WorldWideScience

Sample records for physiology human

  1. [Human physiology: kidney].

    Science.gov (United States)

    Natochin, Iu V

    2010-01-01

    The content of human physiology as an independent part of current physiology is discussed. Substantiated is the point that subjects of human physiology are not only special sections of physiology where functions are inherent only in human (physiology of intellectual activity, speech, labor, sport), but also in peculiarities of functions, specificity of regulation of each of physiological systems. By the example of physiology of kidney and water-salt balance there are shown borders of norm, peculiarities of regulation in human, new chapters of renal physiology which have appeared in connection with achievements of molecular physiology.

  2. Human physiology in space

    Science.gov (United States)

    Vernikos, J.

    1996-01-01

    The universality of gravity (1 g) in our daily lives makes it difficult to appreciate its importance in morphology and physiology. Bone and muscle support systems were created, cellular pumps developed, neurons organised and receptors and transducers of gravitational force to biologically relevant signals evolved under 1g gravity. Spaceflight provides the only microgravity environment where systematic experimentation can expand our basic understanding of gravitational physiology and perhaps provide new insights into normal physiology and disease processes. These include the surprising extent of our body's dependence on perceptual information, and understanding the effect and importance of forces generated within the body's weightbearing structures such as muscle and bones. Beyond this exciting prospect is the importance of this work towards opening the solar system for human exploration. Although both appear promising, we are only just beginning to taste what lies ahead.

  3. Assessing prebaccalaureate human physiology courses.

    Science.gov (United States)

    McCleary, V L

    1998-12-01

    Two surveys were conducted between 1994 and 1996. The purpose of the initial survey was to obtain demographic information about prebaccaulareate human physiology courses. Of the 117 responding physiology departments, 50% offered human physiology at the prebaccalaureate level to 14,185 students during the 1994-1995 academic year. The mean was 245 students per year (+/- 30 SE). Class size was limited by 44% of the respondents. Prebaccaluareate human physiology was offered as a separate course from anatomy by 93% of the departments. Sixty-one percent scheduled the course once a year. The purpose of the second survey was to determine how physiology departments evaluated prebaccalaureate physiology courses and faculty. All responding departments utilized student feedback; 38% of the departments included physiology chair review, 38% peer review, and 9% allied health faculty review. Twenty-eight percent of allied health programs evaluated the course. Results indicated that, whereas a significant number of undergraduate students are enrolled in prebaccaluareate physiology courses annually, those courses appear to lack formal, consistent formative evaluation.

  4. Electronic Textbook in Human Physiology.

    Science.gov (United States)

    Broering, Naomi C.; Lilienfield, Lawrence S.

    1994-01-01

    Describes the development of an electronic textbook in human physiology at the Georgetown University Medical Center Library that was designed to enhance learning and visualization through a prototype knowledge base of core instructional materials stored in digital format on Macintosh computers. The use of computers in the medical curriculum is…

  5. Virtual physiological human: training challenges.

    Science.gov (United States)

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

    2010-06-28

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

  6. Design Projects in Human Anatomy & Physiology

    Science.gov (United States)

    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,…

  7. Design Projects in Human Anatomy & Physiology

    Science.gov (United States)

    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,…

  8. Concepts of Human Physiology in Ayurveda

    OpenAIRE

    Patwardhan, Dr. Kishor

    2008-01-01

    Human Physiology’, or the study of functional aspects of human body, is designated by the term ‘Śarīra Vicaya’ in Ayurvedic literature. The word ‘Vicaya’ means the special or detailed knowledge. Detailed knowledge of normal human body i.e., ‘Śarīra’, is considered helpful in understanding the factors influencing the health. Though most of the basic concepts of human physiology explained in Ayurveda are strikingly similar to the concepts of modern physiology, some concepts like ‘Ātmā’, ‘Ma...

  9. [Immune response genes products in human physiology].

    Science.gov (United States)

    Khaitov, R M; Alekseev, L P

    2012-09-01

    Current data on physiological role of human immune response genes' proteomic products (antigens) are discussed. The antigens are specified by a very high level of diversity that mediates a wide specter ofphysiological functions. They actually provide integrity and biological stability of human as species. These data reveal new ideas on many pathological processes as well as drafts new approaches for prophylaxis and treatment.

  10. Gravitational Effects on Human Physiology.

    Science.gov (United States)

    Atomi, Yoriko

    2015-01-01

    Physical working capacity decreases with age and also in microgravity. Regardless of age, increased physical activity can always improve the physical adaptability of the body, although the mechanisms of this adaptability are unknown. Physical exercise produces various mechanical stimuli in the body, and these stimuli may be essential for cell survival in organisms. The cytoskeleton plays an important role in maintaining cell shape and tension development, and in various molecular and/or cellular organelles involved in cellular trafficking. Both intra and extracellular stimuli send signals through the cytoskeleton to the nucleus and modulate gene expression via an intrinsic property, namely the "dynamic instability" of cytoskeletal proteins. αB-crystallin is an important chaperone for cytoskeletal proteins in muscle cells. Decreases in the levels of αB-crystallin are specifically associated with a marked decrease in muscle mass (atrophy) in a rat hindlimb suspension model that mimics muscle and bone atrophy that occurs in space and increases with passive stretch. Moreover, immunofluorescence data show complete co-localization of αB-crystallin and the tubulin/microtubule system in myoblast cells. This association was further confirmed in biochemical experiments carried out in vitro showing that αB-crystallin acts as a chaperone for heat-denatured tubulin and prevents microtubule disassembly induced by calcium. Physical activity induces the constitutive expression of αB-crystallin, which helps to maintain the homeostasis of cytoskeleton dynamics in response to gravitational forces. This relationship between chaperone expression levels and regulation of cytoskeletal dynamics observed in slow anti-gravitational muscles as well as in mammalian striated muscles, such as those in the heart, diaphragm and tongue, may have been especially essential for human evolution in particular. Elucidation of the intrinsic properties of the tubulin/microtubule and chaperone

  11. Predictors of success in undergraduate human physiology.

    Science.gov (United States)

    McCleary, V L; Aasen, G; Slotnick, H B

    1999-12-01

    This study tested the hypothesis that measurable attributes in students' backgrounds are related to their successful completion of an undergraduate human physiology course. Demographic, general academic performance, and science achievement data were obtained from student records for students enrolled during the 1995-1996 academic year, and additional demographic data were obtained from students enrolled during the 1996-1998 academic years. A hierarchical logistic regression analysis explored the relationship fo these variables to the percentage of students passing the human physiology course. Predicted passing versus failing showed a sensitivity of 85.5% and specificity of 69.7%. Two independent validations of the logistical regression equation correctly predicted the performance of subsequent groups of students 75.9% and 77.6% of the time.

  12. Earthing the human body influences physiologic processes.

    Science.gov (United States)

    Sokal, Karol; Sokal, Pawel

    2011-04-01

    This study was designed to answer the question: Does the contact of the human organism with the Earth via a copper conductor affect physiologic processes? Subjects and experiments: Five (5) experiments are presented: experiment 1-effect of earthing on calcium-phosphate homeostasis and serum concentrations of iron (N = 84 participants); experiment 2-effect of earthing on serum concentrations of electrolytes (N = 28); experiment 3-effect of earthing on thyroid function (N = 12); experiment 4-effect of earthing on glucose concentration (N = 12); experiment 5-effect of earthing on immune response to vaccine (N = 32). Subjects were divided into two groups. One (1) group of people was earthed, while the second group remained without contact with the Earth. Blood and urine samples were examined. Earthing of an electrically insulated human organism during night rest causes lowering of serum concentrations of iron, ionized calcium, inorganic phosphorus, and reduction of renal excretion of calcium and phosphorus. Earthing during night rest decreases free tri-iodothyronine and increases free thyroxine and thyroid-stimulating hormone. The continuous earthing of the human body decreases blood glucose in patients with diabetes. Earthing decreases sodium, potassium, magnesium, iron, total protein, and albumin concentrations while the levels of transferrin, ferritin, and globulins α1, α2, β, and γ increase. These results are statistically significant. Earthing the human body influences human physiologic processes. This influence is observed during night relaxation and during physical activity. Effect of the earthing on calcium-phosphate homeostasis is the opposite of that which occurs in states of weightlessness. It also increases the activity of catabolic processes. It may be the primary factor regulating endocrine and nervous systems.

  13. The human hair: from anatomy to physiology.

    Science.gov (United States)

    Buffoli, Barbara; Rinaldi, Fabio; Labanca, Mauro; Sorbellini, Elisabetta; Trink, Anna; Guanziroli, Elena; Rezzani, Rita; Rodella, Luigi F

    2014-03-01

    Hair is a unique character of mammals and has several functions, from protection of the skin to sexual and social communication. In literature, there are various studies about hair that take into consideration different aspects within many fields of science, including biology, dermatology, cosmetics, forensic sciences, and medicine. We carried out a search of studies published in PubMed up to 2013. In this review, we summarized the principal anatomical and physiological aspects of the different types of human hair, and we considered the clinical significance of the different structures and the distribution of the hair in the human body. This review could be the basis for improvement and progression in the field of hair research. © 2013 The International Society of Dermatology.

  14. Leptin in human physiology and pathophysiology.

    Science.gov (United States)

    Mantzoros, Christos S; Magkos, Faidon; Brinkoetter, Mary; Sienkiewicz, Elizabeth; Dardeno, Tina A; Kim, Sang-Yong; Hamnvik, Ole-Petter R; Koniaris, Anastasia

    2011-10-01

    Leptin, discovered through positional cloning 15 years ago, is an adipocyte-secreted hormone with pleiotropic effects in the physiology and pathophysiology of energy homeostasis, endocrinology, and metabolism. Studies in vitro and in animal models highlight the potential for leptin to regulate a number of physiological functions. Available evidence from human studies indicates that leptin has a mainly permissive role, with leptin administration being effective in states of leptin deficiency, less effective in states of leptin adequacy, and largely ineffective in states of leptin excess. Results from interventional studies in humans demonstrate that leptin administration in subjects with congenital complete leptin deficiency or subjects with partial leptin deficiency (subjects with lipoatrophy, congenital or related to HIV infection, and women with hypothalamic amenorrhea) reverses the energy homeostasis and neuroendocrine and metabolic abnormalities associated with these conditions. More specifically, in women with hypothalamic amenorrhea, leptin helps restore abnormalities in hypothalamic-pituitary-peripheral axes including the gonadal, thyroid, growth hormone, and to a lesser extent adrenal axes. Furthermore, leptin results in resumption of menses in the majority of these subjects and, in the long term, may increase bone mineral content and density, especially at the lumbar spine. In patients with congenital or HIV-related lipoatrophy, leptin treatment is also associated with improvements in insulin sensitivity and lipid profile, concomitant with reduced visceral and ectopic fat deposition. In contrast, leptin's effects are largely absent in the obese hyperleptinemic state, probably due to leptin resistance or tolerance. Hence, another emerging area of research pertains to the discovery and/or usefulness of leptin sensitizers. Results from ongoing studies are expected to further increase our understanding of the role of leptin and the potential clinical

  15. Leptin in human physiology and pathophysiology

    Science.gov (United States)

    Magkos, Faidon; Brinkoetter, Mary; Sienkiewicz, Elizabeth; Dardeno, Tina A.; Kim, Sang-Yong; Hamnvik, Ole-Petter R.; Koniaris, Anastasia

    2011-01-01

    Leptin, discovered through positional cloning 15 years ago, is an adipocyte-secreted hormone with pleiotropic effects in the physiology and pathophysiology of energy homeostasis, endocrinology, and metabolism. Studies in vitro and in animal models highlight the potential for leptin to regulate a number of physiological functions. Available evidence from human studies indicates that leptin has a mainly permissive role, with leptin administration being effective in states of leptin deficiency, less effective in states of leptin adequacy, and largely ineffective in states of leptin excess. Results from interventional studies in humans demonstrate that leptin administration in subjects with congenital complete leptin deficiency or subjects with partial leptin deficiency (subjects with lipoatrophy, congenital or related to HIV infection, and women with hypothalamic amenorrhea) reverses the energy homeostasis and neuroendocrine and metabolic abnormalities associated with these conditions. More specifically, in women with hypothalamic amenorrhea, leptin helps restore abnormalities in hypothalamic-pituitary-peripheral axes including the gonadal, thyroid, growth hormone, and to a lesser extent adrenal axes. Furthermore, leptin results in resumption of menses in the majority of these subjects and, in the long term, may increase bone mineral content and density, especially at the lumbar spine. In patients with congenital or HIV-related lipoatrophy, leptin treatment is also associated with improvements in insulin sensitivity and lipid profile, concomitant with reduced visceral and ectopic fat deposition. In contrast, leptin's effects are largely absent in the obese hyperleptinemic state, probably due to leptin resistance or tolerance. Hence, another emerging area of research pertains to the discovery and/or usefulness of leptin sensitizers. Results from ongoing studies are expected to further increase our understanding of the role of leptin and the potential clinical

  16. Human physiologically based pharmacokinetic model for propofol

    Directory of Open Access Journals (Sweden)

    Schnider Thomas W

    2005-04-01

    Full Text Available Abstract Background Propofol is widely used for both short-term anesthesia and long-term sedation. It has unusual pharmacokinetics because of its high lipid solubility. The standard approach to describing the pharmacokinetics is by a multi-compartmental model. This paper presents the first detailed human physiologically based pharmacokinetic (PBPK model for propofol. Methods PKQuest, a freely distributed software routine http://www.pkquest.com, was used for all the calculations. The "standard human" PBPK parameters developed in previous applications is used. It is assumed that the blood and tissue binding is determined by simple partition into the tissue lipid, which is characterized by two previously determined set of parameters: 1 the value of the propofol oil/water partition coefficient; 2 the lipid fraction in the blood and tissues. The model was fit to the individual experimental data of Schnider et. al., Anesthesiology, 1998; 88:1170 in which an initial bolus dose was followed 60 minutes later by a one hour constant infusion. Results The PBPK model provides a good description of the experimental data over a large range of input dosage, subject age and fat fraction. Only one adjustable parameter (the liver clearance is required to describe the constant infusion phase for each individual subject. In order to fit the bolus injection phase, for 10 or the 24 subjects it was necessary to assume that a fraction of the bolus dose was sequestered and then slowly released from the lungs (characterized by two additional parameters. The average weighted residual error (WRE of the PBPK model fit to the both the bolus and infusion phases was 15%; similar to the WRE for just the constant infusion phase obtained by Schnider et. al. using a 6-parameter NONMEM compartmental model. Conclusion A PBPK model using standard human parameters and a simple description of tissue binding provides a good description of human propofol kinetics. The major advantage of a

  17. A dynamic model of human physiology

    Science.gov (United States)

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

    2010-11-01

    To study the systems-level transport in the human body, we develop the Computational Man (CMAN): a set of one-dimensional unsteady elastic flow simulations created to model a variety of coupled physiological systems including the circulatory, respiratory, excretory, and lymphatic systems. The model systems are collapsed from three spatial dimensions and time to one spatial dimension and time by assuming axisymmetric vessel geometry and a parabolic velocity profile across the cylindrical vessels. To model the actions of a beating heart or expanding lungs, the flow is driven by user-defined changes to the equilibrium areas of the elastic vessels. The equations are then iteratively solved for pressure, area, and average velocity. The model is augmented with valves and contractions to resemble the biological structure of the different systems. CMAN will be used to track material transport throughout the human body for diagnostic and predictive purposes. Parameters will be adjustable to match those of individual patients. Validation of CMAN has used both higher-dimensional simulations of similar geometries and benchmark measurement from medical literature.

  18. Leptin in human physiology and therapeutics.

    Science.gov (United States)

    Dardeno, Tina A; Chou, Sharon H; Moon, Hyun-Seuk; Chamberland, John P; Fiorenza, Christina G; Mantzoros, Christos S

    2010-07-01

    Leptin regulates energy homeostasis and reproductive, neuroendocrine, immune, and metabolic functions. In this review, we describe the role of leptin in human physiology and review evidence from recent "proof of concept" clinical trials using recombinant human leptin in subjects with congenital leptin deficiency, hypoleptinemia associated with energy-deficient states, and hyperleptinemia associated with garden-variety obesity. Since most obese individuals are largely leptin-tolerant or -resistant, therapeutic uses of leptin are currently limited to patients with complete or partial leptin deficiency, including hypothalamic amenorrhea and lipoatrophy. Leptin administration in these energy-deficient states may help restore associated neuroendocrine, metabolic, and immune function and bone metabolism. Leptin treatment is currently available for individuals with congenital leptin deficiency and congenital lipoatrophy. The long-term efficacy and safety of leptin treatment in hypothalamic amenorrhea and acquired lipoatrophy are currently under investigation. Whether combination therapy with leptin and potential leptin sensitizers will prove effective in the treatment of garden-variety obesity and whether leptin may have a role in weight loss maintenance is being greatly anticipated.

  19. Leptin in Human Physiology and Therapeutics

    Science.gov (United States)

    Dardeno, Tina A.; Chou, Sharon H.; Moon, Hyun-Seuk; Chamberland, John P.; Fiorenza, Christina G.; Mantzoros, Christos S.

    2010-01-01

    Leptin regulates energy homeostasis and reproductive, neuroendocrine, immune, and metabolic functions. In this review, we describe the role of leptin in human physiology and review evidence from recent “proof of concept” clinical trials using recombinant human leptin in subjects with congenital leptin deficiency, hypoleptinemia associated with energy-deficient states, and hyperleptinemia associated with garden-variety obesity. Since most obese individuals are largely leptin-tolerant or -resistant, therapeutic uses of leptin are currently limited to patients with complete or partial leptin deficiency, including hypothalamic amenorrhea and lipoatrophy. Leptin administration in these energy-deficient states may help restore associated neuroendocrine, metabolic, and immune function and bone metabolism. Leptin treatment is currently available for individuals with congenital leptin deficiency and congenital lipoatrophy. The long-term efficacy and safety of leptin treatment in hypothalamic amenorrhea and acquired lipoatrophy are currently under investigation. Whether combination therapy with leptin and potential leptin sensitizers will prove effective in the treatment of garden-variety obesity and whether leptin may have a role in weight loss maintenance is being greatly anticipated. PMID:20600241

  20. Physiological basis for human autonomic rhythms

    Science.gov (United States)

    Eckberg, D. L.

    2000-01-01

    Oscillations of arterial pressures, heart periods, and muscle sympathetic nerve activity have been studied intensively in recent years to explore otherwise obscure human neurophysiological mechanisms. The best-studied rhythms are those occurring at breathing frequencies. Published evidence indicates that respiratory fluctuations of muscle sympathetic nerve activity and electrocardiographic R-R intervals result primarily from the action of a central 'gate' that opens during expiration and closes during inspiration. Parallel respiratory fluctuations of arterial pressures and R-R intervals are thought to be secondary to arterial baroreflex physiology: changes in systolic pressure provoke changes in the R-R interval. However, growing evidence suggests that these parallel oscillations result from the influence of respiration on sympathetic and vagal-cardiac motoneurones rather than from baroreflex physiology. There is a rapidly growing literature on the use of mathematical models of low- and high-frequency (respiratory) R-R interval fluctuations in characterizing instantaneous 'sympathovagal balance'. The case for this approach is based primarily on measurements made with patients in upright tilt. However, the strong linear relation between such measures as the ratio of low- to high-frequency R-R interval oscillations and the angle of the tilt reflects exclusively the reductions of the vagal (high-frequency) component. As the sympathetic component does not change in tilt, the low- to high-frequency R-R interval ratio provides no proof that sympathetic activity increases. Moreover, the validity of extrapolating from measurements performed during upright tilt to measurements during supine rest has not been established. Nonetheless, it is clear that measures of heart rate variability provide important prognostic information in patients with cardiovascular diseases. It is not known whether reduced heart rate variability is merely a marker for the severity of disease or a

  1. Hydration Effects on Human Physiology and Exercise-Heat Performance

    Science.gov (United States)

    1989-11-01

    AD REPORT NO T7-90 HYDRATION EFFECTS :N HUMAN PHYSIOLOGY AND EXERCISE-HEA PERFORMANCE Co U S ARMY RESEARCH INSTITUTE N OF I ENVIRONMENTAL MEDICINE...effects on human physiology and exercise.-heat performance 12 PERSONAL AUTHOR(S) Michael N. Sawka, Andrew J. Young. William A. Latzka, P. Darrell...acknowledge Ms. Patricia DeMusis for preparing the manuscript. AD Report No. HYDRATION EFFECTS ON HUMAN PHYSIOLOGY AND EXERCISE-HEAT PERFORMANCE by Michael N

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

    Science.gov (United States)

    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.

  3. The Virtual Physiological Human ToolKit.

    Science.gov (United States)

    Cooper, Jonathan; Cervenansky, Frederic; De Fabritiis, Gianni; Fenner, John; Friboulet, Denis; Giorgino, Toni; Manos, Steven; Martelli, Yves; Villà-Freixa, Jordi; Zasada, Stefan; Lloyd, Sharon; McCormack, Keith; Coveney, Peter V

    2010-08-28

    The Virtual Physiological Human (VPH) is a major European e-Science initiative intended to support the development of patient-specific computer models and their application in personalized and predictive healthcare. The VPH Network of Excellence (VPH-NoE) project is tasked with facilitating interaction between the various VPH projects and addressing issues of common concern. A key deliverable is the 'VPH ToolKit'--a collection of tools, methodologies and services to support and enable VPH research, integrating and extending existing work across Europe towards greater interoperability and sustainability. Owing to the diverse nature of the field, a single monolithic 'toolkit' is incapable of addressing the needs of the VPH. Rather, the VPH ToolKit should be considered more as a 'toolbox' of relevant technologies, interacting around a common set of standards. The latter apply to the information used by tools, including any data and the VPH models themselves, and also to the naming and categorizing of entities and concepts involved. Furthermore, the technologies and methodologies available need to be widely disseminated, and relevant tools and services easily found by researchers. The VPH-NoE has thus created an online resource for the VPH community to meet this need. It consists of a database of tools, methods and services for VPH research, with a Web front-end. This has facilities for searching the database, for adding or updating entries, and for providing user feedback on entries. Anyone is welcome to contribute.

