Sample records for human physiologically based

  1. 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…

  2. 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...

  3. 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...

  4. 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.

  5. 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.

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  8. 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

  9. 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

  10. Estimation of bio-signal based on human motion for integrated visualization of daily-life.

    PubMed

    Umetani, Tomohiro; Matsukawa, Tsuyoshi; Yokoyama, Kiyoko

    2007-01-01

    This paper describes a method for the estimation of bio-signals based on human motion in daily life for an integrated visualization system. The recent advancement of computers and measurement technology has facilitated the integrated visualization of bio-signals and human motion data. It is desirable to obtain a method to understand the activities of muscles based on human motion data and evaluate the change in physiological parameters according to human motion for visualization applications. We suppose that human motion is generated by the activities of muscles reflected from the brain to bio-signals such as electromyograms. This paper introduces a method for the estimation of bio-signals based on neural networks. This method can estimate the other physiological parameters based on the same procedure. The experimental results show the feasibility of the proposed method.

  11. 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.

  12. 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.

  13. 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

  14. Noncontact measurement of heart rate using facial video illuminated under natural light and signal weighted analysis.

    PubMed

    Yan, Yonggang; Ma, Xiang; Yao, Lifeng; Ouyang, Jianfei

    2015-01-01

    Non-contact and remote measurements of vital physical signals are important for reliable and comfortable physiological self-assessment. We presented a novel optical imaging-based method to measure the vital physical signals. Using a digital camera and ambient light, the cardiovascular pulse waves were extracted better from human color facial videos correctly. And the vital physiological parameters like heart rate were measured using a proposed signal-weighted analysis method. The measured HRs consistent with those measured simultaneously with reference technologies (r=0.94, p<0.001 for HR). The results show that the imaging-based method is suitable for measuring the physiological parameters, and provide a reliable and comfortable measurement mode. The study lays a physical foundation for measuring multi-physiological parameters of human noninvasively.

  15. 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.

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

    EPA Science Inventory

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

  17. Development of a Physiologically Based Pharmacokinetic Model for Triadimefon and Triadimenol in Rats and Humans

    EPA Science Inventory

    A physiologically based pharmacokinetic (PBPK) model was developed for the conazole fungicide triadimefon and its primary metabolite, triadimenol. Rat tissue:blood partition coefficients and metabolic constants were measured in vitro for both compounds. Kinetic time course data...

  18. Development of a Physiologically Based Pharmacokinetic Model for Triadimefon and its Metabolite Triandimenol in Rats and Humans

    EPA Science Inventory

    physiologically based pharmacokinetic (PBPK) model was developed for the conazole fungicide triadimefon and its primary metabolite, triadimenol. Rat tissue:blood partition coefficients and metabolic constants were measured in vitro for both compounds. Pharmacokinetic data for par...

  19. [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.

  20. 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.

  1. Flexible and wearable electronic silk fabrics for human physiological monitoring

    NASA Astrophysics Data System (ADS)

    Mao, Cuiping; Zhang, Huihui; Lu, Zhisong

    2017-09-01

    The development of textile-based devices for human physiological monitoring has attracted tremendous interest in recent years. However, flexible physiological sensing elements based on silk fabrics have not been realized. In this paper, ZnO nanorod arrays are grown in situ on reduced graphene oxide-coated silk fabrics via a facile electro-deposition method for the fabrication of silk-fabric-based mechanical sensing devices. The data show that well-aligned ZnO nanorods with hexagonal wurtzite crystalline structures are synthesized on the conductive silk fabric surface. After magnetron sputtering of gold electrodes, silk-fabric-based devices are produced and applied to detect periodic bending and twisting. Based on the electric signals, the deformation and release processes can be easily differentiated. Human arterial pulse and respiration can also be real-time monitored to calculate the pulse rate and respiration frequency, respectively. Throat vibrations during coughing and singing are detected to demonstrate the voice recognition capability. This work may not only help develop silk-fabric-based mechanical sensing elements for potential applications in clinical diagnosis, daily healthcare monitoring and voice recognition, but also provide a versatile method for fabricating textile-based flexible electronic devices.

  2. A Physiologically-Based Description of the Inhalation Pharmacokinetics of Styrene in Rats and Humans

    DTIC Science & Technology

    1983-01-01

    model for rat were scaled to give a description of human kinetics and the predictions agreed closely with available data from the literature (Fig. 4...for predicting human kinetics from a data base in other mammalian species. The ability to anticipate kinetic behavior in humans could very much improve

  3. A DYNAMIC PHYSIOLOGICALLY-BASED TOXICOKINETIC (DPBTK) MODEL FOR SIMULATION OF COMPLEX TOLUENE EXPOSURE SCENARIOS IN HUMANS

    EPA Science Inventory

    A GENERAL PHYSIOLOGICAL AND TOXICOKINETIC (GPAT) MODEL FOR SIMULATION OF COMPLEX TOLUENE EXPOSURE SCENARIOS IN HUMANS. E M Kenyon1, T Colemen2, C R Eklund1 and V A Benignus3. 1U.S. EPA, ORD, NHEERL, ETD, PKB, RTP, NC, USA; 2Biological Simulators, Inc., Jackson MS, USA, 3U.S. EP...

  4. The Use of Team-Based, Guided Inquiry Learning to Overcome Educational Disadvantages in Learning Human Physiology: A Structural Equation Model

    ERIC Educational Resources Information Center

    Rathner, Joseph A.; Byrne, Graeme

    2014-01-01

    The study of human bioscience is viewed as a crucial curriculum in allied health. Nevertheless, bioscience (and particularly physiology) is notoriously difficult for undergraduates, particularly academically disadvantaged students. So endemic are the high failure rates (particularly in nursing) that it has come to be known as "the human…

  5. Contactless physiological signals extraction based on skin color magnification

    NASA Astrophysics Data System (ADS)

    Suh, Kun Ha; Lee, Eui Chul

    2017-11-01

    Although the human visual system is not sufficiently sensitive to perceive blood circulation, blood flow caused by cardiac activity makes slight changes on human skin surfaces. With advances in imaging technology, it has become possible to capture these changes through digital cameras. However, it is difficult to obtain clear physiological signals from such changes due to its fineness and noise factors, such as motion artifacts and camera sensing disturbances. We propose a method for extracting physiological signals with improved quality from skin colored-videos recorded with a remote RGB camera. The results showed that our skin color magnification method reveals the hidden physiological components remarkably in the time-series signal. A Korea Food and Drug Administration-approved heart rate monitor was used for verifying the resulting signal synchronized with the actual cardiac pulse, and comparisons of signal peaks showed correlation coefficients of almost 1.0. In particular, our method can be an effective preprocessing before applying additional postfiltering techniques to improve accuracy in image-based physiological signal extractions.

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

    EPA Science Inventory

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

  7. Integrating Cellular Metabolism into a Multiscale Whole-Body Model

    PubMed Central

    Krauss, Markus; Schaller, Stephan; Borchers, Steffen; Findeisen, Rolf; Lippert, Jörg; Kuepfer, Lars

    2012-01-01

    Cellular metabolism continuously processes an enormous range of external compounds into endogenous metabolites and is as such a key element in human physiology. The multifaceted physiological role of the metabolic network fulfilling the catalytic conversions can only be fully understood from a whole-body perspective where the causal interplay of the metabolic states of individual cells, the surrounding tissue and the whole organism are simultaneously considered. We here present an approach relying on dynamic flux balance analysis that allows the integration of metabolic networks at the cellular scale into standardized physiologically-based pharmacokinetic models at the whole-body level. To evaluate our approach we integrated a genome-scale network reconstruction of a human hepatocyte into the liver tissue of a physiologically-based pharmacokinetic model of a human adult. The resulting multiscale model was used to investigate hyperuricemia therapy, ammonia detoxification and paracetamol-induced toxication at a systems level. The specific models simultaneously integrate multiple layers of biological organization and offer mechanistic insights into pathology and medication. The approach presented may in future support a mechanistic understanding in diagnostics and drug development. PMID:23133351

  8. Local air gap thickness and contact area models for realistic simulation of human thermo-physiological response

    NASA Astrophysics Data System (ADS)

    Psikuta, Agnes; Mert, Emel; Annaheim, Simon; Rossi, René M.

    2018-02-01

    To evaluate the quality of new energy-saving and performance-supporting building and urban settings, the thermal sensation and comfort models are often used. The accuracy of these models is related to accurate prediction of the human thermo-physiological response that, in turn, is highly sensitive to the local effect of clothing. This study aimed at the development of an empirical regression model of the air gap thickness and the contact area in clothing to accurately simulate human thermal and perceptual response. The statistical model predicted reliably both parameters for 14 body regions based on the clothing ease allowances. The effect of the standard error in air gap prediction on the thermo-physiological response was lower than the differences between healthy humans. It was demonstrated that currently used assumptions and methods for determination of the air gap thickness can produce a substantial error for all global, mean, and local physiological parameters, and hence, lead to false estimation of the resultant physiological state of the human body, thermal sensation, and comfort. Thus, this model may help researchers to strive for improvement of human thermal comfort, health, productivity, safety, and overall sense of well-being with simultaneous reduction of energy consumption and costs in built environment.

  9. Micro-patterned graphene-based sensing skins for human physiological monitoring

    NASA Astrophysics Data System (ADS)

    Wang, Long; Loh, Kenneth J.; Chiang, Wei-Hung; Manna, Kausik

    2018-03-01

    Ultrathin, flexible, conformal, and skin-like electronic transducers are emerging as promising candidates for noninvasive and nonintrusive human health monitoring. In this work, a wearable sensing membrane is developed by patterning a graphene-based solution onto ultrathin medical tape, which can then be attached to the skin for monitoring human physiological parameters and physical activity. Here, the sensor is validated for monitoring finger bending/movements and for recognizing hand motion patterns, thereby demonstrating its future potential for evaluating athletic performance, physical therapy, and designing next-generation human-machine interfaces. Furthermore, this study also quantifies the sensor’s ability to monitor eye blinking and radial pulse in real-time, which can find broader applications for the healthcare sector. Overall, the printed graphene-based sensing skin is highly conformable, flexible, lightweight, nonintrusive, mechanically robust, and is characterized by high strain sensitivity.

  10. Dealing with noise and physiological artifacts in human EEG recordings: empirical mode methods

    NASA Astrophysics Data System (ADS)

    Runnova, Anastasiya E.; Grubov, Vadim V.; Khramova, Marina V.; Hramov, Alexander E.

    2017-04-01

    In the paper we propose the new method for removing noise and physiological artifacts in human EEG recordings based on empirical mode decomposition (Hilbert-Huang transform). As physiological artifacts we consider specific oscillatory patterns that cause problems during EEG analysis and can be detected with additional signals recorded simultaneously with EEG (ECG, EMG, EOG, etc.) We introduce the algorithm of the proposed method with steps including empirical mode decomposition of EEG signal, choosing of empirical modes with artifacts, removing these empirical modes and reconstructing of initial EEG signal. We show the efficiency of the method on the example of filtration of human EEG signal from eye-moving artifacts.

  11. Development of mathematical models of environmental physiology

    NASA Technical Reports Server (NTRS)

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

    1971-01-01

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

  12. Do Targeted Written Comments and the Rubric Method of Delivery Affect Performance on Future Human Physiology Laboratory Reports?

    ERIC Educational Resources Information Center

    Clayton, Zachary S.; Wilds, Gabriel P.; Mangum, Joshua E.; Hocker, Austin D.; Dawson, Sierra M.

    2016-01-01

    We investigated how students performed on weekly two-page laboratory reports based on whether the grading rubric was provided to the student electronically or in paper form and the inclusion of one- to two-sentence targeted comments. Subjects were registered for a 289-student, third-year human physiology class with laboratory and were randomized…

  13. On the Physiological Modulation and Potential Mechanisms Underlying Parieto-Occipital Alpha Oscillations

    PubMed Central

    Lozano-Soldevilla, Diego

    2018-01-01

    The parieto-occipital alpha (8–13 Hz) rhythm is by far the strongest spectral fingerprint in the human brain. Almost 90 years later, its physiological origin is still far from clear. In this Research Topic I review human pharmacological studies using electroencephalography (EEG) and magnetoencephalography (MEG) that investigated the physiological mechanisms behind posterior alpha. Based on results from classical and recent experimental studies, I find a wide spectrum of drugs that modulate parieto-occipital alpha power. Alpha frequency is rarely affected, but this might be due to the range of drug dosages employed. Animal and human pharmacological findings suggest that both GABA enhancers and NMDA blockers systematically decrease posterior alpha power. Surprisingly, most of the theoretical frameworks do not seem to embrace these empirical findings and the debate on the functional role of alpha oscillations has been polarized between the inhibition vs. active poles hypotheses. Here, I speculate that the functional role of alpha might depend on physiological excitation as much as on physiological inhibition. This is supported by animal and human pharmacological work showing that GABAergic, glutamatergic, cholinergic, and serotonergic receptors in the thalamus and the cortex play a key role in the regulation of alpha power and frequency. This myriad of physiological modulations fit with the view that the alpha rhythm is a complex rhythm with multiple sources supported by both thalamo-cortical and cortico-cortical loops. Finally, I briefly discuss how future research combining experimental measurements derived from theoretical predictions based of biophysically realistic computational models will be crucial to the reconciliation of these disparate findings. PMID:29670518

  14. An Active Learning Exercise to Facilitate Understanding of Nephron Function: Anatomy and Physiology of Renal Transporters

    ERIC Educational Resources Information Center

    Dirks-Naylor, Amie J.

    2016-01-01

    Renal transport is a central mechanism underlying electrolyte homeostasis, acid base balance and other essential functions of the kidneys in human physiology. Thus, knowledge of the anatomy and physiology of the nephron is essential for the understanding of kidney function in health and disease. However, students find this content difficult to…

  15. Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from Pharmacokinetics in Rats and Human.

    PubMed

    Yang, Fen; Wang, Baolian; Liu, Zhihao; Xia, Xuejun; Wang, Weijun; Yin, Dali; Sheng, Li; Li, Yan

    2017-01-01

    Physiologically based pharmacokinetic (PBPK)/pharmacodynamic (PD) models can contribute to animal-to-human extrapolation and therapeutic dose predictions. Buagafuran is a novel anxiolytic agent and phase I clinical trials of buagafuran have been completed. In this paper, a potentially effective dose for buagafuran of 30 mg t.i.d. in human was estimated based on the human brain concentration predicted by a PBPK/PD modeling. The software GastroPlus TM was used to build the PBPK/PD model for buagafuran in rat which related the brain tissue concentrations of buagafuran and the times of animals entering the open arms in the pharmacological model of elevated plus-maze. Buagafuran concentrations in human plasma were fitted and brain tissue concentrations were predicted by using a human PBPK model in which the predicted plasma profiles were in good agreement with observations. The results provided supportive data for the rational use of buagafuran in clinic.

  16. 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.

  17. Physiological studies of the brain: Implications for science teaching

    NASA Astrophysics Data System (ADS)

    Esler, William K.

    Physiological changes resulting from repeated, long-term stimulation have been observed in the brains of both humans and laboratory animals. It may be speculated that these changes are related to short-term and long-term memory processes. A physiologically based model for memory processing (PBMMP) can serve to explain the interrelations of various areas of the brain as they process new stimuli and recall past events. The model can also serve to explain many current principles of learning theory and serve as a foundation for developing new theories of learning based upon the physiology of the brain.

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

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

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

    2008-03-01

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

  19. EVALUATION OF ORAL AND INTRAVENOUS ROUTE PHARMACOKINETICS, PLASMA PROTEIN BINDING AND UTERINE TISSUE DOSE METRICS OF BPA: A PHYSIOLOGICALLY BASED PHARMACOKINETIC APPROACH

    EPA Science Inventory

    Bisphenol A (BPA) is a weakly estrogenic monomer used in the production of polycarbonate plastics and epoxy resins, both of which are used in food contact applications. A physiologically based pharmacokinetic (PBPK) model of BPA pharmacokinetics in rats and humans was developed t...

  20. EVALUATION OF ORAL AND INTRAVENOUS ROUTE PHARMACOKINETICS, PLASMA PROTEIN BINDING AND UTERINE TISSUE DOSE METRICS OF BPA: A PHYSIOLOGICALLY BASED PHARMACOKINETIC APPROACH

    EPA Science Inventory

    Bisphenol A (BPA) is a weakly estrogenic monomer used in the production of polycarbonate plastics and epoxy resins, both of which are used in food contact applications. A physiologically based pharmacokinetic (PBPK) model of BPA pharmacokinetics in rats and humans was developed ...

  1. In Vitro Measurements of Metabolism for Application in Pharmacokinetic Modeling

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

    Lipscomb, John C.; Poet, Torka S.

    2008-04-01

    Abstract Human risk and exposure assessments require dosimetry information. Species-specific tissue dose response will be driven by physiological and biochemical processes. While metabolism and pharmacokinetic data are often not available in humans, they are much more available in laboratory animals; metabolic rate constants can be readily derived in vitro. The physiological differences between laboratory animals and humans are known. Biochemical processes, especially metabolism, can be measured in vitro and extrapolated to account for in vivo metabolism through clearance models or when linked to a physiologically based biological (PBPK) model to describe the physiological processes, such as drug delivery to themore » metabolic organ. This review focuses on the different organ, cellular, and subcellular systems that can be used to measure in vitro metabolic rate constants and how that data is extrapolated to be used in biokinetic modeling.« less

  2. The use of team-based, guided inquiry learning to overcome educational disadvantages in learning human physiology: a structural equation model.

    PubMed

    Rathner, Joseph A; Byrne, Graeme

    2014-09-01

    The study of human bioscience is viewed as a crucial curriculum in allied health. Nevertheless, bioscience (and particularly physiology) is notoriously difficult for undergraduates, particularly academically disadvantaged students. So endemic are the high failure rates (particularly in nursing) that it has come to be known as "the human bioscience problem." In the present report, we describe the outcomes for individual success in studying first-year human physiology in a subject that emphasises team-based active learning as the major pedagogy for mastering subject learning outcomes. Structural equation modeling was used to develop a model of the impact team learning had on individual performance. Modeling was consistent with the idea that students with similar academic abilities (as determined by tertiary entrance rank) were advantaged (scored higher on individual assessment items) by working in strong teams (teams that scored higher in team-based assessments). Analysis of covariance revealed that students who studied the subject with active learning as the major mode of learning activities outperformed students who studied the subject using the traditional didactic teaching format (lectures and tutorials, P = 0.000). After adjustment for tertiary entrance rank (via analysis of covariance) on two individual tests (the final exam and a late-semester in-class test), individual student grades improved by 8% (95% confidence interval: 6-10%) and 12% (95% confidence interval: 10-14%) when students engaged in team-based active learning. These data quantitatively support the notion that weaker students working in strong teams can overcome their educational disadvantages. Copyright © 2014 The American Physiological Society.

  3. 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

  4. Alamos: An International Collaboration to Provide a Space Based Environmental Monitoring Solution for the Deep Space Network

    NASA Astrophysics Data System (ADS)

    Kennedy, S. O.; Dunn, A.; Lecomte, J.; Buchheim, K.; Johansson, E.; Berger, T.

    2018-02-01

    This abstract proposes the advantages of an externally mounted instrument in support of the human physiology, space biology, and human health and performance key science area. Alamos provides Space-Based Environmental Monitoring capabilities.

  5. Estimating human-equivalent no observed adverse-effect levels for VOCs (volatile organic compounds) based on minimal knowledge of physiological parameters. Technical paper

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

    Overton, J.H.; Jarabek, A.M.

    1989-01-01

    The U.S. EPA advocates the assessment of health-effects data and calculation of inhaled reference doses as benchmark values for gauging systemic toxicity to inhaled gases. The assessment often requires an inter- or intra-species dose extrapolation from no observed adverse effect level (NOAEL) exposure concentrations in animals to human equivalent NOAEL exposure concentrations. To achieve this, a dosimetric extrapolation procedure was developed based on the form or type of equations that describe the uptake and disposition of inhaled volatile organic compounds (VOCs) in physiologically-based pharmacokinetic (PB-PK) models. The procedure assumes allometric scaling of most physiological parameters and that the value ofmore » the time-integrated human arterial-blood concentration must be limited to no more than to that of experimental animals. The scaling assumption replaces the need for most parameter values and allows the derivation of a simple formula for dose extrapolation of VOCs that gives equivalent or more-conservative exposure concentrations values than those that would be obtained using a PB-PK model in which scaling was assumed.« less

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

    PubMed

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

    2017-06-01

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

  7. 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.

  8. Grandma's TUM-my Trouble: A Case Study in Renal Physiology and Acid-Base Balance

    ERIC Educational Resources Information Center

    Massey, Ann T.

    2015-01-01

    This case study involves the role of the kidneys in regulating blood pH and electrolytes. The case was used near the end of a two-semester Human Anatomy and Physiology course sequence, during the time when renal physiology was under study. Groups of two to three students were given the case and associated information (lab values, etc.). Students…

  9. Wearable carbon nanotube-based fabric sensors for monitoring human physiological performance

    NASA Astrophysics Data System (ADS)

    Wang, Long; Loh, Kenneth J.

    2017-05-01

    A target application of wearable sensors is to detect human motion and to monitor physical activity for improving athletic performance and for delivering better physical therapy. In addition, measuring human vital signals (e.g., respiration rate and body temperature) provides rich information that can be used to assess a subject’s physiological or psychological condition. This study aims to design a multifunctional, wearable, fabric-based sensing system. First, carbon nanotube (CNT)-based thin films were fabricated by spraying. Second, the thin films were integrated with stretchable fabrics to form the fabric sensors. Third, the strain and temperature sensing properties of sensors fabricated using different CNT concentrations were characterized. Furthermore, the sensors were demonstrated to detect human finger bending motions, so as to validate their practical strain sensing performance. Finally, to monitor human respiration, the fabric sensors were integrated with a chest band, which was directly worn by a human subject. Quantification of respiration rates were successfully achieved. Overall, the fabric sensors were characterized by advantages such as flexibility, ease of fabrication, lightweight, low-cost, noninvasiveness, and user comfort.

  10. Molecular physiology of weight regulation in mice and humans

    PubMed Central

    Leibel, RL

    2009-01-01

    Evolutionary considerations relating to efficiency in reproduction, and survival in hostile environments, suggest that body energy stores are sensed and actively regulated, with stronger physiological and behavioral responses to loss than gain of stored energy. Many physiological studies support this inference, and suggest that a critical axis runs between body fat and the hypothalamus. The molecular cloning of leptin and its receptor—projects based explicitly on the search for elements in this axis—confirmed the existence of this axis and provided important tools with which to understand its molecular physiology. Demonstration of the importance of this soma-brain reciprocal connection in body weight regulation in humans has been pursued using both classical genetic approaches and studies of physiological responses to experimental weight perturbation. This paper reviews the history of the rationale and methodology of the cloning of leptin (Lep) and the leptin receptor (Lepr), and describes some of the clinical investigation characterizing this axis. PMID:19136999

  11. Filtration of human EEG recordings from physiological artifacts with empirical mode method

    NASA Astrophysics Data System (ADS)

    Grubov, Vadim V.; Runnova, Anastasiya E.; Khramova, Marina V.

    2017-03-01

    In the paper we propose the new method for dealing with noise and physiological artifacts in experimental human EEG recordings. The method is based on analysis of EEG signals with empirical mode decomposition (Hilbert-Huang transform). We consider noises and physiological artifacts on EEG as specific oscillatory patterns that cause problems during EEG analysis and can be detected with additional signals recorded simultaneously with EEG (ECG, EMG, EOG, etc.) We introduce the algorithm of the method with following steps: empirical mode decomposition of EEG signal, choosing of empirical modes with artifacts, removing empirical modes with artifacts, reconstruction of the initial EEG signal. We test the method on filtration of experimental human EEG signals from eye-moving artifacts and show high efficiency of the method.

  12. Developmental and Life-Stage Physiologically-Based Pharmacokinetic (PBPK) Models in Humans and Animal Models.

    EPA Science Inventory

    PBPK models provide a computational framework for incorporating pertinent physiological and biochemical information to estimate in vivo levels of xenobiotics in biological tissues. In general, PBPK models are used to correlate exposures to target tissue levels of chemicals and th...

  13. Application of physiologically based pharmacokinetic (PBPK) model of trichloroethylene in rats for estimation of internal dose

    EPA Science Inventory

    Potential human health risk from chemical exposure must often be assessed for conditions for which suitable human or animal data are not available, requiring extrapolation across duration and concentration. The default method for exposure-duration adjustment is based on Haber's r...

  14. Commensal bacteria produce GPCR ligands that mimic human signaling molecules

    PubMed Central

    Cohen, Louis J.; Esterhazy, Daria; Kim, Seong-Hwan; Lemetre, Christophe; Aguilar, Rhiannon R.; Gordon, Emma A.; Pickard, Amanda J.; Cross, Justin R.; Emiliano, Ana B.; Han, Sun M.; Chu, John; Vila-Farres, Xavier; Kaplitt, Jeremy; Rogoz, Aneta; Calle, Paula Y.; Hunter, Craig; Bitok, J. Kipchirchir; Brady, Sean F.

    2017-01-01

    Summary Statement Commensal bacteria are believed to play important roles in human health. The mechanisms by which they affect mammalian physiology are poorly understood; however, bacterial metabolites are likely to be key components of host interactions. Here, we use bioinformatics and synthetic biology to mine the human microbiota for N-acyl amides that interact with G-protein-coupled receptors (GPCRs). We found that N-acyl amide synthase genes are enriched in gastrointestinal bacteria and the lipids they encode interact with GPCRs that regulate gastrointestinal tract physiology. Mouse and cell-based models demonstrate that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as efficiently as human ligands although future studies are needed to define their potential physiologic role in humans. This work suggests that chemical mimicry of eukaryotic signaling molecules may be common among commensal bacteria and that manipulation of microbiota genes encoding metabolites that elicit host cellular responses represents a new small molecule therapeutic modality (microbiome-biosynthetic-gene-therapy). PMID:28854168

  15. 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.

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

    EPA Science Inventory

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

  17. UNCERTAINTIES IN TRICHLOROETHYLENE PHARMACOKINETIC MODELS

    EPA Science Inventory

    Understanding the pharmacokinetics of a chemical¯its absorption, distribution, metabolism, and excretion in humans and laboratory animals ¯ is critical to the assessment of its human health risks. For trichloroethylene (TCE), numerous physiologically-based pharmacokinetic (PBPK)...

  18. Life-Stage Physiologically-Based Pharmacokinetic (PBPK) Model Applications to Screen Environmental Hazards.

    EPA Science Inventory

    This presentation discusses methods used to extrapolate from in vitro high-throughput screening (HTS) toxicity data for an endocrine pathway to in vivo for early life stages in humans, and the use of a life stage PBPK model to address rapidly changing physiological parameters. A...

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

    EPA Pesticide Factsheets

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

  20. Toward Scalable Trustworthy Computing Using the Human-Physiology-Immunity Metaphor

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

    Hively, Lee M; Sheldon, Frederick T

    The cybersecurity landscape consists of an ad hoc patchwork of solutions. Optimal cybersecurity is difficult for various reasons: complexity, immense data and processing requirements, resource-agnostic cloud computing, practical time-space-energy constraints, inherent flaws in 'Maginot Line' defenses, and the growing number and sophistication of cyberattacks. This article defines the high-priority problems and examines the potential solution space. In that space, achieving scalable trustworthy computing and communications is possible through real-time knowledge-based decisions about cyber trust. This vision is based on the human-physiology-immunity metaphor and the human brain's ability to extract knowledge from data and information. The article outlines future steps towardmore » scalable trustworthy systems requiring a long-term commitment to solve the well-known challenges.« less

  1. Scaling Factor Variability and Toxicokinetic Outcomes in Children

    EPA Science Inventory

    Abstract title: Scaling Factor Variability and Toxicokinetic Outcomes in ChildrenBackgroundBiotransformation rates (Vmax) extrapolated from in vitro data are used increasingly in human physiologically based pharmacokinetic (PBPK) models. PBPK models are widely used in human hea...

  2. The cooperative economy of food: Implications for human life history and physiology.

    PubMed

    Kramer, Karen L

    2018-04-06

    The human diet has undergone substantial modifications since the emergence of modern humans and varies considerably in today's traditional societies. Despite these changes and cross-cultural differences, the human diet can be characterized by several common elements. These include diverse, high quality foods, technological complexity to acquire and process food, and the establishment of home bases for storage, processing and consumption. Together these aspects of the human diet challenge any one individual to independently meet all of his or her daily caloric needs. Humans solve this challenge through food sharing, labor exchange and the division of labor. The cooperative nature of the human diet is associated with many downstream effects on our life history and physiology. This paper overviews the constellation of traits that likely led to a cooperative economy of food, and draws on ethnographic examples to illustrate its effects on human life history and physiology. Two detailed examples using body composition, time allocation and food acquisition data show how cooperation among Savanna Pumé hunter-gatherers affects activity levels, sexual dimorphism in body fat, maturational pace and age at first birth. Copyright © 2018. Published by Elsevier Inc.

  3. Complete scanpaths analysis toolbox.

    PubMed

    Augustyniak, Piotr; Mikrut, Zbigniew

    2006-01-01

    This paper presents a complete open software environment for control, data processing and assessment of visual experiments. Visual experiments are widely used in research on human perception physiology and the results are applicable to various visual information-based man-machine interfacing, human-emulated automatic visual systems or scanpath-based learning of perceptual habits. The toolbox is designed for Matlab platform and supports infra-red reflection-based eyetracker in calibration and scanpath analysis modes. Toolbox procedures are organized in three layers: the lower one, communicating with the eyetracker output file, the middle detecting scanpath events on a physiological background and the one upper consisting of experiment schedule scripts, statistics and summaries. Several examples of visual experiments carried out with use of the presented toolbox complete the paper.

  4. MOVING FROM EXTERNAL EXPOSURE CONCENTRATION TO INTERNAL DOSE: DURATION EXTRAPOLATION BASED ON PHYSIOLOGICALLY-BASED PHARMACOKINETIC-MODEL DERIVED ESTIMATES OF INTERNAL DOSE

    EPA Science Inventory

    The potential human health risk(s) from exposure to chemicals under conditions for which adequate human or animal data are not available must frequently be assessed. Exposure scenario is particularly important for the acute neurotoxic effects of volatile organic compounds (VOCs)...

  5. Home-based vs. laboratory-based practical activities in the learning of human physiology: the perception of students.

    PubMed

    Neves, Ben-Hur S; Altermann, Caroline; Gonçalves, Rithiele; Lara, Marcus Vinícius; Mello-Carpes, Pâmela B

    2017-03-01

    Different tools have been used to facilitate the teaching and learning process in different areas of knowledge. Practical activities represent a form of teaching in which students not only listen to theoretical concepts but are also able to link theory and practice, and their importance in the biological sciences is notable. Sometimes, however, there is neither the time nor the resources to promote laboratory practices in physiology classes. In this sense, home-based practical activities may be an interesting alternative. Here, different approaches of practical activities were used and students' perceptions of the contributions of home-based practical activities (HBPA) and laboratory-based practical activities (LBPA) for physiology learning were collected. After each approach, the students evaluated the activities through an anonymous questionnaire. A total of 49 students completed the questionnaires, and the results demonstrate that both HBPA and LBPA were considered important contributors to physiology learning but that this contribution was more significant in the case of LBPA (χ 2 = 4.356, P = 0.037). Copyright © 2017 the American Physiological Society.

  6. 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.

  7. Singular value decomposition based feature extraction technique for physiological signal analysis.

    PubMed

    Chang, Cheng-Ding; Wang, Chien-Chih; Jiang, Bernard C

    2012-06-01

    Multiscale entropy (MSE) is one of the popular techniques to calculate and describe the complexity of the physiological signal. Many studies use this approach to detect changes in the physiological conditions in the human body. However, MSE results are easily affected by noise and trends, leading to incorrect estimation of MSE values. In this paper, singular value decomposition (SVD) is adopted to replace MSE to extract the features of physiological signals, and adopt the support vector machine (SVM) to classify the different physiological states. A test data set based on the PhysioNet website was used, and the classification results showed that using SVD to extract features of the physiological signal could attain a classification accuracy rate of 89.157%, which is higher than that using the MSE value (71.084%). The results show the proposed analysis procedure is effective and appropriate for distinguishing different physiological states. This promising result could be used as a reference for doctors in diagnosis of congestive heart failure (CHF) disease.

  8. Scanpath-based analysis of objects conspicuity in context of human vision physiology.

    PubMed

    Augustyniak, Piotr

    2007-01-01

    This paper discusses principal aspects of objects conspicuity investigated with use of an eye tracker and interpreted on the background of human vision physiology. Proper management of objects conspicuity is fundamental in several leading edge applications in the information society like advertisement, web design, man-machine interfacing and ergonomics. Although some common rules of human perception are applied since centuries in the art, the interest of human perception process is motivated today by the need of gather and maintain the recipient attention by putting selected messages in front of the others. Our research uses the visual tasks methodology and series of progressively modified natural images. The modifying details were attributed by their size, color and position while the scanpath-derived gaze points confirmed or not the act of perception. The statistical analysis yielded the probability of detail perception and correlations with the attributes. This probability conforms to the knowledge about the retina anatomy and perception physiology, although we use noninvasive methods only.

  9. Space Medicine

    NASA Technical Reports Server (NTRS)

    Pool, Sam L.

    2000-01-01

    The National Academy of Sciences Committee on Space Biology and Medicine points out that space medicine is unique among space sciences, because in addition to addressing questions of fundamental scientific interest, it must address clinical or human health and safety issues as well. Efforts to identify how microgravity affects human physiology began in earnest by the United States in 1960 with the establishment of the National Aeronautics and Space Administration (NASA's) Life Sciences program. Before the first human space missions, prediction about the physiological effects of microgravity in space ranged from extremely severe to none at all. The understanding that has developed from our experiences in space to date allows us to be guardedly optimistic about the ultimate accommodations of humans to space flight. Only by our travels into the microgravity environment of space have we begun to unravel the mysteries associated with gravity's role in shaping human physiology. Space medicine is still at its very earliest stages. Development of this field has been slow for several reasons, including the limited number of space flights, the small number of research subjects, and the competition within the life sciences community and other disciplines for flight opportunities. The physiological changes incurred during space flight may have a dramatic effect on the course of an injury or illness. These physiological changes present an exciting challenge for the field of space medicine: how to best preserve human health and safety while simultaneously deciphering the effects of microgravity on human performance. As the United States considers the future of humans in long-term space travel, it is essential that the many mysteries as to how microgravity affects human systems be addressed with vigor. Based on the current state of our knowledge, the justification is excellent indeed compelling- for NASA to develop a sophisticated capability in space medicine. Teams of physicians and scientists should be actively engaged in fundamental and applied research designed to ensure that it is safe for humans to routinely and repeatedly stay and work in the microgravity environment of space.

  10. LINKING 'OMIC AND GENETIC DATA TO PHYSIOLOGICALLY-BASED PHARMACOKINETIC AND PHARMACODYNAMIC MODELING TO ENHANCE ECOLOGICAL AND HUMAN HEALTH RISK ASSESSMENT

    EPA Science Inventory

    A great deal of academic, private sector, and government research has been initiated to apply advanced molecular biological methods to the discovery of toxicity pathways in wildlife and humans. One aim is the prediction of health outcomes based on the combination of refined chemi...

  11. 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.

  12. Human and rodent aryl hydrocarbon receptor (AHR): from mediator of dioxin toxicity to physiologic AHR functions and therapeutic options.

    PubMed

    Bock, Karl Walter

    2017-04-01

    Metabolism of aryl hydrocarbons and toxicity of dioxins led to the discovery of the aryl hydrocarbon receptor (AHR). Tremendous advances have been made on multiplicity of AHR signaling and identification of endogenous ligands including the tryptophan metabolites FICZ and kynurenine. However, human AHR functions are still poorly understood due to marked species differences as well as cell-type- and cell context-dependent AHR functions. Observations in dioxin-poisoned individuals may provide hints to physiologic AHR functions in humans. Based on these observations three human AHR functions are discussed: (1) Chemical defence and homeostasis of endobiotics. The AHR variant Val381 in modern humans leads to reduced AHR affinity to aryl hydrocarbons in comparison with Neanderthals and primates expressing the Ala381 variant while affinity to indoles remains unimpaired. (2) Homeostasis of stem/progenitor cells. Dioxins dysregulate homeostasis in sebocyte stem cells. (3) Modulation of immunity. In addition to microbial defence, AHR may be involved in a 'disease tolerance defence pathway'. Further characterization of physiologic AHR functions may lead to therapeutic options.

  13. Biomedical Monitoring By A Novel Noncontact Radio Frequency Technology Project

    NASA Technical Reports Server (NTRS)

    Oliva-Buisson, Yvette J. (Compiler)

    2014-01-01

    The area of Space Health and Medicine is one of the NASA's Space Technology Grand Challenges. Space is an extreme environment which is not conducive to human life. The extraterrestrial environment can result in the deconditioning of various human physiological systems and thus require easy to use physiological monitoring technologies in order to better monitor space crews for appropriate health management and successful space missions and space operations. Furthermore, the Space Technology Roadmap's Technology Area Breakdown Structure calls for improvements in research to support human health and performance (Technology Area 06). To address these needs, this project investigated a potential noncontact and noninvasive radio frequency-based technique of monitoring central hemodynamic function in human research subjects in response to orthostatic stress.

  14. 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

  15. 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.

  16. Use of Interactive Live Digital Imaging to Enhance Histology Learning in Introductory Level Anatomy and Physiology Classes

    ERIC Educational Resources Information Center

    Higazi, Tarig B.

    2011-01-01

    Histology is one of the main subjects in introductory college-level Human Anatomy and Physiology classes. Institutions are moving toward the replacement of traditional microscope-based histology learning with virtual microscopy learning amid concerns of losing the valuable learning experience of traditional microscopy. This study used live digital…

  17. Life-Stage Physiologically-Based Pharmacokinetic (PBPK) ...

    EPA Pesticide Factsheets

    This presentation discusses methods used to extrapolate from in vitro high-throughput screening (HTS) toxicity data for an endocrine pathway to in vivo for early life stages in humans, and the use of a life stage PBPK model to address rapidly changing physiological parameters. Adverse outcome pathways (AOPs), in this case endocrine disruption during development, provide a biologically-based framework for linking molecular initiating events triggered by chemical exposures to key events leading to adverse outcomes. The application of AOPs to human health risk assessment requires extrapolation of in vitro HTS toxicity data to in vivo exposures (IVIVE) in humans, which can be achieved through the use of a PBPK/PD model. Exposure scenarios for chemicals in the PBPK/PD model will consider both placental and lactational transfer of chemicals, with a focus on age dependent dosimetry during fetal development and after birth for a nursing infant. This talk proposes a universal life-stage computational model that incorporates changing physiological parameters to link environmental exposures to in vitro levels of HTS assays related to a developmental toxicological AOP for vascular disruption. In vitro toxicity endpoints discussed are based on two mechanisms: 1) Fetal vascular disruption, and 2) Neurodevelopmental toxicity induced by altering thyroid hormone levels in neonates via inhibition of thyroperoxidase in the thyroid gland. Application of our Life-stage computati

  18. 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.

  19. Linguistic Analysis of the Human Heartbeat Using Frequency and Rank Order Statistics

    NASA Astrophysics Data System (ADS)

    Yang, Albert C.-C.; Hseu, Shu-Shya; Yien, Huey-Wen; Goldberger, Ary L.; Peng, C.-K.

    2003-03-01

    Complex physiologic signals may carry unique dynamical signatures that are related to their underlying mechanisms. We present a method based on rank order statistics of symbolic sequences to investigate the profile of different types of physiologic dynamics. We apply this method to heart rate fluctuations, the output of a central physiologic control system. The method robustly discriminates patterns generated from healthy and pathologic states, as well as aging. Furthermore, we observe increased randomness in the heartbeat time series with physiologic aging and pathologic states and also uncover nonrandom patterns in the ventricular response to atrial fibrillation.

  20. Microphysiological modeling of the reproductive tract: a fertile endeavor.

    PubMed

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

    2014-09-01

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

  1. The use of team-based, guided inquiry learning to overcome educational disadvantages in learning human physiology: a structural equation model

    PubMed Central

    Byrne, Graeme

    2014-01-01

    The study of human bioscience is viewed as a crucial curriculum in allied health. Nevertheless, bioscience (and particularly physiology) is notoriously difficult for undergraduates, particularly academically disadvantaged students. So endemic are the high failure rates (particularly in nursing) that it has come to be known as “the human bioscience problem.” In the present report, we describe the outcomes for individual success in studying first-year human physiology in a subject that emphasises team-based active learning as the major pedagogy for mastering subject learning outcomes. Structural equation modeling was used to develop a model of the impact team learning had on individual performance. Modeling was consistent with the idea that students with similar academic abilities (as determined by tertiary entrance rank) were advantaged (scored higher on individual assessment items) by working in strong teams (teams that scored higher in team-based assessments). Analysis of covariance revealed that students who studied the subject with active learning as the major mode of learning activities outperformed students who studied the subject using the traditional didactic teaching format (lectures and tutorials, P = 0.000). After adjustment for tertiary entrance rank (via analysis of covariance) on two individual tests (the final exam and a late-semester in-class test), individual student grades improved by 8% (95% confidence interval: 6–10%) and 12% (95% confidence interval: 10–14%) when students engaged in team-based active learning. These data quantitatively support the notion that weaker students working in strong teams can overcome their educational disadvantages. PMID:25179611

  2. Image feature extraction based on the camouflage effectiveness evaluation

    NASA Astrophysics Data System (ADS)

    Yuan, Xin; Lv, Xuliang; Li, Ling; Wang, Xinzhu; Zhang, Zhi

    2018-04-01

    The key step of camouflage effectiveness evaluation is how to combine the human visual physiological features, psychological features to select effectively evaluation indexes. Based on the predecessors' camo comprehensive evaluation method, this paper chooses the suitable indexes combining with the image quality awareness, and optimizes those indexes combining with human subjective perception. Thus, it perfects the theory of index extraction.

  3. Smart sensors and virtual physiology human approach as a basis of personalized therapies in diabetes mellitus.

    PubMed

    Fernández Peruchena, Carlos M; Prado-Velasco, Manuel

    2010-01-01

    Diabetes mellitus (DM) has a growing incidence and prevalence in modern societies, pushed by the aging and change of life styles. Despite the huge resources dedicated to improve their quality of life, mortality and morbidity rates, these are still very poor. In this work, DM pathology is revised from clinical and metabolic points of view, as well as mathematical models related to DM, with the aim of justifying an evolution of DM therapies towards the correction of the physiological metabolic loops involved. We analyze the reliability of mathematical models, under the perspective of virtual physiological human (VPH) initiatives, for generating and integrating customized knowledge about patients, which is needed for that evolution. Wearable smart sensors play a key role in this frame, as they provide patient's information to the models.A telehealthcare computational architecture based on distributed smart sensors (first processing layer) and personalized physiological mathematical models integrated in Human Physiological Images (HPI) computational components (second processing layer), is presented. This technology was designed for a renal disease telehealthcare in earlier works and promotes crossroads between smart sensors and the VPH initiative. We suggest that it is able to support a truly personalized, preventive, and predictive healthcare model for the delivery of evolved DM therapies.

  4. Smart Sensors and Virtual Physiology Human Approach as a Basis of Personalized Therapies in Diabetes Mellitus

    PubMed Central

    Fernández Peruchena, Carlos M; Prado-Velasco, Manuel

    2010-01-01

    Diabetes mellitus (DM) has a growing incidence and prevalence in modern societies, pushed by the aging and change of life styles. Despite the huge resources dedicated to improve their quality of life, mortality and morbidity rates, these are still very poor. In this work, DM pathology is revised from clinical and metabolic points of view, as well as mathematical models related to DM, with the aim of justifying an evolution of DM therapies towards the correction of the physiological metabolic loops involved. We analyze the reliability of mathematical models, under the perspective of virtual physiological human (VPH) initiatives, for generating and integrating customized knowledge about patients, which is needed for that evolution. Wearable smart sensors play a key role in this frame, as they provide patient’s information to the models. A telehealthcare computational architecture based on distributed smart sensors (first processing layer) and personalized physiological mathematical models integrated in Human Physiological Images (HPI) computational components (second processing layer), is presented. This technology was designed for a renal disease telehealthcare in earlier works and promotes crossroads between smart sensors and the VPH initiative. We suggest that it is able to support a truly personalized, preventive, and predictive healthcare model for the delivery of evolved DM therapies. PMID:21625646

  5. A conceptual review on systems biology in health and diseases: from biological networks to modern therapeutics.

    PubMed

    Somvanshi, Pramod Rajaram; Venkatesh, K V

    2014-03-01

    Human physiology is an ensemble of various biological processes spanning from intracellular molecular interactions to the whole body phenotypic response. Systems biology endures to decipher these multi-scale biological networks and bridge the link between genotype to phenotype. The structure and dynamic properties of these networks are responsible for controlling and deciding the phenotypic state of a cell. Several cells and various tissues coordinate together to generate an organ level response which further regulates the ultimate physiological state. The overall network embeds a hierarchical regulatory structure, which when unusually perturbed can lead to undesirable physiological state termed as disease. Here, we treat a disease diagnosis problem analogous to a fault diagnosis problem in engineering systems. Accordingly we review the application of engineering methodologies to address human diseases from systems biological perspective. The review highlights potential networks and modeling approaches used for analyzing human diseases. The application of such analysis is illustrated in the case of cancer and diabetes. We put forth a concept of cell-to-human framework comprising of five modules (data mining, networking, modeling, experimental and validation) for addressing human physiology and diseases based on a paradigm of system level analysis. The review overtly emphasizes on the importance of multi-scale biological networks and subsequent modeling and analysis for drug target identification and designing efficient therapies.

  6. ['Anatomia actuosa et apta'. The mechanist 'proto'-physiology of B.S. Albinus].

    PubMed

    van der Korst, J K

    1993-01-01

    Already during his tenure as professor of anatomy and surgery (1721-1746) and before he became a professor of physiology and medicine at the University of Leiden, Bernard Siegfried Albinus held private lecture courses on physiology. In these lectures he pleaded for a separation of physiology from theoretical medicine, which was still its customary place in the medical curriculum of the first half of the eighteenth century. According to Albinus, physiology was a science in its own right and should be solely based on the careful observation of forms and structures of the human body. From the 'fabrica', the function ('aptitudo') could be derived by careful reasoning. As shown by a set of lecture notes, which recently came to light, Albinus adhered, initially, to a strictly mechanistic explanatory model, which was almost completely based on the physiological concepts of Herman Boerhaave. However, in contrast to the latter, he even rejected the involvement of chemical processes in digestion. Although his lectures were highly acclaimed as demonstrations of minute anatomy, Albinus met with little or no direct response in regard to his concept of physiology.

  7. Exposure of engineered nanomaterials to plants: Insights into the physiological and biochemical responses-A review.

    PubMed

    Zuverza-Mena, Nubia; Martínez-Fernández, Domingo; Du, Wenchao; Hernandez-Viezcas, Jose A; Bonilla-Bird, Nestor; López-Moreno, Martha L; Komárek, Michael; Peralta-Videa, Jose R; Gardea-Torresdey, Jorge L

    2017-01-01

    Recent investigations show that carbon-based and metal-based engineered nanomaterials (ENMs), components of consumer goods and agricultural products, have the potential to build up in sediments and biosolid-amended agricultural soils. In addition, reports indicate that both carbon-based and metal-based ENMs affect plants differently at the physiological, biochemical, nutritional, and genetic levels. The toxicity threshold is species-dependent and responses to ENMs are driven by a series of factors including the nanomaterial characteristics and environmental conditions. Effects on the growth, physiological and biochemical traits, production and food quality, among others, have been reported. However, a complete understanding of the dynamics of interactions between plants and ENMs is not clear enough yet. This review presents recent publications on the physiological and biochemical effects that commercial carbon-based and metal-based ENMs have in terrestrial plants. This document focuses on crop plants because of their relevance in human nutrition and health. We have summarized the mechanisms of interaction between plants and ENMs as well as identified gaps in knowledge for future investigations. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Guiding the osteogenic fate of mouse and human mesenchymal stem cells through feedback system control.

    PubMed

    Honda, Yoshitomo; Ding, Xianting; Mussano, Federico; Wiberg, Akira; Ho, Chih-Ming; Nishimura, Ichiro

    2013-12-05

    Stem cell-based disease modeling presents unique opportunities for mechanistic elucidation and therapeutic targeting. The stable induction of fate-specific differentiation is an essential prerequisite for stem cell-based strategy. Bone morphogenetic protein 2 (BMP-2) initiates receptor-regulated Smad phosphorylation, leading to the osteogenic differentiation of mesenchymal stromal/stem cells (MSC) in vitro; however, it requires supra-physiological concentrations, presenting a bottleneck problem for large-scale drug screening. Here, we report the use of a double-objective feedback system control (FSC) with a differential evolution (DE) algorithm to identify osteogenic cocktails of extrinsic factors. Cocktails containing significantly reduced doses of BMP-2 in combination with physiologically relevant doses of dexamethasone, ascorbic acid, beta-glycerophosphate, heparin, retinoic acid and vitamin D achieved accelerated in vitro mineralization of mouse and human MSC. These results provide insight into constructive approaches of FSC to determine the applicable functional and physiological environment for MSC in disease modeling, drug screening and tissue engineering.

