without the need to be familiar with the computer programming languages or markup languages used by DA modeling software.

Potential health benefits of simulated laughter: a narrative review of the literature and recommendations for future research.

PubMed

Mora-Ripoll, Ramon

2011-06-01

Scientific research has shown that laughter may have both preventive and therapeutic values. Health-related benefits of laughter are mainly reported from spontaneous laughter interventional studies. While the human mind can make a distinction between simulated and spontaneous laughter, the human body cannot. Either way health-related outcomes are deemed to be produced. Simulated laughter is thus a relatively under-researched treatment modality with potential health benefits. The aim of this review was firstly to identify, critically evaluate and summarize the laughter literature; secondly to assess to which extent simulated laughter health-related benefits are currently sustained by empirical evidence; and lastly to provide recommendations and future directions for further research. A comprehensive laughter literature search was performed. A list of inclusion and exclusion criteria was identified. Thematic analysis was applied to summarize laughter health-related outcomes, relationships, and general robustness. Laughter has shown different physiological and psychological benefits. Adverse effects are very limited and laughter is practically lacking in counter-indications. Despite the limited number of publications, there is some evidence to suggest that simulated laughter has also some effects on certain aspects of health, though further well-designed research is warranted. Simulated laughter techniques can be easily implemented in traditional clinical settings for health and patient care. Their effective use for therapeutic purposes needs to be learned, practiced, and developed as any other medical strategy. Practical guidelines and further research are needed to help health care professionals (and others) implement laughter techniques in their health care portfolio. Copyright © 2011 Elsevier Ltd. All rights reserved.

Mathematical modeling and simulation in animal health. Part I: Moving beyond pharmacokinetics.

PubMed

Riviere, J E; Gabrielsson, J; Fink, M; Mochel, J

2016-06-01

The application of mathematical modeling to problems in animal health has a rich history in the form of pharmacokinetic modeling applied to problems in veterinary medicine. Advances in modeling and simulation beyond pharmacokinetics have the potential to streamline and speed-up drug research and development programs. To foster these goals, a series of manuscripts will be published with the following goals: (i) expand the application of modeling and simulation to issues in veterinary pharmacology; (ii) bridge the gap between the level of modeling and simulation practiced in human and veterinary pharmacology; (iii) explore how modeling and simulation concepts can be used to improve our understanding of common issues not readily addressed in human pharmacology (e.g. breed differences, tissue residue depletion, vast weight ranges among adults within a single species, interspecies differences, small animal species research where data collection is limited to sparse sampling, availability of different sampling matrices); and (iv) describe how quantitative pharmacology approaches could help understanding key pharmacokinetic and pharmacodynamic characteristics of a drug candidate, with the goal of providing explicit, reproducible, and predictive evidence for optimizing drug development plans, enabling critical decision making, and eventually bringing safe and effective medicines to patients. This study introduces these concepts and introduces new approaches to modeling and simulation as well as clearly articulate basic assumptions and good practices. The driving force behind these activities is to create predictive models that are based on solid physiological and pharmacological principles as well as adhering to the limitations that are fundamental to applying mathematical and statistical models to biological systems. © 2015 John Wiley & Sons Ltd.

Mechanical response of the herniated human abdomen to the placement of different prostheses.

PubMed

Hernández-Gascón, Belén; Peña, Estefanía; Grasa, Jorge; Pascual, Gemma; Bellón, Juan M; Calvo, Begoña

2013-05-01

This paper describes a method designed to model the repaired herniated human abdomen just after surgery and examine its static mechanical response to the maximum intra-abdominal pressure provoked by a physiological movement (standing cough). The model is based on the real geometry of the human abdomen bearing a large incisional hernia with several anatomical structures differentiated by MRI. To analyze the outcome of hernia repair, the surgical procedure was simulated by modeling a prosthesis placed over the hernia. Three surgical meshes with different mechanical properties were considered: an isotropic heavy-weight mesh (Surgipro®), a slightly anisotropic light-weight mesh (Optilene®), and a highly anisotropic medium-weight mesh (Infinit®). Our findings confirm that anisotropic implants need to be positioned such that the most compliant axis of the mesh coincides with the craneo-caudal direction of the body.

Animal-Related Computer Simulation Programs for Use in Education and Research. AWIC Series Number 1.

ERIC Educational Resources Information Center

Engler, Kevin P.

Computer models have definite limitations regarding the representation of biological systems, but they do have useful applications in reducing the number of animals used to study physiological systems, especially for educational purposes. This guide lists computer models that simulate living systems and can be used to demonstrate physiological,…

Computer simulation studies in fluid and calcium regulation and orthostatic intolerance

NASA Technical Reports Server (NTRS)

1985-01-01

The systems analysis approach to physiological research uses mathematical models and computer simulation. Major areas of concern during prolonged space flight discussed include fluid and blood volume regulation; cardiovascular response during shuttle reentry; countermeasures for orthostatic intolerance; and calcium regulation and bone atrophy. Potential contributions of physiologic math models to future flight experiments are examined.

A physiologically based in silico model for trans-2-hexenal detoxification and DNA adduct formation in human including interindividual variation indicates efficient detoxification and a negligible genotoxicity risk.

PubMed

Kiwamoto, R; Spenkelink, A; Rietjens, I M C M; Punt, A

2013-09-01

A number of α,β-unsaturated aldehydes are present in food both as natural constituents and as flavouring agents. Their reaction with DNA due to their electrophilic α,β-unsaturated aldehyde moiety may result in genotoxicity as observed in some in vitro models, thereby raising a safety concern. A question that remains is whether in vivo detoxification would be efficient enough to prevent DNA adduct formation and genotoxicity. In this study, a human physiologically based kinetic/dynamic (PBK/D) model of trans-2-hexenal (2-hexenal), a selected model α,β-unsaturated aldehyde, was developed to examine dose-dependent detoxification and DNA adduct formation in humans upon dietary exposure. The kinetic model parameters for detoxification were quantified using relevant pooled human tissue fractions as well as tissue fractions from 11 different individual subjects. In addition, a Monte Carlo simulation was performed so that the impact of interindividual variation in 2-hexenal detoxification on the DNA adduct formation in the population as a whole could be examined. The PBK/D model revealed that DNA adduct formation due to 2-hexenal exposure was 0.039 adducts/10⁸ nucleotides (nt) at the estimated average 2-hexenal dietary intake (0.04 mg 2-hexenal/kg bw) and 0.18 adducts/10⁸ nt at the 95th percentile of the dietary intake (0.178 mg 2-hexenal/kg bw) in the most sensitive people. These levels are three orders of magnitude lower than natural background DNA adduct levels that have been reported in disease-free humans (6.8-110 adducts/10⁸ nt), suggesting that the genotoxicity risk for the human population at realistic dietary daily intakes of 2-hexenal may be negligible.

Body-on-a-chip systems for animal-free toxicity testing.

PubMed

Mahler, Gretchen J; Esch, Mandy B; Stokol, Tracy; Hickman, James J; Shuler, Michael L

2016-10-01

Body-on-a-chip systems replicate the size relationships of organs, blood distribution and blood flow, in accordance with human physiology. When operated with tissues derived from human cell sources, these systems are capable of simulating human metabolism, including the conversion of a prodrug to its effective metabolite, as well as its subsequent therapeutic actions and toxic side-effects. The system also permits the measurement of human tissue electrical and mechanical reactions, which provide a measure of functional response. Since these devices can be operated with human tissue samples or with in vitro tissues derived from induced pluripotent stem cells (iPS), they can play a significant role in determining the success of new pharmaceuticals, without resorting to the use of animals. By providing a platform for testing in the context of human metabolism, as opposed to animal models, the systems have the potential to eliminate the use of animals in preclinical trials. This article will review progress made and work achieved as a direct result of the 2015 Lush Science Prize in support of animal-free testing. 2016 FRAME.

The Virtual Physiological Human

PubMed Central

Coveney, Peter V.; Diaz, Vanessa; Hunter, Peter; Kohl, Peter; Viceconti, Marco

2011-01-01

The Virtual Physiological Human is synonymous with a programme in computational biomedicine that aims to develop a framework of methods and technologies to investigate the human body as a whole. It is predicated on the transformational character of information technology, brought to bear on that most crucial of human concerns, our own health and well-being.

Simulations and experiments of photon propagation in biological tissue and liquid crystal waveguides

NASA Astrophysics Data System (ADS)

Lines, Collin M.

The development of non-invasive methods to probe human tissue is an ongoing challenge in biomedical optics. In vivo measurements by conventional methods are limited by the mean free path (MFP) of a photon, which is governed by the spatial distribution of chromophores and the absorption and scattering properties of the tissue. As one of the strongest chromophores in human tissues, hemoglobin concentrations in human tissue greatly affect the MFP of photons in visible wavelengths (i.e. bruising). Changes in the concentration of hemoglobin and other chromophores within the tissue (minor trauma causing a contusion, increased bilirubin due to jaundice, etc.) will affect the MFP, leading to a visibly different appearance (color) of the tissue. As color perception is a complex physiological process, these changes are diffcult to quantify by human observation alone. The transport of hemoglobin and its breakdown products in tissue is related to a number of medical conditions that could benefit from a non-invasive method to determine the hemoglobin levels.

Coupling of three-dimensional field and human thermoregulatory models in a crowded enclosure

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

Xue, H.; Kang, Z.J.; Bong, T.Y.

1999-11-12

Health, comfort, and energy conservation are important factors to consider in the design of a building and its HVAC systems. Advanced tools are required to evaluate parameters regarding airflow, temperature, and humidity ratio in buildings, with the end results being better indoor air quality and thermal environment as well as increased confidence in the performance of buildings. A numerical model coupling the three-dimensional field and human thermoregulatory models is proposed and developed. A high-Re {kappa}-{epsilon} turbulence model is used for the field simulation. A modified 25-mode model of human thermoregulation is adopted to predict human thermal response in physiological parameters,more » such as body temperature and body heat loss. Distributions of air velocity, temperature, and moisture content are demonstrated in a crowded enclosure with mechanical ventilation under two ventilation rates. The results are analyzed and discussed. The coupling model is useful in assisting and verifying ventilation and air-conditioning system designs.« less

Comparative analysis of international standards for the fatigue testing of posterior spinal fixation systems.

PubMed

Villa, Tomaso; La Barbera, Luigi; Galbusera, Fabio

2014-04-01

Preclinical evaluation of the long-term reliability of devices for lumbar fixation is a mandatory activity before they are put into market. The experimental setups are described in two different standards edited by the International Organization for Standardization (ISO) and the American Society for Testing Materials (ASTM), but the evaluation of the suitability of such tests to simulate the actual loading with in vivo situations has never been performed. To calculate through finite element (FE) simulations the stress in the rods of the fixator when subjected to ASTM and ISO standards. To compare the calculated stresses arising in the same fixator once it has been virtually mounted in a physiological environment and loaded with physiological forces and moments. FE simulations and validation experimental tests. FE models of the ISO and ASTM setups were created to conduct simulations of the tests prescribed by standards and calculate stresses in the rods. Validation of the simulations were performed through experimental tests; the same fixator was virtually mounted in an L2-L4 FE model of the lumbar spine and stresses in the rods were calculated when the spine was subjected to physiological forces and moments. The comparison between FE simulations and experimental tests showed good agreement between results obtained using the two methodologies, thus confirming the suitability of the FE method to evaluate stresses in the device in different loading situations. The usage of a physiological load with ASTM standard is impossible due to the extreme severity of the ASTM configuration; in this circumstance, the presence of an anterior support is suggested. Also, ISO prescriptions, although the choice of the setup correctly simulates the mechanical contribution of the discs, seem to overstress the device as compared with a physiological loading condition. Some daily activities, other than walking, can induce a further state of stress in the device that should be taken into account in setting up new experimental procedures. ISO standard loading prescriptions seems to be more severe than the expected physiological ones. The ASTM standard should be completed by including some anterior supporting device and declaring the value of the load to be imposed. Moreover, a further enhancement of standards would be simulating other movements representative of daily activities different from walking. Copyright © 2014 Elsevier Inc. All rights reserved.

Electrochemical characterization of AISI 316L stainless steel in contact with simulated body fluid under infection conditions.

PubMed

López, Danián Alejandro; Durán, Alicia; Ceré, Silvia Marcela

2008-05-01

Titanium and cobalt alloys, as well as some stainless steels, are among the most frequently used materials in orthopaedic surgery. In industrialized countries, stainless steel devices are used only for temporary implants due to their lower corrosion resistance in physiologic media when compared to other alloys. However, due to economical reasons, the use of stainless steel alloys for permanent implants is very common in developing countries. The implantation of foreign bodies is sometimes necessary in the modern medical practice. However, the complex interactions between the host and the can implant weaken the local immune system, increasing the risk of infections. Therefore, it is necessary to further study these materials as well as the characteristics of the superficial film formed in physiologic media in infection conditions in order to control their potential toxicity due to the release of metallic ions in the human body. This work presents a study of the superficial composition and the corrosion resistance of AISI 316L stainless steel and the influence of its main alloying elements when they are exposed to an acidic solution that simulates the change of pH that occurs when an infection develops. Aerated simulated body fluid (SBF) was employed as working solution at 37 degrees C. The pH was adjusted to 7.25 and 4 in order to reproduce normal body and disease state respectively. Corrosion resistance was measured by means of electrochemical impedance spectroscopy (EIS) and anodic polarization curves.

Surface mesh to voxel data registration for patient-specific anatomical modeling

NASA Astrophysics Data System (ADS)

de Oliveira, Júlia E. E.; Giessler, Paul; Keszei, András.; Herrler, Andreas; Deserno, Thomas M.

2016-03-01

Virtual Physiological Human (VPH) models are frequently used for training, planning, and performing medical procedures. The Regional Anaesthesia Simulator and Assistant (RASimAs) project has the goal of increasing the application and effectiveness of regional anesthesia (RA) by combining a simulator of ultrasound-guided and electrical nerve-stimulated RA procedures and a subject-specific assistance system through an integration of image processing, physiological models, subject-specific data, and virtual reality. Individualized models enrich the virtual training tools for learning and improving regional anaesthesia (RA) skills. Therefore, we suggest patient-specific VPH models that are composed by registering the general mesh-based models with patient voxel data-based recordings. Specifically, the pelvis region has been focused for the support of the femoral nerve block. The processing pipeline is composed of different freely available toolboxes such as MatLab, the open Simulation framework (SOFA), and MeshLab. The approach of Gilles is applied for mesh-to-voxel registration. Personalized VPH models include anatomical as well as mechanical properties of the tissues. Two commercial VPH models (Zygote and Anatomium) were used together with 34 MRI data sets. Results are presented for the skin surface and pelvic bones. Future work will extend the registration procedure to cope with all model tissue (i.e., skin, muscle, bone, vessel, nerve, fascia) in a one-step procedure and extrapolating the personalized models to body regions actually being out of the captured field of view.

Model-based sensorimotor integration for multi-joint control: development of a virtual arm model.

PubMed

Song, D; Lan, N; Loeb, G E; Gordon, J

2008-06-01

An integrated, sensorimotor virtual arm (VA) model has been developed and validated for simulation studies of control of human arm movements. Realistic anatomical features of shoulder, elbow and forearm joints were captured with a graphic modeling environment, SIMM. The model included 15 musculotendon elements acting at the shoulder, elbow and forearm. Muscle actions on joints were evaluated by SIMM generated moment arms that were matched to experimentally measured profiles. The Virtual Muscle (VM) model contained appropriate admixture of slow and fast twitch fibers with realistic physiological properties for force production. A realistic spindle model was embedded in each VM with inputs of fascicle length, gamma static (gamma(stat)) and dynamic (gamma(dyn)) controls and outputs of primary (I(a)) and secondary (II) afferents. A piecewise linear model of Golgi Tendon Organ (GTO) represented the ensemble sampling (I(b)) of the total muscle force at the tendon. All model components were integrated into a Simulink block using a special software tool. The complete VA model was validated with open-loop simulation at discrete hand positions within the full range of alpha and gamma drives to extrafusal and intrafusal muscle fibers. The model behaviors were consistent with a wide variety of physiological phenomena. Spindle afferents were effectively modulated by fusimotor drives and hand positions of the arm. These simulations validated the VA model as a computational tool for studying arm movement control. The VA model is available to researchers at website http://pt.usc.edu/cel .

Performance assessment in a flight simulator test—Validation of a space psychology methodology

NASA Astrophysics Data System (ADS)

Johannes, B.; Salnitski, Vyacheslav; Soll, Henning; Rauch, Melina; Goeters, Klaus-Martin; Maschke, Peter; Stelling, Dirk; Eißfeldt, Hinnerk

2007-02-01

The objective assessment of operator performance in hand controlled docking of a spacecraft on a space station has 30 years of tradition and is well established. In the last years the performance assessment was successfully combined with a psycho-physiological approach for the objective assessment of the levels of physiological arousal and psychological load. These methods are based on statistical reference data. For the enhancement of the statistical power of the evaluation methods, both were actually implemented into a comparable terrestrial task: the flight simulator test of DLR in the selection procedure for ab initio pilot applicants for civil airlines. In the first evaluation study 134 male subjects were analysed. Subjects underwent a flight simulator test including three tasks, which were evaluated by instructors applying well-established and standardised rating scales. The principles of the performance algorithms of the docking training were adapted for the automated flight performance assessment. They are presented here. The increased human errors under instrument flight conditions without visual feedback required a manoeuvre recognition algorithm before calculating the deviation of the flown track from the given task elements. Each manoeuvre had to be evaluated independently of former failures. The expert rated performance showed a highly significant correlation with the automatically calculated performance for each of the three tasks: r=.883, r=.874, r=.872, respectively. An automated algorithm successfully assessed the flight performance. This new method will possibly provide a wide range of other future applications in aviation and space psychology.

Optimal Control of Inspired Perfluorocarbon Temperature for Ultrafast Hypothermia Induction by Total Liquid Ventilation in an Adult Patient Model.

PubMed

Nadeau, Mathieu; Sage, Michael; Kohlhauer, Matthias; Mousseau, Julien; Vandamme, Jonathan; Fortin-Pellerin, Etienne; Praud, Jean-Paul; Tissier, Renaud; Walti, Herve; Micheau, Philippe

2017-12-01

Recent preclinical studies have shown that therapeutic hypothermia induced in less than 30 min by total liquid ventilation (TLV) strongly improves the survival rate after cardiac arrest. When the lung is ventilated with a breathable perfluorocarbon liquid, the inspired perfluorocarbon allows us to control efficiently the cooling process of the organs. While TLV can rapidly cool animals, the cooling speed in humans remains unknown. The objective is to predict the efficiency and safety of ultrafast cooling by TLV in adult humans. It is based on a previously published thermal model of ovines in TLV and the design of a direct optimal controller to compute the inspired perfluorocarbon temperature profile. The experimental results in an adult sheep are presented. The thermal model of sheep is subsequently projected to a human model to simulate the optimal hypothermia induction and its sensitivity to physiological parameter uncertainties. The results in the sheep showed that the computed inspired perfluorocarbon temperature command can avoid arterial temperature undershoot. The projection to humans revealed that mild hypothermia should be ultrafast (reached in fewer than 3 min (-72 °C/h) for the brain and 20 min (-10 °C/h) for the entire body). The projection to human model allows concluding that therapeutic hypothermia induction by TLV can be ultrafast and safe. This study is the first to simulate ultrafast cooling by TLV in a human model and is a strong motivation to translate TLV to humans to improve the quality of life of postcardiac arrest patients.

Medical, Psychophysiological, and Human Performance Problems During Extended EVA

NASA Technical Reports Server (NTRS)

1997-01-01

In this session, Session JP1, the discussion focuses on the following topics: New Developments in the Assessment of the Risk of Decompression Sickness in Null Gravity During Extravehicular Activity; The Dynamic of Physiological Reactions of Cosmonauts Under the Influence of Repeated EVA Workouts, The Russian Experience; Medical Emergencies in Space; The Evolution from 'Physiological Adequacy' to 'Physiological Tuning'; Five Zones of Symmetrical and Asymmetrical Conflicting Temperatures on the Human Body, Physiological Consequences; Human Performance and Subjective Perception in Nonuniform Thermal Conditions; The Hand as a Control System, Implications for Hand-Finger Dexterity During Extended EVA; and Understanding the Skill of Extravehicular Mass Handling.

In-vitro characterization of stress corrosion cracking of aluminium-free magnesium alloys for temporary bio-implant applications.

PubMed

Choudhary, Lokesh; Singh Raman, R K; Hofstetter, Joelle; Uggowitzer, Peter J

2014-09-01

The complex interaction between physiological stresses and corrosive human body fluid may cause premature failure of metallic biomaterials due to the phenomenon of stress corrosion cracking. In this study, the susceptibility to stress corrosion cracking of biodegradable and aluminium-free magnesium alloys ZX50, WZ21 and WE43 was investigated by slow strain rate tensile testing in a simulated human body fluid. Slow strain rate tensile testing results indicated that each alloy was susceptible to stress corrosion cracking, and this was confirmed by fractographic features of transgranular and/or intergranular cracking. However, the variation in alloy susceptibility to stress corrosion cracking is explained on the basis of their electrochemical and microstructural characteristics. Copyright © 2014 Elsevier B.V. All rights reserved.