  4. Quantitative Circulatory Physiology: an integrative mathematical model of human physiology for medical education.

    Science.gov (United States)

    Abram, Sean R; Hodnett, Benjamin L; Summers, Richard L; Coleman, Thomas G; Hester, Robert L

    2007-06-01

    We have developed Quantitative Circulatory Physiology (QCP), a mathematical model of integrative human physiology containing over 4,000 variables of biological interactions. This model provides a teaching environment that mimics clinical problems encountered in the practice of medicine. The model structure is based on documented physiological responses within peer-reviewed literature and serves as a dynamic compendium of physiological knowledge. The model is solved using a desktop, Windows-based program, allowing students to calculate time-dependent solutions and interactively alter over 750 parameters that modify physiological function. The model can be used to understand proposed mechanisms of physiological function and the interactions among physiological variables that may not be otherwise intuitively evident. In addition to open-ended or unstructured simulations, we have developed 30 physiological simulations, including heart failure, anemia, diabetes, and hemorrhage. Additional stimulations include 29 patients in which students are challenged to diagnose the pathophysiology based on their understanding of integrative physiology. In summary, QCP allows students to examine, integrate, and understand a host of physiological factors without causing harm to patients. This model is available as a free download for Windows computers at http://physiology.umc.edu/themodelingworkshop.

  5. Motion Sickness: A Study of Its Effects on Human Physiology.

    Science.gov (United States)

    1987-12-01

    SICKNESS: A STUDY OF ITS EFFECTS ON HUMAN PHYSIOLOGY THESIS Pierre J. Gaudreault Captain, USAF AFIT/GE/ENG/87D- 2 0 TO STEC TEo VN;FB 1 0 1988...ENG/87D-20 MOTION SICKNESS: A STUDY OF ITS EFFECTS ON HUMAN PHYSIOLOGY THESIS Pierre J. Gaudreault Captain, USAF AFIT/GE/ENG/87D-20 Approved for public...SICKNESS: A STUDY OF ITS EFFECTS ON HUMAN PHYSIOLOGY THESIS Presented to the Faculty of the School of Engineering of the Air Force Institute of Technology

  6. subjective approach to subjective approach to human physiological ...

    African Journals Online (AJOL)

    eobe

    approach on human physiology and this focuses on the skin temperature which is the primary ... digital anemometer (Lutron Electronics Enterprise co. Ltd, Taiwan). .... that on the warm side of the comfort zone the relative humidity should not ...

  7. Human Adaptation to Space: Space Physiology and Countermeasures

    Science.gov (United States)

    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;

  8. [Human physiology: images and practices of the reflex].

    Science.gov (United States)

    Wübben, Yvonne

    2010-01-01

    The essay examines the function of visualizations and practices in the formation of the reflex concept from Thomas Willis to Marshall Hall. It focuses on the specific form of reflex knowledge that images and practices can contain. In addition, the essay argues that it is through visual representations and experimental practices that technical knowledge is transferred to the field of human reflex physiology. When using technical metaphors in human physiology authors often seem to feel obliged to draw distinctions between humans, machines and animals. On closer scrutiny, these distinctions sometimes fail to establish firm borders between the human and the technical.

  9. Human Physiology in an Aquatic Environment.

    Science.gov (United States)

    Pendergast, David R; Moon, Richard E; Krasney, John J; Held, Heather E; Zamparo, Paola

    2015-09-20

    Water covers over 70% of the earth, has varying depths and temperatures and contains much of the earth's resources. Head-out water immersion (HOWI) or submersion at various depths (diving) in water of thermoneutral (TN) temperature elicits profound cardiorespiratory, endocrine, and renal responses. The translocation of blood into the thorax and elevation of plasma volume by autotransfusion of fluid from cells to the vascular compartment lead to increased cardiac stroke volume and output and there is a hyperperfusion of some tissues. Pulmonary artery and capillary hydrostatic pressures increase causing a decline in vital capacity with the potential for pulmonary edema. Atrial stretch and increased arterial pressure cause reflex autonomic responses which result in endocrine changes that return plasma volume and arterial pressure to preimmersion levels. Plasma volume is regulated via a reflex diuresis and natriuresis. Hydrostatic pressure also leads to elastic loading of the chest, increasing work of breathing, energy cost, and thus blood flow to respiratory muscles. Decreases in water temperature in HOWI do not affect the cardiac output compared to TN; however, they influence heart rate and the distribution of muscle and fat blood flow. The reduced muscle blood flow results in a reduced maximal oxygen consumption. The properties of water determine the mechanical load and the physiological responses during exercise in water (e.g. swimming and water based activities). Increased hydrostatic pressure caused by submersion does not affect stroke volume; however, progressive bradycardia decreases cardiac output. During submersion, compressed gas must be breathed which introduces the potential for oxygen toxicity, narcosis due to nitrogen, and tissue and vascular gas bubbles during decompression and after may cause pain in joints and the nervous system.

  10. Physiological Determinants of Human Acute Hypoxia Tolerance

    Science.gov (United States)

    2013-11-01

    approved in advance by the Civil Aerospace Medical Institute (CAMI) Institutional Review Board for the Protection of Human Subjects, which conforms to the...45.72 ± 10.40 (25.30 – 70.43) Resting VO2 (ml/kg/min) 3.93 ± 0.90 (2.76 – 6.35) DLO2 (ml/mm Hg/min) 40.65 ± 7.72 (25.83 – 59.00) Total Hgb...less SpO2 fell during the 5-min exposure. Max velocity of MCA flow gradually increased after the start of the hypoxia exposure in all subjects and

  11. Measuring Entropy Change in a Human Physiological System

    Directory of Open Access Journals (Sweden)

    Satish Boregowda

    2016-01-01

    Full Text Available The paper presents a novel approach involving the use of Maxwell relations to combine multiple physiological measures to provide a measure of entropy change. The physiological measures included blood pressure (BP, heart rate (HR, skin temperature (ST, electromyogram (EMG, and electrodermal response (EDR. The multiple time-series physiological data were collected from eight subjects in an experimental pilot study conducted at the Human Engineering Laboratory of NASA Langley Research Center. The methodology included data collection during a relaxation period of eighteen minutes followed by a sixty-minute cognitive task. Two types of entropy change were computed: (a entropy change (ΔSBP due to blood pressure, heart rate, and skin temperature and (b entropy change (ΔSEMG due to electromyogram, electrodermal response, and skin temperature. The results demonstrate that entropy change provides a valuable composite measure of individual physiological response to various stressors that could be valuable in the areas of medical research, diagnosis, and clinical practice.

  12. Drawing on student knowledge in human anatomy and physiology

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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…

  14. Development and Implementation of a PSI Course in Human Physiology.

    Science.gov (United States)

    Giese, Maurine; Lawler, Michael

    1978-01-01

    The paper describes the Personalized System of Instruction (PSI) used in an allied health course in human physiology at the University of Texas. Distinguishing features of the PSI system of individualizing courses are mastery learning, self-pacing, and immediate feedback, with the instructor as class manager rather than lecturer. (MF)

  15. Human Physiology: Improving Students' Achievements through Intelligent Studyware.

    Science.gov (United States)

    Dori, Yehudit J.; Yochim, Jerome M.

    1994-01-01

    A studyware comprising a set of interconnected modules on human physiology has been developed and used to improve undergraduate students' achievements. Study results show the scores of students who used the optional computer laboratory sessions were enhanced over those who did not use the studyware. Presents examples from the modules. (LZ)

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

    Science.gov (United States)

    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…

  17. Linking adult hippocampal neurogenesis with human physiology and disease.

    Science.gov (United States)

    Bowers, Megan; Jessberger, Sebastian

    2016-07-01

    We here review the existing evidence linking adult hippocampal neurogenesis and human brain function in physiology and disease. Furthermore, we aim to point out where evidence is missing, highlight current promising avenues of investigation, and suggest future tools and approaches to foster the link between life-long neurogenesis and human brain function. Developmental Dynamics 245:702-709, 2016. © 2016 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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.

  19. Dietary boron: progress in establishing essential roles in human physiology.

    Science.gov (United States)

    Hunt, Curtiss D

    2012-06-01

    This review summarizes the progress made in establishing essential roles for boron in human physiology and assesses that progress in view of criteria for essentiality of elements. The evidence to date suggests that humans and at least some higher animals may use boron to support normal biological functions. These include roles in calcium metabolism, bone growth and maintenance, insulin metabolism, and completion of the life cycle. The biochemical mechanisms responsible for these effects are poorly understood but the nature of boron biochemistry suggests further characterization of the cell signaling molecules capable of complexing with boron. Such characterization may provide insights into the biochemical function(s) of boron in humans.

  20. The physiology of the normal human breast: an exploratory study.

    Science.gov (United States)

    Mills, Dixie; Gordon, Eva J; Casano, Ashley; Lahti, Sarah Michelle; Nguyen, Tinh; Preston, Alex; Tondre, Julie; Wu, Kuan; Yanase, Tiffany; Chan, Henry; Chia, David; Esfandiari, Mahtash; Himmel, Tiffany; Love, Susan M

    2011-12-01

    The physiology of the nonlactating human breast likely plays a key role in factors that contribute to the etiology of breast cancer and other breast conditions. Although there has been extensive research into the physiology of lactation, few reports explore the physiology of the resting mammary gland, including mechanisms by which compounds such as hormones, drugs, and potential carcinogens enter the breast ducts. The purpose of this study was to explore transport of exogenous drugs into ductal fluid in nonlactating women and determine if their concentrations in the fluid are similar to those observed in the breast milk of lactating women. We selected two compounds that have been well characterized during lactation, caffeine and cimetidine. Caffeine passively diffuses into breast milk, but cimetidine is actively transported and concentrated in breast milk. After ingestion of caffeine and cimetidine, 14 nonlactating subjects had blood drawn and underwent ductal lavage at five time points over 12 h to measure drug levels in the fluid and blood. The concentrations of both caffeine and cimetidine in lavage fluid were substantially less than those observed in breast milk. Our results support recent evidence that the cimetidine transporter is not expressed in the nonlactating mammary gland, and highlight intriguing differences in the physiology and molecular transport of the lactating and nonlactating breast. The findings of this exploratory study warrant further exploration into the physiology of the nonlactating mammary gland to elucidate factors involved in disease initiation and progression.

  1. Sunspot Dynamics Are Reflected in Human Physiology and Pathophysiology

    Science.gov (United States)

    Hrushesky, William J. M.; Sothern, Robert B.; Du-Quiton, Jovelyn; Quiton, Dinah Faith T.; Rietveld, Wop; Boon, Mathilde E.

    2011-03-01

    Periodic episodes of increased sunspot activity (solar electromagnetic storms) occur with 10-11 and 5-6 year periodicities and may be associated with measurable biological events. We investigated whether this sunspot periodicity characterized the incidence of Pap smear-determined cervical epithelial histopathologies and human physiologic functions. From January 1983 through December 2003, monthly averages were obtained for solar flux and sunspot numbers; six infectious, premalignant and malignant changes in the cervical epithelium from 1,182,421 consecutive, serially independent, screening Pap smears (59°9"N, 4°29"E); and six human physiologic functions of a healthy man (oral temperature, pulse, systolic and diastolic blood pressure, respiration, and peak expiratory flow), which were measured ∼5 times daily during ∼34,500 self-measurement sessions (44°56"N, 93°8"W). After determining that sunspot numbers and solar flux, which were not annually rhythmic, occurred with a prominent 10-year and a less-prominent 5.75-year periodicity during this 21-year study span, each biological data set was analyzed with the same curve-fitting procedures. All six annually rhythmic Pap smear-detected infectious, premalignant and malignant cervical epithelial pathologies showed strong 10-year and weaker 5.75-year cycles, as did all six self-measured, annually rhythmic, physiologic functions. The phases (maxima) for the six histopathologic findings and five of six physiologic measurements were very near, or within, the first two quarters following the 10-year solar maxima. These findings add to the growing evidence that solar magnetic storm periodicities are mirrored by cyclic phase-locked rhythms of similar period length or lengths in human physiology and pathophysiology.

  2. The biology of human sexuality: evolution, ecology and physiology

    Directory of Open Access Journals (Sweden)

    PW Bateman

    2006-09-01

    Full Text Available Many evolutionary biologists argue that human sexual behaviour can be studied in exactly the same way as that of other species. Many sociologists argue that social influences effectively obscure, and are more important than, a reductionist biological approach to human sexual behaviour. Here,we authors attempt to provide a broad introduction to human sexual behaviour from a biological standpoint and to indicate where the ambiguous areas are. We outline the evolutionary selective pressures that are likely to have influenced human behaviour and mate choice in the past and in the present; ecological features that influence such things as degree of parental care and polygamy; and the associated physiology of human sexuality. Then they end with a discussion of �abnormal� sexuality.

  3. Knowledge environments representing molecular entities for the virtual physiological human.

    Science.gov (United States)

    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.

  4. Effects of weightlessness on human fluid and electrolyte physiology

    Science.gov (United States)

    Leach, Carolyn S.; Johnson, Philip C., Jr.

    1991-01-01

    Skylab and Spacelab data on changes occurring in human fluid and electrolyte physiology during the acute and adaptive phases of adaptation to spaceflight are summarized. The combined results for all three Spacelab studies show that hyponatremia developed within 20 h after the onset of weightlessness and continued throughout the flights, and hypokalemia developed by 40 h. Antidiuretic hormone was increased in plasma throughout the flights. Aldosterone decreased by 40 h, but after 7 days it had reached preflight levels.

  5. DigitalHuman (DH): An Integrative Mathematical Model ofHuman Physiology

    Science.gov (United States)

    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

  6. Physiology

    Science.gov (United States)

    Kay, Ian

    2008-01-01

    Underlying recent developments in health care and new treatments for disease are advances in basic medical sciences. This edition of "Webwatch" focuses on sites dealing with basic medical sciences, with particular attention given to physiology. There is a vast amount of information on the web related to physiology. The sites that are included here…

  7. Is Lutein a Physiologically Important Ligand for Transthyretin in Humans?

    Energy Technology Data Exchange (ETDEWEB)

    Liwei Chen

    2003-05-31

    Lutein and zeaxanthin are the only carotenoids accumulated in the macula of the human retina and are known as the macular pigments (MP). These pigments account for the yellow color of the macula and appear to play an important role in protecting against age-related macular degeneration (AMD). The uptake of lutein and zeaxanthin in human eyes is remarkably specific. It is likely that specific transport or binding proteins are involved. The objective is to determine whether transthyretin (TTR) is a transport protein in human plasma and could thus deliver lutein from the blood to the retina. In this study, they used a biosynthetic {sup 13}C-lutein tracer and gas chromatography-combustion interfaced-isotope ratio mass spectrometry (GCC-IRMS) to gain the requisite sensitivity to detect the minute amounts of lutein expected as a physiological ligand for human transthyretin. The biosynthetic {sup 13}C-labeled lutein tracer was purified from algae. Healthy women (n = 4) each ingested 1 mg of {sup 13}C-labeled lutein daily for 3 days and a blood sample was collected 24 hours after the final dose. Plasma TTR was isolated by retinol-binding protein (RBP)-sepharose affinity chromatography and extracted with chloroform. The {sup 13}C/{sup 12}C ratio in the TTR extract was measured by GCC-IRMS. There was no {sup 13}C-lutein enrichment in the pure TTR extract. This result indicated that lutein is not associated with TTR in human plasma after ingestion in physiological amounts. Some hydrophobic compounds with yellow color may bind to human TTR in the plasma. However, this association needs to be further proved by showing specificity. The study provides a new approach for carotenoid-binding protein studies using a stable isotope tracer method combined with the high precision of GCC-IRMS. The mechanism of selective transport, uptake, and accumulation of lutein in human macula remain to be determined.

  8. Is Lutein a Physiologically Important Ligand for Transthyretin in Humans?

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Liwei [Iowa State Univ., Ames, IA (United States)

    2003-01-01

    Lutein and zeaxanthin are the only carotenoids accumulated in the macula of the human retina and are known as the macular pigments (MP). These pigments account for the yellow color of the macula and appear to play an important role in protecting against age-related macular degeneration (AMD). The uptake of lutein and zeaxanthin in human eyes is remarkably specific. It is likely that specific transport or binding proteins are involved. The objective is to determine whether transthyretin (TTR) is a transport protein in human plasma and could thus deliver lutein from the blood to the retina. In this study, they used a biosynthetic 13C-lutein tracer and gas chromatography-combustion interfaced-isotope ratio mass spectrometry (GCC-IRMS) to gain the requisite sensitivity to detect the minute amounts of lutein expected as a physiological ligand for human transthyretin. The biosynthetic 13C-labeled lutein tracer was purified from algae. Healthy women (n = 4) each ingested 1 mg of 13C-labeled lutein daily for 3 days and a blood sample was collected 24 hours after the final dose. Plasma TTR was isolated by retinol-binding protein (RBP)-sepharose affinity chromatography and extracted with chloroform. The 13C/12C ratio in the TTR extract was measured by GCC-IRMS. There was no 13C-lutein enrichment in the pure TTR extract. This result indicated that lutein is not associated with TTR in human plasma after ingestion in physiological amounts. Some hydrophobic compounds with yellow color may bind to human TTR in the plasma. However, this association needs to be further proved by showing specificity. The study provides a new approach for carotenoid-binding protein studies using a stable isotope tracer method combined with the high precision of GCC-IRMS. The mechanism of selective transport, uptake, and accumulation of lutein in human macula remain to be determined.

  9. PIXE microanalysis in human cells: physiology and pharmacology

    Energy Technology Data Exchange (ETDEWEB)

    Moretto, P.; Llabador, Y.; Ortega, R.; Simonoff, M.; Razafindrabe, L. (Centre d' Etudes Nucleaires Bordeaux/Gradignan, 33 - Gradignan (France))

    1993-04-01

    The micro-PIXE technique has been regularly carried out for more than two years to provide elemental distributions in human cells. Using this technique in the framework of cellular biology, two research axes have been developed: The cellular pharmacology of chemotherapeutic agents and the physiology of ionic cellular exchanges. These studies are based upon in vitro experimental models of human cells, either under the form of isolated cultured cells or as part of well-structured tissues. The aim of this paper is to present the experimental procedures and methodological aspects of cellular and subcellular quantitative mapping. Cell processing, identification of intracellular structures, quantitatives results and beam damage will be discussed and illustrated by examples issuing from the above-mentioned studies. (orig.).

  10. Coupling of the Models of Human Physiology and Thermal Comfort

    Science.gov (United States)

    Pokorny, J.; Jicha, M.

    2013-04-01

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

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

    Science.gov (United States)

    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.

  12. THERMOREGULATION AND HUMAN PERFORMANCE: PHYSIOLOGICAL AND BIOLOGICAL ASPECTS

    Directory of Open Access Journals (Sweden)

    Frank E Marino

    2008-12-01

    Full Text Available Vol 53 (Medicine & Sport Science This collection on the latest interpretation of research data about the relationship between thermoregulation, exercise performance and fatigue is published as the 53rd volume of Medicine and Sport Science Journal. PURPOSE The book aims to explain how the advances in technology and methodology allowed studying the affects of the changing body temperature on metabolism and the role played by the nervous system in shaping human performance under challenging thermal situations. FEATURES This publication provides different interpretations of recent research for a better understanding of the limitations of thermoregulation in nine titles. The presented titles are: The Evolutionary Basis of Thermoregulation and Exercise Performance; Comparative Thermoregulation and the Quest for Athletic Supremacy; Thermoregulation, Fatigue and Exercise Modality; Neuromuscular Response to Exercise Heat Stress; Intestinal Barrier Dysfunction, Endotoxemia and Gastrointestinal Symptoms: The 'Canary in the Coal Mine' during Exercise-Heat Stress?; Effects of Peripheral Cooling on Characteristics of Local Muscle; Cooling Interventions for the Protection and Recovery of Exercise Performance from Exercise-Induced Heat Stress; Ethnicity and Temperature Regulation; Exercise Heat Stress and Metabolism. The evidence for the human's ability to adjust their performance according to the thermal limits in order to preserve cellular homeostasis is particularly noteworthy. AUDIENCE This is a fundamental book for any students and/or researchers involved in the fields of medicine, exercise physiology and human performance with special reference to thermal regulation. ASSESSMENT This publication is a must-read text for all those working in thermal medicine, exercise physiology and human performance fields

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

    Science.gov (United States)

    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…

  14. Human Factors Evaluation of the Hidalgo Equivital EQ-02 Physiological Status Monitoring System

    Science.gov (United States)

    2013-10-11

    Equivital™ EQ-02 physiological status monitoring ( PSM ) system. The usability and acceptability of this system has been tested previously and generally...under CBRNE- PPE provided utility and was comfortable to wear. Thermal strain; CBRNE; PPE; physiological status monitoring; PSM ; human factors; chem...real-time physiological monitoring. The Hidalgo, Ltd. (Cambridge, UK) Equivital™ EQ-02 physiological status monitoring ( PSM ) system is a typical

  15. Modeling physiological and pathological human neurogenesis in the dish

    Directory of Open Access Journals (Sweden)

    Vania eBroccoli

    2014-07-01

    Full Text Available New advances in directing the neuronal differentiation of human embryonic and induced pluripotent stem cells (hPSCs, abbreviation intended to convey both categories of pluripotent stem cells have promoted the development of culture systems capable of modeling early neurogenesis and neural specification at some of their critical milestones. The hPSC-derived neural rosette can be considered the in vitro counterpart of the developing neural tube, since both structures share a virtually equivalent architecture and related functional properties. Epigenetic stimulation methods can modulate the identity of the rosette neural progenitors in order to generate authentic neuronal subtypes, as well as a full spectrum of neural crest derivatives. The intrinsic capacity of induced pluripotent cell-derived neural tissue to self-organize has become fully apparent with the emergence of innovative in vitro systems that are able to shape the neuronal differentiation of hPSCs into organized tissues that develop in three dimensions. However, significant hurdles remain that must be completely solved in order to facilitate the use of hPSCs in modeling (e.g., late-onset disorders or in building therapeutic strategies for cell replacement. In this direction, new procedures have been established to promote the maturation and functionality of hPSC-derived neurons. Meanwhile, new methods to accelerate the aging of in vitro differentiating cells are still in development. hPSC-based technology has matured enough to offer a significant and reliable model system for early and late neurogenesis that could be extremely informative for the study of the physiological and pathological events that occur during this process. Thus, full exploitation of this cellular system can provide a better understanding of the physiological events that shape human brain structures, as well as a solid platform to investigate the pathological mechanisms at the root of human diseases.