  9. Guiding the osteogenic fate of mouse and human mesenchymal stem cells through feedback system control

    PubMed Central

    Honda, Yoshitomo; Ding, Xianting; Mussano, Federico; Wiberg, Akira; Ho, Chih-ming; Nishimura, Ichiro

    2013-01-01

    Stem cell-based disease modeling presents unique opportunities for mechanistic elucidation and therapeutic targeting. The stable induction of fate-specific differentiation is an essential prerequisite for stem cell-based strategy. Bone morphogenetic protein 2 (BMP-2) initiates receptor-regulated Smad phosphorylation, leading to the osteogenic differentiation of mesenchymal stromal/stem cells (MSC) in vitro; however, it requires supra-physiological concentrations, presenting a bottleneck problem for large-scale drug screening. Here, we report the use of a double-objective feedback system control (FSC) with a differential evolution (DE) algorithm to identify osteogenic cocktails of extrinsic factors. Cocktails containing significantly reduced doses of BMP-2 in combination with physiologically relevant doses of dexamethasone, ascorbic acid, beta-glycerophosphate, heparin, retinoic acid and vitamin D achieved accelerated in vitro mineralization of mouse and human MSC. These results provide insight into constructive approaches of FSC to determine the applicable functional and physiological environment for MSC in disease modeling, drug screening and tissue engineering. PMID:24305548

  10. Biomedical research on the International Space Station postural and manipulation problems of the human upper limb in weightlessness

    NASA Astrophysics Data System (ADS)

    Neri, Gianluca; Zolesi, Valfredo

    2000-01-01

    Accumulated evidence, based on information gathered on space flight missions and ground based models involving both humans and animals, clearly suggests that exposure to states of microgravity conditions for varying duration induces certain physiological changes; they involve cardiovascular deconditioning, balance disorders, bone weakening, muscle hypertrophy, disturbed sleep patterns and depressed immune responses. The effects of the microgravity on the astronauts' movement and attitude have been studied during different space missions, increasing the knowledge of the human physiology in weightlessness. The purpose of the research addressed in the present paper is to understand and to assess the performances of the upper limb, especially during grasp. Objects of the research are the physiological changes related to the long-term duration spaceflight environment. Specifically, the changes concerning the upper limb are investigated, with particular regard to the performances of the hand in zero-g environments. This research presents also effects on the Earth, improving the studies on a number of pathological states, on the health care and the rehabilitation. In this perspective, a set of experiments are proposed, aimed at the evaluation of the effects of the zero-g environments on neurophysiology of grasping movements, fatigue assessment, precision grip. .

  11. 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.

  12. 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

  13. Effect of an Interactive Web-Based Instruction in the Performance of Undergraduate Anatomy and Physiology Lab Students

    ERIC Educational Resources Information Center

    Gopal, Tamilselvi; Herron, Sherry S.; Mohn, Richard S.; Hartsell, Taralynn; Jawor, Jodie M.; Blickenstaff, Jacob C.

    2010-01-01

    This study provides an understanding of how different interactive technology tools that are integrated into a Website can be used for teaching undergraduate human anatomy and physiology laboratory students. Technology tools refer to a Website that the authors created to teach the Cardiovascular System that includes dynamic tools such as the…

  14. Unique life sciences research facilities at NASA Ames Research Center

    NASA Technical Reports Server (NTRS)

    Mulenburg, G. M.; Vasques, M.; Caldwell, W. F.; Tucker, J.

    1994-01-01

    The Life Science Division at NASA's Ames Research Center has a suite of specialized facilities that enable scientists to study the effects of gravity on living systems. This paper describes some of these facilities and their use in research. Seven centrifuges, each with its own unique abilities, allow testing of a variety of parameters on test subjects ranging from single cells through hardware to humans. The Vestibular Research Facility allows the study of both centrifugation and linear acceleration on animals and humans. The Biocomputation Center uses computers for 3D reconstruction of physiological systems, and interactive research tools for virtual reality modeling. Psycophysiological, cardiovascular, exercise physiology, and biomechanical studies are conducted in the 12 bed Human Research Facility and samples are analyzed in the certified Central Clinical Laboratory and other laboratories at Ames. Human bedrest, water immersion and lower body negative pressure equipment are also available to study physiological changes associated with weightlessness. These and other weightlessness models are used in specialized laboratories for the study of basic physiological mechanisms, metabolism and cell biology. Visual-motor performance, perception, and adaptation are studied using ground-based models as well as short term weightlessness experiments (parabolic flights). The unique combination of Life Science research facilities, laboratories, and equipment at Ames Research Center are described in detail in relation to their research contributions.

  15. Beyond Fractals and 1/f Noise: Multifractal Analysis of Complex Physiological Time Series

    NASA Astrophysics Data System (ADS)

    Ivanov, Plamen Ch.; Amaral, Luis A. N.; Ashkenazy, Yosef; Stanley, H. Eugene; Goldberger, Ary L.; Hausdorff, Jeffrey M.; Yoneyama, Mitsuru; Arai, Kuniharu

    2001-03-01

    We investigate time series with 1/f-like spectra generated by two physiologic control systems --- the human heartbeat and human gait. We show that physiological fluctuations exhibit unexpected ``hidden'' structures often described by scaling laws. In particular, our studies indicate that when analyzed on different time scales the heartbeat fluctuations exhibit cascades of branching patterns with self-similar (fractal) properties, characterized by long-range power-law anticorrelations. We find that these scaling features change during sleep and wake phases, and with pathological perturbations. Further, by means of a new wavelet-based technique, we find evidence of multifractality in the healthy human heartbeat even under resting conditions, and show that the multifractal character and nonlinear properties of the healthy heart are encoded in the Fourier phases. We uncover a loss of multifractality for a life-threatening condition, congestive heart failure. In contrast to the heartbeat, we find that the interstride interval time series of healthy human gait, a voluntary process under neural regulation, is described by a single fractal dimension (such as classical 1/f noise) indicating monofractal behavior. Thus our approach can help distinguish physiological and physical signals with comparable frequency spectra and two-point correlations, and guide modeling of their control mechanisms.

  16. 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

  17. Proceedings of a conference on Cardiovascular Bioinstrumentation

    NASA Technical Reports Server (NTRS)

    Ballard, Rodney W.; Fuller, Charles A.; Mains, Richard; Finger, Herbert J.

    1988-01-01

    The Ames Research Center (ARC) has a long history in the development of cardiovascular (CV) instrumentation for human and animal research. The ARC Cardiovascular Research Lab under the Space Physiology Branch, Space Research Directorate, supports both ground-based and space-based animal and human research goals. The Cardiovascular Research Laboratory was established at ARC in the mid 1960's to conduct ground-based animal research and support development of advanced cardiovascular instrumentation applicable to spaceflight. The ARC Biomedical Research Program also conducts human studies with a CV instrumentation focus.

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

    EPA Science Inventory

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

  19. 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

  20. Monitoring Physiological Variables with Membrane Probes

    NASA Technical Reports Server (NTRS)

    Janle, Elsa M.

    1997-01-01

    This project has demonstrated the possibility of using membrane probes in rodents to monitor physiological variables for extended periods of time. The utility of these probes in physiological studies of microgravity has been demonstrated. The feasibility of developing on-line sensors has also been demonstrated and allows for the possibility of developing real-time automated monitoring systems which can be used in ground-base physiological research as well as in research and medical monitoring in space. In addition to space applications these techniques can be extended to medical monitoring in critical care situations on earth as well as facilitating research in many human and animal diseases.

  1. The first 1000 cultured species of the human gastrointestinal microbiota

    PubMed Central

    Rajilić-Stojanović, Mirjana; de Vos, Willem M

    2014-01-01

    The microorganisms that inhabit the human gastrointestinal tract comprise a complex ecosystem with functions that significantly contribute to our systemic metabolism and have an impact on health and disease. In line with its importance, the human gastrointestinal microbiota has been extensively studied. Despite the fact that a significant part of the intestinal microorganisms has not yet been cultured, presently over 1000 different microbial species that can reside in the human gastrointestinal tract have been identified. This review provides a systematic overview and detailed references of the total of 1057 intestinal species of Eukarya (92), Archaea (8) and Bacteria (957), based on the phylogenetic framework of their small subunit ribosomal RNA gene sequences. Moreover, it unifies knowledge about the prevalence, abundance, stability, physiology, genetics and the association with human health of these gastrointestinal microorganisms, which is currently scattered over a vast amount of literature published in the last 150 years. This detailed physiological and genetic information is expected to be instrumental in advancing our knowledge of the gastrointestinal microbiota. Moreover, it opens avenues for future comparative and functional metagenomic and other high-throughput approaches that need a systematic and physiological basis to have an impact. PMID:24861948

  2. 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.

  3. Nutriproteomics: facts, concepts, and perspectives.

    PubMed

    Sauer, Sascha; Luge, Toni

    2015-03-01

    Nutrition is a basic component of life. Nowadays, human nutrition research focuses amongst others on health-related aspects of food ingredients and extracts, and on analyzing the outcomes of specific diets. Usually, food ingredients such as bioactive peptides come in complex matrices. Single compounds, multiple interactions thereof and the underlying food matrix can vary physiological response of the organism. Proteins and peptides derived from food and beverages can cause adverse allergic reactions but are in general required for multiple functions such as growth and homeostatic regulation. Endogenously expressed human proteins and peptides can be used as biomarkers to monitor physiological deregulation and the effects of food consumption. The intestinal microbiome seems to play a fundamental role in establishing and maintaining physiological regulation and in digesting proteins and peptides and other biomolecules derived from food. Notably, the subtle interplay of flavor naturals in food and beverages with olfactory receptors can result in establishing human taste preferences, which again influences overall physiology. This article presents basic approaches and concepts to address scientific questions in nutritional proteomics and discusses potential benefits of proteomics-based methodologies to help advance the field of molecular nutrition research. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Biological Awareness: Statements for Self-Discovery.

    ERIC Educational Resources Information Center

    Edington, D.W.; Cunningham, Lee

    This guide to biological awareness through guided self-discovery is based on 51 single focus statements concerning the human body. For each statement there are explanations of the underlying physiological principles and suggested activities and discussion ideas to encourage understanding of the statement in terms of the human body's functions,…

  5. A stochastic whole-body physiologically based pharmacokinetic model to assess the impact of inter-individual variability on tissue dosimetry over the human lifespan.

    PubMed

    Beaudouin, Rémy; Micallef, Sandrine; Brochot, Céline

    2010-06-01

    Physiologically based pharmacokinetic (PBPK) models have proven to be successful in integrating and evaluating the influence of age- or gender-dependent changes with respect to the pharmacokinetics of xenobiotics throughout entire lifetimes. Nevertheless, for an effective application of toxicokinetic modelling to chemical risk assessment, a PBPK model has to be detailed enough to include all the multiple tissues that could be targeted by the various xenobiotics present in the environment. For this reason, we developed a PBPK model based on a detailed compartmentalization of the human body and parameterized with new relationships describing the time evolution of physiological and anatomical parameters. To take into account the impact of human variability on the predicted toxicokinetics, we defined probability distributions for key parameters related to the xenobiotics absorption, distribution, metabolism and excretion. The model predictability was evaluated by a direct comparison between computational predictions and experimental data for the internal concentrations of two chemicals (1,3-butadiene and 2,3,7,8-tetrachlorodibenzo-p-dioxin). A good agreement between predictions and observed data was achieved for different scenarios of exposure (e.g., acute or chronic exposure and different populations). Our results support that the general stochastic PBPK model can be a valuable computational support in the area of chemical risk analysis. (c)2010 Elsevier Inc. All rights reserved.

  6. An Individualized, Perception-Based Protocol to Investigate Human Physiological Responses to Cooling

    PubMed Central

    Coolbaugh, Crystal L.; Bush, Emily C.; Galenti, Elizabeth S.; Welch, E. Brian; Towse, Theodore F.

    2018-01-01

    Cold exposure, a known stimulant of the thermogenic effects of brown adipose tissue (BAT), is the most widely used method to study BAT physiology in adult humans. Recently, individualized cooling has been recommended to standardize the physiological cold stress applied across participants, but critical experimental details remain unclear. The purpose of this work was to develop a detailed methodology for an individualized, perception-based protocol to investigate human physiological responses to cooling. Participants were wrapped in two water-circulating blankets and fitted with skin temperature probes to estimate BAT activity and peripheral vasoconstriction. We created a thermoesthesia graphical user interface (tGUI) to continuously record the subject's perception of cooling and shivering status during the cooling protocol. The protocol began with a 15 min thermoneutral phase followed by a series of 10 min cooling phases and concluded when sustained shivering (>1 min duration) occurred. Researchers used perception of cooling feedback (tGUI ratings) to manually adjust and personalize the water temperature at each cooling phase. Blanket water temperatures were recorded continuously during the protocol. Twelve volunteers (ages: 26.2 ± 1.4 years; 25% female) completed a feasibility study to evaluate the proposed protocol. Water temperature, perception of cooling, and shivering varied considerably across participants in response to cooling. Mean clavicle skin temperature, a surrogate measure of BAT activity, decreased (−0.99°C, 95% CI: −1.7 to −0.25°C, P = 0.16) after the cooling protocol, but an increase in supraclavicular skin temperature was observed in 4 participants. A strong positive correlation was also found between thermoesthesia and peripheral vasoconstriction (ρ = 0.84, P < 0.001). The proposed individualized, perception-based protocol therefore has potential to investigate the physiological responses to cold stress applied across populations with varying age, sex, body composition, and cold sensitivity characteristics. PMID:29593558

  7. Biomechanics-based in silico medicine: the manifesto of a new science.

    PubMed

    Viceconti, Marco

    2015-01-21

    In this perspective article we discuss the role of contemporary biomechanics in the light of recent applications such as the development of the so-called Virtual Physiological Human technologies for physiology-based in silico medicine. In order to build Virtual Physiological Human (VPH) models, computer models that capture and integrate the complex systemic dynamics of living organisms across radically different space-time scales, we need to re-formulate a vast body of existing biology and physiology knowledge so that it is formulated as a quantitative hypothesis, which can be expressed in mathematical terms. Once the predictive accuracy of these models is confirmed against controlled experiments and against clinical observations, we will have VPH model that can reliably predict certain quantitative changes in health status of a given patient, but also, more important, we will have a theory, in the true meaning this word has in the scientific method. In this scenario, biomechanics plays a very important role, biomechanics is one of the few areas of life sciences where we attempt to build full mechanistic explanations based on quantitative observations, in other words, we investigate living organisms like physical systems. This is in our opinion a Copernican revolution, around which the scope of biomechanics should be re-defined. Thus, we propose a new definition for our research domain "Biomechanics is the study of living organisms as mechanistic systems". Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. 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.

  9. Rodent growth, behavior, and physiology resulting from flight on the Space Life Sciences-1 mission

    NASA Technical Reports Server (NTRS)

    Jahns, G.; Meylor, J.; Fast, T.; Hawes, N.; Zarow, G.

    1992-01-01

    A rodent-based spaceflight study is conducted to investigate physiological changes in rats vs humans and the effects of changes in the design of the Research Animal Holding Facility (RAHF) and the Animal Enclosure Module (AEM). Rats were housed in the AEM and the RAHF, and controls were kept in identical flight hardware on earth subjected to the same flight-environmental profile. Biosamples and organ weights are taken to compare the rats before and after flight, and food/water intake are also compared. Weight gain, body weight, and food consumptions in the flight rats are significantly lower than corresponding values for the control subjects. Flight rats tend to have smaller postexperiment spleens and hearts, and flight rats consumed more water in the AEM than in the RAHF. The rodents' behavior is analogous to humans with respect to physiological and reconditioning effects, showing that the rat is a good model for basic research into the effects of spaceflight on humans.

  10. 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

  11. A shift in paradigm towards human biology-based systems for cholestatic-liver diseases.

    PubMed

    Noor, Fozia

    2015-12-01

    Cholestatic-liver diseases (CLDs) arise from diverse causes ranging from genetic factors to drug-induced cholestasis. The so-called diseases of civilization (obesity, diabetes, metabolic disorders, non-alcoholic liver disease, cardiovascular diseases, etc.) are intricately implicated in liver and gall bladder diseases. Although CLDs have been extensively studied, there seem to be important gaps in the understanding of human disease. Despite the fact that many animal models exist and substantial clinical data are available, translation of this knowledge towards therapy has been disappointingly limited. Recent advances in liver cell culture such as in vivo-like 3D cultivation of human primary hepatic cells, human induced pluripotent stem cell-derived hepatocytes; and cutting-edge analytical techniques such as 'omics' technologies and high-content screenings could play a decisive role in deeper mechanistic understanding of CLDs. This Topical Review proposes a roadmap to human biology-based research using omics technologies providing quantitative information on mechanisms in an adverse outcome/disease pathway framework. With modern sensitive tools, a shift in paradigm in human disease research seems timely and even inevitable to overcome species barriers in translation. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  12. 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.

  13. 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

  14. 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

  15. Evolution of brain-computer interfaces: going beyond classic motor physiology

    PubMed Central

    Leuthardt, Eric C.; Schalk, Gerwin; Roland, Jarod; Rouse, Adam; Moran, Daniel W.

    2010-01-01

    The notion that a computer can decode brain signals to infer the intentions of a human and then enact those intentions directly through a machine is becoming a realistic technical possibility. These types of devices are known as brain-computer interfaces (BCIs). The evolution of these neuroprosthetic technologies could have significant implications for patients with motor disabilities by enhancing their ability to interact and communicate with their environment. The cortical physiology most investigated and used for device control has been brain signals from the primary motor cortex. To date, this classic motor physiology has been an effective substrate for demonstrating the potential efficacy of BCI-based control. However, emerging research now stands to further enhance our understanding of the cortical physiology underpinning human intent and provide further signals for more complex brain-derived control. In this review, the authors report the current status of BCIs and detail the emerging research trends that stand to augment clinical applications in the future. PMID:19569892

  16. Sex Differences in Human Fatigability: Mechanisms and Insight to Physiological Responses

    PubMed Central

    Hunter, Sandra K.

    2014-01-01

    Sex-related differences in physiology and anatomy are responsible for profound differences in neuromuscular performance and fatigability between men and women. Women are usually less fatigable than men for similar intensity isometric fatiguing contractions. This sex difference in fatigability, however, is task specific because different neuromuscular sites will be stressed when the requirements of the task are altered, and the stress on these sites can differ for men and women. Task variables that can alter the sex difference in fatigue include the type, intensity and speed of contraction, the muscle group assessed, and the environmental conditions. Physiological mechanisms that are responsible for sex-based differences in fatigability may include activation of the motor neuron pool from cortical and subcortical regions, synaptic inputs to the motor neuron pool via activation of metabolically-sensitive small afferent fibres in the muscle, muscle perfusion, and skeletal muscle metabolism and fibre type properties. Non-physiological factors such as the sex bias of studying more males than females in human and animal experiments can also mask a true understanding of the magnitude and mechanisms of sex-based differences in physiology and fatigability. Despite recent developments, there is a tremendous lack of understanding of sex differences in neuromuscular function and fatigability, the prevailing mechanisms and the functional consequences. This review emphasises the need to understand sex-based differences in fatigability in order to shed light on the benefits and limitations that fatigability can exert for men and women during daily tasks, exercise performance, training and rehabilitation in both health and disease. PMID:24433272

  17. Physiologically Based Pharmacokinetic Model for Terbinafine in Rats and Humans

    PubMed Central

    Hosseini-Yeganeh, Mahboubeh; McLachlan, Andrew J.

    2002-01-01

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

  18. 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

  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…

  20. Success stories and emerging themes in conservation physiology.

    PubMed

    Madliger, Christine L; Cooke, Steven J; Crespi, Erica J; Funk, Jennifer L; Hultine, Kevin R; Hunt, Kathleen E; Rohr, Jason R; Sinclair, Brent J; Suski, Cory D; Willis, Craig K R; Love, Oliver P

    2016-01-01

    The potential benefits of physiology for conservation are well established and include greater specificity of management techniques, determination of cause-effect relationships, increased sensitivity of health and disturbance monitoring and greater capacity for predicting future change. While descriptions of the specific avenues in which conservation and physiology can be integrated are readily available and important to the continuing expansion of the discipline of 'conservation physiology', to date there has been no assessment of how the field has specifically contributed to conservation success. However, the goal of conservation physiology is to foster conservation solutions and it is therefore important to assess whether physiological approaches contribute to downstream conservation outcomes and management decisions. Here, we present eight areas of conservation concern, ranging from chemical contamination to invasive species to ecotourism, where physiological approaches have led to beneficial changes in human behaviour, management or policy. We also discuss the shared characteristics of these successes, identifying emerging themes in the discipline. Specifically, we conclude that conservation physiology: (i) goes beyond documenting change to provide solutions; (ii) offers a diversity of physiological metrics beyond glucocorticoids (stress hormones); (iii) includes approaches that are transferable among species, locations and times; (iv) simultaneously allows for human use and benefits to wildlife; and (v) is characterized by successes that can be difficult to find in the primary literature. Overall, we submit that the field of conservation physiology has a strong foundation of achievements characterized by a diversity of conservation issues, taxa, physiological traits, ecosystem types and spatial scales. We hope that these concrete successes will encourage the continued evolution and use of physiological tools within conservation-based research and management plans.

  1. 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

  2. Ames Life Science Data Archive: Translational Rodent Research at Ames

    NASA Technical Reports Server (NTRS)

    Wood, Alan E.; French, Alison J.; Ngaotheppitak, Ratana; Leung, Dorothy M.; Vargas, Roxana S.; Maese, Chris; Stewart, Helen

    2014-01-01

    The Life Science Data Archive (LSDA) office at Ames is responsible for collecting, curating, distributing and maintaining information pertaining to animal and plant experiments conducted in low earth orbit aboard various space vehicles from 1965 to present. The LSDA will soon be archiving data and tissues samples collected on the next generation of commercial vehicles; e.g., SpaceX & Cygnus Commercial Cargo Craft. To date over 375 rodent flight experiments with translational application have been archived by the Ames LSDA office. This knowledge base of fundamental research can be used to understand mechanisms that affect higher organisms in microgravity and help define additional research whose results could lead the way to closing gaps identified by the Human Research Program (HRP). This poster will highlight Ames contribution to the existing knowledge base and how the LSDA can be a resource to help answer the questions surrounding human health in long duration space exploration. In addition, it will illustrate how this body of knowledge was utilized to further our understanding of how space flight affects the human system and the ability to develop countermeasures that negate the deleterious effects of space flight. The Ames Life Sciences Data Archive (ALSDA) includes current descriptions of over 700 experiments conducted aboard the Shuttle, International Space Station (ISS), NASA/MIR, Bion/Cosmos, Gemini, Biosatellites, Apollo, Skylab, Russian Foton, and ground bed rest studies. Research areas cover Behavior and Performance, Bone and Calcium Physiology, Cardiovascular Physiology, Cell and Molecular Biology, Chronobiology, Developmental Biology, Endocrinology, Environmental Monitoring, Gastrointestinal Physiology, Hematology, Immunology, Life Support System, Metabolism and Nutrition, Microbiology, Muscle Physiology, Neurophysiology, Pharmacology, Plant Biology, Pulmonary Physiology, Radiation Biology, Renal, Fluid and Electrolyte Physiology, and Toxicology. These experiment descriptions and data can be accessed online via the public LSDA website (http://lsda.jsc.nasa.gov) and information can be requested via the Data Request form at http://lsda.jsc.nasa.gov/common/dataRequest/dataRequest.aspx or by contacting the ALSDA Office at: Alison.J.French@nasa.gov

  3. Modern embalming, circulation of fluids, and the voyage through the human arterial system: Carl L. Barnes and the culture of immortality in America.

    PubMed

    Podgorny, Irina

    2011-01-01

    By considering the work of American embalmer, lawyer, and physician Carl Lewis Barnes (1872-1927), this paper analyzes the emergence of modern embalming in America. Barnes experimented with and exhibited the techniques by which embalming fluids travelled into the most remote cavities of the human body. In this sense, modem embalmers based their skills and methods on experimental medicine, turning the anatomy of blood vessels, physiology of circulation, and composition of blood into a circuit that allowed embalming fluids to move throughout the corpse. Embalmers in the late 19th century took ownership of the laws of hydrodynamics and the physiology of blood circulation to market their fluids and equipment, thus playing the role of physiologists of death, performing and demonstrating physiological experiments with dead bodies.

  4. Local spatio-temporal analysis in vision systems

    NASA Astrophysics Data System (ADS)

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

    1994-07-01

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

  5. 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)

  6. System and method for leveraging human physiological traits to control microprocessor frequency

    DOEpatents

    Shye, Alex; Pan, Yan; Scholbrock, Benjamin; Miller, J. Scott; Memik, Gokhan; Dinda, Peter A; Dick, Robert P

    2014-03-25

    A system and method for leveraging physiological traits to control microprocessor frequency are disclosed. In some embodiments, the system and method may optimize, for example, a particular processor-based architecture based on, for example, end user satisfaction. In some embodiments, the system and method may determine, for example, whether their users are satisfied to provide higher efficiency, improved reliability, reduced power consumption, increased security, and a better user experience. The system and method may use, for example, biometric input devices to provide information about a user's physiological traits to a computer system. Biometric input devices may include, for example, one or more of the following: an eye tracker, a galvanic skin response sensor, and/or a force sensor.

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

    PubMed Central

    Saylor, Kyle; Zhang, Chenming

    2017-01-01

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

  8. Thermal responses and perceptions under distinct ambient temperature and wind conditions.

    PubMed

    Shimazaki, Yasuhiro; Yoshida, Atsumasa; Yamamoto, Takanori

    2015-01-01

    Wind conditions are widely recognized to influence the thermal states of humans. In this study, we investigated the relationship between wind conditions and thermal perception and energy balance in humans. The study participants were exposed for 20 min to 3 distinct ambient temperatures, wind speeds, and wind angles. During the exposure, the skin temperatures as a physiological reaction and mental reactions of the human body were measured and the energy balance was calculated based on the human thermal-load method. The results indicate that the human thermal load is an accurate indicator of human thermal states under all wind conditions. Furthermore, wind speed and direction by themselves do not account for the human thermal experience. Because of the thermoregulation that occurs to prevent heat loss and protect the core of the body, a low skin temperature was maintained and regional differences in skin temperature were detected under cool ambient conditions. Thus, the human thermal load, which represents physiological parameters such as skin-temperature change, adequately describes the mixed sensation of the human thermal experience. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Toxicity challenges in environmental chemicals: Prediction of human plasma protein binding through quantitative structure-activity relationship (QSAR) models (2016 IVIVE Workshop Proceedings)

    EPA Science Inventory

    Physiologically based pharmacokinetic (PBPK) models bridge the gap between in vitro assays and in vivo effects by accounting for the adsorption, distribution, metabolism, and excretion of xenobiotics, which is especially useful in the assessment of human toxicity. Quantitative st...

  10. Matters of Taste: Bridging Molecular Physiology and the Humanities

    ERIC Educational Resources Information Center

    Rangachari, P. K.; Rangachari, Usha

    2015-01-01

    Taste perception was the focus of an undergraduate course in the health sciences that bridged the sciences and humanities. A problem-based learning approach was used to study the biological issues, whereas the cultural transmutations of these molecular mechanisms were explored using a variety of resources (novels, cookbooks, and films). Multiple…

  11. Regulatory physiology discipline science plan

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The focus of the Regulatory Physiology discipline of the Space Physiology and Countermeasures Program is twofold. First, to determine and study how microgravity and associated factors of space flight affect the regulatory mechanisms by which humans adapt and achieve homeostasis and thereby regulate their ability to respond to internal and external signals; and, second, to study selected physiological systems that have been demonstrated to be influenced by gravity. The Regulatory Physiology discipline, as defined here, is composed of seven subdisciplines: (1) Circadian Rhythms, (2) Endocrinology, (3) Fluid and Electrolyte Regulation, (4) Hematology, (5) Immunology, (6) Metabolism and Nutrition, and (7) Temperature Regulation. The purpose of this Discipline Science Plan is to provide a conceptual strategy for NASA's Life Sciences Division research and development activities in the area of regulatory physiology. It covers the research areas critical to NASA's programmatic requirements for the Extended-Duration Orbiter, Space Station Freedom, and exploration mission science activities. These science activities include ground-based and flight; basic, applied, and operational; and animal and human research and development. This document summarizes the current status of the program, outlines available knowledge, establishes goals and objectives, identifies science priorities, and defines critical questions in regulatory physiology. It contains a general plan that will be used by both NASA Headquarters Program Offices and the field centers to review and plan basic, applied, and operational intramural and extramural research and development activities in this area.

  12. Success stories and emerging themes in conservation physiology

    PubMed Central

    Madliger, Christine L.; Cooke, Steven J.; Crespi, Erica J.; Funk, Jennifer L.; Hultine, Kevin R.; Hunt, Kathleen E.; Rohr, Jason R.; Sinclair, Brent J.; Suski, Cory D.; Willis, Craig K. R.; Love, Oliver P.

    2016-01-01

    The potential benefits of physiology for conservation are well established and include greater specificity of management techniques, determination of cause–effect relationships, increased sensitivity of health and disturbance monitoring and greater capacity for predicting future change. While descriptions of the specific avenues in which conservation and physiology can be integrated are readily available and important to the continuing expansion of the discipline of ‘conservation physiology’, to date there has been no assessment of how the field has specifically contributed to conservation success. However, the goal of conservation physiology is to foster conservation solutions and it is therefore important to assess whether physiological approaches contribute to downstream conservation outcomes and management decisions. Here, we present eight areas of conservation concern, ranging from chemical contamination to invasive species to ecotourism, where physiological approaches have led to beneficial changes in human behaviour, management or policy. We also discuss the shared characteristics of these successes, identifying emerging themes in the discipline. Specifically, we conclude that conservation physiology: (i) goes beyond documenting change to provide solutions; (ii) offers a diversity of physiological metrics beyond glucocorticoids (stress hormones); (iii) includes approaches that are transferable among species, locations and times; (iv) simultaneously allows for human use and benefits to wildlife; and (v) is characterized by successes that can be difficult to find in the primary literature. Overall, we submit that the field of conservation physiology has a strong foundation of achievements characterized by a diversity of conservation issues, taxa, physiological traits, ecosystem types and spatial scales. We hope that these concrete successes will encourage the continued evolution and use of physiological tools within conservation-based research and management plans. PMID:27382466

  13. Major component analysis of dynamic networks of physiologic organ interactions

    NASA Astrophysics Data System (ADS)

    Liu, Kang K. L.; Bartsch, Ronny P.; Ma, Qianli D. Y.; Ivanov, Plamen Ch

    2015-09-01

    The human organism is a complex network of interconnected organ systems, where the behavior of one system affects the dynamics of other systems. Identifying and quantifying dynamical networks of diverse physiologic systems under varied conditions is a challenge due to the complexity in the output dynamics of the individual systems and the transient and nonlinear characteristics of their coupling. We introduce a novel computational method based on the concept of time delay stability and major component analysis to investigate how organ systems interact as a network to coordinate their functions. We analyze a large database of continuously recorded multi-channel physiologic signals from healthy young subjects during night-time sleep. We identify a network of dynamic interactions between key physiologic systems in the human organism. Further, we find that each physiologic state is characterized by a distinct network structure with different relative contribution from individual organ systems to the global network dynamics. Specifically, we observe a gradual decrease in the strength of coupling of heart and respiration to the rest of the network with transition from wake to deep sleep, and in contrast, an increased relative contribution to network dynamics from chin and leg muscle tone and eye movement, demonstrating a robust association between network topology and physiologic function.

  14. 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).

  15. Tree physiology research in a changing world.

    PubMed

    Kaufmann, Merrill R.; Linder, Sune

    1996-01-01

    Changes in issues and advances in methodology have contributed to substantial progress in tree physiology research during the last several decades. Current research focuses on process interactions in complex systems and the integration of processes across multiple spatial and temporal scales. An increasingly important challenge for future research is assuring sustainability of production systems and forested ecosystems in the face of increased demands for natural resources and human disturbance of forests. Meeting this challenge requires significant shifts in research approach, including the study of limitations of productivity that may accompany achievement of system sustainability, and a focus on the biological capabilities of complex land bases altered by human activity.

  16. The effect of active learning on student characteristics in a human physiology course for nonmajors.

    PubMed

    Wilke, R Russell

    2003-12-01

    This study investigated the effect of active-learning strategies on college students' achievement, motivation, and self-efficacy in a human physiology course for nonmajors. Variables were studied via a quasi-experimental, Solomon four-group design on 141 students at a small west-Texas university. Treatment groups were taught using a continuum-based, active-learning model implemented over the course of a semester. Control groups were taught using traditional didactic lecture methods. To assess the effects of the continuum-based active learning strategies, students were administered a comprehensive physiology content exam, the Motivated Strategies for Learning Questionnaire, and attitude surveys. Factorial analyses indicated that the treatment groups acquired significantly more content knowledge and were significantly more self-efficacious than students in the control groups. There were no significant differences in motivation. Attitude surveys indicated that students in both the treatment and control groups demonstrated a positive attitude toward active learning, believed it helped (or would help) them to learn the material, and would choose an active learning course in the future.

  17. Puzzle-based versus traditional lecture: comparing the effects of pedagogy on academic performance in an undergraduate human anatomy and physiology II lab.

    PubMed

    Stetzik, Lucas; Deeter, Anthony; Parker, Jamie; Yukech, Christine

    2015-06-23

    A traditional lecture-based pedagogy conveys information and content while lacking sufficient development of critical thinking skills and problem solving. A puzzle-based pedagogy creates a broader contextual framework, and fosters critical thinking as well as logical reasoning skills that can then be used to improve a student's performance on content specific assessments. This paper describes a pedagogical comparison of traditional lecture-based teaching and puzzle-based teaching in a Human Anatomy and Physiology II Lab. Using a single subject/cross-over design half of the students from seven sections of the course were taught using one type of pedagogy for the first half of the semester, and then taught with a different pedagogy for the second half of the semester. The other half of the students were taught the same material but with the order of the pedagogies reversed. Students' performance on quizzes and exams specific to the course, and in-class assignments specific to this study were assessed for: learning outcomes (the ability to form the correct conclusion or recall specific information), and authentic academic performance as described by (Am J Educ 104:280-312, 1996). Our findings suggest a significant improvement in students' performance on standard course specific assessments using a puzzle-based pedagogy versus a traditional lecture-based teaching style. Quiz and test scores for students improved by 2.1 and 0.4% respectively in the puzzle-based pedagogy, versus the traditional lecture-based teaching. Additionally, the assessments of authentic academic performance may only effectively measure a broader conceptual understanding in a limited set of contexts, and not in the context of a Human Anatomy and Physiology II Lab. In conclusion, a puzzle-based pedagogy, when compared to traditional lecture-based teaching, can effectively enhance the performance of students on standard course specific assessments, even when the assessments only test a limited conceptual understanding of the material.

  18. Characterizing Uncertainty and Variability in PBPK Models: State of the Science and Needs for Research and Implementation

    EPA Science Inventory

    Mode-of-action based risk and safety assessments can rely upon tissue dosimetry estimates in animals and humans obtained from physiologically-based pharmacokinetic (PBPK) modeling. However, risk assessment also increasingly requires characterization of uncertainty and variabilit...

  19. Addressing Early Life Sensitivity Using Physiologically Based Pharmacokinetic Modeling and In Vitro to In Vivo Extrapolation

    PubMed Central

    Yoon, Miyoung; Clewell, Harvey J.

    2016-01-01

    Physiologically based pharmacokinetic (PBPK) modeling can provide an effective way to utilize in vitro and in silico based information in modern risk assessment for children and other potentially sensitive populations. In this review, we describe the process of in vitro to in vivo extrapolation (IVIVE) to develop PBPK models for a chemical in different ages in order to predict the target tissue exposure at the age of concern in humans. We present our on-going studies on pyrethroids as a proof of concept to guide the readers through the IVIVE steps using the metabolism data collected either from age-specific liver donors or expressed enzymes in conjunction with enzyme ontogeny information to provide age-appropriate metabolism parameters in the PBPK model in the rat and human, respectively. The approach we present here is readily applicable to not just to other pyrethroids, but also to other environmental chemicals and drugs. Establishment of an in vitro and in silico-based evaluation strategy in conjunction with relevant exposure information in humans is of great importance in risk assessment for potentially vulnerable populations like early ages where the necessary information for decision making is limited. PMID:26977255

  20. Addressing Early Life Sensitivity Using Physiologically Based Pharmacokinetic Modeling and In Vitro to In Vivo Extrapolation.

    PubMed

    Yoon, Miyoung; Clewell, Harvey J

    2016-01-01

    Physiologically based pharmacokinetic (PBPK) modeling can provide an effective way to utilize in vitro and in silico based information in modern risk assessment for children and other potentially sensitive populations. In this review, we describe the process of in vitro to in vivo extrapolation (IVIVE) to develop PBPK models for a chemical in different ages in order to predict the target tissue exposure at the age of concern in humans. We present our on-going studies on pyrethroids as a proof of concept to guide the readers through the IVIVE steps using the metabolism data collected either from age-specific liver donors or expressed enzymes in conjunction with enzyme ontogeny information to provide age-appropriate metabolism parameters in the PBPK model in the rat and human, respectively. The approach we present here is readily applicable to not just to other pyrethroids, but also to other environmental chemicals and drugs. Establishment of an in vitro and in silico-based evaluation strategy in conjunction with relevant exposure information in humans is of great importance in risk assessment for potentially vulnerable populations like early ages where the necessary information for decision making is limited.

  1. A tale of two CLCs: biophysical insights toward understanding ClC-5 and ClC-7 function in endosomes and lysosomes

    PubMed Central

    Zifarelli, Giovanni

    2015-01-01

    Abstract The CLC protein family comprises both Cl− channels and H+-coupled anion transporters. The understanding of the critical role of CLC proteins in a number of physiological functions has greatly contributed to a revision of the classical paradigm that attributed to Cl− ions only a marginal role in human physiology. The endosomal ClC-5 and the lysosomal ClC-7 are the best characterized human CLC transporters. Their dysfunction causes Dent’s disease and osteopetrosis, respectively. It had been originally proposed that they would provide a Cl− shunt conductance allowing efficient acidification of intracellular compartments. However, this model seems to conflict with the transport properties of these proteins and with recent physiological evidence. Currently, there is no consensus on their specific physiological role. CLC proteins present also a number of peculiar biophysical properties, such as the dimeric architecture, the co-existence of intrinsically different thermodynamic modes of transport based on similar structural principles, and the gating mechanism recently emerging for the transporters, just to name a few. This review focuses on the biophysical properties and physiological roles of ClC-5 and ClC-7. PMID:26036722

  2. Advantages and Disadvantages of Physiological Assessment For Next Generation Control Room Design

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

    Tuan Q. Tran; Ronald L. Boring; Donald D. Dudenhoeffer

    2007-08-01

    Abstract - We propose using non-obtrusive physiological assessment (e.g., eye tracking,) to assess human information processing errors (e.g., loss of vigilance) and limitations (e.g., workload) for advanced energy systems early in the design process. This physiological approach for assessing risk will circumvent many limitations of current risk methodologies such as subjective rating (e.g., rater’s biases) and performance modeling (e.g., risk assessment is scripted and is based upon the individual modeler’s judgment). Key uses will be to evaluate (early in the design process) novel control room equipment and configurations as well as newly developed automated systems that will inevitably place amore » high information load on operators. The physiological risk assessment tool will allow better precision in pinpointing problematic design issues and will provide a “real-time” assessment of risk. Furthermore, this physiological approach would extend the state-of-the-art of human reliability methods from a “static” measure to more “dynamic.” This paper will discuss a broad range of the current popular online performance gauges as well as its advantages and disadvantages for use in next generation control room.« less

  3. 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.

  4. Building an experimental model of the human body with non-physiological parameters.

    PubMed

    Labuz, Joseph M; Moraes, Christopher; Mertz, David R; Leung, Brendan M; Takayama, Shuichi

    2017-03-01

    New advances in engineering and biomedical technology have enabled recent efforts to capture essential aspects of human physiology in microscale, in-vitro systems. The application of these advances to experimentally model complex processes in an integrated platform - commonly called a 'human-on-a-chip (HOC)' - requires that relevant compartments and parameters be sized correctly relative to each other and to the system as a whole. Empirical observation, theoretical treatments of resource distribution systems and natural experiments can all be used to inform rational design of such a system, but technical and fundamental challenges (e.g. small system blood volumes and context-dependent cell metabolism, respectively) pose substantial, unaddressed obstacles. Here, we put forth two fundamental principles for HOC design: inducing in-vivo -like cellular metabolic rates is necessary and may be accomplished in-vitro by limiting O 2 availability and that the effects of increased blood volumes on drug concentration can be mitigated through pharmacokinetics-based treatments of solute distribution. Combining these principles with natural observation and engineering workarounds, we derive a complete set of design criteria for a practically realizable, physiologically faithful, five-organ millionth-scale (× 10 -6 ) microfluidic model of the human body.

  5. Building an experimental model of the human body with non-physiological parameters

    PubMed Central

    Labuz, Joseph M.; Moraes, Christopher; Mertz, David R.; Leung, Brendan M.; Takayama, Shuichi

    2017-01-01

    New advances in engineering and biomedical technology have enabled recent efforts to capture essential aspects of human physiology in microscale, in-vitro systems. The application of these advances to experimentally model complex processes in an integrated platform — commonly called a ‘human-on-a-chip (HOC)’ — requires that relevant compartments and parameters be sized correctly relative to each other and to the system as a whole. Empirical observation, theoretical treatments of resource distribution systems and natural experiments can all be used to inform rational design of such a system, but technical and fundamental challenges (e.g. small system blood volumes and context-dependent cell metabolism, respectively) pose substantial, unaddressed obstacles. Here, we put forth two fundamental principles for HOC design: inducing in-vivo-like cellular metabolic rates is necessary and may be accomplished in-vitro by limiting O2 availability and that the effects of increased blood volumes on drug concentration can be mitigated through pharmacokinetics-based treatments of solute distribution. Combining these principles with natural observation and engineering workarounds, we derive a complete set of design criteria for a practically realizable, physiologically faithful, five-organ millionth-scale (× 10−6) microfluidic model of the human body. PMID:28713851

  6. Organ-specific physiological responses to acute physical exercise and long-term training in humans.

    PubMed

    Heinonen, Ilkka; Kalliokoski, Kari K; Hannukainen, Jarna C; Duncker, Dirk J; Nuutila, Pirjo; Knuuti, Juhani

    2014-11-01

    Virtually all tissues in the human body rely on aerobic metabolism for energy production and are therefore critically dependent on continuous supply of oxygen. Oxygen is provided by blood flow, and, in essence, changes in organ perfusion are also closely associated with alterations in tissue metabolism. In response to acute exercise, blood flow is markedly increased in contracting skeletal muscles and myocardium, but perfusion in other organs (brain and bone) is only slightly enhanced or is even reduced (visceral organs). Despite largely unchanged metabolism and perfusion, repeated exposures to altered hemodynamics and hormonal milieu produced by acute exercise, long-term exercise training appears to be capable of inducing effects also in tissues other than muscles that may yield health benefits. However, the physiological adaptations and driving-force mechanisms in organs such as brain, liver, pancreas, gut, bone, and adipose tissue, remain largely obscure in humans. Along these lines, this review integrates current information on physiological responses to acute exercise and to long-term physical training in major metabolically active human organs. Knowledge is mostly provided based on the state-of-the-art, noninvasive human imaging studies, and directions for future novel research are proposed throughout the review. ©2014 Int. Union Physiol. Sci./Am. Physiol. Soc.

  7. Evaluation of chest ultrasound integrated teaching of respiratory system physiology to medical students.

    PubMed

    Paganini, Matteo; Bondì, Michela; Rubini, Alessandro

    2017-12-01

    Ultrasound imaging is a widely used diagnostic technique, whose integration in medical education is constantly growing. The aim of this study was to evaluate chest ultrasound usefulness in teaching respiratory system physiology, students' perception of chest ultrasound integration into a traditional lecture in human physiology, and short-term concept retention. A lecture about respiratory physiology was integrated with ultrasound and delivered to third-year medical students. It included basic concepts of ultrasound imaging and the physiology of four anatomic sectors of the body of a male volunteer, shown with a portable ultrasound device (pleural sliding, diaphragmatic movement, inferior vena cava diameter variations, cardiac movements). Students' perceptions of the integrated lecture were assessed, and attendance recorded. After 4 mo, four multiple-choice questions about respiratory physiology were administered during the normal human physiology examinations, and the results of students who attended the lesson and those of who did not were compared. One hundred thirty-four students attended the lecture. Most of them showed encouragement for the study of the subject and considered the ultrasound integrated lecture more interesting than a traditional one and pertinent to the syllabus. Exposed students achieved a better score at the examination and committed less errors than did nonexposed students. The chest ultrasound integrated lecture was appreciated by students. A possible association between the exposure to the lecture and short-term concept retention is shown by better performances of the exposed cohort at the examination. A systematic introduction of ultrasound into physiology traditional teaching will be promoted by the Ultrasound-Based Medical Education movement. Copyright © 2017 the American Physiological Society.

  8. Multi-sector thermo-physiological head simulator for headgear research

    NASA Astrophysics Data System (ADS)

    Martinez, Natividad; Psikuta, Agnes; Corberán, José Miguel; Rossi, René M.; Annaheim, Simon

    2017-02-01

    A novel thermo-physiological human head simulator for headgear testing was developed by coupling a thermal head manikin with a thermo-physiological model. As the heat flux at head-site is directly measured by the head manikin, this method provides a realistic quantification of the heat transfer phenomena occurring in the headgear, such as moisture absorption-desorption cycles, condensation, or moisture migration across clothing layers. Before coupling, the opportunities of the head manikin for representing the human physiology were evaluated separately. The evaluation revealed reduced precision in forehead and face temperature predictions under extreme heterogeneous temperature distributions and no initial limitation for simulating temperature changes observed in the human physiology. The thermo-physiological model predicted higher sweat rates when applied for coupled than for pure virtual simulations. After coupling, the thermo-physiological human head simulator was validated using eight human experiments. It precisely predicted core, mean skin, and forehead temperatures with average rmsd values within the average experimental standard deviation (rmsd of 0.20 ± 0.15, 0.83 ± 0.34, and 1.04 ± 0.54 °C, respectively). However, in case of forehead, precision was lower for the exposures including activity than for the sedentary exposures. The representation of the human sweat evaporation could be affected by a reduced evaporation efficiency and the manikin sweat dynamics. The industry will benefit from this thermo-physiological human head simulator leading to the development of helmet designs with enhanced thermal comfort and, therefore, with higher acceptance by users.

  9. Improved inhalation technology for setting safe exposure levels for workplace chemicals

    NASA Technical Reports Server (NTRS)

    Stuart, Bruce O.

    1993-01-01

    Threshold Limit Values recommended as allowable air concentrations of a chemical in the workplace are often based upon a no-observable-effect-level (NOEL) determined by experimental inhalation studies using rodents. A 'safe level' for human exposure must then be estimated by the use of generalized safety factors in attempts to extrapolate from experimental rodents to man. The recent development of chemical-specific physiologically-based toxicokinetics makes use of measured physiological, biochemical, and metabolic parameters to construct a validated model that is able to 'scale-up' rodent response data to predict the behavior of the chemical in man. This procedure is made possible by recent advances in personal computer software and the emergence of appropriate biological data, and provides an analytical tool for much more reliable risk evaluation and airborne chemical exposure level setting for humans.

  10. Evidence for altered metabolic pathways during environmental stress: (1)H-NMR spectroscopy based metabolomics and clinical studies on subjects of sea-voyage and Antarctic-stay.

    PubMed

    Yadav, Anand Prakash; Chaturvedi, Shubhra; Mishra, Kamla Prasad; Pal, Sunil; Ganju, Lilly; Singh, Shashi Bala

    2014-08-01

    The Antarctic context is an analogue of space travel, with close similarity in ambience of extreme climate, isolation, constrained living spaces, disrupted sleep cycles, and environmental stress. The present study examined the impact of the harsh habitat of Antarctica on human physiology and its metabolic pathways, by analyzing human serum samples, using (1)H-NMR spectroscopy for identification of metabolites; and quantifying other physiological and clinical parameters for correlation between expression data and metabolite data. Sera from seven adult males (of median age 36years) who participated in this study, from the 28th Indian Expeditionary group to the Antarctica station Maitri, were collected in chronological sequence. These included: i) baseline control; ii) during ship journey; iii) at Antarctica, in the months of March, May, August and November; to enable study of temporal evolution of monitored physiological states. 29 metabolites in serum were identified from the 400MHz (1)H-NMR spectra. Out of these, 19 metabolites showed significant variations in levels, during the ship journey and the stay at Maitri, compared to the base-line levels. Further biochemical analysis also supported these results, indicating that the ship journey, and the long-term Antarctic exposure, affected kidney and liver functioning. Our metabolite data highlights for the first time the effect of environmental stress on the patho-physiology of the human system. Multivariate analysis tools were employed for this metabonomics study, using (1)H-NMR spectroscopy. Copyright © 2014. Published by Elsevier Inc.