Resistance of Magnesium Alloys to Corrosion Fatigue for Biodegradable Implant Applications: Current Status and Challenges

PubMed Central

Raman, R. K. Singh; Harandi, Shervin Eslami

2017-01-01

Magnesium (Mg) alloys are attracting increasing interest as the most suitable metallic materials for construction of biodegradable and bio-absorbable temporary implants. However, Mg-alloys can suffer premature and catastrophic fracture under the synergy of cyclic loading and corrosion (i.e., corrosion fatigue (CF)). Though Mg alloys are reported to be susceptible to CF also in the corrosive human body fluid, there are very limited studies on this topic. Furthermore, the in vitro test parameters employed in these investigations have not properly simulated the actual conditions in the human body. This article presents an overview of the findings of available studies on the CF of Mg alloys in pseudo-physiological solutions and the employed testing procedures, as well as identifying the knowledge gap. PMID:29144428

Resistance of Magnesium Alloys to Corrosion Fatigue for Biodegradable Implant Applications: Current Status and Challenges.

PubMed

Raman, R K Singh; Harandi, Shervin Eslami

2017-11-16

Magnesium (Mg) alloys are attracting increasing interest as the most suitable metallic materials for construction of biodegradable and bio-absorbable temporary implants. However, Mg-alloys can suffer premature and catastrophic fracture under the synergy of cyclic loading and corrosion (i.e., corrosion fatigue (CF)). Though Mg alloys are reported to be susceptible to CF also in the corrosive human body fluid, there are very limited studies on this topic. Furthermore, the in vitro test parameters employed in these investigations have not properly simulated the actual conditions in the human body. This article presents an overview of the findings of available studies on the CF of Mg alloys in pseudo-physiological solutions and the employed testing procedures, as well as identifying the knowledge gap.

MEDES clinical research facility as a tool to prepare ISSA space flights

NASA Astrophysics Data System (ADS)

Maillet, A.; Traon, A. Pavy-Le

This new multi-disciplinary medical experimentation center provides the ideal scientific, medical and technical environment required for research programs and to prepare international space station Alpha (ISSA) missions, where space and healthcare industries can share their expertise. Different models are available to simulate space flight effects (bed-rest, confinement,…). This is of particular interest for research in Human psychology, physiology, physiopathology and ergonomics, validation of biomedical materials and procedures, testing of drugs, and other healthcare related products. This clinical research facility (CRF) provides valuable services in various fields of Human research requiring healthy volunteers. CRF is widely accessible to national and international, scientific, medical and industrial organisations. Furthermore, users have at their disposal the multi-disciplinary skills of MEDES staff and all MEDES partners on a single site.

Aortic Root Biomechanics After Sleeve and David Sparing Techniques: A Finite Element Analysis.

PubMed

Tasca, Giordano; Selmi, Matteo; Votta, Emiliano; Redaelli, Paola; Sturla, Francesco; Redaelli, Alberto; Gamba, Amando

2017-05-01

Aortic root aneurysm can be treated with valve-sparing procedures. The David and Yacoub techniques have shown excellent long-term results but are technically demanding. Recently, a new and simpler procedure, the Sleeve technique, was proposed with encouraging results. We aimed to quantify the biomechanics of the initially aneurysmal aortic root (AR) after the Sleeve procedure to assess whether it induces abnormal stresses, potentially undermining its durability. Two finite element (FE) models of the physiologic and aneurysmal AR were built, accounting for the anatomical asymmetry and the nonlinear and anisotropic mechanical properties of human AR tissues. On the aneurysmal model, the Sleeve and David techniques were simulated based on the corresponding published technical features. Aortic root biomechanics throughout 2 consecutive cardiac cycles were computed in each simulated configuration. Both sparing techniques restored physiologic-like kinematics of aortic valve (AV) leaflets but induced different leaflets stresses. The time course averaged over the leaflets' bellies was 35% higher in the David model than in the Sleeve model. Commissural stresses, which were equal to 153 and 318 kPa in the physiologic and aneurysmal models, respectively, became 369 and 208 kPa in the David and Sleeve models, respectively. No intrinsic structural problems were detected in the Sleeve model that might jeopardize the durability of the procedure. If corroborated by long-term clinical outcomes, the results obtained suggest that using this new technique could successfully simplify the surgical repair of AR aneurysms and reduce intraoperative complications. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Pros and Cons of Using Water Immersion to Simulate Physiological Responses to Microgravity

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Tomko, David L. (Technical Monitor)

1995-01-01

Head-out water immersion (HOI) has been employed as a remedial treatment for various ills and ailments for many millennia, and total body immersion even longer as protective encapsulation for the mammalian fetus. Two discrete differences between stimuli induced by true microgravity (10(exp -4) g) and HOI are readily apparent. External water pressure on the skin and accompanying negative pressure breathing cause blood to shift headward. Secondly, the gravitational force is ever present during immersion and microgravity, but its effect is essentially neutralized during Earth orbital flight. Thus, the physiological responses to immersion should not be expected to match those during microgravity. Immersion has been used mainly to study and understand kidney function and associated cardiovascular responses for control of body fluid volume and osmotic content, with some application to and simulation of microgravity responses. There is a plethora of data from human HOI studies, but relatively few controlled data from microgravity studies. In general, it appears that physiological responses occur more quickly with water immersion than in microgravity, but this may be due to less rigorous control (voluntary and involuntary) of the preflight state of crew members. The central venous pressure-vasopressin (Gauer-Henry) reflex control for fluid balance may not be of prime importance in microgravity. Gross functions such as reduced body weight and water, level of hypovolemia, decreased isokinetic strength, and lower nitrogen balance found during immersion are qualitatively similar in microgravity, but the mechanisms controlling these and other functions are, for the most part, unclear. Only acquisition of data from well-controlled microgravity experiments will resolve this discrepancy.

Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A Systematic Review of Published Models, Applications, and Model Verification

PubMed Central

Sager, Jennifer E.; Yu, Jingjing; Ragueneau-Majlessi, Isabelle

2015-01-01

Modeling and simulation of drug disposition has emerged as an important tool in drug development, clinical study design and regulatory review, and the number of physiologically based pharmacokinetic (PBPK) modeling related publications and regulatory submissions have risen dramatically in recent years. However, the extent of use of PBPK modeling by researchers, and the public availability of models has not been systematically evaluated. This review evaluates PBPK-related publications to 1) identify the common applications of PBPK modeling; 2) determine ways in which models are developed; 3) establish how model quality is assessed; and 4) provide a list of publically available PBPK models for sensitive P450 and transporter substrates as well as selective inhibitors and inducers. PubMed searches were conducted using the terms “PBPK” and “physiologically based pharmacokinetic model” to collect published models. Only papers on PBPK modeling of pharmaceutical agents in humans published in English between 2008 and May 2015 were reviewed. A total of 366 PBPK-related articles met the search criteria, with the number of articles published per year rising steadily. Published models were most commonly used for drug-drug interaction predictions (28%), followed by interindividual variability and general clinical pharmacokinetic predictions (23%), formulation or absorption modeling (12%), and predicting age-related changes in pharmacokinetics and disposition (10%). In total, 106 models of sensitive substrates, inhibitors, and inducers were identified. An in-depth analysis of the model development and verification revealed a lack of consistency in model development and quality assessment practices, demonstrating a need for development of best-practice guidelines. PMID:26296709

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

PubMed

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

2016-04-01

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

An object-oriented computational model to study cardiopulmonary hemodynamic interactions in humans.

PubMed

Ngo, Chuong; Dahlmanns, Stephan; Vollmer, Thomas; Misgeld, Berno; Leonhardt, Steffen

2018-06-01

This work introduces an object-oriented computational model to study cardiopulmonary interactions in humans. Modeling was performed in object-oriented programing language Matlab Simscape, where model components are connected with each other through physical connections. Constitutive and phenomenological equations of model elements are implemented based on their non-linear pressure-volume or pressure-flow relationship. The model includes more than 30 physiological compartments, which belong either to the cardiovascular or respiratory system. The model considers non-linear behaviors of veins, pulmonary capillaries, collapsible airways, alveoli, and the chest wall. Model parameters were derisved based on literature values. Model validation was performed by comparing simulation results with clinical and animal data reported in literature. The model is able to provide quantitative values of alveolar, pleural, interstitial, aortic and ventricular pressures, as well as heart and lung volumes during spontaneous breathing and mechanical ventilation. Results of baseline simulation demonstrate the consistency of the assigned parameters. Simulation results during mechanical ventilation with PEEP trials can be directly compared with animal and clinical data given in literature. Object-oriented programming languages can be used to model interconnected systems including model non-linearities. The model provides a useful tool to investigate cardiopulmonary activity during spontaneous breathing and mechanical ventilation. Copyright © 2018 Elsevier B.V. All rights reserved.

Impact of correction factors in human brain lesion-behavior inference.

PubMed

Sperber, Christoph; Karnath, Hans-Otto

2017-03-01

Statistical voxel-based lesion-behavior mapping (VLBM) in neurological patients with brain lesions is frequently used to examine the relationship between structure and function of the healthy human brain. Only recently, two simulation studies noted reduced anatomical validity of this method, observing the results of VLBM to be systematically misplaced by about 16 mm. However, both simulation studies differed from VLBM analyses of real data in that they lacked the proper use of two correction factors: lesion size and "sufficient lesion affection." In simulation experiments on a sample of 274 real stroke patients, we found that the use of these two correction factors reduced misplacement markedly compared to uncorrected VLBM. Apparently, the misplacement is due to physiological effects of brain lesion anatomy. Voxel-wise topographies of collateral damage in the real data were generated and used to compute a metric for the inter-voxel relation of brain damage. "Anatomical bias" vectors that were solely calculated from these inter-voxel relations in the patients' real anatomical data, successfully predicted the VLBM misplacement. The latter has the potential to help in the development of new VLBM methods that provide even higher anatomical validity than currently available by the proper use of correction factors. Hum Brain Mapp 38:1692-1701, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Salivary Pharmacodynamics and Bioavailability of Promethazine in Human Subjects

NASA Technical Reports Server (NTRS)

Putcha, Lakshmi; Harm, Deborah L.; Nimmagudda, Ram; Berens, Kurt L.; Bourne, David W. A.

1999-01-01

The acute effects of exposure to microgravity include the development of space motion sickness which usually requires therapeutic intervention. The current drug of choice, promethazine (PMZ), has side effects which include nausea, drowsiness, dizziness, sedation and impaired psychomotor performance. In a ground-based study with commercial airline pilots and shuttle simulator trainers, we measured sleep and psychomotor performance variables, and physiological variables such as blood pressure and heart rate, as a function of circulating drug concentrations in the body. We evaluated a non-invasive sampling method (saliva) as a means of assessing pharmacodynamics following a single intramuscular (IM) dose of PMZ.

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

EPA Science Inventory

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

From innervation density to tactile acuity: 1. Spatial representation.

PubMed

Brown, Paul B; Koerber, H Richard; Millecchia, Ronald

2004-06-11

We tested the hypothesis that the population receptive field representation (a superposition of the excitatory receptive field areas of cells responding to a tactile stimulus) provides spatial information sufficient to mediate one measure of static tactile acuity. In psychophysical tests, two-point discrimination thresholds on the hindlimbs of adult cats varied as a function of stimulus location and orientation, as they do in humans. A statistical model of the excitatory low threshold mechanoreceptive fields of spinocervical, postsynaptic dorsal column and spinothalamic tract neurons was used to simulate the population receptive field representations in this neural population of the one- and two-point stimuli used in the psychophysical experiments. The simulated and observed thresholds were highly correlated. Simulated and observed thresholds' relations to physiological and anatomical variables such as stimulus location and orientation, receptive field size and shape, map scale, and innervation density were strikingly similar. Simulated and observed threshold variations with receptive field size and map scale obeyed simple relationships predicted by the signal detection model, and were statistically indistinguishable from each other. The population receptive field representation therefore contains information sufficient for this discrimination.

PAVA: Physiological and Anatomical Visual Analytics for Mapping of Tissue-Specific Concentration and Time-Course Data

EPA Science Inventory

We describe the development and implementation of a Physiological and Anatomical Visual Analytics tool (PAVA), a web browser-based application, used to visualize experimental/simulated chemical time-course data (dosimetry), epidemiological data and Physiologically-Annotated Data ...

In Vitro Model Simulating Gastro-Intestinal Digestion in the Pediatric Population (Neonates and Young Infants).

PubMed

Kamstrup, Danna; Berthelsen, Ragna; Sassene, Philip Jonas; Selen, Arzu; Müllertz, Anette

2017-02-01

The focus on drug delivery for the pediatric population has been steadily increasing in the last decades. In terms of developing in vitro models simulating characteristics of the targeted pediatric population, with the purpose of predicting drug product performance after oral administration, it is important to simulate the gastro-intestinal conditions and processes the drug will encounter upon oral administration. When a drug is administered in the fed state, which is commonly the case for neonates, as they are typically fed every 3 h, the digestion of the milk will affect the composition of the fluid available for drug dissolution/solubilization. Therefore, in order to predict the solubilized amount of drug available for absorption, an in vitro model simulating digestion in the gastro-intestinal tract should be utilized. In order to simulate the digestion process and the drug solubilization taking place in vivo, the following aspects should be considered; physiologically relevant media, media volume, use of physiological enzymes in proper amounts, as well as correct pH and addition of relevant co-factors, e.g., bile salts and co-enzymes. Furthermore, physiological transit times and appropriate mixing should be considered and mimicked as close as possible. This paper presents a literature review on physiological factors relevant for digestion and drug solubilization in neonates. Based on the available literature data, a novel in vitro digestion model simulating digestion and drug solubilization in the neonate and young infant pediatric population (2 months old and younger) was designed.

Effect of a Six-Week Preparation Period on Acute Physiological Responses to a Simulated Combat in Young National-Level Taekwondo Athletes.

PubMed

Nikolaidis, Pantelis T; Chtourou, Hamdi; Torres-Luque, Gema; Tasiopoulos, Ioannis G; Heller, Jan; Padulo, Johnny

2015-09-29

The aim of this study was to examine changes in physical attributes, physiological characteristics and responses that occurred in a simulated combat during a six-week preparatory period in young taekwondo athletes. Seven athletes (age 12.17 ± 1.11 years) were examined before (pre-intervention) and after (post-intervention) a preparatory period for physical fitness and physiological responses to a 2×90 s simulated bout with a 30 s rest period. The heart rate (HR) was monitored during the simulated combat, and handgrip muscle strength (HMS) along with the countermovement jump (CMJ) were recorded before and after the combat. When compared with pre-intervention values, in post-intervention we observed a decrease in body mass, body fat percentage, and the HR at rest and during recovery after a 3 min step test, and an increase in maximal velocity of the cycle ergometer force-velocity test, the CMJ and mean power during the 30 s continuous jumping test (p<0.05). Furthermore, HR responses to a simulated combat were lower in the post-intervention session (p<0.05). CMJ values increased after the bout in both pre and post-intervention, with higher absolute values in the latter case (p<0.05), whereas there was no difference in HMS. Based on these findings, it can be concluded that the acute physiological responses to a simulated taekwondo combat vary during a season, which might be explained by changes in physical fitness.

Effect of a Six-Week Preparation Period on Acute Physiological Responses to a Simulated Combat in Young National-Level Taekwondo Athletes

PubMed Central

Nikolaidis, Pantelis T.; Chtourou, Hamdi; Torres-Luque, Gema; Tasiopoulos, Ioannis G.; Heller, Jan; Padulo, Johnny

2015-01-01

The aim of this study was to examine changes in physical attributes, physiological characteristics and responses that occurred in a simulated combat during a six-week preparatory period in young taekwondo athletes. Seven athletes (age 12.17 ± 1.11 years) were examined before (pre-intervention) and after (post-intervention) a preparatory period for physical fitness and physiological responses to a 2×90 s simulated bout with a 30 s rest period. The heart rate (HR) was monitored during the simulated combat, and handgrip muscle strength (HMS) along with the countermovement jump (CMJ) were recorded before and after the combat. When compared with pre-intervention values, in post-intervention we observed a decrease in body mass, body fat percentage, and the HR at rest and during recovery after a 3 min step test, and an increase in maximal velocity of the cycle ergometer force-velocity test, the CMJ and mean power during the 30 s continuous jumping test (p<0.05). Furthermore, HR responses to a simulated combat were lower in the post-intervention session (p<0.05). CMJ values increased after the bout in both pre and post-intervention, with higher absolute values in the latter case (p<0.05), whereas there was no difference in HMS. Based on these findings, it can be concluded that the acute physiological responses to a simulated taekwondo combat vary during a season, which might be explained by changes in physical fitness. PMID:26557196

Influence of Physiological Gastrointestinal Surfactant Ratio on the Equilibrium Solubility of BCS Class II Drugs Investigated Using a Four Component Mixture Design

PubMed Central

2017-01-01

The absorption of poorly water-soluble drugs is influenced by the luminal gastrointestinal fluid content and composition, which control solubility. Simulated intestinal fluids have been introduced into dissolution testing including endogenous amphiphiles and digested lipids at physiological levels; however, in vivo individual variation exists in the concentrations of these components, which will alter drug absorption through an effect on solubility. The use of a factorial design of experiment and varying media by introducing different levels of bile, lecithin, and digested lipids has been previously reported, but here we investigate the solubility variation of poorly soluble drugs through more complex biorelevant amphiphile interactions. A four-component mixture design was conducted to understand the solubilization capacity and interactions of bile salt, lecithin, oleate, and monoglyceride with a constant total concentration (11.7 mM) but varying molar ratios. The equilibrium solubility of seven low solubility acidic (zafirlukast), basic (aprepitant, carvedilol), and neutral (fenofibrate, felodipine, griseofulvin, and spironolactone) drugs was investigated. Solubility results are comparable with literature values and also our own previously published design of experiment studies. Results indicate that solubilization is not a sum accumulation of individual amphiphile concentrations, but a drug specific effect through interactions of mixed amphiphile compositions with the drug. This is probably due to a combined interaction of drug characteristics; for example, lipophilicity, molecular shape, and ionization with amphiphile components, which can generate specific drug–micelle affinities. The proportion of each component can have a remarkable influence on solubility with, in some cases, the highest and lowest points close to each other. A single-point solubility measurement in a fixed composition simulated media or human intestinal fluid sample will therefore provide a value without knowledge of the surrounding solubility topography meaning that variability may be overlooked. This study has demonstrated how the amphiphile ratios influence drug solubility and highlights the importance of the envelope of physiological variation when simulating in vivo drug behavior. PMID:28749696

Impacts of the removal of shrubs on the physiological and biochemical characteristics of Syntrichia caninervis Mitt: in a temperate desert

PubMed Central

Yin, Ben-feng; Zhang, Yuan-ming; Lou, An-ru

2017-01-01

Moss crusts play important roles in biological soil crusts biomass and soil surface stabilization. However, because of increasingly intensive human activities, especially grazing, the growth and survival of shrubs are seriously threatened. This study aimed to test whether the presence of shrubs affects the physiological state of the bryophyte Syntrichia caninervis Mitt. in this desert ecosystem. We simulated animal-grazed shrubs at three levels in the Gurbantunggut Desert and compared these simulations to exposed areas, measuring the indicators of growth and stress tolerance exhibited by bryophytes. The results showed that the removal of shrubs significantly decreased chlorophyll fluorescence activity and soluble protein content in S. caninervis, especially under the total shrub removal treatment. The ratio between the total removal of shrubs and other treatments in antioxidative enzymes and in osmotic adjustment substances of S. caninervis exhibited two types of responses. With the exception of malonyldialdehyde (MDA) and superoxide dismutase (SOD), the variables examined fitted as downward parabolic then upward parabolic temporal dynamics. The removal of shrubs is harmful to the survival of S.caninervis. In resource-constrained conditions, SOD is an important antioxidant enzyme that of peroxidase (POD), catalase (CAT) and osmotic adjustment substances, for S. caninervis survival. PMID:28374741

Impacts of the removal of shrubs on the physiological and biochemical characteristics of Syntrichia caninervis Mitt: in a temperate desert.