  16. Physiological and Biomechanical Mechanisms of Distance Specific Human Running Performance.

    Science.gov (United States)

    Thompson, M A

    2017-08-01

    Running events range from 60-m sprints to ultra-marathons covering 100 miles or more, which presents an interesting diversity in terms of the parameters for successful performance. Here, we review the physiological and biomechanical variations underlying elite human running performance in sprint to ultramarathon distances. Maximal running speeds observed in sprint disciplines are achieved by high vertical ground reaction forces applied over short contact times. To create this high force output, sprint events rely heavily on anaerobic metabolism, as well as a high number and large cross-sectional area of type II fibers in the leg muscles. Middle distance running performance is characterized by intermediates of biomechanical and physiological parameters, with the possibility of unique combinations of each leading to high-level performance. The relatively fast velocities in mid-distance events require a high mechanical power output, though ground reaction forces are less than in sprinting. Elite mid-distance runners exhibit local muscle adaptations that, along with a large anaerobic capacity, provide the ability to generate a high power output. Aerobic capacity starts to become an important aspect of performance in middle distance events, especially as distance increases. In distance running events, V˙O2max is an important determinant of performance, but is relatively homogeneous in elite runners. V˙O2 and velocity at lactate threshold have been shown to be superior predictors of elite distance running performance. Ultramarathons are relatively new running events, as such, less is known about physiological and biomechanical parameters that underlie ultra-marathon performance. However, it is clear that performance in these events is related to aerobic capacity, fuel utilization, and fatigue resistance. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology 2017. This work is written by US Government employees and is in

  17. The role of leptin in human physiology and pathophysiology.

    Science.gov (United States)

    Janeckova, R

    2001-01-01

    This review focuses on current knowledge of leptin biology and the role of leptin in various physiological and pathophysiological states. Leptin is involved in the regulation of body weight. Serum leptin can probably be considered as one of the best biological markers reflecting total body fat in both animals and humans. Obesity in man is accompanied by increased circulating leptin concentrations. Gender differences clearly exist. Leptin is not only correlated to a series of endocrine parameters such as insulin, glucocorticoids, thyroid hormones, testosterone, but it also seems to be involved in mediating some endocrine mechanisms (onset of puberty, insulin secretion) and diseases (obesity, polycystic ovary syndrome). It has also been suggested that leptin can act as a growth factor in the fetus and the neonate.

  18. Integrating an Interprofessional Education Experience Into a Human Physiology Course.

    Science.gov (United States)

    Edwards, Scott; Molina, Patricia E; McDonough, Kathleen H; Mercante, Donald E; Gunaldo, Tina P

    2017-09-01

    To obtain physician assistant (PA) student perceptions about an interprofessional education (IPE) training experience embedded in a multidisciplinary science course. An IPE training experience was integrated into a graduate human physiology course offered to PA, physical therapy, and graduate studies students. The focus of the activity related to the Interprofessional Education Collaborative (IPEC) competency domains of (1) roles and responsibilities and (2) teams and teamwork. Effectiveness was assessed in pretraining and posttraining surveys, which included questions addressing student self-perceptions of IPEC competency domains, student assessment of the learning activity, and student reflection. We observed a statistically significant positive change in PA student perceptions of IPEC competency domains. Students also provided a positive evaluation of the IPE activity and communicated personal improvements in IPE perspectives. Incorporating planned IPE experiences into multidisciplinary health science courses represents an appropriate venue for PA students to learn and apply interprofessional competencies, which may benefit future interprofessional practice.

  19. Human physiological reaction to geomagnetic disturbances of solar origin

    Science.gov (United States)

    Dimitrova, Sv.; Stoilova, I.

    2002-12-01

    During the last two decades publications about the influence of geomagnetic activity on human health increase but there are not still strong evidences for this relationship. We performed measurements and observations of 86 working volunteers during the period of autumn and spring equinox. We examined systolic, diastolic blood pressure and pulse rate. We also collected data for some personal health condition complaints. Four-way analyses of variance (MANOVA method) were employed and the influence of factors geomagnetic activity level, sequence of the days of measurements with respect to the increased geomagnetic activity, medicaments and sex was investigated. We also performed three-way analyses of variance and investigated influence of atmospheric pressure, medicaments and sex on the physiological parameters under consideration. Our investigations indicate that most of the persons examined irrespectively to their health status could be sensitive to the geomagnetic changes, which influence directly self-confidence and working ability.

  20. Anatomical and physiological development of the human inner ear.

    Science.gov (United States)

    Lim, Rebecca; Brichta, Alan M

    2016-08-01

    We describe the development of the human inner ear with the invagination of the otic vesicle at 4 weeks gestation (WG), the growth of the semicircular canals from 5 WG, and the elongation and coiling of the cochlea at 10 WG. As the membranous labyrinth takes shape, there is a concomitant development of the sensory neuroepithelia and their associated structures within. This review details the growth and differentiation of the vestibular and auditory neuroepithelia, including synaptogenesis, the expression of stereocilia and kinocilia, and innervation of hair cells by afferent and efferent nerve fibres. Along with development of essential sensory structures we outline the formation of crucial accessory structures of the vestibular system - the cupula and otolithic membrane and otoconia as well as the three cochlea compartments and the tectorial membrane. Recent molecular studies have elaborated on classical anatomical studies to characterize the development of prosensory and sensory regions of the fetal human cochlea using the transcription factors, PAX2, MAF-B, SOX2, and SOX9. Further advances are being made with recent physiological studies that are beginning to describe when hair cells become functionally active during human gestation. This article is part of a Special Issue entitled Reviews 2016>.

  1. Physiological Health Challenges for Human Missions to Mars

    Science.gov (United States)

    Norsk, Peter

    2015-01-01

    During the next decades, manned space missions are expected to be aiming at the Lagrange points, near Earth asteroids, and Mars flyby and/or landing. The question is therefore: Are we ready to go? To answer this with a yes, we are currently using the International Space Station to develop an integrated human physiological countermeasure suite. The integrated countermeasure suite will most likely encounter: 1) Exercise devices for aerobic, dynamic and resistive exercise training; 2) sensory-motor computer training programs and anti-motion sickness medication for preparing EVAs and G-transitions; 3) lower limb bracelets for preventing and/or treating the VIIP (vision impairment and intracranial pressure) syndrome; 4) nutritional components for maintenance of bone, muscle, the cardiovascular system and preventing oxidative stress and damage and immune deficiencies (e. g. omega-3 fatty acids, PRO/K, anti-oxidants and less salt and iron); 5) bisphosphonates for preventing bone degradation.; 6) lower body compression garment and oral salt and fluid loading for landing on a planetary surface to combat orthostatic intolerance; 7) laboratory analysis equipment for individualized monitoring of biomarkers in blood, urine and saliva for estimation of health status in; 8) advanced ultrasound techniques for monitoring bone and cardiovascular health; and 9) computer modeling programs for individual health status assessments of efficiency and subsequent adjustments of countermeasures. In particular for future missions into deep space, we are concerned with the synergistic effects of weightlessness, radiation, operational constraints and other spaceflight environmental factors. Therefore, increased collaboration between physiological, behavioral, radiation and space vehicle design disciplines are strongly warranted. Another venue we are exploring in NASA's Human Research Program is the usefulness of artificial gravity for mitigating the health risks of long duration weightlessness.

  2. Potential applications of gut microbiota to control human physiology.

    Science.gov (United States)

    Umu, Ozgün Candan Onarman; Oostindjer, Marije; Pope, Phillip B; Svihus, Birger; Egelandsdal, Bjørg; Nes, Ingolf F; Diep, Dzung B

    2013-11-01

    The microorganisms living in our gut have been a black box to us for a long time. However, with the recent advances in high throughput DNA sequencing technologies, it is now possible to assess virtually all microorganisms in our gut including non-culturable ones. With the use of powerful bioinformatics tools to deal with multivariate analyses of huge amounts of data from metagenomics, metatranscriptomics, metabolomics, we now start to gain some important insights into these tiny gut inhabitants. Our knowledge is increasing about who they are, to some extent, what they do and how they affect our health. Gut microbiota have a broad spectrum of possible effects on health, from preventing serious diseases, improving immune system and gut health to stimulating the brain centers responsible for appetite and food intake control. Further, we may be on the verge of being capable of manipulating the gut microbiota by diet control to possibly improve our health. Diets consisting of different components that are fermentable by microbiota are substrates for different kinds of microbes in the gut. Thus, diet control can be used to favor the growth of some selected gut inhabitants. Nowadays, the gut microbiota is taken into account as a separate organ in human body and their activities and metabolites in gut have many physiological and neurological effects. In this mini-review, we discuss the diversity of gut microbiota, the technologies used to assess them, factors that affect microbial composition and metabolites that affect human physiology, and their potential applications in satiety control via the gut-brain axis.

  3. Mitochondrial uncoupling proteins in human physiology and disease.

    Science.gov (United States)

    Hagen, T; Vidal-Puig, A

    2002-02-01

    Uncoupling proteins are mitochondrial carrier proteins that catalyse a regulated proton leak across the inner mitochondrial membrane, diverting free energy from ATP synthesis by the mitochondrial F0F1-ATP synthase to the production of heat. Uncoupling protein 1 (UCP1), which is exclusively expressed in brown adipose tissue, is the mediator of thermogenesis in response to beta-adrenergic stimulation. Using gene a knockout mouse model, UCP1 has been shown to be required for cold acclimation. Two homologues of UCP1, UCP2 and UCP3, have been identified recently and show a much wider tissue distribution. UCP2 and UCP3 have been postulated to play a role in the regulation of cold acclimation, energy expenditure and diet-induced thermogenesis in humans, who, in contrast to rodents, have very little brown fat in adult life. However, evidence is accumulating that thermogenesis and regulation of body weight may not be the physiological functions of UCP2 and UCP3. For instance, mice deficient for UCP2 or UCP3 are not cold-intolerant and do not develop obesity. Alternative functions were suggested, primarily based on findings in UCP2 and UCP3 gene knockout mice. Both UCP2- and UCP3-deficient mice were found to overproduce reactive oxygen species and UCP2-deficient mice to hypersecrete insulin. Thus, the UCP1 homologues may play a role in regulating mitochondrial production of reactive oxygen species and b-cell function. In this review, we discuss the role of UCP1, UCP2 and UCP3 in human physiology and disease, primarily based on findings from the various animal models that have been generated.

  4. The physiology and pathophysiology of human breath-hold diving.

    Science.gov (United States)

    Lindholm, Peter; Lundgren, Claes E G

    2009-01-01

    This is a brief overview of physiological reactions, limitations, and pathophysiological mechanisms associated with human breath-hold diving. Breath-hold duration and ability to withstand compression at depth are the two main challenges that have been overcome to an amazing degree as evidenced by the current world records in breath-hold duration at 10:12 min and depth of 214 m. The quest for even further performance enhancements continues among competitive breath-hold divers, even if absolute physiological limits are being approached as indicated by findings of pulmonary edema and alveolar hemorrhage postdive. However, a remarkable, and so far poorly understood, variation in individual disposition for such problems exists. Mortality connected with breath-hold diving is primarily concentrated to less well-trained recreational divers and competitive spearfishermen who fall victim to hypoxia. Particularly vulnerable are probably also individuals with preexisting cardiac problems and possibly, essentially healthy divers who may have suffered severe alternobaric vertigo as a complication to inadequate pressure equilibration of the middle ears. The specific topics discussed include the diving response and its expression by the cardiovascular system, which exhibits hypertension, bradycardia, oxygen conservation, arrhythmias, and contraction of the spleen. The respiratory system is challenged by compression of the lungs with barotrauma of descent, intrapulmonary hemorrhage, edema, and the effects of glossopharyngeal insufflation and exsufflation. Various mechanisms associated with hypoxia and loss of consciousness are discussed, including hyperventilation, ascent blackout, fasting, and excessive postexercise O(2) consumption. The potential for high nitrogen pressure in the lungs to cause decompression sickness and N(2) narcosis is also illuminated.

  5. PERCEPTIONS REGARDING THE INTEGRATED HUMAN ANATOMY AND PHYSIOLOGY COURSE AMONG UNDERGRADUATE PHARMACY STUDENTS

    OpenAIRE

    Joan Bryant*1, Manjunatha Goud BK2, Anand Srinivasan3 and Vijayalakshmi SB3

    2016-01-01

    Human Anatomy and Physiology is an important core component for all allied healthcare professional education. At our university, we offer an integrated Human Anatomy and Physiology course (HAP) to the first year Pharmacy students. The main objective of this study was to ascertain and compare Pharmacy undergraduate students’ opinions and attitudes towards the integrated course of human anatomy and physiology. A pre-validated questionnaire was given to students of first year pharma...

  6. Estrogen receptor polymorphisms: significance to human physiology, disease and therapy.

    Science.gov (United States)

    Figtree, Gemma A; Noonan, Jonathon E; Bhindi, Ravinay; Collins, Peter

    2009-01-01

    Other than its well-recognized effects on reproductive physiology, estrogen has important actions in a wide variety of other body systems with important examples including bone, blood vessels and the heart. These effects are seen in both females and males. Investigators have hypothesized those genetic variants in the genes coding for estrogen signaling proteins may cause variable sensitivity to the hormone and influence an individual's estrogen-sensitive phenotypes. The most obvious candidate genes are the estrogen receptors alpha and (ERalpha and beta). However, the regulation of these genes is complex and not well understood. Furthermore, their coding exons, and regulatory sequences are dispersed across large segments of the genome. A number of common polymorphisms have been identified in both ERalpha and ERbeta, with variable degrees of evidence of their direct biological significance and their association with human disease. The identification of genetic variations associated with altered estrogen response is of potential public health importance. Insights may be gained into the pathogenesis of estrogen sensitive diseases such as osteoporosis, breast cancer and cardiovascular disease contributing to the development and application of newer therapies for these disorders. Furthermore, genetic variants that alter sensitivity to estrogen may affect both therapeutic and harmful responses to exogenous estrogen administered in the form of the oral contraceptive pill or hormone replacement therapy. This clinical significance has led to the publication of a number of patents which will be reviewed.

  7. HuPSON: the human physiology simulation ontology.

    Science.gov (United States)

    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.

  8. How consumer physical activity monitors could transform human physiology research.

    Science.gov (United States)

    Wright, Stephen P; Hall Brown, Tyish S; Collier, Scott R; Sandberg, Kathryn

    2017-03-01

    A sedentary lifestyle and lack of physical activity are well-established risk factors for chronic disease and adverse health outcomes. Thus, there is enormous interest in measuring physical activity in biomedical research. Many consumer physical activity monitors, including Basis Health Tracker, BodyMedia Fit, DirectLife, Fitbit Flex, Fitbit One, Fitbit Zip, Garmin Vivofit, Jawbone UP, MisFit Shine, Nike FuelBand, Polar Loop, Withings Pulse O2, and others have accuracies similar to that of research-grade physical activity monitors for measuring steps. This review focuses on the unprecedented opportunities that consumer physical activity monitors offer for human physiology and pathophysiology research because of their ability to measure activity continuously under real-life conditions and because they are already widely used by consumers. We examine current and potential uses of consumer physical activity monitors as a measuring or monitoring device, or as an intervention in strategies to change behavior and predict health outcomes. The accuracy, reliability, reproducibility, and validity of consumer physical activity monitors are reviewed, as are limitations and challenges associated with using these devices in research. Other topics covered include how smartphone apps and platforms, such as the Apple ResearchKit, can be used in conjunction with consumer physical activity monitors for research. Lastly, the future of consumer physical activity monitors and related technology is considered: pattern recognition, integration of sleep monitors, and other biosensors in combination with new forms of information processing.

  9. Physiological significance of nitrergic transmission in human penile erection

    Institute of Scientific and Technical Information of China (English)

    P.G.Adaikan; S.C.Ng

    2000-01-01

    The corpora cavemosa (CC) muscles of the human penis and their structural arrangements are essential for the physiology of erection. Contraction of this muscle causes detumescence, and relaxation, tumescence. The motor excitatory neurotransmission is adrenergic, acting through the alpha adrenoceptors. Continuous adrenergic transmitter (noradrenaline) release is necessary for the maintenance of non-erectile (contractile) state of the penis. The inhibitory neurotransmitter that relaxes CC muscle to produce erection is nitrergic i.e., the chemical messenger being nitric oxide (NO). The latter can also be released from cavernous endothelium. Presence of NO increases intracellular cGMP through activation of the enzyme guanylate cyclase. This causes relaxation of CC muscle. Phosphodiesterase type 5 (PDE5) is responsible for the degradation of cGMP and regulation of CC muscle tone. Specific PDE inhibitors such as sildenafil enhance the intracellular cGMP to improve erection. Increase in intracellular cAMP can also bring about pharmacological erection in man (eg. PGE1, papaverine and histamine). Inhibition of excessive adrenergic tone with appropriate alpha - adrenergic blocking agents (eg. phentolamine) can also contribute to the onset of pharmacological erection. ( Asian J Androl 2000 ; 2 : 51 - 56 )

  10. Physiological stress reactivity in human pregnancy - a review

    NARCIS (Netherlands)

    Weerth, C. de; Buitelaar, J.K.

    2005-01-01

    Prenatal maternal stress has been found to have long-lasting effects on the behavioral and physiological development of the offspring. These programming effects on the fetus would be physiologically mediated through heightened and/or abnormal activity of the maternal sympathetic-adrenal-medullary sy

  11. Physiological stress reactivity in human pregnancy--a review.

    NARCIS (Netherlands)

    Weerth, C. de; Buitelaar, J.K.

    2005-01-01

    Prenatal maternal stress has been found to have long-lasting effects on the behavioral and physiological development of the offspring. These programming effects on the fetus would be physiologically mediated through heightened and/or abnormal activity of the maternal sympathetic-adrenal-medullary sy

  12. Physiological stress reactivity in human pregnancy--a review.

    NARCIS (Netherlands)

    Weerth, C. de; Buitelaar, J.K.

    2005-01-01

    Prenatal maternal stress has been found to have long-lasting effects on the behavioral and physiological development of the offspring. These programming effects on the fetus would be physiologically mediated through heightened and/or abnormal activity of the maternal sympathetic-adrenal-medullary

  13. Physiological stress reactivity in human pregnancy - a review

    NARCIS (Netherlands)

    Weerth, C. de; Buitelaar, J.K.

    2005-01-01

    Prenatal maternal stress has been found to have long-lasting effects on the behavioral and physiological development of the offspring. These programming effects on the fetus would be physiologically mediated through heightened and/or abnormal activity of the maternal sympathetic-adrenal-medullary

  14. Inhibition of human pancreatic and biliary output but not intestinal motility by physiological intraileal lipid loads

    DEFF Research Database (Denmark)

    Keller, Jutta; Holst, Jens Juul; Layer, Peter

    2005-01-01

    . Physiological postprandial ileal lipid concentrations dose dependently inhibited human digestive pancreatic protease and bile acid output, but not intestinal motor activity. Thus physiological postprandial ileal nutrient exposure may be of importance for the termination of digestive secretory responses......Lipid perfusion into the distal ileal lumen at supraphysiological loads inhibits pancreatic exocrine secretion and gastrointestinal motility in humans. In the present study, we sought to determine the effects of physiological postprandial intraileal lipid concentrations on endogenously stimulated...

  15. Physiological characterization of human muscle acetylcholine receptors from ALS patients

    Science.gov (United States)

    Palma, Eleonora; Inghilleri, Maurizio; Conti, Luca; Deflorio, Cristina; Frasca, Vittorio; Manteca, Alessia; Pichiorri, Floriana; Roseti, Cristina; Torchia, Gregorio; Limatola, Cristina; Grassi, Francesca; Miledi, Ricardo

    2011-01-01

    Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motor neurons leading to muscle paralysis. Research in transgenic mice suggests that the muscle actively contributes to the disease onset, but such studies are difficult to pursue in humans and in vitro models would represent a good starting point. In this work we show that tiny amounts of muscle from ALS or from control denervated muscle, obtained by needle biopsy, are amenable to functional characterization by two different technical approaches: “microtransplantation” of muscle membranes into Xenopus oocytes and culture of myogenic satellite cells. Acetylcholine (ACh)-evoked currents and unitary events were characterized in oocytes and multinucleated myotubes. We found that ALS acetylcholine receptors (AChRs) retain their native physiological characteristics, being activated by ACh and nicotine and blocked by α-bungarotoxin (α-BuTX), d-tubocurarine (dTC), and galantamine. The reversal potential of ACh-evoked currents and the unitary channel behavior were also typical of normal muscle AChRs. Interestingly, in oocytes injected with muscle membranes derived from ALS patients, the AChRs showed a significant decrease in ACh affinity, compared with denervated controls. Finally, riluzole, the only drug currently used against ALS, reduced, in a dose-dependent manner, the ACh-evoked currents, indicating that its action remains to be fully characterized. The two methods described here will be important tools for elucidating the role of muscle in ALS pathogenesis and for developing drugs to counter the effects of this disease. PMID:22128328

  16. Human insulin dynamics in women: a physiologically based model.

    Science.gov (United States)

    Weiss, Michael; Tura, Andrea; Kautzky-Willer, Alexandra; Pacini, Giovanni; D'Argenio, David Z

    2016-02-01

    Currently available models of insulin dynamics are mostly based on the classical compartmental structure and, thus, their physiological utility is limited. In this work, we describe the development of a physiologically based model and its application to data from 154 patients who underwent an insulin-modified intravenous glucose tolerance test (IM-IVGTT). To determine the time profile of endogenous insulin delivery without using C-peptide data and to evaluate the transcapillary transport of insulin, the hepatosplanchnic, renal, and peripheral beds were incorporated into the circulatory model as separate subsystems. Physiologically reasonable population mean estimates were obtained for all estimated model parameters, including plasma volume, interstitial volume of the peripheral circulation (mainly skeletal muscle), uptake clearance into the interstitial space, hepatic and renal clearance, as well as total insulin delivery into plasma. The results indicate that, at a population level, the proposed physiologically based model provides a useful description of insulin disposition, which allows for the assessment of muscle insulin uptake.