  11. A feasiblity study of an ultrasonic test phantom arm

    NASA Astrophysics Data System (ADS)

    Schneider, Philip

    This thesis is a feasibility study for the creation of a test phantom that replicates the physiological features, from an acoustic and mechanical standpoint, of that of a human arm. Physiological feature set includes; Heart, Arteries, Veins, Bone, Muscle, Fat, Skin, and Dermotographic Features (finger prints). Mechanical Aspects include, vascular compression and distention, elasticity of tissue layers, mechanics of human heart. The end goal of which to have a working understanding of each component in order to create a controllable, real time, physiologically accurate, test phantom for a wide range of ultrasonic based applications. These applications can range from devices like wearable technologies to medical training, to biometric "Liveness" detection methods. The proposed phantom would allow for a number of natural bodily functions to be measured including but not limited to vascular mapping, blood pressure, heart rate, subdermal imaging, and general ultrasonic imaging.

  12. From in vitro to in vivo: Integration of the virtual cell based assay with physiologically based kinetic modelling.

    PubMed

    Paini, Alicia; Sala Benito, Jose Vicente; Bessems, Jos; Worth, Andrew P

    2017-12-01

    Physiologically based kinetic (PBK) models and the virtual cell based assay can be linked to form so called physiologically based dynamic (PBD) models. This study illustrates the development and application of a PBK model for prediction of estragole-induced DNA adduct formation and hepatotoxicity in humans. To address the hepatotoxicity, HepaRG cells were used as a surrogate for liver cells, with cell viability being used as the in vitro toxicological endpoint. Information on DNA adduct formation was taken from the literature. Since estragole induced cell damage is not directly caused by the parent compound, but by a reactive metabolite, information on the metabolic pathway was incorporated into the model. In addition, a user-friendly tool was developed by implementing the PBK/D model into a KNIME workflow. This workflow can be used to perform in vitro to in vivo extrapolation and forward as backward dosimetry in support of chemical risk assessment. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. On making nursing undergraduate human reproductive physiology content meaningful and relevant: discussion of human pleasure in its biological context.

    PubMed

    McClusky, Leon Mendel

    2012-01-01

    The traditional presentation of the Reproductive Physiology component in an Anatomy and Physiology course to nursing undergraduates focuses on the broad aspects of hormonal regulation of reproduction and gonadal anatomy, with the role of the higher centres of the brain omitted. An introductory discussion is proposed which could precede the lectures on the reproductive organs. The discussion gives an overview of the biological significance of human pleasure, the involvement of the neurotransmitter dopamine, and the role of pleasure in the survival of the individual and even species. Pleasure stimuli (positive and negative) and the biological significance of naturally-induced pleasurable experiences are briefly discussed in the context of reproduction and the preservation of genetic material with an aim to foster relevancy between subject material and human behaviour in any type of society. The tenderness of this aspect of the human existence is well-understood because of its invariable association with soul-revealing human expressions such as love, infatuation, sexual flirtations, all of which are underpinned by arousal, desire and/or pleasure. Assuming that increased knowledge correlates with increased confidence, the proposed approach may provide the nurse with an adequate knowledge base to overcome well-known barriers in communicating with their patients about matters of sexual health and intimacy. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. TXNIP links redox circuitry to glucose control.

    PubMed

    Muoio, Deborah M

    2007-06-01

    Thioredoxin-interacting protein (TXNIP) binds and inhibits the reducing activity of thioredoxin. A new study (Parikh et al., 2007) implicates this redox rheostat as a negative regulator of peripheral glucose metabolism in humans. Investigators combined human physiology, genomic screening, and cell-based genetic studies to highlight TNXIP as a potential culprit in the pathogenesis of type 2 diabetes.

  15. Phi in physiology, psychology and biomechanics: The golden ratio between myth and science.

    PubMed

    Iosa, Marco; Morone, Giovanni; Paolucci, Stefano

    2018-03-01

    In recent years, there has been a renewed interest in the use of the so-called golden ratio (Phi, ϕ), an irrational number with fractal properties, used in artworks since V century BC. and now for modelling complex biological structures and functions. This number, in fact, recursively pops-up in human history, from Ancient Greeks to Renaissance, and to contemporary scientific studies. Nevertheless, recent scientific results often fall between two extremes: those of a priori sceptic researchers accusing the artificial emergence of ϕ in many studies, and those of researchers that find a mystic meaning in the presence of ϕ in human physiology. This review moves between these two extremes to provide a scientifically based discussion about the possible presence of Phi in human physiology, psychology, and biomechanics of heart and locomotion. We provide scientific evidence, analysing reasons for the presence of Phi, reporting the weakness of some studies overstating the potential meaning of this number, and reporting the reasons for which it could be actually found in some biological structures and functions. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Monitoring and Correcting Autonomic Function Aboard Mir: NASA Technology Used in Space and on Earth to Facilitate Adaptation

    NASA Technical Reports Server (NTRS)

    Cowings, P.; Toscano, W.; Taylor, B.; DeRoshia, C.; Kornilova, L.; Koslovskaya, I.; Miller, N.

    1999-01-01

    The broad objective of the research was to study individual characteristics of human adaptation to long duration spaceflight and possibilities of their correction using autonomic conditioning. The changes in autonomic state during adaptation to microgravity can have profound effects on the operational efficiency of crewmembers and may result in debilitating biomedical symptoms. Ground-based and inflight experiment results showed that certain responses of autonomic nervous system were correlated with, or consistently preceded, reports of performance decrements or the symptoms. Autogenic-Feedback-Training Exercise (AFTE) is a physiological conditioning method that has been used to train people to voluntary control several of their own physiological responses. The specific objectives were: 1) To study human autonomic nervous system (ANS) responses to sustained exposure to microgravity; 2) To study human behavior/performance changes related to physiology; 3) To evaluate the effectiveness of preflight autonomic conditioning (AFTE) for facilitating adaptation to space and readaptation to Earth; and 4) To archive these data for the NASA Life Sciences Data Archive and thereby make this information available to the international scientific community.

  17. Use of a probabilistic PBPK/PD model to calculate Data Derived Extrapolation Factors for chlorpyrifos.

    PubMed

    Poet, Torka S; Timchalk, Charles; Bartels, Michael J; Smith, Jordan N; McDougal, Robin; Juberg, Daland R; Price, Paul S

    2017-06-01

    A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model combined with Monte Carlo analysis of inter-individual variation was used to assess the effects of the insecticide, chlorpyrifos and its active metabolite, chlorpyrifos oxon in humans. The PBPK/PD model has previously been validated and used to describe physiological changes in typical individuals as they grow from birth to adulthood. This model was updated to include physiological and metabolic changes that occur with pregnancy. The model was then used to assess the impact of inter-individual variability in physiology and biochemistry on predictions of internal dose metrics and quantitatively assess the impact of major sources of parameter uncertainty and biological diversity on the pharmacodynamics of red blood cell acetylcholinesterase inhibition. These metrics were determined in potentially sensitive populations of infants, adult women, pregnant women, and a combined population of adult men and women. The parameters primarily responsible for inter-individual variation in RBC acetylcholinesterase inhibition were related to metabolic clearance of CPF and CPF-oxon. Data Derived Extrapolation Factors that address intra-species physiology and biochemistry to replace uncertainty factors with quantitative differences in metrics were developed in these same populations. The DDEFs were less than 4 for all populations. These data and modeling approach will be useful in ongoing and future human health risk assessments for CPF and could be used for other chemicals with potential human exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Gravity, the third dimension of life support in space

    NASA Technical Reports Server (NTRS)

    Burton, Russell R.

    1994-01-01

    The ascent of the human into high altitudes required a 2-D life support system that supplied: oxygen, and heat. At lower altitudes, increased oxygen concentration in the inhaled gases was useful, but at higher altitudes for longer durations, this 'clever' life support approach was no longer adequate--physiologic requirements had to provide a natural pressure-based environment. In space, the life support system requires a third dimension, gravity. Although substituting for gravity has been successful on a limited number of physiologic functions for short-duration stays in space, long durations will require the effects of the real thing for critical physiologic functions. It has been known for over a hundred years that the forces of acceleration (G) and gravity are equivalent. Therefore, gravitational stimulation in space can be achieved with centrifugation. However, for this stimulation to be effective, the dosage of G required to maintain normal physiologic function must be determined. An approximation of this dosage of G for the human can be determined with 3-day bed-rest studies including periodic centrifuge exposure. Recent research on this topic is reviewed.

  19. 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,…

  20. Two Archetypes of Motor Control Research.

    PubMed

    Latash, Mark L

    2010-07-01

    This reply to the Commentaries is focused on two archetypes of motor control research, one based on physics and physiology and the other based on control theory and ideas of neural computations. The former approach, represented by the equilibrium-point hypothesis, strives to discover the physical laws and salient physiological variables that make purposeful coordinated movements possible. The latter approach, represented by the ideas of internal models and optimal control, tries to apply methods of control developed for man-made inanimate systems to the human body. Specific issues related to control with subthreshold membrane depolarization, motor redundancy, and the idea of synergies are briefly discussed.

  1. Experimental and numerical study of physiological responses in hot environments.

    PubMed

    Yang, Jie; Weng, Wenguo; Zhang, Baoting

    2014-10-01

    This paper proposed a multi-node human thermal model to predict human thermal responses in hot environments. The model was extended based on the Tanabe's work by considering the effects of high temperature on heat production, blood flow rate, and heat exchange coefficients. Five healthy men dressed in shorts were exposed in thermal neutral (29 °C) and high temperature (45 °C) environments. The rectal temperatures and skin temperatures of seven human body segments were continuously measured during the experiment. Validation of this model was conducted with experimental data. The results showed that the current model could accurately predict the skin and core temperatures in terms of the tendency and absolute values. In the human body segments expect calf and trunk, the temperature differences between the experimental data and the predicted results in high temperature environment were smaller than those in the thermally neutral environment conditions. The extended model was proved to be capable of predicting accurately human physiological responses in hot environments. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Developing Hydrogeological Site Characterization Strategies based on Human Health Risk

    NASA Astrophysics Data System (ADS)

    de Barros, F.; Rubin, Y.; Maxwell, R. M.

    2013-12-01

    In order to provide better sustainable groundwater quality management and minimize the impact of contamination in humans, improved understanding and quantification of the interaction between hydrogeological models, geological site information and human health are needed. Considering the joint influence of these components in the overall human health risk assessment and the corresponding sources of uncertainty aid decision makers to better allocate resources in data acquisition campaigns. This is important to (1) achieve remediation goals in a cost-effective manner, (2) protect human health and (3) keep water supplies clean in order to keep with quality standards. Such task is challenging since a full characterization of the subsurface is unfeasible due to financial and technological constraints. In addition, human exposure and physiological response to contamination are subject to uncertainty and variability. Normally, sampling strategies are developed with the goal of reducing uncertainty, but less often they are developed in the context of their impacts on the overall system uncertainty. Therefore, quantifying the impact from each of these components (hydrogeological, behavioral and physiological) in final human health risk prediction can provide guidance for decision makers to best allocate resources towards minimal prediction uncertainty. In this presentation, a multi-component human health risk-based framework is presented which allows decision makers to set priorities through an information entropy-based visualization tool. Results highlight the role of characteristic length-scales characterizing flow and transport in determining data needs within an integrated hydrogeological-health framework. Conditions where uncertainty reduction in human health risk predictions may benefit from better understanding of the health component, as opposed to a more detailed hydrogeological characterization, are also discussed. Finally, results illustrate how different dose-response models can impact the probability of human health risk exceeding a regulatory threshold.

  3. 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

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

    PubMed Central

    Majewicz Fey, Ann

    2018-01-01

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

  5. Multi-sector thermo-physiological head simulator for headgear research.

    PubMed

    Martinez, Natividad; Psikuta, Agnes; Corberán, José Miguel; Rossi, René M; Annaheim, Simon

    2017-02-01

    A novel thermo-physiological human head simulator for headgear testing was developed by coupling a thermal head manikin with a thermo-physiological model. As the heat flux at head-site is directly measured by the head manikin, this method provides a realistic quantification of the heat transfer phenomena occurring in the headgear, such as moisture absorption-desorption cycles, condensation, or moisture migration across clothing layers. Before coupling, the opportunities of the head manikin for representing the human physiology were evaluated separately. The evaluation revealed reduced precision in forehead and face temperature predictions under extreme heterogeneous temperature distributions and no initial limitation for simulating temperature changes observed in the human physiology. The thermo-physiological model predicted higher sweat rates when applied for coupled than for pure virtual simulations. After coupling, the thermo-physiological human head simulator was validated using eight human experiments. It precisely predicted core, mean skin, and forehead temperatures with average rmsd values within the average experimental standard deviation (rmsd of 0.20 ± 0.15, 0.83 ± 0.34, and 1.04 ± 0.54 °C, respectively). However, in case of forehead, precision was lower for the exposures including activity than for the sedentary exposures. The representation of the human sweat evaporation could be affected by a reduced evaporation efficiency and the manikin sweat dynamics. The industry will benefit from this thermo-physiological human head simulator leading to the development of helmet designs with enhanced thermal comfort and, therefore, with higher acceptance by users.

  6. Physiologically based pharmacokinetic and pharmacodynamic modeling of an antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in a mouse xenograft model of human breast cancer.

    PubMed

    Zhang, Tao; Li, Yanyan; Zou, Peng; Yu, Jing-yu; McEachern, Donna; Wang, Shaomeng; Sun, Duxin

    2013-09-01

    The inhibitors of apoptosis proteins (IAPs) are a class of key apoptosis regulators overexpressed or dysregulated in cancer. SM-406/AT-406 is a potent and selective small molecule mimetic of Smac that antagonizes the inhibitor of apoptosis proteins (IAPs). A physiologically based pharmacokinetic and pharmacodynamic (PBPK-PD) model was developed to predict the tissue concentration-time profiles of SM-406, the related onco-protein levels in tumor, and the tumor growth inhibition in a mouse model bearing human breast cancer xenograft. In the whole body physiologically based pharmacokinetic (PBPK) model for pharmacokinetics characterization, a well stirred (perfusion rate-limited) model was used to describe SM-406 pharmacokinetics in the lung, heart, kidney, intestine, liver and spleen, and a diffusion rate-limited (permeability limited) model was used for tumor. Pharmacodynamic (PD) models were developed to correlate the SM-406 concentration in tumor to the cIAP1 degradation, pro-caspase 8 decrease, CL-PARP accumulation and tumor growth inhibition. The PBPK-PD model well described the experimental pharmacokinetic data, the pharmacodynamic biomarker responses and tumor growth. This model may be helpful to predict tumor and plasma SM-406 concentrations in the clinic. Copyright © 2013 John Wiley & Sons, Ltd.

  7. HUMAN--A Comprehensive Physiological Model.

    ERIC Educational Resources Information Center

    Coleman, Thomas G.; Randall, James E.

    1983-01-01

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

  8. Monitoring of endogenous carbon monoxide dynamics in human breath by tunable diode laser

    NASA Astrophysics Data System (ADS)

    Stepanov, Eugene V.; Daraselia, Mikhail V.; Zyrianov, Pavel V.; Shulagin, Yurii A.; Skrupskii, Vladimir A.

    1996-01-01

    High sensitive CO gas analyzer based on tunable diode laser (TDL) was used as a real time monitor of endogenous carbon monoxide in a set of breath physiology experiments. The measurements of the CO content dynamics in exhaled air with 10 ppb sensitivity were attended with detection of carbon dioxide and O2 in breath, lung ventilation parameters, heart rate and blood analysis using conventional techniques. Temporal variations of endogenous CO in human breath caused by hyperoxia, hypoxia, hyperventilation and sport loading were first studied in real time. Scattering of the CO variation time constants was observed for different tested persons. Possible reasons for this scattering related with the organisms' physiology peculiarities are discussed.

  9. Human Milk Banking-Facts and Issues to Resolve

    PubMed Central

    Corpeleijn, Willemijn E.; Vermeulen, Marijn J.; van Vliet, Ineke; Kruger, Caroline; van Goudoever, Johannes B.

    2010-01-01

    The number of human milk banks is increasing worldwide. Although the beneficial effects of feeding premature infants with their mother’s milk are well documented, less is known about the effects of feeding these infants with pasteurized donor milk. We propose a randomized trial comparing the effects of a 100% human milk-based diet (human milk supplemented with a human milk-derived fortifier) and a diet (partially) based on bovine milk. In theory, human milk has a beneficial effect on various aspects of human physiology, most of which become apparent after infancy. We therefore propose an extensive follow-up program that takes this aspect into consideration. Other issues concerning the practice of human milk banks need to be addressed as well as optimization of the feeding strategies for preterm infants. PMID:22254053

  10. Human milk banking-facts and issues to resolve.

    PubMed

    Corpeleijn, Willemijn E; Vermeulen, Marijn J; van Vliet, Ineke; Kruger, Caroline; van Goudoever, Johannes B

    2010-07-01

    The number of human milk banks is increasing worldwide. Although the beneficial effects of feeding premature infants with their mother's milk are well documented, less is known about the effects of feeding these infants with pasteurized donor milk. We propose a randomized trial comparing the effects of a 100% human milk-based diet (human milk supplemented with a human milk-derived fortifier) and a diet (partially) based on bovine milk. In theory, human milk has a beneficial effect on various aspects of human physiology, most of which become apparent after infancy. We therefore propose an extensive follow-up program that takes this aspect into consideration. Other issues concerning the practice of human milk banks need to be addressed as well as optimization of the feeding strategies for preterm infants.

  11. 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.

  12. Mapping visual cortex in monkeys and humans using surface-based atlases

    NASA Technical Reports Server (NTRS)

    Van Essen, D. C.; Lewis, J. W.; Drury, H. A.; Hadjikhani, N.; Tootell, R. B.; Bakircioglu, M.; Miller, M. I.

    2001-01-01

    We have used surface-based atlases of the cerebral cortex to analyze the functional organization of visual cortex in humans and macaque monkeys. The macaque atlas contains multiple partitioning schemes for visual cortex, including a probabilistic atlas of visual areas derived from a recent architectonic study, plus summary schemes that reflect a combination of physiological and anatomical evidence. The human atlas includes a probabilistic map of eight topographically organized visual areas recently mapped using functional MRI. To facilitate comparisons between species, we used surface-based warping to bring functional and geographic landmarks on the macaque map into register with corresponding landmarks on the human map. The results suggest that extrastriate visual cortex outside the known topographically organized areas is dramatically expanded in human compared to macaque cortex, particularly in the parietal lobe.

  13. Recognition of emotions using multimodal physiological signals and an ensemble deep learning model.

    PubMed

    Yin, Zhong; Zhao, Mengyuan; Wang, Yongxiong; Yang, Jingdong; Zhang, Jianhua

    2017-03-01

    Using deep-learning methodologies to analyze multimodal physiological signals becomes increasingly attractive for recognizing human emotions. However, the conventional deep emotion classifiers may suffer from the drawback of the lack of the expertise for determining model structure and the oversimplification of combining multimodal feature abstractions. In this study, a multiple-fusion-layer based ensemble classifier of stacked autoencoder (MESAE) is proposed for recognizing emotions, in which the deep structure is identified based on a physiological-data-driven approach. Each SAE consists of three hidden layers to filter the unwanted noise in the physiological features and derives the stable feature representations. An additional deep model is used to achieve the SAE ensembles. The physiological features are split into several subsets according to different feature extraction approaches with each subset separately encoded by a SAE. The derived SAE abstractions are combined according to the physiological modality to create six sets of encodings, which are then fed to a three-layer, adjacent-graph-based network for feature fusion. The fused features are used to recognize binary arousal or valence states. DEAP multimodal database was employed to validate the performance of the MESAE. By comparing with the best existing emotion classifier, the mean of classification rate and F-score improves by 5.26%. The superiority of the MESAE against the state-of-the-art shallow and deep emotion classifiers has been demonstrated under different sizes of the available physiological instances. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Introductory anatomy and physiology in an undergraduate nursing curriculum.

    PubMed

    Brown, S J; White, S; Power, N

    2017-03-01

    Using an educational data mining approach, first-year academic achievement of undergraduate nursing students, which included two compulsory courses in introductory human anatomy and physiology, was compared with achievement in a final semester course that transitioned students into the workplace. We hypothesized that students could be grouped according to their first-year academic achievement using a two-step cluster analysis method and that grades achieved in the human anatomy and physiology courses would be strong predictors of overall achievement. One cohort that graduated in 2014 (n = 105) and one that graduated in 2015 (n = 94) were analyzed separately, and for both cohorts, two groups were identified, these being "high achievers" (HIGH) and "low achievers" (LOW). Consistently, the anatomy and physiology courses were the strongest predictors of group assignment, such that a good grade in these was much more likely to put a student into a high-achieving group. Students in the HIGH groups also scored higher in the Transition to Nursing course when compared with students in the LOW groups. The higher predictor importance of the anatomy and physiology courses suggested that if a first-year grade-point average was calculated for students, an increased weighting should be attributed to these courses. Identifying high-achieving students based on first-year academic scores may be a useful method to predict future academic performance. Copyright © 2017 the American Physiological Society.

  15. 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.

  16. On optics of human meridians

    NASA Astrophysics Data System (ADS)

    Yang, Hongqin; Xie, Shusen; Li, Hui; Wang, Yuhua

    2009-04-01

    A new concept and its methodology for studying human meridians are presented based on rigorous and scientific observation on the objective existence of human meridians in view of biomedical optics. According to this methodology, the infrared radiant characteristics of acupuncture meridians over human body and the optical transport properties of light propagating along the meridian are reported. This study, thus, confirms the existence of acupuncture meridians, sheds new light on an approach to investigation of human meridians and offers a new perspective in understanding the potential meridian functions such as energy and information transfer and physiological regulation.

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

    PubMed Central

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

    2015-01-01

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

  18. 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.

  19. Audited credential delegation: a usable security solution for the virtual physiological human toolkit.

    PubMed

    Haidar, Ali N; Zasada, Stefan J; Coveney, Peter V; Abdallah, Ali E; Beckles, Bruce; Jones, Mike A S

    2011-06-06

    We present applications of audited credential delegation (ACD), a usable security solution for authentication, authorization and auditing in distributed virtual physiological human (VPH) project environments that removes the use of digital certificates from end-users' experience. Current security solutions are based on public key infrastructure (PKI). While PKI offers strong security for VPH projects, it suffers from serious usability shortcomings in terms of end-user acquisition and management of credentials which deter scientists from exploiting distributed VPH environments. By contrast, ACD supports the use of local credentials. Currently, a local ACD username-password combination can be used to access grid-based resources while Shibboleth support is underway. Moreover, ACD provides seamless and secure access to shared patient data, tools and infrastructure, thus supporting the provision of personalized medicine for patients, scientists and clinicians participating in e-health projects from a local to the widest international scale.

  20. Audited credential delegation: a usable security solution for the virtual physiological human toolkit

    PubMed Central

    Haidar, Ali N.; Zasada, Stefan J.; Coveney, Peter V.; Abdallah, Ali E.; Beckles, Bruce; Jones, Mike A. S.

    2011-01-01

    We present applications of audited credential delegation (ACD), a usable security solution for authentication, authorization and auditing in distributed virtual physiological human (VPH) project environments that removes the use of digital certificates from end-users' experience. Current security solutions are based on public key infrastructure (PKI). While PKI offers strong security for VPH projects, it suffers from serious usability shortcomings in terms of end-user acquisition and management of credentials which deter scientists from exploiting distributed VPH environments. By contrast, ACD supports the use of local credentials. Currently, a local ACD username–password combination can be used to access grid-based resources while Shibboleth support is underway. Moreover, ACD provides seamless and secure access to shared patient data, tools and infrastructure, thus supporting the provision of personalized medicine for patients, scientists and clinicians participating in e-health projects from a local to the widest international scale. PMID:22670214

  1. Human Research Program Human Health Countermeasures Element Nutrition Risk Standing Review Panel

    NASA Technical Reports Server (NTRS)

    Bistrian, Bruce

    2009-01-01

    The Nutrition Risk Standing Review Panel (SRP) reviewed and discussed the specific gaps and tasks for the Human Health Countermeasures (HHC) Element related to nutrition identified in the Human Research Program (HRP) Integrated Research Plan. There was general consensus that the described gaps and proposed tasks were critical to future NASA mission success. The SRP acknowledged the high scientific quality of the work currently being undertaken by the Nutritional Biochemistry group under the direction of Dr. Scott Smith. In review of the entire HRP, four new gaps were identified that complement the Element's existing research activities. Given the limitations of ground-based analogs for many of the unique physiological and metabolic alterations in space, future studies are needed to quantify nutritional factors that change during actual space flight. In addition, future tasks should seek to better evaluate the time course of physiological and metabolic alterations during flight to better predict alterations during longer duration missions. Finally, given the recent data suggesting a potential role for increased inflammatory responses during space flight, the role of inflammation needs to be explored in detail, including the development of potential countermeasures and new ground based analogs, if this possibility is confirmed.

  2. 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.

  3. A physically based analytical spatial air temperature and humidity model

    Treesearch

    Yang Yang; Theodore A. Endreny; David J. Nowak

    2013-01-01

    Spatial variation of urban surface air temperature and humidity influences human thermal comfort, the settling rate of atmospheric pollutants, and plant physiology and growth. Given the lack of observations, we developed a Physically based Analytical Spatial Air Temperature and Humidity (PASATH) model. The PASATH model calculates spatial solar radiation and heat...

  4. Overview of Dioxin Kinetics and Application of Dioxin Physiologically Based Phannacokinetic (PBPK) Models to Risk Assessment

    EPA Science Inventory

    The available data on the pharmacokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in animals and humans have been thoroughly reviewed in literature. It is evident based on these reviews and other analyses that three distinctive features of TCDD play important roles in dete...

  5. 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;

  6. 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.

  7. Sensing human physiological response using wearable carbon nanotube-based fabrics

    NASA Astrophysics Data System (ADS)

    Wang, Long; Loh, Kenneth J.; Koo, Helen S.

    2016-04-01

    Flexible and wearable sensors for human monitoring have received increased attention. Besides detecting motion and physical activity, measuring human vital signals (e.g., respiration rate and body temperature) provide rich data for assessing subjects' physiological or psychological condition. Instead of using conventional, bulky, sensing transducers, the objective of this study was to design and test a wearable, fabric-like sensing system. In particular, multi-walled carbon nanotube (MWCNT)-latex thin films of different MWCNT concentrations were first fabricated using spray coating. Freestanding MWCNT-latex films were then sandwiched between two layers of flexible fabric using iron-on adhesive to form the wearable sensor. Second, to characterize its strain sensing properties, the fabric sensors were subjected to uniaxial and cyclic tensile load tests, and they exhibited relatively stable electromechanical responses. Finally, the wearable sensors were placed on a human subject for monitoring simple motions and for validating their practical strain sensing performance. Overall, the wearable fabric sensor design exhibited advances such as flexibility, ease of fabrication, light weight, low cost, noninvasiveness, and user comfort.

  8. Epigenomics and human adaptation to high altitude.

    PubMed

    Julian, Colleen G

    2017-11-01

    Over the past decade, major technological and analytical advancements have propelled efforts toward identifying the molecular mechanisms that govern human adaptation to high altitude. Despite remarkable progress with respect to the identification of adaptive genomic signals that are strongly associated with the "hypoxia-tolerant" physiological characteristics of high-altitude populations, many questions regarding the fundamental biological processes underlying human adaptation remain unanswered. Vital to address these enduring questions will be determining the role of epigenetic processes, or non-sequence-based features of the genome, that are not only critical for the regulation of transcriptional responses to hypoxia but heritable across generations. This review proposes that epigenomic processes are involved in shaping patterns of adaptation to high altitude by influencing adaptive potential and phenotypic variability under conditions of limited oxygen supply. Improved understanding of the interaction between genetic, epigenetic, and environmental factors holds great promise to provide deeper insight into the mechanisms underlying human adaptive potential, and clarify its implications for biomedical research. Copyright © 2017 the American Physiological Society.

  9. Physiological pharmacokinetic modeling

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

    Menzel, D.B.

    1987-10-01

    Risk assessment often defines the approach and the degree of regulation, decisions in risk assessment often have major regulatory impacts. Chemicals that have economic value or that were byproducts of the chemical industry are common subjects of such decisions. Regrettably, decisions related to risk assessment, science, or regulatory matters will frequently be made with incomplete information and on the basis of intuitive reasoning. Statistical fits to experimental data have been used to estimate risks in humans from experimental data in animals. These treatments have not taken into account the obvious differences in physiology, biochemistry, and size between aniamals and humans.more » In this article the use of mathematical models based on continuous relationships, rather than quantal events, are discussed. The mathematical models can be used to adjust the dose in the quantal response model, but the emphasis will be on how these mathematical models are conceived and what implications their use holds for risk assessment. Experiments with humans that produce toxic effects cannot be done. Data for human toxicity will always be lacking.« less

  10. Space medicine research: Needs for the 21st century

    NASA Technical Reports Server (NTRS)

    Pepper, L. J.

    1992-01-01

    Space medicine research in the 21st century will continue to focus on the four major areas including: (1) expansion of the current incomplete knowledge base of clinical and subclinical physiological changes due to microgravity; (2) development of countermeasures to extend the capabilities of the human performance envelope in extended duration flights; (3) development of novel methods for delivering all aspects of a comprehensive health care system in extreme remote conditions: and (4) further research and application of systems for biological materials processing. New space transportation vehicles will place unique physiologic and human factors demands on the human system, while providing better access to platforms for materials processing. Success in meeting the demands in each of the noted research areas will require an extensive, interactive team approach. Personnel from the medical research,operational, developmental, and basic science communities will be essential to success.

  11. 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.

  12. A novel non-contact radar sensor for affective and interactive analysis.

    PubMed

    Lin, Hong-Dun; Lee, Yen-Shien; Shih, Hsiang-Lan; Chuang, Bor-Nian

    2013-01-01

    Currently, many physiological signal sensing techniques have been applied for affective analysis in Human-Computer Interaction applications. Most known maturely developed sensing methods (EEG/ECG/EMG/Temperature/BP etc. al.) replied on contact way to obtain desired physiological information for further data analysis. However, those methods might cause some inconvenient and uncomfortable problems, and not easy to be used for affective analysis in interactive performing. To improve this issue, a novel technology based on low power radar technology (Nanosecond Pulse Near-field Sensing, NPNS) with 300 MHz radio-frequency was proposed to detect humans' pulse signal by the non-contact way for heartbeat signal extraction. In this paper, a modified nonlinear HRV calculated algorithm was also developed and applied on analyzing affective status using extracted Peak-to-Peak Interval (PPI) information from detected pulse signal. The proposed new affective analysis method is designed to continuously collect the humans' physiological signal, and validated in a preliminary experiment with sound, light and motion interactive performance. As a result, the mean bias between PPI (from NPNS) and RRI (from ECG) shows less than 1ms, and the correlation is over than 0.88, respectively.

  13. Big data in wildlife research: remote web-based monitoring of hibernating black bears.

    PubMed

    Laske, Timothy G; Garshelis, David L; Iaizzo, Paul A

    2014-12-11

    Numerous innovations for the management and collection of "big data" have arisen in the field of medicine, including implantable computers and sensors, wireless data transmission, and web-based repositories for collecting and organizing information. Recently, human clinical devices have been deployed in captive and free-ranging wildlife to aid in the characterization of both normal physiology and the interaction of animals with their environment, including reactions to humans. Although these devices have had a significant impact on the types and quantities of information that can be collected, their utility has been limited by internal memory capacities, the efforts required to extract and analyze information, and by the necessity to handle the animals in order to retrieve stored data. We surgically implanted miniaturized cardiac monitors (1.2 cc, Reveal LINQ™, Medtronic Inc.), a newly developed human clinical system, into hibernating wild American black bears (N = 6). These devices include wireless capabilities, which enabled frequent transmissions of detailed physiological data from bears in their remote den sites to a web-based data storage and management system. Solar and battery powered telemetry stations transmitted detailed physiological data over the cellular network during the winter months. The system provided the transfer of large quantities of data in near-real time. Observations included changes in heart rhythms associated with birthing and caring for cubs, and in all bears, long periods without heart beats (up to 16 seconds) occurred during each respiratory cycle. For the first time, detailed physiological data were successfully transferred from an animal in the wild to a web-based data collection and management system, overcoming previous limitations on the quantities of data that could be transferred. The system provides an opportunity to detect unusual events as they are occurring, enabling investigation of the animal and site shortly afterwards. Although the current study was limited to bears in winter dens, we anticipate that future systems will transmit data from implantable monitors to wearable transmitters, allowing for big data transfer on non-stationary animals.

  14. Parameters for Pesticide QSAR and PBPK/PD Models to inform Human Risk Assessments

    EPA Science Inventory

    Physiologically-based pharmacokinetic and pharmacodynamic (PBPK/PD) modeling has emerged as an important computational approach supporting quantitative risk assessment of agrochemicals. However, before complete regulatory acceptance of this tool, an assessment of assets and liabi...

  15. Design of Tactile Sensor Using Dynamic Wafer Technology Based on VLSI Technique

    DTIC Science & Technology

    2001-10-25

    Charles Noback, Rober Carola," Human Anatomy and Physiology" third edition, 1995. [5] M.H. Raibert and John E. Tanner, "Design and Implementation of VLSI Tactile Sensing Computer" Robotics Research vol 1, 1983.

  16. PREDICTIVE PHYSIOLOGICALLY BASED PHARMACOKINETICS MODELING (PBPK) OF PYRETHROID PESTICIDES

    EPA Science Inventory

    Pyrethroids are a class of neurotoxic pesticides that have many different applications in agriculture, horticulture, and homes, and medicinal uses for animals and humans. Differences in the toxicity of pyrethroids are the result of their pharmacokinetic and/or pharmacodynamic pr...

  17. Parameters for Pyrethroid Insecticide QSAR and PBPK/PD Models for Human Risk Assessment

    EPA Science Inventory

    This pyrethroid insecticide parameter review is an extension of our interest in developing quantitative structure–activity relationship–physiologically based pharmacokinetic/pharmacodynamic (QSAR-PBPK/PD) models for assessing health risks, which interest started with the organoph...

  18. 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.

  19. 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

  20. Heparin-based hydrogels induce human renal tubulogenesis in vitro.

    PubMed

    Weber, Heather M; Tsurkan, Mikhail V; Magno, Valentina; Freudenberg, Uwe; Werner, Carsten

    2017-07-15

    Dialysis or kidney transplantation is the only therapeutic option for end stage renal disease. Accordingly, there is a large unmet clinical need for new causative therapeutic treatments. Obtaining robust models that mimic the complex nature of the human kidney is a critical step in the development of new therapeutic strategies. Here we establish a synthetic in vitro human renal tubulogenesis model based on a tunable glycosaminoglycan-hydrogel platform. In this system, renal tubulogenesis can be modulated by the adjustment of hydrogel mechanics and degradability, growth factor signaling, and the presence of insoluble adhesion cues, potentially providing new insights for regenerative therapy. Different hydrogel properties were systematically investigated for their ability to regulate renal tubulogenesis. Hydrogels based on heparin and matrix metalloproteinase cleavable peptide linker units were found to induce the morphogenesis of single human proximal tubule epithelial cells into physiologically sized tubule structures. The generated tubules display polarization markers, extracellular matrix components, and organic anion transport functions of the in vivo renal proximal tubule and respond to nephrotoxins comparable to the human clinical response. The established hydrogel-based human renal tubulogenesis model is thus considered highly valuable for renal regenerative medicine and personalized nephrotoxicity studies. The only cure for end stage kidney disease is kidney transplantation. Hence, there is a huge need for reliable human kidney models to study renal regeneration and establish alternative treatments. Here we show the development and application of an in vitro human renal tubulogenesis model using heparin-based hydrogels. To the best of our knowledge, this is the first system where human renal tubulogenesis can be monitored from single cells to physiologically sized tubule structures in a tunable hydrogel system. To validate the efficacy of our model as a drug toxicity platform, a chemotherapy drug was incubated with the model, resulting in a drug response similar to human clinical pathology. The established model could have wide applications in the field of nephrotoxicity and renal regenerative medicine and offer a reliable alternative to animal models. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  1. Investigating the physiology of brain activation with MRI

    NASA Astrophysics Data System (ADS)

    Buxton, Richard B.; Uludag, Kamil; Dubowitz, David J.

    2004-04-01

    Functional magnetic resonance imaging (fMRI) has become a powerful tool for investigating the working human brain based on the blood oxygenation level dependent (BOLD) effect on the MR signal. However, despite the widespread use of fMRI techniques for mapping brain activation, the basic physiological mechanisms underlying the observed signal changes are still poorly understood. Arterial spin labeling (ASL) techniques, which measure cerebral blood flow (CBF) and the BOLD effect simultaneously, provide a useful tool for investigating these physiological questions. In this paper, recent results of studies manipulating the baseline CBF both pharmacologically and physiologically will be discussed. These data are consistent with a feed-forward mechanism of neurovascular coupling, and suggest that the CBF change itself may be a more robust reflection of neural activity changes than the BOLD effect. Consistent with these data, a new thermodynamic hypothesis is proposed for the physiological function of CBF regulation: maintenance of the [O2]/[CO2] concentration ratio at the mitochondria in order to preserve the free energy available from oxidative metabolism. A kinetic model based on this hypothesis provides a reasonable quantitative description of the CBF changes associated with neural activity and altered blood gases (CO2 and O2).

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

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

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

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

  3. Dose selection based on physiologically based pharmacokinetic (PBPK) approaches.

    PubMed

    Jones, Hannah M; Mayawala, Kapil; Poulin, Patrick

    2013-04-01

    Physiologically based pharmacokinetic (PBPK) models are built using differential equations to describe the physiology/anatomy of different biological systems. Readily available in vitro and in vivo preclinical data can be incorporated into these models to not only estimate pharmacokinetic (PK) parameters and plasma concentration-time profiles, but also to gain mechanistic insight into compound properties. They provide a mechanistic framework to understand and extrapolate PK and dose across in vitro and in vivo systems and across different species, populations and disease states. Using small molecule and large molecule examples from the literature and our own company, we have shown how PBPK techniques can be utilised for human PK and dose prediction. Such approaches have the potential to increase efficiency, reduce the need for animal studies, replace clinical trials and increase PK understanding. Given the mechanistic nature of these models, the future use of PBPK modelling in drug discovery and development is promising, however some limitations need to be addressed to realise its application and utility more broadly.

  4. Incorporating Human Interindividual Biotransformation ...

    EPA Pesticide Factsheets

    The protection of sensitive individuals within a population dictates that measures other than central tendencies be employed to estimate risk. The refinement of human health risk assessments for chemicals metabolized by the liver to reflect data on human variability can be accomplished through (1) the characterization of enzyme expression in large banks of human liver samples, (2) the employment of appropriate techniques for the quantification and extrapolation of metabolic rates derived in vitro, and (3) the judicious application of physiologically based pharmacokinetic (PBPK) modeling. While in vitro measurements of specific biochemical reactions from multiple human samples can yield qualitatively valuable data on human variance, such measures must be put into the perspective of the intact human to yield the most valuable predictions of metabolic differences among humans. For quantitative metabolism data to be the most valuable in risk assessment, they must be tied to human anatomy and physiology, and the impact of their variance evaluated under real exposure scenarios. For chemicals metabolized in the liver, the concentration of parent chemical in the liver represents the substrate concentration in the MichaelisMenten description of metabolism. Metabolic constants derived in vitro may be extrapolated to the intact liver, when appropriate conditions are met. Metabolic capacity Vmax; the maximal rate of the reaction) can be scaled directly to the concentration

  5. Clinical and Physiological Perspectives of β-Glucans: The Past, Present, and Future

    PubMed Central

    Bashir, Khawaja Muhammad Imran; Choi, Jae-Suk

    2017-01-01

    β-Glucans are a group of biologically-active fibers or polysaccharides from natural sources with proven medical significance. β-Glucans are known to have antitumor, anti-inflammatory, anti-obesity, anti-allergic, anti-osteoporotic, and immunomodulating activities. β-Glucans are natural bioactive compounds and can be taken orally, as a food supplement, or as part of a daily diet, and are considered safe to use. The medical significance and efficiency of β-glucans are confirmed in vitro, as well as using animal- and human-based clinical studies. However, systematic study on the clinical and physiological significance of β-glucans is scarce. In this review, we not only discuss the clinical and physiological importance of β-glucans, we also compare their biological activities through the existing in vitro and animal-based in vivo studies. This review provides extensive data on the clinical study of β-glucans. PMID:28872611

  6. Risk Interfaces to Support Integrated Systems Analysis and Development

    NASA Technical Reports Server (NTRS)

    Mindock, Jennifer; Lumpkins, Sarah; Shelhamer, Mark; Anton, Wilma; Havenhill, Maria

    2016-01-01

    Objectives for systems analysis capability: Develop integrated understanding of how a complex human physiological-socio-technical mission system behaves in spaceflight. Why? Support development of integrated solutions that prevent unwanted outcomes (Implementable approaches to minimize mission resources(mass, power, crew time, etc.)); Support development of tools for autonomy (need for exploration) (Assess and maintain resilience -individuals, teams, integrated system). Output of this exercise: -Representation of interfaces based on Human System Risk Board (HSRB) Risk Summary information and simple status based on Human Research Roadmap; Consolidated HSRB information applied to support communication; Point-of-Departure for HRP Element planning; Ability to track and communicate status of collaborations. 4

  7. Comparing Biology Grades Based on Instructional Delivery and Instructor at a Community College: Face-to-Face Course Versus Online Course

    NASA Astrophysics Data System (ADS)

    Rosenzweig, Amanda H.

    Through distance learning, the community college system has been able to serve more students by providing educational opportunities to students who would otherwise be unable to attend college. The community college of focus in the study increased its online enrollments and online course offerings due to the growth of overall enrollment. The need and purpose of the study is to address if there is a difference in students' grades between face-to-face and online biology related courses and if there are differences in grades between face-to-face and online biology courses taught by different instructors and the same instructor. The study also addresses if online course delivery is a viable method to educate students in biology-related fields. The study spanned 14 semesters between spring 2006 and summer 2011. Data were collected for 6,619 students. For each student, demographic information, cumulative grade point average, ACT, and data on course performance were gathered. Student data were gathered from General Biology I, Microbiology of Human Pathogens, Human Anatomy and Physiology I, and Human Anatomy and Physiology II courses. Univariate analysis of variance, linear regression, and descriptive analysis were used to analyze the data and determine which variables significantly impacted grade achievement for face-to-face and online students in biology classes. The findings from the study showed that course type, face-to-face or online, was significant for Microbiology of Human Pathogens and Human Anatomy and Physiology I, both upper level courses. Teachers were significant for General Biology I, a lower level course, Human Anatomy and Physiology I, and Human Anatomy and Physiology II. However, in every class, there were teachers who had significant differences within their courses between their face-to-face and online courses. This study will allow information to be concluded about the relationship between the students' final grades and class type, face-to-face or online, and instructor. Administrators, faculty and students can use this information to understand what needs to be done to successfully teach and enroll in biology courses, face-to-face or online. biology courses, online courses, face-to-face courses, class type, teacher influence, grades, CGPA, community college

  8. 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.

  9. 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

  10. Reconstructing Exposures from Biomarkers using Exposure-Pharmacokinetic Modeling - A Case Study with Carbaryl

    EPA Science Inventory

    Sources of uncertainty involved in exposure reconstruction for a short half-life chemical, carbaryl, were characterized using the Cumulative and Aggregate Risk Evaluation System (CARES), an exposure model, and a human physiologically based pharmacokinetic (PBPK) model. CARES was...

  11. Risk estimates for CO exposure in man based on behavioral and physiological responses in rodents

    NASA Technical Reports Server (NTRS)

    Gross, M. K.

    1983-01-01

    An examination of animal response to CO is studied along with potential models for extrapolating animal test data to humans. The best models for extrapolating data were found to be the Probit and Weibull models.

  12. Physiologically Based Pharmacokinetic (PBPK) Modeling of Interstrain Variability in Trichloroethylene Metabolism in the Mouse

    EPA Science Inventory

    Background: Quantitative estimation of toxicokinetic variability in the human population is a persistent challenge in risk assessment of environmental chemicals. Traditionally, inter-individual differences in the population are accounted for by default assumptions or, in rare cas...

  13. EXPOSURE RELATED DOSE ESTIMATING MODEL (ERDEM)

    EPA Science Inventory

    ERDEM is a physiologically-based pharmacokinetic (PBPK) model with a graphical user interface (GUI) front end. Such a mathematical model was needed to make reliable estimates of the chemical dose to organs of animals or humans because of uncertainties of making route-to route, lo...

  14. Back to the future! Revisiting the physiological cost of negative work as a team-based activity for exercise physiology students.

    PubMed

    Kilgas, Matthew A; Elmer, Steven J

    2017-03-01

    We implemented a team-based activity in our exercise physiology teaching laboratory that was inspired from Abbott et al.'s classic 1952 Journal of Physiology paper titled "The physiological cost of negative work." Abbott et al. connected two bicycles via one chain. One person cycled forward (muscle shortening contractions, positive work) while the other resisted the reverse moving pedals (muscle lengthening contractions, negative work), and the cost of work was compared. This study was the first to link human whole body energetics with isolated muscle force-velocity characteristics. The laboratory activity for our students ( n = 35) was designed to reenact Abbott et al.'s experiment, integrate previously learned techniques, and illustrate differences in physiological responses to muscle shortening and lengthening contractions. Students (11-12 students/laboratory section) were split into two teams (positive work vs. negative work). One student from each team volunteered to cycle against the other for ~10 min. The remaining students in each team were tasked with measuring: 1 ) O 2 consumption, 2 ) heart rate, 3 ) blood lactate, and 4 ) perceived exertion. Students discovered that O 2 consumption during negative work was about one-half that of positive work and all other physiological parameters were also substantially lower. Muscle lengthening contractions were discussed and applied to rehabilitation and sport training. The majority of students (>90%) agreed or strongly agreed that they stayed engaged during the activity and it improved their understanding of exercise physiology. All students recommended the activity be performed again. This activity was engaging, emphasized teamwork, yielded clear results, was well received, and preserved the history of classic physiological experiments. Copyright © 2017 the American Physiological Society.

  15. 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.

  16. 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.

  17. Alternative Polyadenylation and Nonsense-Mediated Decay Coordinately Regulate the Human HFE mRNA Levels

    PubMed Central

    Martins, Rute; Proença, Daniela; Silva, Bruno; Barbosa, Cristina; Silva, Ana Luísa; Faustino, Paula; Romão, Luísa

    2012-01-01

    Nonsense-mediated decay (NMD) is an mRNA surveillance pathway that selectively recognizes and degrades defective mRNAs carrying premature translation-termination codons. However, several studies have shown that NMD also targets physiological transcripts that encode full-length proteins, modulating their expression. Indeed, some features of physiological mRNAs can render them NMD-sensitive. Human HFE is a MHC class I protein mainly expressed in the liver that, when mutated, can cause hereditary hemochromatosis, a common genetic disorder of iron metabolism. The HFE gene structure comprises seven exons; although the sixth exon is 1056 base pairs (bp) long, only the first 41 bp encode for amino acids. Thus, the remaining downstream 1015 bp sequence corresponds to the HFE 3′ untranslated region (UTR), along with exon seven. Therefore, this 3′ UTR encompasses an exon/exon junction, a feature that can make the corresponding physiological transcript NMD-sensitive. Here, we demonstrate that in UPF1-depleted or in cycloheximide-treated HeLa and HepG2 cells the HFE transcripts are clearly upregulated, meaning that the physiological HFE mRNA is in fact an NMD-target. This role of NMD in controlling the HFE expression levels was further confirmed in HeLa cells transiently expressing the HFE human gene. Besides, we show, by 3′-RACE analysis in several human tissues that HFE mRNA expression results from alternative cleavage and polyadenylation at four different sites – two were previously described and two are novel polyadenylation sites: one located at exon six, which confers NMD-resistance to the corresponding transcripts, and another located at exon seven. In addition, we show that the amount of HFE mRNA isoforms resulting from cleavage and polyadenylation at exon seven, although present in both cell lines, is higher in HepG2 cells. These results reveal that NMD and alternative polyadenylation may act coordinately to control HFE mRNA levels, possibly varying its protein expression according to the physiological cellular requirements. PMID:22530027

  18. 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.

  19. Chemical Warfare Agent Operational Exposure Hazard Assessment Research: FY07 Report and Analysis

    DTIC Science & Technology

    2010-07-01

    of the nerve agents sarin, soman, cyclohexylsarin, VX, and Russian VX in human urine using isotope-dilution gas chromatography-tandem mass...Needham L.L.; Barr, D.B. Quantitation of organophosphorous nerve agent metabolites in human urine using isotope dilution gas chromatography-tandem mass... nerve agents , VX, GB, or GF, and to determine lethal percutaneous (PC) levels of VX. Calibration of Physiologically-based pharmacokinetic biomarkers

  20. Wearable health monitoring using capacitive voltage-mode Human Body Communication.

    PubMed

    Maity, Shovan; Das, Debayan; Sen, Shreyas

    2017-07-01

    Rapid miniaturization and cost reduction of computing, along with the availability of wearable and implantable physiological sensors have led to the growth of human Body Area Network (BAN) formed by a network of such sensors and computing devices. One promising application of such a network is wearable health monitoring where the collected data from the sensors would be transmitted and analyzed to assess the health of a person. Typically, the devices in a BAN are connected through wireless (WBAN), which suffers from energy inefficiency due to the high-energy consumption of wireless transmission. Human Body Communication (HBC) uses the relatively low loss human body as the communication medium to connect these devices, promising order(s) of magnitude better energy-efficiency and built-in security compared to WBAN. In this paper, we demonstrate a health monitoring device and system built using Commercial-Off-The-Shelf (COTS) sensors and components, that can collect data from physiological sensors and transmit it through a) intra-body HBC to another device (hub) worn on the body or b) upload health data through HBC-based human-machine interaction to an HBC capable machine. The system design constraints and signal transfer characteristics for the implemented HBC-based wearable health monitoring system are measured and analyzed, showing reliable connectivity with >8× power savings compared to Bluetooth low-energy (BTLE).