PubMed

Yin, Ben-Feng; Zhang, Yuan-Ming; Lou, An-Ru

2017-04-04

Moss crusts play important roles in biological soil crusts biomass and soil surface stabilization. However, because of increasingly intensive human activities, especially grazing, the growth and survival of shrubs are seriously threatened. This study aimed to test whether the presence of shrubs affects the physiological state of the bryophyte Syntrichia caninervis Mitt. in this desert ecosystem. We simulated animal-grazed shrubs at three levels in the Gurbantunggut Desert and compared these simulations to exposed areas, measuring the indicators of growth and stress tolerance exhibited by bryophytes. The results showed that the removal of shrubs significantly decreased chlorophyll fluorescence activity and soluble protein content in S. caninervis, especially under the total shrub removal treatment. The ratio between the total removal of shrubs and other treatments in antioxidative enzymes and in osmotic adjustment substances of S. caninervis exhibited two types of responses. With the exception of malonyldialdehyde (MDA) and superoxide dismutase (SOD), the variables examined fitted as downward parabolic then upward parabolic temporal dynamics. The removal of shrubs is harmful to the survival of S.caninervis. In resource-constrained conditions, SOD is an important antioxidant enzyme that of peroxidase (POD), catalase (CAT) and osmotic adjustment substances, for S. caninervis survival.

THz and mm-Wave Sensing of Corneal Tissue Water Content: Electromagnetic Modeling and Analysis

PubMed Central

Taylor, Zachary D.; Garritano, James; Sung, Shijun; Bajwa, Neha; Bennett, David B.; Nowroozi, Bryan; Tewari, Priyamvada; Sayre, James; Hubschman, Jean-Pierre; Deng, Sophie; Brown, Elliott R.; Grundfest, Warren S.

2015-01-01

Terahertz (THz) spectral properties of human cornea are explored as a function of central corneal thickness (CCT) and corneal water content, and the clinical utility of THz-based corneal water content sensing is discussed. Three candidate corneal tissue water content (CTWC) perturbations, based on corneal physiology, are investigated that affect the axial water distribution and total thickness. The THz frequency reflectivity properties of the three CTWC perturbations were simulated and explored with varying system center frequency and bandwidths (Q-factors). The modeling showed that at effective optical path lengths on the order of a wavelength the cornea presents a lossy etalon bordered by air at the anterior and the aqueous humor at the posterior. The simulated standing wave peak-to-valley ratio is pronounced at lower frequencies and its effect on acquired data can be modulated by adjusting the bandwidth of the sensing system. These observations are supported with experimental spectroscopic data. The results suggest that a priori knowledge of corneal thickness can be utilized for accurate assessments of corneal tissue water content. The physiologic variation of corneal thickness with respect to the wavelengths spanned by the THz band is extremely limited compared to all other structures in the body making CTWC sensing unique amongst all proposed applications of THz medical imaging. PMID:26322247

Impacts of the removal of shrubs on the physiological and biochemical characteristics of Syntrichia caninervis Mitt: in a temperate desert

NASA Astrophysics Data System (ADS)

Yin, Ben-Feng; Zhang, Yuan-Ming; Lou, An-Ru

2017-04-01

Moss crusts play important roles in biological soil crusts biomass and soil surface stabilization. However, because of increasingly intensive human activities, especially grazing, the growth and survival of shrubs are seriously threatened. This study aimed to test whether the presence of shrubs affects the physiological state of the bryophyte Syntrichia caninervis Mitt. in this desert ecosystem. We simulated animal-grazed shrubs at three levels in the Gurbantunggut Desert and compared these simulations to exposed areas, measuring the indicators of growth and stress tolerance exhibited by bryophytes. The results showed that the removal of shrubs significantly decreased chlorophyll fluorescence activity and soluble protein content in S. caninervis, especially under the total shrub removal treatment. The ratio between the total removal of shrubs and other treatments in antioxidative enzymes and in osmotic adjustment substances of S. caninervis exhibited two types of responses. With the exception of malonyldialdehyde (MDA) and superoxide dismutase (SOD), the variables examined fitted as downward parabolic then upward parabolic temporal dynamics. The removal of shrubs is harmful to the survival of S.caninervis. In resource-constrained conditions, SOD is an important antioxidant enzyme that of peroxidase (POD), catalase (CAT) and osmotic adjustment substances, for S. caninervis survival.

Development and validation of an improved mechanical thorax for simulating cardiopulmonary resuscitation with adjustable chest stiffness and simulated blood flow.

PubMed

Eichhorn, Stefan; Spindler, Johannes; Polski, Marcin; Mendoza, Alejandro; Schreiber, Ulrich; Heller, Michael; Deutsch, Marcus Andre; Braun, Christian; Lange, Rüdiger; Krane, Markus

2017-05-01

Investigations of compressive frequency, duty cycle, or waveform during CPR are typically rooted in animal research or computer simulations. Our goal was to generate a mechanical model incorporating alternate stiffness settings and an integrated blood flow system, enabling defined, reproducible comparisons of CPR efficacy. Based on thoracic stiffness data measured in human cadavers, such a model was constructed using valve-controlled pneumatic pistons and an artificial heart. This model offers two realistic levels of chest elasticity, with a blood flow apparatus that reflects compressive depth and waveform changes. We conducted CPR at opposing levels of physiologic stiffness, using a LUCAS device, a motor-driven plunger, and a group of volunteers. In high-stiffness mode, blood flow generated by volunteers was significantly less after just 2min of CPR, whereas flow generated by LUCAS device was superior by comparison. Optimal blood flow was obtained via motor-driven plunger, with trapezoidal waveform. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

A mathematical tool to generate complex whole body motor tasks and test hypotheses on underlying motor planning.

PubMed

Tagliabue, Michele; Pedrocchi, Alessandra; Pozzo, Thierry; Ferrigno, Giancarlo

2008-01-01

In spite of the complexity of human motor behavior, difficulties in mathematical modeling have restricted to rather simple movements attempts to identify the motor planning criterion used by the central nervous system. This paper presents a novel-simulation technique able to predict the "desired trajectory" corresponding to a wide range of kinematic and kinetic optimality criteria for tasks involving many degrees of freedom and the coordination between goal achievement and balance maintenance. Employment of proper time discretization, inverse dynamic methods and constrained optimization technique are combined. The application of this simulator to a planar whole body pointing movement shows its effectiveness in managing system nonlinearities and instability as well as in ensuring the anatomo-physiological feasibility of predicted motor plans. In addition, the simulator's capability to simultaneously optimize competing movement aspects represents an interesting opportunity for the motor control community, in which the coexistence of several controlled variables has been hypothesized.

Free energy surface of an intrinsically disordered protein: comparison between temperature replica exchange molecular dynamics and bias-exchange metadynamics.

PubMed

Zerze, Gül H; Miller, Cayla M; Granata, Daniele; Mittal, Jeetain

2015-06-09

Intrinsically disordered proteins (IDPs), which are expected to be largely unstructured under physiological conditions, make up a large fraction of eukaryotic proteins. Molecular dynamics simulations have been utilized to probe structural characteristics of these proteins, which are not always easily accessible to experiments. However, exploration of the conformational space by brute force molecular dynamics simulations is often limited by short time scales. Present literature provides a number of enhanced sampling methods to explore protein conformational space in molecular simulations more efficiently. In this work, we present a comparison of two enhanced sampling methods: temperature replica exchange molecular dynamics and bias exchange metadynamics. By investigating both the free energy landscape as a function of pertinent order parameters and the per-residue secondary structures of an IDP, namely, human islet amyloid polypeptide, we found that the two methods yield similar results as expected. We also highlight the practical difference between the two methods by describing the path that we followed to obtain both sets of data.

Motion Artifact Reduction in Ultrasound Based Thermal Strain Imaging of Atherosclerotic Plaques Using Time Series Analysis

PubMed Central

Dutta, Debaditya; Mahmoud, Ahmed M.; Leers, Steven A.; Kim, Kang

2013-01-01

Large lipid pools in vulnerable plaques, in principle, can be detected using US based thermal strain imaging (US-TSI). One practical challenge for in vivo cardiovascular application of US-TSI is that the thermal strain is masked by the mechanical strain caused by cardiac pulsation. ECG gating is a widely adopted method for cardiac motion compensation, but it is often susceptible to electrical and physiological noise. In this paper, we present an alternative time series analysis approach to separate thermal strain from the mechanical strain without using ECG. The performance and feasibility of the time-series analysis technique was tested via numerical simulation as well as in vitro water tank experiments using a vessel mimicking phantom and an excised human atherosclerotic artery where the cardiac pulsation is simulated by a pulsatile pump. PMID:24808628

LASER APPLICATIONS IN MEDICINE: Effect of glucose concentration in a model light-scattering suspension on propagation of ultrashort laser pulses

NASA Astrophysics Data System (ADS)

Popov, A. P.; Priezzhev, A. V.; Myllylä, Risto

2005-11-01

The propagation of laser pulses in the 2% aqueous solution of intralipid — a suspension of lipid particles with optical properties close to those of the human skin, is numerically simulated at different glucose concentrations. The temporal profiles of 820-nm laser pulses diffusely backscattered from a flat, 2-mm thick solution layer are simulated. The laser pulse profiles are detected by fibreoptic detectors of diameter 0.3 mm with the numerical apertures 0.19, 0.29, and 0.39. It is shown that this method can be used to detect changes in the glucose level in the physiological concentration range (100-500 mg dL-1) by monitoring variations in the peak intensity and area of the laser pulse temporal profile (pulse energy).

Spaceflight-induced neuroplasticity in humans as measured by MRI: what do we know so far?

PubMed

Van Ombergen, Angelique; Laureys, Steven; Sunaert, Stefan; Tomilovskaya, Elena; Parizel, Paul M; Wuyts, Floris L

2017-01-01

Space travel poses an enormous challenge on the human body; microgravity, ionizing radiation, absence of circadian rhythm, confinement and isolation are just some of the features associated with it. Obviously, all of the latter can have an impact on human physiology and even induce detrimental changes. Some organ systems have been studied thoroughly under space conditions, however, not much is known on the functional and morphological effects of spaceflight on the human central nervous system. Previous studies have already shown that central nervous system changes occur during and after spaceflight in the form of neurovestibular problems, alterations in cognitive function and sensory perception, cephalic fluid shifts and psychological disturbances. However, little is known about the underlying neural substrates. In this review, we discuss the current limited knowledge on neuroplastic changes in the human central nervous system associated with spaceflight (actual or simulated) as measured by magnetic resonance imaging-based techniques. Furthermore, we discuss these findings as well as their future perspectives, since this can encourage future research into this delicate and intriguing aspect of spaceflight. Currently, the literature suffers from heterogeneous experimental set-ups and therefore, the lack of comparability of findings among studies. However, the cerebellum, cortical sensorimotor and somatosensory areas and vestibular-related pathways seem to be involved across different studies, suggesting that these brain regions are most affected by (simulated) spaceflight. Extending this knowledge is crucial, especially with the eye on long-duration interplanetary missions (e.g. Mars) and space tourism.

Martian Feeling: An Analogue Study to Simulate a Round-Trip to Mars using the International Space Station

NASA Astrophysics Data System (ADS)

Felix, C. V.; Gini, A.

When talking about human space exploration, Mars missions are always present. It is clear that sooner or later, humanity will take this adventure. Arguably the most important aspect to consider for the success of such an endeavour is the human element. The safety of the crew throughout a Martian mission is a top priority for all space agencies. Therefore, such a mission should not take place until all the risks have been fully understood and mitigated. A mission to Mars presents unique human and technological challenges in terms of isolation, confinement, autonomy, reliance on mission control, communication delays and adaptation to different gravity levels. Analogue environments provide the safest way to simulate these conditions, mitigate the risks and evaluate the effects of long-term space travel on the crew. Martian Feeling is one of nine analogue studies, from the Mars Analogue Path (MAP) report [1], proposed by the TP Analogue group of ISU Masters class 2010. It is an integrated analogue study which simulates the psychological, physiological and operational conditions that an international, six-person, mixed gender crew would experience on a mission to Mars. Set both onboard the International Space Station (ISS) and on Earth, the Martian Feeling study will perform a ``dress rehearsal'' of a mission to Mars. The study proposes to test both human performance and operational procedures in a cost-effective manner. Since Low Earth Orbit (LEO) is more accessible than other space-based locations, an analogue studies in LEO would provide the required level of realism to a simulated transit mission to Mars. The sustained presence of microgravity and other elements of true spaceflight are features of LEO that are neither currently feasible nor possible to study in terrestrial analogue sites. International collaboration, economics, legal and ethical issues were considered when the study was proposed. As an example of international collaboration, the ISS would demonstrate an effective model for an international effort to send humans to Mars. The proposed starting date is the year 2017, before the planned retirement of the ISS, which is currently scheduled for 2020.

CO2-O2 interactions in extension of tolerance to acute hypoxia

NASA Technical Reports Server (NTRS)

Lambertsen, C. J.

1995-01-01

Objectives and results of experimental projects a re summarized. The scope of information desired included (1) physiological and performance consequences of exposures to simulated microgravity, in rest and graded physical activity, (2) separate influences of graded degrees of atmospheric hypercapnia and hypoxia, and (3) composite effects of hypoxia and hypercapnia. The research objectives were selected for close relevance to existing quantitative information concerning interactions of hypercapnia and hypoxia on respiratory and brain circulatory control. They include: (1) to determine influences of normoxic immersion on interrelations of pulmonary ventilation, arterial PCO2 and PO2, and brain blood flow, in rest and physical work; (2) to determine influence of normoxic immersion on respiratory reactivity to atmospheric hypercapnia at rest; (3) to determine influence of atmospheric hypoxia on respiratory reactivity to hypercapnia at rest and in work; and (4) to provide physiological baselines of data concerning adaptations in acute exposures to aid in investigation of rates of adaptation or deteriorations in physiological or performance capability during subsequent multi-day exposures. A list of publications related to the present grant period is included along with an appendix describing the Performance Measurement System (human perceptual, cognitive and psychomotor functions).

Metabolic Adaptation to Muscle Ischemia

NASA Technical Reports Server (NTRS)

Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.

2000-01-01

Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

Alteration of infant attention and activity by polychlorinated biphenyls: unravelling critical windows of susceptibility using physiologically based pharmacokinetic modeling.

PubMed

Verner, M-A; Plusquellec, P; Muckle, G; Ayotte, P; Dewailly, E; Jacobson, S W; Jacobson, J L; Charbonneau, M; Haddad, S

2010-09-01

Pre- and postnatal exposure to polychlorinated biphenyls (PCBs) can impair behavioural function in animal models at doses within the range at which humans are commonly exposed. Yet, epidemiologic studies conducted in the US and Europe are inconsistent with regard to the developmental effects of lactational exposure to these chemicals. This inconsistency may be due to limitations in the current methodological approaches for assessing postnatal exposure to PCBs. Our study used a physiologically based pharmacokinetic (PBPK) model to simulate blood PCB levels during specific pre- and postnatal periods and to evaluate the relation of those levels to infant behaviour. A previously validated PBPK model was used to simulate infant blood PCB-153 levels at delivery and on a month-by-month basis during the first year of life for Inuit infants enrolled in a longitudinal birth cohort. Infant behaviour was assessed using the Behaviour Rating Scales (BRS) of the Bayley Scales of Infant Development (BSID-II) at 11 months of age and video coding of inattention and activity measured during the administration of the mental development subscale of the BSID-II. The estimated pre- and postnatal PCB exposure measures predicted significant increases in inattention and activity at 11 months. Whereas inattention was related to prenatal exposure, activity level, measured by non-elicited activity, was best predicted by postnatal exposure, with the strongest association obtained for simulated PCB levels during the 4th month of life. These findings are consistent with previous reports indicating PCB-induced behavioural alteration in attention and activity level. Simulated infant toxicokinetic profiles for the first year of life revealed windows of susceptibility during which PCBs may impair infant attention and activity. Copyright © 2010 Elsevier Inc. All rights reserved.

The Integrated Impact of Diet on Human Immune Response, the Gut Microbiota, and Nutritional Status During Adaptation to a Spaceflight Analog

NASA Technical Reports Server (NTRS)

Douglas, G. L.; Zwart, S. R.; Young, M.; Kloeris, V.; Crucian, B.; Smith, S. M.; Lorenzi, H.

2018-01-01

Spaceflight impacts human physiology, including well documented immune system dysregulation. Diet, immune function, and the microbiome are interlinked, but diet is the only one of these factors that we have the ability to easily, and significantly, alter on Earth or during flight. As we understand dietary impacts on physiology more thoroughly, we may then improve the spaceflight diet to improve crew health and potentially reduce spaceflight-associated physiological alterations. It is expected that increasing the consumption of fruits and vegetables and bioactive compounds (e.g., omega-3 fatty acids, lycopene, flavonoids) and therefore enhancing overall nutritional intake from the nominal shelf-stable, fully-processed space food system could serve as a countermeasure to improve human immunological profiles, the taxonomic profile of the gut microbiota, and nutritional status, especially where currently dysregulated during spaceflight. This interdisciplinary study will determine the effect of the current shelf-stable spaceflight diet compared to an "enhanced" shelf-stable spaceflight diet (25% more foods rich in omega-3 fatty acids, lycopene, flavonoids, and more fruits, and vegetables in general). The NASA Human Exploration Research Analog (HERA) 2017 missions, consisting of four 45-day missions with closed chamber confinement and realistic mission simulation in a high-fidelity mock space vehicle, will serve as a platform to replicate mission stressors and the effects on crew biochemistry, immunology, and the gut microbiome. Bio sampling of crewmembers is scheduled for selected intervals pre- and in-mission. Data collection also includes dietary intake recording. Outcome measures will include immune markers (e.g., peripheral leukocyte distribution, inflammatory cytokine profiles, T cell function), the taxonomic and metatranscriptomic profile of the gut microbiome, and nutritional status biomarkers and metabolites. Statistical evaluations will determine physiological and biochemical shifts in relation to nutrient intake and study phase. To date, sample collection has been completed for 2 crewmembers from the first mission, aka Campaign 4 Mission 1. Mission 2 was terminated after 22 days due to effects of Hurricane Harvey, and sample collection was not completed. Sample collection will continue for Campaign 4 Mission 3 and 4 prior to comprehensive sample analysis. Beneficial improvements will provide evidence of the impact of diet on crew health and adaptation to this spaceflight analog, and will aid in the design and development of more-efficient targeted dietary interventions for exploration missions.

Evaluating the influence of plant-specific physiological parameterizations on the partitioning of land surface energy fluxes

NASA Astrophysics Data System (ADS)

Sulis, Mauro; Langensiepen, Matthias; Shrestha, Prabhakar; Schickling, Anke; Simmer, Clemens; Kollet, Stefan

2015-04-01

Vegetation has a significant influence on the partitioning of radiative forcing, the spatial and temporal variability of soil water and soil temperature. Therefore plant physiological properties play a key role in mediating and amplifying interactions and feedback mechanisms in the soil-vegetation-atmosphere continuum. Because of the direct impact on latent heat fluxes, these properties may also influence weather generating processes, such as the evolution of the atmospheric boundary layer (ABL). In land surface models, plant physiological properties are usually obtained from literature synthesis by unifying several plant/crop species in predefined vegetation classes. In this work, crop-specific physiological characteristics, retrieved from detailed field measurements, are included in the bio-physical parameterization of the Community Land Model (CLM), which is a component of the Terrestrial Systems Modeling Platform (TerrSysMP). The measured set of parameters for two typical European mid-latitudinal crops (sugar beet and winter wheat) is validated using eddy covariance measurements (sensible heat and latent heat) over multiple years from three measurement sites located in the North Rhine-Westphalia region, Germany. We found clear improvements of CLM simulations, when using the crop-specific physiological characteristics of the plants instead of the generic crop type when compared to the measurements. In particular, the increase of latent heat fluxes in conjunction with decreased sensible heat fluxes as simulated by the two new crop-specific parameter sets leads to an improved quantification of the diurnal energy partitioning. These findings are cross-validated using estimates of gross primary production extracted from net ecosystem exchange measurements. This independent analysis reveals that the better agreement between observed and simulated latent heat using the plant-specific physiological properties largely stems from an improved simulation of the photosynthesis process owing to a better estimation of the Rubisco enzyme kinematics. Finally, to evaluate the effects of the crop-specific parameterizations on the ABL dynamics, we perform a series of semi-idealized land-atmosphere coupled simulations by hypothesizing three cropland configurations. These numerical experiments reveal different heat and moisture budgets of the ABL that clearly impact the evolution of the boundary layer when using the crop-specific physiological properties.

Dynamic biological exposure indexes for n-hexane and 2,5-hexanedione, suggested by a physiologically based pharmacokinetic model

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

Perbellini, L.; Mozzo, P.; Olivato, D.

Biological exposure index (BEI) of n-hexane was studied for accuracy using a physiologically based pharmacokinetic (PB-PK) model. The kinetics of n-hexane in alveolar air, blood, urine, and other tissues were simulated for different values of alveolar ventilations and also for constant and variable exposures. The kinetics of 2,5-hexanedione, the toxic n-hexane metabolite, were also simulated. The ranges of n-hexane concentrations in biological media and the urinary concentrations of 2,5-hexanedione are discussed in connection with a mean n-hexane exposure of 180 mg/m3 (50 ppm) (threshold limit value (TLV) suggested by American Conference of Governmental Industrial Hygienists (ACGIH) for 1988-89). The experimentalmore » and field data as well as those predicted by simulation with the PB-PK model were comparable. The physiological-pharmacokinetic simulations are used to propose the dynamic BEIs of n-hexane and 2,5-hexanedione. The use of simulation with PB-PK models enables a better understanding of the limits, advantages, and issues associated with biological monitoring of exposures to industrial solvents.« less

Integrative Physiology: At the Crossroads of Nutrition, Microbiota, Animal Physiology, and Human Health.