  17. Molecular clocks and the human condition: approaching their characterization in human physiology and disease.

    Science.gov (United States)

    Fitzgerald, G A; Yang, G; Paschos, G K; Liang, X; Skarke, C

    2015-09-01

    Molecular clockworks knit together diverse biological networks and compelling evidence from model systems infers their importance in metabolism, immunological and cardiovascular function. Despite this and the diurnal variation in many aspects of human physiology and the phenotypic expression of disease, our understanding of the role and importance of clock function and dysfunction in humans is modest. There are tantalizing hints of connection across the translational divide and some correlative evidence of gene variation and human disease but most of what we know derives from forced desynchrony protocols in controlled environments. We now have the ability to monitor quantitatively ex vivo or in vivo the genome, metabolome, proteome and microbiome of humans in the wild. Combining this capability, with the power of mobile telephony and the evolution of remote sensing, affords a new opportunity for deep phenotyping, including the characterization of diurnal behaviour and the assessment of the impact of the clock on approved drug function.

  18. New dimensions in tissue engineering: possible models for human physiology.

    Science.gov (United States)

    Baar, Keith

    2005-11-01

    Tissue engineering is a discipline of great promise. In some areas, such as the cornea, tissues engineered in the laboratory are already in clinical use. In other areas, where the tissue architecture is more complex, there are a number of obstacles to manoeuvre before clinically relevant tissues can be produced. However, even in areas where clinically relevant tissues are decades away, the tissues being produced at the moment provide powerful new models to aid the understanding of complex physiological processes. This article provides a personal view of the role of tissue engineering in advancing our understanding of physiology, with specific attention being paid to musculoskeletal tissues.

  19. 'Systems biology' in human exercise physiology: is it something different from integrative physiology?

    Science.gov (United States)

    Greenhaff, Paul L; Hargreaves, Mark

    2011-03-01

    On first impression the 'whole-istic approach to understanding biology' that has been used to describe Systems Biology bears a striking resemblance to what many of us know as Integrative Physiology. However, closer scrutiny reveals that at the present time Systems Biology is rooted in processes operating at a cellular level ('the study of an organism, viewed as an integrated and interacting network of genes, proteins and biochemical reactions which give rise to life ultimately responsible for an organism's form and functions'; http://www.systemsbiology.org), and appears to have evolved as a direct result of advances in high throughput molecular biology platforms (and associated bioinformatics) over the past decade. The Systems Biology approach is in many ways laudable, but it will be immediately apparent to most exercise or integrative physiologists that the challenge of understanding the whole-animal response to exercise as a network of integrated and interacting genes, proteins and biochemical reactions is unlikely to be realized in the near future. This short review will attempt to clarify conceptual inconsistencies between the fields of Systems Biology and Integrative Physiology in the context of exercise science, and will attempt to identify the challenges to whole-body physiologists wishing to harness the tools of Systems Biology.

  20. Physiological responses to exposure to carbon dioxide and human bioeffluents

    DEFF Research Database (Denmark)

    Zhang, Xiaojing; Wargocki, Pawel; Lian, Zhiwei

    2015-01-01

    Present paper describes physiological responses as a result of exposures to CO2 (between 500 ppm to 3,000 ppm) with and without bioeffluents. Twenty-five subjects participated. They were exposed in the climate chamber for 255 minutes in groups of five at a time. During exposure, they performed di...

  1. Selected physiologic compatibilities and incompatibilities between human and porcine organ systems.

    Science.gov (United States)

    Ibrahim, Zuhaib; Busch, Jamie; Awwad, Michel; Wagner, Robert; Wells, Kevin; Cooper, David K C

    2006-11-01

    The shortage of donor organs is a major barrier to clinical organ transplantation. Although xenotransplantation is considered one of the alternatives to human organ transplantation, there are immunologic and physiologic incompatibilities between humans and pigs. With the exception of coagulation, the major potential physiologic incompatibilities relating to function of the kidney, heart, liver, lungs, pancreatic islets, and hormones are reviewed. Some of these physiologic differences can be overcome by producing genetically altered pigs to improve compatibility with humans. The possibility of producing such pigs for organ transplantation is considered.

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

    Science.gov (United States)

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

    2008-12-01

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

  3. [Foods and drinks in a 19th century human physiology textbook].

    Science.gov (United States)

    Chiancone, Francesco M

    2004-01-01

    The Author reports on the chapter of "Nutrition" in the Human Physiology textbook by P. Albertoni and A. Stefani published in the first half of the 19th century. This is one of the first textbooks that treats Physiology as an experimental science in contrast with the thinking of the previous century which was still dominated by Galen and Dioscorides.

  4. Acute and phase-shifting effects of ocular and extraocular light in human circadian physiology

    NARCIS (Netherlands)

    Ruger, M; Gordijn, MCM; Beersma, DGM; de Vries, B; Daan, S

    2003-01-01

    Light can influence physiology and performance of humans in two distinct ways. It can acutely change the level of physiological and behavioral parameters, and it can induce a phase shift in the circadian oscillators underlying variations in these levels. Until recently, both effects were thought to

  5. Translational applications of evaluating physiologic variability in human endotoxemia.

    Science.gov (United States)

    Scheff, Jeremy D; Mavroudis, Panteleimon D; Calvano, Steve E; Androulakis, Ioannis P

    2013-08-01

    Dysregulation of the inflammatory response is a critical component of many clinically challenging disorders such as sepsis. Inflammation is a biological process designed to lead to healing and recovery, ultimately restoring homeostasis; however, the failure to fully achieve those beneficial results can leave a patient in a dangerous persistent inflammatory state. One of the primary challenges in developing novel therapies in this area is that inflammation is comprised of a complex network of interacting pathways. Here, we discuss our approaches towards addressing this problem through computational systems biology, with a particular focus on how the presence of biological rhythms and the disruption of these rhythms in inflammation may be applied in a translational context. By leveraging the information content embedded in physiologic variability, ranging in scale from oscillations in autonomic activity driving short-term heart rate variability to circadian rhythms in immunomodulatory hormones, there is significant potential to gain insight into the underlying physiology.

  6. Predicting physiological capacity of human load carriage - a review.

    Science.gov (United States)

    Drain, Jace; Billing, Daniel; Neesham-Smith, Daniel; Aisbett, Brad

    2016-01-01

    This review article aims to evaluate a proposed maximum acceptable work duration model for load carriage tasks. It is contended that this concept has particular relevance to physically demanding occupations such as military and firefighting. Personnel in these occupations are often required to perform very physically demanding tasks, over varying time periods, often involving load carriage. Previous research has investigated concepts related to physiological workload limits in occupational settings (e.g. industrial). Evidence suggests however, that existing (unloaded) workload guidelines are not appropriate for load carriage tasks. The utility of this model warrants further work to enable prediction of load carriage durations across a range of functional workloads for physically demanding occupations. If the maximum duration for which personnel can physiologically sustain a load carriage task could be accurately predicted, commanders and supervisors could better plan for and manage tasks to ensure operational imperatives were met whilst minimising health risks for their workers.

  7. HumMod: A modeling environment for the simulation of integrative human physiology

    Directory of Open Access Journals (Sweden)

    Robert eHester

    2011-04-01

    Full Text Available Mathematical models and simulations are important tools in discovering key causal relationships governing physiological processes. Simulations guide and improve outcomes of medical interventions involving complex physiology. We developed HumMod, a Windows-based model of integrative human physiology. HumMod consists of 5000 variables describing cardiovascular, respiratory, renal, neural, endocrine, skeletal muscle and metabolic physiology. The model is constructed from empirical data obtained from peer-reviewed physiological literature. All model details, including variables, parameters and quantitative relationships, are described in Extensible Markup Language (XML files. The executable (HumMod.exe parses the XML and displays the results of the physiological simulations. The XML description of physiology in HumMod¹s modeling environment allows investigators to add detailed descriptions of human physiology to test new concepts. Additional or revised XML content is parsed and incorporated into the model. The model accurately predicts both qualitative and quantitative changes in clinical and experimental responses. The model is useful in understanding proposed physiological mechanisms and physiological interactions that are not evident, allowing one to observe higher level emergent properties of the complex physiological systems. HumMod has many uses, for instance, analysis of renal control of blood pressure, central role of the liver in creating and maintaining insulin resistance, and mechanisms causing orthostatic hypotension in astronauts. Users simulate different physiological and pathophysiological situations by interactively altering numerical parameters and viewing time-dependent responses. HumMod provides a modeling environment to understand the complex interactions of integrative physiology. HumMod can be downloaded at http://hummod.org

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

    Science.gov (United States)

    Hester, Robert L; Brown, Alison J; Husband, Leland; Iliescu, Radu; Pruett, Drew; Summers, Richard; Coleman, Thomas G

    2011-01-01

    Mathematical models and simulations are important tools in discovering key causal relationships governing physiological processes. Simulations guide and improve outcomes of medical interventions involving complex physiology. We developed HumMod, a Windows-based model of integrative human physiology. HumMod consists of 5000 variables describing cardiovascular, respiratory, renal, neural, endocrine, skeletal muscle, and metabolic physiology. The model is constructed from empirical data obtained from peer-reviewed physiological literature. All model details, including variables, parameters, and quantitative relationships, are described in Extensible Markup Language (XML) files. The executable (HumMod.exe) parses the XML and displays the results of the physiological simulations. The XML description of physiology in HumMod's modeling environment allows investigators to add detailed descriptions of human physiology to test new concepts. Additional or revised XML content is parsed and incorporated into the model. The model accurately predicts both qualitative and quantitative changes in clinical and experimental responses. The model is useful in understanding proposed physiological mechanisms and physiological interactions that are not evident, allowing one to observe higher level emergent properties of the complex physiological systems. HumMod has many uses, for instance, analysis of renal control of blood pressure, central role of the liver in creating and maintaining insulin resistance, and mechanisms causing orthostatic hypotension in astronauts. Users simulate different physiological and pathophysiological situations by interactively altering numerical parameters and viewing time-dependent responses. HumMod provides a modeling environment to understand the complex interactions of integrative physiology. HumMod can be downloaded at http://hummod.org.

  9. A physiologically based in silico kinetic model predicting plasma cholesterol concentrations in humans

    NARCIS (Netherlands)

    Pas, van de N.C.A.; Woutersen, R.A.; Ommen, van B.; Rietjens, I.M.C.M.; Graaf, de A.A.

    2012-01-01

    Increased plasma cholesterol concentration is associated with increased risk of cardiovascular disease. This study describes the development, validation, and analysis of a physiologically based kinetic (PBK) model for the prediction of plasma cholesterol concentrations in humans. This model was dire

  10. Chemical regeneration of human tooth enamel under near-physiological conditions.

    Science.gov (United States)

    Yin, Yujing; Yun, Song; Fang, Jieshi; Chen, Haifeng

    2009-10-21

    Regenerating the microstructure of human tooth enamel under near-physiological conditions (pH 6.0, 37 degrees C, 1 atm) using a simple chemical approach demonstrates a potential application to repair enamel damage in dental clinics.

  11. A physiologically based in silico kinetic model predicting plasma cholesterol concentrations in humans

    NARCIS (Netherlands)

    Pas, N.C.A. van de; Woutersen, R.A.; Ommen, B. van; Rietjens, I.M.C.M.; Graaf, A.A. de

    2012-01-01

    Increased plasma cholesterol concentration is associated with increased risk of cardiovascular disease. This study describes the development, validation, and analysis of a physiologically based kinetic (PBK) model for the prediction of plasma cholesterol concentrations in humans. This model was

  12. Critical review evaluating the pig as a model for human nutritional physiology

    NARCIS (Netherlands)

    Roura, Eugeni; Koopmans, Sietse-Jan; Lallès, Jean-Paul; Huerou-Luron, Le Isabelle; Jager, de Nadia; Schuurman, Teun; Val-Laillet, David

    2016-01-01

    The present review examines the pig as a model for physiological studies in human subjects related to nutrient sensing, appetite regulation, gut barrier function, intestinal microbiota and nutritional neuroscience. The nutrient-sensing mechanisms regarding acids (sour), carbohydrates (sweet), glutam

  13. Critical review evaluating the pig as a model for human nutritional physiology

    National Research Council Canada - National Science Library

    Roura, Eugeni; Koopmans, Sietse-Jan; Lallès, Jean-Paul; Le Huerou-Luron, Isabelle; de Jager, Nadia; Schuurman, Teun; Val-Laillet, David

    2016-01-01

    The present review examines the pig as a model for physiological studies in human subjects related to nutrient sensing, appetite regulation, gut barrier function, intestinal microbiota and nutritional neuroscience...

  14. Critical review evaluating the pig as a model for human nutritional physiology

    NARCIS (Netherlands)

    Roura, Eugeni; Koopmans, Sietse-Jan; Lallès, Jean-Paul; Huerou-Luron, Le Isabelle; Jager, de Nadia; Schuurman, Teun; Val-Laillet, David

    2016-01-01

    The present review examines the pig as a model for physiological studies in human subjects related to nutrient sensing, appetite regulation, gut barrier function, intestinal microbiota and nutritional neuroscience. The nutrient-sensing mechanisms regarding acids (sour), carbohydrates (sweet),

  15. The biology of human sexuality: evolution, ecology and physiology

    OpenAIRE

    PW Bateman; NC Bennett

    2006-01-01

    Many evolutionary biologists argue that human sexual behaviour can be studied in exactly the same way as that of other species. Many sociologists argue that social influences effectively obscure, and are more important than, a reductionist biological approach to human sexual behaviour. Here,we authors attempt to provide a broad introduction to human sexual behaviour from a biological standpoint and to indicate where the ambiguous areas are. We outline the evolutionary selective pressures that...

  16. The human cerebellum: a review of physiologic neuroanatomy.

    Science.gov (United States)

    Roostaei, Tina; Nazeri, Arash; Sahraian, Mohammad Ali; Minagar, Alireza

    2014-11-01

    The cerebellum resides in the posterior cranial fossa dorsal to the brainstem and has diverse connections to the cerebrum, brain stem, and spinal cord. It is anatomically and physiologically divided into distinct functional compartments and is composed of highly regular arrays of neuronal units, each sharing the same basic cerebellar microcircuitry. Its circuitry is critically involved in motor control and motor learning, and its role in nonmotor cognitive and affective functions is becoming increasingly recognized. This article describes the cerebellar gross and histologic neuroanatomy in relation to its function, and the relevance of cerebellar circuitry and firing patterns to motor learning.

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

    Science.gov (United States)

    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.

  18. Gastrointestinal Physiology During Head Down Tilt Bedrest in Human Subjects

    Science.gov (United States)

    Vaksman, Z.; Guthienz, J.; Putcha, L.

    2008-01-01

    Introduction: Gastrointestinal (GI) motility plays a key role in the physiology and function of the GI tract. It directly affects absorption of medications and nutrients taken by mouth, in addition to indirectly altering GI physiology by way of changes in the microfloral composition and biochemistry of the GI tract. Astronauts have reported nausea, loss of appetite and constipation during space flight all of which indicate a reduction in GI motility and function similar to the one seen in chronic bed rest patients. The purpose of this study is to determine GI motility and bacterial proliferation during -6 degree head down tilt bed rest (HTD). Methods: Healthy male and female subjects between the ages of 25-40 participated in a 60 day HTD study protocol. GI transit time (GITT) was determined using lactulose breath hydrogen test and bacterial overgrowth was measured using glucose breath hydrogen test. H. Pylori colonization was determined using C13-urea breath test (UBIT#). All three tests were conducted on 9 days before HDT, and repeated on HDT days 2, 28, 58, and again on day 7 after HDT. Results: GITT increased during HTD compared to the respective ambulatory control values; GITT was significantly lower on day 7 after HTD. A concomitant increase in bacterial colonization was also noticed during HDT starting after approximately 28 days of HDT. However, H. Pylori proliferation was not recorded during HDT as indicated by UBIT#. Conclusion: GITT significantly decreased during HDT with a concomitant increase in the proliferation of GI bacterial flora but not H. pylori.

  19. The role of adiponectin in human vascular physiology.

    Science.gov (United States)

    Vaiopoulos, Aristeidis G; Marinou, Kyriakoula; Christodoulides, Constantinos; Koutsilieris, Michael

    2012-03-08

    Adiponectin (ApN) is an adipose tissue-derived hormone which is involved in a wide variety of physiological processes including energy metabolism, inflammation, and vascular physiology via actions on a broad spectrum of target organs including liver, skeletal muscle, and vascular endothelium. Besides possessing insulin sensitizing and anti-inflammatory properties ApN also exerts a pivotal role in vascular protection through activation of multiple intracellular signaling cascades. Enhancement of nitric oxide generation and attenuation of reactive oxygen species production in endothelial cells along with reduced vascular smooth muscle cell proliferation and migration constitute some of ApN's vasoprotective actions. Additionally, recent data indicate that ApN has direct myocardio-protective effects. Decreased plasma ApN levels are implicated in the pathogenesis of the metabolic syndrome and atherosclerosis and may serve as a diagnostic and prognostic biomarker as well as a rational pharmaco-therapeutic target to treat these disorders. This review article summarizes recent work on the cardiovascular actions of ApN.

  20. Nutrition and human physiological adaptations to space flight

    Science.gov (United States)

    Lane, H. W.; LeBlanc, A. D.; Putcha, L.; Whitson, P. A.

    1993-01-01

    Space flight provides a model for the study of healthy individuals undergoing unique stresses. This review focuses on how physiological adaptations to weightlessness may affect nutrient and food requirements in space. These adaptations include reductions in body water and plasma volume, which affect the renal and cardiovascular systems and thereby fluid and electrolyte requirements. Changes in muscle mass and function may affect requirements for energy, protein and amino acids. Changes in bone mass lead to increased urinary calcium concentrations, which may increase the risk of forming renal stones. Space motion sickness may influence putative changes in gastro-intestinal-hepatic function; neurosensory alterations may affect smell and taste. Some or all of these effects may be ameliorated through the use of specially designed dietary countermeasures.

  1. [Human orgasm from the physiological perspective--part I].

    Science.gov (United States)

    Gałecki, Piotr; Depko, Andrzej; Jedrzejewska, Sylwia; Talarowska, Monika

    2012-07-01

    Physiological phenomenon of sexuality occurring in both sexes that brings physical and mental satisfaction, and often affects the quality of life is an orgasm. The ability to experience regular orgasms affects relationship with partner. The definition of orgasm is not an easy task. The way of experiencing it is subjective, and the possibility of observing significantly reduced. Contemporary works on the phenomenon of orgasm are concentrated on several aspects: biological perspective (neurophysiological and biochemical determinants of orgasm), psychological perspective and on the differences in its course in both sexes. In sexology are two models of sexual response: a linear model of sexual response (by W. Masters and V. Johnson, and H. S. Kaplan) and the circular model of sexual response (created by R. Basson). The ability to experiencing an orgasm is inherent in men. In women, that phenomenon is acquired, is the consequence of further experience.

  2. Trace elements in human physiology and pathology. Copper.

    Science.gov (United States)

    Tapiero, H; Townsend, D M; Tew, K D

    2003-11-01

    Copper is a trace element, important for the function of many cellular enzymes. Copper ions can adopt distinct redox states oxidized Cu(II) or reduced (I), allowing the metal to play a pivotal role in cell physiology as a catalytic cofactor in the redox chemistry of enzymes, mitochondrial respiration, iron absorption, free radical scavenging and elastin cross-linking. If present in excess, free copper ions can cause damage to cellular components and a delicate balance between the uptake and efflux of copper ions determines the amount of cellular copper. In biological systems, copper homeostasis has been characterized at the molecular level. It is coordinated by several proteins such as glutathione, metallothionein, Cu-transporting P-type ATPases, Menkes and Wilson proteins and by cytoplasmic transport proteins called copper chaperones to ensure that it is delivered to specific subcellular compartments and thereby to copper-requiring proteins.

  3. Biochemical and physiological effects of phenols on human health

    Directory of Open Access Journals (Sweden)

    Danuta Wojcieszyńska

    2011-03-01

    Full Text Available Introduction of phenol compounds into environment results from human activities.. Moreover plants produce polyphenols as by products of metabolism Their influence on human health is very important. It is observed, that polyphenols found in groceries are the most abundant dietary antioxidants, anti-inflammatory, anti allergic, antiarteriosclerotic and antitumour factors. Alkylphenols, chlorophenols, nitrophenols or biphenyls can be toxic for body systems and because of their similarity to ligands of steroid receptors they can influence the activity of endocrine system. Their appearance in organisms enhances the risk of developing type 2 diabetes mellitus, hypertension, dyslipidemia, cancer, problems with fertility. Moreover strong genotoxic activities of these compounds is observed. Because they influence human health in many different ways continuous monitoring of phenols content in environment seems to be very important.

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

    Science.gov (United States)

    Hinderliter, P M; Thrall, K D; Corley, R A; Bloemen, L J; Bogdanffy, M S

    2005-05-01

    Vinyl acetate has been shown to induce nasal lesions in rodents in inhalation bioassays. A physiologically based pharmacokinetic (PBPK) model for vinyl acetate has been used in human risk assessment, but previous in vivo validation was conducted only in rats. Controlled human exposures to vinyl acetate were conducted to provide validation data for the application of the model in humans. Five volunteers were exposed to 1, 5, and 10 ppm 13C1,13C2 vinyl acetate via inhalation. A probe inserted into the nasopharyngeal region sampled both 13C1,13C2 vinyl acetate and the major metabolite 13C1,13C2 acetaldehyde during rest and light exercise. Nasopharyngeal air concentrations were analyzed in real time by ion trap mass spectrometry (MS/MS). Experimental concentrations of both vinyl acetate and acetaldehyde were then compared to predicted concentrations calculated from the previously published human model. Model predictions of vinyl acetate nasal extraction compared favorably with measured values of vinyl acetate, as did predictions of nasopharyngeal acetaldehyde when compared to measured acetaldehyde. The results showed that the current PBPK model structure and parameterization are appropriate for vinyl acetate. These analyses were conducted from 1 to 10 ppm vinyl acetate, a range relevant to workplace exposure standards but which would not be expected to saturate vinyl acetate metabolism. Risk assessment based on this model further concluded that 24 h per day exposures up to 1 ppm do not present concern regarding cancer or non-cancer toxicity. Validation of the vinyl acetate human PBPK model provides support for these conclusions.