  1. Translating dosages from animal models to human clinical trials--revisiting body surface area scaling.

    PubMed

    Blanchard, Otis L; Smoliga, James M

    2015-05-01

    Body surface area (BSA) scaling has been used for prescribing individualized dosages of various drugs and has also been recommended by the U.S. Food and Drug Administration as one method for using data from animal model species to establish safe starting dosages for first-in-human clinical trials. Although BSA conversion equations have been used in certain clinical applications for decades, recent recommendations to use BSA to derive interspecies equivalents for therapeutic dosages of drug and natural products are inappropriate. A thorough review of the literature reveals that BSA conversions are based on antiquated science and have little justification in current translational medicine compared to more advanced allometric and physiologically based pharmacokinetic modeling. Misunderstood and misinterpreted use of BSA conversions may have disastrous consequences, including underdosing leading to abandonment of potentially efficacious investigational drugs, and unexpected deadly adverse events. We aim to demonstrate that recent recommendations for BSA are not appropriate for animal-to-human dosage conversions and use pharmacokinetic data from resveratrol studies to demonstrate how confusion between the "human equivalent dose" and "pharmacologically active dose" can lead to inappropriate dose recommendations. To optimize drug development, future recommendations for interspecies scaling must be scientifically justified using physiologic, pharmacokinetic, and toxicology data rather than simple BSA conversion. © FASEB.

  2. 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.

  3. 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.

  4. Accuracy and Efficiency of Recording Pediatric Early Warning Scores Using an Electronic Physiological Surveillance System Compared With Traditional Paper-Based Documentation.

    PubMed

    Sefton, Gerri; Lane, Steven; Killen, Roger; Black, Stuart; Lyon, Max; Ampah, Pearl; Sproule, Cathryn; Loren-Gosling, Dominic; Richards, Caitlin; Spinty, Jean; Holloway, Colette; Davies, Coral; Wilson, April; Chean, Chung Shen; Carter, Bernie; Carrol, E D

    2017-05-01

    Pediatric Early Warning Scores are advocated to assist health professionals to identify early signs of serious illness or deterioration in hospitalized children. Scores are derived from the weighting applied to recorded vital signs and clinical observations reflecting deviation from a predetermined "norm." Higher aggregate scores trigger an escalation in care aimed at preventing critical deterioration. Process errors made while recording these data, including plotting or calculation errors, have the potential to impede the reliability of the score. To test this hypothesis, we conducted a controlled study of documentation using five clinical vignettes. We measured the accuracy of vital sign recording, score calculation, and time taken to complete documentation using a handheld electronic physiological surveillance system, VitalPAC Pediatric, compared with traditional paper-based charts. We explored the user acceptability of both methods using a Web-based survey. Twenty-three staff participated in the controlled study. The electronic physiological surveillance system improved the accuracy of vital sign recording, 98.5% versus 85.6%, P < .02, Pediatric Early Warning Score calculation, 94.6% versus 55.7%, P < .02, and saved time, 68 versus 98 seconds, compared with paper-based documentation, P < .002. Twenty-nine staff completed the Web-based survey. They perceived that the electronic physiological surveillance system offered safety benefits by reducing human error while providing instant visibility of recorded data to the entire clinical team.

  5. Constitutive laws with damage effect for the human great saphenous vein.

    PubMed

    Li, Wenguang

    2018-05-01

    Strain energy-based constitutive laws with damage effect were proposed by using existing both uniaxial tensile test and tubular biaxial inflation test data on the human great saphenous vein (GSV) segments. These laws were applied into GSV coronary artery bypass grafts (CABG) by employing a thin-walled vessel model to evaluate their passive biomechanical performance under coronary artery physiological conditions at a fixed axial pre-stretch. At a peak systolic pressure in 100-150 mmHg, a 20-33% GSV diameter dilation was predicted with the law based on tubular biaxial inflation test data and agreed well with 25% dilation in clinical observation in comparison with as small as 2-4% dilation estimated with the law based on uniaxial tensile test data. The constitutive law generated by tubular biaxial inflation test data was mostly suitable for GSV CABG under coronary artery physiological conditions than that based on uniaxial tensile test results. With these laws, the fibre ultimate stretch was extracted from uniaxial tensile test data and the structural sub-failure/damage threshold of 1.0731 was decided for the human GSV. GSV fibres could exhibit damage effect but unlikely undergo a structure failure/break, suggesting a damage factor might exist during CABG arterialization. The damage in GSV tissue might initiate or contribute to early remodelling of CABG after implantation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. The physiological equivalent temperature - a universal index for the biometeorological assessment of the thermal environment

    NASA Astrophysics Data System (ADS)

    Höppe, P.

    With considerably increased coverage of weather information in the news media in recent years in many countries, there is also more demand for data that are applicable and useful for everyday life. Both the perception of the thermal component of weather as well as the appropriate clothing for thermal comfort result from the integral effects of all meteorological parameters relevant for heat exchange between the body and its environment. Regulatory physiological processes can affect the relative importance of meteorological parameters, e.g. wind velocity becomes more important when the body is sweating. In order to take into account all these factors, it is necessary to use a heat-balance model of the human body. The physiological equivalent temperature (PET) is based on the Munich Energy-balance Model for Individuals (MEMI), which models the thermal conditions of the human body in a physiologically relevant way. PET is defined as the air temperature at which, in a typical indoor setting (without wind and solar radiation), the heat budget of the human body is balanced with the same core and skin temperature as under the complex outdoor conditions to be assessed. This way PET enables a layperson to compare the integral effects of complex thermal conditions outside with his or her own experience indoors. On hot summer days, for example, with direct solar irradiation the PET value may be more than 20 K higher than the air temperature, on a windy day in winter up to 15 K lower.

  7. Human cold stress of strong local-wind "Hijikawa-arashi" in Japan, based on the UTCI index and thermo-physiological responses

    NASA Astrophysics Data System (ADS)

    Ohashi, Yukitaka; Katsuta, Takumi; Tani, Haruka; Okabayashi, Taiki; Miyahara, Satoshi; Miyashita, Ryoji

    2018-03-01

    We investigated the cold stress caused by a strong local wind called "Hijikawa-arashi," through in situ vital measurements and the Universal Thermal Climate Index (UTCI). This wind is a very interesting winter phenomenon, localized in an area within 1 km of the seashore in Ozu City, Ehime Prefecture in Japan. When a strong Hijikawa-arashi (HA) occurred at 14-15 m s-1, the UTCI decreased to - 30 °C along the bridge where commuting residents are the most exposed to strong and cold winds. On the bridge, most participants in our experiment felt "very cold" or "extremely cold." The UTCI of HA can be predicted from a multiple regression equation using wind speed and air temperature. The cold HA wind is also harmful to human thermo-physiological responses. It leads to higher blood pressure and increased heart rate, both of which act as cardiovascular stress triggers. Increases of 6-10 mmHg and 3-6 bpm for every 10 °C reduction in UTCI were seen on all observational days, including HA and non-HA days. In fact, the participants' body skin temperatures decreased by approximately 1.2 to 1.7 °C for every 10 °C reduction in UTCI. Thus, the UTCI variation due to the HA outbreak corresponded well with the cold sensation and thermo-physiological responses in humans. This result suggests that daily UTCI monitoring enables the prediction of thermo-physiological responses to the HA cold stress.

  8. Physiological stress and Hendra virus in flying-foxes (Pteropus spp.), Australia.

    PubMed

    McMichael, Lee; Edson, Daniel; Smith, Craig; Mayer, David; Smith, Ina; Kopp, Steven; Meers, Joanne; Field, Hume

    2017-01-01

    Pteropid bats (flying-foxes) are the natural reservoir of Hendra virus, an emergent paramyxovirus responsible for fatal infection in horses and humans in Australia. Pteropus alecto (the Black flying-fox) and the paraphyletic P. conspicillatus (the Spectacled flying-fox) appear to be the primary reservoir hosts. Previous studies have suggested that physiological and ecological factors may underpin infection dynamics in flying-foxes, and subsequent spillover to horses and in turn humans. We sought to examine temporal trends in urinary cortisol concentration in wild Australian flying-fox populations, to elucidate the putative relationship between Hendra virus infection and physiological stress. Pooled and individual urine samples were non-invasively collected from under roosting flying-foxes at two latitudinally disparate regions in the eastern Australian state of Queensland. Hendra virus detection, and (in individual urine samples) sex and species determination were PCR-based. Urinary cortisol measurement used a validated enzyme immunoassay. We found no direct correlation between increased urinary cortisol and Hendra virus excretion, but our findings do suggest a biologically plausible association between low winter temperatures and elevated cortisol levels in P. alecto in the lower latitude Southeast Queensland roosts. We hypothesize an indirect association between low winter temperatures and increased Hendra virus infection and excretion, mediated by the physiological cost of thermoregulation. Our findings and our approach are directly relevant to elaboration of the disease ecology of Nipah virus and other emerging henipaviruses in bats. More broadly, they inform investigation of emerging disease infection dynamics across the wildlife/livestock/human interface.

  9. 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.

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

    PubMed

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

    2016-03-01

    Combining the strengths of an advanced mathematical model of human physiology and a thermal manikin is a new paradigm for simulating thermal behaviour of humans. However, the forerunners of such adaptive manikins showed some substantial limitations. This project aimed to determine the opportunities and constraints of the existing thermal manikins when dynamically controlled by a mathematical model of human thermal physiology. Four thermal manikins were selected and evaluated for their heat flux measurement uncertainty including lateral heat flows between manikin body parts and the response of each sector to the frequent change of the set-point temperature typical when using a physiological model for control. In general, all evaluated manikins are suitable for coupling with a physiological model with some recommendations for further improvement of manikin dynamic performance. The proposed methodology is useful to improve the performance of the adaptive manikins and help to provide a reliable and versatile tool for the broad research and development domain of clothing, automotive and building engineering.

  11. 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.

  12. Convergent evolution of adenosine aptamers spanning bacterial, human, and random sequences revealed by structure-based bioinformatics and genomic SELEX

    PubMed Central

    Vu, Michael M. K.; Jameson, Nora E.; Masuda, Stuart J.; Lin, Dana; Larralde-Ridaura, Rosa; Lupták, Andrej

    2012-01-01

    SUMMARY Aptamers are structured macromolecules in vitro evolved to bind molecular targets, whereas in nature they form the ligand-binding domains of riboswitches. Adenosine aptamers of a single structural family were isolated several times from random pools but they have not been identified in genomic sequences. We used two unbiased methods, structure-based bioinformatics and human genome-based in vitro selection, to identify aptamers that form the same adenosine-binding structure in a bacterium, and several vertebrates, including humans. Two of the human aptamers map to introns of RAB3C and FGD3 genes. The RAB3C aptamer binds ATP with dissociation constants about ten times lower than physiological ATP concentration, while the minimal FGD3 aptamer binds ATP only co-transcriptionally. PMID:23102219

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

    PubMed Central

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

    2014-01-01

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

  14. MODEL DEVELOPMENT AND APPLICATION FOR ASSESSING HUMAN EXPOSURE AND DOSE TO TOXIC CHEMICALS AND POLLUTANTS

    EPA Science Inventory

    This project aims to strengthen the general scientific foundation of EPA's exposure and risk assessment processes by developing state-of-the-art exposure to dose computational models. This research will produce physiologically-based pharmacokinetic (PBPK) and pharmacodynamic (PD)...

  15. Foundations of space biology and medicine. Volume 2, book 1: Ecological and physiological bases of space biology and medicine

    NASA Technical Reports Server (NTRS)

    Calvin, M. (Editor); Gazenko, O. G. (Editor)

    1975-01-01

    Barometric pressure, gas composition, toxicity, and thermal exchange of spacecraft cabin atmospheres are discussed. Effects of gravitation, acceleration, weightlessness, noise, and vibration on human behavior and performance during space flight are also described.

  16. Home-Based vs. Laboratory-Based Practical Activities in the Learning of Human Physiology: The Perception of Students

    ERIC Educational Resources Information Center

    Neves, Ben-Hur S.; Altermann, Caroline; Gonçalves, Rithiele; Lara, Marcus Vinícius; Mello-Carpes, Pâmela B.

    2017-01-01

    Different tools have been used to facilitate the teaching and learning process in different areas of knowledge. Practical activities represent a form of teaching in which students not only listen to theoretical concepts but are also able to link theory and practice, and their importance in the biological sciences is notable. Sometimes, however,…

  17. 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.

  18. The pharmacology of the human female orgasm - its biological and physiological backgrounds.

    PubMed

    Levin, Roy J

    2014-06-01

    The female orgasm has been examined over the years by numerous scientific disciplines yet it still has many secrets to be disclosed. Because its physiology, especially its neurophysiology, is sparingly understood its pharmacology is necessarily limited based mainly on the side effects of drugs. Few published studies have used a placebo group as controls. The paucity of focussed studies is well illustrated by the fact that there still is no approved medication to treat female orgasmic dysfunction. The present brief overview examines the most important aspects of its biology and especially its physiology highlighting the many questions that need answering if we are to have a comprehensive pharmacology of the female orgasm. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Towards a psycho-physiological model of thermal perception

    NASA Astrophysics Data System (ADS)

    Auliciems, A.

    1981-06-01

    Recommendations for indoor thermal requirements have been based upon verbalized responses on traditional assumptions that (1) minimal thermoregulatory activity may be equated to maximum subjective acceptability (2) sensations and levels of discomfort are synonymous and (3) perception of warmth is exclusively the function of thermal stimulus — physiological response. These concepts are reviewed in the light of recent researches which indicate the inadequacy of the existing physiological models and methods of research. In particular, recognition is made of higher levels of mental integration of information flows which, it is argued, must include parameters of past cultural and climatic experiences and expectations. The aim is to initiate a more holistic approach to research into human thermal environments, and, a clearer definition of concepts significant to practical application.

  20. Quantitative characterization of mechanically indented in vivo human skin in adults and infants using optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Huang, Pin-Chieh; Pande, Paritosh; Shelton, Ryan L.; Joa, Frank; Moore, Dave; Gillman, Elisa; Kidd, Kimberly; Nolan, Ryan M.; Odio, Mauricio; Carr, Andrew; Boppart, Stephen A.

    2017-03-01

    Influenced by both the intrinsic viscoelasticity of the tissue constituents and the time-evolved redistribution of fluid within the tissue, the biomechanical response of skin can reflect not only localized pathology but also systemic physiology of an individual. While clinical diagnosis of skin pathologies typically relies on visual inspection and manual palpation, a more objective and quantitative approach for tissue characterization is highly desirable. Optical coherence tomography (OCT) is an interferometry-based imaging modality that enables in vivo assessment of cross-sectional tissue morphology with micron-scale resolution, which surpasses those of most standard clinical imaging tools, such as ultrasound imaging and magnetic resonance imaging. This pilot study investigates the feasibility of characterizing the biomechanical response of in vivo human skin using OCT. OCT-based quantitative metrics were developed and demonstrated on the human subject data, where a significant difference between deformed and nondeformed skin was revealed. Additionally, the quantified postindentation recovery results revealed differences between aged (adult) and young (infant) skin. These suggest that OCT has the potential to quantitatively assess the mechanically perturbed skin as well as distinguish different physiological conditions of the skin, such as changes with age or disease.

  1. Metabolomic Modularity Analysis (MMA) to Quantify Human Liver Perfusion Dynamics.

    PubMed

    Sridharan, Gautham Vivek; Bruinsma, Bote Gosse; Bale, Shyam Sundhar; Swaminathan, Anandh; Saeidi, Nima; Yarmush, Martin L; Uygun, Korkut

    2017-11-13

    Large-scale -omics data are now ubiquitously utilized to capture and interpret global responses to perturbations in biological systems, such as the impact of disease states on cells, tissues, and whole organs. Metabolomics data, in particular, are difficult to interpret for providing physiological insight because predefined biochemical pathways used for analysis are inherently biased and fail to capture more complex network interactions that span multiple canonical pathways. In this study, we introduce a nov-el approach coined Metabolomic Modularity Analysis (MMA) as a graph-based algorithm to systematically identify metabolic modules of reactions enriched with metabolites flagged to be statistically significant. A defining feature of the algorithm is its ability to determine modularity that highlights interactions between reactions mediated by the production and consumption of cofactors and other hub metabolites. As a case study, we evaluated the metabolic dynamics of discarded human livers using time-course metabolomics data and MMA to identify modules that explain the observed physiological changes leading to liver recovery during subnormothermic machine perfusion (SNMP). MMA was performed on a large scale liver-specific human metabolic network that was weighted based on metabolomics data and identified cofactor-mediated modules that would not have been discovered by traditional metabolic pathway analyses.

  2. A physiologically based pharmacokinetic model for ethylene oxide in mouse, rat, and human.

    PubMed

    Fennell, T R; Brown, C D

    2001-06-15

    Ethylene oxide (EO) is widely used as a gaseous sterilant and industrial intermediate and is a direct-acting mutagen and carcinogen. The objective of these studies was to develop physiologically based pharmacokinetic (PB-PK) models for EO to describe the exposure-tissue dose relationship in rodents and humans. We previously reported results describing in vitro and in vivo kinetics of EO metabolism in male and female F344 rats and B6C3F1 mice. These studies were extended by determining the kinetics of EO metabolism in human liver cytosol and microsomes. The results indicate enzymatically catalyzed GSH conjugation via cytosolic glutathione S-transferase (cGST) and hydrolysis via microsomal epoxide hydrolase (mEH) occur in both rodents and humans. The in vitro kinetic constants were scaled to account for cytosolic (cGST) and microsomal (mEH) protein content and incorporated into PB-PK descriptions for mouse, rat, and human. Flow-limited models adequately predicted blood and tissue EO levels, disposition, and elimination kinetics determined experimentally in rats and mice, with the exception of testis concentrations, which were overestimated. Incorporation of a diffusion-limited description for testis improved the ability of the model to describe testis concentrations. The model accounted for nonlinear increases in blood and tissue concentrations that occur in mice on exposure to EO concentrations greater than 200 ppm. Species differences are predicted in the metabolism and exposure-dose relationship, with a nonlinear relationship observed in the mouse as a result of GSH depletion. These models represent an essential step in developing a mechanistically based EO exposure-dose-response description for estimating human risk from exposure to EO. Copyright 2001 Academic Press.

  3. A meta-analysis of human disturbance impacts on Antarctic wildlife.

    PubMed

    Coetzee, Bernard W T; Chown, Steven L

    2016-08-01

    Evidence-based assessments are increasingly recognized as the best-practice approach to determine appropriate conservation interventions, but such assessments of the impact of human disturbance on wildlife are rare. Human disturbance comprises anthropogenic activities that are typically non-lethal, but may cause short- and/or longer-term stress and fitness responses in wildlife. Expanding human activity in the Antarctic region is of particular concern because it increases the scope and potential for increased human disturbance to wildlife in a region that is often thought of as relatively untouched by anthropogenic influences. Here, we use a meta-analytical approach to synthesise research on human disturbance to wildlife over the last three decades in the Antarctic and sub-Antarctic region. We combine data from 62 studies across 21 species on the behavioural, physiological and population responses of wildlife to pedestrian, vehicle and research disturbances. The overall effect size indicated a small, albeit statistically significant negative effect of disturbance (-0.39; 95% CI: -0.60 to -0.18). Negative effects were found for both physiological and population responses, but no evidence was found for a significant impact on wildlife behavioural responses. Negative effects were found across pedestrian, vehicle and research disturbances. Significant and high among-study heterogeneity was found in both disturbance and response sub-groups. Among species, it remains unclear to what extent different forms of disturbance translate into negative population responses. Most current guidelines to limit wildlife disturbance impacts in Antarctica recommend that approaches be tailored to animal behavioural cues, but our work demonstrates that behavioural changes do not necessarily reflect more cryptic, and more deleterious impacts, such as changes in physiology. In consequence, we recommend that pedestrian approach guidelines in the Antarctic region be revisited. Due to the high heterogeneity in effects, management guidelines for different sites and species will need to be developed on a case-by-case basis, ideally in conjunction with carefully designed experiments. Guidelines to reduce the impact of research activities per se require development to reduce the potential impacts of conducting research. We identify research questions that, if answered, will further improve the evidence base for guidelines to manage human disturbance in Antarctica. © 2015 Cambridge Philosophical Society.

  4. 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.

  5. 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.

  6. 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.

  7. Heart rate variation and electroencephalograph--the potential physiological factors for thermal comfort study.

    PubMed

    Yao, Y; Lian, Z; Liu, W; Jiang, C; Liu, Y; Lu, H

    2009-04-01

    Human thermal comfort researches mainly focus on the relation between the environmental factors (e.g. ambient temperature, air humidity, and air velocity, etc.) and the thermal comfort sensation based on a large amount of subjective field investigations. Although some physiological factors, such as skin temperature and metabolism were used in many thermal comfort models,they are not enough to establish a perfect thermal comfort model. In this paper,another two physiological factors, i.e. heart rate variation (HRV) and electroencephalograph (EEG), are explored for the thermal comfort study. Experiments were performed to investigate how these physiological factors respond to the environmental temperatures, and what is the relationship between HRV and EEG and thermal comfort. The experimental results indicate that HRV and EEG may be related to thermal comfort, and they may be useful to understand the mechanism of thermal comfort.

  8. 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.

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

    PubMed

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

    2018-04-01

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

  10. Blinded Prospective Evaluation of Computer-Based Mechanistic Schizophrenia Disease Model for Predicting Drug Response

    PubMed Central

    Geerts, Hugo; Spiros, Athan; Roberts, Patrick; Twyman, Roy; Alphs, Larry; Grace, Anthony A.

    2012-01-01

    The tremendous advances in understanding the neurobiological circuits involved in schizophrenia have not translated into more effective treatments. An alternative strategy is to use a recently published ‘Quantitative Systems Pharmacology’ computer-based mechanistic disease model of cortical/subcortical and striatal circuits based upon preclinical physiology, human pathology and pharmacology. The physiology of 27 relevant dopamine, serotonin, acetylcholine, norepinephrine, gamma-aminobutyric acid (GABA) and glutamate-mediated targets is calibrated using retrospective clinical data on 24 different antipsychotics. The model was challenged to predict quantitatively the clinical outcome in a blinded fashion of two experimental antipsychotic drugs; JNJ37822681, a highly selective low-affinity dopamine D2 antagonist and ocaperidone, a very high affinity dopamine D2 antagonist, using only pharmacology and human positron emission tomography (PET) imaging data. The model correctly predicted the lower performance of JNJ37822681 on the positive and negative syndrome scale (PANSS) total score and the higher extra-pyramidal symptom (EPS) liability compared to olanzapine and the relative performance of ocaperidone against olanzapine, but did not predict the absolute PANSS total score outcome and EPS liability for ocaperidone, possibly due to placebo responses and EPS assessment methods. Because of its virtual nature, this modeling approach can support central nervous system research and development by accounting for unique human drug properties, such as human metabolites, exposure, genotypes and off-target effects and can be a helpful tool for drug discovery and development. PMID:23251349

  11. Physiologically based Pharmacokinetic Modeling of 1,4-Dioxane in Rats, Mice, and Humans

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

    Sweeney, Lisa M.; Thrall, Karla D.; Poet, Torka S.

    2008-01-01

    ABSTRACT 1,4-Dioxane (CAS No. 123-91-1) is used primarily as a solvent or as a solvent stabilizer. It can cause lung, liver and kidney damage at sufficiently high exposure levels. Two physiologically-based pharmacokinetic (PBPK) models of 1,4-dioxane and its major metabolite, hydroxyethoxyacetic acid (HEAA), were published in 1990. These models have uncertainties and deficiencies that could be addressed and the model strengthened for use in a contemporary cancer risk assessment for 1,4-dioxane. Studies were performed to fill data gaps and reduce uncertainties pertaining to the pharmacokinetics of 1,4-dioxane and HEAA in rats, mice, and humans. Three types of studies were performed:partitionmore » coefficient measurements, blood time course in mice, and in vitro pharmacokinetics using rat, mouse, and human hepatocytes. Updated PBPK models were developed based on these new data and previously available data. The optimized rate of metabolism for the mouse was significantly higher than the value previously estimated. The optimized rat kinetic parameters were similar to those in the 1990 models. Only two human studies were identified. Model predictions were consistent with one study, but did not fit the second as well. In addition, a rat nasal exposure was completed. The results confirmed water directly contacts rat nasal tissues during drinking water under bioassays. Consistent with previous PBPK models, nasal tissues were not specifically included in the model. Use of these models will reduce the uncertainty in future 1,4-dioxane risk assessments.« less

  12. A DOSIMETRIC ANALYSIS OF THE ACUTE BEHAVIORAL EFFECTS OF INHALED TOLUENE IN RATS

    EPA Science Inventory

    Knowledge of the appropriate metric of dose for a toxic chemical facilitates quantitative extrapolation of toxicity observed in the laboratory to the risk of adverse effects in the human population. Here we utilize a physiologically-based toxicokinetic (PBTK) model for toluene, a...

  13. Human health and the environment: Predicting plasma protein binding and metabolic clearance rates of environmentally relevant chemicals.

    EPA Science Inventory

    In silico methods provide a rapid, inexpensive means of screening a wide array of environmentally relevant pollutants, pesticides, fungicides and consumer products for further toxicity testing. Physiologically based pharmacokinetic (PBPK) models bridge the gap between in vitro as...

  14. Breaking the Toxic Leadership Paradigm in the U.S. Army

    DTIC Science & Technology

    2012-02-28

    psychologist Abraham Maslow’s Hierarchy of Needs. Maslow categorized human needs into a five-level pyramid with physiological needs forming the base...followed by safety needs, love and belonging needs, esteem needs, and finally, self actualization. Maslow theorized that people could only realize and

  15. Chlorpyrifos PBPK/PD model for multiple routes of exposure.

    PubMed

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

    2014-10-01

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

  16. Study of physiological responses to acute carbon monoxide exposure with a human patient simulator.

    PubMed

    Cesari, Whitney A; Caruso, Dominique M; Zyka, Enela L; Schroff, Stuart T; Evans, Charles H; Hyatt, Jon-Philippe K

    2006-12-01

    Human patient simulators are widely used to train health professionals and students in a clinical setting, but they also can be used to enhance physiology education in a laboratory setting. Our course incorporates the human patient simulator for experiential learning in which undergraduate university juniors and seniors are instructed to design, conduct, and present (orally and in written form) their project testing physiological adaptation to an extreme environment. This article is a student report on the physiological response to acute carbon monoxide exposure in a simulated healthy adult male and a coal miner and represents how 1) human patient simulators can be used in a nonclinical way for experiential hypothesis testing; 2) students can transition from traditional textbook learning to practical application of their knowledge; and 3) student-initiated group investigation drives critical thought. While the course instructors remain available for consultation throughout the project, the relatively unstructured framework of the assignment drives the students to create an experiment independently, troubleshoot problems, and interpret the results. The only stipulation of the project is that the students must generate an experiment that is physiologically realistic and that requires them to search out and incorporate appropriate data from primary scientific literature. In this context, the human patient simulator is a viable educational tool for teaching integrative physiology in a laboratory environment by bridging textual information with experiential investigation.

  17. Physiologically Based Pharmacokinetic (PBPK) Modeling of Interstrain Variability in Trichloroethylene Metabolism in the Mouse

    PubMed Central

    Campbell, Jerry L.; Clewell, Harvey J.; Zhou, Yi-Hui; Wright, Fred A.; Guyton, Kathryn Z.

    2014-01-01

    Background: Quantitative estimation of toxicokinetic variability in the human population is a persistent challenge in risk assessment of environmental chemicals. Traditionally, interindividual differences in the population are accounted for by default assumptions or, in rare cases, are based on human toxicokinetic data. Objectives: We evaluated the utility of genetically diverse mouse strains for estimating toxicokinetic population variability for risk assessment, using trichloroethylene (TCE) metabolism as a case study. Methods: We used data on oxidative and glutathione conjugation metabolism of TCE in 16 inbred and 1 hybrid mouse strains to calibrate and extend existing physiologically based pharmacokinetic (PBPK) models. We added one-compartment models for glutathione metabolites and a two-compartment model for dichloroacetic acid (DCA). We used a Bayesian population analysis of interstrain variability to quantify variability in TCE metabolism. Results: Concentration–time profiles for TCE metabolism to oxidative and glutathione conjugation metabolites varied across strains. Median predictions for the metabolic flux through oxidation were less variable (5-fold range) than that through glutathione conjugation (10-fold range). For oxidative metabolites, median predictions of trichloroacetic acid production were less variable (2-fold range) than DCA production (5-fold range), although the uncertainty bounds for DCA exceeded the predicted variability. Conclusions: Population PBPK modeling of genetically diverse mouse strains can provide useful quantitative estimates of toxicokinetic population variability. When extrapolated to lower doses more relevant to environmental exposures, mouse population-derived variability estimates for TCE metabolism closely matched population variability estimates previously derived from human toxicokinetic studies with TCE, highlighting the utility of mouse interstrain metabolism studies for addressing toxicokinetic variability. Citation: Chiu WA, Campbell JL Jr, Clewell HJ III, Zhou YH, Wright FA, Guyton KZ, Rusyn I. 2014. Physiologically based pharmacokinetic (PBPK) modeling of interstrain variability in trichloroethylene metabolism in the mouse. Environ Health Perspect 122:456–463; http://dx.doi.org/10.1289/ehp.1307623 PMID:24518055

  18. Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis.

    PubMed

    Gao, Wei; Emaminejad, Sam; Nyein, Hnin Yin Yin; Challa, Samyuktha; Chen, Kevin; Peck, Austin; Fahad, Hossain M; Ota, Hiroki; Shiraki, Hiroshi; Kiriya, Daisuke; Lien, Der-Hsien; Brooks, George A; Davis, Ronald W; Javey, Ali

    2016-01-28

    Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual's state of health. Sampling human sweat, which is rich in physiological information, could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications.

  19. Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis

    NASA Astrophysics Data System (ADS)

    Gao, Wei; Emaminejad, Sam; Nyein, Hnin Yin Yin; Challa, Samyuktha; Chen, Kevin; Peck, Austin; Fahad, Hossain M.; Ota, Hiroki; Shiraki, Hiroshi; Kiriya, Daisuke; Lien, Der-Hsien; Brooks, George A.; Davis, Ronald W.; Javey, Ali

    2016-01-01

    Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual’s state of health. Sampling human sweat, which is rich in physiological information, could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications.

  20. 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.

  1. Synthesis of a selective ratiometric fluorescent probe based on Naphthalimide and its application in human cytochrome P450 1A.

    PubMed

    Zhang, Xiuxuan; Zhou, Yan; Gu, Xiaofei; Cheng, Yu; Hong, Manxin; Yan, Liqiang; Ma, Fulong; Qi, Zhengjian

    2018-08-15

    Cytochrome P450s have brought considerable attention to researchers for their significant correlations with metabolic behaviors of procarcinogenic chemicals. To better understand the roles of CYP1A in biological and physiological systems, we developed a novel ratiometric fluorescence probe N-((2-hydroxyl ethoxy) ethyl)- 4-methoxy-1, 8-naphthalimide (NEMN) allowing for selectively and sensitively monitoring the target enzymes under physiological conditions and living cells. The probe was designed based on substrate predilection of CYP1A and its outstanding O-dealkylation capacity, and 1, 8-naphthalimide was chosen as fluorophore on account of its desirable photophysical properties. Absorption and emission spectra of the probe solution and reacted metabolism showed obvious red-shift with remarkable colour changes, which indicated that NEMN could be a promising ratiometric detector of CYP1A. Additionally, the selectivity assays displayed that NEMN only sensitive to CYP1A1 and CYP1A2 enzymes with scarce interference of other CYPs. Furthermore, the excellent linear relationships between the ratio of fluorescent intensities and incubation time and enzymes concentration signified time- and concentration- dependence of the probe, which were of desire benefit to quantify and monitor the CYP1A-involved biological behaviors in physiological conditions. The assay in real living samples (Human liver microsomes) further proved the analytical utility of the probe. Finally, the cytotoxicity assay and confocal fluorescence imaging demonstrated that this probe was of great promise for detecting the activity of endogenous CYP1A in human living cells. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Calibration-free technique for the measurement of oxygen saturation changes in muscles of marine mammals and its proof of concept

    NASA Astrophysics Data System (ADS)

    Ortega-Martinez, Antonio; Goenka, Chhavi; Booker, Marloes; Grange, Robert M. H.; Hindle, Allyson G.; Franco, Walfre

    2018-02-01

    Marine mammals possess impressive breath-holding capabilities made possible by physiological adjustments during dives. Studying marine mammals in their natural environment unravels vital information about these physiological adjustments particularly when we can monitor altered dive behavior in response to stressful situations such as human-induced oceanic disturbances, presence of predators and altered prey distributions. An important indicator of physiological status during submergence is the change in oxygen saturation in the muscles and blood of these mammals. In this work, we aim to investigate oxygen storage and consumption in the muscles of free-diving elephant seals when exposed to disturbances such as sonar or predator sounds while they are at sea. Optical oxygen sensors are a mature technology with multiple medical applications that provide a way to measure oxygenation changes in biological tissues in a minimally invasive manner. While these sensors are well calibrated and readily available for humans, they are still inadequate for marine mammals primarily due to a very small number of test candidates and therefore little data is available for validation and calibration. We propose a probe geometry and associated mathematical model for measuring muscle oxygenation in seals based on near infrared diffuse transport with no need for calibration. A prototype based on this concept has been designed and tested on humans and rats. We use the test results to discuss the advantages and limitations of the approach. We also detail the constraints on size, sensor location, electronics, light source properties and detector characteristics posed by the unique biology of seals.

  3. 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.

  4. Single-trial lie detection using a combined fNIRS-polygraph system

    PubMed Central

    Bhutta, M. Raheel; Hong, Melissa J.; Kim, Yun-Hee; Hong, Keum-Shik

    2015-01-01

    Deception is a human behavior that many people experience in daily life. It involves complex neuronal activities in addition to several physiological changes in the body. A polygraph, which can measure some of the physiological responses from the body, has been widely employed in lie-detection. Many researchers, however, believe that lie detection can become more precise if the neuronal changes that occur in the process of deception can be isolated and measured. In this study, we combine both measures (i.e., physiological and neuronal changes) for enhanced lie-detection. Specifically, to investigate the deception-related hemodynamic response, functional near-infrared spectroscopy (fNIRS) is applied at the prefrontal cortex besides a commercially available polygraph system. A mock crime scenario with a single-trial stimulus is set up as a deception protocol. The acquired data are classified into “true” and “lie” classes based on the fNIRS-based hemoglobin-concentration changes and polygraph-based physiological signal changes. Linear discriminant analysis is utilized as a classifier. The results indicate that the combined fNIRS-polygraph system delivers much higher classification accuracy than that of a singular system. This study demonstrates a plausible solution toward single-trial lie-detection by combining fNIRS and the polygraph. PMID:26082733

  5. Understanding Kidney Disease: Toward the Integration of Regulatory Networks Across Species

    PubMed Central

    Ju, Wenjun; Brosius, Frank C.

    2010-01-01

    Animal models have long been useful in investigating both normal and abnormal human physiology. Systems biology provides a relatively new set of approaches to identify similarities and differences between animal models and humans that may lead to a more comprehensive understanding of human kidney pathophysiology. In this review, we briefly describe how genome-wide analyses of mouse models have helped elucidate features of human kidney diseases, discuss strategies to achieve effective network integration, and summarize currently available web-based tools that may facilitate integration of data across species. The rapid progress in systems biology and orthology, as well as the advent of web-based tools to facilitate these processes, now make it possible to take advantage of knowledge from distant animal species in targeted identification of regulatory networks that may have clinical relevance for human kidney diseases. PMID:21044762

  6. 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.

  7. 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.

  8. 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.

  9. Scientific/Technical Report Bioenergetics Research Initiative Award number-DE-FG02-05ER64092

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

    Trappe, Scott A

    2009-12-04

    General Project Overview and Final Technical Report This equipment grant was utilized to enhance the infrastructure of the Human Performance Laboratory at Ball State University. The laboratories primary focus is human based exercise physiology conducting research in the areas of sports performance, aging and exercise, unloading (space flight and bed rest), pediatric exercise and clinical exercise physiology. The main equipment supported by this grant was an ultrasound unit for cardiac and skeletal muscle imaging at the whole organ level, microscope system for micro imaging of skeletal muscle tissue, running treadmill for energy expenditure assessment, autoclave for sterilization, and upgrade tomore » our dual x–ray absorptiometry (DEXA) system that was utilized for body composition measurements. The equipment was involved in several human metabolic and skeletal muscle research projects as highlighted above. In particular, this equipment served a support role for other large–scale clinical projects funded by the National Institutes of Health (NIH), National Aeronautics and Space Administration (NASA), and corporate sponsors.« less

  10. 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

  11. Emulating Host-Microbiome Ecosystem of Human Gastrointestinal Tract in Vitro.

    PubMed

    Park, Gun-Seok; Park, Min Hee; Shin, Woojung; Zhao, Connie; Sheikh, Sameer; Oh, So Jung; Kim, Hyun Jung

    2017-06-01

    The human gut microbiome performs prodigious physiological functions such as production of microbial metabolites, modulation of nutrient digestion and drug metabolism, control of immune system, and prevention of infection. Paradoxically, gut microbiome can also negatively orchestrate the host responses in diseases or chronic disorders, suggesting that the regulated and balanced host-gut microbiome crosstalk is a salient prerequisite in gastrointestinal physiology. To understand the pathophysiological role of host-microbiome crosstalk, it is critical to recreate in vivo relevant models of the host-gut microbiome ecosystem in human. However, controlling the multi-species microbial communities and their uncontrolled growth has remained a notable technical challenge. Furthermore, conventional two-dimensional (2D) or 3D culture systems do not recapitulate multicellular microarchitectures, mechanical dynamics, and tissue-specific functions. Here, we review recent advances and current pitfalls of in vitro and ex vivo models that display human GI functions. We also discuss how the disruptive technologies such as 3D organoids or a human organ-on-a-chip microphysiological system can contribute to better emulate host-gut microbiome crosstalks in health and disease. Finally, the medical and pharmaceutical significance of the gut microbiome-based personalized interventions is underlined as a future perspective.

  12. 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

  13. 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...

  14. 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

  15. 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

  16. Comparison of rotator cuff muscle architecture between humans and other selected vertebrate species

    PubMed Central

    Mathewson, Margie A.; Kwan, Alan; Eng, Carolyn M.; Lieber, Richard L.; Ward, Samuel R.

    2014-01-01

    In this study, we compare rotator cuff muscle architecture of typically used animal models with that of humans and quantify the scaling relationships of these muscles across mammals. The four muscles that correspond to the human rotator cuff – supraspinatus, infraspinatus, subscapularis and teres minor – of 10 commonly studied animals were excised and subjected to a series of comparative measurements. When body mass among animals was regressed against physiological cross-sectional area, muscle mass and normalized fiber length, the confidence intervals suggested geometric scaling but did not exclude other scaling relationships. Based on the architectural difference index (ADI), a combined measure of fiber length-to-moment arm ratio, fiber length-to-muscle length ratio and the fraction of the total rotator cuff physiological cross-sectional area contributed by each muscle, chimpanzees were found to be the most similar to humans (ADI=2.15), followed closely by capuchins (ADI=2.16). Interestingly, of the eight non-primates studied, smaller mammals such as mice, rats and dogs were more similar to humans in architectural parameters compared with larger mammals such as sheep, pigs or cows. The force production versus velocity trade-off (indicated by fiber length-to-moment arm ratio) and the excursion ability (indicated by fiber length-to-muscle length ratio) of humans were also most similar to those of primates, followed by the small mammals. Overall, primates provide the best architectural representation of human muscle architecture. However, based on the muscle architectural parameters of non-primates, smaller rather than larger mammals may be better models for studying muscles related to the human rotator cuff. PMID:24072803

  17. Estimating psycho-physiological state of a human by speech analysis

    NASA Astrophysics Data System (ADS)

    Ronzhin, A. L.

    2005-05-01

    Adverse effects of intoxication, fatigue and boredom could degrade performance of highly trained operators of complex technical systems with potentially catastrophic consequences. Existing physiological fitness for duty tests are time consuming, costly, invasive, and highly unpopular. Known non-physiological tests constitute a secondary task and interfere with the busy workload of the tested operator. Various attempts to assess the current status of the operator by processing of "normal operational data" often lead to excessive amount of computations, poorly justified metrics, and ambiguity of results. At the same time, speech analysis presents a natural, non-invasive approach based upon well-established efficient data processing. In addition, it supports both behavioral and physiological biometric. This paper presents an approach facilitating robust speech analysis/understanding process in spite of natural speech variability and background noise. Automatic speech recognition is suggested as a technique for the detection of changes in the psycho-physiological state of a human that typically manifest themselves by changes of characteristics of voice tract and semantic-syntactic connectivity of conversation. Preliminary tests have confirmed that the statistically significant correlation between the error rate of automatic speech recognition and the extent of alcohol intoxication does exist. In addition, the obtained data allowed exploring some interesting correlations and establishing some quantitative models. It is proposed to utilize this approach as a part of fitness for duty test and compare its efficiency with analyses of iris, face geometry, thermography and other popular non-invasive biometric techniques.

  18. Application of Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling in Cumulative Risk Assessment for N-Methyl Carbamate Insecticides

    EPA Science Inventory

    Human exposure to xenobiotics may occur through multiple pathways and routes of entry punctuated by exposure intervals throughout a work or leisure day. Exposure to a single environmental chemical along multiple pathways and routes (aggregate exposure) may have an influence on an...

  19. THE IMPACT OF SCALING FACTOR VARIABILITY ON RISK-RELEVANT TOXICOKINETIC OUTCOMES IN CHILDREN: A CASE STUDY USING BROMODICHLOROMETHANE (BDCM)

    EPA Science Inventory

    Biotransformation rates (Vmax) extrapolated from in vitro data are used increasingly in human physiologically based pharmacokinetic (PBPK) models. Extrapolation of Vmax from in vitro data requires use of scaling factors, including mg of microsomal protein/g liver (MPPGL), nmol of...

  20. 77 FR 72975 - Zeta Cypermethrin; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-07

    ... confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA without prior notice. Submit the non... physiological differences between abraded and non-abraded animals, further undermining the relevance of these... classified as a Group C ``Possible human carcinogen,'' based on an increased incidence of lung adenomas and...

  1. 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...

  2. A pharmacokinetic model of cis- and trans-permethrin disposition in rats and humans with aggregate exposure application

    EPA Science Inventory

    Permethrin is a broad-spectrum pyrethroid insecticide and among the most widely used insecticides in homes and crops. Managing the risks for pesticides such as permethrin depends on the ability to consider diverse exposure scenarios and their relative risks. Physiologically-base...

  3. [Methods for measuring skin aging].

    PubMed

    Zieger, M; Kaatz, M

    2016-02-01

    Aging affects human skin and is becoming increasingly important with regard to medical, social and aesthetic issues. Detection of intrinsic and extrinsic components of skin aging requires reliable measurement methods. Modern techniques, e.g., based on direct imaging, spectroscopy or skin physiological measurements, provide a broad spectrum of parameters for different applications.

  4. PHYSIOLOGICALLY-BASED PHARMACOKINETICS/PHARMACODYNAMIC MODELING AND CUMULATIVE RISK ASSESSMENT: CASE STUDY FOR THE N-METHYL CARBMATE PESTICIDES

    EPA Science Inventory

    The Food Quality Protection Act of 1996 [PL 104-170: 110 STAT. 1513] requires EPA to consider potential cumulative human health risks resulting from aggregate exposure to pesticide chemicals acting through a common mechanism of toxicity. This includes all anticipated dietary e...

  5. XENOBIOTIC METABOLISM RESEARCH AND ITS APPLICATION TO HUMAN AND ECOLOGICAL EXPOSURE AND RISK ASSESSMENT

    EPA Science Inventory

    A major uncertainty in risk assessment is determining the exposure of a target organism to a chemical stressor, and a confounding factor is the transformation of the chemical to a toxic metabolite inside the target organism. Physiologically-based pharmacokinetic (PBPK) models are...

  6. Effective Student Motivation Commences with Resolving "Dissatisfiers"

    ERIC Educational Resources Information Center

    Prescott, Ann; Simpson, Edward

    2004-01-01

    The evolution in students' expectations based on Maslow's theory of human motivation shows a transition from expectations having an effect upon motivation towards those providing a satisfactory experience. Maslow's argument was that once the lower level needs, such as physiological and safety needs, are met other higher needs emerge. In the…

  7. Reengineering Human Performance and Fatigue Research Through Use of Physiological Monitoring Devices, Web-Based and Mobile Device Data Collection Methods, and Integrated Data Storage Techniques

    DTIC Science & Technology

    2003-12-01

    Lin, T. M. and Sadhu, P. XML How to Program . Prentice Hall, 2001. Dement, W. and Greenberg, S. (1966) “Changes in Total Amount of Stage Four Sleep...training in the science of conducting human research as well as how to use the collection equipment and analysis tools available to them at NPS. In order...redesign? • How will development of a PDA based tracking log give support to process redesign? D. SCOPE OF THESIS In efforts to improve data

  8. Accuracy and Efficiency of Recording Pediatric Early Warning Scores Using an Electronic Physiological Surveillance System Compared With Traditional Paper-Based Documentation

    PubMed Central

    Sefton, Gerri; Lane, Steven; Killen, Roger; Black, Stuart; Lyon, Max; Ampah, Pearl; Sproule, Cathryn; Loren-Gosling, Dominic; Richards, Caitlin; Spinty, Jean; Holloway, Colette; Davies, Coral; Wilson, April; Chean, Chung Shen; Carter, Bernie; Carrol, E.D.

    2017-01-01

    Pediatric Early Warning Scores are advocated to assist health professionals to identify early signs of serious illness or deterioration in hospitalized children. Scores are derived from the weighting applied to recorded vital signs and clinical observations reflecting deviation from a predetermined “norm.” Higher aggregate scores trigger an escalation in care aimed at preventing critical deterioration. Process errors made while recording these data, including plotting or calculation errors, have the potential to impede the reliability of the score. To test this hypothesis, we conducted a controlled study of documentation using five clinical vignettes. We measured the accuracy of vital sign recording, score calculation, and time taken to complete documentation using a handheld electronic physiological surveillance system, VitalPAC Pediatric, compared with traditional paper-based charts. We explored the user acceptability of both methods using a Web-based survey. Twenty-three staff participated in the controlled study. The electronic physiological surveillance system improved the accuracy of vital sign recording, 98.5% versus 85.6%, P < .02, Pediatric Early Warning Score calculation, 94.6% versus 55.7%, P < .02, and saved time, 68 versus 98 seconds, compared with paper-based documentation, P < .002. Twenty-nine staff completed the Web-based survey. They perceived that the electronic physiological surveillance system offered safety benefits by reducing human error while providing instant visibility of recorded data to the entire clinical team. PMID:27832032

  9. 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.

  10. Movement Performance of Human-Robot Cooperation Control Based on EMG-Driven Hill-Type and Proportional Models for an Ankle Power-Assist Exoskeleton Robot.

    PubMed

    Ao, Di; Song, Rong; Gao, JinWu

    2017-08-01

    Although the merits of electromyography (EMG)-based control of powered assistive systems have been certified, the factors that affect the performance of EMG-based human-robot cooperation, which are very important, have received little attention. This study investigates whether a more physiologically appropriate model could improve the performance of human-robot cooperation control for an ankle power-assist exoskeleton robot. To achieve the goal, an EMG-driven Hill-type neuromusculoskeletal model (HNM) and a linear proportional model (LPM) were developed and calibrated through maximum isometric voluntary dorsiflexion (MIVD). The two control models could estimate the real-time ankle joint torque, and HNM is more accurate and can account for the change of the joint angle and muscle dynamics. Then, eight healthy volunteers were recruited to wear the ankle exoskeleton robot and complete a series of sinusoidal tracking tasks in the vertical plane. With the various levels of assist based on the two calibrated models, the subjects were instructed to track the target displayed on the screen as accurately as possible by performing ankle dorsiflexion and plantarflexion. Two measurements, the root mean square error (RMSE) and root mean square jerk (RMSJ), were derived from the assistant torque and kinematic signals to characterize the movement performances, whereas the amplitudes of the recorded EMG signals from the tibialis anterior (TA) and the gastrocnemius (GAS) were obtained to reflect the muscular efforts. The results demonstrated that the muscular effort and smoothness of tracking movements decreased with an increase in the assistant ratio. Compared with LPM, subjects made lower physical efforts and generated smoother movements when using HNM, which implied that a more physiologically appropriate model could enable more natural and human-like human-robot cooperation and has potential value for improvement of human-exoskeleton interaction in future applications.