PubMed

Leulier, François; MacNeil, Lesley T; Lee, Won-Jae; Rawls, John F; Cani, Patrice D; Schwarzer, Martin; Zhao, Liping; Simpson, Stephen J

2017-03-07

Nutrition is paramount in shaping all aspects of animal biology. In addition, the influence of the intestinal microbiota on physiology is now widely recognized. Given that diet also shapes the intestinal microbiota, this raises the question of how the nutritional environment and microbial assemblages together influence animal physiology. This research field constitutes a new frontier in the field of organismal biology that needs to be addressed. Here we review recent studies using animal models and humans and propose an integrative framework within which to define the study of the diet-physiology-microbiota systems and ultimately link it to human health. Nutritional Geometry sits centrally in the proposed framework and offers means to define diet compositions that are optimal for individuals and populations. Copyright © 2017 Elsevier Inc. All rights reserved.

Microgravity-Induced Physiological Fluid Redistribution: Computational Analysis to Assess Influence of Physiological Parameters

NASA Technical Reports Server (NTRS)

Myers, J. G.; Eke, Chika; Werner, C.; Nelson, E. S.; Mulugeta, L.; Feola, A.; Raykin, J.; Samuels, B.; Ethier, C. R.

2016-01-01

Space flight impacts human physiology in many ways, the most immediate being the marked cephalad (headward) shift of fluid upon introduction into the microgravity environment. This physiological response to microgravity points to the redistribution of blood and interstitial fluid as a major factor in the loss of venous tone and reduction in heart muscle efficiency which impact astronaut performance. In addition, researchers have hypothesized that a reduction in astronaut visual acuity, part of the Visual Impairment and Intracranial Pressure (VIIP) syndrome, is associated with this redistribution of fluid. VIIP arises within several months of beginning space flight and includes a variety of ophthalmic changes including posterior globe flattening, distension of the optic nerve sheath, and kinking of the optic nerve. We utilize a suite of lumped parameter models to simulate microgravity-induced fluid redistribution in the cardiovascular, central nervous and ocular systems to provide initial and boundary data to a 3D finite element simulation of ocular biomechanics in VIIP. Specifically, the lumped parameter cardiovascular model acts as the primary means of establishing how microgravity, and the associated lack of hydrostatic gradient, impacts fluid redistribution. The cardiovascular model consists of 16 compartments, including three cerebrospinal fluid (CSF) compartments, three cranial blood compartments, and 10 thoracic and lower limb blood compartments. To assess the models capability to address variations in physiological parameters, we completed a formal uncertainty and sensitivity analysis that evaluated the relative importance of 42 input parameters required in the model on relative compartment flows and compartment pressures. Utilizing the model in a pulsatile flow configuration, the sensitivity analysis identified the ten parameters that most influenced each compartment pressure. Generally, each compartment responded appropriately to parameter variations associated with itself and adjacent compartments. However, several unexpected interactions between components, such as between the choroid plexus and the lower capillaries, were found, and are due to simplifications in the formulation of the model. The analysis illustrates that highly influential parameters and those that have unique influences within the model formulation must be tightly controlled for successful model application.

The source-filter theory of whistle-like calls in marmosets: Acoustic analysis and simulation of helium-modulated voices.

PubMed

Koda, Hiroki; Tokuda, Isao T; Wakita, Masumi; Ito, Tsuyoshi; Nishimura, Takeshi

2015-06-01

Whistle-like high-pitched "phee" calls are often used as long-distance vocal advertisements by small-bodied marmosets and tamarins in the dense forests of South America. While the source-filter theory proposes that vibration of the vocal fold is modified independently from the resonance of the supralaryngeal vocal tract (SVT) in human speech, a source-filter coupling that constrains the vibration frequency to SVT resonance effectively produces loud tonal sounds in some musical instruments. Here, a combined approach of acoustic analyses and simulation with helium-modulated voices was used to show that phee calls are produced principally with the same mechanism as in human speech. The animal keeps the fundamental frequency (f0) close to the first formant (F1) of the SVT, to amplify f0. Although f0 and F1 are primarily independent, the degree of their tuning can be strengthened further by a flexible source-filter interaction, the variable strength of which depends upon the cross-sectional area of the laryngeal cavity. The results highlight the evolutionary antiquity and universality of the source-filter model in primates, but the study can also explore the diversification of vocal physiology, including source-filter interaction and its anatomical basis in non-human primates.

Influence of the magnesium aspartate hydrochloride administration to the maternal circuit on the aspartate concentration of the fetal circuit under in vitro perfusion of human placenta.

PubMed

Malek, A; Leiser, R

2009-01-01

Magnesium aspartate hydrochloride (Magnesiocard, Mg-Asp-HCl) is proposed as a substitute of magnesium sulfate for the treatment of preeclampsia and premature labor. After an i.v. administration of a dose equivalent to that used in the treatment of preeclampsia to nonpregnant volunteers, a 10-fold increase of aspartic acid (Asp) over the physiological level was observed. Animal experiments have demonstrated that highly increased fetal levels of acidic amino acids such as Asp could be associated with neurotoxic damage in the fetal brain. The influence of such an elevation of Asp concentration in the maternal circuit on the fetal level, using the in vitro perfusion model of human placenta, was investigated. After a control phase (2h), a therapeutic dose of Mg combined with Asp (Magnesiocard, Mg-Asp-HCl) was applied to the maternal circuit approaching 10 times the physiological level of Asp. The administration was performed in two different phases simulating either a peak of maximum concentration (bolus application, 2h) or a steady state level (initially added, 4h). In four experiments, during experimental phases (6h) a slow increase in concentration in the fetal circuit was seen for Mg, AIB (alpha-aminoisobutyric acid, artificial amino acid) and creatinine confirming previous observations. In contrast, no net transfer of Asp across the placenta was seen. A continuous decrease in the concentration of Asp on both maternal and fetal side suggests active uptake and metabolization by the placenta. Viability control parameters remained stable indicating the absence of an effect on placental metabolism, permeability and morphology. Elevation of Asp concentration up to 10 times the physiological level by the administration of Mg-Asp-HCl to the maternal circuit under in vitro perfusion conditions of human placenta has no influence on the fetal level of Asp suggesting no transfer of Asp from the maternal to fetal compartment. Therefore, the administration of Mg-Asp-HCl to preeclamptic patients would be beneficial for the patients without any impact on placental or fetal physiology.

Physiological system integrations with emphasis on the respiratory-cardiovascular system

NASA Technical Reports Server (NTRS)

Gallagher, R. R.

1975-01-01

The integration of two types of physiological system simulations is presented. The long term model is a circulatory system model which simulates long term blood flow variations and compartmental fluid shifts. The short term models simulate transient phenomena of the respiratory, thermoregulatory, and pulsatile cardiovascular systems as they respond to stimuli such as LBNP, exercise, and environmental gaseous variations. An overview of the interfacing approach is described. Descriptions of the variable interface for long term to short term and between the three short term models are given.

Improving the physiological realism of experimental models.

PubMed

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

2016-04-06

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

Superposed epoch analysis of physiological fluctuations: possible space weather connections

NASA Astrophysics Data System (ADS)

Wanliss, James; Cornélissen, Germaine; Halberg, Franz; Brown, Denzel; Washington, Brien

2018-03-01

There is a strong connection between space weather and fluctuations in technological systems. Some studies also suggest a statistical connection between space weather and subsequent fluctuations in the physiology of living creatures. This connection, however, has remained controversial and difficult to demonstrate. Here we present support for a response of human physiology to forcing from the explosive onset of the largest of space weather events—space storms. We consider a case study with over 16 years of high temporal resolution measurements of human blood pressure (systolic, diastolic) and heart rate variability to search for associations with space weather. We find no statistically significant change in human blood pressure but a statistically significant drop in heart rate during the main phase of space storms. Our empirical findings shed light on how human physiology may respond to exogenous space weather forcing.

Superposed epoch analysis of physiological fluctuations: possible space weather connections.

PubMed

Wanliss, James; Cornélissen, Germaine; Halberg, Franz; Brown, Denzel; Washington, Brien

2018-03-01

There is a strong connection between space weather and fluctuations in technological systems. Some studies also suggest a statistical connection between space weather and subsequent fluctuations in the physiology of living creatures. This connection, however, has remained controversial and difficult to demonstrate. Here we present support for a response of human physiology to forcing from the explosive onset of the largest of space weather events-space storms. We consider a case study with over 16 years of high temporal resolution measurements of human blood pressure (systolic, diastolic) and heart rate variability to search for associations with space weather. We find no statistically significant change in human blood pressure but a statistically significant drop in heart rate during the main phase of space storms. Our empirical findings shed light on how human physiology may respond to exogenous space weather forcing.

The thermal environment of the human being on the global scale

PubMed Central

Jendritzky, Gerd; Tinz, Birger

2009-01-01

Background The close relationship between human health, performance, well-being and the thermal environment is obvious. Nevertheless, most studies of climate and climate change impacts show amazing shortcomings in the assessment of the environment. Populations living in different climates have different susceptibilities, due to socio-economic reasons, and different customary behavioural adaptations. The global distribution of risks of hazardous thermal exposure has not been analysed before. Objective To produce maps of the baseline and future bioclimate that allows a direct comparison of the differences in the vulnerability of populations to thermal stress across the world. Design The required climatological data fields are obtained from climate simulations with the global General Circulation Model ECHAM4 in T106-resolution. For the thermo-physiologically relevant assessment of these climate data a complete heat budget model of the human being, the ‘Perceived Temperature’ procedure has been applied which already comprises adaptation by clothing to a certain degree. Short-term physiological acclimatisation is considered via Health Related Assessment of the Thermal Environment. Results The global maps 1971–1980 (control run, assumed as baseline climate) show a pattern of thermal stress intensities as frequencies of heat. The heat load for people living in warm–humid climates is the highest. Climate change will lead to clear differences in health-related thermal stress between baseline climate and the future bioclimate 2041–2050 based on the ‘business-as-usual’ greenhouse gas scenario IS92a. The majority of the world's population will be faced with more frequent and more intense heat strain in spite of an assumed level of acclimatisation. Further adaptation measures are crucial in order to reduce the vulnerability of the populations. Conclusions This bioclimatology analysis provides a tool for various questions in climate and climate change impact research. Considerations of regional or local scale require climate simulations with higher resolution. As adaptation is the key term in understanding the role of climate/climate change for human health, performance and well-being, further research in this field is crucial. PMID:20052427

Organizing Heterogeneous Samples Using Community Detection of GIMME-Derived Resting State Functional Networks

PubMed Central

Gates, Kathleen M.; Molenaar, Peter C. M.; Iyer, Swathi P.; Nigg, Joel T.; Fair, Damien A.

2014-01-01

Clinical investigations of many neuropsychiatric disorders rely on the assumption that diagnostic categories and typical control samples each have within-group homogeneity. However, research using human neuroimaging has revealed that much heterogeneity exists across individuals in both clinical and control samples. This reality necessitates that researchers identify and organize the potentially varied patterns of brain physiology. We introduce an analytical approach for arriving at subgroups of individuals based entirely on their brain physiology. The method begins with Group Iterative Multiple Model Estimation (GIMME) to assess individual directed functional connectivity maps. GIMME is one of the only methods to date that can recover both the direction and presence of directed functional connectivity maps in heterogeneous data, making it an ideal place to start since it addresses the problem of heterogeneity. Individuals are then grouped based on similarities in their connectivity patterns using a modularity approach for community detection. Monte Carlo simulations demonstrate that using GIMME in combination with the modularity algorithm works exceptionally well - on average over 97% of simulated individuals are placed in the accurate subgroup with no prior information on functional architecture or group identity. Having demonstrated reliability, we examine resting-state data of fronto-parietal regions drawn from a sample (N = 80) of typically developing and attention-deficit/hyperactivity disorder (ADHD) -diagnosed children. Here, we find 5 subgroups. Two subgroups were predominantly comprised of ADHD, suggesting that more than one biological marker exists that can be used to identify children with ADHD based from their brain physiology. Empirical evidence presented here supports notions that heterogeneity exists in brain physiology within ADHD and control samples. This type of information gained from the approach presented here can assist in better characterizing patients in terms of outcomes, optimal treatment strategies, potential gene-environment interactions, and the use of biological phenomenon to assist with mental health. PMID:24642753

Modeling interchild differences in pharmacokinetics on the basis of subject-specific data on physiology and hepatic CYP2E1 levels: A case study with toluene

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

Nong, A.; McCarver, D.G.; Hines, R.N.

2006-07-01

The objective of the present study was to evaluate the magnitude of interindividual variability in the internal dose of toluene in children of various age groups, on the basis of subject-specific hepatic CYP2E1 content and physiology. The methodology involved the use of a previously validated physiologically based pharmacokinetic (PBPK) model, in which the intrinsic clearance for hepatic metabolism (CL{sub int}) was expressed in terms of the CYP2E1 content. The adult toluene PBPK model, with enzyme content-normalized CL{sub int}, facilitated the calculation of child-specific CL{sub int} based on knowledge of hepatic CYP2E1 protein levels. The child-specific physiological parameters, except liver volume,more » were computed with knowledge of age and body weight, whereas physicochemical parameters for toluene were kept age-invariant based on available data. The actual individual-specific liver volume (autopsy data) was also included in the model. The resulting model was used to simulate the blood concentration profiles in children exposed by inhalation, to 1 ppm toluene for 24 h. For this exposure scenario, the area under the venous blood concentration vs. time curve (AUC) ranged from 0.30 to 1.01 {mu}g/ml x h in neonates with low CYP2E1 concentration (<3.69 pmol/mg protein). The simulations indicated that neonates with higher levels of CYP2E1 (4.33 to 55.93 pmol/mg protein) as well as older children would have lower AUC (0.16 to 0.43 {mu}g/ml x h). The latter values were closer to those simulated for adults. Similar results were also obtained for 7 h exposure to 17 ppm toluene, a scenario previously evaluated in human volunteers. The interindividual variability factor for each subgroup of children and adults, calculated as the ratio of the 95th and 50th percentile values of AUC, was within a factor of 2. The 95th percentile value of the low metabolizing neonate group, however, was greater than the mean adult AUC by a factor of 3.9. This study demonstrates the feasibility of incorporating subject-specific data on hepatic CYP2E1 content and physiology within PBPK models for evaluating the age, interchild and population variability of internal dose for use in risk assessment of inhaled volatile organics.« less

Evaluation of the Virtual Physiology of Exercise Laboratory Program

ERIC Educational Resources Information Center

Dobson, John L.

2009-01-01

The Virtual Physiology of Exercise Laboratory (VPEL) program was created to simulate the test design, data collection, and analysis phases of selected exercise physiology laboratories. The VPEL program consists of four modules: (1) cardiovascular, (2) maximal O[subscript 2] consumption [Vo[subscript 2max], (3) lactate and ventilatory thresholds,…

Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways

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

Kabilan, S.; Suffield, S. R.; Recknagle, K. P.

Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived respectively from computed tomography (CT) and µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation–exhalation breathingmore » conditions using average species-specific minute volumes. Two different exposure scenarios were modeled in the rabbit based upon experimental inhalation studies. For comparison, human simulations were conducted at the highest exposure concentration used during the rabbit experimental exposures. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the nasal sinus compared to the human at the same air concentration of anthrax spores. In contrast, higher spore deposition was predicted in the lower conducting airways of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology for deposition.« less

Computational Fluid Dynamics Modeling of Bacillus anthracis Spore Deposition in Rabbit and Human Respiratory Airways

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

Kabilan, Senthil; Suffield, Sarah R.; Recknagle, Kurtis P.

Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived from computed tomography (CT) or µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditionsmore » using average species-specific minute volumes. The highest exposure concentration was modeled in the rabbit based upon prior acute inhalation studies. For comparison, human simulation was also conducted at the same concentration. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the upper conducting airways compared to the human at the same air concentration of anthrax spores. As a result, higher particle deposition was predicted in the conducting airways and deep lung of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology.« less

Winter wheat: A model for the simulation of growth and yield in winter wheat

NASA Technical Reports Server (NTRS)

Baker, D. N.; Smika, D. E.; Black, A. L.; Willis, W. O.; Bauer, A. (Principal Investigator)

1981-01-01

The basic ideas and constructs for a general physical/physiological process level winter wheat simulation model are documented. It is a materials balance model which calculates daily increments of photosynthate production and respiratory losses in the crop canopy. The partitioning of the resulting dry matter to the active growing tissues in the plant each day, transpiration and the uptake of nitrogen from the soil profile are simulated. It incorporates the RHIZOS model which simulates, in two dimensions, the movement of water, roots, and soluble nutrients through the soil profile. It records the time of initiation of each of the plant organs. These phenological events are calculated from temperature functions with delays resulting from physiological stress. Stress is defined mathematically as an imbalance in the metabolite supply; demand ratio. Physiological stress is also the basis for the calculation of rates of tiller and floret abortion. Thus, tillering and head differentiation are modeled as the resulants of the two processes, morphogenesis and abortion, which may be occurring simulaneously.

iAB-RBC-283: A proteomically derived knowledge-base of erythrocyte metabolism that can be used to simulate its physiological and patho-physiological states.

PubMed

Bordbar, Aarash; Jamshidi, Neema; Palsson, Bernhard O

2011-07-12

The development of high-throughput technologies capable of whole cell measurements of genes, proteins, and metabolites has led to the emergence of systems biology. Integrated analysis of the resulting omic data sets has proved to be hard to achieve. Metabolic network reconstructions enable complex relationships amongst molecular components to be represented formally in a biologically relevant manner while respecting physical constraints. In silico models derived from such reconstructions can then be queried or interrogated through mathematical simulations. Proteomic profiling studies of the mature human erythrocyte have shown more proteins present related to metabolic function than previously thought; however the significance and the causal consequences of these findings have not been explored. Erythrocyte proteomic data was used to reconstruct the most expansive description of erythrocyte metabolism to date, following extensive manual curation, assessment of the literature, and functional testing. The reconstruction contains 281 enzymes representing functions from glycolysis to cofactor and amino acid metabolism. Such a comprehensive view of erythrocyte metabolism implicates the erythrocyte as a potential biomarker for different diseases as well as a 'cell-based' drug-screening tool. The analysis shows that 94 erythrocyte enzymes are implicated in morbid single nucleotide polymorphisms, representing 142 pathologies. In addition, over 230 FDA-approved and experimental pharmaceuticals have enzymatic targets in the erythrocyte. The advancement of proteomic technologies and increased generation of high-throughput proteomic data have created the need for a means to analyze these data in a coherent manner. Network reconstructions provide a systematic means to integrate and analyze proteomic data in a biologically meaning manner. Analysis of the red cell proteome has revealed an unexpected level of complexity in the functional capabilities of human erythrocyte metabolism.

An innovative design for cardiopulmonary resuscitation manikins based on a human-like thorax and embedded flow sensors.

PubMed

Thielen, Mark; Joshi, Rohan; Delbressine, Frank; Bambang Oetomo, Sidarto; Feijs, Loe

2017-03-01

Cardiopulmonary resuscitation manikins are used for training personnel in performing cardiopulmonary resuscitation. State-of-the-art cardiopulmonary resuscitation manikins are still anatomically and physiologically low-fidelity designs. The aim of this research was to design a manikin that offers high anatomical and physiological fidelity and has a cardiac and respiratory system along with integrated flow sensors to monitor cardiac output and air displacement in response to cardiopulmonary resuscitation. This manikin was designed in accordance with anatomical dimensions using a polyoxymethylene rib cage connected to a vertebral column from an anatomical female model. The respiratory system was composed of silicon-coated memory foam mimicking lungs, a polyvinylchloride bronchus and a latex trachea. The cardiovascular system was composed of two sets of latex tubing representing the pulmonary and aortic arteries which were connected to latex balloons mimicking the ventricles and lumped abdominal volumes, respectively. These balloons were filled with Life/form simulation blood and placed inside polyether foam. The respiratory and cardiovascular systems were equipped with flow sensors to gather data in response to chest compressions. Three non-medical professionals performed chest compressions on this manikin yielding data corresponding to force-displacement while the flow sensors provided feedback. The force-displacement tests on this manikin show a desirable nonlinear behaviour mimicking chest compressions during cardiopulmonary resuscitation in humans. In addition, the flow sensors provide valuable data on the internal effects of cardiopulmonary resuscitation. In conclusion, scientifically designed and anatomically high-fidelity designs of cardiopulmonary resuscitation manikins that embed flow sensors can improve physiological fidelity and provide useful feedback data.

Adaptive Filtration of Physiological Artifacts in EEG Signals in Humans Using Empirical Mode Decomposition

NASA Astrophysics Data System (ADS)

Grubov, V. V.; Runnova, A. E.; Hramov, A. E.