  5. Human physiology as the determining factor in protective clothing design

    NARCIS (Netherlands)

    Daanen, Hein

    2014-01-01

    Protective clothing is designed to protect humans against risks like fire, chemicals or blunt impact. Although protect¡ve clothing diminishes the effects of external risks, it may hinder people in functioning and it may also introduce new (internal) risks. Manufacturers are often not aware of the se

  6. Transporters in human platelets: physiologic function and impact for pharmacotherapy.

    Science.gov (United States)

    Jedlitschky, Gabriele; Greinacher, Andreas; Kroemer, Heyo K

    2012-04-12

    Platelets store signaling molecules (eg, serotonin and ADP) within their granules. Transporters mediate accumulation of these molecules in platelet granules and, on platelet activation, their translocation across the plasma membrane. The balance between transporter-mediated uptake and elimination of signaling molecules and drugs in platelets determines their intracellular concentrations and effects. Several members of the 2 major transporter families, ATP-binding cassette (ABC) transporters and solute carriers (SLCs), have been identified in platelets. An example of an ABC transporter is MRP4 (ABCC4), which facilitates ADP accumulation in dense granules. MRP4 is a versatile transporter, and various additional functions have been proposed, notably lipid mediator release and a role in aspirin resistance. Several other ABC proteins have been detected in platelets with functions in glutathione and lipid homeostasis. The serotonin transporter (SERT, SLC6A4) in the platelet plasma membrane represents a well-characterized example of the SLC family. Moreover, recent experiments indicate expression of OATP2B1 (SLCO2B1), a high affinity transporter for certain statins, in platelets. Changes in transporter localization and expression can affect platelet function and drug sensitivity. This review summarizes available data on the physiologic and pharmacologic role of transporters in platelets.

  7. Physiological models of body composition and human obesity

    Directory of Open Access Journals (Sweden)

    Shapses Sue A

    2007-09-01

    Full Text Available Abstract Background The body mass index (BMI is the standard parameter for predicting body fat fraction and for classifying degrees of obesity. Currently available regression equations between BMI and fat are based on 2 or 3 parameter empirical fits and have not been validated for highly obese subjects. We attempt to develop regression relations that are based on realistic models of body composition changes in obesity. These models, if valid, can then be extrapolated to the high fat fraction of the morbidly obese. Methods The analysis was applied to 3 compartment (density and total body water measurements of body fat. The data was collected at the New York Obesity Research Center, Body Composition Unit, as part of ongoing studies. A total of 1356 subjects were included, with a BMI range of 17 to 50 for males and 17 to 65 for females. The body composition model assumes that obese subjects can be represented by the sum of a standard lean reference subject plus an extra weight that has a constant adipose, bone and muscle fraction. Results There is marked age and sex dependence in the relationship between BMI and fat fraction. There was no significant difference among Caucasians, Blacks and Hispanics while Asians had significantly greater fat fraction for the same BMI. A linear relationship between BMI and fat fraction provides a good description for men but overestimates the fat fraction in morbidly obese women for whom a non-linear regression should be used. New regression relations for predicting body fat just from experimental measurements of body density are described that are more accurate then those currently used. From the fits to the experimental BMI and density data, a quantitative description of the bone, adipose and muscle body composition of lean and obese subjects is derived. Conclusion Physiologically realistic models of body composition provide both accurate regression relations and new insights about changes in body composition in

  8. Adipose circadian rhythms: translating cellular and animal studies to human physiology.

    Science.gov (United States)

    Johnston, Jonathan D

    2012-02-05

    Emerging links between circadian rhythms and metabolism promise much for the understanding of metabolic physiology and pathophysiology, in which white adipose tissue (WAT) plays a prominent role. Many WAT endocrine molecules, termed adipokines, display rhythmic plasma concentration. Moreover, similar to most other tissues, WAT exhibits widespread 24-h variation in gene expression, with approximately 20% of the murine adipose transcriptome estimated to undergo daily variation. A major limitation to human chronobiology research is the availability of physiologically defined peripheral tissues. To date most analyses of in vivo human peripheral clocks has been limited to blood leucocytes. However, subcutaneous adipose tissue represents a novel opportunity to study peripheral molecular rhythms that are of clearly defined metabolic relevance. This review summarises basic concepts of circadian and metabolic physiology before then comparing alternative protocols used to analyse the rhythmic properties of human adipose tissue.

  9. Smart sensor: a platform for an interactive human physiological state recognition study

    Directory of Open Access Journals (Sweden)

    Andrej Gorochovik

    2013-03-01

    Full Text Available This paper describes a concept of making interactive human state recognition systems based on smart sensor design. The token measures on proper ADC signal processing had significantly lowered the interference level. A more reliable way of measuring human skin temperature was offered by using Maxim DS18B20 digital thermometers. They introduced a more sensible response to temperature changes compared to previously used analog LM35 thermometers. An adaptive HR measuring algorithm was introduced to suppress incorrect ECG signal readings caused by human muscular activities. User friendly interactive interface for touch sensitive GLCD screen was developed to present real time physiological data readings both in numerals and graphics. User was granted an ability to dynamically customize data processing methods according to his needs. Specific procedures were developed to simplify physiological state recording for further analysis. The introduced physiological data sampling and preprocessing platform was optimized to be compatible with “ATmega Oscilloscope” PC data collecting and visualizing software.

  10. Trace elements in human physiology and pathology: zinc and metallothioneins.

    Science.gov (United States)

    Tapiero, Haim; Tew, Kenneth D

    2003-11-01

    Zinc is one of the most abundant nutritionally essential elements in the human body. It is found in all body tissues with 85% of the whole body zinc in muscle and bone, 11% in the skin and the liver and the remaining in all the other tissues. In multicellular organisms, virtually all zinc is intracellular, 30-40% is located in the nucleus, 50% in the cytoplasm, organelles and specialized vesicles (for digestive enzymes or hormone storage) and the remainder in the cell membrane. Zinc intake ranges from 107 to 231 micromol/d depending on the source, and human zinc requirement is estimated at 15 mg/d. Zinc has been shown to be essential to the structure and function of a large number of macromolecules and for over 300 enzymic reactions. It has both catalytic and structural roles in enzymes, while in zinc finger motifs, it provides a scaffold that organizes protein sub-domains for the interaction with either DNA or other proteins. It is critical for the function of a number of metalloproteins, inducing members of oxido-reductase, hydrolase ligase, lyase family and has co-activating functions with copper in superoxide dismutase or phospholipase C. The zinc ion (Zn(++)) does not participate in redox reactions, which makes it a stable ion in a biological medium whose potential is in constant flux. Zinc ions are hydrophilic and do not cross cell membranes by passive diffusion. In general, transport has been described as having both saturable and non-saturable components, depending on the Zn(II) concentrations involved. Zinc ions exist primarily in the form of complexes with proteins and nucleic acids and participate in all aspects of intermediary metabolism, transmission and regulation of the expression of genetic information, storage, synthesis and action of peptide hormones and structural maintenance of chromatin and biomembranes.

  11. Rowing, the ultimate challenge to the human body - implications for physiological variables

    DEFF Research Database (Denmark)

    Volianitis, S.; Secher, Niels H.

    2009-01-01

    Clinical diagnoses depend on a variety of physiological variables but the full range of these variables is seldom known. With the load placed on the human body during competitive rowing, the physiological range for several variables is illustrated. The extreme work produced during rowing...... is explained by the seated position and the associated ability to increase venous return and, thus, cardiac output. This review highlights experimental work on Olympic rowing that presents a unique challenge to the human capacities, including cerebral metabolism, to unprecedented limits, and provides a unique...

  12. Cholesterol sulfate in human physiology: what's it all about?

    Science.gov (United States)

    Strott, Charles A; Higashi, Yuko

    2003-07-01

    Cholesterol sulfate is quantitatively the most important known sterol sulfate in human plasma, where it is present in a concentration that overlaps that of the other abundant circulating steroid sulfate, dehydroepiandrosterone (DHEA) sulfate. Although these sulfolipids have similar production and metabolic clearance rates, they arise from distinct sources and are metabolized by different pathways. While the function of DHEA sulfate remains an enigma, cholesterol sulfate has emerged as an important regulatory molecule. Cholesterol sulfate is a component of cell membranes where it has a stabilizing role, e.g., protecting erythrocytes from osmotic lysis and regulating sperm capacitation. It is present in platelet membranes where it supports platelet adhesion. Cholesterol sulfate can regulate the activity of serine proteases, e.g., those involved in blood clotting, fibrinolysis, and epidermal cell adhesion. As a result of its ability to regulate the activity of selective protein kinase C isoforms and modulate the specificity of phosphatidylinositol 3-kinase, cholesterol sulfate is involved in signal transduction. Cholesterol sulfate functions in keratinocyte differentiation, inducing genes that encode for key components involved in development of the barrier. The accumulating evidence demonstrating a regulatory function for cholesterol sulfate appears solid; the challenge now is to work out the molecular mechanisms whereby this interesting molecule carries out its various roles.

  13. Matters of taste: bridging molecular physiology and the humanities.

    Science.gov (United States)

    Rangachari, P K; Rangachari, Usha

    2015-12-01

    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 evaluation procedures were used: problem summaries and problem-solving exercises (tripartite problem-solving exercise) for the problem-based learning component and group tasks and individual exercises for the cultural issues. Self-selected groups chose specific tasks from a prescribed list of options (setting up a journal in molecular gastronomy, developing an electronic tongue, designing a restaurant for synesthetes, organizing a farmers' market, marketing a culinary tour, framing hedonic scales, exploring changing tastes through works of art or recipe books, and crafting beers for space travel). Individual tasks were selected from a menu of options (book reviews, film reviews, conversations, creative writing, and oral exams). A few guest lecturers (wine making, cultural anthropology, film analysis, and nutritional epidemiology) added more flavor. The course was rated highly for its learning value (8.5 ± 1.2, n = 62) and helped students relate biological mechanisms to cultural issues (9.0 ± 0.9, n = 62).

  14. Thermal imaging to detect physiological indicators of stress in humans

    Science.gov (United States)

    Cross, Carl B.; Skipper, Julie A.; Petkie, Douglas T.

    2013-05-01

    Real-time, stand-off sensing of human subjects to detect emotional state would be valuable in many defense, security and medical scenarios. We are developing a multimodal sensor platform that incorporates high-resolution electro-optical and mid-wave infrared (MWIR) cameras and a millimeter-wave radar system to identify individuals who are psychologically stressed. Recent experiments have aimed to: 1) assess responses to physical versus psychological stressors; 2) examine the impact of topical skin products on thermal signatures; and 3) evaluate the fidelity of vital signs extracted from thermal imagery and radar signatures. Registered image and sensor data were collected as subjects (n=32) performed mental and physical tasks. In each image, the face was segmented into 29 non-overlapping segments based on fiducial points automatically output by our facial feature tracker. Image features were defined that facilitated discrimination between psychological and physical stress states. To test the ability to intentionally mask thermal responses indicative of anxiety or fear, subjects applied one of four topical skin products to one half of their face before performing tasks. Finally, we evaluated the performance of two non-contact techniques to detect respiration and heart rate: chest displacement extracted from the radar signal and temperature fluctuations at the nose tip and regions near superficial arteries to detect respiration and heart rates, respectively, extracted from the MWIR imagery. Our results are very satisfactory: classification of physical versus psychological stressors is repeatedly greater than 90%, thermal masking was almost always ineffective, and accurate heart and respiration rates are detectable in both thermal and radar signatures.

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

    Science.gov (United States)

    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.

  16. Animal Farm: Considerations in Animal Gastrointestinal Physiology and Relevance to Drug Delivery in Humans.

    Science.gov (United States)

    Hatton, Grace B; Yadav, Vipul; Basit, Abdul W; Merchant, Hamid A

    2015-09-01

    "All animals are equal, but some are more equal than others" was the illustrious quote derived from British writer George Orwell's famed work, Animal Farm. Extending beyond the remit of political allegory, however, this statement would appear to hold true for the selection of appropriate animal models to simulate human physiology in preclinical studies. There remain definite gaps in our current knowledge with respect to animal physiology, notably those of intra- and inter-species differences in gastrointestinal (GI) function, which may affect oral drug delivery and absorption. Factors such as cost and availability have often influenced the choice of animal species without clear justification for their similarity to humans, and lack of standardization in techniques employed in past studies using various animals may also have contributed to the generation of contradictory results. As it stands, attempts to identify a single animal species as appropriately representative of human physiology and which may able to adequately simulate human in vivo conditions are limited. In this review, we have compiled and critically reviewed data from numerous studies of GI anatomy and physiology of various animal species commonly used in drug delivery modeling, commenting on the appropriateness of these animals for in vivo comparison and extrapolation to humans.

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

    Science.gov (United States)

    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.

  18. Population physiology: leveraging electronic health record data to understand human endocrine dynamics.

    Directory of Open Access Journals (Sweden)

    D J Albers

    Full Text Available Studying physiology and pathophysiology over a broad population for long periods of time is difficult primarily because collecting human physiologic data can be intrusive, dangerous, and expensive. One solution is to use data that have been collected for a different purpose. Electronic health record (EHR data promise to support the development and testing of mechanistic physiologic models on diverse populations and allow correlation with clinical outcomes, but limitations in the data have thus far thwarted such use. For example, using uncontrolled population-scale EHR data to verify the outcome of time dependent behavior of mechanistic, constructive models can be difficult because: (i aggregation of the population can obscure or generate a signal, (ii there is often no control population with a well understood health state, and (iii diversity in how the population is measured can make the data difficult to fit into conventional analysis techniques. This paper shows that it is possible to use EHR data to test a physiological model for a population and over long time scales. Specifically, a methodology is developed and demonstrated for testing a mechanistic, time-dependent, physiological model of serum glucose dynamics with uncontrolled, population-scale, physiological patient data extracted from an EHR repository. It is shown that there is no observable daily variation the normalized mean glucose for any EHR subpopulations. In contrast, a derived value, daily variation in nonlinear correlation quantified by the time-delayed mutual information (TDMI, did reveal the intuitively expected diurnal variation in glucose levels amongst a random population of humans. Moreover, in a population of continuously (tube fed patients, there was no observable TDMI-based diurnal signal. These TDMI-based signals, via a glucose insulin model, were then connected with human feeding patterns. In particular, a constructive physiological model was shown to correctly

  19. The physiological period length of the human circadian clock in vivo is directly proportional to period in human fibroblasts.

    Directory of Open Access Journals (Sweden)

    Lucia Pagani

    Full Text Available BACKGROUND: Diurnal behavior in humans is governed by the period length of a circadian clock in the suprachiasmatic nuclei of the brain hypothalamus. Nevertheless, the cell-intrinsic mechanism of this clock is present in most cells of the body. We have shown previously that for individuals of extreme chronotype ("larks" and "owls", clock properties measured in human fibroblasts correlated with extreme diurnal behavior. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we have measured circadian period in human primary fibroblasts taken from normal individuals and, for the first time, compared it directly with physiological period measured in vivo in the same subjects. Human physiological period length was estimated via the secretion pattern of the hormone melatonin in two different groups of sighted subjects and one group of totally blind subjects, each using different methods. Fibroblast period length was measured via cyclical expression of a lentivirally delivered circadian reporter. Within each group, a positive linear correlation was observed between circadian period length in physiology and in fibroblast gene expression. Interestingly, although blind individuals showed on average the same fibroblast clock properties as sighted ones, their physiological periods were significantly longer. CONCLUSIONS/SIGNIFICANCE: We conclude that the period of human circadian behaviour is mostly driven by cellular clock properties in normal individuals and can be approximated by measurement in peripheral cells such as fibroblasts. Based upon differences among sighted and blind subjects, we also speculate that period can be modified by prolonged unusual conditions such as the total light deprivation of blindness.

  20. A model of human physiology and comfort for assessing complex thermal environments

    Energy Technology Data Exchange (ETDEWEB)

    Huizenga, C.; Zhang Hui; Arens, E. [University of California, Berkeley, CA (United States). Center for Environmental Design Research

    2001-07-01

    The Berkeley Comfort Model is based on the Stolwijk model of human thermal regulation but includes several significant improvements. Our new model allows an unlimited body segment (compared to six in the Stolwijk model). Each segment is modeled as four body layers (core, muscle, fat, and skin tissues) and a clothing layer. Physiological mechanisms such as vasodilation, vasoconstriction, sweating, and metabolic heat production are explicitly considered. Convection, conduction (such as to a car seat or other surface in contact with any part of the body) and radiation between the body and the environment are treated independently. The model is capable of predicting human physiological response to transient, non-uniform thermal environments. This paper describes the physiological algorithms as well as the implementation of the model. (author)

  1. Physiologically Based Biokinetic (PBBK) Modeling of Safrole Bioactivation and Detoxification in Humans as Compared With Rats

    NARCIS (Netherlands)

    Martati, E.; Boersma, M.G.; Spenkelink, A.; Khadka, D.B.; Bladeren, van P.J.; Rietjens, I.; Punt, A.

    2012-01-01

    A physiologically based biokinetic (PBBK) model for the alkenylbenzene safrole in humans was developed based on in vitro- and in silico-derived kinetic parameters. With the model obtained, the time- and dose-dependent formation of the proximate and ultimate carcinogenic metabolites, 1'-hydroxysafrol

  2. Audio-Tutorial Project: An Audio-Tutorial Approach to Human Anatomy and Physiology.

    Science.gov (United States)

    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…

  3. Understanding Protein Synthesis: A Role-Play Approach in Large Undergraduate Human Anatomy and Physiology Classes

    Science.gov (United States)

    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…

  4. Predicting dopamine D2 receptor occupancy in humans using a physiology-based approach

    NARCIS (Netherlands)

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

    2011-01-01

    Objectives: A hybrid physiology-based pharmacokinetic and pharmacodynamic model (PBPKPD) was used to predict the time course of dopamine receptor occupancy (D2RO) in human striatum following the administration of antipsychotic (AP) drugs, using in vitro and in silico information. Methods: A hybrid P

  5. Characteristics of an Intelligent Computer Assisted Instruction Shell with an Example in Human Physiology.

    Science.gov (United States)

    Dori, Yehudit J.; Yochim, Jerome M.

    1992-01-01

    Discusses exemplary teacher and student characteristics that can provide the base to generate an Intelligent Computer Assisted Instruction (ICAI) shell. Outlines the expertise, learning, student-model, and inference modules of an ICAI shell. Describes the development of an ICAI shell for an undergraduate course in human physiology. (33 references)…

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

    Science.gov (United States)

    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…

  7. Coursera's Introductory Human Physiology Course: Factors That Characterize Successful Completion of a MOOC

    Science.gov (United States)

    Engle, Deborah; Mankoff, Chris; Carbrey, Jennifer

    2015-01-01

    Since Massive Open Online Courses (MOOCs) are accessible by anyone in the world at no cost, they have large enrollments that are conducive to educational research. This study examines students in the Coursera MOOC, Introductory Human Physiology. Of the 33,378 students who accessed the course, around 15,000 students responded to items on the…

  8. Simulating the physiology of athletes during endurance sports events: Modelling human energy conversion and metabolism

    NARCIS (Netherlands)

    Beek, J.H.G.M. van; Supandi, F.; Gavai, A.K.; Graaf, A.A. de; Binsl, T.W.; Hettling, H.

    2011-01-01

    The human physiological system is stressed to its limits during endurance sports competition events.We describe a whole body computational model for energy conversion during bicycle racing. About 23 per cent of the metabolic energy is used for muscle work, the rest is converted to heat. We

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

    Science.gov (United States)

    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.

  10. Simulating the physiology of athletes during endurance sports events: Modelling human energy conversion and metabolism

    NARCIS (Netherlands)

    Beek, J.H.G.M. van; Supandi, F.; Gavai, A.K.; Graaf, A.A. de; Binsl, T.W.; Hettling, H.

    2011-01-01

    The human physiological system is stressed to its limits during endurance sports competition events.We describe a whole body computational model for energy conversion during bicycle racing. About 23 per cent of the metabolic energy is used for muscle work, the rest is converted to heat. We calculate

  11. Understanding Protein Synthesis: A Role-Play Approach in Large Undergraduate Human Anatomy and Physiology Classes

    Science.gov (United States)

    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…

  12. Beyond diet reconstruction: stable isotope applications to human physiology, health, and nutrition.

    Science.gov (United States)

    Reitsema, Laurie J

    2013-01-01

    Analysis of stable carbon and nitrogen isotopes from soft or mineralized tissues is a direct and widely-used technique for modeling diets. In addition to its continued role in paleodiet analysis, stable isotope analysis is now contributing to studies of physiology, disease, and nutrition in archaeological and living human populations. In humans and other animals, dietary uptake and distribution of carbon and nitrogen among mineralized and soft tissue is carried out with varying efficiency due to factors of internal biology. Human pathophysiologies may lead to pathology-influenced isotopic fractionation that can be exploited to understand not just skeletal health and diet, but physiological health and nutrition. This study reviews examples from human biology, non-human animal ecology, biomedicine, and bioarchaeology demonstrating how stable isotope analyses are usefully applied to the study of physiological adaptation and adaptability. Suggestions are made for future directions in applying stable isotope analysis to the study of nutritional stress, disease, and growth and development in living and past human populations.

  13. Evidence for a physiological role of intracellularly occurring photolabile nitrogen oxides in human skin fibroblasts.

    Science.gov (United States)

    Opländer, Christian; Wetzel, Wiebke; Cortese, Miriam M; Pallua, Norbert; Suschek, Christoph V

    2008-05-01

    Nitric oxide (NO) plays a pivotal role in human skin biology. Cutaneous NO can be produced enzymatically by NO synthases (NOS) as well as enzyme independently via photodecomposition of photolabile nitrogen oxides (PNOs) such as nitrite or nitroso compounds, both found in human skin tissue in comparably high concentrations. Although the physiological role of NOS-produced NO in human skin is well defined, nothing is known about the biological relevance or the chemical origin of intracellularly occurring PNOs. We here, for the first time, give evidence that in human skin fibroblasts (FB) PNOs represent the oxidation products of NOS-produced NO and that in human skin fibroblasts intracellularly occurring PNOs effectively protect against the injurious effects of UVA radiation by a NO-dependent mechanism. In contrast, in PNO-depleted FB cultures an increased susceptibility to UVA-induced lipid peroxidation and cell death is observed, whereas supplementation of PNO-depleted FB cultures with physiological nitrite concentrations (10 microM) or with exogenously applied NO completely restores UVA-increased injuries. Thus, intracellular PNOs are biologically relevant and represent an important initial shield functioning in human skin physiology against UVA radiation. Consequently, nonphysiological low PNO concentrations might promote known UVA-related skin injuries such as premature aging and carcinogenesis.