  11. A nanofiber based artificial electronic skin with high pressure sensitivity and 3D conformability

    NASA Astrophysics Data System (ADS)

    Zhong, Weibin; Liu, Qiongzhen; Wu, Yongzhi; Wang, Yuedan; Qing, Xing; Li, Mufang; Liu, Ke; Wang, Wenwen; Wang, Dong

    2016-06-01

    Pressure sensors with 3D conformability are highly desirable components for artificial electronic skin or e-textiles that can mimic natural skin, especially for application in real-time monitoring of human physiological signals. Here, a nanofiber based electronic skin with ultra-high pressure sensitivity and 3D conformability is designed and built by interlocking two elastic patterned nanofibrous membranes. The patterned membrane is facilely prepared by casting conductive nanofiber ink into a silicon mould to form an array of semi-spheroid-like protuberances. The protuberances composed of intertwined elastic POE nanofibers and PPy@PVA-co-PE nanofibers afford a tunable effective elastic modulus that is capable of capturing varied strains and stresses, thereby contributing to a high sensitivity for pressure sensing. This electronic skin-like sensor demonstrates an ultra-high sensitivity (1.24 kPa-1) below 150 Pa with a detection limit as low as about 1.3 Pa. The pixelated sensor array and a RGB-LED light are then assembled into a circuit and show a feasibility for visual detection of spatial pressure. Furthermore, a nanofiber based proof-of-concept wireless pressure sensor with a bluetooth module as a signal transmitter is proposed and has demonstrated great promise for wireless monitoring of human physiological signals, indicating a potential for large scale wearable electronic devices or e-skin.Pressure sensors with 3D conformability are highly desirable components for artificial electronic skin or e-textiles that can mimic natural skin, especially for application in real-time monitoring of human physiological signals. Here, a nanofiber based electronic skin with ultra-high pressure sensitivity and 3D conformability is designed and built by interlocking two elastic patterned nanofibrous membranes. The patterned membrane is facilely prepared by casting conductive nanofiber ink into a silicon mould to form an array of semi-spheroid-like protuberances. The protuberances composed of intertwined elastic POE nanofibers and PPy@PVA-co-PE nanofibers afford a tunable effective elastic modulus that is capable of capturing varied strains and stresses, thereby contributing to a high sensitivity for pressure sensing. This electronic skin-like sensor demonstrates an ultra-high sensitivity (1.24 kPa-1) below 150 Pa with a detection limit as low as about 1.3 Pa. The pixelated sensor array and a RGB-LED light are then assembled into a circuit and show a feasibility for visual detection of spatial pressure. Furthermore, a nanofiber based proof-of-concept wireless pressure sensor with a bluetooth module as a signal transmitter is proposed and has demonstrated great promise for wireless monitoring of human physiological signals, indicating a potential for large scale wearable electronic devices or e-skin. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr02678h

  12. Human cold stress of strong local-wind "Hijikawa-arashi" in Japan, based on the UTCI index and thermo-physiological responses.

    PubMed

    Ohashi, Yukitaka; Katsuta, Takumi; Tani, Haruka; Okabayashi, Taiki; Miyahara, Satoshi; Miyashita, Ryoji

    2018-03-30

    We investigated the cold stress caused by a strong local wind called "Hijikawa-arashi," through in situ vital measurements and the Universal Thermal Climate Index (UTCI). This wind is a very interesting winter phenomenon, localized in an area within 1 km of the seashore in Ozu City, Ehime Prefecture in Japan. When a strong Hijikawa-arashi (HA) occurred at 14-15 m s -1 , the UTCI decreased to - 30 °C along the bridge where commuting residents are the most exposed to strong and cold winds. On the bridge, most participants in our experiment felt "very cold" or "extremely cold." The UTCI of HA can be predicted from a multiple regression equation using wind speed and air temperature. The cold HA wind is also harmful to human thermo-physiological responses. It leads to higher blood pressure and increased heart rate, both of which act as cardiovascular stress triggers. Increases of 6-10 mmHg and 3-6 bpm for every 10 °C reduction in UTCI were seen on all observational days, including HA and non-HA days. In fact, the participants' body skin temperatures decreased by approximately 1.2 to 1.7 °C for every 10 °C reduction in UTCI. Thus, the UTCI variation due to the HA outbreak corresponded well with the cold sensation and thermo-physiological responses in humans. This result suggests that daily UTCI monitoring enables the prediction of thermo-physiological responses to the HA cold stress.

  13. Comparison of fabric skins for the simulation of sweating on thermal manikins

    NASA Astrophysics Data System (ADS)

    Koelblen, Barbara; Psikuta, Agnes; Bogdan, Anna; Annaheim, Simon; Rossi, René M.

    2017-09-01

    Sweating is an important thermoregulatory process helping to dissipate heat and, thus, to prevent overheating of the human body. Simulations of human thermo-physiological responses in hot conditions or during exercising are helpful for assessing heat stress; however, realistic sweating simulation and evaporative cooling is needed. To this end, thermal manikins dressed with a tight fabric skin can be used, and the properties of this skin should help human-like sweat evaporation simulation. Four fabrics, i.e., cotton with elastane, polyester, polyamide with elastane, and a skin provided by a manikin manufacturer (Thermetrics) were compared in this study. The moisture management properties of the fabrics have been investigated in basic tests with regard to all phases of sweating relevant for simulating human thermo-physiological responses, namely, onset of sweating, fully developed sweating, and drying. The suitability of the fabrics for standard tests, such as clothing evaporative resistance measurements, was evaluated based on tests corresponding to the middle phase of sweating. Simulations with a head manikin coupled to a thermo-physiological model were performed to evaluate the overall performance of the skins. The results of the study showed that three out of four evaluated fabrics have adequate moisture management properties with regard to the simulation of sweating, which was confirmed in the coupled simulation with the head manikin. The presented tests are helpful for comparing the efficiency of different fabrics to simulate sweat-induced evaporative cooling on thermal manikins.

  14. [What is an emotion? An introduction to the study of emotions].

    PubMed

    Derouesné, Christian

    2011-03-01

    Human emotions are hypothetic constructs based on psychological and physiological data. According to the psychoevolutionnist theories, all emotions derive from a set of discrete basic emotions, common to human and animals, genetically determined. Basic emotions are thus considered as physiological processes based on specific neuronal circuits. On the contrary, for appraisal and social theories, emotions are psychological processes resulting from the cognitive appraisal of the stimulus-event for the well-being and objectives of the subject, and are of social origin. They develop during life, especially in childhood, from interactions between the individual and his environement. According to the appraisal or constructivist theories, no sharp distinction is to be made between emotions and other manifestations of the affective life. Emotions require the global functioning of the brain, even if more specialized regions are involved. They play a fundamental role in the development of the child's psychological and social life. They mediate the subject's response to the stimulus-event, allowing more appropriate reactions than fixed instinctive ones. Nevertheless, the adaptative function of every emotion or their every component can be questioned. Emotional disturbances are major consequences of psychiatric or neurological disorders. The link between the results of neuropsychological studies of emotions based on the recognition of emotional facal expression according to the basic emotion theory, and the emotional disturbances experienced in daily life is highly questionable on account of the high complexity of human affective life.

  15. BIOTEX--biosensing textiles for personalised healthcare management.

    PubMed

    Coyle, Shirley; Lau, King-Tong; Moyna, Niall; O'Gorman, Donal; Diamond, Dermot; Di Francesco, Fabio; Costanzo, Daniele; Salvo, Pietro; Trivella, Maria Giovanna; De Rossi, Danilo Emilio; Taccini, Nicola; Paradiso, Rita; Porchet, Jacque-André; Ridolfi, Andrea; Luprano, Jean; Chuzel, Cyril; Lanier, Thierry; Revol-Cavalier, Frdéric; Schoumacker, Sébastien; Mourier, Véronique; Chartier, Isabelle; Convert, Reynald; De-Moncuit, Henri; Bini, Christina

    2010-03-01

    Textile-based sensors offer an unobtrusive method of continually monitoring physiological parameters during daily activities. Chemical analysis of body fluids, noninvasively, is a novel and exciting area of personalized wearable healthcare systems. BIOTEX was an EU-funded project that aimed to develop textile sensors to measure physiological parameters and the chemical composition of body fluids, with a particular interest in sweat. A wearable sensing system has been developed that integrates a textile-based fluid handling system for sample collection and transport with a number of sensors including sodium, conductivity, and pH sensors. Sensors for sweat rate, ECG, respiration, and blood oxygenation were also developed. For the first time, it has been possible to monitor a number of physiological parameters together with sweat composition in real time. This has been carried out via a network of wearable sensors distributed around the body of a subject user. This has huge implications for the field of sports and human performance and opens a whole new field of research in the clinical setting.

  16. Customized Body Mapping to Facilitate the Ergonomic Design of Sportswear.

    PubMed

    Cao, Mingliang; Li, Yi; Guo, Yueping; Yao, Lei; Pan, Zhigeng

    2016-01-01

    A successful high-performance sportswear design that considers human factors should result in a significant increase in thermal comfort and reduce energy loss. The authors describe a body-mapping approach that facilitates the effective ergonomic design of sportswear. Their general framework can be customized based on the functional requirements of various sports and sportswear, the desired combination and selection of mapping areas for the human body, and customized quantitative data distribution of target physiological indicators.

  17. Dataset from Dick et al published in Sawyer et al 2016

    EPA Pesticide Factsheets

    Dataset is a time course description of lindane disappearance in blood plasma after dermal exposure in human volunteersThis dataset is associated with the following publication:Sawyer, M.E., M.V. Evans , C. Wilson, L.J. Beesley, L. Leon, C. Eklund , E. Croom, and R. Pegram. Development of a Human Physiologically Based Pharmacokinetics (PBPK) Model For Dermal Permeability for Lindane. TOXICOLOGY LETTERS. Elsevier Science Ltd, New York, NY, USA, 14(245): pp106-109, (2016).

  18. Interim methods for development of inhalation reference concentrations. Draft report

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

    Blackburn, K.; Dourson, M.; Erdreich, L.

    1990-08-01

    An inhalation reference concentration (RfC) is an estimate of continuous inhalation exposure over a human lifetime that is unlikely to pose significant risk of adverse noncancer health effects and serves as a benchmark value for assisting in risk management decisions. Derivation of an RfC involves dose-response assessment of animal data to determine the exposure levels at which no significant increase in the frequency or severity of adverse effects between the exposed population and its appropriate control exists. The assessment requires an interspecies dose extrapolation from a no-observed-adverse-effect level (NOAEL) exposure concentration of an animal to a human equivalent NOAEL (NOAEL(HBC)).more » The RfC is derived from the NOAEL(HBC) by the application of generally order-of-magnitude uncertainty factors. Intermittent exposure scenarios in animals are extrapolated to chronic continuous human exposures. Relationships between external exposures and internal doses depend upon complex simultaneous and consecutive processes of absorption, distribution, metabolism, storage, detoxification, and elimination. To estimate NOAEL(HBC)s when chemical-specific physiologically-based pharmacokinetic models are not available, a dosimetric extrapolation procedure based on anatomical and physiological parameters of the exposed human and animal and the physical parameters of the toxic chemical has been developed which gives equivalent or more conservative exposure concentrations values than those that would be obtained with a PB-PK model.« less

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

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

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

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

  20. 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.

  1. Study of Physiological Responses to Acute Carbon Monoxide Exposure with a Human Patient Simulator

    ERIC Educational Resources Information Center

    Cesari, Whitney A.; Caruso, Dominique M.; Zyka, Enela L.; Schroff, Stuart T.; Evans, Charles H., Jr.; Hyatt, Jon-Philippe K.

    2006-01-01

    Human patient simulators are widely used to train health professionals and students in a clinical setting, but they also can be used to enhance physiology education in a laboratory setting. Our course incorporates the human patient simulator for experiential learning in which undergraduate university juniors and seniors are instructed to design,…

  2. Organophosphorus Insecticide Pharmacokinetics

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

    Timchalk, Charles

    2010-01-01

    This chapter highlights a number of current and future applications of pharmacokinetics to assess organophosphate (OP) insecticide dosimetry, biological response and risk in humans exposed to these agents. Organophosphates represent a large family of pesticides where insecticidal as well as toxicological mode of action is associated with their ability to target and inhibit acetylcholinesterase (AChE). Pharmacokinetics entails the quantitative integration of physiological and metabolic processes associated with the absorption, distribution, metabolism and excretion (ADME) of drugs and xenobiotics. Pharmacokinetic studies provide important data on the amount of toxicant delivered to a target site as well as species-, age-, gender-specific andmore » dose-dependent differences in biological response. These studies have been conducted with organophosphorus insecticides in multiple species, at various dose levels, and across different routes of exposure to understand their in vivo pharmacokinetics and how they contribute to the observed toxicological response. To access human exposure to organophosphorus insecticides, human pharmacokinetic studies have been conducted and used to develop biological monitoring strategies based on the quantitation of key metabolites in biological fluids. Pharmacokinetic studies with these insecticides are also useful to facilitate extrapolation of dosimetry and biological response from animals to humans and for the assessment of human health risk. In this regard, physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) models are being utilized to assess risk and understand the toxicological implications of known or suspected exposures to various insecticides. In this chapter a number of examples are presented that illustrate the utility and limitation of pharmacokinetic studies to address human health concerns associated with organophosphorus insecticides.« less

  3. 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.

  4. 3Mo: A Model for Music-Based Biofeedback

    PubMed Central

    Maes, Pieter-Jan; Buhmann, Jeska; Leman, Marc

    2016-01-01

    In the domain of sports and motor rehabilitation, it is of major importance to regulate and control physiological processes and physical motion in most optimal ways. For that purpose, real-time auditory feedback of physiological and physical information based on sound signals, often termed “sonification,” has been proven particularly useful. However, the use of music in biofeedback systems has been much less explored. In the current article, we assert that the use of music, and musical principles, can have a major added value, on top of mere sound signals, to the benefit of psychological and physical optimization of sports and motor rehabilitation tasks. In this article, we present the 3Mo model to describe three main functions of music that contribute to these benefits. These functions relate the power of music to Motivate, and to Monitor and Modify physiological and physical processes. The model brings together concepts and theories related to human sensorimotor interaction with music, and specifies the underlying psychological and physiological principles. This 3Mo model is intended to provide a conceptual framework that guides future research on musical biofeedback systems in the domain of sports and motor rehabilitation. PMID:27994535

  5. Complexity analysis of human physiological signals based on case studies

    NASA Astrophysics Data System (ADS)

    Angelova, Maia; Holloway, Philip; Ellis, Jason

    2015-04-01

    This work focuses on methods for investigation of physiological time series based on complexity analysis. It is a part of a wider programme to determine non-invasive markers for healthy ageing. We consider two case studies investigated with actigraphy: (a) sleep and alternations with insomnia, and (b) ageing effects on mobility patterns. We illustrate, using these case studies, the application of fractal analysis to the investigation of regulation patterns and control, and change of physiological function. In the first case study, fractal analysis techniques were implemented to study the correlations present in sleep actigraphy for individuals suffering from acute insomnia in comparison with healthy controls. The aim was to investigate if complexity analysis can detect the onset of adverse health-related events. The subjects with acute insomnia displayed significantly higher levels of complexity, possibly a result of too much activity in the underlying regulatory systems. The second case study considered mobility patterns during night time and their variations with age. It showed that complexity metrics can identify change in physiological function with ageing. Both studies demonstrated that complexity analysis can be used to investigate markers of health, disease and healthy ageing.

  6. Multiplexed Activity-based Protein Profiling of the Human Pathogen Aspergillus fumigatus Reveals Large Functional Changes upon Exposure to Human Serum*

    PubMed Central

    Wiedner, Susan D.; Burnum, Kristin E.; Pederson, LeeAnna M.; Anderson, Lindsey N.; Fortuin, Suereta; Chauvigné-Hines, Lacie M.; Shukla, Anil K.; Ansong, Charles; Panisko, Ellen A.; Smith, Richard D.; Wright, Aaron T.

    2012-01-01

    Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli. PMID:22865858

  7. Multiplexed activity-based protein profiling of the human pathogen Aspergillus fumigatus reveals large functional changes upon exposure to human serum.

    PubMed

    Wiedner, Susan D; Burnum, Kristin E; Pederson, LeeAnna M; Anderson, Lindsey N; Fortuin, Suereta; Chauvigné-Hines, Lacie M; Shukla, Anil K; Ansong, Charles; Panisko, Ellen A; Smith, Richard D; Wright, Aaron T

    2012-09-28

    Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli.

  8. 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)

  9. 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.

  10. Bayesian analysis of physiologically based toxicokinetic and toxicodynamic models.

    PubMed

    Hack, C Eric

    2006-04-17

    Physiologically based toxicokinetic (PBTK) and toxicodynamic (TD) models of bromate in animals and humans would improve our ability to accurately estimate the toxic doses in humans based on available animal studies. These mathematical models are often highly parameterized and must be calibrated in order for the model predictions of internal dose to adequately fit the experimentally measured doses. Highly parameterized models are difficult to calibrate and it is difficult to obtain accurate estimates of uncertainty or variability in model parameters with commonly used frequentist calibration methods, such as maximum likelihood estimation (MLE) or least squared error approaches. The Bayesian approach called Markov chain Monte Carlo (MCMC) analysis can be used to successfully calibrate these complex models. Prior knowledge about the biological system and associated model parameters is easily incorporated in this approach in the form of prior parameter distributions, and the distributions are refined or updated using experimental data to generate posterior distributions of parameter estimates. The goal of this paper is to give the non-mathematician a brief description of the Bayesian approach and Markov chain Monte Carlo analysis, how this technique is used in risk assessment, and the issues associated with this approach.

  11. Physiologically Based Pharmacokinetic (PBPK) Modeling of ...

    EPA Pesticide Factsheets

    Background: Quantitative estimation of toxicokinetic variability in the human population is a persistent challenge in risk assessment of environmental chemicals. Traditionally, inter-individual differences in the population are accounted for by default assumptions or, in rare cases, are based on human toxicokinetic data.Objectives: To evaluate the utility of genetically diverse mouse strains for estimating toxicokinetic population variability for risk assessment, using trichloroethylene (TCE) metabolism as a case study. Methods: We used data on oxidative and glutathione conjugation metabolism of TCE in 16 inbred and one hybrid mouse strains to calibrate and extend existing physiologically-based pharmacokinetic (PBPK) models. We added one-compartment models for glutathione metabolites and a two-compartment model for dichloroacetic acid (DCA). A Bayesian population analysis of inter-strain variability was used to quantify variability in TCE metabolism. Results: Concentration-time profiles for TCE metabolism to oxidative and glutathione conjugation metabolites varied across strains. Median predictions for the metabolic flux through oxidation was less variable (5-fold range) than that through glutathione conjugation (10-fold range). For oxidative metabolites, median predictions of trichloroacetic acid production was less variable (2-fold range) than DCA production (5-fold range), although uncertainty bounds for DCA exceeded the predicted variability. Conclusions:

  12. The effect of temperament and responsiveness towards humans on the behavior, physiology and milk production of multi-parous dairy cows in a familiar and novel milking environment.

    PubMed

    Sutherland, Mhairi A; Rogers, Andrea R; Verkerk, Gwyneth A

    2012-10-10

    The objectives of this study were to investigate whether; 1) temperament or 2) behavioral responsiveness to humans, can affect the behavior, physiology and productivity of dairy cows being milked in a familiar and novel milking environment. Temperament of multi-parous cows was defined based on exit time from a restraint device, as High Responders (HR; n=10), Medium Responders (MR; n=10) or Low Responders (LR; n=10). The behavioral response of cows to humans was assessed using four tests: restraint, exit speed, avoidance distance test and a voluntary approach test. Cows were milked according to their established routines in a rotary (familiar) milking parlor and behavioral, physiological and production data were collected over five consecutive days, including heart rate, cortisol and oxytocin concentrations and milk yield. The following week, cows were milked in a novel environment (herringbone parlor within the same farm facility) over five consecutive days, and the data and sample collection program was repeated. Cows were then given an exogenous adrenocorticotropic hormone (ACTH) challenge to measure adrenal responsiveness. Exit time was negatively correlated with the behavioral responses of cows to restraint and human avoidance distance (HAD) in the paddock and arena. The behavioral response of cows to the milking process was greater in MR than LR and HR cows in the familiar and novel milking environments. Milk yields were greater in LR than HR cows in the novel but not the familiar milking parlor. Oxytocin concentrations increased during milking in the novel environment, regardless of cow temperament. In the familiar and novel environments, heart rates were higher in HR than LR cows before and during milking and rMSSD was lower in HR cows during milking in a novel environment. There was no difference in cortisol concentrations between LR and HR cows in response to an ACTH challenge, but HR cows had higher baseline cortisol levels than LR cows. The number of leg lifts cows performed when restrained in the crush was associated with several physiological and milk production measures. These results indicate that cows with different temperaments vary in their basal physiology as well as their behavioral and physiological responses to milking and stress associated with being milked in a novel environment. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. 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.

  14. The Central Endocrine Glands: Intertwining Physiology and Pharmacy

    PubMed Central

    2007-01-01

    The initial courses in didactic pharmacy curriculum are designed to provide core scientific knowledge and develop learning skills that are the basis for highly competent application and practice of pharmacy. Commonly, students interpret this scientific base as ancillary to the practice of pharmacy. Physiology courses present a natural opportunity for the instructor to introduce basic pharmaceutical principles that form the foundation of pharmacological application early in the professional curriculum. Human Physiology I is the first of a 2-course physiology sequence that pharmacy students take upon matriculating into Midwestern University College of Pharmacy-Glendale. The endocrine physiology section of this course is designed to emphasize the regulatory and compensatory nature of this system in maintaining homeostasis, but also includes aspects of basic pharmaceutical principles. In this way the dependency of physiology and pharmacy upon one another is accentuated. The lecture format and content described in this manuscript focus on the central endocrine glands and illustrates their vital role in normal body function, compensatory responses to disease states, and their components as pharmacotherapy targets. The integration of these pharmaceutical principles at the introductory level supports an environment that can alleviate any perceived disparity between science foundation and practical application in the profession of pharmacy. PMID:17998993

  15. 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

  16. 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.

  17. Microencapsulated fluorescent pH probe as implantable sensor for monitoring the physiological state of fish embryos.

    PubMed

    Gurkov, Anton; Sadovoy, Anton; Shchapova, Ekaterina; Teh, Cathleen; Meglinski, Igor; Timofeyev, Maxim

    2017-01-01

    In vivo physiological measurement is a major challenge in modern science and technology, as is environment conservation at the global scale. Proper toxicological testing of widely produced mixtures of chemicals is a necessary step in the development of new products, allowing us to minimize the human impact on aquatic ecosystems. However, currently available bioassay-based techniques utilizing small aquatic organisms such as fish embryos for toxicity testing do not allow assessing in time the changes in physiological parameters in the same individual. In this study, we introduce microencapsulated fluorescent probes as a promising tool for in vivo monitoring of internal pH variation in zebrafish embryos. The pH alteration identified under stress conditions demonstrates the applicability of the microencapsulated fluorescent probes for the repeated analysis of the embryo's physiological state. The proposed approach has strong potential to simultaneously measure a range of physiological characteristics using a set of specific fluorescent probes and to finally bring toxicological bioassays and related research fields to a new level of effectiveness and sensitivity.

  18. 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.…

  19. 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

  20. 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.

  1. 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.

  2. Physiologically based kinetic modeling of bioactivation and detoxification of the alkenylbenzene methyleugenol in human as compared with rat

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

    Al-Subeihi, Ala' A.A., E-mail: ala.alsubeihi@wur.nl; BEN-HAYYAN-Aqaba International Laboratories, Aqaba Special Economic Zone Authority; Spenkelink, Bert

    2012-05-01

    This study defines a physiologically based kinetic (PBK) model for methyleugenol (ME) in human based on in vitro and in silico derived parameters. With the model obtained, bioactivation and detoxification of methyleugenol (ME) at different doses levels could be investigated. The outcomes of the current model were compared with those of a previously developed PBK model for methyleugenol (ME) in male rat. The results obtained reveal that formation of 1′-hydroxymethyleugenol glucuronide (1′HMEG), a major metabolic pathway in male rat liver, appears to represent a minor metabolic pathway in human liver whereas in human liver a significantly higher formation of 1′-oxomethyleugenolmore » (1′OME) compared with male rat liver is observed. Furthermore, formation of 1′-sulfooxymethyleugenol (1′HMES), which readily undergoes desulfonation to a reactive carbonium ion (CA) that can form DNA or protein adducts (DA), is predicted to be the same in the liver of both human and male rat at oral doses of 0.0034 and 300 mg/kg bw. Altogether despite a significant difference in especially the metabolic pathways of the proximate carcinogenic metabolite 1′-hydroxymethyleugenol (1′HME) between human and male rat, the influence of species differences on the ultimate overall bioactivation of methyleugenol (ME) to 1′-sulfooxymethyleugenol (1′HMES) appears to be negligible. Moreover, the PBK model predicted the formation of 1′-sulfooxymethyleugenol (1′HMES) in the liver of human and rat to be linear from doses as high as the benchmark dose (BMD{sub 10}) down to as low as the virtual safe dose (VSD). This study shows that kinetic data do not provide a reason to argue against linear extrapolation from the rat tumor data to the human situation. -- Highlights: ► A PBK model is made for bioactivation and detoxification of methyleugenol in human. ► Comparison to the PBK model in male rat revealed species differences. ► PBK results support linear extrapolation from high to low dose and from rat to human.« less

  3. 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.

  4. Annotation of Tutorial Dialogue Goals for Natural Language Generation

    ERIC Educational Resources Information Center

    Kim, Jung Hee; Freedman, Reva; Glass, Michael; Evens, Martha W.

    2006-01-01

    We annotated transcripts of human tutoring dialogue for the purpose of constructing a dialogue-based intelligent tutoring system, CIRCSIM-Tutor. The tutors were professors of physiology who were also expert tutors. The students were 1st year medical students who communicated with the tutors using typed communication from separate rooms. The tutors…

  5. Problem-Based Learning in Physics: The Power of Students Teaching Students.

    ERIC Educational Resources Information Center

    Duch, Barbara J.

    1996-01-01

    Describes an honors general physics course designed to demonstrate to students that physics is vital to their understanding of physiology, medicine, the human body, rehabilitation, and other health fields. Presents evidence that indicates that active group learning and connections to real-world applications help students learn physics and apply…

  6. DEVELOPMENT OF PATHWAY SELECTIVE CELLS AND ASSAYS FOR SENSITIVE DETECTION OF ENVIRONMENTAL TOXICANTS VIA HIGH THROUGHPUT LABEL-FREE CELL-BASED SCREENING - PHASE I

    EPA Science Inventory

    Environmental pollutants that impact critical biological pathways involved in human development and physiology can have unpredictable effects on health. Among these critical pathways, various receptor tyrosine kinases, such as...

  7. MONTE CARLO ANALYSIS OF THE HUMAN CHLORPYRIFOS-OXONASE (PON1) POLYMORPHISM USING A PHYSIOLOGICALLY BASED PHARMACOKINETIC AND PHARMACODYNAMIC (PBPK/PD) MODEL. (R828608)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  8. Another Strategy for Teaching Histology to A&P Students: Classification versus Memorization.

    ERIC Educational Resources Information Center

    Bavis, Ryan W.; Seveyka, Jerred; Shigeoka, Cassie A.

    2000-01-01

    Defines dichotomous keys as common learning tools based on identification rather than memorization. Provides an example of a dichotomous key developed for introducing histology in human anatomy and physiology (A&P) courses and explains how students can use the dichotomous key. Discusses the goals of the exercises and the process of…

  9. DEVELOPMENT OF PHYSIOLOGICAL-BASED PHARMACOKINETIC MODEL FOR DERMAL ABSORPTION NAD PENETRATION OF METHYL TERTIARY BUTYL ETHER IN HUMANS

    EPA Science Inventory

    Background: Methyl tertiary butyl ether (MTBE) is a volatile organic chemical that is added to gasoline as an octane booster and to reduce vehicular emissions of carbon monoxide. MTBE is introduced into the environment through fuel spills, leakage of storage tanks, and evaporat...

  10. COMPARISON OF THE USE OF A PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODEL AND A CLASSICAL PHARMACOKINETIC MODEL FOR DIOXIN EXPOSURE ASSESSMENTS

    EPA Science Inventory

    In epidemiological studies, exposure assessments to TCDD, known as a possible human carcinogen, assume mono or biphasic elimination rates. Recent data suggests a dose dependent elimination rate for TCDD. A PBPK model, which uses a body burden dependent elimination rate, was dev...

  11. The study of human venous system dynamics using hybrid computer modeling

    NASA Technical Reports Server (NTRS)

    Snyder, M. F.; Rideout, V. C.

    1972-01-01

    A computer-based model of the cardiovascular system was created emphasizing effects on the systemic venous system. Certain physiological aspects were emphasized: effects of heart rate, tilting, changes in respiration, and leg muscular contractions. The results from the model showed close correlation with findings previously reported in the literature.

  12. The Physiological Basis and Clinical Use of the Binaural Interaction Component of the Auditory Brainstem Response

    PubMed Central

    Klump, Georg M.; Tollin, Daniel J.

    2016-01-01

    The auditory brainstem response (ABR) is a sound-evoked non-invasively measured electrical potential representing the sum of neuronal activity in the auditory brainstem and midbrain. ABR peak amplitudes and latencies are widely used in human and animal auditory research and for clinical screening. The binaural interaction component (BIC) of the ABR stands for the difference between the sum of the monaural ABRs and the ABR obtained with binaural stimulation. The BIC comprises a series of distinct waves, the largest of which (DN1) has been used for evaluating binaural hearing in both normal hearing and hearing-impaired listeners. Based on data from animal and human studies, we discuss the possible anatomical and physiological bases of the BIC (DN1 in particular). The effects of electrode placement and stimulus characteristics on the binaurally evoked ABR are evaluated. We review how inter-aural time and intensity differences affect the BIC and, analyzing these dependencies, draw conclusion about the mechanism underlying the generation of the BIC. Finally, the utility of the BIC for clinical diagnoses are summarized. PMID:27232077

  13. 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.

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

    PubMed

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

    2017-12-07

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

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

    PubMed Central

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

    2017-01-01

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

  16. Digital Health: Tracking Physiomes and Activity Using Wearable Biosensors Reveals Useful Health-Related Information

    PubMed Central

    Zhou, Gao; Zhou, Wenyu; Schüssler-Fiorenza Rose, Sophia Miryam; Perelman, Dalia; Colbert, Elizabeth; Runge, Ryan; Rego, Shannon; Sonecha, Ria; Datta, Somalee; McLaughlin, Tracey; Snyder, Michael P.

    2017-01-01

    A new wave of portable biosensors allows frequent measurement of health-related physiology. We investigated the use of these devices to monitor human physiological changes during various activities and their role in managing health and diagnosing and analyzing disease. By recording over 250,000 daily measurements for up to 43 individuals, we found personalized circadian differences in physiological parameters, replicating previous physiological findings. Interestingly, we found striking changes in particular environments, such as airline flights (decreased peripheral capillary oxygen saturation [SpO2] and increased radiation exposure). These events are associated with physiological macro-phenotypes such as fatigue, providing a strong association between reduced pressure/oxygen and fatigue on high-altitude flights. Importantly, we combined biosensor information with frequent medical measurements and made two important observations: First, wearable devices were useful in identification of early signs of Lyme disease and inflammatory responses; we used this information to develop a personalized, activity-based normalization framework to identify abnormal physiological signals from longitudinal data for facile disease detection. Second, wearables distinguish physiological differences between insulin-sensitive and -resistant individuals. Overall, these results indicate that portable biosensors provide useful information for monitoring personal activities and physiology and are likely to play an important role in managing health and enabling affordable health care access to groups traditionally limited by socioeconomic class or remote geography. PMID:28081144

  17. Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis

    PubMed Central

    Nyein, Hnin Yin Yin; Challa, Samyuktha; Chen, Kevin; Peck, Austin; Fahad, Hossain M.; Ota, Hiroki; Shiraki, Hiroshi; Kiriya, Daisuke; Lien, Der-Hsien; Brooks, George A.; Davis, Ronald W.; Javey, Ali

    2016-01-01

    Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual's state of health1–12. Sampling human sweat, which is rich in physiological information13, could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state14–18. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications. PMID:26819044

  18. Applications of minimal physiologically-based pharmacokinetic models

    PubMed Central

    Cao, Yanguang

    2012-01-01

    Conventional mammillary models are frequently used for pharmacokinetic (PK) analysis when only blood or plasma data are available. Such models depend on the quality of the drug disposition data and have vague biological features. An alternative minimal-physiologically-based PK (minimal-PBPK) modeling approach is proposed which inherits and lumps major physiologic attributes from whole-body PBPK models. The body and model are represented as actual blood and tissue usually total body weight) volumes, fractions (fd) of cardiac output with Fick’s Law of Perfusion, tissue/blood partitioning (Kp), and systemic or intrinsic clearance. Analyzing only blood or plasma concentrations versus time, the minimal-PBPK models parsimoniously generate physiologically-relevant PK parameters which are more easily interpreted than those from mam-millary models. The minimal-PBPK models were applied to four types of therapeutic agents and conditions. The models well captured the human PK profiles of 22 selected beta-lactam antibiotics allowing comparison of fitted and calculated Kp values. Adding a classical hepatic compartment with hepatic blood flow allowed joint fitting of oral and intravenous (IV) data for four hepatic elimination drugs (dihydrocodeine, verapamil, repaglinide, midazolam) providing separate estimates of hepatic intrinsic clearance, non-hepatic clearance, and pre-hepatic bioavailability. The basic model was integrated with allometric scaling principles to simultaneously describe moxifloxacin PK in five species with common Kp and fd values. A basic model assigning clearance to the tissue compartment well characterized plasma concentrations of six monoclonal antibodies in human subjects, providing good concordance of predictions with expected tissue kinetics. The proposed minimal-PBPK modeling approach offers an alternative and more rational basis for assessing PK than compartmental models. PMID:23179857

  19. Human reproductive issues in space

    NASA Technical Reports Server (NTRS)

    Santy, Patricia A.; Jennings, Richard T.

    1992-01-01

    A review of reproductive functioning in animal species studied during space flight demonstrated that most species were affected significantly by the absence of gravity and/or the presence of radiation. These two factors induced alterations in normal reproductive functioning independently of, as well as in combination with, each other. Based on animal models, several potential problem areas regarding human reproductive physiology and functioning in the space environment were identified. While there are no current space flight investigations, the animal studies suggest priorities for future research in human reproduction. Such studies will be critical for the successful colonization of the space frontier.

  20. Relevance of human anatomy in daily clinical practice.

    PubMed

    Arráez-Aybar, Luis-Alfonso; Sánchez-Montesinos, Indalecio; Mirapeix, Rosa-M; Mompeo-Corredera, Blanca; Sañudo-Tejero, Jose-Ramón

    2010-12-20

    the aim of this study has been to evaluate the relevance of gross human anatomy in daily clinical practice and to compare it to that of other basic sciences (biochemistry, bioethics, cytohistology, microbiology, pharmacology, physiology, psychology). a total of 1250 questionnaires were distributed among 38 different medical speciality professionals. Answers were analyzed taking into account speciality (medical, surgery and others), professional status (training physician or staff member) and professional experience. the response rate was 42.9% (n=536). Gross human anatomy was considered the most relevant basic discipline for surgical specialists, while pharmacology and physiology were most relevant for medical specialists. Knowledge of anatomy was also considered fundamental for understanding neurological or musculoskeletal disorders. In undergraduate programmes, the most important focuses in teaching anatomy were radiological, topographical and functional anatomy followed by systematic anatomy. In daily medical practice anatomy was considered basic for physical examination, symptom interpretation and interpretation of radiological images. When professional status or professional experience was considered, small variations were shown and there were no significant differences related to gender or community. our results underline the relevance of basic sciences (gross anatomy, physiology, and pharmacology) in daily professional activity. Evidence-based studies such as ours, lend greater credibility and objectivity to the role of gross anatomy in the undergraduate training of health professionals and should help to establish a more appropriate curriculum for future professionals. 2010 Elsevier GmbH. All rights reserved.

  1. Human adaptation to isolated and confined environments: Preliminary findings of a seven month Antarctic winter-over human factors study

    NASA Technical Reports Server (NTRS)

    Evans, Gary W.; Stokols, Daniel; Carrere, Sybil

    1988-01-01

    This field study was conducted during the last decade of an austral winter-over at Palmer Station in the Antarctic. The purpose of the study was to understand temporal patterns in physiological arousal and psychological mood over the course of the mission. The investigators were principally interested in how people adapted over time to chronic and acute stressors, and how people use and modify their built environment. Physiological and psychological data were collected several times a week, and information on behavior and the use of physical facilities was collected monthly. Physiological and psychological data were compared with social changes in the setting toward the development of a sequential model of human-environment transactional relationships. Based on the study results, guidelines for design of future isolated and confined environments (ICEs) included: plan space for items which make people feel at home, provide materials to allow people to personalize their environment, allow for flexible environments, provide areas for visual and auditory privacy, equip areas for socializing and remove them from private areas, and provide facilities for exercise and for projects involving physical activity. The study offers guidelines about patterns of adaption that could be expected in an ICE, discusses how these settings can be programmed to facilitate successful adjustment, and provides information about how to design future ICE habitats to maximize a healthy living environment.

  2. 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.

  3. An unavoidable modulation? Sensory attention and human primary motor cortex excitability.

    PubMed

    Ruge, Diane; Muggleton, Neil; Hoad, Damon; Caronni, Antonio; Rothwell, John C

    2014-09-01

    The link between basic physiology and its modulation by cognitive states, such as attention, is poorly understood. A significant association becomes apparent when patients with movement disorders describe experiences with changing their attention focus and the fundamental effect that this has on their motor symptoms. Moreover, frequently used mental strategies for treating such patients, e.g. with task-specific dystonia, widely lack laboratory-based knowledge about physiological mechanisms. In this largely unexplored field, we looked at how the locus of attention, when it changed between internal (locus hand) and external (visual target), influenced excitability in the primary motor cortex (M1) in healthy humans. Intriguingly, both internal and external attention had the capacity to change M1 excitability. Both led to a reduced stimulation-induced GABA-related inhibition and a change in motor evoked potential size, i.e. an overall increased M1 excitability. These previously unreported findings indicated: (i) that cognitive state differentially interacted with M1 physiology, (ii) that our view of distraction (attention locus shifted towards external or distant location), which is used as a prevention or management strategy for use-dependent motor disorders, is too simple and currently unsupported for clinical application, and (iii) the physiological state reached through attention modulation represents an alternative explanation for frequently reported electrophysiology findings in neuropsychiatric disorders, such as an aberrant inhibition. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  4. Association between human and animal thermal comfort indices and physiological heat stress indicators in dairy calves.

    PubMed

    Kovács, L; Kézér, F L; Ruff, F; Szenci, O; Jurkovich, V

    2018-06-06

    Warm summer episodes have a significant effect on the overall health and well-being of young cattle; however, it is not known which temperature measure should be used for estimating heat stress in dairy calves. In this study, generalized linear mixed-effects models were used to estimate the relationships between thermal comfort indices and animal-based heat stress indicators in sixteen Holstein bull calves that were housed in individual calf hutches. Data were collected under continental weather characteristics over a 5-day period: day 1 (lower-temperature day), days 2 and 3 (heat stress days), and a 2-day post-stress period. Relative humidity, ambient temperature, the heat index, the humidex and five different temperature-humidity indices (THI) were used as thermal indices. Physiological variables monitored included respiratory rate, rectal temperature, ear skin temperature and heart rate. The heat index and the humidex measuring human thermal comfort were more closely associated with physiological measures than were the ambient temperature or the THIs (in case of heat index: R 2 = 0.87 for respiratory rate, R 2 = 0.63 for rectal temperature, R 2 = 0.70 for ear skin temperature, and R 2 = 0.78 for heart rate, respectively; in case of humidex: R 2 = 0.85 for respiratory rate, R 2 = 0.60 for rectal temperature, R 2 = 0.68 for ear skin temperature, and R 2 = 0.75 for heart rate, respectively). Based on our results, parameters of human outdoor comfort seem better to estimate heat stress in dairy calves in a continental region than those of THIs or ambient temperature. Copyright © 2018. Published by Elsevier Inc.

  5. Treatment guidelines for Circadian Rhythm Sleep-Wake Disorders of the Polish Sleep Research Society and the Section of Biological Psychiatry of the Polish Psychiatric Association. Part I. Physiology, assessment and therapeutic methods.

    PubMed

    Wichniak, Adam; Jankowski, Konrad S; Skalski, Michal; Skwarło-Sońta, Krystyna; Zawilska, Jolanta B; Żarowski, Marcin; Poradowska, Ewa; Jernajczyk, Wojciech

    2017-10-29

    Majority of the physiological processes in the human organism are rhythmic. The most common are the diurnal changes that repeat roughly every 24 hours, called circadian rhythms. Circadian rhythms disorders have negative influence on human functioning. The aim of this article is to present the current understanding of the circadian rhythms physiological role, with particular emphasis on the circadian rhythm sleep-wake disorders (CRSWD), principles of their diagnosis and chronobiological therapy. The guidelines are based on the review of recommendations from the scientific societies involved in sleep medicine and the clinical experiences of the authors. Researchers participating in the preparation of guidelines were invited by the Polish Sleep Research Society and the Section of Biological Psychiatry of the Polish Psychiatric Association, based on their significant contributions in circadian rhythm research and/or clinical experience in the treatment of such disorders. Finally, the guidelines were adjusted to the questions and comments given by the members of both Societies. CRSWD have a significant negative impact on human health and functioning. Standard methods used to assess CRSWD are sleep diaries and sleep logs, while the actigraphy, when available, should be also used. The most effective methods of CRSWD treatment are melatonin administration and light therapy. Behavioral interventions are also recommended. Afourteen-day period of sleep-wake rhythm assessment in CRSWD enables accurate diagnosis, adequate selection of chronobiological interventions, and planning adequate diurnal timing of their application. This type of assessment is quite easy, low-cost, and provides valuable indications how to adjust the therapeutic approach to the circadian phase of the particular patient.

  6. 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.

  7. 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.

  8. Message-adjusted network (MAN) hypothesis in gastro-entero-pancreatic (GEP) endocrine system.

    PubMed

    Aykan, N Faruk

    2007-01-01

    Several types of communication coordinate body functions to maintain homeostasis. Clarifying intercellular communication systems is as important as intracellular signal mechanisms. In this study, we propose an intercellular network model to establish novel targets in GEP-endocrine system, based on up-to-date information from medical publications. As materials, two physiologic events which are Pavlov's sham-feeding assay and bicarbonate secretion into the duodenum from pancreas were explored by new biologic data from the literature. Major key words used in Pub-Med were modes of regulations (autocrine, paracrine, endocrine, neurocrine, juxtacrine, lumencrine), GEP cells, hormones, peptides and neuro-transmitters. In these two examples of physiologic events, we can design a model of network to clarify transmission of a message. When we take a simple, unique message, we can observe a complete intercellular network. In our examples, these messages are "food is coming" and "hydrogen ions are increasing" in human language (humanese). We need to find molecular counterparts of these unique messages in cell language (cellese). In this network (message-adjusted network; MAN), message is an input which can affect the physiologic equilibrium, mission is an output to improve the disequilibrium and aim is always maintenance of homeostasis. If we orientate to a transmission of a unique message we can distinguish that different cells use different chemical messengers in different modes of regulations to transmit the same message. This study also supports Shannon's information theory and cell language theories such as von Neumann-Patte principles. After human genome project (HU-GO) and protein organisations (HU-PO), finding true messages and the establishment of their networks (in our model HU-MAN project) can be a novel and exciting field in cell biology. We established an intercellular network model to understand intercellular communication in the physiology of GEP endocrine system. This model could help to explain complex physiologic events as well as to generate new treatment concepts.

  9. Update on apelin peptides as putative targets for cardiovascular drug discovery.

    PubMed

    Charles, Christopher J

    2011-06-01

    The physiological importance of GPCR/ligand pathways is highlighted by the fact that numerous pathologies are attributed to their signaling dysfunction. Over 50% of the pharmaceutical drugs currently used to treat human disease are based on compounds that interact with GPCRs. Apelin/APJ constitutes a novel endogenous peptide/GPCR system proposed to be involved in a wide range of physiological functions. Early evidence suggests that apelin/APJ may hold promise as a target for development of novel therapeutic agents which may counteract a number of pathologies including cardiovascular disease. Despite advances in treatment of cardiovascular disease, incidence, prevalence, morbidity and economic costs remain high necessitating the development of new treatment paradigms. This review summarizes apelin/APJ structure, distribution and regulation; presents evidence for a role of apelin in pressure/volume homeostasis and in the pathophysiology of cardiovascular disease; summarizes data on beneficial effects of apelin in preclinical, animal models of cardiovascular disease and measurement of plasma levels of apelin across the full spectrum of cardiovascular disease in humans; and notes the first studies describing bioactivity of apelin peptides in human healthy volunteers and patients with heart failure. More clarity is needed on the precise physiological/pathophysiological role of the apelin/APJ system in human health and disease. Nonetheless, preclinical studies and initial studies in humans show that APJ antagonism may represent a novel therapeutic target for patients with cardiovascular disease. Development of appropriately validated assays for apelin will clarify circulating levels of the peptide in health and disease. Development of suitable agonists/antagonists will pave the way for much needed future studies essential for advancing this promising field of drug discovery.

  10. Dilution space ratio of 2H and 18O of doubly labeled water method in humans.

    PubMed

    Sagayama, Hiroyuki; Yamada, Yosuke; Racine, Natalie M; Shriver, Timothy C; Schoeller, Dale A

    2016-06-01

    Variation of the dilution space ratio (Nd/No) between deuterium ((2)H) and oxygen-18 ((18)O) impacts the calculation of total energy expenditure (TEE) by doubly labeled water (DLW). Our aim was to examine the physiological and methodological sources of variation of Nd/No in humans. We analyzed data from 2,297 humans (0.25-89 yr old). This included the variables Nd/No, total body water, TEE, body mass index (BMI), and percent body fat (%fat). To differentiate between physiologic and methodologic sources of variation, the urine samples from 54 subjects were divided and blinded and analyzed separately, and repeated DLW dosing was performed in an additional 55 participants after 6 mo. Sex, BMI, and %fat did not significantly affect Nd/No, for which the interindividual SD was 0.017. The measurement error from the duplicate urine sample sets was 0.010, and intraindividual SD of Nd/No in repeats experiments was 0.013. An additional SD of 0.008 was contributed by calibration of the DLW dose water. The variation of measured Nd/No in humans was distributed within a small range and measurement error accounted for 68% of this variation. There was no evidence that Nd/No differed with respect to sex, BMI, and age between 1 and 80 yr, and thus use of a constant value is suggested to minimize the effect of stable isotope analysis error on calculation of TEE in the DLW studies in humans. Based on a review of 103 publications, the average dilution space ratio is 1.036 for individuals between 1 and 80 yr of age. Copyright © 2016 the American Physiological Society.

  11. 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

  12. 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.

  13. Physiological determinants of human acute hypoxia tolerance.

    DOT National Transportation Integrated Search

    2013-11-01

    AbstractIntroduction. We investigated possible physiological determinants of variability in hypoxia tolerance in subjects given a 5-minute normobaric exposure to 25,000 ft equivalent. Physiological tolerance to hypoxia was defined as the magnitude of...

  14. Medical considerations for extending human presence in space

    NASA Technical Reports Server (NTRS)

    Leach, C. S.; Dietlein, L. F.; Pool, S. L.; Nicogossian, A. E.

    1990-01-01

    The prospects for extending the length of time that humans can safely remain in space depend partly on resolution of a number of medical issues. Physiologic effects of weightlessness that may affect health during flight include loss of body fluid, functional alterations in the cardiovascular system, loss of red blood cells and bone mineral, compromised immune system function, and neurosensory disturbances. Some of the physiologic adaptations to weightlessness contribute to difficulties with readaptation to Earth's gravity. These include cardiovascular deconditioning and loss of body fluids and electrolytes; red blood cell mass; muscle mass, strength, and endurance; and bone mineral. Potentially harmful factors in space flight that are not related to weightlessness include radiation, altered circadian rhythms and rest/work cycles, and the closed, isolated environment of the spacecraft. There is no evidence that space flight has long-term effects on humans, except that bone mass lost during flight may not be replaced, and radiation damage is cumulative. However, the number of people who have spent several months or longer in space is still small. Only carefully-planned experiments in space preceded by thorough ground-based studies can provide the information needed to increase the amount of time humans can safely spend in space.

  15. "Omic" investigations of protozoa and worms for a deeper understanding of the human gut "parasitome".

    PubMed

    Marzano, Valeria; Mancinelli, Livia; Bracaglia, Giorgia; Del Chierico, Federica; Vernocchi, Pamela; Di Girolamo, Francesco; Garrone, Stefano; Tchidjou Kuekou, Hyppolite; D'Argenio, Patrizia; Dallapiccola, Bruno; Urbani, Andrea; Putignani, Lorenza

    2017-11-01

    The human gut has been continuously exposed to a broad spectrum of intestinal organisms, including viruses, bacteria, fungi, and parasites (protozoa and worms), over millions of years of coevolution, and plays a central role in human health. The modern lifestyles of Western countries, such as the adoption of highly hygienic habits, the extensive use of antimicrobial drugs, and increasing globalisation, have dramatically altered the composition of the gut milieu, especially in terms of its eukaryotic "citizens." In the past few decades, numerous studies have highlighted the composition and role of human intestinal bacteria in physiological and pathological conditions, while few investigations exist on gut parasites and particularly on their coexistence and interaction with the intestinal microbiota. Studies of the gut "parasitome" through "omic" technologies, such as (meta)genomics, transcriptomics, proteomics, and metabolomics, are herein reviewed to better understand their role in the relationships between intestinal parasites, host, and resident prokaryotes, whether pathogens or commensals. Systems biology-based profiles of the gut "parasitome" under physiological and severe disease conditions can indeed contribute to the control of infectious diseases and offer a new perspective of omics-assisted tropical medicine.