2018-05-01

A new method for adaptive filtration of experimental EEG signals in humans and for removal of different physiological artifacts has been proposed. The algorithm of the method includes empirical mode decomposition of EEG, determination of the number of empirical modes that are considered, analysis of the empirical modes and search for modes that contains artifacts, removal of these modes, and reconstruction of the EEG signal. The method was tested on experimental human EEG signals and demonstrated high efficiency in the removal of different types of physiological EEG artifacts.

Limitations to Thermoregulation and Acclimatization Challenge Human Adaptation to Global Warming.

PubMed

Hanna, Elizabeth G; Tait, Peter W

2015-07-15

Human thermoregulation and acclimatization are core components of the human coping mechanism for withstanding variations in environmental heat exposure. Amidst growing recognition that curtailing global warming to less than two degrees is becoming increasing improbable, human survival will require increasing reliance on these mechanisms. The projected several fold increase in extreme heat events suggests we need to recalibrate health protection policies and ratchet up adaptation efforts. Climate researchers, epidemiologists, and policy makers engaged in climate change adaptation and health protection are not commonly drawn from heat physiology backgrounds. Injecting a scholarly consideration of physiological limitations to human heat tolerance into the adaptation and policy literature allows for a broader understanding of heat health risks to support effective human adaptation and adaptation planning. This paper details the physiological and external environmental factors that determine human thermoregulation and acclimatization. We present a model to illustrate the interrelationship between elements that modulate the physiological process of thermoregulation. Limitations inherent in these processes, and the constraints imposed by differing exposure levels, and thermal comfort seeking on achieving acclimatization, are then described. Combined, these limitations will restrict the likely contribution that acclimatization can play in future human adaptation to global warming. We postulate that behavioral and technological adaptations will need to become the dominant means for human individual and societal adaptations as global warming progresses.

Physical Test Validation for Job Selection. Chapter 5

DTIC Science & Technology

2000-09-21

Borgs perceived exertion andlpain scaling method. Champaign: Human Kinetics . 17. Brooks, G., & Fahey, T (1984). Exercise physiology: Human bioenergetics...Eds.), Measurement concepts in physical education and exercise science. Champaign: Human Kinetics . 44. Jackson, A. S., Blair, S. N., Mahar, M. T...Chapter 5: Physical Test Evaluation for Job Selection 94. Wilmore, J. H., & Costill, D. L. (1994). Physiology of sport and exercise. Champaign, IL: Human

Physiological responses to simulated firefighter exercise protocols in varying environments.

PubMed

Horn, Gavin P; Kesler, Richard M; Motl, Robert W; Hsiao-Wecksler, Elizabeth T; Klaren, Rachel E; Ensari, Ipek; Petrucci, Matthew N; Fernhall, Bo; Rosengren, Karl S

2015-01-01

For decades, research to quantify the effects of firefighting activities and personal protective equipment on physiology and biomechanics has been conducted in a variety of testing environments. It is unknown if these different environments provide similar information and comparable responses. A novel Firefighting Activities Station, which simulates four common fireground tasks, is presented for use with an environmental chamber in a controlled laboratory setting. Nineteen firefighters completed three different exercise protocols following common research practices. Simulated firefighting activities conducted in an environmental chamber or live-fire structures elicited similar physiological responses (max heart rate: 190.1 vs 188.0 bpm, core temperature response: 0.047°C/min vs 0.043°C/min) and accelerometry counts. However, the response to a treadmill protocol commonly used in laboratory settings resulted in significantly lower heart rate (178.4 vs 188.0 bpm), core temperature response (0.037°C/min vs 0.043°C/min) and physical activity counts compared with firefighting activities in the burn building. Practitioner Summary: We introduce a new approach for simulating realistic firefighting activities in a controlled laboratory environment for ergonomics assessment of fire service equipment and personnel. Physiological responses to this proposed protocol more closely replicate those from live-fire activities than a traditional treadmill protocol and are simple to replicate and standardise.

Numerical simulation of aerobic exercise as a countermeasure in human spaceflight

NASA Astrophysics Data System (ADS)

Perez-Poch, Antoni

The objective of this work is to analyse the efficacy of long-term regular exercise on relevant cardiovascular parameters when the human body is also exposed to microgravity. Computer simulations are an important tool which may be used to predict and analyse these possible effects, and compare them with in-flight experiments. We based our study on a electrical-like computer model (NELME: Numerical Evaluation of Long-term Microgravity Effects) which was developed in our laboratory and validated with the available data, focusing on the cardiovascu-lar parameters affected by changes in gravity exposure. NELME is based on an electrical-like control system model of the physiological changes, that are known to take place when grav-ity changes are applied. The computer implementation has a modular architecture. Hence, different output parameters, potential effects, organs and countermeasures can be easily imple-mented and evaluated. We added to the previous cardiovascular system module a perturbation module to evaluate the effect of regular exercise on the output parameters previously studied. Therefore, we simulated a well-known countermeasure with different protocols of exercising, as a pattern of input electric-like perturbations on the basic module. Different scenarios have been numerically simulated for both men and women, in different patterns of microgravity, reduced gravity and time exposure. Also EVAs were simulated as perturbations to the system. Results show slight differences in gender, with more risk reduction for women than for men after following an aerobic exercise pattern during a simulated mission. Also, risk reduction of a cardiovascular malfunction is evaluated, with a ceiling effect found in all scenarios. A turning point in vascular resistance for a long-term exposure of microgravity below 0.4g has been found of particular interest. In conclusion, we show that computer simulations are a valuable tool to analyse different effects of long-term microgravity exposure on the human body. Potential countermeasures such as physical exercise can also be evaluated as an induced perturbation into the system. Relevant results are compatible with existing data, and are of valuable interest as an assessment of the efficacy of aerobic exercise as a countermeasure in future missions to Mars.

Physiological correlates of stress-induced decrements in human perceptual performance.

DOT National Transportation Integrated Search

1993-11-01

Stress-induced changes in human performance have been thought to result from alterations in the "multidimensional arousal state" of the individual, as indexed by alterations in the physiological and psychological mechanisms controlling performance. I...

Improving the physiological realism of experimental models

PubMed Central

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

2016-01-01

The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide an in silico platform for drug screening. Ultimately, these models rely on the analysis and integration of experimental data. As such, the success of VPH depends on the availability of physiologically realistic experimental models (E-Models) of human organ function that can be parametrized to test the numerical models. Here, the current state of suitable E-models, ranging from in vitro non-human cell organelles to in vivo human organ systems, is discussed. Specifically, challenges and recent progress in improving the physiological realism of E-models that may benefit the VPH project are highlighted and discussed using examples from the field of research on cardiovascular disease, musculoskeletal disorders, diabetes and Parkinson's disease. PMID:27051507

Visible implant elastomer (VIE) tagging and simulated predation risk elicit similar physiological stress responses in three-spined stickleback Gasterosteus aculeatus.

PubMed

Fürtbauer, I; King, A J; Heistermann, M

2015-05-01

The effect of visible implant elastomer (VIE) tagging on the immediate physiological stress response was tested in female three-spined stickleback Gasterosteus aculeatus, using non-invasive waterborne cortisol analysis. Post-tagging cortisol levels were significantly higher compared with pretreatment baseline concentrations; however, when comparing post-tagging cortisol levels with cortisol levels after exposure to a simulated aerial predator, no significant differences were found. This study indicates that VIE tagging elicits a physiological stress response similar to those occurring in the everyday lives of this important biological model organism. © 2015 The Fisheries Society of the British Isles.

Less is sometimes more: a comparison of distance-control and navigated-control concepts of image-guided navigation support for surgeons.

PubMed

Luz, Maria; Manzey, Dietrich; Modemann, Susanne; Strauss, Gero

2015-01-01

Image-guided navigation (IGN) systems provide automation support of intra-operative information analysis and decision-making for surgeons. Previous research showed that navigated-control (NC) systems which represent high levels of decision-support and directly intervene in surgeons' workflow provide benefits with respect to patient safety and surgeons' physiological stress but also involve several cost effects (e.g. prolonged surgery duration, reduced secondary-task performance). It was hypothesised that less automated distance-control (DC) systems would provide a better solution in terms of human performance consequences. N = 18 surgeons performed a simulated mastoidectomy with NC, DC and without IGN assistance. Effects on surgical performance, physiological effort, workload and situation awareness (SA) were compared. As expected, DC technology had the same benefits as the NC system but also led to less unwanted side effects on surgery duration, subjective workload and SA. This suggests that IGN systems just providing information analysis support are overall more beneficial than higher automated decision-support. This study investigates human performance consequences of different concepts of IGN support for surgeons. Less automated DC systems turned out to provide advantages for patient safety and surgeons' stress similar to higher automated NC systems with, at the same time, reduced negative consequences on surgery time and subjective workload.

Nature's Autonomous Oscillators

NASA Technical Reports Server (NTRS)

Mayr, H. G.; Yee, J.-H.; Mayr, M.; Schnetzler, R.

2012-01-01

Nonlinearity is required to produce autonomous oscillations without external time dependent source, and an example is the pendulum clock. The escapement mechanism of the clock imparts an impulse for each swing direction, which keeps the pendulum oscillating at the resonance frequency. Among nature's observed autonomous oscillators, examples are the quasi-biennial oscillation and bimonthly oscillation of the Earth atmosphere, and the 22-year solar oscillation. The oscillations have been simulated in numerical models without external time dependent source, and in Section 2 we summarize the results. Specifically, we shall discuss the nonlinearities that are involved in generating the oscillations, and the processes that produce the periodicities. In biology, insects have flight muscles, which function autonomously with wing frequencies that far exceed the animals' neural capacity; Stretch-activation of muscle contraction is the mechanism that produces the high frequency oscillation of insect flight, discussed in Section 3. The same mechanism is also invoked to explain the functioning of the cardiac muscle. In Section 4, we present a tutorial review of the cardio-vascular system, heart anatomy, and muscle cell physiology, leading up to Starling's Law of the Heart, which supports our notion that the human heart is also a nonlinear oscillator. In Section 5, we offer a broad perspective of the tenuous links between the fluid dynamical oscillators and the human heart physiology.

Visual detection following retinal damage: predictions of an inhomogeneous retino-cortical model

NASA Astrophysics Data System (ADS)

Arnow, Thomas L.; Geisler, Wilson S.

1996-04-01

A model of human visual detection performance has been developed, based on available anatomical and physiological data for the primate visual system. The inhomogeneous retino- cortical (IRC) model computes detection thresholds by comparing simulated neural responses to target patterns with responses to a uniform background of the same luminance. The model incorporates human ganglion cell sampling distributions; macaque monkey ganglion cell receptive field properties; macaque cortical cell contrast nonlinearities; and a optical decision rule based on ideal observer theory. Spatial receptive field properties of cortical neurons were not included. Two parameters were allowed to vary while minimizing the squared error between predicted and observed thresholds. One parameter was decision efficiency, the other was the relative strength of the ganglion-cell center and surround. The latter was only allowed to vary within a small range consistent with known physiology. Contrast sensitivity was measured for sinewave gratings as a function of spatial frequency, target size and eccentricity. Contrast sensitivity was also measured for an airplane target as a function of target size, with and without artificial scotomas. The results of these experiments, as well as contrast sensitivity data from the literature were compared to predictions of the IRC model. Predictions were reasonably good for grating and airplane targets.

An innovative nonintrusive driver assistance system for vital signal monitoring.

PubMed

Sun, Ye; Yu, Xiong Bill

2014-11-01

This paper describes an in-vehicle nonintrusive biopotential measurement system for driver health monitoring and fatigue detection. Previous research has found that the physiological signals including eye features, electrocardiography (ECG), electroencephalography (EEG) and their secondary parameters such as heart rate and HR variability are good indicators of health state as well as driver fatigue. A conventional biopotential measurement system requires the electrodes to be in contact with human body. This not only interferes with the driver operation, but also is not feasible for long-term monitoring purpose. The driver assistance system in this paper can remotely detect the biopotential signals with no physical contact with human skin. With delicate sensor and electronic design, ECG, EEG, and eye blinking can be measured. Experiments were conducted on a high fidelity driving simulator to validate the system performance. The system was found to be able to detect the ECG/EEG signals through cloth or hair with no contact with skin. Eye blinking activities can also be detected at a distance of 10 cm. Digital signal processing algorithms were developed to decimate the signal noise and extract the physiological features. The extracted features from the vital signals were further analyzed to assess the potential criterion for alertness and drowsiness determination.

Crew activities, science, and hazards of manned missions to Mars

NASA Technical Reports Server (NTRS)

Clark, Benton C.

1988-01-01

The crew scientific and nonscientific activities that will occur at each stage of a mission to Mars are examined. Crew activities during the interplanetary flight phase will include simulations, maintenance and monitoring, communications, upgrading procedures and operations, solar activity monitoring, cross-training and sharpening of skills, physical conditioning, and free-time activities. Scientific activities will address human physiology, human psychology, sociology, astronomy, space environment effects, manufacturing, and space agriculture. Crew activities on the Martian surface will include exploration, construction, manufacturing, food production, maintenance and training, and free time. Studies of Martian geology and atmosphere, of the life forms that may exist there, and of the Martian moons will occur on the planet's surface. Crew activities and scientific studies that will occur in Mars orbit, and the hazards relevant to each stage of the mission, are also addressed.

The calcium-frequency response in the rat ventricular myocyte: an experimental and modelling study.

PubMed

Gattoni, Sara; Røe, Åsmund Treu; Frisk, Michael; Louch, William E; Niederer, Steven A; Smith, Nicolas P

2016-08-01

In the majority of species, including humans, increased heart rate increases cardiac contractility. This change is known as the force-frequency response (FFR). The majority of mammals have a positive force-frequency relationship (FFR). In rat the FFR is controversial. We derive a species- and temperature-specific data-driven model of the rat ventricular myocyte. As a measure of the FFR, we test the effects of changes in frequency and extracellular calcium on the calcium-frequency response (CFR) in our model and three altered models. The results show a biphasic peak calcium-frequency response, due to biphasic behaviour of the ryanodine receptor and the combined effect of the rapid calmodulin buffer and the frequency-dependent increase in diastolic calcium. Alterations to the model reveal that inclusion of Ca(2+) /calmodulin-dependent protein kinase II (CAMKII)-mediated L-type channel and transient outward K(+) current activity enhances the positive magnitude calcium-frequency response, and the absence of CAMKII-mediated increase in activity of the sarco/endoplasmic reticulum Ca(2+) -ATPase induces a negative magnitude calcium-frequency response. An increase in heart rate affects the strength of cardiac contraction by altering the Ca(2+) transient as a response to physiological demands. This is described by the force-frequency response (FFR), a change in developed force with pacing frequency. The majority of mammals, including humans, have a positive FFR, and cardiac contraction strength increases with heart rate. However, the rat and mouse are exceptions, with the majority of studies reporting a negative FFR, while others report either a biphasic or a positive FFR. Understanding the differences in the FFR between humans and rats is fundamental to interpreting rat-based experimental findings in the context of human physiology. We have developed a novel model of rat ventricular electrophysiology and calcium dynamics, derived predominantly from experimental data recorded under physiological conditions. As a measure of FFR, we tested the effects of changes in stimulation frequency and extracellular calcium concentration on the simulated Ca(2+) transient characteristics and showed a biphasic peak calcium-frequency relationship, consistent with recent observations of a shift from negative to positive FFR when approaching the rat physiological frequency range. We tested the hypotheses that (1) inhibition of Ca(2+) /calmodulin-dependent protein kinase II (CAMKII)-mediated increase in sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) activity, (2) CAMKII modulation of SERCA, L-type channel and transient outward K(+) current activity and (3) Na(+) /K(+) pump dynamics play a significant role in the rat FFR. The results reveal a major role for CAMKII modulation of SERCA in the peak Ca(2+) -frequency response, driven most significantly by the cytosolic calcium buffering system and changes in diastolic Ca(2+) . © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Assessment of physiological performance and perception of pushing different wheelchairs on indoor modular units simulating a surface roughness often encountered in under-resourced settings.

PubMed

Sasaki, Kotaro; Rispin, Karen

2017-01-01

In under-resourced settings where motorized wheelchairs are rarely available, manual wheelchair users with limited upper-body strength and functionalities need to rely on assisting pushers for their mobility. Because traveling surfaces in under-resourced settings are often unpaved and rough, wheelchair pushers could experience high physiological loading. In order to evaluate pushers' physiological loading and to improve wheelchair designs, we built indoor modular units that simulate rough surface conditions, and tested a hypothesis that pushing different wheelchairs would result in different physiological performances and pushers' perception of difficulty on the simulated rough surface. Eighteen healthy subjects pushed two different types of pediatric wheelchairs (Moti-Go manufactured by Motivation, and KidChair by Hope Haven) fitted with a 50-kg dummy on the rough and smooth surfaces at self-selected speeds. Oxygen uptake, traveling distance for 6 minutes, and the rating of difficulty were obtained. The results supported our hypothesis, showing that pushing Moti-Go on the rough surface was physiologically less loading than KidChair, but on the smooth surface, the two wheelchairs did not differ significantly. These results indicate wheelchair designs to improve pushers' performance in under-resourced settings should be evaluated on rough surfaces.

An integrated coronary circulation teaching model.

PubMed

van Oostrom, Johannes H; Kentgens, S; Beneken, J E W; Gravenstein, J S

2006-08-01

We present in this paper a model of the coronary circulation. This model is integrated with a model of the systemic circulation, and contains models for oxygen supply and demand. Three compartments are created: one for the right ventricle, one for the epicardial segment of the left ventricle and one for the endo-cardial segment of the left ventricle. The model was implemented in the Java programming language and contains a visual representation of the left and right ventricles which beat in real time. Color shading is used to represent the partial pressure of oxygen in the segments. A multitude of model parameters can be changed to simulate different scenarios. The output of the model was characterized under different conditions and the results verified by clinicians. Educational models of human physiology can be very useful for a more in depth understanding of complete physiologic systems. The models must however have enough complexity, interaction with other systems, and realism to show the concepts being taught.

Pilot physiology, cognition and flight performance during flight simulation exposed to a 3810-m hypoxic condition.

PubMed

Peacock, Corey A; Weber, Raymond; Sanders, Gabriel J; Seo, Yongsuk; Kean, David; Pollock, Brandon S; Burns, Keith J; Cain, Mark; LaScola, Phillip; Glickman, Ellen L

2017-03-01

Hypoxia is a physiological state defined as a reduction in the distribution of oxygen to the tissues of the body. It has been considered a major factor in aviation safety worldwide because of its potential for pilot disorientation. Pilots are able to operate aircrafts up to 3810 m without the use of supplemental oxygen and may exhibit symptoms associated with hypoxia. To determine the effects of 3810 m on physiology, cognition and performance in pilots during a flight simulation. Ten healthy male pilots engaged in a counterbalanced experimental protocol comparing a 0-m normoxic condition (NORM) with a 3810-m hypoxic condition (HYP) on pilot physiology, cognition and flight performance. Repeated-measures analysis of variance demonstrated a significant (p ≤ 0.05) time by condition interaction for physiological and cognitive alterations during HYP. A paired-samples t test demonstrated no differences in pilot performance (p ≥ 0.05) between conditions. Pilots exhibited physiological and cognitive impairments; however, pilot performance was not affected by HYP.

State-of-the-Art Review on Physiologically Based Pharmacokinetic Modeling in Pediatric Drug Development.

PubMed

Yellepeddi, Venkata; Rower, Joseph; Liu, Xiaoxi; Kumar, Shaun; Rashid, Jahidur; Sherwin, Catherine M T

2018-05-18

Physiologically based pharmacokinetic modeling and simulation is an important tool for predicting the pharmacokinetics, pharmacodynamics, and safety of drugs in pediatrics. Physiologically based pharmacokinetic modeling is applied in pediatric drug development for first-time-in-pediatric dose selection, simulation-based trial design, correlation with target organ toxicities, risk assessment by investigating possible drug-drug interactions, real-time assessment of pharmacokinetic-safety relationships, and assessment of non-systemic biodistribution targets. This review summarizes the details of a physiologically based pharmacokinetic modeling approach in pediatric drug research, emphasizing reports on pediatric physiologically based pharmacokinetic models of individual drugs. We also compare and contrast the strategies employed by various researchers in pediatric physiologically based pharmacokinetic modeling and provide a comprehensive overview of physiologically based pharmacokinetic modeling strategies and approaches in pediatrics. We discuss the impact of physiologically based pharmacokinetic models on regulatory reviews and product labels in the field of pediatric pharmacotherapy. Additionally, we examine in detail the current limitations and future directions of physiologically based pharmacokinetic modeling in pediatrics with regard to the ability to predict plasma concentrations and pharmacokinetic parameters. Despite the skepticism and concern in the pediatric community about the reliability of physiologically based pharmacokinetic models, there is substantial evidence that pediatric physiologically based pharmacokinetic models have been used successfully to predict differences in pharmacokinetics between adults and children for several drugs. It is obvious that the use of physiologically based pharmacokinetic modeling to support various stages of pediatric drug development is highly attractive and will rapidly increase, provided the robustness and reliability of these techniques are well established.