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

    Science.gov (United States)

    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.

  15. Policy needs and options for a common approach towards modelling and simulation of human physiology and diseases with a focus on the virtual physiological human.

    Science.gov (United States)

    Viceconti, Marco; McCulloch, Andrew D

    2011-01-01

    Life is the result of an intricate systemic interaction between many processes occurring at radically different spatial and temporal scales. Every day, worldwide biomedical research and clinical practice produce a huge amount of information on such processes. However, this information being highly fragmented, its integration is largely left to the human actors who find this task increasingly and ever more demanding in a context where the information available continues to increase exponentially. Investments in the Virtual Physiological Human (VPH) research are largely motivated by the need for integration in healthcare. As all health information becomes digital, the complexity of health care will continue to evolve, translating into an ever increasing pressure which will result from a growing demand in parallel to limited budgets. Hence, the best way to achieve the dream of personalised, preventive, and participative medicine at sustainable costs will be through the integration of all available data, information and knowledge.

  16. Physiological Effects Associated with Quinoa Consumption and Implications for Research Involving Humans: a Review.

    Science.gov (United States)

    Simnadis, Thomas George; Tapsell, Linda C; Beck, Eleanor J

    2015-09-01

    Quinoa is a pseudo-grain consumed as a dietary staple in South America. In recent years, consumer demand for quinoa in the developed world has grown steadily. Its perceived health benefits have been cited as a driving force behind this trend, but there are very few human studies investigating the impact of quinoa consumption. The aim of this review was to identify physiological effects of quinoa consumption with potential for human health. A critical evaluation of animal model studies was conducted. The quality of identified studies was assessed using a methodological quality assessment tool and summative conclusions were drawn to guide the direction of future human research. The majority of studies were of fair quality. Purported physiological effects of quinoa consumption included decreased weight gain, improved lipid profile and improved capacity to respond to oxidative stress. These physiological effects were attributed to the presence of saponins, protein and 20-hydroxyecdysone in the quinoa seed. The implications of these findings are that human studies should investigate the impact of quinoa consumption on weight gain and lipid levels. The role of quinoa as an antioxidant is still unclear and requires further elucidation in animal models.

  17. Identifying blood biomarkers and physiological processes that distinguish humans with superior performance under psychological stress.

    Directory of Open Access Journals (Sweden)

    Amanda M Cooksey

    Full Text Available BACKGROUND: Attrition of students from aviation training is a serious financial and operational concern for the U.S. Navy. Each late stage navy aviator training failure costs the taxpayer over $1,000,000 and ultimately results in decreased operational readiness of the fleet. Currently, potential aviators are selected based on the Aviation Selection Test Battery (ASTB, which is a series of multiple-choice tests that evaluate basic and aviation-related knowledge and ability. However, the ASTB does not evaluate a person's response to stress. This is important because operating sophisticated aircraft demands exceptional performance and causes high psychological stress. Some people are more resistant to this type of stress, and consequently better able to cope with the demands of naval aviation, than others. METHODOLOGY/PRINCIPAL FINDINGS: Although many psychological studies have examined psychological stress resistance none have taken advantage of the human genome sequence. Here we use high-throughput -omic biology methods and a novel statistical data normalization method to identify plasma proteins associated with human performance under psychological stress. We identified proteins involved in four basic physiological processes: innate immunity, cardiac function, coagulation and plasma lipid physiology. CONCLUSIONS/SIGNIFICANCE: The proteins identified here further elucidate the physiological response to psychological stress and suggest a hypothesis that stress-susceptible pilots may be more prone to shock. This work also provides potential biomarkers for screening humans for capability of superior performance under stress.

  18. Impact of indoor thermal comfort on physiological parameters of human body

    Institute of Scientific and Technical Information of China (English)

    郑洁; 张瑜; 姚润明

    2009-01-01

    With the living standards gradually improved,the buildings with safe,comfortable,healthy indoor thermal environment would be the ideal pursuit. But to create the preferable indoor thermal environment,it is necessary to research physiological influence of indoor thermal environment on human body. So a typical region of hot-humid climate in Chongqing,China,was considered as the object to study physiological indexes of human body. And the indoor thermal environment parameters and physiological indexes of human body were the main measurements. 20 volunteer students were organized to take part in the experiments in the laboratory during this summer. And two methods,physical measuring and questionnaire investigation,were used in the experiments. The results show that the increase in indoor air temperature reduces the uncomfortable feeling of air draft. Indoor air temperature has visible effects on MCS (motor nerve conduction speed),SCS (sensory nerve conduction speed),HR (heart rate),the ECG (electrocardiogram)-QT segment and SSEP (short somatosensory evoked potential)-latent period of N9. Therefore,a safe,comfortable and healthful indoor environment can be created by considering these factors.

  19. Identifying Blood Biomarkers and Physiological Processes That Distinguish Humans with Superior Performance under Psychological Stress

    Science.gov (United States)

    Cooksey, Amanda M.; Momen, Nausheen; Stocker, Russell; Burgess, Shane C.

    2009-01-01

    Background Attrition of students from aviation training is a serious financial and operational concern for the U.S. Navy. Each late stage navy aviator training failure costs the taxpayer over $1,000,000 and ultimately results in decreased operational readiness of the fleet. Currently, potential aviators are selected based on the Aviation Selection Test Battery (ASTB), which is a series of multiple-choice tests that evaluate basic and aviation-related knowledge and ability. However, the ASTB does not evaluate a person's response to stress. This is important because operating sophisticated aircraft demands exceptional performance and causes high psychological stress. Some people are more resistant to this type of stress, and consequently better able to cope with the demands of naval aviation, than others. Methodology/Principal Findings Although many psychological studies have examined psychological stress resistance none have taken advantage of the human genome sequence. Here we use high-throughput -omic biology methods and a novel statistical data normalization method to identify plasma proteins associated with human performance under psychological stress. We identified proteins involved in four basic physiological processes: innate immunity, cardiac function, coagulation and plasma lipid physiology. Conclusions/Significance The proteins identified here further elucidate the physiological response to psychological stress and suggest a hypothesis that stress-susceptible pilots may be more prone to shock. This work also provides potential biomarkers for screening humans for capability of superior performance under stress. PMID:20020041

  20. A probabilistic model of human variability in physiology for future application to dose reconstruction and QIVIVE

    Directory of Open Access Journals (Sweden)

    Kevin eMcNally

    2015-10-01

    Full Text Available The risk assessment of environmental chemicals and drugs is undergoing a paradigm shift in approach which seeks the full replacement of animal testing with high throughput, mechanistic, in vitro systems. This new approach will be reliant on the measurement in vitro, of concentration-dependent responses where prolonged excessive perturbations of specific biochemical pathways are likely to lead to adverse health effects in an intact organism. Such an approach requires a framework, into which disparate data generated by in vitro, in silico and in chemico systems can be integrated and utilised for quantitative in vitro-to-in vivo extrapolation (QIVIVE, ultimately to the human population level. Physiologically based pharmacokinetic (PBPK models are ideally suited to this and are needed to translate in vitro concentration- response relationships to an exposure or dose, route and duration regime in human populations. Thus a realistic description of the variation in the physiology of the human population being modelled is critical. Whilst various studies in the past decade have made progress in describing human variability, the algorithms are typically coded in computer programs and as such are unsuitable for reverse dosimetry. In this report we overcome this limitation by developing a hierarchical statistical model using standard probability distributions for the specification of a virtual US and UK human population. The work draws on information from both population databases and cadaver studies.

  1. Recreating the Cardiac Microenvironment in Pluripotent Stem Cell Models of Human Physiology and Disease.

    Science.gov (United States)

    Atmanli, Ayhan; Domian, Ibrahim John

    2016-12-19

    The advent of human pluripotent stem cell (hPSC) biology has opened unprecedented opportunities for the use of tissue engineering to generate human cardiac tissue for in vitro study. Engineering cardiac constructs that recapitulate human development and disease requires faithful recreation of the cardiac niche in vitro. Here we discuss recent progress in translating the in vivo cardiac microenvironment into PSC models of the human heart. We review three key physiologic features required to recreate the cardiac niche and facilitate normal cardiac differentiation and maturation: the biochemical, biophysical, and bioelectrical signaling cues. Finally, we discuss key barriers that must be overcome to fulfill the promise of stem cell biology in preclinical applications and ultimately in clinical practice.

  2. Central respiratory chemosensitivity and cerebrovascular CO2 reactivity: a rebreathing demonstration illustrating integrative human physiology.

    Science.gov (United States)

    MacKay, Christina M; Skow, Rachel J; Tymko, Michael M; Boulet, Lindsey M; Davenport, Margie H; Steinback, Craig D; Ainslie, Philip N; Lemieux, Chantelle C M; Day, Trevor A

    2016-03-01

    One of the most effective ways of engaging students of physiology and medicine is through laboratory demonstrations and case studies that combine 1) the use of equipment, 2) problem solving, 3) visual representations, and 4) manipulation and interpretation of data. Depending on the measurements made and the type of test, laboratory demonstrations have the added benefit of being able to show multiple organ system integration. Many research techniques can also serve as effective demonstrations of integrative human physiology. The "Duffin" hyperoxic rebreathing test is often used in research settings as a test of central respiratory chemosensitivity and cerebrovascular reactivity to CO2. We aimed to demonstrate the utility of the hyperoxic rebreathing test for both respiratory and cerebrovascular responses to increases in CO2 and illustrate the integration of the respiratory and cerebrovascular systems. In the present article, methods such as spirometry, respiratory gas analysis, and transcranial Doppler ultrasound are described, and raw data traces can be adopted for discussion in a tutorial setting. If educators have these instruments available, instructions on how to carry out the test are provided so students can collect their own data. In either case, data analysis and quantification are discussed, including principles of linear regression, calculation of slope, the coefficient of determination (R(2)), and differences between plotting absolute versus normalized data. Using the hyperoxic rebreathing test as a demonstration of the complex interaction and integration between the respiratory and cerebrovascular systems provides senior undergraduate, graduate, and medical students with an advanced understanding of the integrative nature of human physiology.

  3. Latent physiological factors of complex human diseases revealed by independent component analysis of clinarrays

    Directory of Open Access Journals (Sweden)

    Chen David P

    2010-10-01

    Full Text Available Abstract Background Diagnosis and treatment of patients in the clinical setting is often driven by known symptomatic factors that distinguish one particular condition from another. Treatment based on noticeable symptoms, however, is limited to the types of clinical biomarkers collected, and is prone to overlooking dysfunctions in physiological factors not easily evident to medical practitioners. We used a vector-based representation of patient clinical biomarkers, or clinarrays, to search for latent physiological factors that underlie human diseases directly from clinical laboratory data. Knowledge of these factors could be used to improve assessment of disease severity and help to refine strategies for diagnosis and monitoring disease progression. Results Applying Independent Component Analysis on clinarrays built from patient laboratory measurements revealed both known and novel concomitant physiological factors for asthma, types 1 and 2 diabetes, cystic fibrosis, and Duchenne muscular dystrophy. Serum sodium was found to be the most significant factor for both type 1 and type 2 diabetes, and was also significant in asthma. TSH3, a measure of thyroid function, and blood urea nitrogen, indicative of kidney function, were factors unique to type 1 diabetes respective to type 2 diabetes. Platelet count was significant across all the diseases analyzed. Conclusions The results demonstrate that large-scale analyses of clinical biomarkers using unsupervised methods can offer novel insights into the pathophysiological basis of human disease, and suggest novel clinical utility of established laboratory measurements.

  4. Delineating the Impact of Weightlessness on Human Physiology Using Computational Models

    Science.gov (United States)

    Kassemi, Mohammad

    2015-01-01

    Microgravity environment has profound effects on several important human physiological systems. The impact of weightlessness is usually indirect as mediated by changes in the biological fluid flow and transport and alterations in the deformation and stress fields of the compliant tissues. In this context, Fluid-Structural and Fluid-Solid Interaction models provide a valuable tool in delineating the physical origins of the physiological changes so that systematic countermeasures can be devised to reduce their adverse effects. In this presentation, impact of gravity on three human physiological systems will be considered. The first case involves prediction of cardiac shape change and altered stress distributions in weightlessness. The second, presents a fluid-structural-interaction (FSI) analysis and assessment of the vestibular system and explores the reasons behind the unexpected microgravity caloric stimulation test results performed aboard the Skylab. The last case investigates renal stone development in microgravity and the possible impact of re-entry into partial gravity on the development and transport of nucleating, growing, and agglomerating renal calculi in the nephron. Finally, the need for model validation and verification and application of the FSI models to assess the effects of Artificial Gravity (AG) are also briefly discussed.

  5. Differences in fuel utilization between trout and human thrombocytes in physiological media.

    Science.gov (United States)

    Guppy, M; Hill, D J; Arthur, P; Rowley, A F

    1999-10-01

    Cell culture preparations now play a significant and essential role in physiological and biochemical studies of cell biology. However, the fuels offered in cell culture media are only glucose and glutamine, plus whatever might be in the added sera. It is currently difficult to find a rational way forward on this problem, as there are few data on what fuels cells use in vivo or even in an in vitro physiological situation. A recent study on human platelets redressed the situation somewhat by finding that 75% of ATP turnover could be accounted for by aerobic glycolysis, and by the oxidation of glucose, hydroxybutyrate, acetate, glutamine, palmitate and oleate. In the present study we used a similar strategy to investigate fuel choices by trout thymocytes, cells with a similar function but from a different phylogenetic group. When these cells were presented with a physiological medium, we found that aerobic glycolysis accounted for 9% of total ATP turnover, glucose and glutamine oxidation made a combined contribution of 2.3%, oleate and palmitate oxidation accounted for 15%, and 74% was unaccounted for. These patterns of fuel use are very different from that in human platelets. They demonstrate the cell- and animal-specific nature of cellular metabolism and again expose the inadequacy of the fuel component in culture media.

  6. Critical review evaluating the pig as a model for human nutritional physiology.

    Science.gov (United States)

    Roura, Eugeni; Koopmans, Sietse-Jan; Lallès, Jean-Paul; Le Huerou-Luron, Isabelle; de Jager, Nadia; Schuurman, Teun; Val-Laillet, David

    2016-06-01

    The present review examines the pig as a model for physiological studies in human subjects related to nutrient sensing, appetite regulation, gut barrier function, intestinal microbiota and nutritional neuroscience. The nutrient-sensing mechanisms regarding acids (sour), carbohydrates (sweet), glutamic acid (umami) and fatty acids are conserved between humans and pigs. In contrast, pigs show limited perception of high-intensity sweeteners and NaCl and sense a wider array of amino acids than humans. Differences on bitter taste may reflect the adaptation to ecosystems. In relation to appetite regulation, plasma concentrations of cholecystokinin and glucagon-like peptide-1 are similar in pigs and humans, while peptide YY in pigs is ten to twenty times higher and ghrelin two to five times lower than in humans. Pigs are an excellent model for human studies for vagal nerve function related to the hormonal regulation of food intake. Similarly, the study of gut barrier functions reveals conserved defence mechanisms between the two species particularly in functional permeability. However, human data are scant for some of the defence systems and nutritional programming. The pig model has been valuable for studying the changes in human microbiota following nutritional interventions. In particular, the use of human flora-associated pigs is a useful model for infants, but the long-term stability of the implanted human microbiota in pigs remains to be investigated. The similarity of the pig and human brain anatomy and development is paradigmatic. Brain explorations and therapies described in pig, when compared with available human data, highlight their value in nutritional neuroscience, particularly regarding functional neuroimaging techniques.

  7. The apelinergic system: the role played in human physiology and pathology and potential therapeutic applications.

    Science.gov (United States)

    Ladeiras-Lopes, Ricardo; Ferreira-Martins, João; Leite-Moreira, Adelino F

    2008-05-01

    Apelin is a recently discovered peptide, identified as an endogenous ligand of receptor APJ. Apelin and receptor APJ are expressed in a wide variety of tissues including heart, brain, kidneys and lungs. Their interaction may have relevant pathophysiologic effects in those tissues. In fact, the last decade has been rich in illustrating the possible roles played by apelin in human physiology, namely as a regulating peptide of cardiovascular, hypothalamus-hypophysis, gastrointestinal, and immune systems. The possible involvement of apelin in the pathogenesis of high prevalence conditions and comorbidities - such as hypertension, heart failure, and Diabetes Mellitus Type 2 (T2DM) - rank it as a likely therapeutic target to be investigated in the future. The present paper is an overview of apelin physiologic effects and presents the possible role played by this peptide in the pathogenesis of a number of conditions as well as the therapeutic implications that might, therefore, be investigated.

  8. Cortisol as a Biomarker of Stress in Term Human Labor: Physiological and Methodological Issues

    Science.gov (United States)

    Newton, Edward R.; Tanner, Charles J.; Heitkemper, Margaret M.

    2013-01-01

    Literature on the use of plasma cortisol to quantify psychophysiological stress in humans is extensive. However, in parturition at term gestation the use of cortisol as a biomarker of stress is particularly complex. Plasma cortisol levels increase as labor progresses. This increase seems to be important for maintenance of maternal/fetal wellbeing and facilitation of normal labor progress. Unique physiological and methodological issues involved in the use of cortisol as a biomarker of stress in labor present challenges for researchers. This review examines these issues, suggests mixed methods and within-subject repeated measures designs, and offers recommendations for assay procedures for parturient sampling. Documentation of clinical interventions and delivery outcomes may elucidate relationships among psychophysiological stressors, cortisol and normal labor progress. With attention to these methodological issues, analysis of plasma cortisol may lead to clinical interventions that support normal labor physiology. PMID:23338011

  9. The Relationship between Human Operators' Psycho-physiological Condition and Human Errors in Nuclear Power Plants

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Arryum; Jang, Inseok; Kang, Hyungook; Seong, Poonghyun [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

    2013-05-15

    The safe operation of nuclear power plants (NPPs) is substantially dependent on the performance of the human operators who operate the systems. In this environment, human errors caused by inappropriate performance of operator have been considered to be critical since it may lead serious problems in the safety-critical plants. In order to provide meaningful insights to prevent human errors and enhance the human performance, operators' physiological conditions such as stress and workload have been investigated. Physiological measurements were considered as reliable tools to assess the stress and workload. T. Q. Tran et al. and J. B. Brooking et al pointed out that operators' workload can be assessed using eye tracking, galvanic skin response, electroencephalograms (EEGs), heart rate, respiration and other measurements. The purpose of this study is to investigate the effect of the human operators' tense level and knowledge level to the number of human errors. For this study, the experiments were conducted in the mimic of the main control rooms (MCR) in NPP. It utilized the compact nuclear simulator (CNS) which is modeled based on the three loop Pressurized Water Reactor, 993MWe, Kori unit 3 and 4 in Korea and the subjects were asked to follow the tasks described in the emergency operating procedures (EOP). During the simulation, three kinds of physiological measurement were utilized; Electrocardiogram (ECG), EEG and nose temperature. Also, subjects were divided into three groups based on their knowledge of the plant operation. The result shows that subjects who are tense make fewer errors. In addition, subjects who are in higher knowledge level tend to be tense and make fewer errors. For the ECG data, subjects who make fewer human errors tend to be located in higher tense level area of high SNS activity and low PSNS activity. The results of EEG data are also similar to ECG result. Beta power ratio of subjects who make fewer errors was higher. Since beta

  10. Effect of NADPH on formation and decay of human metarhodopsin III at physiological temperatures.

    Science.gov (United States)

    Szundi, I; Lewis, J W; van Kuijk, F J; Kliger, D S

    2000-01-01

    Difference absorption spectra were recorded during the formation and decay of metarhodopsin III after sonicated membrane suspensions of rhodopsin were bleached at 37 degrees C. The data were analyzed using SVD, spectral decomposition and global exponential fitting. By comparison of the results in the presence or absence of 70 microM NADPH and those for bovine or human rhodopsin, a single comprehensive scheme was fit to all the data, including reduction of retinal to retinol by the intrinsic retinol dehydrogenase. On the time scale studied the mechanism involves two 382 nm absorbing species and two 468 nm, absorbing species, supporting the notion that human metarhodopsin III is not a homogeneous species. The results confirm that metarhodopsin III forms and persists sufficiently long in the human retina under physiological conditions that it could undergo secondary photoisomerization.

  11. Complex for monitoring visual acuity and its application for evaluation of human psycho-physiological state

    Science.gov (United States)

    Sorokoumov, P. S.; Khabibullin, T. R.; Tolstaya, A. M.

    2017-01-01

    The existing psychological theories associate the movement of a human eye with its reactions to external change: what we see, hear and feel. By analyzing the glance, we can compare the external human response (which shows the behavior of a person), and the natural reaction (that they actually feels). This article describes the complex for detection of visual activity and its application for evaluation of the psycho-physiological state of a person. The glasses with a camera capture all the movements of the human eye in real time. The data recorded by the camera are transmitted to the computer for processing implemented with the help of the software developed by the authors. The result is given in an informative and an understandable report, which can be used for further analysis. The complex shows a high efficiency and stable operation and can be used both, for the pedagogic personnel recruitment and for testing students during the educational process.

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

    Science.gov (United States)

    Edwards, Lindsay M; Thiele, Ines

    2013-03-22

    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.

  13. An investigative laboratory course in human physiology using computer technology and collaborative writing.

    Science.gov (United States)

    FitzPatrick, Kathleen A

    2004-12-01

    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 second-year students in sports medicine and biology at a small private comprehensive college. The course builds on skills and abilities first introduced in an introductory investigations course and introduces additional higher-level skills and more complex human experimental models. In four multiweek experimental modules, involving neuromuscular, reflex, and cardiovascular physiology, by use of computerized hardware/software with a variety of transducers, students carry out self-designed experiments with human subjects and perform data collection and analysis, collaborative writing, and peer editing. In assessments, including standard course evaluations and the Salgains Web-based evaluation, student responses to this approach are enthusiastic, and gains in their skills and abilities are evident in their comments and in improved performance.