  16. “Omic” investigations of protozoa and worms for a deeper understanding of the human gut “parasitome”

    PubMed Central

    Marzano, Valeria; Mancinelli, Livia; Bracaglia, Giorgia; Del Chierico, Federica; Vernocchi, Pamela; Di Girolamo, Francesco; Garrone, Stefano; Tchidjou Kuekou, Hyppolite; D’Argenio, Patrizia; Dallapiccola, Bruno; Urbani, Andrea

    2017-01-01

    The human gut has been continuously exposed to a broad spectrum of intestinal organisms, including viruses, bacteria, fungi, and parasites (protozoa and worms), over millions of years of coevolution, and plays a central role in human health. The modern lifestyles of Western countries, such as the adoption of highly hygienic habits, the extensive use of antimicrobial drugs, and increasing globalisation, have dramatically altered the composition of the gut milieu, especially in terms of its eukaryotic “citizens.” In the past few decades, numerous studies have highlighted the composition and role of human intestinal bacteria in physiological and pathological conditions, while few investigations exist on gut parasites and particularly on their coexistence and interaction with the intestinal microbiota. Studies of the gut “parasitome” through “omic” technologies, such as (meta)genomics, transcriptomics, proteomics, and metabolomics, are herein reviewed to better understand their role in the relationships between intestinal parasites, host, and resident prokaryotes, whether pathogens or commensals. Systems biology–based profiles of the gut “parasitome” under physiological and severe disease conditions can indeed contribute to the control of infectious diseases and offer a new perspective of omics-assisted tropical medicine. PMID:29095820

  17. The universal existence of myodural bridge in mammals: an indication of a necessary function.

    PubMed

    Zheng, Nan; Yuan, Xiao-Ying; Chi, Yan-Yan; Liu, Pei; Wang, Bing; Sui, Jia-Ying; Han, Seung-Ho; Yu, Sheng-Bo; Sui, Hong-Jin

    2017-08-15

    The "myodural bridge" was described in literatures as a dense fibrous tissue connecting the sub-occipital musculature with the spinal dura mater in human studies. Now the concept of "myodural bridge" was perceived as an exact anatomical structure presumably essential for critical physiological functions in human body, and might exist in other mammals as well. To determine the existence of the "myodural bridge" in other mammals and to lay a foundation for the functional study, we examined representatives in five different mammalian orders. Based on the anatomical dissections, P45 plastinated sections and histological sections, we found that a dense fibrous tissue connected the rectus capitisdorsalis minor and the spinal dura mater through the dorsal atlanto-occipital interspace with or without the medium of the posterior atlanto-occipital membrane. These observed connective tissues were very similar to the "myodural bridge" previously described in humans. We proposed that the "myodural bridge", as an evolutionally conserved structure, presents in many other mammals. Moreover, we believed that the "myodural bridge" might be a homologous organ in mammals. Thus, this study could provide an insight for our understanding the physiological significance of the "myodural bridge", especially in human.

  18. On Optimizing H. 264/AVC Rate Control by Improving R-D Model and Incorporating HVS Characteristics

    NASA Astrophysics Data System (ADS)

    Zhu, Zhongjie; Wang, Yuer; Bai, Yongqiang; Jiang, Gangyi

    2010-12-01

    The state-of-the-art JVT-G012 rate control algorithm of H.264 is improved from two aspects. First, the quadratic rate-distortion (R-D) model is modified based on both empirical observations and theoretical analysis. Second, based on the existing physiological and psychological research findings of human vision, the rate control algorithm is optimized by incorporating the main characteristics of the human visual system (HVS) such as contrast sensitivity, multichannel theory, and masking effect. Experiments are conducted, and experimental results show that the improved algorithm can simultaneously enhance the overall subjective visual quality and improve the rate control precision effectively.

  19. 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.

  20. Wireless body sensor networks for health-monitoring applications.

    PubMed

    Hao, Yang; Foster, Robert

    2008-11-01

    Current wireless technologies, such as wireless body area networks and wireless personal area networks, provide promising applications in medical monitoring systems to measure specified physiological data and also provide location-based information, if required. With the increasing sophistication of wearable and implantable medical devices and their integration with wireless sensors, an ever-expanding range of therapeutic and diagnostic applications is being pursued by research and commercial organizations. This paper aims to provide a comprehensive review of recent developments in wireless sensor technology for monitoring behaviour related to human physiological responses. It presents background information on the use of wireless technology and sensors to develop a wireless physiological measurement system. A generic miniature platform and other available technologies for wireless sensors have been studied in terms of hardware and software structural requirements for a low-cost, low-power, non-invasive and unobtrusive system.

  1. The Citius End: World Records Progression Announces the Completion of a Brief Ultra-Physiological Quest

    PubMed Central

    Berthelot, Geoffroy; Thibault, Valérie; Tafflet, Muriel; Escolano, Sylvie; El Helou, Nour; Jouven, Xavier; Hermine, Olivier; Toussaint, Jean-François

    2008-01-01

    World records (WR) in sports illustrate the ultimate expression of human integrated muscle biology, through speed or strength performances. Analysis and prediction of man's physiological boundaries in sports and impact of external (historical or environmental) conditions on WR occurrence are subject to scientific controversy. Based on the analysis of 3263 WR established for all quantifiable official contests since the first Olympic Games, we show here that WR progression rate follows a piecewise exponential decaying pattern with very high accuracy (mean adjusted r2 values = 0.91±0.08 (s.d.)). Starting at 75% of their estimated asymptotic values in 1896, WR have now reached 99%, and, present conditions prevailing, half of all WR will not be improved by more than 0,05% in 2027. Our model, which may be used to compare future athletic performances or assess the impact of international antidoping policies, forecasts that human species' physiological frontiers will be reached in one generation. This will have an impact on the future conditions of athlete training and on the organization of competitions. It may also alter the Olympic motto and spirit. PMID:18253499

  2. Changing undergraduate human anatomy and physiology laboratories: perspectives from a large-enrollment course.

    PubMed

    Griff, Edwin R

    2016-09-01

    In the present article, a veteran lecturer of human anatomy and physiology taught several sections of the laboratory component for the first time and shares his observations and analysis from this unique perspective. The article discusses a large-enrollment, content-heavy anatomy and physiology course in relationship to published studies on learning and student self-efficacy. Changes in the laboratory component that could increase student learning are proposed. The author also points out the need for research to assess whether selective curricular changes could increase the depth of understanding and retention of learned material. Copyright © 2016 The American Physiological Society.

  3. 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.

  4. Physiological Information Database (PID)

    EPA Science Inventory

    EPA has developed a physiological information database (created using Microsoft ACCESS) intended to be used in PBPK modeling. The database contains physiological parameter values for humans from early childhood through senescence as well as similar data for laboratory animal spec...

  5. A Large Radius Human Centrifuge: The Human Hypergravity Havitat

    NASA Astrophysics Data System (ADS)

    van Loon, J. J. W. A.

    2008-06-01

    Life on Earth has developed at unit gravity, 9.81 m/s2, but how would plants and animals have evolved on a larger planet, i.e. larger than Earth? We are able to address this question simply by studies using centrifuges. In the past decades numerous experiments have been performed on cells, plants and animals grown for longer durations, even multi generations, under hypergravity conditions. Based on these studies we have gained interesting insights in the physiological process of these systems when exposed to artificial gravity. Animals and plants adapt themselves to this new high-g environment. Information of adaptation to hyper-g in mammals is interesting, or maybe even proof vital, for future human space flight programs especially in light of long duration missions to Moon and Mars. We know from long duration animal studies that numerous physiological processes and structures like muscles, bones, neuro-vestibular, or the cardiovascular system are affected. However, humans have never been exposed to a hyper-g environment for long durations. Human studies are mostly in the order of hours at most. Current work on human centrifuges is all focused on short arm systems to apply artificial gravity in long duration space missions. In this paper we want to address the possible usefulness of a large radius human centrifuge on Earth, or even on Moon or Mars, for both basic research and possible applications. In such a centrifuge a group of humans may be exposed to hypergravity for, in principle, an unlimited period of time.

  6. Concept Analysis: Music Therapy.

    PubMed

    Murrock, Carolyn J; Bekhet, Abir K

    2016-01-01

    Down through the ages, music has been universally valued for its therapeutic properties based on the psychological and physiological responses in humans. However, the underlying mechanisms of the psychological and physiological responses to music have been poorly identified and defined. Without clarification, a concept can be misused, thereby diminishing its importance for application to nursing research and practice. The purpose of this article was for the clarification of the concept of music therapy based on Walker and Avant's concept analysis strategy. A review of recent nursing and health-related literature covering the years 2007-2014 was performed on the concepts of music, music therapy, preferred music, and individualized music. As a result of the search, the attributes, antecedents, and consequences of music therapy were identified, defined, and used to develop a conceptual model of music therapy. The conceptual model of music therapy provides direction for developing music interventions for nursing research and practice to be tested in various settings to improve various patient outcomes. Based on Walker and Avant's concept analysis strategy, model and contrary cases are included. Implications for future nursing research and practice to use the psychological and physiological responses to music therapy are discussed.

  7. 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.

  8. Physiological and subjective evaluation of a human-robot object hand-over task.

    PubMed

    Dehais, Frédéric; Sisbot, Emrah Akin; Alami, Rachid; Causse, Mickaël

    2011-11-01

    In the context of task sharing between a robot companion and its human partners, the notions of safe and compliant hardware are not enough. It is necessary to guarantee ergonomic robot motions. Therefore, we have developed Human Aware Manipulation Planner (Sisbot et al., 2010), a motion planner specifically designed for human-robot object transfer by explicitly taking into account the legibility, the safety and the physical comfort of robot motions. The main objective of this research was to define precise subjective metrics to assess our planner when a human interacts with a robot in an object hand-over task. A second objective was to obtain quantitative data to evaluate the effect of this interaction. Given the short duration, the "relative ease" of the object hand-over task and its qualitative component, classical behavioral measures based on accuracy or reaction time were unsuitable to compare our gestures. In this perspective, we selected three measurements based on the galvanic skin conductance response, the deltoid muscle activity and the ocular activity. To test our assumptions and validate our planner, an experimental set-up involving Jido, a mobile manipulator robot, and a seated human was proposed. For the purpose of the experiment, we have defined three motions that combine different levels of legibility, safety and physical comfort values. After each robot gesture the participants were asked to rate them on a three dimensional subjective scale. It has appeared that the subjective data were in favor of our reference motion. Eventually the three motions elicited different physiological and ocular responses that could be used to partially discriminate them. Copyright © 2011 Elsevier Ltd and the Ergonomics Society. All rights reserved.

  9. An Investigative Laboratory Course in Human Physiology Using Computer Technology and Collaborative Writing

    ERIC Educational Resources Information Center

    FitzPatrick, Kathleen A.

    2004-01-01

    Active investigative student-directed experiences in laboratory science are being encouraged by national science organizations. A growing body of evidence from classroom assessment supports their effectiveness. This study describes four years of implementation and assessment of an investigative laboratory course in human physiology for 65…

  10. Colonic Fermentation: A Neglected Topic in Human Physiology Education

    ERIC Educational Resources Information Center

    Valeur, Jorgen; Berstad, Arnold

    2010-01-01

    Human physiology textbooks tend to limit their discussion of colonic functions to those of absorbing water and electrolytes and storing waste material. However, the colon is a highly active metabolic organ, containing an exceedingly complex society of microbes. By means of fermentation, gastrointestinal microbes break down nutrients that cannot be…

  11. Using the Electrocorticographic Speech Network to Control a Brain-Computer Interface in Humans

    PubMed Central

    Leuthardt, Eric C.; Gaona, Charles; Sharma, Mohit; Szrama, Nicholas; Roland, Jarod; Freudenberg, Zac; Solis, Jamie; Breshears, Jonathan; Schalk, Gerwin

    2013-01-01

    Electrocorticography (ECoG) has emerged as a new signal platform for brain-computer interface (BCI) systems. Classically, the cortical physiology that has been commonly investigated and utilized for device control in humans has been brain signals from sensorimotor cortex. Hence, it was unknown whether other neurophysiological substrates, such as the speech network, could be used to further improve on or complement existing motor-based control paradigms. We demonstrate here for the first time that ECoG signals associated with different overt and imagined phoneme articulation can enable invasively monitored human patients to control a one-dimensional computer cursor rapidly and accurately. This phonetic content was distinguishable within higher gamma frequency oscillations and enabled users to achieve final target accuracies between 68 and 91% within 15 minutes. Additionally, one of the patients achieved robust control using recordings from a microarray consisting of 1 mm spaced microwires. These findings suggest that the cortical network associated with speech could provide an additional cognitive and physiologic substrate for BCI operation and that these signals can be acquired from a cortical array that is small and minimally invasive. PMID:21471638

  12. The Human Blood Metabolome-Transcriptome Interface

    PubMed Central

    Schramm, Katharina; Adamski, Jerzy; Gieger, Christian; Herder, Christian; Carstensen, Maren; Peters, Annette; Rathmann, Wolfgang; Roden, Michael; Strauch, Konstantin; Suhre, Karsten; Kastenmüller, Gabi; Prokisch, Holger; Theis, Fabian J.

    2015-01-01

    Biological systems consist of multiple organizational levels all densely interacting with each other to ensure function and flexibility of the system. Simultaneous analysis of cross-sectional multi-omics data from large population studies is a powerful tool to comprehensively characterize the underlying molecular mechanisms on a physiological scale. In this study, we systematically analyzed the relationship between fasting serum metabolomics and whole blood transcriptomics data from 712 individuals of the German KORA F4 cohort. Correlation-based analysis identified 1,109 significant associations between 522 transcripts and 114 metabolites summarized in an integrated network, the ‘human blood metabolome-transcriptome interface’ (BMTI). Bidirectional causality analysis using Mendelian randomization did not yield any statistically significant causal associations between transcripts and metabolites. A knowledge-based interpretation and integration with a genome-scale human metabolic reconstruction revealed systematic signatures of signaling, transport and metabolic processes, i.e. metabolic reactions mainly belonging to lipid, energy and amino acid metabolism. Moreover, the construction of a network based on functional categories illustrated the cross-talk between the biological layers at a pathway level. Using a transcription factor binding site enrichment analysis, this pathway cross-talk was further confirmed at a regulatory level. Finally, we demonstrated how the constructed networks can be used to gain novel insights into molecular mechanisms associated to intermediate clinical traits. Overall, our results demonstrate the utility of a multi-omics integrative approach to understand the molecular mechanisms underlying both normal physiology and disease. PMID:26086077

  13. Prediction of Losartan-Active Carboxylic Acid Metabolite Exposure Following Losartan Administration Using Static and Physiologically Based Pharmacokinetic Models.

    PubMed

    Nguyen, Hoa Q; Lin, Jian; Kimoto, Emi; Callegari, Ernesto; Tse, Susanna; Obach, R Scott

    2017-09-01

    The aim of this study was to evaluate a strategy based on static and dynamic physiologically based pharmacokinetic (PBPK) modeling for the prediction of metabolite and parent drug area under the time-concentration curve ratio (AUC m /AUC p ) and their PK profiles in humans using in vitro data when active transport processes are involved in disposition. The strategy was applied to losartan and its pharmacologically active metabolite carboxylosartan as test compounds. Hepatobiliary transport including transport-mediated uptake, canilicular and basolateral efflux, and metabolic clearance estimates were obtained from in vitro studies using human liver microsomes and sandwich-cultured hepatocytes. Human renal clearance of carboxylosartan was estimated from dog renal clearance using allometric scaling approach. All clearance mechanisms were mechanistically incorporated in a static model to predict the relative exposure of carboxylosartan versus losartan (AUC m /AUC p ). The predicted AUC m /AUC p were consistent with the observed data following intravenous and oral administration of losartan. Moreover, the in vitro parameters were used as initial parameters in PBPK permeability-limited disposition models to predict the concentration-time profiles for both parent and its active metabolite after oral administration of losartan. The PBPK model was able to recover the plasma profiles of both losartan and carboxylosartan, further substantiating the validity of this approach. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  14. Neuronal glycogen synthesis contributes to physiological aging

    PubMed Central

    Sinadinos, Christopher; Valles-Ortega, Jordi; Boulan, Laura; Solsona, Estel; Tevy, Maria F; Marquez, Mercedes; Duran, Jordi; Lopez-Iglesias, Carmen; Calbó, Joaquim; Blasco, Ester; Pumarola, Marti; Milán, Marco; Guinovart, Joan J

    2014-01-01

    Glycogen is a branched polymer of glucose and the carbohydrate energy store for animal cells. In the brain, it is essentially found in glial cells, although it is also present in minute amounts in neurons. In humans, loss-of-function mutations in laforin and malin, proteins involved in suppressing glycogen synthesis, induce the presence of high numbers of insoluble polyglucosan bodies in neuronal cells. Known as Lafora bodies (LBs), these deposits result in the aggressive neurodegeneration seen in Lafora’s disease. Polysaccharide-based aggregates, called corpora amylacea (CA), are also present in the neurons of aged human brains. Despite the similarity of CA to LBs, the mechanisms and functional consequences of CA formation are yet unknown. Here, we show that wild-type laboratory mice also accumulate glycogen-based aggregates in the brain as they age. These structures are immunopositive for an array of metabolic and stress-response proteins, some of which were previously shown to aggregate in correlation with age in the human brain and are also present in LBs. Remarkably, these structures and their associated protein aggregates are not present in the aged mouse brain upon genetic ablation of glycogen synthase. Similar genetic intervention in Drosophila prevents the accumulation of glycogen clusters in the neuronal processes of aged flies. Most interestingly, targeted reduction of Drosophila glycogen synthase in neurons improves neurological function with age and extends lifespan. These results demonstrate that neuronal glycogen accumulation contributes to physiological aging and may therefore constitute a key factor regulating age-related neurological decline in humans. PMID:25059425

  15. 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

  16. Subject-independent emotion recognition based on physiological signals: a three-stage decision method.

    PubMed

    Chen, Jing; Hu, Bin; Wang, Yue; Moore, Philip; Dai, Yongqiang; Feng, Lei; Ding, Zhijie

    2017-12-20

    Collaboration between humans and computers has become pervasive and ubiquitous, however current computer systems are limited in that they fail to address the emotional component. An accurate understanding of human emotions is necessary for these computers to trigger proper feedback. Among multiple emotional channels, physiological signals are synchronous with emotional responses; therefore, analyzing physiological changes is a recognized way to estimate human emotions. In this paper, a three-stage decision method is proposed to recognize four emotions based on physiological signals in the multi-subject context. Emotion detection is achieved by using a stage-divided strategy in which each stage deals with a fine-grained goal. The decision method consists of three stages. During the training process, the initial stage transforms mixed training subjects to separate groups, thus eliminating the effect of individual differences. The second stage categorizes four emotions into two emotion pools in order to reduce recognition complexity. The third stage trains a classifier based on emotions in each emotion pool. During the testing process, a test case or test trial will be initially classified to a group followed by classification into an emotion pool in the second stage. An emotion will be assigned to the test trial in the final stage. In this paper we consider two different ways of allocating four emotions into two emotion pools. A comparative analysis is also carried out between the proposal and other methods. An average recognition accuracy of 77.57% was achieved on the recognition of four emotions with the best accuracy of 86.67% to recognize the positive and excited emotion. Using differing ways of allocating four emotions into two emotion pools, we found there is a difference in the effectiveness of a classifier on learning each emotion. When compared to other methods, the proposed method demonstrates a significant improvement in recognizing four emotions in the multi-subject context. The proposed three-stage decision method solves a crucial issue which is 'individual differences' in multi-subject emotion recognition and overcomes the suboptimal performance with respect to direct classification of multiple emotions. Our study supports the observation that the proposed method represents a promising methodology for recognizing multiple emotions in the multi-subject context.

  17. Authorized Course of Instruction for the Quinmester Program. Science: Introduction to Anatomy and Physiology; Human Reproduction; Man and Disease; Man's Senses; and Introduction to the Human Body.

    ERIC Educational Resources Information Center

    Dade County Public Schools, Miami, FL.

    Performance objectives are stated for each of the five secondary school units included in this package of instructional guides prepared for the Dade County Florida Quinmester Program. All five units are concerned with aspects of physiology; three require no prerequisite study of biology ("Introduction to the Human Body,""Man and…

  18. Successful Implantation of Bioengineered, Intrinsically Innervated, Human Internal Anal Sphincter

    PubMed Central

    Raghavan, Shreya; Gilmont, Robert R.; Miyasaka, Eiichi A.; Somara, Sita; Srinivasan, Shanthi; Teitelbaum, Daniel H; Bitar, Khalil N.

    2011-01-01

    Background & Aims To restore fecal continence, the weakened pressure of the internal anal sphincter (IAS) must be increased. We bioengineered intrinsically innervated human IAS, to emulate sphincteric physiology, in vitro. Methods We co-cultured human IAS circular smooth muscle with immortomouse fetal enteric neurons. We investigated the ability of bioengineered innervated human IAS, implanted in RAG1−/− mice, to undergo neovascularization and preserve the physiology of the constituent myogenic and neuronal components. Results The implanted IAS was neovascularized in vivo; numerous blood vessels were observed with no signs of inflammation or infection. Real-time force acquisition from implanted and pre-implant IAS showed distinct characteristics of IAS physiology. Features included the development of spontaneous myogenic basal tone; relaxation of 100% of basal tone in response to inhibitory neurotransmitter vasoactive intestinal peptide (VIP) and direct electrical field stimulation of the intrinsic innervation; inhibition of nitrergic and VIPergic EFS-induced relaxation (by antagonizing nitric oxide synthesis or receptor interaction); contraction in response to cholinergic stimulation with acetylcholine; and intact electromechanical coupling (evidenced by direct response to potassium chloride). Implanted, intrinsically innervated bioengineered human IAS tissue preserved the integrity and physiology of myogenic and neuronal components. Conclusion Intrinsically innervated human IAS bioengineered tissue can be successfully implanted in mice. This approach might be used to treat patients with fecal incontinence. PMID:21463628

  19. Long-term in vivo harmonics imaging of zebrafish embryonic development based on a femtosecond Cr:forsterite laser

    NASA Astrophysics Data System (ADS)

    Chen, S.-Y.; Tsai, T.-H.; Hsieh, C.-S.; Tai, S.-P.; Lin, C.-Y.; Ko, C.-Y.; Chen, Y.-C.; Tsai, H.-J.; Hu, C.-H.; Sun, C.-K.

    2005-03-01

    Based on a femtosecond Cr:forsterite laser, harmonics optical microscopy (HOM) provides a truly "noninvasive" tool for in vivo and long-term study of vertebrate embryonic development. Based on optical nonlinearity, HOM provides sub-micrometer 3D spatial resolution and high 3D optical-sectioning power without using invasive and toxic fluorophores. Since only virtual-level-transition is involved, HOM is known to leave no energy deposition and no photodamage. Combined with second harmonic generation, which is sensitive to specific structure such as nerve and muscle fibers, HOM can perform functional studies of early developmental dynamics of many vertebrate physiological systems. Recently, zebrafish has become a standard model for many biological and medical studies of vertebrates, due to the similarity between embryonic development of zebrafish and human being. Here we demonstrate in vivo HOM studies of developmental dynamics of several important embryonic physiological systems in live zebrafish embryos, with focuses on the developments of brains, eyes, ears, and hearts. Based on a femtosecond Cr:forsterite laser, which provides the deepest penetration (~1.5mm) and least photodamage in the zebrafish embryo, complete developing processes of different physiological systems within a period of time longer than 20 hours can be non-invasively observed inside the same embryo.

  20. EXPOSURE RELATED DOSE ESTIMATING MODEL ( ERDEM ) A PHYSIOLOGICALLY-BASED PHARMACOKINETIC AND PHARMACODYNAMIC ( PBPK/PD ) MODEL FOR ASSESSING HUMAN EXPOSURE AND RISK

    EPA Science Inventory

    The Exposure Related Dose Estimating Model (ERDEM) is a PBPK/PD modeling system that was developed by EPA's National Exposure Research Laboratory (NERL). The ERDEM framework provides the flexibility either to use existing models and to build new PBPK and PBPK/PD models to address...

  1. ASSESSING THE IMPACT OF HUMAN PON1 POLYMORPHISMS: SENSITIVITY AND MONTE CARLO ANALYSES USING A PHYSIOLOGICALLY BASED PHARMACOKINETIC/ PHARMACODYNAMIC (PBPK/PD) MODEL FOR CHLORPYRIFOS. (R828608)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  2. Drawing on student knowledge in human anatomy and physiology

    NASA Astrophysics Data System (ADS)

    Slominski, Tara Nicole

    Prior to instruction, students may have developed alternative conceptions about the mechanics behind human physiology. To help students re-shape these ideas into correct reasoning, the faulty characteristics reinforcing the alternative conceptions need to made explicit. This study used student-generated drawings to expose alternative conceptions Human Anatomy and Physiology students had prior to instruction on neuron physiology. Specifically, we investigated how students thought about neuron communication across a synapse (n=355) and how neuron activity can be modified (n=311). When asked to depict basic communication between two neurons, at least 80% of students demonstrated incorrect ideas about synaptic transmission. When targeting spatial and temporal summation, only eleven students (3.5%) were able to accurately depict at least one form of summation. In response to both drawing questions, student drawings revealed multiple alternative conceptions that resulted in a deeper analysis and characterization of the wide variation of student ideas.

  3. Human Physiological Responses to Acute and Chronic Cold Exposure

    NASA Technical Reports Server (NTRS)

    Stocks, Jodie M.; Taylor, Nigel A. S.; Tipton, Michael J.; Greenleaf, John E.

    2001-01-01

    When inadequately protected humans are exposed to acute cold, excessive body heat is lost to the environment and unless heat production is increased and heat loss attenuated, body temperature will decrease. The primary physiological responses to counter the reduction in body temperature include marked cutaneous vasoconstriction and increased metabolism. These responses, and the hazards associated with such exposure, are mediated by a number of factors which contribute to heat production and loss. These include the severity and duration of the cold stimulus; exercise intensity; the magnitude of the metabolic response; and individual characteristics such as body composition, age, and gender. Chronic exposure to a cold environment, both natural and artificial, results in physiological alterations leading to adaptation. Three quite different, but not necessarily exclusive, patterns of human cold adaptation have been reported: metabolic, hypothermic, and insulative. Cold adaptation has also been associated with an habituation response, in which there is a desensitization, or damping, of the normal response to a cold stress. This review provides a comprehensive analysis of the human physiological and pathological responses to cold exposure. Particular attention is directed to the factors contributing to heat production and heat loss during acute cold stress, and the ability of humans to adapt to cold environments.

  4. Sasang Constitutional Medicine and Traditional Chinese Medicine: A Comparative Overview

    PubMed Central

    Yoo, Junghee; Lee, Euiju; Kim, Chungmi; Lee, Junhee; Lixing, Lao

    2012-01-01

    Sasang constitutional medicine (SCM) is a holistic typological constitution medicine which balances psychological, social, and physical aspects of an individual to achieve wellness and increase longevity. SCM has the qualities of preventative medicine, as it emphasizes daily health management based on constitutionally differentiated regimens and self-cultivation of the mind and body. This review's goal is to establish a fundamental understanding of SCM and to provide a foundation for further study. It compares the similarities and differences of philosophical origins, perspectives on the mind (heart), typological systems, pathology, and therapeutics between SCM and traditional Chinese medicine (TCM). TCM is based on the Taoist view of the universe and humanity. The health and longevity of an individual depends on a harmonious relationship with the universe. On the other hand, SCM is based on the Confucian view of the universe and humanity. SCM focuses on the influence of human affairs on the psyche, physiology, and pathology. PMID:21941592

  5. Lunar and Mars missions - Challenges for advanced life support

    NASA Technical Reports Server (NTRS)

    Duke, Michael B.

    1988-01-01

    The development of a suite of scenarios is a prerequisite to the studies that will enable an informed decision by the United States on a program to meet the recently announced space policy goal to expand human presence beyond earth orbit. NASA's Office of Exploration is currently studying a range of initiative options that would extend the sphere of human activity in space to Mars and include permanent bases or outposts on the moon and on Mars. This paper describes the evolutionary lunar base and the Mars expedition scenarios in some detail so that an evaluation can be made from the point of view of human support and opportunities. Alternative approaches in the development of lunar outposts are outlined along with Mars expeditionary scenarios. Human environmental issues are discussed, including: closed loop life support systems; EVA systems; mobility systems; and medical support, physiological deconditioning, and psychological effects associated with long-duration missions.

  6. Why did Kant reject physiological explanations in his anthropology?

    PubMed

    Sturm, Thomas

    2008-12-01

    One of Kant's central tenets concerning the human sciences is the claim that one need not, and should not, use a physiological vocabulary if one studies human cognitions, feelings, desires, and actions from the point of view of his 'pragmatic' anthropology. The claim is well known, but the arguments Kant advances for it have not been closely discussed. I argue against misguided interpretations of the claim, and I present his actual reasons in favor of it. Contemporary critics of a 'physiological anthropology' reject physiological explanations of mental states as more or less epistemologically dubious. Kant does not favor such ignorance claims--and this is for the good, since none of these claims was sufficiently justified at that time. Instead, he develops an original irrelevance thesis concerning the empirical knowledge of the physiological basis of the mind. His arguments for this claim derive from his original and, up to now, little understood criticism of a certain conception of pragmatic history, related to his anthropological insights concerning our ability to create new rules of action, the social dynamics of human action, and the relative inconstancy of human nature. The irrelevance thesis also changes his views of the goal and methodology of anthropology. Kant thereby argues for a distinctive approach in quest for a general 'science of man'.

  7. Anorectal physiology measurements are of no value in clinical practice. True or false?

    PubMed Central

    Carty, N. J.; Moran, B.; Johnson, C. D.

    1994-01-01

    This article examines whether there is any clinical value in anorectal physiology measurements. The function of the human rectum is poorly understood and the factors which affect function of the anal sphincters are complex. Several laboratories have reported results of anorectal physiology measurements, but there is extensive variation between normal values in different laboratories. It is argued that anorectal physiology measurements fail to meet the criteria of a useful clinical test: 1. It is not widely available to clinicians; 2. It is not possible to establish a reproducible normal range; 3. Abnormal measurements do not correlate with disease entities or explain symptoms; 4. The results are often unhelpful in diagnosis and management; 5. Clinical outcome after intervention does not correlate with alteration in the measurements obtained. On the other hand it can be argued that anorectal physiology measurements do provide information that assists in the management of conditions such as constipation, anismus, Hirschsprung's disease, faecal incontinence and tenesmus. Management based on biofeedback modification of physiological responses requires these techniques as part of the biofeedback system. There is evidence that this may be appropriate in anismus and solitary rectal ulcer syndrome. However, the assessment of these difficult conditions and the interpretation of the results are probably at present best confined to specialist units. PMID:8074392

  8. Thermoregulatory responses in exercising rats: methodological aspects and relevance to human physiology.

    PubMed

    Wanner, Samuel Penna; Prímola-Gomes, Thales Nicolau; Pires, Washington; Guimarães, Juliana Bohnen; Hudson, Alexandre Sérvulo Ribeiro; Kunstetter, Ana Cançado; Fonseca, Cletiana Gonçalves; Drummond, Lucas Rios; Damasceno, William Coutinho; Teixeira-Coelho, Francisco

    2015-01-01

    Rats are used worldwide in experiments that aim to investigate the physiological responses induced by a physical exercise session. Changes in body temperature regulation, which may affect both the performance and the health of exercising rats, are evident among these physiological responses. Despite the universal use of rats in biomedical research involving exercise, investigators often overlook important methodological issues that hamper the accurate measurement of clear thermoregulatory responses. Moreover, much debate exists regarding whether the outcome of rat experiments can be extrapolated to human physiology, including thermal physiology. Herein, we described the impact of different exercise intensities, durations and protocols and environmental conditions on running-induced thermoregulatory changes. We focused on treadmill running because this type of exercise allows for precise control of the exercise intensity and the measurement of autonomic thermoeffectors associated with heat production and loss. Some methodological issues regarding rat experiments, such as the sites for body temperature measurements and the time of day at which experiments are performed, were also discussed. In addition, we analyzed the influence of a high body surface area-to-mass ratio and limited evaporative cooling on the exercise-induced thermoregulatory responses of running rats and then compared these responses in rats to those observed in humans. Collectively, the data presented in this review represent a reference source for investigators interested in studying exercise thermoregulation in rats. In addition, the present data indicate that the thermoregulatory responses of exercising rats can be extrapolated, with some important limitations, to human thermal physiology.

  9. Thermoregulatory responses in exercising rats: methodological aspects and relevance to human physiology

    PubMed Central

    Wanner, Samuel Penna; Prímola-Gomes, Thales Nicolau; Pires, Washington; Guimarães, Juliana Bohnen; Hudson, Alexandre Sérvulo Ribeiro; Kunstetter, Ana Cançado; Fonseca, Cletiana Gonçalves; Drummond, Lucas Rios; Damasceno, William Coutinho; Teixeira-Coelho, Francisco

    2015-01-01

    Rats are used worldwide in experiments that aim to investigate the physiological responses induced by a physical exercise session. Changes in body temperature regulation, which may affect both the performance and the health of exercising rats, are evident among these physiological responses. Despite the universal use of rats in biomedical research involving exercise, investigators often overlook important methodological issues that hamper the accurate measurement of clear thermoregulatory responses. Moreover, much debate exists regarding whether the outcome of rat experiments can be extrapolated to human physiology, including thermal physiology. Herein, we described the impact of different exercise intensities, durations and protocols and environmental conditions on running-induced thermoregulatory changes. We focused on treadmill running because this type of exercise allows for precise control of the exercise intensity and the measurement of autonomic thermoeffectors associated with heat production and loss. Some methodological issues regarding rat experiments, such as the sites for body temperature measurements and the time of day at which experiments are performed, were also discussed. In addition, we analyzed the influence of a high body surface area-to-mass ratio and limited evaporative cooling on the exercise-induced thermoregulatory responses of running rats and then compared these responses in rats to those observed in humans. Collectively, the data presented in this review represent a reference source for investigators interested in studying exercise thermoregulation in rats. In addition, the present data indicate that the thermoregulatory responses of exercising rats can be extrapolated, with some important limitations, to human thermal physiology. PMID:27227066

  10. What happens in the skin? Integrating skin permeation kinetics into studies of developmental and reproductive toxicity following topical exposure.

    PubMed

    Dancik, Yuri; Bigliardi, Paul L; Bigliardi-Qi, Mei

    2015-12-01

    Animal-based developmental and reproductive toxicological studies involving skin exposure rarely incorporate information on skin permeation kinetics. For practical reasons, animal studies cannot investigate the many factors which can affect human skin permeation and systemic uptake kinetics in real-life scenarios. Traditional route-to-route extrapolation is based on the same types of experiments and requires assumptions regarding route similarity. Pharmacokinetic modeling based on skin physiology and structure is the most efficient way to incorporate the variety of intrinsic skin and exposure-dependent parameters occurring in clinical and occupational settings into one framework. Physiologically-based pharmacokinetic models enable the integration of available in vivo, in vitro and in silico data to quantitatively predict the kinetics of uptake at the site of interest, as needed for 21st century toxicology and risk assessment. As demonstrated herein, proper interpretation and integration of these data is a multidisciplinary endeavor requiring toxicological, risk assessment, mathematical, pharmaceutical, biological and dermatological expertise. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Physiological Parameters Database for PBPK Modeling (External Review Draft)

    EPA Science Inventory

    EPA released for public comment a physiological parameters database (created using Microsoft ACCESS) intended to be used in PBPK modeling. The database contains physiological parameter values for humans from early childhood through senescence. It also contains similar data for an...

  12. 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

  13. 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

  14. Design of Secure ECG-Based Biometric Authentication in Body Area Sensor Networks

    PubMed Central

    Peter, Steffen; Pratap Reddy, Bhanu; Momtaz, Farshad; Givargis, Tony

    2016-01-01

    Body area sensor networks (BANs) utilize wireless communicating sensor nodes attached to a human body for convenience, safety, and health applications. Physiological characteristics of the body, such as the heart rate or Electrocardiogram (ECG) signals, are promising means to simplify the setup process and to improve security of BANs. This paper describes the design and implementation steps required to realize an ECG-based authentication protocol to identify sensor nodes attached to the same human body. Therefore, the first part of the paper addresses the design of a body-area sensor system, including the hardware setup, analogue and digital signal processing, and required ECG feature detection techniques. A model-based design flow is applied, and strengths and limitations of each design step are discussed. Real-world measured data originating from the implemented sensor system are then used to set up and parametrize a novel physiological authentication protocol for BANs. The authentication protocol utilizes statistical properties of expected and detected deviations to limit the number of false positive and false negative authentication attempts. The result of the described holistic design effort is the first practical implementation of biometric authentication in BANs that reflects timing and data uncertainties in the physical and cyber parts of the system. PMID:27110785

  15. Design of Secure ECG-Based Biometric Authentication in Body Area Sensor Networks.

    PubMed

    Peter, Steffen; Reddy, Bhanu Pratap; Momtaz, Farshad; Givargis, Tony

    2016-04-22

    Body area sensor networks (BANs) utilize wireless communicating sensor nodes attached to a human body for convenience, safety, and health applications. Physiological characteristics of the body, such as the heart rate or Electrocardiogram (ECG) signals, are promising means to simplify the setup process and to improve security of BANs. This paper describes the design and implementation steps required to realize an ECG-based authentication protocol to identify sensor nodes attached to the same human body. Therefore, the first part of the paper addresses the design of a body-area sensor system, including the hardware setup, analogue and digital signal processing, and required ECG feature detection techniques. A model-based design flow is applied, and strengths and limitations of each design step are discussed. Real-world measured data originating from the implemented sensor system are then used to set up and parametrize a novel physiological authentication protocol for BANs. The authentication protocol utilizes statistical properties of expected and detected deviations to limit the number of false positive and false negative authentication attempts. The result of the described holistic design effort is the first practical implementation of biometric authentication in BANs that reflects timing and data uncertainties in the physical and cyber parts of the system.

  16. Physiologic Basis for Understanding Quantitative Dehydration Assessment

    DTIC Science & Technology

    2012-01-01

    Perspective Physiologic basis for understanding quantitative dehydration assessment1–4 Samuel N Cheuvront, Robert W Kenefick, Nisha Charkoudian, and...Michael N Sawka ABSTRACT Dehydration (body water deficit) is a physiologic state that can have profound implications for human health and performance...review the physiologic basis for understanding quantitative dehydration as- sessment. We highlight how phenomenologic interpretations of de- hydration

  17. RADIOISOTOPES IN MEDICINE AND HUMAN PHYSIOLOGY. A Selected List of References

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

    McCormick, J.A. comp.

    1958-08-01

    This bibliography contains 2862 references on uses of radioisotopes in diagnostic medicine, therapeutic medicine, clinical research, human physiology, general medical research, and immunology. The references were taken from the 1948 to 1956 open literature. A list of the journals from which the references were selected and an author index are included. (auth)'

  18. A contribution towards establishing more comfortable space weather to cope with increased human space passengers for ISS shuttles

    NASA Astrophysics Data System (ADS)

    Kalu, A.

    Space Weather is a specialized scienctific descipline in Meteorology which has recently emerged from man's continued research efforts to create a familiar spacecraft environment which is physiologically stable and life sustaining for astronauts and human passengers in distant space travels. As the population of human passengers in space shuttles rapidly increases, corresponding research on sustained micro-climate of spacecrafts is considered necessary and timely. This is because existing information is not meant for a large population in spacecrafts. The paper therefore discusses the role of meteorology (specifically micrometeorology) in relation to internal communication, spacecraft instrumentation and physiologic comfort of astronauts and space passengers (the later may not necessarily be trained astronauts, but merely business men or tourist space travellers for business transactions in the International Space Station (ISS)). It is recognized that me eorology which is a fundamental science amongt multidiscplinary sciences has been found to be vital in space travels and communication. Space weather therefore appears in slightly different format where temperature and humidity changes and variability within the spacecraft exert very significant influences on the efficiency of astronauts and the effectiveness of the various delicate instrument gadgets aimed at reducing the frequency of computer failures and malfunction of other instruments on which safety of the spacecraft depends. Apart from the engineering and technological problems which space scientists must have to overcome when human population in space shuttles increases as we now expect, based on evidence from successful missions to ISS, the maint enace of physiologic comfort state of astronauts, which, as far as scientifically possible, should be as near as possible to their Earth-Atmosphere condition. This is one of the most important and also most difficult conditions to attain. It demands a mor e detailed research on space thermodynamics as future passengers to the ISS must be assured of their physiologic comfort and safety before they could accept to pay the huge cost for the space travels. The presentation of the paper is divided into the following four basic sections: (a) Take-off or Blast-off (b) Cruising and SpaceWalk (c) Re-entry into the Terrestial Atmosphere, and (d) Landing and Rescue Operations. Experience shows that each of the above four distinct stages of space travel demands a careful assessment of the micro-climate of the indoor spacecraft and these will each be investigated to ensure that relevant micro - climate information that will maintain effective physiologic comfort level of astronauts and specimen will be attained. Finally, the paper discusses a method to predict indoor weather condition in spacecrafts based on observed ambient data especially temperature and humidity and micro-indoor air circulation for differenct timescales during space shuttles to the ISS. An active multidisciplinary research in which Engineers, Meteorologists, Medical Experts, etc., will work together collaboratively on the problem on ambient indoor space weather for increased human population during proposed International Space Station shuttle missions later this century is strongly recommended.

  19. Insights into horizontal canal benign paroxysmal positional vertigo from a human case report.

    PubMed

    Aron, Margaret; Bance, Manohar

    2013-12-01

    For horizontal canal benign paroxysmal positional vertigo, determination of the pathologic side is difficult and based on many physiological assumptions. This article reports findings on a patient who had one dysfunctional inner ear and who presented with horizontal canal benign paroxysmal positional vertigo, giving us a relatively pure model for observing nystagmus arising in a subject in whom the affected side is known a priori. It is an interesting human model corroborating theories of nystagmus generation in this pathology and also serves to validate Ewald's second law in a living human subject. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  20. Polyamines: Bio-Molecules with Diverse Functions in Plant and Human Health and Disease

    PubMed Central

    Handa, Avtar K.; Fatima, Tahira; Mattoo, Autar K.

    2018-01-01

    Biogenic amines—polyamines (PAs), particularly putrescine, spermidine and spermine are ubiquitous in all living cells. Their indispensable roles in many biochemical and physiological processes are becoming commonly known, including promoters of plant life and differential roles in human health and disease. PAs positively impact cellular functions in plants—exemplified by increasing longevity, reviving physiological memory, enhancing carbon and nitrogen resource allocation/signaling, as well as in plant development and responses to extreme environments. Thus, one or more PAs are commonly found in genomic and metabolomics studies using plants, particulary during different abiotic stresses. In humans, a general decline in PA levels with aging occurs parallel with some human health disorders. Also, high PA dose is detrimental to patients suffering from cancer, aging, innate immunity and cognitive impairment during Alzheimer and Parkinson diseases. A dichotomy exists in that while PAs may increase longevity and reduce some age-associated cardiovascular diseases, in disease conditions involving higher cellular proliferation, their intake has negative consequences. Thus, it is essential that PA levels be rigorously quantified in edible plant sources as well as in dietary meats. Such a database can be a guide for medical experts in order to recommend which foods/meats a patient may consume and which ones to avoid. Accordingly, designing both high and low polyamine diets for human consumption are in vogue, particularly in medical conditions where PA intake may be detrimental, for instance, cancer patients. In this review, literature data has been collated for the levels of the three main PAs, putrescine, spermidine and spermine, in different edible sources—vegetables, fruits, cereals, nuts, meat, sea food, cheese, milk, and eggs. Based on our analysis of vast literature, the effects of PAs in human/animal health fall into two broad, Yang and Yin, categories: beneficial for the physiological processes in healthy cells and detrimental under pathological conditions. PMID:29468148

  1. Polyamines: Bio-Molecules with diverse functions in plant and human health and disease

    NASA Astrophysics Data System (ADS)

    Handa, Avtar K.; Fatima, Tahira; Mattoo, Autar K.

    2018-02-01

    Biogenic amines – polyamines (PAs), particularly putrescine, spermidine and spermine (and thermospermine) are ubiquitous in all living cells. Their indispensable roles in many biochemical and physiological processes are becoming commonly known, including promoters of plant life and differential roles in human health and disease. PAs positively impact cellular functions in plants – exemplified by increasing longevity, reviving physiological memory, enhancing carbon and nitrogen resource allocation/signaling, as well as in plant development and responses to extreme environments. Thus, one or more PAs are commonly found in genomic and metabolomics studies using plants, particulary during different abiotic stresses. In humans, a general decline in PA levels with aging occurs parallel with some human health disorders. Also, high PA dose is detrimental to patients suffering from cancer, aging, innate immunity and cognitive impairment during Alzheimer and Parkinson diseases. A dichotomy exists in that while PAs may increase longevity and reduce some age-associated cardiovascular diseases, in disease conditions involving higher cellular proliferation, their intake has negative consequences. Thus, it is essential that PA levels be rigorously quantified in edible plant sources as well as in dietary meats. Such a database can be a guide for medical experts in order to recommend which foods/meats a patient may consume and which ones to avoid. Accordingly, designing both high and low polyamine diets for human consumption are in vogue, particularly in medical conditions where PA intake may be detrimental, for instance, cancer patients. In this review, literature data has been collated for the levels of the three main PAs, putrescine, spermidine and spermine, in different edible sources - vegetables, fruits, cereals, nuts, meat, sea food, cheese, milk and eggs. Based on our analysis of vast literature, the effects of PAs in human/animal health fall into two broad, Yang and Yin, categories: beneficial for the physiological processes in healthy cells and detrimental under pathological conditions.

  2. The relevance and potential roles of microphysiological systems in biology and medicine.

    PubMed

    Wikswo, John P

    2014-09-01

    Microphysiological systems (MPS), consisting of interacting organs-on-chips or tissue-engineered, 3D organ constructs that use human cells, present an opportunity to bring new tools to biology, medicine, pharmacology, physiology, and toxicology. This issue of Experimental Biology and Medicine describes the ongoing development of MPS that can serve as in-vitro models for bone and cartilage, brain, gastrointestinal tract, lung, liver, microvasculature, reproductive tract, skeletal muscle, and skin. Related topics addressed here are the interconnection of organs-on-chips to support physiologically based pharmacokinetics and drug discovery and screening, and the microscale technologies that regulate stem cell differentiation. The initial motivation for creating MPS was to increase the speed, efficiency, and safety of pharmaceutical development and testing, paying particular regard to the fact that neither monolayer monocultures of immortal or primary cell lines nor animal studies can adequately recapitulate the dynamics of drug-organ, drug-drug, and drug-organ-organ interactions in humans. Other applications include studies of the effect of environmental toxins on humans, identification, characterization, and neutralization of chemical and biological weapons, controlled studies of the microbiome and infectious disease that cannot be conducted in humans, controlled differentiation of induced pluripotent stem cells into specific adult cellular phenotypes, and studies of the dynamics of metabolism and signaling within and between human organs. The technical challenges are being addressed by many investigators, and in the process, it seems highly likely that significant progress will be made toward providing more physiologically realistic alternatives to monolayer monocultures or whole animal studies. The effectiveness of this effort will be determined in part by how easy the constructs are to use, how well they function, how accurately they recapitulate and report human pharmacology and toxicology, whether they can be generated in large numbers to enable parallel studies, and if their use can be standardized consistent with the practices of regulatory science. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  3. The relevance and potential roles of microphysiological systems in biology and medicine

    PubMed Central

    Wikswo, John P.

    2014-01-01

    Microphysiological systems (MPS), consisting of interacting organs-on-chips or tissue-engineered, 3D organ constructs that use human cells, present an opportunity to bring new tools to biology, medicine, pharmacology, physiology, and toxicology. This issue of Experimental Biology and Medicine describes the ongoing development of MPS that can serve as in vitro models for bone and cartilage, brain, gastrointestinal tract, lung, liver, microvasculature, reproductive tract, skeletal muscle, and skin. Related topics addressed here are the interconnection of organs-on-chips to support physiologically based pharmacokinetics and drug discovery and screening, and the microscale technologies that regulate stem cell differentiation. The initial motivation for creating MPS was to increase the speed, efficiency, and safety of pharmaceutical development and testing, paying particular regard to the fact that neither monolayer monocultures of immortal or primary cell lines nor animal studies can adequately recapitulate the dynamics of drug-organ, drug-drug, and drug-organ-organ interactions in humans. Other applications include studies of the effect of environmental toxins on humans, identification, characterization, and neutralization of chemical and biological weapons, controlled studies of the microbiome and infectious disease that cannot be conducted in humans, controlled differentiation of induced pluripotent stem cells into specific adult cellular phenotypes, and studies of the dynamics of metabolism and signaling within and between human organs. The technical challenges are being addressed by many investigators, and in the process, it seems highly likely that significant progress will be made toward providing more physiologically realistic alternatives to monolayer monocultures or whole animal studies. The effectiveness of this effort will be determined in part by how easy the constructs are to use, how well they function, how accurately they recapitulate and report human pharmacology and toxicology, whether they can be generated in large numbers to enable parallel studies, and if their use can be standardized consistent with the practices of regulatory science. PMID:25187571

  4. The Human Centrifuge

    NASA Astrophysics Data System (ADS)

    van Loon, Jack J. W. A.