Relative contributions of the major human CYP450 to the metabolism of icotinib and its implication in prediction of drug-drug interaction between icotinib and CYP3A4 inhibitors/inducers using physiologically based pharmacokinetic modeling.

PubMed

Chen, Jia; Liu, Dongyang; Zheng, Xin; Zhao, Qian; Jiang, Ji; Hu, Pei

2015-06-01

Icotinib is an anticancer drug, but relative contributions of CYP450 have not been identified. This study was carried out to identify the contribution percentage of CYP450 to icotinib and use the results to develop a physiologically based pharmacokinetic (PBPK) model, which can help to predict drug-drug interaction (DDI). Human liver microsome (HLM) and supersome using relative activity factor (RAF) were employed to determine the relative contributions of the major human P450 to the net hepatic metabolism of icotinib. These values were introduced to develop a PBPK model using SimCYP. The model was validated by the observed data in a Phase I clinical trial in Chinese healthy subjects. Finally, the model was used to simulate the DDI with ketoconazole or rifampin. Final contribution of CYP450 isoforms determined by HLM showed that CYP3A4 provided major contributions to the metabolism of icotinib. The percentage contributions of the P450 to the net hepatic metabolism of icotinib were determined by HLM inhibition assay and RAF. The AUC ratio under concomitant use of ketoconazole and rifampin was 3.22 and 0.55, respectively. Percentage of contribution of CYP450 to icotinib metabolism was calculated by RAF. The model has been proven to fit the observed data and is used in predicting icotinib-ketoconazole/rifampin interaction.

A mathematical approach to HIV infection dynamics

NASA Astrophysics Data System (ADS)

Ida, A.; Oharu, S.; Oharu, Y.

2007-07-01

In order to obtain a comprehensive form of mathematical models describing nonlinear phenomena such as HIV infection process and AIDS disease progression, it is efficient to introduce a general class of time-dependent evolution equations in such a way that the associated nonlinear operator is decomposed into the sum of a differential operator and a perturbation which is nonlinear in general and also satisfies no global continuity condition. An attempt is then made to combine the implicit approach (usually adapted for convective diffusion operators) and explicit approach (more suited to treat continuous-type operators representing various physiological interactions), resulting in a semi-implicit product formula. Decomposing the operators in this way and considering their individual properties, it is seen that approximation-solvability of the original model is verified under suitable conditions. Once appropriate terms are formulated to describe treatment by antiretroviral therapy, the time-dependence of the reaction terms appears, and such product formula is useful for generating approximate numerical solutions to the governing equations. With this knowledge, a continuous model for HIV disease progression is formulated and physiological interpretations are provided. The abstract theory is then applied to show existence of unique solutions to the continuous model describing the behavior of the HIV virus in the human body and its reaction to treatment by antiretroviral therapy. The product formula suggests appropriate discrete models describing the dynamics of host pathogen interactions with HIV1 and is applied to perform numerical simulations based on the model of the HIV infection process and disease progression. Finally, the results of our numerical simulations are visualized and it is observed that our results agree with medical and physiological aspects.

Annual National Teachers Workshop on ’Human Biology’ Held in San Jose, California on 7-13 November 1995.

DTIC Science & Technology

1994-11-01

Conference teacher program were to enable participating teachers to: (1) understand basic human anatomy and physiology content. (2) understand appropriate...teaching methodology for American Indian students. (3) engage in classroom activities that focus on human anatomy and physiology which can be transferred and applied to their own classrooms.

Visual motor response of crewmen during a simulated 90 day space mission as measured by the critical task battery

NASA Technical Reports Server (NTRS)

Allen, R. W.; Jex, H. R.

1972-01-01

In order to test various components of a regenerative life support system and to obtain data on the physiological and psychological effects of long-duration exposure to confinement in a space station atmosphere, four carefully screened young men were sealed in space station simulator for 90 days. A tracking test battery was administered during the above experiment. The battery included a clinical test (critical instability task) related to the subject's dynamic time delay, and a conventional steady tracking task, during which dynamic response (describing functions) and performance measures were obtained. Good correlation was noted between the clinical critical instability scores and more detailed tracking parameters such as dynamic time delay and gain-crossover frequency. The comprehensive data base on human operator tracking behavior obtained in this study demonstrate that sophisticated visual-motor response properties can be efficiently and reliably measured over extended periods of time.

Cardiovascular correlates of emotional state, cognitive workload and time-on-task effect during a realistic flight simulation.

PubMed

Hidalgo-Muñoz, Antonio R; Mouratille, Damien; Matton, Nadine; Causse, Mickaël; Rouillard, Yves; El-Yagoubi, Radouane

2018-04-05

In aviation, emotion and cognitive workload can considerably increase the probability of human error. An accurate online physiological monitoring of pilot's mental state could prevent accidents. The heart rate (HR) and heart rate variability (HRV) of 21 private pilots were analysed during two realistic flight simulator scenarios. Emotion was manipulated by a social stressor and cognitive workload with the difficulty of a secondary task. Our results confirmed the sensitivity of the HR to cognitive demand and training effects, with increased HR when the task was more difficult and decreased HR with training (time-on-task). Training was also associated with an increased HRV, with increased values along the flight scenario time course. Finally, the social stressor seemed to provoke an emotional reaction that enhanced motivation and performance on the secondary task. However, this was not reflected by the cardiovascular activity. Copyright © 2018 Elsevier B.V. All rights reserved.

Disuse of the musculo-skeletal system in space and on earth.

PubMed

Narici, M V; de Boer, M D

2011-03-01

Muscle mass and strength are well known to decline in response to actual and simulated microgravity exposure. However, despite the considerable knowledge gained on the physiological changes induced by spaceflight, the mechanisms of muscle atrophy and the effectiveness of in-flight countermeasures still need to be fully elucidated. The present review examines the effects and mechanisms of actual and simulated microgravity on single fibre and whole muscle structural and functional properties, protein metabolism, tendon mechanical properties, neural drive and reflex excitability. The effects of inflight countermeasures are also discussed in the light of recent advances in resistive loading techniques, in combined physical, pharmacological and nutritional interventions as well as in the development of artificial gravity systems. Emphasis has been given to the pioneering work of Pietro Enrico di Prampero in the development of artificial gravity systems and in the progress of knowledge on the limits of human muscular performance in space.

An Integrated Analysis of the Physiological Effects of Space Flight: Executive Summary

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1985-01-01

A large array of models were applied in a unified manner to solve problems in space flight physiology. Mathematical simulation was used as an alternative way of looking at physiological systems and maximizing the yield from previous space flight experiments. A medical data analysis system was created which consist of an automated data base, a computerized biostatistical and data analysis system, and a set of simulation models of physiological systems. Five basic models were employed: (1) a pulsatile cardiovascular model; (2) a respiratory model; (3) a thermoregulatory model; (4) a circulatory, fluid, and electrolyte balance model; and (5) an erythropoiesis regulatory model. Algorithms were provided to perform routine statistical tests, multivariate analysis, nonlinear regression analysis, and autocorrelation analysis. Special purpose programs were prepared for rank correlation, factor analysis, and the integration of the metabolic balance data.

Determination of torque-limits for human and cat lumbar spine specimens during displacement-controlled physiological motions.

PubMed

Ianuzzi, Allyson; Pickar, Joel G; Khalsa, Partap S

2009-01-01

Quadruped animal models have been validated and used as biomechanical models for the lumbar spine. The biomechanics of the cat lumbar spine has not been well characterized, even though it is a common model used in neuromechanical studies. Compare the physiological ranges of motion and determine torque-limits for cat and human lumbar spine specimens during physiological motions. Biomechanics study. Cat and human lumbar spine specimens. Intervertebral angle (IVA), joint moment, yield point, torque-limit, and correlation coefficients. Cat (L2-sacrum) and human (T12-sacrum) lumbar spine specimens were mechanically tested to failure during displacement-controlled extension (E), lateral bending (LB), and axial rotation (AR). Single trials consisted of 10 cycles (10mm/s or 5 degrees /s) to a target displacement where the magnitude of the target displacement was increased for subsequent trials until failure occurred. Whole-lumbar stiffness, torque at yield point, and joint stiffness were determined. Scaling relationships were established using equations analogous to those that describe the load response of elliptically shaped beams. IVA magnitudes for cat and human lumbar spines were similar during physiological motions. Human whole-lumbar and joint stiffness magnitudes were significantly greater than those for cat spine specimens (p<.05). Torque-limits were also greater for humans compared with cats. Scaling relationships with high correlation (R(2) greater than 0.77) were established during later LB and AR. The current study defined "physiological ranges of movement" for human and cat lumbar spine specimens during displacement-controlled testing, and should be observed in future biomechanical studies conducted under displacement control.

Computational Toxicology of Chloroform: Reverse Dosimetry Using Bayesian Inference, Markov Chain Monte Carlo Simulation, and Human Biomonitoring Data

PubMed Central

Lyons, Michael A.; Yang, Raymond S.H.; Mayeno, Arthur N.; Reisfeld, Brad

2008-01-01

Background One problem of interpreting population-based biomonitoring data is the reconstruction of corresponding external exposure in cases where no such data are available. Objectives We demonstrate the use of a computational framework that integrates physiologically based pharmacokinetic (PBPK) modeling, Bayesian inference, and Markov chain Monte Carlo simulation to obtain a population estimate of environmental chloroform source concentrations consistent with human biomonitoring data. The biomonitoring data consist of chloroform blood concentrations measured as part of the Third National Health and Nutrition Examination Survey (NHANES III), and for which no corresponding exposure data were collected. Methods We used a combined PBPK and shower exposure model to consider several routes and sources of exposure: ingestion of tap water, inhalation of ambient household air, and inhalation and dermal absorption while showering. We determined posterior distributions for chloroform concentration in tap water and ambient household air using U.S. Environmental Protection Agency Total Exposure Assessment Methodology (TEAM) data as prior distributions for the Bayesian analysis. Results Posterior distributions for exposure indicate that 95% of the population represented by the NHANES III data had likely chloroform exposures ≤ 67 μg/L in tap water and ≤ 0.02 μg/L in ambient household air. Conclusions Our results demonstrate the application of computer simulation to aid in the interpretation of human biomonitoring data in the context of the exposure–health evaluation–risk assessment continuum. These results should be considered as a demonstration of the method and can be improved with the addition of more detailed data. PMID:18709138

Simulated night shift work induces circadian misalignment of the human peripheral blood mononuclear cell transcriptome.

PubMed

Kervezee, Laura; Cuesta, Marc; Cermakian, Nicolas; Boivin, Diane B

2018-05-22

Misalignment of the endogenous circadian timing system leads to disruption of physiological rhythms and may contribute to the development of the deleterious health effects associated with night shift work. However, the molecular underpinnings remain to be elucidated. Here, we investigated the effect of a 4-day simulated night shift work protocol on the circadian regulation of the human transcriptome. Repeated blood samples were collected over two 24-hour measurement periods from eight healthy subjects under highly controlled laboratory conditions before and 4 days after a 10-hour delay of their habitual sleep period. RNA was extracted from peripheral blood mononuclear cells to obtain transcriptomic data. Cosinor analysis revealed a marked reduction of significantly rhythmic transcripts in the night shift condition compared with baseline at group and individual levels. Subsequent analysis using a mixed-effects model selection approach indicated that this decrease is mainly due to dampened rhythms rather than to a complete loss of rhythmicity: 73% of transcripts rhythmically expressed at baseline remained rhythmic during the night shift condition with a similar phase relative to habitual bedtimes, but with lower amplitudes. Functional analysis revealed that key biological processes are affected by the night shift protocol, most notably the natural killer cell-mediated immune response and Jun/AP1 and STAT pathways. These results show that 4 days of simulated night shifts leads to a loss in temporal coordination between the human circadian transcriptome and the external environment and impacts biological processes related to the adverse health effects associated to night shift work.

Twelfth Annual Conference on Manual Control

NASA Technical Reports Server (NTRS)

Wempe, T. E.

1976-01-01

Main topics discussed cover multi-task decision making, attention allocation and workload measurement, displays and controls, nonvisual displays, tracking and other psychomotor tasks, automobile driving, handling qualities and pilot ratings, remote manipulation, system identification, control models, and motion and visual cues. Sixty-five papers are included with presentations on results of analytical studies to develop and evaluate human operator models for a range of control task, vehicle dynamics and display situations; results of tests of physiological control systems and applications to medical problems; and on results of simulator and flight tests to determine display, control and dynamics effects on operator performance and workload for aircraft, automobile, and remote control systems.

Aerospace Medicine and Biology: A Continuing Bibliography With Indexes. Supplement 497

NASA Technical Reports Server (NTRS)

2000-01-01

This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP#2000-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention.

Research in human performance related to space: A compilation of three projects/proposals

NASA Technical Reports Server (NTRS)

Hasson, Scott M.

1989-01-01

Scientific projects were developed in order to maximize performance in space and assure physiological homeostatis upon return. Three projects that are related to this common goal were either initiated or formulated during the Faculty Fellowship Summer Program. The projects were entitled: (1) Effect of simulated weightlessness (bed rest) on muscle performance and morphology; (2) Effect of submaximal eccentric muscle contractions on muscle injury, soreness and performance: A grant proposal; and (3) Correlation between isolated joint dynamic muscle strength to end-effector strength of the push and pull extravehicular activity (EVA) ratchet maneuver. The purpose is to describe each of these studies in greater detail.

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 366)

NASA Technical Reports Server (NTRS)

1992-01-01

This bibliography lists 248 reports, articles, and other documents introduced into the NASA Scientific and Technical Information System during Aug. 1992. Subject coverage concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 492

NASA Technical Reports Server (NTRS)

1999-01-01

This report lists reports, articles and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

The Atlas of Physiology and Pathophysiology: Web-based multimedia enabled interactive simulations.

PubMed

Kofranek, Jiri; Matousek, Stanislav; Rusz, Jan; Stodulka, Petr; Privitzer, Pavol; Matejak, Marek; Tribula, Martin

2011-11-01

The paper is a presentation of the current state of development for the Atlas of Physiology and Pathophysiology (Atlas). Our main aim is to provide a novel interactive multimedia application that can be used for biomedical education where (a) simulations are combined with tutorials and (b) the presentation layer is simplified while the underlying complexity of the model is retained. The development of the Atlas required the cooperation of many professionals including teachers, system analysts, artists, and programmers. During the design of the Atlas, tools were developed that allow for component-based creation of simulation models, creation of interactive multimedia and their final coordination into a compact unit based on the given design. The Atlas is a freely available online application, which can help to explain the function of individual physiological systems and the causes and symptoms of their disorders. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

A Simulated Heat Wave Has Diverse Effects on Immune Function and Oxidative Physiology in the Corn Snake (Pantherophis guttatus).

PubMed

Stahlschmidt, Z R; French, S S; Ahn, A; Webb, A; Butler, M W

Animals will continue to encounter increasingly warm environments, including more frequent and intense heat waves. Yet the physiological consequences of heat waves remain equivocal, potentially because of variation in adaptive plasticity (reversible acclimation) and/or aspects of experimental design. Thus, we measured a suite of physiological variables in the corn snake (Pantherophis guttatus) after exposure to field-parameterized, fluctuating temperature regimes (moderate temperature and heat wave treatments) to address two hypotheses: (1) a heat wave causes physiological stress, and (2) thermal performance of immune function exhibits adaptive plasticity in response to a heat wave. We found little support for our first hypothesis because a simulated heat wave had a negative effect on body mass, but it also reduced oxidative damage and did not affect peak performance of three immune metrics. Likewise, we found only partial support for our second hypothesis. After exposure to a simulated heat wave, P. guttatus exhibited greater performance breadth and reduced temperature specialization (the standardized difference between peak performance and performance breadth) for only one of three immune metrics and did so in a sex-dependent manner. Further, a simulated heat wave did not elicit greater performance of any immune metric at higher temperatures. Yet a heat wave likely reduced innate immune function in P. guttatus because each metric of innate immune performance in this species (as in most vertebrates) was lower at elevated temperatures. Together with previous research, our study indicates that a heat wave may have complex, modest, and even positive physiological effects in some taxa.

Physiological responses and match characteristics in professional tennis players during a one-hour simulated tennis match

PubMed Central

Şenel, Ömer; Arslan, Erşan; Can, Sema

2016-01-01

Abstract The purpose of this study was to investigate the effects of serve and return game situations on physiological responses and match characteristics in professional male tennis players during one hour-long simulated singles tennis matches. Ten internationally ranked tennis players (age 22.2 ± 2.8 years; body height 180.7 ± 4.4 cm; body mass 75.9 ± 8.9 kg) participated in this study. Their physiological responses were measured using two portable analyzers during indoor hard court matches. Ratings of perceived exertion were also determined at the end of the game. The variables describing the characteristics of the matches determined from video recordings were: (a) duration of rallies; (b) rest time; (c) work-to-rest ratio; (d) effective playing time; and (d) strokes per rally. Significant differences (p<0.05) were found between serving and returning conditions in an hour-long simulated singles tennis match in terms of oxygen uptake, a heart rate, ratings of perceived exertion, pulmonary ventilation, respiration frequency and a respiratory gas exchange ratio. In addition, both the heart rate and ratings of perceived exertion responses were moderately correlated with the duration of rallies and strokes per rally (r = 0.60 to 0.26; p<0.05). Taken together, these results indicate that the serve game situation has a significant effect on the physiological response in an hour-long simulated tennis match between professional male tennis players. These findings might be used for the physiological adaptations required for tennis-specific aerobic endurance. PMID:28149371

The Directed Case Method.

ERIC Educational Resources Information Center

Cliff, William H.; Curtin, Leslie Nesbitt

2000-01-01

Provides an example of a directed case on human anatomy and physiology. Uses brief real life newspaper articles and clinical descriptions of medical reference texts to describe an actual, fictitious, or composite event. Includes interrelated human anatomy and physiology topics in the scenario. (YDS)

An investigation of thermal comfort inside an automobile during the heating period.

PubMed

Kaynakli, Omer; Kilic, Muhsin

2005-05-01

This paper describes a combined theoretical and experimental study of thermal comfort during the heating period inside an automobile. To investigate the effects of thermal conditions on the human physiology and thermal comfort during the heating period, temperature, humidity and air velocity were measured at a number of points inside the automobile, so thermal conditions were accurately determined. The human body was divided into 16 sedentary segments, and the change of temperature was observed both experimentally and theoretically. During transient conditions of the heating period, heat and mass transfer between the human body and the interior environment of an automobile were simulated by a computational model, and predictions were compared with the measured data. It is shown that there is a good agreement between the model predictions and experimental results. By means of the present model, the effects of the fast transient conditions of the heating period on the sensible and latent heat transfer from the body, body segments skin temperatures and thermal sensation were investigated in detail.

Toxicokinetic Model Development for the Insensitive Munitions Component 2,4-Dinitroanisole.

PubMed

Sweeney, Lisa M; Goodwin, Michelle R; Hulgan, Angela D; Gut, Chester P; Bannon, Desmond I

2015-01-01

The Armed Forces are developing new explosives that are less susceptible to unintentional detonation (insensitive munitions [IMX]). 2,4-Dinitroanisole (DNAN) is a component of IMX. Toxicokinetic data for DNAN are required to support interpretation of toxicology studies and refinement of dose estimates for human risk assessment. Male Sprague-Dawley rats were dosed by gavage (5, 20, or 80 mg DNAN/kg), and blood and tissue samples were analyzed to determine the levels of DNAN and its metabolite 2,4-dinitrophenol (DNP). These data and data from the literature were used to develop preliminary physiologically based pharmacokinetic (PBPK) models. The model simulations indicated saturable metabolism of DNAN in rats at higher tested doses. The PBPK model was extrapolated to estimate the toxicokinetics of DNAN and DNP in humans, allowing the estimation of human-equivalent no-effect levels of DNAN exposure from no-observed adverse effect levels determined in laboratory animals, which may guide the selection of exposure limits for DNAN. © The Author(s) 2015.

Limitations to Thermoregulation and Acclimatization Challenge Human Adaptation to Global Warming

PubMed Central

Hanna, Elizabeth G.; Tait, Peter W.

2015-01-01

Human thermoregulation and acclimatization are core components of the human coping mechanism for withstanding variations in environmental heat exposure. Amidst growing recognition that curtailing global warming to less than two degrees is becoming increasing improbable, human survival will require increasing reliance on these mechanisms. The projected several fold increase in extreme heat events suggests we need to recalibrate health protection policies and ratchet up adaptation efforts. Climate researchers, epidemiologists, and policy makers engaged in climate change adaptation and health protection are not commonly drawn from heat physiology backgrounds. Injecting a scholarly consideration of physiological limitations to human heat tolerance into the adaptation and policy literature allows for a broader understanding of heat health risks to support effective human adaptation and adaptation planning. This paper details the physiological and external environmental factors that determine human thermoregulation and acclimatization. We present a model to illustrate the interrelationship between elements that modulate the physiological process of thermoregulation. Limitations inherent in these processes, and the constraints imposed by differing exposure levels, and thermal comfort seeking on achieving acclimatization, are then described. Combined, these limitations will restrict the likely contribution that acclimatization can play in future human adaptation to global warming. We postulate that behavioral and technological adaptations will need to become the dominant means for human individual and societal adaptations as global warming progresses. PMID:26184272

Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part I: Theory and model validation.