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

    Science.gov (United States)

    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 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.

  15. Physiological time structure of the tibialis anterior motor activity during sleep in mice, rats and humans.

    Science.gov (United States)

    Silvani, Alessandro; Lo Martire, Viviana; Salvadè, Agnese; Bastianini, Stefano; Ferri, Raffaele; Berteotti, Chiara; Baracchi, Francesca; Pace, Marta; Bassetti, Claudio L; Zoccoli, Giovanna; Manconi, Mauro

    2015-12-01

    The validation of rodent models for restless legs syndrome (Willis-Ekbom disease) and periodic limb movements during sleep requires knowledge of physiological limb motor activity during sleep in rodents. This study aimed to determine the physiological time structure of tibialis anterior activity during sleep in mice and rats, and compare it with that of healthy humans. Wild-type mice (n = 9) and rats (n = 8) were instrumented with electrodes for recording the electroencephalogram and electromyogram of neck muscles and both tibialis anterior muscles. Healthy human subjects (31 ± 1 years, n = 21) underwent overnight polysomnography. An algorithm for automatic scoring of tibialis anterior electromyogram events of mice and rats during non-rapid eye movement sleep was developed and validated. Visual scoring assisted by this algorithm had inter-rater sensitivity of 92-95% and false-positive rates of 13-19% in mice and rats. The distribution of the time intervals between consecutive tibialis anterior electromyogram events during non-rapid eye movement sleep had a single peak extending up to 10 s in mice, rats and human subjects. The tibialis anterior electromyogram events separated by intervals Willis-Ekbom disease. © 2015 European Sleep Research Society.

  16. The Serum Amyloid p Component (SAP) Interactome in Human Plasma Containing Physiological Calcium Levels

    DEFF Research Database (Denmark)

    Poulsen, Ebbe Toftgaard; Pedersen, Kata Wolff; Marzeda, Anna Maria

    2017-01-01

    containing the physiological Ca2+ concentration using SAP affinity pull-down and co-immunoprecipitation experiments followed by mass spectrometry analyses. The analyses resulted in the identification of 33 proteins of which 24 were direct or indirect integration partners not previously reported. The SAP...... involves the humoral innate immune system spanning the complement system, inflammation, and coagulation. Also, SAP is known to binding to the generic structure of amyloid deposits and possibly to protect these against proteolysis. In this study, we have characterized the SAP interactome in human plasma...

  17. Effects of human activity on physiological and behavioral responses of an endangered steppe bird

    OpenAIRE

    Tarjuelo, Rocío; Barja, Isabel; Morales, Manuel B.; Traba, Juan; Benítez-López, Ana; Casas, Fabián; Arroyo, Beatriz; Delgado, M. Paula; Mougeot, François

    2015-01-01

    This is a pre-copyedited, author-produced PDF of an article accepted for publication in Behavioral Ecology following peer review. The version of recordBehavioral Ecology 26.3 (2015): 828-838 is available online at: http://beheco.oxfordjournals.org/content/early/2015/04/02/beheco.arv016 Animals may perceive humans as a form of predatory threat, a disturbance, triggering behavioral changes together with the activation of physiological stress responses. These adaptive responses may allow indi...

  18. Animal models and their importance to human physiological responses in microgravity

    Science.gov (United States)

    Tipton, C. M.

    1996-01-01

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

  19. Design and fabrication of a sensor integrated MEMS/NANO-skin system for human physiological response measurement

    Science.gov (United States)

    Leng, Hongjie; Lin, Yingzi

    2010-04-01

    Human state in human-machine systems highly affects the system performance, and should be monitored. Physiological cues are more suitable for monitoring the human state in human-machine system. This study was focused on developing a new sensing system, i.e. NANO-Skin, to non-intrusively measure physiological cues from human-machine contact surfaces for human state recognition. The first part was to analyze the relation between human state and physiological cues. Generally, heart rate, skin conductance, skin temperature, operating force, blood alcohol concentration, sweat rate, and electromyography have close relation with human state, and can be measured from human skin. The second part was to compare common sensors, MEMS sensors, and NANO sensors. It was found that MEMS sensors and NANO sensors can offer unique contributions to the development of NANO-Skin. The third part was to discuss the design and manufacture of NANO-Skin. The NANO-Skin involves five components, the flexible substrate, sensors, special integrated circuit, interconnection between sensors and special integrated circuit, and protection layer. Experiments were performed to verify the measurement accuracy of NANO-Skin. It is feasible to use NANO-Skins to non-intrusively measure physiological cues from human-machine contact surfaces for human state recognition.

  20. Dehydroepiandrosterone (DHEA)--a precursor steroid or an active hormone in human physiology.

    Science.gov (United States)

    Traish, Abdulmaged M; Kang, H Paco; Saad, Farid; Guay, Andre T

    2011-11-01

    The circulation of large amounts of dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEA-S) suggests a physiological role in human physiology. In the central nervous system, DHEA is considered a neurosteroid with a wide range of functions. The goal of this review is to discuss metabolism, biochemical, and physiological mechanism of DHEA action and the potential role of DHEA in aging and in ameliorating a host of pathological conditions, associated with aging. We examined preclinical and clinical data reported in various studies from the available literature concerning the effects of DHEA in normal and pathological conditions. Data reported in the literature were analyzed, reviewed, and discussed. DHEA mediates its action via multiple signaling pathways involving specific membrane receptors and via transformation into androgen and estrogen derivatives (e.g., androgens, estrogens, 7α and 7β DHEA, and 7α and 7β epiandrosterone derivatives) acting through their specific receptors. These pathways include: nitric oxide synthase activation, modulation of γ-amino butyric acid receptors, N-methyl D-aspartate, receptors sigma receptors (Sigma-1), differential expression of inflammatory factors, adhesion molecules and reactive oxygen species, among others. Clinical and epidemiological studies suggested that low DHEA levels might be associated with ischemic heart disease, endothelial dysfunction, atherosclerosis, bone loss, inflammatory diseases, and sexual dysfunction. Most importantly, no significant adverse or negative side effects of DHEA were reported in clinical studies of men and women. DHEA modulates endothelial function, reduces inflammation, improves insulin sensitivity, blood flow, cellular immunity, body composition, bone metabolism, sexual function, and physical strength in frailty and provides neuroprotection, improves cognitive function, and memory enhancement. DHEA possesses pleiotropic effects and reduced levels of DHEA and DHEA-S may be

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

    Energy Technology Data Exchange (ETDEWEB)

    Hively, Lee M [ORNL; Sheldon, Frederick T [ORNL

    2011-01-01

    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 toward scalable trustworthy systems requiring a long-term commitment to solve the well-known challenges.

  2. The molecular machinery regulating apoptosis signal transduction and its implication in human physiology and pathophysiologies.

    Science.gov (United States)

    Hellwig, C T; Passante, E; Rehm, M

    2011-02-01

    The regulation of apoptotic cell death, a terminal and fatal cell fate decision, has been intensely investigated and, due to its paramount implications for human health and disease, has sparked one of the most prolific and competitive research fields in biological and biomedical sciences of the past decades. Many key components of the molecular machinery processing and transducing apoptotic cell death signals have been described in great detail by now, dramatically advancing our understanding of how the network of apoptosis signaling proteins integrates and regulates cell death signals, and ultimately executes apoptosis. Building on the latest significant advances in deciphering apoptosis signal transduction as well as on the central original groundbreaking discoveries in cell death research, we here present an in-depth description of the current knowledge on the core molecular machinery of apoptotic signaling and how it is implicated in human physiology and pathophysiologies.

  3. An integrative view on the physiology of human early placental villi.

    Science.gov (United States)

    Huppertz, Berthold; Ghosh, Debabrata; Sengupta, Jayasree

    2014-01-01

    The placenta is an indispensable organ for intrauterine protection, development and growth of the embryo and fetus. It provides tight contact between mother and conceptus, enabling the exchange of gas, nutrients and waste products. The human placenta is discoidal in shape, and bears a hemo-monochorial interface as well as villous materno-fetal interdigitations. Since Peter Medawar's astonishment to the paradoxical nature of the mother-fetus relationship in 1953, substantial knowledge in the domain of placental physiology has been gathered. In the present essay, an attempt has been made to build an integrated understanding of morphological dynamics, cell biology, and functional aspects of genomic and proteomic expression of human early placental villous trophoblast cells followed by a commentary on the future directions of research in this field.

  4. The elite cross-country skier provides unique insights into human exercise physiology.

    Science.gov (United States)

    Holmberg, H-C

    2015-12-01

    Successful cross-country skiing, one of the most demanding of endurance sports, involves considerable physiological challenges posed by the combined upper- and lower-body effort of varying intensity and duration, on hilly terrain, often at moderate altitude and in a cold environment. Over the years, this unique sport has helped physiologists gain novel insights into the limits of human performance and regulatory capacity. There is a long-standing tradition of researchers in this field working together with coaches and athletes to improve training routines, monitor progress, and refine skiing techniques. This review summarizes research on elite cross-country skiers, with special emphasis on the studies initiated by Professor Bengt Saltin. He often employed exercise as a means to learn more about the human body, successfully engaging elite endurance athletes to improve our understanding of the demands, characteristics, and specific effects associated with different types of exercise.

  5. Transcriptional and functional adaptations of human endothelial cells to physiological chronic low oxygen.

    Science.gov (United States)

    Jiang, Yi-Zhou; Wang, Kai; Li, Yan; Dai, Cai-Feng; Wang, Ping; Kendziorski, Christina; Chen, Dong-Bao; Zheng, Jing

    2013-05-01

    Endothelial cells chronically reside in low-O2 environments in vivo (2%-13% O2), which are believed to be critical for cell homeostasis. To elucidate the roles of this physiological chronic normoxia in human endothelial cells, we examined transcriptomes of human umbilical vein endothelial cells (HUVECs), proliferation and migration of HUVECs in response to fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA), and underlying signaling mechanisms under physiological chronic normoxia. Immediately after isolation, HUVECs were cultured steadily under standard cell culture normoxia (SCN; 21% O2) or physiological chronic normoxia (PCN; 3% O2) up to 25 days. We found that PCN up-regulated 41 genes and down-regulated 21 genes, 90% of which differed from those previously reported from HUVECs cultured under SCN and exposed to acute low O2. Gene ontology analysis indicated that PCN-regulated genes were highly related to cell proliferation and migration, consistent with the results from benchtop assays that showed that PCN significantly enhanced FGF2- and VEGFA-stimulated cell proliferation and migration. Interestingly, preexposing the PCN cells to 21% O2 up to 5 days did not completely diminish PCN-enhanced cell proliferation and migration. These PCN-enhanced cell proliferations and migrations were mediated via augmented activation of MEK1/MEK2/ERK1/ERK2 and/or PI3K/AKT1. Importantly, these PCN-enhanced cellular responses were associated with an increase in activation of VEGFR2 but not FGFR1, without altering their expression. Thus, PCN programs endothelial cells to undergo dramatic changes in transcriptomes and sensitizes cellular proliferative and migratory responses to FGF2 and VEGFA. These PCN cells may offer a unique endothelial model, more closely mimicking the in vivo states.

  6. Platelet serotonin transporter (5HTt): physiological influences on kinetic characteristics in a large human population.

    Science.gov (United States)

    Banović, Miroslav; Bordukalo-Niksić, Tatjana; Balija, Melita; Cicin-Sain, Lipa; Jernej, Branimir

    2010-01-01

    The present study had two goals: first, to give a detailed description of a reliable method for full kinetic analysis of serotonin transporter (5HTt) on the membrane of human platelets, and second, as a main issue, to report on physiological influences on kinetic characteristics of this transmembrane transport on a large population of healthy individuals. Full kinetic analyses of platelet serotonin uptake were performed on 334 blood donors of both sexes by the use of 14C-radioisotopic method, which was first optimized according to assumptions of enzyme kinetic analyses, with regard to platelet concentration, duration of uptake, concentration of substrate as well as important technical parameters (underpressure of filtration, blanks, incubating temperature, etc). Kinetic parameters of platelet serotonin uptake in the whole population were for V(max): 142 +/- 25.3 pmol 5HT/10(8) platelets/minute and for K(m): 0.404 +/- 0.089 microM 5HT. Besides the report on kinetic values of 5HT transporter protein, we have also described major physiological influences on the mentioned parameters, V(max), K(m) and their derivative, V(max)/K(m) (transporter efficiency): range and frequency distribution of normal values, intraindividual stability over time, lack of age influence, gender dependence and seasonal variations. The report on kinetic values and main physiological influences on platelet serotonin transport kinetics, obtained by the use of thoroughly reassessed methodology, and on by far the largest human population studied until now, offers a reliable frame of reference for pathophysiological studies of this parameter in various clinical fields.

  7. Mutation of von Hippel-Lindau tumour suppressor and human cardiopulmonary physiology.

    Directory of Open Access Journals (Sweden)

    Thomas G Smith

    2006-07-01

    Full Text Available BACKGROUND: The von Hippel-Lindau tumour suppressor protein-hypoxia-inducible factor (VHL-HIF pathway has attracted widespread medical interest as a transcriptional system controlling cellular responses to hypoxia, yet insights into its role in systemic human physiology remain limited. Chuvash polycythaemia has recently been defined as a new form of VHL-associated disease, distinct from the classical VHL-associated inherited cancer syndrome, in which germline homozygosity for a hypomorphic VHL allele causes a generalised abnormality in VHL-HIF signalling. Affected individuals thus provide a unique opportunity to explore the integrative physiology of this signalling pathway. This study investigated patients with Chuvash polycythaemia in order to analyse the role of the VHL-HIF pathway in systemic human cardiopulmonary physiology. METHODS AND FINDINGS: Twelve participants, three with Chuvash polycythaemia and nine controls, were studied at baseline and during hypoxia. Participants breathed through a mouthpiece, and pulmonary ventilation was measured while pulmonary vascular tone was assessed echocardiographically. Individuals with Chuvash polycythaemia were found to have striking abnormalities in respiratory and pulmonary vascular regulation. Basal ventilation and pulmonary vascular tone were elevated, and ventilatory, pulmonary vasoconstrictive, and heart rate responses to acute hypoxia were greatly increased. CONCLUSIONS: The features observed in this small group of patients with Chuvash polycythaemia are highly characteristic of those associated with acclimatisation to the hypoxia of high altitude. More generally, the phenotype associated with Chuvash polycythaemia demonstrates that VHL plays a major role in the underlying calibration and homeostasis of the respiratory and cardiovascular systems, most likely through its central role in the regulation of HIF.

  8. Translational medicine in fish-derived peptides: from fish endocrinology to human physiology and diseases.

    Science.gov (United States)

    Takahashi, Kazuhiro

    2004-02-01

    Recent studies have revealed the importance of fish-derived peptide hormones to human endocrinology. These peptides include melanin-concentrating hormone (MCH), urocortins (human urotensin-I), and urotensin-II. MCH, a hypothalamic peptide, is a potent stimulator on appetite. Urocortins, e.g. urocortin 1 and urocortin 3 (stresscopin), are endogenous ligands for the corticotropin-releasing factor (CRF) receptors, particularly CRF type 2 receptor, that mediates a vasodilator action, a positive inotropic action and a central appetite-inhibiting action. These actions mediated by CRF type 2 receptor may ameliorate the stress response. Human urotensin-II is a potent vasoconstrictor peptide, while it acts as a vasodilator on some arteries. Human urotensin-II is expressed in various types of cells and tissues, including cardiovascular tissues, as well as many types of tumor cells. Thus, these fish-derived peptides appear to play important roles in human physiology, such as appetite regulation, stress response and cardiovascular regulation, and also in diseases, for example, obesity, cardiovascular diseases and tumors. Development of antagonists/agonists against the receptors for these peptides may open new strategies for the treatment of various diseases, including obesity-related diseases, hypertension, heart failure and malignant tumors.

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

    Science.gov (United States)

    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. [Carbon monoxide in human physiology--its role in the gastrointestinal tract].

    Science.gov (United States)

    Jasnos, Katarzyna; Magierowski, Marcin; Kwiecień, Sławomir; Brzozowski, Tomasz

    2014-01-30

    Carbon monoxide (CO) is produced endogenously in the body as a byproduct of heme degradation catalyzed by the action of heme oxygenase (HO) enzymes. An inducible form, HO-1, responds to many factors such as oxidative stress, hypoxia, heme, bacterial endotoxins, proinflammatory cytokines and heavy metals. HO-2 is constitutively expressed under basal conditions in most human tissues including brain and gonads. Recent data show that CO is a gaseous mediator with multidirectional biological activity. It is involved in maintaining cellular homeostasis and many physiological and pathophysiological processes. CO shares many properties with another established vasodilatator and neurotransmitter - nitric oxide (NO). Both CO and NO are involved in neural transmission, modulation of blood vessel function and inhibition of platelet aggregation. The binding to guanylate cyclase, stimulation of the production of cGMP, activation of Ca2+-dependent potassium channels and stimulation of mitogen-activated protein kinases are well known cellular targets of CO action. Since CO is nowadays a subject of extensive investigation in many centers worldwide, the aim of the present study was to present the role of CO in various aspects of human physiology with special focus on its activity in the gastrointestinal tract.

  11. The EuroPhysiome, STEP and a roadmap for the virtual physiological human.

    Science.gov (United States)

    Fenner, J W; Brook, B; Clapworthy, G; Coveney, P V; Feipel, V; Gregersen, H; Hose, D R; Kohl, P; Lawford, P; McCormack, K M; Pinney, D; Thomas, S R; Van Sint Jan, S; Waters, S; Viceconti, M

    2008-09-13

    Biomedical science and its allied disciplines are entering a new era in which computational methods and technologies are poised to play a prevalent role in supporting collaborative investigation of the human body. Within Europe, this has its focus in the virtual physiological human (VPH), which is an evolving entity that has emerged from the EuroPhysiome initiative and the strategy for the EuroPhysiome (STEP) consortium. The VPH is intended to be a solution to common infrastructure needs for physiome projects across the globe, providing a unifying architecture that facilitates integration and prediction, ultimately creating a framework capable of describing Homo sapiens in silico. The routine reliance of the biomedical industry, biomedical research and clinical practice on information technology (IT) highlights the importance of a tailor-made and robust IT infrastructure, but numerous challenges need to be addressed if the VPH is to become a mature technological reality. Appropriate investment will reap considerable rewards, since it is anticipated that the VPH will influence all sectors of society, with implications predominantly for improved healthcare, improved competitiveness in industry and greater understanding of (patho)physiological processes. This paper considers issues pertinent to the development of the VPH, highlighted by the work of the STEP consortium.

  12. Human Spirometry: Computerized Data Acquisition in the Undergraduate Human Physiology Laboratory.

    Science.gov (United States)

    Braun, Bradley T.; Mulstay, Richard E.

    1993-01-01

    Applies microcomputer technology to the development of a data acquisition and analysis system for the study of measuring the human lung capacity and metabolism. Discusses the chain-compensated spirometer, interfacing hardware, data acquisition hardware and software, and the applicability of the system to other biological measurements. (MDH)

  13. Preliminary results of Physiological plant growth modelling for human life support in space

    Science.gov (United States)

    Sasidharan L, Swathy; Dussap, Claude-Gilles; Hezard, Pauline

    2012-07-01

    Human life support is fundamental and crucial in any kind of space explorations. MELiSSA project of European Space Agency aims at developing a closed, artificial ecological life support system involving human, plants and micro organisms. Consuming carbon dioxide and water from the life support system, plants grow in one of the chambers and convert it into food and oxygen along with potable water. The environmental conditions, nutrient availability and its consumption of plants should be studied and necessarily modeled to predict the amount of food, oxygen and water with respect to the environmental changes and limitations. The reliability of a completely closed system mainly depends on the control laws and strategies used. An efficient control can occur, only if the system to control is itself well known, described and ideally if the responses of the system to environmental changes are predictable. In this aspect, the general structure of plant growth model has been designed together with physiological modelling.The physiological model consists of metabolic models of leaves, stem and roots, of which concern specific metabolisms of the associated plant parts. On the basis of the carbon source transport (eg. sucrose) through stem, the metabolic models (leaf and root) can be interconnected to each other and finally coupled to obtain the entire plant model. For the first step, leaf metabolic model network was built using stoichiometric, mass and energy balanced metabolic equations under steady state approach considering all necessary plant pathways for growth and maintenance of leaves. As the experimental data for lettuce plants grown in closed and controlled environmental chambers were available, the leaf metabolic model has been established for lettuce leaves. The constructed metabolic network is analyzed using known stoichiometric metabolic technique called metabolic flux analysis (MFA). Though, the leaf metabolic model alone is not sufficient to achieve the

  14. MicroRNAs: control and loss of control in human physiology and disease.

    Science.gov (United States)

    Li, Min; Marin-Muller, Christian; Bharadwaj, Uddalak; Chow, Kwong-Hon; Yao, Qizhi; Chen, Changyi

    2009-04-01

    Analysis of the human genome indicates that a large fraction of the genome sequences are RNAs that do not encode any proteins, also known as non-coding RNAs. MicroRNAs (miRNAs) are a group of small non-coding RNA molecules 20-22 nucleotides (nt) in length that are predicted to control the activity of approximately 30% of all protein-coding genes in mammals. miRNAs play important roles in many diseases, including cancer, cardiovascular disease, and immune disorders. The expression of miRNAs can be regulated by epigenetic modification, DNA copy number change, and genetic mutations. miRNAs can serve as a valuable therapeutic target for a large number of diseases. For miRNAs with oncogenic capabilities, potential therapies include miRNA silencing, antisense blocking, and miRNA modifications. For miRNAs with tumor suppression functions, overexpression of those miRNAs might be a useful strategy to inhibit tumor growth. In this review, we discuss the current progress of miRNA research, regulation of miRNA expression, prediction of miRNA targets, and regulatory role of miRNAs in human physiology and diseases, with a specific focus on miRNAs in pancreatic cancer, liver cancer, colorectal cancer, cardiovascular disease, the immune system, and infectious disease. This review provides valuable information for clinicians and researchers who want to recognize the newest advances in this new field and identify possible lines of investigation in miRNAs as important mediators in human physiology and diseases.