    2009-01-01

    Life on Earth has developed at unit gravity, 9.81 m/s2, which was a major factor especially when vertebrates emerged from water onto land in the late Devonian, some 375 million years ago. But how would nature have evolved on a larger planet? We are able to address this question simply in experiments using centrifuges. Based on these studies we have gained valuable insights in the physiological process in plants and animals. They adapt to a new steady state suitable for the high-g environments applied. Information on mammalian adaptations to hyper-g is interesting or may be even vital for human space exploration programs. It has been shown in long duration animal hypergravity studies, ranging from snails, rats to primates, that various structures like muscles, bones, neuro-vestibular, or the cardio-vascular system are affected. However, humans have never been exposed to a hyper-g environment for long durations. Centrifuge studies involving humans are mostly in the order of hours. The current work on human centrifuges are all focused on short arm systems to apply short periods of artificial gravity in support of long duration space missions in ISS or to Mars. In this paper we will address the possible usefulness of a large human centrifuge on Earth. In such a centrifuge a group of humans can be exposed to hypergravity for, in principle, an unlimited period of time like living on a larger planet. The input from a survey under scientists working in the field of gravitational physiology, but also other disciplines, will be discussed.

  5. Pharmacokinetics and Pharmacodynamics in Space

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshmi; Cintron, Nitza M.

    1990-01-01

    The Pharmacokinetics and Pharmacodynamics Panel met on 29-30 Aug. 1988 at the Lunar and Planetary Institute in Houston, Texas to discuss pharmacokinetic and pharmacodynamic implications of space flight and make recommendations for operational and research strategies. Based on the knowledge available on the physiological changes that occur during space flight, the dependence of pharmacokinetics on physiological factors, and the therapeutic requirements for future space missions, the panel made several recommendations for research. It was suggested that using medications available with a large (wide) therapeutic window will avoid unforeseen therapeutic consequences during flight. The sequence for conducting research was outlined as follows: (1) identify ground-based simulation models (e.g., antiorthostatic bed rest) for conducting pharmacokinetic and pharmacodynamic research; (2) estimate parametric changes in these models using pharmacologic agents that have different pharmacokinetic characteristics and a narrow therapeutic index; (3) verify these findings during flight; and (4) develop and identify appropriate and effective drug delivery systems, dosage forms, and regimens. The panel recommended gaining a thorough understanding of the pharmacokinetic deviations of medications that have a narrow therapeutic index (e.g. cardiovascular drugs and sedative hypnotics) in order to ensure safe and effective treatment during flight with these agents. It was also suggested that basic information on physiological factors such as organ blood flow, protein composition and binding, tissue distribution, and metabolism by hepatic enzymes must be accumulated by conducting ground-based animal and human studies using models of weightlessness. This information will be useful to construct and identify physiologically based pharmacokinetic models that can provide valuable information on the pharmacodynamic consequences of space flight and aid in identifying appropriate therapeutic regimens.

  6. Scale-up of a physiologically-based pharmacokinetic model to predict the disposition of monoclonal antibodies in monkeys.

    PubMed

    Glassman, Patrick M; Chen, Yang; Balthasar, Joseph P

    2015-10-01

    Preclinical assessment of monoclonal antibody (mAb) disposition during drug development often includes investigations in non-human primate models. In many cases, mAb exhibit non-linear disposition that relates to mAb-target binding [i.e., target-mediated disposition (TMD)]. The goal of this work was to develop a physiologically-based pharmacokinetic (PBPK) model to predict non-linear mAb disposition in plasma and in tissues in monkeys. Physiological parameters for monkeys were collected from several sources, and plasma data for several mAbs associated with linear pharmacokinetics were digitized from prior literature reports. The digitized data displayed great variability; therefore, parameters describing inter-antibody variability in the rates of pinocytosis and convection were estimated. For prediction of the disposition of individual antibodies, we incorporated tissue concentrations of target proteins, where concentrations were estimated based on categorical immunohistochemistry scores, and with assumed localization of target within the interstitial space of each organ. Kinetics of target-mAb binding and target turnover, in the presence or absence of mAb, were implemented. The model was then employed to predict concentration versus time data, via Monte Carlo simulation, for two mAb that have been shown to exhibit TMD (2F8 and tocilizumab). Model predictions, performed a priori with no parameter fitting, were found to provide good prediction of dose-dependencies in plasma clearance, the areas under plasma concentration versu time curves, and the time-course of plasma concentration data. This PBPK model may find utility in predicting plasma and tissue concentration versus time data and, potentially, the time-course of receptor occupancy (i.e., mAb-target binding) to support the design and interpretation of preclinical pharmacokinetic-pharmacodynamic investigations in non-human primates.

  7. Identification of resilient individuals and those at risk for performance deficits under stress.

    PubMed

    Winslow, Brent D; Carroll, Meredith B; Martin, Jonathan W; Surpris, Glenn; Chadderdon, George L

    2015-01-01

    Human task performance is affected by exposure to physiological and psychological stress. The ability to measure the physiological response to stressors and correlate that to task performance could be used to identify resilient individuals or those at risk for stress-related performance decrements. Accomplishing this prior to performance under severe stress or the development of clinical stress disorders could facilitate focused preparation such as tailoring training to individual needs. Here we measure the effects of stress on physiological response and performance through behavior, physiological sensors, and subjective ratings, and identify which individuals are at risk for stress-related performance decrements. Participants performed military-relevant training tasks under stress in a virtual environment, with autonomic and hypothalamic-pituitary-adrenal axis (HPA) reactivity analyzed. Self-reported stress, as well as physiological indices of stress, increased in the group pre-exposed to socioevaluative stress. Stress response was effectively captured via electrodermal and cardiovascular measures of heart rate and skin conductance level. A resilience classification algorithm was developed based upon physiological reactivity, which correlated with baseline unstressed physiological and self-reported stress values. Outliers were identified in the experimental group that had a significant mismatch between self-reported stress and salivary cortisol. Baseline stress measurements were predictive of individual resilience to stress, including the impact stress had on physiological reactivity and performance. Such an approach may have utility in identifying individuals at risk for problems performing under severe stress. Continuing work has focused on adapting this method for military personnel, and assessing the utility of various coping and decision-making strategies on performance and physiological stress.

  8. Identification of resilient individuals and those at risk for performance deficits under stress

    PubMed Central

    Winslow, Brent D.; Carroll, Meredith B.; Martin, Jonathan W.; Surpris, Glenn; Chadderdon, George L.

    2015-01-01

    Human task performance is affected by exposure to physiological and psychological stress. The ability to measure the physiological response to stressors and correlate that to task performance could be used to identify resilient individuals or those at risk for stress-related performance decrements. Accomplishing this prior to performance under severe stress or the development of clinical stress disorders could facilitate focused preparation such as tailoring training to individual needs. Here we measure the effects of stress on physiological response and performance through behavior, physiological sensors, and subjective ratings, and identify which individuals are at risk for stress-related performance decrements. Participants performed military-relevant training tasks under stress in a virtual environment, with autonomic and hypothalamic-pituitary-adrenal axis (HPA) reactivity analyzed. Self-reported stress, as well as physiological indices of stress, increased in the group pre-exposed to socioevaluative stress. Stress response was effectively captured via electrodermal and cardiovascular measures of heart rate and skin conductance level. A resilience classification algorithm was developed based upon physiological reactivity, which correlated with baseline unstressed physiological and self-reported stress values. Outliers were identified in the experimental group that had a significant mismatch between self-reported stress and salivary cortisol. Baseline stress measurements were predictive of individual resilience to stress, including the impact stress had on physiological reactivity and performance. Such an approach may have utility in identifying individuals at risk for problems performing under severe stress. Continuing work has focused on adapting this method for military personnel, and assessing the utility of various coping and decision-making strategies on performance and physiological stress. PMID:26441503

  9. 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.

  10. Ultrasound in space

    NASA Technical Reports Server (NTRS)

    Martin, David S.; South, Donna A.; Garcia, Kathleen M.; Arbeille, Philippe

    2003-01-01

    Physiology of the human body in space has been a major concern for space-faring nations since the beginning of the space era. Ultrasound (US) is one of the most cost effective and versatile forms of medical imaging. As such, its use in characterizing microgravity-induced changes in physiology is being realized. In addition to the use of US in related ground-based studies, equipment has also been modified to fly in space. This involves alteration to handle the stresses of launch and different power and cooling requirements. Study protocols also have been altered to accommodate the microgravity environment. Ultrasound studies to date have shown a pattern of adaptation to microgravity that includes changes in cardiac chamber sizes and vertebral spacing. Ultrasound has been and will continue to be an important component in the investigation of physiological and, possibly, pathologic changes occurring in space or as a result of spaceflight.

  11. 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.

  12. ITC Recommendations for Transporter Kinetic Parameter Estimation and Translational Modeling of Transport-Mediated PK and DDIs in Humans

    PubMed Central

    Zamek-Gliszczynski, MJ; Lee, CA; Poirier, A; Bentz, J; Chu, X; Ellens, H; Ishikawa, T; Jamei, M; Kalvass, JC; Nagar, S; Pang, KS; Korzekwa, K; Swaan, PW; Taub, ME; Zhao, P; Galetin, A

    2013-01-01

    This white paper provides a critical analysis of methods for estimating transporter kinetics and recommendations on proper parameter calculation in various experimental systems. Rational interpretation of transporter-knockout animal findings and application of static and dynamic physiologically based modeling approaches for prediction of human transporter-mediated pharmacokinetics and drug–drug interactions (DDIs) are presented. The objective is to provide appropriate guidance for the use of in vitro, in vivo, and modeling tools in translational transporter science. PMID:23588311

  13. 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.

  14. Skin blotting: a noninvasive technique for evaluating physiological skin status.

    PubMed

    Minematsu, Takeo; Horii, Motoko; Oe, Makoto; Sugama, Junko; Mugita, Yuko; Huang, Lijuan; Nakagami, Gojiro; Sanada, Hiromi

    2014-06-01

    The skin performs important structural and physiological functions, and skin assessment represents an important step in identifying skin problems. Although noninvasive techniques for assessing skin status exist, no such techniques for monitoring its physiological status are available. This study aimed to develop a novel skin-assessment technique known as skin blotting, based on the leakage of secreted proteins from inside the skin following overhydration in mice. The applicability of this technique was further investigated in a clinical setting. Skin blotting involves 2 steps: collecting proteins by attaching a damp nitrocellulose membrane to the surface of the skin, and immunostaining the collected proteins. The authors implanted fluorescein-conjugated dextran (F-DEX)-containing agarose gels into mice and detected the tissue distribution of F-DEX under different blotting conditions. They also analyzed the correlations between inflammatory cytokine secretion and leakage following ultraviolet irradiation in mice and in relation to body mass index in humans. The F-DEX in mice was distributed in the deeper and shallower layers of skin and leaked through the transfollicular and transepidermal routes, respectively. Ultraviolet irradiation induced tumor necrosis factor secretion in the epidermis in mice, which was detected by skin blotting, whereas follicular tumor necrosis factor was associated with body mass index in obese human subjects. These results support the applicability of skin blotting for skin assessment. Skin blotting represents a noninvasive technique for assessing skin physiology and has potential as a predictive and diagnostic tool for skin disorders.

  15. Non-Euclidean stress-free configuration of arteries accounting for curl of axial strips sectioned from vessels.

    PubMed

    Takamizawa, Keiichi; Nakayama, Yasuhide

    2013-11-01

    It is well known that arteries are subject to residual stress. In earlier studies, the residual stress in the arterial ring relieved by a radial cut was considered in stress analysis. However, it has been found that axial strips sectioned from arteries also curled into arcs, showing that the axial residual stresses were relieved from the arterial walls. The combined relief of circumferential and axial residual stresses must be considered to accurately analyze stress and strain distributions under physiological loading conditions. In the present study, a mathematical model of a stress-free configuration of artery was proposed using Riemannian geometry. Stress analysis for arterial walls under unloaded and physiologically loaded conditions was performed using exponential strain energy functions for porcine and human common carotid arteries. In the porcine artery, the circumferential stress distribution under physiological loading became uniform compared with that without axial residual strain, whereas a gradient of axial stress distribution increased through the wall thickness. This behavior showed almost the same pattern that was observed in a recent study in which approximate analysis accounting for circumferential and axial residual strains was performed, whereas the circumferential and axial stresses increased from the inner surface to the outer surface under a physiological condition in the human common carotid artery of a two-layer model based on data of other recent studies. In both analyses, Riemannian geometry was appropriate to define the stress-free configurations of the arterial walls with both circumferential and axial residual strains.

  16. EPM - The European Facility for human physiology research on ISS.

    PubMed

    Rieschel, Mats; Nasca, Rosario; Junk, Peter; Gerhard, Ingo

    2002-07-01

    The European Physiology Modules (EPM) Facility is one of the four major Space Station facilities being developed within the framework of ESA's Microgravity Facilities for Columbus (MFC) programme. In order to allow a wide spectrum of physiological studies in weightlessness conditions, the facility provides the infrastructure to accommodate a variable set of scientific equipment. The initial EPM configuration supports experiments in the fields of neuroscience, bone & muscle research, cardiovascular research and metabolism. The International Space Life Science Working Group (ISLSWG) has recommended co-locating EPM with the 2 NASA Human Research Facility racks.

  17. Collaborative filtering for brain-computer interaction using transfer learning and active class selection.

    PubMed

    Wu, Dongrui; Lance, Brent J; Parsons, Thomas D

    2013-01-01

    Brain-computer interaction (BCI) and physiological computing are terms that refer to using processed neural or physiological signals to influence human interaction with computers, environment, and each other. A major challenge in developing these systems arises from the large individual differences typically seen in the neural/physiological responses. As a result, many researchers use individually-trained recognition algorithms to process this data. In order to minimize time, cost, and barriers to use, there is a need to minimize the amount of individual training data required, or equivalently, to increase the recognition accuracy without increasing the number of user-specific training samples. One promising method for achieving this is collaborative filtering, which combines training data from the individual subject with additional training data from other, similar subjects. This paper describes a successful application of a collaborative filtering approach intended for a BCI system. This approach is based on transfer learning (TL), active class selection (ACS), and a mean squared difference user-similarity heuristic. The resulting BCI system uses neural and physiological signals for automatic task difficulty recognition. TL improves the learning performance by combining a small number of user-specific training samples with a large number of auxiliary training samples from other similar subjects. ACS optimally selects the classes to generate user-specific training samples. Experimental results on 18 subjects, using both k nearest neighbors and support vector machine classifiers, demonstrate that the proposed approach can significantly reduce the number of user-specific training data samples. This collaborative filtering approach will also be generalizable to handling individual differences in many other applications that involve human neural or physiological data, such as affective computing.

  18. Collaborative Filtering for Brain-Computer Interaction Using Transfer Learning and Active Class Selection

    PubMed Central

    Wu, Dongrui; Lance, Brent J.; Parsons, Thomas D.

    2013-01-01

    Brain-computer interaction (BCI) and physiological computing are terms that refer to using processed neural or physiological signals to influence human interaction with computers, environment, and each other. A major challenge in developing these systems arises from the large individual differences typically seen in the neural/physiological responses. As a result, many researchers use individually-trained recognition algorithms to process this data. In order to minimize time, cost, and barriers to use, there is a need to minimize the amount of individual training data required, or equivalently, to increase the recognition accuracy without increasing the number of user-specific training samples. One promising method for achieving this is collaborative filtering, which combines training data from the individual subject with additional training data from other, similar subjects. This paper describes a successful application of a collaborative filtering approach intended for a BCI system. This approach is based on transfer learning (TL), active class selection (ACS), and a mean squared difference user-similarity heuristic. The resulting BCI system uses neural and physiological signals for automatic task difficulty recognition. TL improves the learning performance by combining a small number of user-specific training samples with a large number of auxiliary training samples from other similar subjects. ACS optimally selects the classes to generate user-specific training samples. Experimental results on 18 subjects, using both nearest neighbors and support vector machine classifiers, demonstrate that the proposed approach can significantly reduce the number of user-specific training data samples. This collaborative filtering approach will also be generalizable to handling individual differences in many other applications that involve human neural or physiological data, such as affective computing. PMID:23437188

  19. A Real-Time Wireless Sweat Rate Measurement System for Physical Activity Monitoring.

    PubMed

    Brueck, Andrew; Iftekhar, Tashfin; Stannard, Alicja B; Yelamarthi, Kumar; Kaya, Tolga

    2018-02-10

    There has been significant research on the physiology of sweat in the past decade, with one of the main interests being the development of a real-time hydration monitor that utilizes sweat. The contents of sweat have been known for decades; sweat provides significant information on the physiological condition of the human body. However, it is important to know the sweat rate as well, as sweat rate alters the concentration of the sweat constituents, and ultimately affects the accuracy of hydration detection. Towards this goal, a calorimetric based flow-rate detection system was built and tested to determine sweat rate in real time. The proposed sweat rate monitoring system has been validated through both controlled lab experiments (syringe pump) and human trials. An Internet of Things (IoT) platform was embedded, with the sensor using a Simblee board and Raspberry Pi. The overall prototype is capable of sending sweat rate information in real time to either a smartphone or directly to the cloud. Based on a proven theoretical concept, our overall system implementation features a pioneer device that can truly measure the rate of sweat in real time, which was tested and validated on human subjects. Our realization of the real-time sweat rate watch is capable of detecting sweat rates as low as 0.15 µL/min/cm², with an average error in accuracy of 18% compared to manual sweat rate readings.

  20. 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.

  1. Cognitive and physiological responses in humans exposed to a TETRA base station signal in relation to perceived electromagnetic hypersensitivity.

    PubMed

    Wallace, Denise; Eltiti, Stacy; Ridgewell, Anna; Garner, Kelly; Russo, Riccardo; Sepulveda, Francisco; Walker, Stuart; Quinlan, Terence; Dudley, Sandra; Maung, Sithu; Deeble, Roger; Fox, Elaine

    2012-01-01

    Terrestrial Trunked Radio (TETRA) technology ("Airwave") has led to public concern because of its potential interference with electrical activity in the brain. The present study is the first to examine whether acute exposure to a TETRA base station signal has an impact on cognitive functioning and physiological responses. Participants were exposed to a 420 MHz TETRA signal at a power flux density of 10 mW/m(2) as well as sham (no signal) under double-blind conditions. Fifty-one people who reported a perceived sensitivity to electromagnetic fields as well as 132 controls participated in a double-blind provocation study. Forty-eight sensitive and 132 control participants completed all three sessions. Measures of short-term memory, working memory, and attention were administered while physiological responses (blood volume pulse, heart rate, skin conductance) were monitored. After applying exclusion criteria based on task performance for each aforementioned cognitive measure, data were analyzed for 36, 43, and 48 sensitive participants for these respective tasks and, likewise, 107,125, and 129 controls. We observed no differences in cognitive performance between sham and TETRA exposure in either group; physiological response also did not differ between the exposure conditions. These findings are similar to previous double-blind studies with other mobile phone signals (900-2100 MHz), which could not establish any clear evidence that mobile phone signals affect health or cognitive function. Copyright © 2011 Wiley Periodicals, Inc.

  2. Use of Gifu Anaerobic Medium for culturing 32 dominant species of human gut microbes and its evaluation based on short-chain fatty acids fermentation profiles.

    PubMed

    Gotoh, Aina; Nara, Misaki; Sugiyama, Yuta; Sakanaka, Mikiyasu; Yachi, Hiroyuki; Kitakata, Aya; Nakagawa, Akira; Minami, Hiromichi; Okuda, Shujiro; Katoh, Toshihiko; Katayama, Takane; Kurihara, Shin

    2017-10-01

    Recently, a "human gut microbial gene catalogue," which ranks the dominance of microbe genus/species in human fecal samples, was published. Most of the bacteria ranked in the catalog are currently publicly available; however, the growth media recommended by the distributors vary among species, hampering physiological comparisons among the bacteria. To address this problem, we evaluated Gifu anaerobic medium (GAM) as a standard medium. Forty-four publicly available species of the top 56 species listed in the "human gut microbial gene catalogue" were cultured in GAM, and out of these, 32 (72%) were successfully cultured. Short-chain fatty acids from the bacterial culture supernatants were then quantified, and bacterial metabolic pathways were predicted based on in silico genomic sequence analysis. Our system provides a useful platform for assessing growth properties and analyzing metabolites of dominant human gut bacteria grown in GAM and supplemented with compounds of interest.

  3. The flaws and human harms of animal experimentation.

    PubMed

    Akhtar, Aysha

    2015-10-01

    Nonhuman animal ("animal") experimentation is typically defended by arguments that it is reliable, that animals provide sufficiently good models of human biology and diseases to yield relevant information, and that, consequently, its use provides major human health benefits. I demonstrate that a growing body of scientific literature critically assessing the validity of animal experimentation generally (and animal modeling specifically) raises important concerns about its reliability and predictive value for human outcomes and for understanding human physiology. The unreliability of animal experimentation across a wide range of areas undermines scientific arguments in favor of the practice. Additionally, I show how animal experimentation often significantly harms humans through misleading safety studies, potential abandonment of effective therapeutics, and direction of resources away from more effective testing methods. The resulting evidence suggests that the collective harms and costs to humans from animal experimentation outweigh potential benefits and that resources would be better invested in developing human-based testing methods.

  4. Procedures of Exercise Physiology Laboratories

    NASA Technical Reports Server (NTRS)

    Bishop, Phillip A.; Fortney, Suzanne; Greenisen, Michael; Siconolfi, Steven F.; Bamman, Marcas M.; Moore, Alan D., Jr.; Squires, William

    1998-01-01

    This manual describes the laboratory methods used to collect flight crew physiological performance data at the Johnson Space Center. The Exercise Countermeasures Project Laboratory is a standard physiology laboratory; only the application to the study of human physiological adaptations to spaceflight is unique. In the absence of any other recently published laboratory manual, this manual should be a useful document staffs and students of other laboratories.

  5. Human physiological responses to cold exposure: Acute responses and acclimatization to prolonged exposure.

    PubMed

    Castellani, John W; Young, Andrew J

    2016-04-01

    Cold exposure in humans causes specific acute and chronic physiological responses. This paper will review both the acute and long-term physiological responses and external factors that impact these physiological responses. Acute physiological responses to cold exposure include cutaneous vasoconstriction and shivering thermogenesis which, respectively, decrease heat loss and increase metabolic heat production. Vasoconstriction is elicited through reflex and local cooling. In combination, vasoconstriction and shivering operate to maintain thermal balance when the body is losing heat. Factors (anthropometry, sex, race, fitness, thermoregulatory fatigue) that influence the acute physiological responses to cold exposure are also reviewed. The physiological responses to chronic cold exposure, also known as cold acclimation/acclimatization, are also presented. Three primary patterns of cold acclimatization have been observed, a) habituation, b) metabolic adjustment, and c) insulative adjustment. Habituation is characterized by physiological adjustments in which the response is attenuated compared to an unacclimatized state. Metabolic acclimatization is characterized by an increased thermogenesis, whereas insulative acclimatization is characterized by enhancing the mechanisms that conserve body heat. The pattern of acclimatization is dependent on changes in skin and core temperature and the exposure duration. Published by Elsevier B.V.

  6. Translating ecology, physiology, biochemistry and molecular biology research to meet grand challenge of tick and tick-borne diseases in North America

    USDA-ARS?s Scientific Manuscript database

    Emerging and re-emerging tick-borne diseases threaten public health and the wellbeing of domestic animals and wildlife globally. The use of science-based technology to diminish the impact of tick-borne diseases should be an active research effort aimed to protect human and animal populations. Here, ...

  7. Macromolecular crowding meets oxygen tension in human mesenchymal stem cell culture - A step closer to physiologically relevant in vitro organogenesis

    NASA Astrophysics Data System (ADS)

    Cigognini, Daniela; Gaspar, Diana; Kumar, Pramod; Satyam, Abhigyan; Alagesan, Senthilkumar; Sanz-Nogués, Clara; Griffin, Matthew; O'Brien, Timothy; Pandit, Abhay; Zeugolis, Dimitrios I.

    2016-08-01

    Modular tissue engineering is based on the cells’ innate ability to create bottom-up supramolecular assemblies with efficiency and efficacy still unmatched by man-made devices. Although the regenerative potential of such tissue substitutes has been documented in preclinical and clinical setting, the prolonged culture time required to develop an implantable device is associated with phenotypic drift and/or cell senescence. Herein, we demonstrate that macromolecular crowding significantly enhances extracellular matrix deposition in human bone marrow mesenchymal stem cell culture at both 20% and 2% oxygen tension. Although hypoxia inducible factor - 1α was activated at 2% oxygen tension, increased extracellular matrix synthesis was not observed. The expression of surface markers and transcription factors was not affected as a function of oxygen tension and macromolecular crowding. The multilineage potential was also maintained, albeit adipogenic differentiation was significantly reduced in low oxygen tension cultures, chondrogenic differentiation was significantly increased in macromolecularly crowded cultures and osteogenic differentiation was not affected as a function of oxygen tension and macromolecular crowding. Collectively, these data pave the way for the development of bottom-up tissue equivalents based on physiologically relevant developmental processes.

  8. Macromolecular crowding meets oxygen tension in human mesenchymal stem cell culture - A step closer to physiologically relevant in vitro organogenesis

    PubMed Central

    Cigognini, Daniela; Gaspar, Diana; Kumar, Pramod; Satyam, Abhigyan; Alagesan, Senthilkumar; Sanz-Nogués, Clara; Griffin, Matthew; O’Brien, Timothy; Pandit, Abhay; Zeugolis, Dimitrios I.

    2016-01-01

    Modular tissue engineering is based on the cells’ innate ability to create bottom-up supramolecular assemblies with efficiency and efficacy still unmatched by man-made devices. Although the regenerative potential of such tissue substitutes has been documented in preclinical and clinical setting, the prolonged culture time required to develop an implantable device is associated with phenotypic drift and/or cell senescence. Herein, we demonstrate that macromolecular crowding significantly enhances extracellular matrix deposition in human bone marrow mesenchymal stem cell culture at both 20% and 2% oxygen tension. Although hypoxia inducible factor - 1α was activated at 2% oxygen tension, increased extracellular matrix synthesis was not observed. The expression of surface markers and transcription factors was not affected as a function of oxygen tension and macromolecular crowding. The multilineage potential was also maintained, albeit adipogenic differentiation was significantly reduced in low oxygen tension cultures, chondrogenic differentiation was significantly increased in macromolecularly crowded cultures and osteogenic differentiation was not affected as a function of oxygen tension and macromolecular crowding. Collectively, these data pave the way for the development of bottom-up tissue equivalents based on physiologically relevant developmental processes. PMID:27478033

  9. 21 CFR 882.1835 - Physiological signal amplifier.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Physiological signal amplifier. 882.1835 Section 882.1835 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1835 Physiological...

  10. 21 CFR 882.1845 - Physiological signal conditioner.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Physiological signal conditioner. 882.1845 Section 882.1845 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1845 Physiological...

  11. 21 CFR 882.1835 - Physiological signal amplifier.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Physiological signal amplifier. 882.1835 Section 882.1835 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1835 Physiological...

  12. 21 CFR 882.1845 - Physiological signal conditioner.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Physiological signal conditioner. 882.1845 Section 882.1845 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1845 Physiological...

  13. Teaching Materials and Methods.

    ERIC Educational Resources Information Center

    Physiologist, 1987

    1987-01-01

    Contains abstracts of presented papers which deal with teaching materials and methods in physiology. Includes papers on preconceptual notions in physiology, somatosensory activity recorded in the dorsal root ganglion of the bull frog, and the use of the Apple Macintosh microcomputer in teaching human anatomy and physiology. (TW)

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

    NASA Technical Reports Server (NTRS)

    White, R. J.

    1974-01-01

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

  15. Doing Peer Review and Receiving Feedback: Impact on Scientific Literacy and Writing Skills

    ERIC Educational Resources Information Center

    Geithner, Christina A.; Pollastro, Alexandria N.

    2016-01-01

    Doing peer review has been effectively implemented to help students develop critical reading and writing skills; however, its application in Human Physiology programs is limited. The purpose of the present study was to determine the impact of peer review on Human Physiology majors' perceptions of their scientific literacy and writing skills.…

  16. Emotion, Emotional Expression, and the Cognitive-Physiological Interaction: A Readout View.

    ERIC Educational Resources Information Center

    Buck, Ross

    A basic tenet of this paper is that, from the time of the ancient Greeks, Western thought has distinguished between rational processes unique to humans and the processes governing animal behavior. A model of motivation, emotion, and the cognitive/physiological interaction that can be applied to both animals and humans is presented. The special…

  17. Family Life and Human Development (Sex Education): The Prince George's County Public Schools Experience.

    ERIC Educational Resources Information Center

    Schaffer, Michael J.

    1981-01-01

    The Prince George's County schools' sex education program for grades K-12 was developed and implemented in the late 1960s and has three focus areas: family life and interpersonal relationships; the physiological and personality changes during puberty; and advanced physiology and psychology of human sexual behavior. The program augments what the…

  18. Physiological responses to prolonged bed rest in humans: A compendium of research, 1981-1988

    NASA Technical Reports Server (NTRS)

    Luu, Phuong B.; Ortiz, Vanessa; Barnes, Paul R.; Greenleaf, John E.

    1990-01-01

    Clinical observations and results form more basic studies that help to elucidate the physiological mechanisms of the adaptation of humans to prolonged bed rest. If the authors' abstract or summary was appropriate, it was included. In some cases a more detailed synopsis was provided under the subheadings of purpose, methods, results, and conclusions.

  19. Legacy of Biomedical Research During the Space Shuttle Program

    NASA Technical Reports Server (NTRS)

    Hayes, Judith C.

    2011-01-01

    The Space Shuttle Program provided many opportunities to study the role of spaceflight on human life for over 30 years and represented the longest and largest US human spaceflight program. Outcomes of the research were understanding the effect of spaceflight on human physiology and performance, countermeasures, operational protocols, and hardware. The Shuttle flights were relatively short, < 16 days and routinely had 4 to 6 crewmembers for a total of 135 flights. Biomedical research was conducted on the Space Shuttle using various vehicle resources. Specially constructed pressurized laboratories called Spacelab and SPACEHAB housed many laboratory instruments to accomplish experiments in the Shuttle s large payload bay. In addition to these laboratory flights, nearly every mission had dedicated human life science research experiments conducted in the Shuttle middeck. Most Shuttle astronauts participated in some life sciences research experiments either as test subjects or test operators. While middeck experiments resulted in a low sample per mission compared to many Earth-based studies, this participation allowed investigators to have repetition of tests over the years on successive Shuttle flights. In addition, as a prelude to the International Space Station (ISS), NASA used the Space Shuttle as a platform for assessing future ISS hardware systems and procedures. The purpose of this panel is to provide an understanding of science integration activities required to implement Shuttle research, review biomedical research, characterize countermeasures developed for Shuttle and ISS as well as discuss lessons learned that may support commercial crew endeavors. Panel topics include research integration, cardiovascular physiology, neurosciences, skeletal muscle, and exercise physiology. Learning Objective: The panel provides an overview from the Space Shuttle Program regarding research integration, scientific results, lessons learned from biomedical research and countermeasure development.

  20. Frequency of infant stroking reported by mothers moderates the effect of prenatal depression on infant behavioural and physiological outcomes.

    PubMed

    Sharp, Helen; Pickles, Andrew; Meaney, Michael; Marshall, Kate; Tibu, Florin; Hill, Jonathan

    2012-01-01

    Animal studies find that prenatal stress is associated with increased physiological and emotional reactivity later in life, mediated via fetal programming of the HPA axis through decreased glucocorticoid receptor (GR) gene expression. Post-natal behaviours, notably licking and grooming in rats, cause decreased behavioural indices of fear and reduced HPA axis reactivity mediated via increased GR gene expression. Post-natal maternal behaviours may therefore be expected to modify prenatal effects, but this has not previously been examined in humans. We examined whether, according to self-report, maternal stroking over the first weeks of life modified associations between prenatal depression and physiological and behavioral outcomes in infancy, hence mimicking effects of rodent licking and grooming. From a general population sample of 1233 first time mothers recruited at 20 weeks gestation we drew a stratified random sample of 316 for assessment at 32 weeks based on reported inter-partner psychological abuse, a risk to child development. Of these 271 provided data at 5, 9 and 29 weeks post delivery. Mothers reported how often they stroked their babies at 5 and 9 weeks. At 29 weeks vagal withdrawal to a stressor, a measure of physiological adaptability, and maternal reported negative emotionality were assessed. There was a significant interaction between prenatal depression and maternal stroking in the prediction of vagal reactivity to a stressor (p = .01), and maternal reports of infant anger proneness (p = .007) and fear (p = .043). Increasing maternal depression was associated with decreasing physiological adaptability, and with increasing negative emotionality, only in the presence of low maternal stroking. These initial findings in humans indicate that maternal stroking in infancy, as reported by mothers, has effects strongly resembling the effects of observed maternal behaviours in animals, pointing to future studies of the epigenetic, physiological and behavioral effects of maternal stroking.

  1. EEG-based alpha neurofeedback training for mood enhancement.

    PubMed

    Phneah, Swee Wu; Nisar, Humaira

    2017-06-01

    The aim of this paper is to develop a preliminary neurofeedback system to improve the mood of the subjects using audio signals by enhancing their alpha brainwaves. Assessment of the effect of music on the human subjects is performed using three methods; subjective assessment of mood with the help of a questionnaire, the effect on brain by analysing EEG signals, and the effect on body by physiological assessment. In this study, two experiments have been designed. The first experiment was to determine the short-term effect of music on soothing human subjects, whereas the second experiment was to determine its long-term effect. Two types of music were used in the first experiment, the favourite music selected by the participants and a relaxing music with alpha wave binaural beats. The research findings showed that the relaxing music has a better soothing effect on the participants psychologically and physiologically. However, the one-way analysis of variance (ANOVA) results showed that the short-term soothing effect of both favourite music and relaxing music was not significant in changing the mean alpha absolute power and mean physiological measures (blood pressure and heart rate) at the significance level of 0.05. The second experiment was somewhat similar to an alpha neurofeedback training whereby the participants trained their brains to produce more alpha brainwaves by listening to the relaxing music with alpha wave binaural beats for a duration of 30 min daily. The results showed that the relaxing music has a long-term psychological and physiological effect on soothing the participants, as can be observed from the increase in alpha power and decrease in physiological measures after each session of training. The training was found to be effective in increasing the alpha power significantly [F(2,12) = 11.5458 and p = 0.0016], but no significant reduction in physiological measures was observed at the significance level of 0.05.

  2. The saliva microbiome of Pan and Homo

    PubMed Central

    2013-01-01

    Background It is increasingly recognized that the bacteria that live in and on the human body (the microbiome) can play an important role in health and disease. The composition of the microbiome is potentially influenced by both internal factors (such as phylogeny and host physiology) and external factors (such as diet and local environment), and interspecific comparisons can aid in understanding the importance of these factors. Results To gain insights into the relative importance of these factors on saliva microbiome diversity, we here analyze the saliva microbiomes of chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) from two sanctuaries in Africa, and from human workers at each sanctuary. The saliva microbiomes of the two Pan species are more similar to one another, and the saliva microbiomes of the two human groups are more similar to one another, than are the saliva microbiomes of human workers and apes from the same sanctuary. We also looked for the existence of a core microbiome and find no evidence for a taxon-based core saliva microbiome for Homo or Pan. In addition, we studied the saliva microbiome from apes from the Leipzig Zoo, and found an extraordinary diversity in the zoo ape saliva microbiomes that is not found in the saliva microbiomes of the sanctuary animals. Conclusions The greater similarity of the saliva microbiomes of the two Pan species to one another, and of the two human groups to one another, are in accordance with both the phylogenetic relationships of the hosts as well as with host physiology. Moreover, the results from the zoo animals suggest that novel environments can have a large impact on the microbiome, and that microbiome analyses based on captive animals should be viewed with caution as they may not reflect the microbiome of animals in the wild. PMID:24025115

  3. Thermal Infrared Imaging-Based Computational Psychophysiology for Psychometrics.

    PubMed

    Cardone, Daniela; Pinti, Paola; Merla, Arcangelo

    2015-01-01

    Thermal infrared imaging has been proposed as a potential system for the computational assessment of human autonomic nervous activity and psychophysiological states in a contactless and noninvasive way. Through bioheat modeling of facial thermal imagery, several vital signs can be extracted, including localized blood perfusion, cardiac pulse, breath rate, and sudomotor response, since all these parameters impact the cutaneous temperature. The obtained physiological information could then be used to draw inferences about a variety of psychophysiological or affective states, as proved by the increasing number of psychophysiological studies using thermal infrared imaging. This paper presents therefore a review of the principal achievements of thermal infrared imaging in computational physiology with regard to its capability of monitoring psychophysiological activity.

  4. Regulation of the cellular and physiological effects of glutamine.

    PubMed

    Chwals, Walter J

    2004-10-01

    Glutamine is the most abundant amino acid in humans and possesses many functions in the body. It is the major transporter of amino-nitrogen between cells and an important fuel source for rapidly dividing cells such as cells of the immune and gastrointestinal systems. It is important in the synthesis of nucleic acids, glutathione, citrulline, arginine, gamma aminobutyric acid, and glucose. It is important for growth, gastrointestinal integrity, acid-base homeostasis, and optimal immune function. The regulation of glutamine levels in cells via glutaminase and glutamine synthetase is discussed. The cellular and physiologic effects of glutamine upon the central nervous system, gastrointestinal function, during metabolic support, and following tissue injury and critical illness is also discussed.

  5. Endogenous CO dynamics monitoring in breath by tunable diode laser

    NASA Astrophysics Data System (ADS)

    Kouznetsov, Andrian I.; Stepanov, Eugene V.; Shulagin, Yurii A.; Skrupskii, Vladimir A.

    1996-04-01

    High sensitive CO gas analyzer based on tunable diode laser (TDL) was used as a real time monitor of endogenous carbon monoxide in a set of breath physiology experiments. The measurements of the CO content dynamics in exhaled air with 10 ppb sensitivity were attended with detection of carbon dioxide and O2 in breath, lung ventilation parameters, heart rate and blood analysis using conventional techniques. Variations of endogenous CO in human breath caused by hyperoxia, hypoxia, hyperventilation as well as sport loading were studied in real time. Scattering of the CO variation time constants was observed for different tested persons. Possible reasons for this scattering related with the organisms' physiology peculiarities are discussed.

  6. Bioengineering an electro-mechanically functional miniature ventricular heart chamber from human pluripotent stem cells.

    PubMed

    Li, Ronald A; Keung, Wendy; Cashman, Timothy J; Backeris, Peter C; Johnson, Bryce V; Bardot, Evan S; Wong, Andy O T; Chan, Patrick K W; Chan, Camie W Y; Costa, Kevin D

    2018-05-01

    Tissue engineers and stem cell biologists have made exciting progress toward creating simplified models of human heart muscles or aligned monolayers to help bridge a longstanding gap between experimental animals and clinical trials. However, no existing human in vitro systems provide the direct measures of cardiac performance as a pump. Here, we developed a next-generation in vitro biomimetic model of pumping human heart chamber, and demonstrated its capability for pharmaceutical testing. From human pluripotent stem cell (hPSC)-derived ventricular cardiomyocytes (hvCM) embedded in collagen-based extracellular matrix hydrogel, we engineered a three-dimensional (3D) electro-mechanically coupled, fluid-ejecting miniature human ventricle-like cardiac organoid chamber (hvCOC). Structural characterization showed organized sarcomeres with myofibrillar microstructures. Transcript and RNA-seq analyses revealed upregulation of key Ca 2+ -handling, ion channel, and cardiac-specific proteins in hvCOC compared to lower-order 2D and 3D cultures of the same constituent cells. Clinically-important, physiologically complex contractile parameters such as ejection fraction, developed pressure, and stroke work, as well as electrophysiological properties including action potential and conduction velocity were measured: hvCOC displayed key molecular and physiological characteristics of the native ventricle, and showed expected mechanical and electrophysiological responses to a range of pharmacological interventions (including positive and negative inotropes). We conclude that such "human-heart-in-a-jar" technology could facilitate the drug discovery process by providing human-specific preclinical data during early stage drug development. Copyright © 2018. Published by Elsevier Ltd.

  7. Research of pulse signal processing based on sleep-monitoring alarm system

    NASA Astrophysics Data System (ADS)

    Zhang, Kaisheng; Zeng, Yuan

    2009-07-01

    From pulse diagnosis of Chinese herbalist doctor to the research of cardiovascular system by modem iatrology,they all have showed and proved that human pulse has a good affinity with diseases,especially cardiovascular diseases. Human pulse contains much physical information, and it will be propitious to know the human healthy state early so as to get therapy and recovery early when pulse signal is often detected and analyzed. study how to use the embedded microcontroller to transmit physiological signal from human to personal computer by infrared communication, and the normal sphygmic parameter in one's sleeping is compared with the one measured in order to judge whether one's sleeping condition is normal, finally ascertain the best control plan.

  8. Evolutionary history of human disease genes reveals phenotypic connections and comorbidity among genetic diseases

    NASA Astrophysics Data System (ADS)

    Park, Solip; Yang, Jae-Seong; Kim, Jinho; Shin, Young-Eun; Hwang, Jihye; Park, Juyong; Jang, Sung Key; Kim, Sanguk

    2012-10-01

    The extent to which evolutionary changes have impacted the phenotypic relationships among human diseases remains unclear. In this work, we report that phenotypically similar diseases are connected by the evolutionary constraints on human disease genes. Human disease groups can be classified into slowly or rapidly evolving classes, where the diseases in the slowly evolving class are enriched with morphological phenotypes and those in the rapidly evolving class are enriched with physiological phenotypes. Our findings establish a clear evolutionary connection between disease classes and disease phenotypes for the first time. Furthermore, the high comorbidity found between diseases connected by similar evolutionary constraints enables us to improve the predictability of the relative risk of human diseases. We find the evolutionary constraints on disease genes are a new layer of molecular connection in the network-based exploration of human diseases.

  9. Characterization of human pineal gland proteome.

    PubMed

    Yelamanchi, Soujanya D; Kumar, Manish; Madugundu, Anil K; Gopalakrishnan, Lathika; Dey, Gourav; Chavan, Sandip; Sathe, Gajanan; Mathur, Premendu P; Gowda, Harsha; Mahadevan, Anita; Shankar, Susarla K; Prasad, T S Keshava

    2016-11-15

    The pineal gland is a neuroendocrine gland located at the center of the brain. It is known to regulate various physiological functions in the body through secretion of the neurohormone melatonin. Comprehensive characterization of the human pineal gland proteome has not been undertaken to date. We employed a high-resolution mass spectrometry-based approach to characterize the proteome of the human pineal gland. A total of 5874 proteins were identified from the human pineal gland in this study. Of these, 5820 proteins were identified from the human pineal gland for the first time. Interestingly, 1136 proteins from the human pineal gland were found to contain a signal peptide domain, which indicates the secretory nature of these proteins. An unbiased global proteomic profile of this biomedically important organ should benefit molecular research to unravel the role of the pineal gland in neuropsychiatric and neurodegenerative diseases.

  10. Evolutionary history of human disease genes reveals phenotypic connections and comorbidity among genetic diseases.

    PubMed

    Park, Solip; Yang, Jae-Seong; Kim, Jinho; Shin, Young-Eun; Hwang, Jihye; Park, Juyong; Jang, Sung Key; Kim, Sanguk

    2012-01-01

    The extent to which evolutionary changes have impacted the phenotypic relationships among human diseases remains unclear. In this work, we report that phenotypically similar diseases are connected by the evolutionary constraints on human disease genes. Human disease groups can be classified into slowly or rapidly evolving classes, where the diseases in the slowly evolving class are enriched with morphological phenotypes and those in the rapidly evolving class are enriched with physiological phenotypes. Our findings establish a clear evolutionary connection between disease classes and disease phenotypes for the first time. Furthermore, the high comorbidity found between diseases connected by similar evolutionary constraints enables us to improve the predictability of the relative risk of human diseases. We find the evolutionary constraints on disease genes are a new layer of molecular connection in the network-based exploration of human diseases.

  11. A microfluidically perfused three dimensional human liver model.

    PubMed

    Rennert, Knut; Steinborn, Sandra; Gröger, Marko; Ungerböck, Birgit; Jank, Anne-Marie; Ehgartner, Josef; Nietzsche, Sandor; Dinger, Julia; Kiehntopf, Michael; Funke, Harald; Peters, Frank T; Lupp, Amelie; Gärtner, Claudia; Mayr, Torsten; Bauer, Michael; Huber, Otmar; Mosig, Alexander S

    2015-12-01

    Within the liver, non-parenchymal cells (NPCs) are critically involved in the regulation of hepatocyte polarization and maintenance of metabolic function. We here report the establishment of a liver organoid that integrates NPCs in a vascular layer composed of endothelial cells and tissue macrophages and a hepatic layer comprising stellate cells co-cultured with hepatocytes. The three-dimensional liver organoid is embedded in a microfluidically perfused biochip that enables sufficient nutrition supply and resembles morphological aspects of the human liver sinusoid. It utilizes a suspended membrane as a cell substrate mimicking the space of Disse. Luminescence-based sensor spots were integrated into the chip to allow online measurement of cellular oxygen consumption. Application of microfluidic flow induces defined expression of ZO-1, transferrin, ASGPR-1 along with an increased expression of MRP-2 transporter protein within the liver organoids. Moreover, perfusion was accompanied by an increased hepatobiliary secretion of 5(6)-carboxy-2',7'-dichlorofluorescein and an enhanced formation of hepatocyte microvilli. From this we conclude that the perfused liver organoid shares relevant morphological and functional characteristics with the human liver and represents a new in vitro research tool to study human hepatocellular physiology at the cellular level under conditions close to the physiological situation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Flight physiology training experiences and perspectives: survey of 117 pilots.

    PubMed

    Patrão, Luís; Zorro, Sara; Silva, Jorge; Castelo-Branco, Miguel; Ribeiro, João

    2013-06-01

    Human factors and awareness of flight physiology play a crucial role in flight safety. Even so, international legislation is vague relative to training requirements in hypoxia and altitude physiology. Based on a previously developed survey, an adapted questionnaire was formulated and released online for Portuguese pilots. Specific questions regarding the need for pilot attention monitoring systems were added to the original survey. There were 117 pilots, 2 of whom were women, who completed the survey. Most of the pilots had a light aviation license and flew in unpressurized cabins at a maximum ceiling of 10,000 ft (3048 m). The majority of the respondents never experienced hypoxic symptoms. In general, most of the individuals agreed with the importance of an introductory hypoxia course without altitude chamber training (ACT) for all pilot populations, and with a pilot monitoring system in order to increase flight safety. Generally, most of the pilots felt that hypoxia education and training for unpressurized aircraft is not extensive enough. However, almost all the respondents were willing to use a flight physiology monitoring system in order to improve flight safety.

  13. Molecular and physiological manifestations and measurement of aging in humans.

    PubMed

    Khan, Sadiya S; Singer, Benjamin D; Vaughan, Douglas E

    2017-08-01

    Biological aging is associated with a reduction in the reparative and regenerative potential in tissues and organs. This reduction manifests as a decreased physiological reserve in response to stress (termed homeostenosis) and a time-dependent failure of complex molecular mechanisms that cumulatively create disorder. Aging inevitably occurs with time in all organisms and emerges on a molecular, cellular, organ, and organismal level with genetic, epigenetic, and environmental modulators. Individuals with the same chronological age exhibit differential trajectories of age-related decline, and it follows that we should assess biological age distinctly from chronological age. In this review, we outline mechanisms of aging with attention to well-described molecular and cellular hallmarks and discuss physiological changes of aging at the organ-system level. We suggest methods to measure aging with attention to both molecular biology (e.g., telomere length and epigenetic marks) and physiological function (e.g., lung function and echocardiographic measurements). Finally, we propose a framework to integrate these molecular and physiological data into a composite score that measures biological aging in humans. Understanding the molecular and physiological phenomena that drive the complex and multifactorial processes underlying the variable pace of biological aging in humans will inform how researchers assess and investigate health and disease over the life course. This composite biological age score could be of use to researchers seeking to characterize normal, accelerated, and exceptionally successful aging as well as to assess the effect of interventions aimed at modulating human aging. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  14. Assessment and effects of Therapeutic Patient Education for patients in hemodialysis: a systematic review.