PubMed

Kolanjiyil, Arun V; Kleinstreuer, Clement

2016-12-01

Computational predictions of aerosol transport and deposition in the human respiratory tract can assist in evaluating detrimental or therapeutic health effects when inhaling toxic particles or administering drugs. However, the sheer complexity of the human lung, featuring a total of 16 million tubular airways, prohibits detailed computer simulations of the fluid-particle dynamics for the entire respiratory system. Thus, in order to obtain useful and efficient particle deposition results, an alternative modeling approach is necessary where the whole-lung geometry is approximated and physiological boundary conditions are implemented to simulate breathing. In Part I, the present new whole-lung-airway model (WLAM) represents the actual lung geometry via a basic 3-D mouth-to-trachea configuration while all subsequent airways are lumped together, i.e., reduced to an exponentially expanding 1-D conduit. The diameter for each generation of the 1-D extension can be obtained on a subject-specific basis from the calculated total volume which represents each generation of the individual. The alveolar volume was added based on the approximate number of alveoli per generation. A wall-displacement boundary condition was applied at the bottom surface of the first-generation WLAM, so that any breathing pattern due to the negative alveolar pressure can be reproduced. Specifically, different inhalation/exhalation scenarios (rest, exercise, etc.) were implemented by controlling the wall/mesh displacements to simulate realistic breathing cycles in the WLAM. Total and regional particle deposition results agree with experimental lung deposition results. The outcomes provide critical insight to and quantitative results of aerosol deposition in human whole-lung airways with modest computational resources. Hence, the WLAM can be used in analyzing human exposure to toxic particulate matter or it can assist in estimating pharmacological effects of administered drug-aerosols. As a practical WLAM application, the transport and deposition of asthma drugs from a commercial dry-powder inhaler is discussed in Part II. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enzymatic Oxidation of Cholesterol: Properties and Functional Effects of Cholestenone in Cell Membranes

PubMed Central

Neuvonen, Maarit; Manna, Moutusi; Mokkila, Sini; Javanainen, Matti; Rog, Tomasz; Liu, Zheng; Bittman, Robert; Vattulainen, Ilpo; Ikonen, Elina

2014-01-01

Bacterial cholesterol oxidase is commonly used as an experimental tool to reduce cellular cholesterol content. That the treatment also generates the poorly degradable metabolite 4-cholesten-3-one (cholestenone) has received less attention. Here, we investigated the membrane partitioning of cholestenone using simulations and cell biological experiments and assessed the functional effects of cholestenone in human cells. Atomistic simulations predicted that cholestenone reduces membrane order, undergoes faster flip-flop and desorbs more readily from membranes than cholesterol. In primary human fibroblasts, cholestenone was released from membranes to physiological extracellular acceptors more avidly than cholesterol, but without acceptors it remained in cells over a day. To address the functional effects of cholestenone, we studied fibroblast migration during wound healing. When cells were either cholesterol oxidase treated or part of cellular cholesterol was exchanged for cholestenone with cyclodextrin, cell migration during 22 h was markedly inhibited. Instead, when a similar fraction of cholesterol was removed using cyclodextrin, cells replenished their cholesterol content in 3 h and migrated similarly to control cells. Thus, cholesterol oxidation produces long-term functional effects in cells and these are in part due to the generated membrane active cholestenone. PMID:25157633

Assessing very high resolution UAV imagery for monitoring forest health during a simulated disease outbreak

NASA Astrophysics Data System (ADS)

Dash, Jonathan P.; Watt, Michael S.; Pearse, Grant D.; Heaphy, Marie; Dungey, Heidi S.

2017-09-01

Research into remote sensing tools for monitoring physiological stress caused by biotic and abiotic factors is critical for maintaining healthy and highly-productive plantation forests. Significant research has focussed on assessing forest health using remotely sensed data from satellites and manned aircraft. Unmanned aerial vehicles (UAVs) may provide new tools for improved forest health monitoring by providing data with very high temporal and spatial resolutions. These platforms also pose unique challenges and methods for health assessments must be validated before use. In this research, we simulated a disease outbreak in mature Pinus radiata D. Don trees using targeted application of herbicide. The objective was to acquire a time-series simulated disease expression dataset to develop methods for monitoring physiological stress from a UAV platform. Time-series multi-spectral imagery was acquired using a UAV flown over a trial at regular intervals. Traditional field-based health assessments of crown health (density) and needle health (discolouration) were carried out simultaneously by experienced forest health experts. Our results showed that multi-spectral imagery collected from a UAV is useful for identifying physiological stress in mature plantation trees even during the early stages of tree stress. We found that physiological stress could be detected earliest in data from the red edge and near infra-red bands. In contrast to previous findings, red edge data did not offer earlier detection of physiological stress than the near infra-red data. A non-parametric approach was used to model physiological stress based on spectral indices and was found to provide good classification accuracy (weighted kappa = 0.694). This model can be used to map physiological stress based on high-resolution multi-spectral data.

It's Difficult to Change the Way We Teach: Lessons from the Integrative Themes in Physiology Curriculum Module Project

ERIC Educational Resources Information Center

Silverthorn, Dee U.; Thorn, Patti M.; Svinicki, Marilla D.

2006-01-01

The Integrative Themes in Physiology (ITIP) project was a National Science Foundation-funded collaboration between the American Physiological Society (APS) and the Human Anatomy and Physiology Society (HAPS). The project goal was to create instructional resources that emphasized active learning in undergraduate anatomy and physiology classrooms.…

JPRS Report Science & Technology USSR: Life Sciences.

DTIC Science & Technology

1988-06-10

V.F. Shilina; GIGIYENA ISANITARIYA No 10, Oct 87] 14 PHYSIOLOGY Changes in Cerebral Electrical Activity of Cats After Intravenous and...from human fibrosarcoma , was studied and compared to expression in normal human leukocytes and slightly transformed cells from human melanoma line...06508 JPRS-ULS-88-009 10 June 1988 PHYSIOLOGY 15 Changes in Cerebral Electrical Activity of Cats After Intravenous and Cerebroventricular

Review of the physiology of human thermal comfort while exercising in urban landscapes and implications for bioclimatic design.

PubMed

Vanos, Jennifer K; Warland, Jon S; Gillespie, Terry J; Kenny, Natasha A

2010-07-01

This review comprehensively examines scientific literature pertaining to human physiology during exercise, including mechanisms of heat formation and dissipation, heat stress on the body, the importance of skin temperature monitoring, the effects of clothing, and microclimatic measurements. This provides a critical foundation for microclimatologists and biometeorologists in the understanding of experiments involving human physiology. The importance of the psychological aspects of how an individual perceives an outdoor environment are also reviewed, emphasizing many factors that can indirectly affect thermal comfort (TC). Past and current efforts to develop accurate human comfort models are described, as well as how these models can be used to develop resilient and comfortable outdoor spaces for physical activity. Lack of suitable spaces plays a large role in the deterioration of human health due to physical inactivity, leading to higher rates of illness, heart disease, obesity and heat-related casualties. This trend will continue if urban designers do not make use of current knowledge of bioclimatic urban design, which must be synthesized with physiology, psychology and microclimatology. Increased research is required for furthering our knowledge on the outdoor human energy balance concept and bioclimatic design for health and well-being in urban areas.

Review of the physiology of human thermal comfort while exercising in urban landscapes and implications for bioclimatic design

NASA Astrophysics Data System (ADS)

Vanos, Jennifer K.; Warland, Jon S.; Gillespie, Terry J.; Kenny, Natasha A.

2010-07-01

This review comprehensively examines scientific literature pertaining to human physiology during exercise, including mechanisms of heat formation and dissipation, heat stress on the body, the importance of skin temperature monitoring, the effects of clothing, and microclimatic measurements. This provides a critical foundation for microclimatologists and biometeorologists in the understanding of experiments involving human physiology. The importance of the psychological aspects of how an individual perceives an outdoor environment are also reviewed, emphasizing many factors that can indirectly affect thermal comfort (TC). Past and current efforts to develop accurate human comfort models are described, as well as how these models can be used to develop resilient and comfortable outdoor spaces for physical activity. Lack of suitable spaces plays a large role in the deterioration of human health due to physical inactivity, leading to higher rates of illness, heart disease, obesity and heat-related casualties. This trend will continue if urban designers do not make use of current knowledge of bioclimatic urban design, which must be synthesized with physiology, psychology and microclimatology. Increased research is required for furthering our knowledge on the outdoor human energy balance concept and bioclimatic design for health and well-being in urban areas.

A novel medical image data-based multi-physics simulation platform for computational life sciences.

PubMed

Neufeld, Esra; Szczerba, Dominik; Chavannes, Nicolas; Kuster, Niels

2013-04-06

Simulating and modelling complex biological systems in computational life sciences requires specialized software tools that can perform medical image data-based modelling, jointly visualize the data and computational results, and handle large, complex, realistic and often noisy anatomical models. The required novel solvers must provide the power to model the physics, biology and physiology of living tissue within the full complexity of the human anatomy (e.g. neuronal activity, perfusion and ultrasound propagation). A multi-physics simulation platform satisfying these requirements has been developed for applications including device development and optimization, safety assessment, basic research, and treatment planning. This simulation platform consists of detailed, parametrized anatomical models, a segmentation and meshing tool, a wide range of solvers and optimizers, a framework for the rapid development of specialized and parallelized finite element method solvers, a visualization toolkit-based visualization engine, a Python scripting interface for customized applications, a coupling framework, and more. Core components are cross-platform compatible and use open formats. Several examples of applications are presented: hyperthermia cancer treatment planning, tumour growth modelling, evaluating the magneto-haemodynamic effect as a biomarker and physics-based morphing of anatomical models.

Mechanical properties of a collagen fibril under simulated degradation.

PubMed

Malaspina, David C; Szleifer, Igal; Dhaher, Yasin

2017-11-01

Collagen fibrils are a very important component in most of the connective tissue in humans. An important process associated with several physiological and pathological states is the degradation of collagen. Collagen degradation is usually mediated by enzymatic and non-enzymatic processes. In this work we use molecular dynamics simulations to study the influence of simulated degradation on the mechanical properties of the collagen fibril. We applied tensile stress to the collagen fiber at different stages of degradation. We compared the difference in the fibril mechanical priorities due the removal of enzymatic crosslink, surface degradation and volumetric degradation. As anticipated, our results indicated that, regardless of the degradation scenario, fibril mechanical properties is reduced. The type of degradation mechanism (crosslink, surface or volumetric) expressed differential effect on the change in the fibril stiffness. Our simulation results showed dramatic change in the fibril stiffness with a small amount of degradation. This suggests that the hierarchical structure of the fibril is a key component for the toughness and is very sensitive to changes in the organization of the fibril. The overall results are intended to provide a theoretical framework for the understanding the mechanical behavior of collagen fibrils under degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Physiology of man and animals in the Tenth Five-Year Plan: Proceedings of the Thirteenth Congress of the I. P. Pavlov All-Union Physiological Society

NASA Technical Reports Server (NTRS)

Lange, K. A.

1980-01-01

Research in the field of animal and human physiology is reviewed. The following topics on problems of physiological science and related fields of knowledge are discussed: neurophysiology and higher nervous activity, physiology of sensory systems, physiology of visceral systems, evolutionary and ecological physiology, physiological cybernetics, computer application in physiology, information support of physiological research, history and theory of development of physiology. Also discussed were: artificial intelligence, physiological problems of reflex therapy, correlation of structure and function of the brain, adaptation and activity, microcirculation, and physiological studies in nerve and mental diseases.

Most suitable mother wavelet for the analysis of fractal properties of stride interval time series via the average wavelet coefficient

PubMed Central

Zhang, Zhenwei; VanSwearingen, Jessie; Brach, Jennifer S.; Perera, Subashan

2016-01-01

Human gait is a complex interaction of many nonlinear systems and stride intervals exhibit self-similarity over long time scales that can be modeled as a fractal process. The scaling exponent represents the fractal degree and can be interpreted as a biomarker of relative diseases. The previous study showed that the average wavelet method provides the most accurate results to estimate this scaling exponent when applied to stride interval time series. The purpose of this paper is to determine the most suitable mother wavelet for the average wavelet method. This paper presents a comparative numerical analysis of sixteen mother wavelets using simulated and real fractal signals. Simulated fractal signals were generated under varying signal lengths and scaling exponents that indicate a range of physiologically conceivable fractal signals. The five candidates were chosen due to their good performance on the mean square error test for both short and long signals. Next, we comparatively analyzed these five mother wavelets for physiologically relevant stride time series lengths. Our analysis showed that the symlet 2 mother wavelet provides a low mean square error and low variance for long time intervals and relatively low errors for short signal lengths. It can be considered as the most suitable mother function without the burden of considering the signal length. PMID:27960102

Predicting bifurcation angle effect on blood flow in the microvasculature.

PubMed

Yang, Jiho; Pak, Y Eugene; Lee, Tae-Rin

2016-11-01

Since blood viscosity is a basic parameter for understanding hemodynamics in human physiology, great amount of research has been done in order to accurately predict this highly non-Newtonian flow property. However, previous works lacked in consideration of hemodynamic changes induced by heterogeneous vessel networks. In this paper, the effect of bifurcation on hemodynamics in a microvasculature is quantitatively predicted. The flow resistance in a single bifurcation microvessel was calculated by combining a new simple mathematical model with 3-dimensional flow simulation for varying bifurcation angles under physiological flow conditions. Interestingly, the results indicate that flow resistance induced by vessel bifurcation holds a constant value of approximately 0.44 over the whole single bifurcation model below diameter of 60μm regardless of geometric parameters including bifurcation angle. Flow solutions computed from this new model showed substantial decrement in flow velocity relative to other mathematical models, which do not include vessel bifurcation effects, while pressure remained the same. Furthermore, when applying the bifurcation angle effect to the entire microvascular network, the simulation results gave better agreements with recent in vivo experimental measurements. This finding suggests a new paradigm in microvascular blood flow properties, that vessel bifurcation itself, regardless of its angle, holds considerable influence on blood viscosity, and this phenomenon will help to develop new predictive tools in microvascular research. Copyright © 2016 Elsevier Inc. All rights reserved.

High Spatial Resolution Multi-Organ Finite Element Modeling of Ventricular-Arterial Coupling

PubMed Central

Shavik, Sheikh Mohammad; Jiang, Zhenxiang; Baek, Seungik; Lee, Lik Chuan

2018-01-01

While it has long been recognized that bi-directional interaction between the heart and the vasculature plays a critical role in the proper functioning of the cardiovascular system, a comprehensive study of this interaction has largely been hampered by a lack of modeling framework capable of simultaneously accommodating high-resolution models of the heart and vasculature. Here, we address this issue and present a computational modeling framework that couples finite element (FE) models of the left ventricle (LV) and aorta to elucidate ventricular—arterial coupling in the systemic circulation. We show in a baseline simulation that the framework predictions of (1) LV pressure—volume loop, (2) aorta pressure—diameter relationship, (3) pressure—waveforms of the aorta, LV, and left atrium (LA) over the cardiac cycle are consistent with the physiological measurements found in healthy human. To develop insights of ventricular-arterial interactions, the framework was then used to simulate how alterations in the geometrical or, material parameter(s) of the aorta affect the LV and vice versa. We show that changing the geometry and microstructure of the aorta model in the framework led to changes in the functional behaviors of both LV and aorta that are consistent with experimental observations. On the other hand, changing contractility and passive stiffness of the LV model in the framework also produced changes in both the LV and aorta functional behaviors that are consistent with physiology principles. PMID:29551977

Impact of human emotions on physiological characteristics

NASA Astrophysics Data System (ADS)

Partila, P.; Voznak, M.; Peterek, T.; Penhaker, M.; Novak, V.; Tovarek, J.; Mehic, Miralem; Vojtech, L.

2014-05-01

Emotional states of humans and their impact on physiological and neurological characteristics are discussed in this paper. This problem is the goal of many teams who have dealt with this topic. Nowadays, it is necessary to increase the accuracy of methods for obtaining information about correlations between emotional state and physiological changes. To be able to record these changes, we focused on two majority emotional states. Studied subjects were psychologically stimulated to neutral - calm and then to the stress state. Electrocardiography, Electroencephalography and blood pressure represented neurological and physiological samples that were collected during patient's stimulated conditions. Speech activity was recording during the patient was reading selected text. Feature extraction was calculated by speech processing operations. Classifier based on Gaussian Mixture Model was trained and tested using Mel-Frequency Cepstral Coefficients extracted from the patient's speech. All measurements were performed in a chamber with electromagnetic compatibility. The article discusses a method for determining the influence of stress emotional state on the human and his physiological and neurological changes.

A Computational Model of Liver Iron Metabolism

PubMed Central

Mitchell, Simon; Mendes, Pedro

2013-01-01

Iron is essential for all known life due to its redox properties; however, these same properties can also lead to its toxicity in overload through the production of reactive oxygen species. Robust systemic and cellular control are required to maintain safe levels of iron, and the liver seems to be where this regulation is mainly located. Iron misregulation is implicated in many diseases, and as our understanding of iron metabolism improves, the list of iron-related disorders grows. Recent developments have resulted in greater knowledge of the fate of iron in the body and have led to a detailed map of its metabolism; however, a quantitative understanding at the systems level of how its components interact to produce tight regulation remains elusive. A mechanistic computational model of human liver iron metabolism, which includes the core regulatory components, is presented here. It was constructed based on known mechanisms of regulation and on their kinetic properties, obtained from several publications. The model was then quantitatively validated by comparing its results with previously published physiological data, and it is able to reproduce multiple experimental findings. A time course simulation following an oral dose of iron was compared to a clinical time course study and the simulation was found to recreate the dynamics and time scale of the systems response to iron challenge. A disease state simulation of haemochromatosis was created by altering a single reaction parameter that mimics a human haemochromatosis gene (HFE) mutation. The simulation provides a quantitative understanding of the liver iron overload that arises in this disease. This model supports and supplements understanding of the role of the liver as an iron sensor and provides a framework for further modelling, including simulations to identify valuable drug targets and design of experiments to improve further our knowledge of this system. PMID:24244122

Recovering fNIRS brain signals: physiological interference suppression with independent component analysis

NASA Astrophysics Data System (ADS)

Zhang, Y.; Shi, M.; Sun, J.; Yang, C.; Zhang, Yajuan; Scopesi, F.; Makobore, P.; Chin, C.; Serra, G.; Wickramasinghe, Y. A. B. D.; Rolfe, P.

2015-02-01

Brain activity can be monitored non-invasively by functional near-infrared spectroscopy (fNIRS), which has several advantages in comparison with other methods, such as flexibility, portability, low cost and fewer physical restrictions. However, in practice fNIRS measurements are often contaminated by physiological interference arising from cardiac contraction, breathing and blood pressure fluctuations, thereby severely limiting the utility of the method. Hence, further improvement is necessary to reduce or eliminate such interference in order that the evoked brain activity information can be extracted reliably from fNIRS data. In the present paper, the multi-distance fNIRS probe configuration has been adopted. The short-distance fNIRS measurement is treated as the virtual channel and the long-distance fNIRS measurement is treated as the measurement channel. Independent component analysis (ICA) is employed for the fNIRS recordings to separate the brain signals and the interference. Least-absolute deviation (LAD) estimator is employed to recover the brain activity signals. We also utilized Monte Carlo simulations based on a five-layer model of the adult human head to evaluate our methodology. The results demonstrate that the ICA algorithm has the potential to separate physiological interference in fNIRS data and the LAD estimator could be a useful criterion to recover the brain activity signals.

3D modeling and characterization of a calorimetric flow rate sensor for sweat rate sensing applications

NASA Astrophysics Data System (ADS)

Iftekhar, Ahmed Tashfin; Ho, Jenny Che-Ting; Mellinger, Axel; Kaya, Tolga

2017-03-01

Sweat-based physiological monitoring has been intensively explored in the last decade with the hopes of developing real-time hydration monitoring devices. Although the content of sweat (electrolytes, lactate, urea, etc.) provides significant information about the physiology, it is also very important to know the rate of sweat at the time of sweat content measurements because the sweat rate is known to alter the concentrations of sweat compounds. We developed a calorimetric based flow rate sensor using PolydimethylSiloxane that is suitable for sweat rate applications. Our simple approach on using temperature-based flow rate detection can easily be adapted to multiple sweat collection and analysis devices. Moreover, we have developed a 3D finite element analysis model of the device using COMSOL Multiphysics™ and verified the flow rate measurements. The experiment investigated flow rate values from 0.3 μl/min up to 2.1 ml/min, which covers the human sweat rate range (0.5 μl/min-10 μl/min). The 3D model simulations and analytical model calculations covered an even wider range in order to understand the main physical mechanisms of the device. With a verified 3D model, different environmental heat conditions could be further studied to shed light on the physiology of the sweat rate.

Optimal back-extrapolation method for estimating plasma volume in humans using the indocyanine green dilution method.

PubMed

Polidori, David; Rowley, Clarence

2014-07-22

The indocyanine green dilution method is one of the methods available to estimate plasma volume, although some researchers have questioned the accuracy of this method. We developed a new, physiologically based mathematical model of indocyanine green kinetics that more accurately represents indocyanine green kinetics during the first few minutes postinjection than what is assumed when using the traditional mono-exponential back-extrapolation method. The mathematical model is used to develop an optimal back-extrapolation method for estimating plasma volume based on simulated indocyanine green kinetics obtained from the physiological model. Results from a clinical study using the indocyanine green dilution method in 36 subjects with type 2 diabetes indicate that the estimated plasma volumes are considerably lower when using the traditional back-extrapolation method than when using the proposed back-extrapolation method (mean (standard deviation) plasma volume = 26.8 (5.4) mL/kg for the traditional method vs 35.1 (7.0) mL/kg for the proposed method). The results obtained using the proposed method are more consistent with previously reported plasma volume values. Based on the more physiological representation of indocyanine green kinetics and greater consistency with previously reported plasma volume values, the new back-extrapolation method is proposed for use when estimating plasma volume using the indocyanine green dilution method.

MioLab, a rat cardiac contractile force simulator: Applications to teaching cardiac cell physiology and biophysics.

PubMed

da Silva, Robson Rodrigues; Bissaco, Marcia Aparecida Silva; Goroso, Daniel Gustavo

2015-12-01

Understanding the basic concepts of physiology and biophysics of cardiac cells can be improved by virtual experiments that illustrate the complex excitation-contraction coupling process in cardiac cells. The aim of this study is to propose a rat cardiac myocyte simulator, with which calcium dynamics in excitation-contraction coupling of an isolated cell can be observed. This model has been used in the course "Mathematical Modeling and Simulation of Biological Systems". In this paper we present the didactic utility of the simulator MioLab(®). The simulator enables virtual experiments that can help studying inhibitors and activators in the sarcoplasmic reticulum sodium-calcium exchanger, thus corroborating a better understanding of the effects of medications, which are used to treat arrhythmias, on these compartments. The graphical interfaces were developed not only to facilitate the use of the simulator, but also to promote a constructive learning on the subject, since there are animations and videos for each stage of the simulation. The effectiveness of the simulator was tested by a group of graduate students. Some examples of simulations were presented in order to describe the overall structure of the simulator. Part of these virtual experiments became an activity for Biomedical Engineering graduate students, who evaluated the simulator based on its didactic quality. As a result, students answered a questionnaire on the usability and functionality of the simulator as a teaching tool. All students performed the proposed activities and classified the simulator as an optimal or good learning tool. In their written questions, students indicated as negative characteristics some problems with visualizing graphs; as positive characteristics, they indicated the simulator's didactic function, especially tutorials and videos on the topic of this study. The results show that the simulator complements the study of the physiology and biophysics of the cardiac cell. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Detection of the human endogenous retrovirus ERV3-encoded Env-protein in human tissues using antibody-based proteomics.

PubMed

Fei, Chen; Atterby, Christina; Edqvist, Per-Henrik; Pontén, Fredrik; Zhang, Wei Wei; Larsson, Erik; Ryan, Frank P

2014-01-01

There is growing evidence to suggest that human endogenous retroviruses (HERVs) have contributed to human evolution, being expressed in development, normal physiology and disease. A key difficulty in the scientific evaluation of this potential viral contribution is the accurate demonstration of virally expressed protein in specific human cells and tissues. In this study, we have adopted the endogenous retrovirus, ERV3, as our test model in developing a reliable high-capacity methodology for the expression of such endogenous retrovirus-coded protein. Two affinity-purified polyclonal antibodies to ERV3 Env-encoded protein were generated to detect the corresponding protein expression pattern in specific human cells, tissues and organs. Sampling included normal tissues from 144 individuals ranging from childhood to old age. This included more than forty different tissues and organs and some 216 different cancer tissues representing the twenty commonest forms of human cancer. The Rudbeck Laboratory, Uppsala University and Uppsala University Hospital, Uppsala, Sweden. The potential expression at likely physiological level of the ERV3Env encoded protein in a wide range of human cells, tissues and organs. We found that ERV3 encoded Env protein is expressed at substantive levels in placenta, testis, adrenal gland, corpus luteum, Fallopian tubes, sebaceous glands, astrocytes, bronchial epithelium and the ducts of the salivary glands. Substantive expression was also seen in a variety of epithelial cells as well as cells known to undergo fusion in inflammation and in normal physiology, including fused macrophages, myocardium and striated muscle. This contrasted strongly with the low levels expressed in other tissues types. These findings suggest that this virus plays a significant role in human physiology and may also play a possible role in disease. This technique can now be extended to the study of other HERV genomes within the human chromosomes that may have contributed to human evolution, physiology and disease.

Human urine and plasma concentrations of bisphenol A extrapolated from pharmacokinetics established in in vivo experiments with chimeric mice with humanized liver and semi-physiological pharmacokinetic modeling.

PubMed

Miyaguchi, Takamori; Suemizu, Hiroshi; Shimizu, Makiko; Shida, Satomi; Nishiyama, Sayako; Takano, Ryohji; Murayama, Norie; Yamazaki, Hiroshi

2015-06-01

The aim of this study was to extrapolate to humans the pharmacokinetics of estrogen analog bisphenol A determined in chimeric mice transplanted with human hepatocytes. Higher plasma concentrations and urinary excretions of bisphenol A glucuronide (a primary metabolite of bisphenol A) were observed in chimeric mice than in control mice after oral administrations, presumably because of enterohepatic circulation of bisphenol A glucuronide in control mice. Bisphenol A glucuronidation was faster in mouse liver microsomes than in human liver microsomes. These findings suggest a predominantly urinary excretion route of bisphenol A glucuronide in chimeric mice with humanized liver. Reported human plasma and urine data for bisphenol A glucuronide after single oral administration of 0.1mg/kg bisphenol A were reasonably estimated using the current semi-physiological pharmacokinetic model extrapolated from humanized mice data using algometric scaling. The reported geometric mean urinary bisphenol A concentration in the U.S. population of 2.64μg/L underwent reverse dosimetry modeling with the current human semi-physiological pharmacokinetic model. This yielded an estimated exposure of 0.024μg/kg/day, which was less than the daily tolerable intake of bisphenol A (50μg/kg/day), implying little risk to humans. Semi-physiological pharmacokinetic modeling will likely prove useful for determining the species-dependent toxicological risk of bisphenol A. Copyright © 2015 Elsevier Inc. All rights reserved.

Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome.

PubMed

Depner, Christopher M; Melanson, Edward L; McHill, Andrew W; Wright, Kenneth P

2018-06-05

Proteomics holds great promise for understanding human physiology, developing health biomarkers, and precision medicine. However, how much the plasma proteome varies with time of day and is regulated by the master circadian suprachiasmatic nucleus brain clock, assessed here by the melatonin rhythm, is largely unknown. Here, we assessed 24-h time-of-day patterns of human plasma proteins in six healthy men during daytime food intake and nighttime sleep in phase with the endogenous circadian clock (i.e., circadian alignment) versus daytime sleep and nighttime food intake out of phase with the endogenous circadian clock (i.e., circadian misalignment induced by simulated nightshift work). We identified 24-h time-of-day patterns in 573 of 1,129 proteins analyzed, with 30 proteins showing strong regulation by the circadian cycle. Relative to circadian alignment, the average abundance and/or 24-h time-of-day patterns of 127 proteins were altered during circadian misalignment. Altered proteins were associated with biological pathways involved in immune function, metabolism, and cancer. Of the 30 circadian-regulated proteins, the majority peaked between 1400 hours and 2100 hours, and these 30 proteins were associated with basic pathways involved in extracellular matrix organization, tyrosine kinase signaling, and signaling by receptor tyrosine-protein kinase erbB-2. Furthermore, circadian misalignment altered multiple proteins known to regulate glucose homeostasis and/or energy metabolism, with implications for altered metabolic physiology. Our findings demonstrate the circadian clock, the behavioral wake-sleep/food intake-fasting cycle, and interactions between these processes regulate 24-h time-of-day patterns of human plasma proteins and help identify mechanisms of circadian misalignment that may contribute to metabolic dysregulation.

Physiologically based pharmacokinetic toolkit to evaluate environmental exposures: Applications of the dioxin model to study real life exposures

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

Emond, Claude, E-mail: claude.emond@biosmc.com

Chlorinated dibenzo-p-dioxins (CDDs) are a series of mono- to octa-chlorinated homologous chemicals commonly referred to as polychlorinated dioxins. One of the most potent, well-known, and persistent member of this family is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). As part of translational research to make computerized models accessible to health risk assessors, we present a Berkeley Madonna recoded version of the human physiologically based pharmacokinetic (PBPK) model used by the U.S. Environmental Protection Agency (EPA) in the recent dioxin assessment. This model incorporates CYP1A2 induction, which is an important metabolic vector that drives dioxin distribution in the human body, and it uses a variable eliminationmore » half-life that is body burden dependent. To evaluate the model accuracy, the recoded model predictions were compared with those of the original published model. The simulations performed with the recoded model matched well with those of the original model. The recoded model was then applied to available data sets of real life exposure studies. The recoded model can describe acute and chronic exposures and can be useful for interpreting human biomonitoring data as part of an overall dioxin and/or dioxin-like compounds risk assessment. - Highlights: • The best available dioxin PBPK model for interpreting human biomonitoring data is presented. • The original PBPK model was recoded from acslX to the Berkeley Madonna (BM) platform. • Comparisons were made of the accuracy of the recoded model with the original model. • The model is a useful addition to the ATSDR's BM based PBPK toolkit that supports risk assessors. • The application of the model to real-life exposure data sets is illustrated.« less

A physiologically based toxicokinetic model for inhaled ethylene and ethylene oxide in mouse, rat, and human.

PubMed

Filser, Johannes Georg; Klein, Dominik

2018-04-01

Ethylene (ET) is the largest volume organic chemical. Mammals metabolize the olefin to ethylene oxide (EO), another important industrial chemical. The epoxide alkylates macromolecules and has mutagenic and carcinogenic properties. In order to estimate the EO burden in mice, rats, and humans resulting from inhalation exposure to gaseous ET or EO, a physiological toxicokinetic model was developed. It consists of the compartments lung, richly perfused tissues, kidneys, muscle, fat, arterial blood, venous blood, and liver containing the sub-compartment endoplasmic reticulum. Modeled ET metabolism is mediated by hepatic cytochrome P450 2E1, EO metabolism by hepatic microsomal epoxide hydrolase or cytosolic glutathione S-transferase in various tissues. EO is also spontaneously hydrolyzed or conjugated with glutathione. The model was validated on experimental data collected in mice, rats, and humans. Modeled were uptake by inhalation, wash-in-wash-out effect in the upper respiratory airways, distribution into tissues and organs, elimination via exhalation and metabolism, and formation of 2-hydroxyethyl adducts with hemoglobin and DNA. Simulated concentration-time courses of ET or EO in inhaled (gas uptake studies) or exhaled air, and of EO in blood during exposures to ET or EO agreed excellently with measured data. Predicted levels of adducts with DNA and hemoglobin, induced by ET or EO, agreed with reported levels. Exposures to 10000 ppm ET were predicted to induce the same adduct levels as EO exposures to 3.95 (mice), 5.67 (rats), or 0.313 ppm (humans). The model is concluded to be applicable for assessing health risks from inhalation exposure to ET or EO. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Determining environmental causes of biological effects: the need for a mechanistic physiological dimension in conservation biology.

PubMed

Seebacher, Frank; Franklin, Craig E

2012-06-19

The emerging field of Conservation Physiology links environmental change and ecological success by the application of physiological theory, approaches and tools to elucidate and address conservation problems. Human activity has changed the natural environment to a point where the viability of many ecosystems is now under threat. There are already many descriptions of how changes in biological patterns are correlated with environmental changes. The next important step is to determine the causative relationship between environmental variability and biological systems. Physiology provides the mechanistic link between environmental change and ecological patterns. Physiological research, therefore, should be integrated into conservation to predict the biological consequences of human activity, and to identify those species or populations that are most vulnerable.

Investigation of an alternative generic model for predicting pharmacokinetic changes during physiological stress.

PubMed

Peng, Henry T; Edginton, Andrea N; Cheung, Bob

2013-10-01

Physiologically based pharmacokinetic models were developed using MATLAB Simulink® and PK-Sim®. We compared the capability and usefulness of these two models by simulating pharmacokinetic changes of midazolam under exercise and heat stress to verify the usefulness of MATLAB Simulink® as a generic PBPK modeling software. Although both models show good agreement with experimental data obtained under resting condition, their predictions of pharmacokinetics changes are less accurate in the stressful conditions. However, MATLAB Simulink® may be more flexible to include physiologically based processes such as oral absorption and simulate various stress parameters such as stress intensity, duration and timing of drug administration to improve model performance. Further work will be conducted to modify algorithms in our generic model developed using MATLAB Simulink® and to investigate pharmacokinetics under other physiological stress such as trauma. © The Author(s) 2013.

Planning a sports training program using Adaptive Particle Swarm Optimization with emphasis on physiological constraints.

PubMed

Kumyaito, Nattapon; Yupapin, Preecha; Tamee, Kreangsak

2018-01-08

An effective training plan is an important factor in sports training to enhance athletic performance. A poorly considered training plan may result in injury to the athlete, and overtraining. Good training plans normally require expert input, which may have a cost too great for many athletes, particularly amateur athletes. The objectives of this research were to create a practical cycling training plan that substantially improves athletic performance while satisfying essential physiological constraints. Adaptive Particle Swarm Optimization using ɛ-constraint methods were used to formulate such a plan and simulate the likely performance outcomes. The physiological constraints considered in this study were monotony, chronic training load ramp rate and daily training impulse. A comparison of results from our simulations against a training plan from British Cycling, which we used as our standard, showed that our training plan outperformed the benchmark in terms of both athletic performance and satisfying all physiological constraints.

Comparison Between THOR Anthropomorphic Test Device and THOR Finite Element Model

NASA Technical Reports Server (NTRS)

Moore, Erik

2014-01-01

Extended time spent in reduced gravity can cause physiologic deconditioning of astronauts, reducing their ability to sustain excessive forces during dynamic phases of spaceflight such as landing. To make certain that the crew is safe during these phases, NASA must take caution when determining what types of landings are acceptable based on the accelerations applied to the astronaut. In order to test acceptable landings, various trials have been run accelerating humans, cadavers, and Anthropomorphic Test Devices (ATDs), or crash test dummies, at different acceleration and velocity rates on a sled testing platform. Using these tests, risks of injury will be created and metrics will be developed for the likelihood of injuries due to the acceleration. A finite element model (FEM) of the Test Device for Human Occupant Restraint (THOR) ATD has been developed that can simulate these test trials and others (Putnam, 2014), reducing the need for human and ATD testing. Additionally, this will give researchers a more effective way to test the accelerations and orientations encountered during spaceflight landings during design of new space vehicles for crewed missions. However, the FEM has not been proven and must be validated by comparing the forces, accelerations, and other measurements of all parts of the body between the physical tests already completed and computer simulated trials. The purpose of my research was to validate the FEM for the ATD using previously run trials with the physical THOR ATD.

The physiological effects of slow breathing in the healthy human

PubMed Central

Russo, Marc A.; Santarelli, Danielle M.; O’Rourke, Dean

2017-01-01

Slow breathing practices have been adopted in the modern world across the globe due to their claimed health benefits. This has piqued the interest of researchers and clinicians who have initiated investigations into the physiological (and psychological) effects of slow breathing techniques and attempted to uncover the underlying mechanisms. The aim of this article is to provide a comprehensive overview of normal respiratory physiology and the documented physiological effects of slow breathing techniques according to research in healthy humans. The review focuses on the physiological implications to the respiratory, cardiovascular, cardiorespiratory and autonomic nervous systems, with particular focus on diaphragm activity, ventilation efficiency, haemodynamics, heart rate variability, cardiorespiratory coupling, respiratory sinus arrhythmia and sympathovagal balance. The review ends with a brief discussion of the potential clinical implications of slow breathing techniques. This is a topic that warrants further research, understanding and discussion. Key points Slow breathing practices have gained popularity in the western world due to their claimed health benefits, yet remain relatively untouched by the medical community. Investigations into the physiological effects of slow breathing have uncovered significant effects on the respiratory, cardiovascular, cardiorespiratory and autonomic nervous systems. Key findings include effects on respiratory muscle activity, ventilation efficiency, chemoreflex and baroreflex sensitivity, heart rate variability, blood flow dynamics, respiratory sinus arrhythmia, cardiorespiratory coupling, and sympathovagal balance. There appears to be potential for use of controlled slow breathing techniques as a means of optimising physiological parameters that appear to be associated with health and longevity, and that may extend to disease states; however, there is a dire need for further research into the area. Educational aims To provide a comprehensive overview of normal human respiratory physiology and the documented effects of slow breathing in healthy humans. To review and discuss the evidence and hypotheses regarding the mechanisms underlying slow breathing physiological effects in humans. To provide a definition of slow breathing and what may constitute “autonomically optimised respiration”. To open discussion on the potential clinical implications of slow breathing techniques and the need for further research. PMID:29209423

Environmental and biological context modulates the physiological stress response of bats to human disturbance.

PubMed

Phelps, Kendra L; Kingston, Tigga

2018-06-01

Environmental and biological context play significant roles in modulating physiological stress responses of individuals in wildlife populations yet are often overlooked when evaluating consequences of human disturbance on individual health and fitness. Furthermore, most studies gauge individual stress responses based on a single physiological biomarker, typically circulating glucocorticoid concentrations, which limits interpretation of the complex, multifaceted responses of individuals to stressors. We selected four physiological biomarkers to capture short-term and prolonged stress responses in a widespread cave-roosting bat, Hipposideros diadema, across multiple gradients of human disturbance in and around caves in the Philippines. We used conditional inference trees and random forest analysis to determine the role of environmental quality (cave complexity, available roosting area), assemblage composition (intra- and interspecific associations and species richness), and intrinsic characteristics of individuals (sex and reproductive status) in modulating responses to disturbance. Direct cave disturbance (hunting pressure and human visitation) was the primary driver of neutrophil-to-lymphocyte ratios, with lower ratios associated with increased disturbance, while context-specific factors were more important in explaining total leukocyte count, body condition, and ectoparasite load. Moreover, conditional inference trees revealed complex interactions among human disturbance and modulating factors. Cave complexity often ameliorated individual responses to human disturbance, whereas conspecific abundance often compounded responses. Our study demonstrates the importance of an integrated approach that incorporates environmental and biological context when identifying drivers of physiological responses, and that assesses responses to gradients of direct and indirect disturbance using multiple complementary biomarkers.

Comparison of the didactic lecture with the simulation/model approach for the teaching of a novel perioperative ultrasound curriculum to anesthesiology residents.

PubMed

Ramsingh, Davinder; Alexander, Brenton; Le, Khanhvan; Williams, Wendell; Canales, Cecilia; Cannesson, Maxime

2014-09-01

To expose residents to two methods of education for point-of-care ultrasound, a traditional didactic lecture and a model/simulation-based lecture, which focus on concepts of cardiopulmonary function, volume status, and evaluation of severe thoracic/abdominal injuries; and to assess which method is more effective. Single-center, prospective, blinded trial. University hospital. Anesthesiology residents who were assigned to an educational day during the two-month research study period. Residents were allocated to two groups to receive either a 90-minute, one-on-one didactic lecture or a 90-minute lecture in a simulation center, during which they practiced on a human model and simulation mannequin (normal pathology). Data points included a pre-lecture multiple-choice test, post-lecture multiple-choice test, and post-lecture, human model-based examination. Post-lecture tests were performed within three weeks of the lecture. An experienced sonographer who was blinded to the education modality graded the model-based skill assessment examinations. Participants completed a follow-up survey to assess the perceptions of the quality of their instruction between the two groups. 20 residents completed the study. No differences were noted between the two groups in pre-lecture test scores (P = 0.97), but significantly higher scores for the model/simulation group occurred on both the post-lecture multiple choice (P = 0.038) and post-lecture model (P = 0.041) examinations. Follow-up resident surveys showed significantly higher scores in the model/simulation group regarding overall interest in perioperative ultrasound (P = 0.047) as well understanding of the physiologic concepts (P = 0.021). A model/simulation-based based lecture series may be more effective in teaching the skills needed to perform a point-of-care ultrasound examination to anesthesiology residents. Copyright © 2014 Elsevier Inc. All rights reserved.