    PubMed

    Idier, Laëtitia; Untas, Aurélie; Koleck, Michèle; Chauveau, Philippe; Rascle, Nicole

    2011-12-01

    This review examined the impact of Therapeutic Patient Education (TPE) programs in hemodialysis and the assessment of these programs. REVIEW METHODS AND DATA SOURCES: A systematic review was performed. Bibliographical research was done with a database in the social and human sciences (PsychINFO, PsycARTICLES, SocINDEX with Full Text and the Psychology and Behavioural Sciences Collection). References were also searched in several reviews specialized in nephrology-dialysis and in patient education. Articles were classified according three different outcomes: (1) physiological outcomes, (2) psychosocial outcomes, (3) or combined criteria. 35 articles were selected. The majority dealt with purely physiological outcomes (18) and the minority concerned only psychosocial outcomes (4). Fifteen articles discussed both physiological and psychosocial outcomes, i.e. combined criteria. Beneficial effects were shown such as improvements in knowledge, adherence and quality of life. Most educational interventions were performed by nurses. This systematic review found that educational programs in dialysis have become more numerous and efficient, with a prevalence of assessment based on physiological outcomes. TPE is a global management method based on both the physiological and the psychological well-being of the patient. Studies that take into account both physiological and psychosocial variables are very useful for understanding the effects of TPE programs on dialysis patients. The review shows that nurses play an important role in TPE and that they require varied communicational, educational, animation and assessment skills. These positive effects are encouraging for nurses to stimulate the development of TPE programs for dialysis patients in their multidisciplinary teams. The nurse's role is important for the commitment of each health caregiver (nurse, physician, dietician, pharmacist, psychologist, etc.) for the global management of patients in the TPE process. 2011 Elsevier Ltd. All rights reserved.

  15. Dunbar's number: group size and brain physiology in humans reexamined.

    PubMed

    de Ruiter, Jan; Weston, Gavin; Lyon, Stephen M

    2011-01-01

    Popular academic ideas linking physiological adaptations to social behaviors are spreading disconcertingly into wider societal contexts. In this article, we note our skepticism with one particularly popular—in our view, problematic—supposed causal correlation between neocortex size and social group size. The resulting Dunbar's Number, as it has come to be called, has been statistically tested against observed group size in different primate species. Although there may be reason to doubt the Dunbar's Number hypothesis among nonhuman primate species, we restrict ourselves here to the application of such an explanatory hypothesis to human, culture-manipulating populations. Human information process management, we argue, cannot be understood as a simple product of brain physiology. Cross-cultural comparison of not only group size but also relationship-reckoning systems like kinship terminologies suggests that although neocortices are undoubtedly crucial to human behavior, they cannot be given such primacy in explaining complex group composition, formation, or management.

  16. Interviewing Suspects with Avatars: Avatars Are More Effective When Perceived as Human

    PubMed Central

    Ströfer, Sabine; Ufkes, Elze G.; Bruijnes, Merijn; Giebels, Ellen; Noordzij, Matthijs L.

    2016-01-01

    It has been consistently demonstrated that deceivers generally can be discriminated from truth tellers by monitoring an increase in their physiological response. But is this still the case when deceivers interact with a virtual avatar? The present research investigated whether the mere “belief” that the virtual avatar is computer or human operated forms a crucial factor for eliciting physiological cues to deception. Participants were interviewed about a transgression they had been seduced to commit, by a human-like virtual avatar. In a between-subject design, participants either deceived or told the truth about this transgression. During the interviews, we measured the physiological responses assessing participants' electrodermal activity (EDA). In line with our hypothesis, EDA differences between deceivers and truth tellers only were significant for participants who believed they interacted with a human operated (compared to a computer operated) avatar. These results have theoretical as well as practical implications which we will discuss. PMID:27148150

  17. UTCI—Why another thermal index?

    NASA Astrophysics Data System (ADS)

    Jendritzky, Gerd; de Dear, Richard; Havenith, George

    2012-05-01

    Existing procedures for the assessment of the thermal environment in the fields of public weather services, public health systems, precautionary planning, urban design, tourism and recreation and climate impact research exhibit significant shortcomings. This is most evident for simple (mostly two-parameter) indices, when comparing them to complete heat budget models developed since the 1960s. ISB Commission 6 took up the idea of developing a Universal Thermal Climate Index (UTCI) based on the most advanced multi-node model of thermoregulation representing progress in science within the last three to four decades, both in thermo-physiological and heat exchange theory. Creating the essential research synergies for the development of UTCI required pooling the resources of multidisciplinary experts in the fields of thermal physiology, mathematical modelling, occupational medicine, meteorological data handling (in particular radiation modelling) and application development in a network. It was possible to extend the expertise of ISB Commission 6 substantially by COST (a European programme promoting Cooperation in Science and Technology) Action 730 so that finally over 45 scientists from 23 countries (Australia, Canada, Israel, several Europe countries, New Zealand, and the United States) worked together. The work was performed under the umbrella of the WMO Commission on Climatology (CCl). After extensive evaluations, Fiala's multi-node human physiology and thermal comfort model (FPC) was adopted for this study. The model was validated extensively, applying as yet unused data from other research groups, and extended for the purposes of the project. This model was coupled with a state-of-the-art clothing model taking into consideration behavioural adaptation of clothing insulation by the general urban population in response to actual environmental temperature. UTCI was then derived conceptually as an equivalent temperature (ET). Thus, for any combination of air temperature, wind, radiation, and humidity (stress), UTCI is defined as the isothermal air temperature of the reference condition that would elicit the same dynamic response (strain) of the physiological model. As UTCI is based on contemporary science its use will standardise applications in the major fields of human biometeorology, thus making research results comparable and physiologically relevant.

  18. Evaluation of the effects of East Indian sandalwood oil and alpha-santalol on humans after transdermal absorption.

    PubMed

    Hongratanaworakit, T; Heuberger, E; Buchbauer, G

    2004-01-01

    The aim of the study was to investigate the effects of East Indian sandalwood oil ( Santalum album, Santalaceae) and alpha-santalol on physiological parameters as well as on mental and emotional conditions in healthy human subjects after transdermal absorption. In order to exclude any olfactory stimulation, the inhalation of the fragrances was prevented by breathing masks. Eight physiological parameters, i. e., blood oxygen saturation, blood pressure, breathing rate, eye-blink rate, pulse rate, skin conductance, skin temperature, and surface electromyogram were recorded. Subjective mental and emotional condition was assessed by means of rating scales. While alpha-santalol caused significant physiological changes which are interpreted in terms of a relaxing/sedative effect, sandalwood oil provoked physiological deactivation but behavioral activation. These findings are likely to represent an uncoupling of physiological and behavioral arousal processes by sandalwood oil.

  19. Vernacularizing the Body: Informational Egalitarianism, Hindu Divine Design, and Race in Physiology Schoolbooks, Bengal 1859-1877.

    PubMed

    Mukharji, Projit Bihari

    2017-01-01

    Government-aided vernacular schools introduced "human physiology" as a subject in 1859. I use the first couple of schoolbooks and the debate running up to the introduction of the subject to open up the particular and specific histories through which modern anatomo-physiological knowledge was vernacularized in colonial Bengal. In so doing I have two interconnected goals in this article. My first goal is to analyze the precocious decision to teach human physiology to colonial schoolboys, at a time when this was the norm neither in Great Britain nor indeed in traditional Bengali schools. My second goal is to use this case to further develop "vernacularization" as a conceptual tool. In pursuing these twin objectives, I simultaneously hope to move the debate on modern anatomo-physiological knowledge in South Asia away from the level of epistemic superiority and onto-politics to the level of concrete historical particularities.

  20. Application of physiologically based absorption modeling to formulation development of a low solubility, low permeability weak base: mechanistic investigation of food effect.

    PubMed

    Zhang, Hefei; Xia, Binfeng; Sheng, Jennifer; Heimbach, Tycho; Lin, Tsu-Han; He, Handan; Wang, Yanfeng; Novick, Steven; Comfort, Ann

    2014-04-01

    Physiologically based pharmacokinetic (PBPK) modeling has been broadly used to facilitate drug development, hereby we developed a PBPK model to systematically investigate the underlying mechanisms of the observed positive food effect of compound X (cpd X) and to strategically explore the feasible approaches to mitigate the food effect. Cpd X is a weak base with pH-dependent solubility; the compound displays significant and dose-dependent food effect in humans, leading to a nonadherence of drug administration. A GastroPlus Opt logD Model was selected for pharmacokinetic simulation under both fasted and fed conditions, where the biopharmaceutic parameters (e.g., solubility and permeability) for cpd X were determined in vitro, and human pharmacokinetic disposition properties were predicted from preclinical data and then optimized with clinical pharmacokinetic data. A parameter sensitivity analysis was performed to evaluate the effect of particle size on the cpd X absorption. A PBPK model was successfully developed for cpd X; its pharmacokinetic parameters (e.g., C max, AUCinf, and t max) predicted at different oral doses were within ±25% of the observed mean values. The in vivo solubility (in duodenum) and mean precipitation time under fed conditions were estimated to be 7.4- and 3.4-fold higher than those under fasted conditions, respectively. The PBPK modeling analysis provided a reasonable explanation for the underlying mechanism for the observed positive food effect of the cpd X in humans. Oral absorption of the cpd X can be increased by reducing the particle size (<100 nm) of an active pharmaceutical ingredient under fasted conditions and therefore, reduce the cpd X food effect correspondingly.

  1. A physiologically based pharmacokinetic model for ionic silver and silver nanoparticles

    PubMed Central

    Bachler, Gerald; von Goetz, Natalie; Hungerbühler, Konrad

    2013-01-01

    Silver is a strong antibiotic that is increasingly incorporated into consumer products as a bulk, salt, or nanosilver, thus potentially causing side-effects related to human exposure. However, the fate and behavior of (nano)silver in the human body is presently not well understood. In order to aggregate the existing experimental information, a physiologically based pharmacokinetic model (PBPK) was developed in this study for ionic silver and nanosilver. The structure of the model was established on the basis of toxicokinetic data from intravenous studies. The number of calibrated parameters was minimized in order to enhance the predictive capability of the model. We validated the model structure for both silver forms by reproducing exposure conditions (dermal, oral, and inhalation) of in vivo experiments and comparing simulated and experimentally assessed organ concentrations. Therefore, the percutaneous, intestinal, or pulmonary absorption fraction was estimated based on the blood silver concentration of the respective experimental data set. In all of the cases examined, the model could successfully predict the biodistribution of ionic silver and 15–150 nm silver nanoparticles, which were not coated with substances designed to prolong the circulatory time (eg, polyethylene glycol). Furthermore, the results of our model indicate that: (1) within the application domain of our model, the particle size and coating had a minor influence on the biodistribution; (2) in vivo, it is more likely that silver nanoparticles are directly stored as insoluble salt particles than dissolve into Ag+; and (3) compartments of the mononuclear phagocytic system play a minor role in exposure levels that are relevant for human consumers. We also give an example of how the model can be used in exposure and risk assessments based on five different exposure scenarios, namely dietary intake, use of three separate consumer products, and occupational exposure. PMID:24039420

  2. L-type Ca2+ channels in mood, cognition and addiction: integrating human and rodent studies with a focus on behavioural endophenotypes.

    PubMed

    Kabir, Z D; Lee, A S; Rajadhyaksha, A M

    2016-10-15

    Brain Ca v 1.2 and Ca v 1.3 L-type Ca 2+ channels play key physiological roles in various neuronal processes that contribute to brain function. Genetic studies have recently identified CACNA1C as a candidate risk gene for bipolar disorder (BD), schizophrenia (SCZ), major depressive disorder (MDD) and autism spectrum disorder (ASD), and CACNA1D for BD and ASD, suggesting a contribution of Ca v 1.2 and Ca v 1.3 Ca 2+ signalling to the pathophysiology of neuropsychiatric disorders. Once considered sole clinical entities, it is now clear that BD, SCZ, MDD and ASD share common phenotypic features, most likely due to overlapping neurocircuitry and common molecular mechanisms. A major future challenge lies in translating the human genetic findings to pathological mechanisms that are translatable back to the patient. One approach for tackling such a daunting scientific endeavour for complex behaviour-based neuropsychiatric disorders is to examine intermediate biological phenotypes in the context of endophenotypes within distinct behavioural domains. This will better allow us to integrate findings from genes to behaviour across species, and improve the chances of translating preclinical findings to clinical practice. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  3. Academic performance in human anatomy and physiology classes: a 2-yr study of academic motivation and grade expectation.

    PubMed

    Sturges, Diana; Maurer, Trent W; Allen, Deborah; Gatch, Delena Bell; Shankar, Padmini

    2016-03-01

    This project used a nonexperimental design with a convenience sample and studied the relationship between academic motivation, grade expectation, and academic performance in 1,210 students enrolled in undergraduate human anatomy and physiology (HAP) classes over a 2-yr period. A 42-item survey that included 28 items of the adapted academic motivation scale for HAP based on self-determination theory was administered in class during the first 3 wk of each semester. Students with higher grade point averages, who studied for longer hours and reported to be more motivated to succeed, did better academically in these classes. There was a significant relationship between students' scores on the adapted academic motivation scale and performance. Students were more extrinsically motivated to succeed in HAP courses than intrinsically motivated to succeed, and the analyses revealed that the most significant predictor of final grade was within the extrinsic scale (introjected and external types). Students' motivations remained stable throughout the course sequence. The data showed a significant relationship between HAP students' expected grade and their final grade in class. Finally, 65.5% of students overestimated their final grade, with 29% of students overestimating by two to four letter grades. Copyright © 2016 The American Physiological Society.

  4. Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome.

    PubMed

    Liu, Guang-Hui; Barkho, Basam Z; Ruiz, Sergio; Diep, Dinh; Qu, Jing; Yang, Sheng-Lian; Panopoulos, Athanasia D; Suzuki, Keiichiro; Kurian, Leo; Walsh, Christopher; Thompson, James; Boue, Stephanie; Fung, Ho Lim; Sancho-Martinez, Ignacio; Zhang, Kun; Yates, John; Izpisua Belmonte, Juan Carlos

    2011-04-14

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature ageing disease, characterized by premature arteriosclerosis and degeneration of vascular smooth muscle cells (SMCs). HGPS is caused by a single point mutation in the lamin A (LMNA) gene, resulting in the generation of progerin, a truncated splicing mutant of lamin A. Accumulation of progerin leads to various ageing-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature ageing. Upon differentiation of HGPS-iPSCs, progerin and its ageing-associated phenotypic consequences are restored. Specifically, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescence phenotypes associated with vascular ageing. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs, also known as PRKDC) as a downstream target of progerin. The absence of nuclear DNAPK holoenzyme correlates with premature as well as physiological ageing. Because progerin also accumulates during physiological ageing, our results provide an in vitro iPSC-based model to study the pathogenesis of human premature and physiological vascular ageing.

  5. Feeding behavior, obesity, and neuroeconomics⋆

    PubMed Central

    Rowland, Neil E.; Vaughan, Cheryl H.; Mathes, Clare M.; Mitra, Anaya

    2008-01-01

    For the past 50 years, the most prevalent theoretical models for regulation of food intake have been based in the physiological concept of energy homeostasis. However, several authors have noted that the simplest form of homeostasis, stability, does not accurately reflect the actual state of affairs and most notably the recent upward trend in body mass index observed in the majority of affluent nations. The present review argues that processes of natural selection have more likely made us first and foremost behavioral opportunists that are adapted to uncertain environments, and that physiological homeostasis is subservient to that reality. Examples are presented from a variety of laboratory studies indicating that food intake is a function of the effort and/or time required to procure that food, and that economic decision making is central to understanding how much and when organisms eat. The discipline of behavioral economics has developed concepts that are useful for this enterprise, and some of these are presented. Lastly, we present demonstrations in which genetic or physiologic investigations using environmental complexity will lead to more realistic ideas about how to understand and treat idiopathic human obesity. The fact is that humans are eating more and gaining weight in favorable food environments in exactly the way predicted from some of these models, and this has implications for the appropriate way to treat obesity. PMID:17825853

  6. Percutaneous Creation of a Central Iliac Arteriovenous Anastomosis for the Treatment of Arterial Hypertension.

    PubMed

    Bertog, Stefan C; Sobotka, Nathan A; Sobotka, Paul A; Lobo, Melvin D; Sievert, Kolja; Vaskelyte, Laura; Sievert, Horst; Schmieder, Roland E

    2018-03-19

    Provision of a summary on the physiologic effects of arteriovenous fistula creation and description of previously published human data on the efficacy of a percutaneously implanted device creating an arteriovenous fistula. Though antihypertensive therapy is effective, some patient's blood pressure remains poorly controlled despite adherence to optimal medical therapy. Moreover, some patients are not compliant with recommended medical therapy due to side effects or personal decision. This has prompted exploration of alternative, device-based antihypertensive therapies including, among others, the percutaneous creation of an arteriovenous fistula. An arteriovenous fistula is accompanied by a number of favorable physiologic changes that may lower blood pressure. These physiologic changes, conduction of the procedure, and previously published human experience are summarized in this review article. The results of a recently published trial comparing arteriovenous fistula creation and standard antihypertensive therapy versus standard antihypertensive therapy alone are summarized. Creation of an arteriovenous fistula is accompanied by a significant blood pressure reduction likely related to a reduction in total arterial resistance, perhaps blood volume reduction, inhibition of the baroreceptor reflex, and release of natriuretic peptides. These findings foster further interest in studying the impact of an arteriovenous fistula and arterial blood pressure. The design of a large randomized trial comparing arteriovenous fistula creation to sham control is outlined.

  7. Synthesis of nitric oxide in human osteoblasts in response to physiologic stimulation of electrotherapy.

    PubMed

    Hamed, Ayman; Kim, Paul; Cho, Michael

    2006-12-01

    Electrotherapy for bone healing, remodeling and wound healing may be mediated by modulation of nitric oxide (NO). Using NO-specific fluorophore (DAF-2), we report here that application of non-invasive, physiologic electrical stimulation induces NO synthesis in human osteoblasts, and that such NO generation is comparable to that induced by estrogen treatment. For example, application of a sinusoidal 1 Hz, 2 V/cm (peak to peak) electrical stimulation (ES) increases NO-bound DAF-2 fluorescence intensity by a 2-fold within 60 min exposure by activating nitric oxide synthase (NOS). Increase in the NO level is found to depend critically on the frequency and strength of ES. While the frequency of 1 Hz ES seems optimal, the ES strength >0.5 V/cm is required to induce significant NO increase, however. Nitric oxide synthesis in response to ES is completely prevented by blocking estrogen receptors using a competitive inhibitor, suggesting that NO generation is likely initiated by activation of estrogen receptors at the cell surface. Based on these findings, physiologic stimulation of electrotherapy appears to represent a potential non-invasive, non-genomic, and novel physical technique that could be used to regulate NO-mediated bone density and facilitate bone remodeling without adverse effects associated with hormone therapy.

  8. Astronaut health monitoring

    NASA Astrophysics Data System (ADS)

    Inscore, Frank; Shende, Chetan; Gift, Alan; Maksymiuk, Paul; Farquharson, Stuart

    2006-10-01

    Extended weightlessness causes numerous deleterious changes in human physiology, including space motion sickness, cephalad fluid shifts, reduced immune response, and breakdown of muscle tissue with subsequent loss of bone mass and formation of renal stones. Furthermore, these physiological changes also influence the metabolism of drugs used by astronauts to minimize these deleterious effects. Unfortunately, the changes in human physiology in space are also reflected in drug metabolism, and current pre-flight analyses designed to set dosage are inadequate. Furthermore, current earth-based analytical laboratory methods that employ liquid or gas chromatography for separation and fluorescence or mass spectrometry for trace detection are labor intensive, slow, massive, and not cost-effective for operation in space. In an effort to overcome these instrument limitations we have been developing a sampling device to both separate these drugs and metabolites from urine, and generate surface-enhanced Raman (SER) spectra. The detailed molecular vibrational information afforded by Raman scattering allows chemical identification, while the surface-enhancement increases sensitivity by six or more orders of magnitude and allows detection of nanogram per milliliter concentrations. Generally no more than 1 milliliter of sample is required and complete analysis can be performed in 5 minutes using a portable, light-weight Raman spectrometer. Here we present the SER analysis of several drugs used by astronauts measured in synthetic urine and reconstituted urine.

  9. Effect of water flow and chemical environment on microbiota growth and composition in the human colon.

    PubMed

    Cremer, Jonas; Arnoldini, Markus; Hwa, Terence

    2017-06-20

    The human gut harbors a dynamic microbial community whose composition bears great importance for the health of the host. Here, we investigate how colonic physiology impacts bacterial growth, which ultimately dictates microbiota composition. Combining measurements of bacterial physiology with analysis of published data on human physiology into a quantitative, comprehensive modeling framework, we show how water flow in the colon, in concert with other physiological factors, determine the abundances of the major bacterial phyla. Mechanistically, our model shows that local pH values in the lumen, which differentially affect the growth of different bacteria, drive changes in microbiota composition. It identifies key factors influencing the delicate regulation of colonic pH, including epithelial water absorption, nutrient inflow, and luminal buffering capacity, and generates testable predictions on their effects. Our findings show that a predictive and mechanistic understanding of microbial ecology in the gut is possible. Such predictive understanding is needed for the rational design of intervention strategies to actively control the microbiota.

  10. Klismaphilia--a physiological perspective.

    PubMed

    Agnew, J

    1982-10-01

    Dr. Joanne Denko coined the work klismaphilia to describe the practices of some of her patients who enjoyed the use of enemas as a sexual stimulant. Since then questions occasionally appear in the professional literature asking about the relationship between enemas and sexual pleasure. This paper considers some of the physiological aspects of the human sexual apparatus that relate to anal sensitivity and explores why klismaphilia can be sexually grafifying. The paper starts with a discussion of the physiological basis for anal sensitivity and anal masturbation in both the human male and the human female. The paper then goes on to relate all this to the sexual sensations received from an enema, and discusses the similarities and differences between all these types of stimulation. Some of the psychological aspects of klismaphilia are also considered in relationship to the physiology involved. The paper concludes with a brief discussion of masked anal masturbation among the population at large. A comprehensive list of references from the literature is given to support these findings.

  11. Psychological and physiological human responses to simulated and real environments: A comparison between Photographs, 360° Panoramas, and Virtual Reality.

    PubMed

    Higuera-Trujillo, Juan Luis; López-Tarruella Maldonado, Juan; Llinares Millán, Carmen

    2017-11-01

    Psychological research into human factors frequently uses simulations to study the relationship between human behaviour and the environment. Their validity depends on their similarity with the physical environments. This paper aims to validate three environmental-simulation display formats: photographs, 360° panoramas, and virtual reality. To do this we compared the psychological and physiological responses evoked by simulated environments set-ups to those from a physical environment setup; we also assessed the users' sense of presence. Analysis show that 360° panoramas offer the closest to reality results according to the participants' psychological responses, and virtual reality according to the physiological responses. Correlations between the feeling of presence and physiological and other psychological responses were also observed. These results may be of interest to researchers using environmental-simulation technologies currently available in order to replicate the experience of physical environments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Effect of water flow and chemical environment on microbiota growth and composition in the human colon

    PubMed Central

    Cremer, Jonas; Arnoldini, Markus; Hwa, Terence

    2017-01-01

    The human gut harbors a dynamic microbial community whose composition bears great importance for the health of the host. Here, we investigate how colonic physiology impacts bacterial growth, which ultimately dictates microbiota composition. Combining measurements of bacterial physiology with analysis of published data on human physiology into a quantitative, comprehensive modeling framework, we show how water flow in the colon, in concert with other physiological factors, determine the abundances of the major bacterial phyla. Mechanistically, our model shows that local pH values in the lumen, which differentially affect the growth of different bacteria, drive changes in microbiota composition. It identifies key factors influencing the delicate regulation of colonic pH, including epithelial water absorption, nutrient inflow, and luminal buffering capacity, and generates testable predictions on their effects. Our findings show that a predictive and mechanistic understanding of microbial ecology in the gut is possible. Such predictive understanding is needed for the rational design of intervention strategies to actively control the microbiota. PMID:28588144

  13. NT3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury.

    PubMed

    Rao, Jia-Sheng; Zhao, Can; Zhang, Aifeng; Duan, Hongmei; Hao, Peng; Wei, Rui-Han; Shang, Junkui; Zhao, Wen; Liu, Zuxiang; Yu, Juehua; Fan, Kevin S; Tian, Zhaolong; He, Qihua; Song, Wei; Yang, Zhaoyang; Sun, Yi Eve; Li, Xiaoguang

    2018-06-12

    Spinal cord injury (SCI) often leads to permanent loss of motor, sensory, and autonomic functions. We have previously shown that neurotrophin3 (NT3)-loaded chitosan biodegradable material allowed for prolonged slow release of NT3 for 14 weeks under physiological conditions. Here we report that NT3-loaded chitosan, when inserted into a 1-cm gap of hemisectioned and excised adult rhesus monkey thoracic spinal cord, elicited robust axonal regeneration. Labeling of cortical motor neurons indicated motor axons in the corticospinal tract not only entered the injury site within the biomaterial but also grew across the 1-cm-long lesion area and into the distal spinal cord. Through a combination of magnetic resonance diffusion tensor imaging, functional MRI, electrophysiology, and kinematics-based quantitative walking behavioral analyses, we demonstrated that NT3-chitosan enabled robust neural regeneration accompanied by motor and sensory functional recovery. Given that monkeys and humans share similar genetics and physiology, our method is likely translatable to human SCI repair.

  14. VESsel GENeration Analysis (VESGEN): Innovative Vascular Mappings for Astronaut Exploration Health Risks and Human Terrestrial Medicine

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, Patricia; Kao, David; Valizadegan, Hamed; Martin, Rodney; Murray, Matthew C.; Ramesh, Sneha; Sekaran, Srinivaas

    2017-01-01

    Currently, astronauts face significant health risks in future long-duration exploration missions such as colonizing the Moon and traveling to Mars. Numerous risks include greatly increased radiation exposures beyond the low earth orbit (LEO) of the ISS, and visual and ocular impairments in response to microgravity environments. The cardiovascular system is a key mediator in human physiological responses to radiation and microgravity. Moreover, blood vessels are necessarily involved in the progression and treatment of vascular-dependent terrestrial diseases such as cancer, coronary vessel disease, wound-healing, reproductive disorders, and diabetes. NASA developed an innovative, globally requested beta-level software, VESsel GENeration Analysis (VESGEN) to map and quantify vascular remodeling for application to astronaut and terrestrial health challenges. VESGEN mappings of branching vascular trees and networks are based on a weighted multi-parametric analysis derived from vascular physiological branching rules. Complex vascular branching patterns are determined by biological signaling mechanisms together with the fluid mechanics of multi-phase laminar blood flow.

  15. Titin truncating variants affect heart function in disease cohorts and the general population

    PubMed Central

    Schafer, Sebastian; de Marvao, Antonio; Adami, Eleonora; Fiedler, Lorna R; Ng, Benjamin; Khin, Ester; Rackham, Owen J L; van Heesch, Sebastiaan; Pua, Chee J; Kui, Miao; Walsh, Roddy; Tayal, Upasana; Prasad, Sanjay K; Dawes, Timothy J W; Ko, Nicole S J; Sim, David; Chan, Laura L; Chin, Calvin W L; Mazzarotto, Francesco; Barton, Paul J; Kreuchwig, Franziska; de Kleijn, Dominique P V; Totman, Teresa; Biffi, Carlo; Tee, Nicole; Rueckert, Daniel; Schneider, Valentin; Faber, Allison; Regitz-Zagrosek, Vera; Seidman, Jonathan G; Seidman, Christine E; Linke, Wolfgang A; Kovalik, Jean-Paul; O’Regan, Declan Patrick; Ware, James S; Hubner, Norbert; Cook, Stuart A

    2016-01-01

    Titin truncating variants (TTNtv) commonly cause dilated cardiomyopathy (DCM). TTNtv are also encountered in ~1% of the general population where they may be silent, perhaps reflecting allelic factors. To better understand TTNtv we integrated TTN allelic series, cardiac imaging and genomic data in humans and studied rat models with disparate TTNtv. In patients with DCM, TTNtv throughout TTN were significantly associated with DCM. Ribosomal profiling in rat revealed the translational footprint of premature stop codons in Ttn, TTNtv position-independent nonsense-mediated degradation of the mutant allele and a signature of perturbed cardiac metabolism. Heart physiology in rats with TTNtv was unremarkable at baseline but became impaired during cardiac stress. In healthy humans, machine-based analysis of high-resolution cardiac scans showed TTNtv to be associated with eccentric cardiac remodelling. These data show that TTNtv have molecular and physiological effects on the heart across species, with a continuum of expressivity in health and disease. PMID:27869827

  16. 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.

  17. TOPICAL REVIEW: FPA-based infrared thermography as applied to the study of cutaneous perspiration and stimulated vascular response in humans

    NASA Astrophysics Data System (ADS)

    Vainer, Boris G.

    2005-12-01

    This review gives an overview of focal plane array (FPA)-based infrared (IR) thermography as a powerful research method in the field of physiology and medicine. Comparison of the gained results with the data previously obtained by other authors with other research tools is given. Outer thermoregulatory manifestations displayed by the human organism subjected to whole-body heating (sauna bath) and physical loads (exercise bicycling) are quantitatively analysed. Some details of human body emotional sweating (psycho-physiological effect) are reported. Particular attention is paid to studying active sweat glands as individual objects. All experimental data were obtained with the help of a high-sensitivity (0.03 °C) fast 128 × 128 InAs IR detector-based thermal imaging system operating in the short-wave spectral region (2.5 to 3 µm) and perfectly suiting medical purposes. It is shown that IR thermography makes it possible to overcome limitations inherent to contact measuring means that were traditionally used before in thermal studies. It is also shown that heterogeneous thermograms displayed by organisms with disturbed inner equilibrium can be quantitatively analysed in terms of statistical parameters of related surface-temperature histograms, such as the mean temperature and the standard deviation of temperature (SDT). The increase and the decrease in SDT turned out to be typical of prolonged physical load and subsequent relaxation, and of external whole-body heating, respectively. Explanation of this result based on a hypothesis advanced within the context of the doctrine of human-organism evolution is given. Skin-temperature distribution function accompanying the relaxed organism in normality was found to closely resemble normal-distribution function. Symmetry break down and variation of the shape of this characteristic may serve as an indicator of homeostasis shift and can be used as a quantitative criterion for the latter. A new phenomenon, stable punctate hidrosis, is discovered and described. The term sweatology is introduced to refer to the discussed specific research area in biomedical science.

  18. FPA-based infrared thermography as applied to the study of cutaneous perspiration and stimulated vascular response in humans.

    PubMed

    Vainer, Boris G

    2005-12-07

    This review gives an overview of focal plane array (FPA)-based infrared (IR) thermography as a powerful research method in the field of physiology and medicine. Comparison of the gained results with the data previously obtained by other authors with other research tools is given. Outer thermoregulatory manifestations displayed by the human organism subjected to whole-body heating (sauna bath) and physical loads (exercise bicycling) are quantitatively analysed. Some details of human body emotional sweating (psycho-physiological effect) are reported. Particular attention is paid to studying active sweat glands as individual objects. All experimental data were obtained with the help of a high-sensitivity (0.03 degrees C) fast 128 x 128 InAs IR detector-based thermal imaging system operating in the short-wave spectral region (2.5 to 3 microm) and perfectly suiting medical purposes. It is shown that IR thermography makes it possible to overcome limitations inherent to contact measuring means that were traditionally used before in thermal studies. It is also shown that heterogeneous thermograms displayed by organisms with disturbed inner equilibrium can be quantitatively analysed in terms of statistical parameters of related surface-temperature histograms, such as the mean temperature and the standard deviation of temperature (SDT). The increase and the decrease in SDT turned out to be typical of prolonged physical load and subsequent relaxation, and of external whole-body heating, respectively. Explanation of this result based on a hypothesis advanced within the context of the doctrine of human-organism evolution is given. Skin-temperature distribution function accompanying the relaxed organism in normality was found to closely resemble normal-distribution function. Symmetry break down and variation of the shape of this characteristic may serve as an indicator of homeostasis shift and can be used as a quantitative criterion for the latter. A new phenomenon, stable punctate hidrosis, is discovered and described. The term sweatology is introduced to refer to the discussed specific research area in biomedical science.

  19. Structural and Biochemical Characterization of a Novel Aminopeptidase from Human Intestine

    DOE PAGES

    Tykvart, Jan; Bařinka, Cyril; Svoboda, Michal; ...

    2015-03-09

    N-acetylated α-linked acidic dipeptidase-like protein (NAALADase L), encoded by the NAALADL1 gene, is a close homolog of glutamate carboxypeptidase II, a metallopeptidase that has been intensively studied as a target for imaging and therapy of solid malignancies and neuropathologies. However, neither the physiological functions nor structural features of NAALADase L are known at present. In this paper, we report a thorough characterization of the protein product of the human NAALADL1 gene, including heterologous overexpression and purification, structural and biochemical characterization, and analysis of its expression profile. By solving the NAALADase L x-ray structure, we provide the first experimental evidence thatmore » it is a zinc-dependent metallopeptidase with a catalytic mechanism similar to that of glutamate carboxypeptidase II yet distinct substrate specificity. A proteome-based assay revealed that the NAALADL1 gene product possesses previously unrecognized aminopeptidase activity but no carboxy- or endopeptidase activity. These findings were corroborated by site-directed mutagenesis and identification of bestatin as a potent inhibitor of the enzyme. Analysis of NAALADL1 gene expression at both the mRNA and protein levels revealed the small intestine as the major site of protein expression and points toward extensive alternative splicing of the NAALADL1 gene transcript. Taken together, our data imply that the NAALADL1 gene product's primary physiological function is associated with the final stages of protein/peptide digestion and absorption in the human digestive system. Finally, based on these results, we suggest a new name for this enzyme: human ileal aminopeptidase (HILAP).« less

  20. Neuronal glycogen synthesis contributes to physiological aging.

    PubMed

    Sinadinos, Christopher; Valles-Ortega, Jordi; Boulan, Laura; Solsona, Estel; Tevy, Maria F; Marquez, Mercedes; Duran, Jordi; Lopez-Iglesias, Carmen; Calbó, Joaquim; Blasco, Ester; Pumarola, Marti; Milán, Marco; Guinovart, Joan J

    2014-10-01

    Glycogen is a branched polymer of glucose and the carbohydrate energy store for animal cells. In the brain, it is essentially found in glial cells, although it is also present in minute amounts in neurons. In humans, loss-of-function mutations in laforin and malin, proteins involved in suppressing glycogen synthesis, induce the presence of high numbers of insoluble polyglucosan bodies in neuronal cells. Known as Lafora bodies (LBs), these deposits result in the aggressive neurodegeneration seen in Lafora's disease. Polysaccharide-based aggregates, called corpora amylacea (CA), are also present in the neurons of aged human brains. Despite the similarity of CA to LBs, the mechanisms and functional consequences of CA formation are yet unknown. Here, we show that wild-type laboratory mice also accumulate glycogen-based aggregates in the brain as they age. These structures are immunopositive for an array of metabolic and stress-response proteins, some of which were previously shown to aggregate in correlation with age in the human brain and are also present in LBs. Remarkably, these structures and their associated protein aggregates are not present in the aged mouse brain upon genetic ablation of glycogen synthase. Similar genetic intervention in Drosophila prevents the accumulation of glycogen clusters in the neuronal processes of aged flies. Most interestingly, targeted reduction of Drosophila glycogen synthase in neurons improves neurological function with age and extends lifespan. These results demonstrate that neuronal glycogen accumulation contributes to physiological aging and may therefore constitute a key factor regulating age-related neurological decline in humans. © 2014 The Authors. Aging cell published by the Anatomical Society and John Wiley & Sons Ltd.

  1. 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

  2. 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

  3. Anatomy and Physiology. Module Set I: Introduction to Anatomy and Physiology. Teacher Edition [and] Student Edition. Surgical Technology.

    ERIC Educational Resources Information Center

    Hilley, Robert

    This document, which is the first part in a two-part set of modules on anatomy and physiology for future surgical technicians, contains the teacher and student editions of an introduction to anatomy and physiology that consists of modules on the following topics: (1) organization of the human body; (2) biochemistry and microbiology; (3) infection,…

  4. Teaching Integrative Physiology Using the Quantitative Circulatory Physiology Model and Case Discussion Method: Evaluation of the Learning Experience

    ERIC Educational Resources Information Center

    Rodriguez-Barbero, A.; Lopez-Novoa, J. M.

    2008-01-01

    One of the problems that we have found when teaching human physiology in a Spanish medical school is that the degree of understanding by the students of the integration between organs and systems is rather poor. We attempted to remedy this problem by using a case discussion method together with the Quantitative Circulatory Physiology (QCP)…

  5. 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.

  6. 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.

  7. Inter-Individual Variability in High-Throughput Risk ...

    EPA Pesticide Factsheets

    We incorporate realistic human variability into an open-source high-throughput (HT) toxicokinetics (TK) modeling framework for use in a next-generation risk prioritization approach. Risk prioritization involves rapid triage of thousands of environmental chemicals, most which have little or no existing TK data. Chemicals are prioritized based on model estimates of hazard and exposure, to decide which chemicals should be first in line for further study. Hazard may be estimated with in vitro HT screening assays, e.g., U.S. EPA’s ToxCast program. Bioactive ToxCast concentrations can be extrapolated to doses that produce equivalent concentrations in body tissues using a reverse TK 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. Here we draw physiological parameters from realistic estimates of distributions of demographic and anthropometric quantities in the modern U.S. population, based on the most recent CDC NHANES data. A Monte Carlo approach, accounting for the correlation structure in physiological parameters, is used to estimate ToxCast equivalent doses for the most sensitive portion of the population. To quantify risk, ToxCast equivalent doses are compared to estimates of exposure rates based on Bayesian inferences drawn from NHANES urinary analyte biomonitoring data. The inclusion

  8. Vegetation physiology controls continental water cycle responses to climate change

    NASA Astrophysics Data System (ADS)

    Lemordant, L. A.; Swann, A. L. S.; Cook, B.; Scheff, J.; Gentine, P.

    2017-12-01

    Abstract per se:Predicting how climate change will affect the hydrologic cycle is of utmost importance for ecological systems and for human life and activities. A typical perspective is that global warming will cause an intensification of the mean state, the so-called "dry gets drier, wet gets wetter" paradigm. While this result is robust over the oceans, recent works suggest it may be less appropriate for terrestrial regions. Using Earth System Models (ESMs) with decoupled surface (vegetation physiology, PHYS) and atmospheric (radiative, ATMO) CO2 responses, we show that the CO2 physiological response dominates the change in the continental hydrologic cycle compared to radiative and precipitation changes due to increased atmospheric CO2, counter to previous assumptions. Using multiple linear regression analysis, we estimate the individual contribution of each of the three main drivers, precipitation, radiation and physiological CO2 forcing (see attached figure). Our analysis reveals that physiological effects dominate changes for 3 key indicators of dryness and/or vegetation stress (namely LAI, P-ET and EF) over the largest fraction of the globe, except for soil moisture which exhibits a more complex response. This highlights the key role of vegetation in controlling future terrestrial hydrologic response.Legend of the Figure attached:Decomposition along the three main drivers of LAI (a), P-ET (b), EF (c) in the control run. Green quantifies the effect of the vegetation physiology based on the run PHYS; red and blue quantify the contribution of, respectively, net radiation and precipitation, based on multiple linear regression in ATMO. Pie charts show for each variable the fraction (labelled in %) of land under the main influence (more than 50% of the changes is attributed to this driver) of one the three main drivers (green for grid points dominated by vegetation physiology, red for grid points dominated by net radiation, and blue for grid points dominated by the precipitation), and under no single driver influence (grey). Based on an article in review at Nature Climate Change as of Aug, 2nd 2017

  9. Dose-dependent DNA adduct formation by cinnamaldehyde and other food-borne α,β-unsaturated aldehydes predicted by physiologically based in silico modelling.

    PubMed

    Kiwamoto, R; Ploeg, D; Rietjens, I M C M; Punt, A

    2016-03-01

    Genotoxicity of α,β-unsaturated aldehydes shown in vitro raises a concern for the use of the aldehydes as food flavourings, while at low dose exposures the formation of DNA adducts may be prevented by detoxification. Unlike many α,β-unsaturated aldehydes for which in vivo data are absent, cinnamaldehyde was shown to be not genotoxic or carcinogenic in vivo. The present study aimed at comparing dose-dependent DNA adduct formation by cinnamaldehyde and 18 acyclic food-borne α,β-unsaturated aldehydes using physiologically based kinetic/dynamic (PBK/D) modelling. In rats, cinnamaldehyde was predicted to induce higher DNA adducts levels than 6 out of the 18 α,β-unsaturated aldehydes, indicating that these 6 aldehydes may also test negative in vivo. At the highest cinnamaldehyde dose that tested negative in vivo, cinnamaldehyde was predicted to form at least three orders of magnitude higher levels of DNA adducts than the 18 aldehydes at their respective estimated daily intake. These results suggest that for all the 18 α,β-unsaturated aldehydes DNA adduct formation at doses relevant for human dietary exposure may not raise a concern. The present study illustrates a possible use of physiologically based in silico modelling to facilitate a science-based comparison and read-across on the possible risks posed by DNA reactive agents. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Understanding Protein Synthesis: A Role-Play Approach in Large Undergraduate Human Anatomy and Physiology Classes

    ERIC Educational Resources Information Center

    Sturges, Diana; Maurer, Trent W.; Cole, Oladipo

    2009-01-01

    This study investigated the effectiveness of role play in a large undergraduate science class. The targeted population consisted of 298 students enrolled in 2 sections of an undergraduate Human Anatomy and Physiology course taught by the same instructor. The section engaged in the role-play activity served as the study group, whereas the section…

  11. Academic Performance in Human Anatomy and Physiology Classes: A 2-Yr Study of Academic Motivation and Grade Expectation

    ERIC Educational Resources Information Center

    Sturges, Diana; Maurer, Trent W.; Allen, Deborah; Gatch, Delena Bell; Shankar, Padmini

    2016-01-01

    This project used a nonexperimental design with a convenience sample and studied the relationship between academic motivation, grade expectation, and academic performance in 1,210 students enrolled in undergraduate human anatomy and physiology (HAP) classes over a 2-yr period. A 42-item survey that included 28 items of the adapted academic…

  12. Active Learning and Flipped Classroom, Hand in Hand Approach to Improve Students Learning in Human Anatomy and Physiology

    ERIC Educational Resources Information Center

    Entezari, Maria; Javdan, Mohammad

    2016-01-01

    Because Human Anatomy and Physiology (A&P), a gateway course for allied health majors, has high dropout rates nationally, it is challenging to find a successful pedagogical intervention. Reports on the effect of integration of flipped classrooms and whether it improves learning are contradictory for different disciplines. Thus many educators…

  13. Audio-Tutorial Project: An Audio-Tutorial Approach to Human Anatomy and Physiology.

    ERIC Educational Resources Information Center

    Muzio, Joseph N.; And Others

    A two course sequence on human anatomy and physiology using the audiotutorial method of instruction was developed for use by nursing students and other students in the health or medical fields at the Kingsborough Community College in New York. The project was motivated by the problems of often underprepared students coming to learn a new field and…

  14. Interteaching within a Human Physiology Course: A Comparison of First- and Second-Year Students' Learning Skills and Perceptions

    ERIC Educational Resources Information Center

    Byrne, Bruce; Guy, Richard

    2016-01-01

    This article describes student perceptions and outcomes in relation to the use of a novel interteaching approach. The study sample (n = 260) was taken from a large human physiology class, which included both first- and second-year students. However, unlike the first-year students, the second-year students had significant prior knowledge, having…

  15. Multivariate Dynamical Modeling to Investigate Human Adaptation to Space Flight: Initial Concepts

    NASA Technical Reports Server (NTRS)

    Shelhamer, Mark; Mindock, Jennifer; Zeffiro, Tom; Krakauer, David; Paloski, William H.; Lumpkins, Sarah

    2014-01-01

    The array of physiological changes that occur when humans venture into space for long periods presents a challenge to future exploration. The changes are conventionally investigated independently, but a complete understanding of adaptation requires a conceptual basis founded in intergrative physiology, aided by appropriate mathematical modeling. NASA is in the early stages of developing such an approach.

  16. Multivariate Dynamic Modeling to Investigate Human Adaptation to Space Flight: Initial Concepts

    NASA Technical Reports Server (NTRS)

    Shelhamer, Mark; Mindock, Jennifer; Zeffiro, Tom; Krakauer, David; Paloski, William H.; Lumpkins, Sarah

    2014-01-01

    The array of physiological changes that occur when humans venture into space for long periods presents a challenge to future exploration. The changes are conventionally investigated independently, but a complete understanding of adaptation requires a conceptual basis founded in integrative physiology, aided by appropriate mathematical modeling. NASA is in the early stages of developing such an approach.

  17. Standing on the Shoulders of Giants: Dean Franklin and His Remarkable Contributions to Physiological Measurements in Animals

    ERIC Educational Resources Information Center

    Sarazan, R. Dustan; Schweitz, Karl T. R.

    2009-01-01

    The use of electronic instrumentation to monitor physiological function in conscious research animals and humans has become routine. Beyond basic research, animal studies using these methods are required by government regulatory agencies worldwide before human testing of potential new drugs. Living, as we do, in an age of miniaturized high-tech…

  18. Integrating multi-scale data to create a virtual physiological mouse heart.

    PubMed

    Land, Sander; Niederer, Steven A; Louch, William E; Sejersted, Ole M; Smith, Nicolas P

    2013-04-06

    While the virtual physiological human (VPH) project has made great advances in human modelling, many of the tools and insights developed as part of this initiative are also applicable for facilitating mechanistic understanding of the physiology of a range of other species. This process, in turn, has the potential to provide human relevant insights via a different scientific path. Specifically, the increasing use of mice in experimental research, not yet fully complemented by a similar increase in computational modelling, is currently missing an important opportunity for using and interpreting this growing body of experimental data to improve our understanding of cardiac function. This overview describes our work to address this issue by creating a virtual physiological mouse model of the heart. We describe the similarities between human- and mouse-focused modelling, including the reuse of VPH tools, and the development of methods for investigating parameter sensitivity that are applicable across species. We show how previous results using this approach have already provided important biological insights, and how these can also be used to advance VPH heart models. Finally, we show an example application of this approach to test competing multi-scale hypotheses by investigating variations in length-dependent properties of cardiac muscle.

  19. Integrating multi-scale data to create a virtual physiological mouse heart

    PubMed Central

    Land, Sander; Niederer, Steven A.; Louch, William E.; Sejersted, Ole M.; Smith, Nicolas P.

    2013-01-01

    While the virtual physiological human (VPH) project has made great advances in human modelling, many of the tools and insights developed as part of this initiative are also applicable for facilitating mechanistic understanding of the physiology of a range of other species. This process, in turn, has the potential to provide human relevant insights via a different scientific path. Specifically, the increasing use of mice in experimental research, not yet fully complemented by a similar increase in computational modelling, is currently missing an important opportunity for using and interpreting this growing body of experimental data to improve our understanding of cardiac function. This overview describes our work to address this issue by creating a virtual physiological mouse model of the heart. We describe the similarities between human- and mouse-focused modelling, including the reuse of VPH tools, and the development of methods for investigating parameter sensitivity that are applicable across species. We show how previous results using this approach have already provided important biological insights, and how these can also be used to advance VPH heart models. Finally, we show an example application of this approach to test competing multi-scale hypotheses by investigating variations in length-dependent properties of cardiac muscle. PMID:24427525

  20. What is conservation physiology? Perspectives on an increasingly integrated and essential science†

    PubMed Central

    Cooke, Steven J.; Sack, Lawren; Franklin, Craig E.; Farrell, Anthony P.; Beardall, John; Wikelski, Martin; Chown, Steven L.

    2013-01-01

    Globally, ecosystems and their constituent flora and fauna face the localized and broad-scale influence of human activities. Conservation practitioners and environmental managers struggle to identify and mitigate threats, reverse species declines, restore degraded ecosystems, and manage natural resources sustainably. Scientific research and evidence are increasingly regarded as the foundation for new regulations, conservation actions, and management interventions. Conservation biologists and managers have traditionally focused on the characteristics (e.g. abundance, structure, trends) of populations, species, communities, and ecosystems, and simple indicators of the responses to environmental perturbations and other human activities. However, an understanding of the specific mechanisms underlying conservation problems is becoming increasingly important for decision-making, in part because physiological tools and knowledge are especially useful for developing cause-and-effect relationships, and for identifying the optimal range of habitats and stressor thresholds for different organisms. When physiological knowledge is incorporated into ecological models, it can improve predictions of organism responses to environmental change and provide tools to support management decisions. Without such knowledge, we may be left with simple associations. ‘Conservation physiology’ has been defined previously with a focus on vertebrates, but here we redefine the concept universally, for application to the diversity of taxa from microbes to plants, to animals, and to natural resources. We also consider ‘physiology’ in the broadest possible terms; i.e. how an organism functions, and any associated mechanisms, from development to bioenergetics, to environmental interactions, through to fitness. Moreover, we consider conservation physiology to include a wide range of applications beyond assisting imperiled populations, and include, for example, the eradication of invasive species, refinement of resource management strategies to minimize impacts, and evaluation of restoration plans. This concept of conservation physiology emphasizes the basis, importance, and ecological relevance of physiological diversity at a variety of scales. Real advances in conservation and resource management require integration and inter-disciplinarity. Conservation physiology and its suite of tools and concepts is a key part of the evidence base needed to address pressing environmental challenges. PMID:27293585

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