  15. The use of computers to teach human anatomy and physiology to allied health and nursing students

    Science.gov (United States)

    Bergeron, Valerie J.

    Educational institutions are under tremendous pressure to adopt the newest technologies in order to prepare their students to meet the challenges of the twenty-first century. For the last twenty years huge amounts of money have been spent on computers, printers, software, multimedia projection equipment, and so forth. A reasonable question is, "Has it worked?" Has this infusion of resources, financial as well as human, resulted in improved learning? Are the students meeting the intended learning goals? Any attempt to develop answers to these questions should include examining the intended goals and exploring the effects of the changes on students and faculty. This project investigated the impact of a specific application of a computer program in a community college setting on students' attitudes and understanding of human anatomy and physiology. In this investigation two sites of the same community college with seemingly similar students populations, seven miles apart, used different laboratory activities to teach human anatomy and physiology. At one site nursing students were taught using traditional dissections and laboratory activities; at the other site two of the dissections, specifically cat and sheep pluck, were replaced with the A.D.A.M.RTM (Animated Dissection of Anatomy for Medicine) computer program. Analysis of the attitude data indicated that students at both sites were extremely positive about their laboratory experiences. Analysis of the content data indicated a statistically significant difference in performance between the two sites in two of the eight content areas that were studied. For both topics the students using the computer program scored higher. A detailed analysis of the surveys, interviews with faculty and students, examination of laboratory materials, and observations of laboratory facilities in both sites, and cost-benefit analysis led to the development of seven recommendations. The recommendations call for action at the level of the

  16. Physiologically based biokinetic (PBBK) modeling of safrole bioactivation and detoxification in humans as compared with rats.

    Science.gov (United States)

    Martati, Erryana; Boersma, Marelle G; Spenkelink, Albertus; Khadka, Dambar B; van Bladeren, Peter J; Rietjens, Ivonne M C M; Punt, Ans

    2012-08-01

    A physiologically based biokinetic (PBBK) model for the alkenylbenzene safrole in humans was developed based on in vitro- and in silico-derived kinetic parameters. With the model obtained, the time- and dose-dependent formation of the proximate and ultimate carcinogenic metabolites, 1-hydroxysafrole and 1-sulfooxysafrole in human liver were estimated and compared with previously predicted levels of these metabolites in rat liver. In addition, Monte Carlo simulations were performed to predict interindividual variation in the formation of these metabolites in the overall population. For the evaluation of the model performance, a comparison was made between the predicted total amount of urinary metabolites of safrole and the reported total levels of metabolites in the urine of humans exposed to safrole, which adequately matched. The model results revealed no dose-dependent shifts in safrole metabolism and no relative increase in bioactivation at dose levels up to 100mg/kg body weight/day. Species differences were mainly observed in the detoxification pathways of 1-hydroxysafrole, with the formation of 1-oxosafrole being a main detoxification pathway of 1-hydroxysafrole in humans but a minor pathway in rats, and glucuronidation of 1-hydroxysafrole being less important in humans than in rats. The formation of 1-sulfooxysafrole was predicted to vary 4- to 17-fold in the population (fold difference between the 95th and median, and 95th and 5th percentile, respectively), with the median being three to five times higher in human than in rat liver. Comparison of the PBBK results for safrole with those previously obtained for the related alkenylbenzenes estragole and methyleugenol revealed that differences in 1-sulfooxy metabolite formation are limited, being only twofold to fivefold.

  17. Synthesis of nitric oxide in human osteoblasts in response to physiologic stimulation of electrotherapy.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  20. Using Noninvasive Wearable Computers to Recognize Human Emotions from Physiological Signals

    Directory of Open Access Journals (Sweden)

    Nasoz Fatma

    2004-01-01

    Full Text Available We discuss the strong relationship between affect and cognition and the importance of emotions in multimodal human computer interaction (HCI and user modeling. We introduce the overall paradigm for our multimodal system that aims at recognizing its users' emotions and at responding to them accordingly depending upon the current context or application. We then describe the design of the emotion elicitation experiment we conducted by collecting, via wearable computers, physiological signals from the autonomic nervous system (galvanic skin response, heart rate, temperature and mapping them to certain emotions (sadness, anger, fear, surprise, frustration, and amusement. We show the results of three different supervised learning algorithms that categorize these collected signals in terms of emotions, and generalize their learning to recognize emotions from new collections of signals. We finally discuss possible broader impact and potential applications of emotion recognition for multimodal intelligent systems.

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

    Science.gov (United States)

    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.

  2. Period of the infradian intensity biorhythms of the physiological processes in the human organism

    Energy Technology Data Exchange (ETDEWEB)

    Shabatura, N.N.; Tkachuk, V.G.; Fed' ko, V.A.; Palienko, S.B.

    1987-04-01

    Individual and group variability in the duration of infradian biorhythm periods in humans was studied using groups of male subjects with various regimes of vital activity (60 or more days under conditions of normal, decreased, or increased daily activity). Physiological parameters (including body temperature, respiration rate, minute respiration volume, pulse rate, EKG parameters, and parameters of neuromuscular activity) were determined every morning. Data were treated statistically to detect rhythms and to determine the median period, standard deviation, and variation coefficient of a period. Circaseptadian (6.5 d) and circadiseptadian (13 d) rhythms were shown to exist in all groups. It was found that a relatively stable average duration of the rhythms was maintained in spite of considerable variability in the periods of individual waves. 14 references.

  3. A vision and strategy for the virtual physiological human in 2010 and beyond.

    Science.gov (United States)

    Hunter, Peter; Coveney, Peter V; de Bono, Bernard; Diaz, Vanessa; Fenner, John; Frangi, Alejandro F; Harris, Peter; Hose, Rod; Kohl, Peter; Lawford, Pat; McCormack, Keith; Mendes, Miriam; Omholt, Stig; Quarteroni, Alfio; Skår, John; Tegner, Jesper; Randall Thomas, S; Tollis, Ioannis; Tsamardinos, Ioannis; van Beek, Johannes H G M; Viceconti, Marco

    2010-06-13

    European funding under framework 7 (FP7) for the virtual physiological human (VPH) project has been in place now for nearly 2 years. The VPH network of excellence (NoE) is helping in the development of common standards, open-source software, freely accessible data and model repositories, and various training and dissemination activities for the project. It is also helping to coordinate the many clinically targeted projects that have been funded under the FP7 calls. An initial vision for the VPH was defined by framework 6 strategy for a European physiome (STEP) project in 2006. It is now time to assess the accomplishments of the last 2 years and update the STEP vision for the VPH. We consider the biomedical science, healthcare and information and communications technology challenges facing the project and we propose the VPH Institute as a means of sustaining the vision of VPH beyond the time frame of the NoE.

  4. Using Noninvasive Wearable Computers to Recognize Human Emotions from Physiological Signals

    Science.gov (United States)

    Lisetti, Christine Lætitia; Nasoz, Fatma

    2004-12-01

    We discuss the strong relationship between affect and cognition and the importance of emotions in multimodal human computer interaction (HCI) and user modeling. We introduce the overall paradigm for our multimodal system that aims at recognizing its users' emotions and at responding to them accordingly depending upon the current context or application. We then describe the design of the emotion elicitation experiment we conducted by collecting, via wearable computers, physiological signals from the autonomic nervous system (galvanic skin response, heart rate, temperature) and mapping them to certain emotions (sadness, anger, fear, surprise, frustration, and amusement). We show the results of three different supervised learning algorithms that categorize these collected signals in terms of emotions, and generalize their learning to recognize emotions from new collections of signals. We finally discuss possible broader impact and potential applications of emotion recognition for multimodal intelligent systems.

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

    Science.gov (United States)

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

    1985-01-01

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

  6. Serum Amyloid P Component (SAP) Interactome in Human Plasma Containing Physiological Calcium Levels.

    Science.gov (United States)

    Poulsen, Ebbe Toftgaard; Pedersen, Kata Wolff; Marzeda, Anna Maria; Enghild, Jan J

    2017-02-14

    The pentraxin serum amyloid P component (SAP) is secreted by the liver and found in plasma at a concentration of approximately 30 mg/L. SAP is a 25 kDa homopentamer known to bind both protein and nonprotein ligands, all in a calcium-dependent manner. The function of SAP is unclear but likely involves the humoral innate immune system spanning the complement system, inflammation, and coagulation. Also, SAP is known to bind to the generic structure of amyloid deposits and possibly to protect them against proteolysis. In this study, we have characterized the SAP interactome in human plasma containing the physiological Ca(2+) concentration using SAP affinity pull-down and co-immunoprecipitation experiments followed by mass spectrometry analyses. The analyses resulted in the identification of 33 proteins, of which 24 were direct or indirect interaction partners not previously reported. The SAP interactome can be divided into categories that include apolipoproteins, the complement system, coagulation, and proteolytic regulation.

  7. Visualization of single receptor molecules bound to human rhinovirus under physiological conditions.

    Science.gov (United States)

    Kienberger, Ferry; Rankl, Christian; Pastushenko, Vassili; Zhu, Rong; Blaas, Dieter; Hinterdorfer, Peter

    2005-09-01

    Dynamic force microscopy (DFM) was used to image human rhinovirus HRV2 alone and complexed with single receptor molecules under near physiological conditions. Specific and site-directed immobilization of HRV2 on a model cell membrane resulted in a crystalline arrangement of virus particles with hexagonal symmetry and 35 nm spacing. High-resolution imaging of the virus capsid revealed about 20 resolvable structural features with 3 nm diameters; this finding is in agreement with protrusions seen by cryo-electron microscopy. Binding of receptor molecules to individual virus particles was observed after injection of soluble receptors into the liquid cell. Virus-receptor complexes with zero, one, two, or three attached receptor molecules were resolved. The number of receptor molecules associated to virions increased over time. Occasionally, dissociation of single receptor molecules from viral particles was also observed.

  8. Development of a Human Physiologically Based Pharmacokinetic (PBPK Toolkit for Environmental Pollutants

    Directory of Open Access Journals (Sweden)

    Patricia Ruiz

    2011-10-01

    Full Text Available Physiologically Based Pharmacokinetic (PBPK models can be used to determine the internal dose and strengthen exposure assessment. Many PBPK models are available, but they are not easily accessible for field use. The Agency for Toxic Substances and Disease Registry (ATSDR has conducted translational research to develop a human PBPK model toolkit by recoding published PBPK models. This toolkit, when fully developed, will provide a platform that consists of a series of priority PBPK models of environmental pollutants. Presented here is work on recoded PBPK models for volatile organic compounds (VOCs and metals. Good agreement was generally obtained between the original and the recoded models. This toolkit will be available for ATSDR scientists and public health assessors to perform simulations of exposures from contaminated environmental media at sites of concern and to help interpret biomonitoring data. It can be used as screening tools that can provide useful information for the protection of the public.

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

    Science.gov (United States)

    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.

  10. Drug Insight: the role of leptin in human physiology and pathophysiology--emerging clinical applications.

    Science.gov (United States)

    Brennan, Aoife M; Mantzoros, Christos S

    2006-06-01

    Leptin is an adipocyte-secreted hormone with a key role in energy homeostasis. Studies in animal models, in humans with congenital complete leptin deficiency, and observational and interventional studies in humans with relative leptin deficiency (lower than normal leptin levels) have all indicated that leptin regulates multiple physiological functions, primarily in states of energy deficiency. This information led to proof-of-concept clinical trials involving leptin administration to individuals with relative or complete leptin deficiency. These conditions include congenital complete leptin deficiency, due to mutations in the leptin gene, and states of relative leptin deficiency including lipoatrophy and some forms of hypothalamic amenorrhea. Leptin, in replacement doses, normalizes neuroendocrine, metabolic and immune function in patients with these conditions, but further clinical studies are required to determine its long-term efficacy and safety. Management of leptin-deficient states with replacement doses of leptin holds promise as a therapeutic option. In addition, elucidation of the mechanisms underlying leptin resistance, which characterizes hyperleptinemic states such as human obesity and diabetes, might provide novel therapeutic targets for these prevalent clinical problems.

  11. Indoor Air Quality Assessment Based on Human Physiology - Part 1. New Criteria Proposal

    Directory of Open Access Journals (Sweden)

    M. V. Jokl

    2003-01-01

    Full Text Available Human physiology research makes evident that the Weber-Fechner law applies not only to noise perception but also to the perception of other environmental components. Based on this fact, new decibel units for dor component representing indoor air quality in majority locations have been proposed: decicarbdiox dCd (for carbon dioxide CO2 and decitvoc dTv (for total volatile organic compound TVOC. Equations of these new units have been proved by application of a experimental relationships between odor intensity (representing odor perception by the human body and odor concentrations of CO2 and TVOC, b individually  measured CO2 and TVOC levels (concentrations – from these new decibel units can be calculated and their values compared with decibel units of noise measured in the same locations. The undoubted benefit of using the decibel scale is that it gives much better approximation to human perception of odor intensity compared to the CO2 and TVOC concentration scales.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sweeney, Lisa M.; Thrall, Karla D.; Poet, Torka S.; Corley, Rick; Weber, Thomas J.; Locey, B. J.; Clarkson, Jacquelyn; Sager, S.; Gargas, M. L.

    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:partition 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.

  13. Physiologically based pharmacokinetic modeling of 1,4-Dioxane in rats, mice, and humans.

    Science.gov (United States)

    Sweeney, Lisa M; Thrall, Karla D; Poet, Torka S; Corley, Richard A; Weber, Thomas J; Locey, Betty J; Clarkson, Jacquelyn; Sager, Shawn; Gargas, Michael L

    2008-01-01

    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: partition 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 bioassay conditions. 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.

  14. The physiological effects of human immunoglobulin on severe bronchiolitis patients before and after treatment.

    Science.gov (United States)

    Shan, Yan-Hua; Zhang, Yong-Gang; Zhang, Jian-Hua; Wang, Dong; Li, Xiao-Xia; Zhang, Jie; Wang, Xi-Mei; Luo, Song-Yuan

    2015-01-01

    The goal of the present study is to explore the physiological effects of injected human immunoglobulin on patients with severe bronchiolitis before and after treatment. 86 young children with severe bronchiolitis were randomly divided into the observation group (43 cases) and the treatment group (43 cases). On the basis of conventional therapy, the children in the treatment group were given human immunoglobulin (400 mg/kg, 1-3 times) via intravenous injection. 60 healthy young children, as determined by a physical examination given at the Zhumadian Central Hospital, were enrolled as the control group. The T lymphocytes, cytokines, IgA, IgG, and IgM immunoglobulins in the peripheral blood of all 3 groups were measured. The clinical efficacy of the immunoglobulins to mitigate the effects of bronchiolitis and the amount of time for the reduction of symptoms to occur were observed. The serum Ca, Fe, and Zn levels of children with severe bronchiolitis were significantly lower than those of the healthy control group (p bronchiolitis than in the children in the healthy control group (p bronchiolitis children was significantly shorter for those in the treatment group than for those in the observation group. Human immunoglobulin via intravenous injection showed active therapeutical effects on trace elements, T lymphocytes, and cytokines in patients with severe bronchiolitis.

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

    Science.gov (United States)

    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.

  16. Designing a socio-economic assessment method for integrative biomedical research: the Osteoporotic Virtual Physiological Human project.

    Science.gov (United States)

    Thiel, Rainer; Stroetmann, Karl A; Stroetmann, Veli N; Viceconti, Marco

    2009-01-01

    In integrative biomedical research, methods assessing the clinical or even socio-economic impact of more complex technologies such as Information and Communication Technology (ICT)-based tools for modelling and simulation of human physiology have rarely been applied. The EU funded Osteoporotic Virtual Physiological Human (VPHOP) research project, part of the Virtual Physiological Human (VPH) European initiative, will create a patient-specific hypermodel to predict the absolute risk of bone fracture much more accurately than predictions based on current clinical practice. The project has developed an innovative, multilevel generic methodological framework to assess the clinical and socio-economic impact of biocomputational models. The assessment framework consists of three components: a socio-economic cost benefit analysis, health economic analysis of care pathways, and disease cost simulation models. Through its holistic perspective, the method provides a tool to appraise the overall value of biocomputational models for society.

  17. THE USE OF FAT EMULSIONS FOR INTRAVENOUS ALIMENTATION AND THEIR PHYSIOLOGIC EFFECT IN HUMANS

    Science.gov (United States)

    BIOCHEMISTRY, *COLLOIDS, *FATS, *PARENTERAL INFUSIONS, ANEMIAS, BLOOD PLASMA, BLOOD PLATELETS, CANCER , CHROMATOGRAPHIC ANALYSIS, ERYTHROCYTES, FATTY ACIDS, HEMORRHAGE, PHOSPHOLIPIDS, PHYSIOLOGY, VENOMS

  18. Physiological Networks: towards systems physiology

    Science.gov (United States)

    Bartsch, Ronny P.; Bashan, Amir; Kantelhardt, Jan W.; Havlin, Shlomo; Ivanov, Plamen Ch.

    2012-02-01

    The human organism is an integrated network where complex physiologic systems, each with its own regulatory mechanisms, continuously interact, and where failure of one system can trigger a breakdown of the entire network. Identifying and quantifying dynamical networks of diverse systems with different types of interactions is a challenge. Here, we develop a framework to probe interactions among diverse systems, and we identify a physiologic network. We find that each physiologic state is characterized by a specific network structure, demonstrating a robust interplay between network topology and function. Across physiologic states the network undergoes topological transitions associated with fast reorganization of physiologic interactions on time scales of a few minutes, indicating high network flexibility in response to perturbations. The proposed system-wide integrative approach may facilitate new dimensions to the field of systems physiology.

  19. Physiological effects of proinsulin-connecting peptide in human subcutaneous adipose tissue.

    Science.gov (United States)

    Ghorbani, A; Shafiee-Nick, R; Zojaji, S A; Rajabi-Mashhadi, M T

    2017-06-01

    Recent studies suggest that proinsulin-connecting peptide (C-peptide) may exhibit characteristics of a hormone and show physiological functions in various tissues. This study was aimed to determine whether C-peptide could be involved in the regulation of lipolysis, adiponectin release, and function of mesenchymal stem cells (MSCs) in adipose tissue. Human subcutaneous adipose tissue was cultured in the presence of C-peptide. The level of lipolysis was determined by glycerol measurement in the conditioned media. Effect of C-peptide on adiponectin secretion was evaluated in differentiated adipocytes. The adipogenic and osteogenic abilities of adipose MSCs were evaluated using oil red and alizarin red staining, respectively. The tetrazolium bromide test was conducted for evaluating the effect of C-peptide on MSCs proliferation. C-peptide induced a significant decrease in basal lipolysis at concentrations of 8 and 16 nM (p effects on isoproterenol-stimulated lipolysis, adiponectin secretion, and adipogenic or osteogenic differentiation of MSCs. At a concentration of 4 nM, this peptide significantly increased the proliferative capability of MSCs (p effects in human subcutaneous adipose tissue and contributes to the regulation of basal lipolysis and pool of MSCs.

  20. Simulating the physiology of athletes during endurance sports events: modelling human energy conversion and metabolism.

    Science.gov (United States)

    van Beek, Johannes H G M; Supandi, Farahaniza; Gavai, Anand K; de Graaf, Albert A; Binsl, Thomas W; Hettling, Hannes

    2011-11-13

    The human physiological system is stressed to its limits during endurance sports competition events. We describe a whole body computational model for energy conversion during bicycle racing. About 23 per cent of the metabolic energy is used for muscle work, the rest is converted to heat. We calculated heat transfer by conduction and blood flow inside the body, and heat transfer from the skin by radiation, convection and sweat evaporation, resulting in temperature changes in 25 body compartments. We simulated a mountain time trial to Alpe d'Huez during the Tour de France. To approach the time realized by Lance Armstrong in 2004, very high oxygen uptake must be sustained by the simulated cyclist. Temperature was predicted to reach 39°C in the brain, and 39.7°C in leg muscle. In addition to the macroscopic simulation, we analysed the buffering of bursts of high adenosine triphosphate hydrolysis by creatine kinase during cyclical muscle activity at the biochemical pathway level. To investigate the low oxygen to carbohydrate ratio for the brain, which takes up lactate during exercise, we calculated the flux distribution in cerebral energy metabolism. Computational modelling of the human body, describing heat exchange and energy metabolism, makes simulation of endurance sports events feasible.

  1. Deiodinases: the balance of thyroid hormone: type 1 iodothyronine deiodinase in human physiology and disease.

    Science.gov (United States)

    Maia, Ana Luiza; Goemann, Iuri Martin; Meyer, Erika L Souza; Wajner, Simone Magagnin

    2011-06-01

    Thyroid hormone is essential for the normal function of virtually all tissues. The iodothyronine deiodinases catalyze the removal of an iodine residue from the pro-hormone thyroxine (T(4)) molecule, thus producing either the active form triiodothyronine (T(3); activation) or inactive metabolites (reverse T(3); inactivation). Type I deiodinase (D1) catalyzes both reactions. Over the last years, several studies have attempted to understand the mechanisms of D1 function, underlying its effects on normal thyroid hormone metabolism and pathological processes. Although peripheral D1-generated T(3) production contributes to a portion of plasma T(3) in euthyroid state, pathologically increased thyroidal D1 activity seems to be the main cause of the elevated T(3) concentrations observed in hyperthyroid patients. On the other hand, D1-deficient mouse models show that, in the absence of D1, inactive and lesser iodothyronines are excreted in feces with the loss of associated iodine, demonstrating the scavenging function for D1 that might be particularly important in an iodine deficiency setting. Polymorphisms in the DIO1 gene have been associated with changes in serum thyroid hormone levels, whereas decreased D1 activity has been reported in the nonthyroid illness syndrome and in several human neoplasias. The current review aims at presenting an updated picture of the recent advances made in the biochemical and molecular properties of D1 as well as its role in human physiology.

  2. Evaluating the risk of liver cancer in humans exposed in trichloroethylene using physiological models

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, J.W. (Armstrong Lab., Wright-Patterson AFB, OH (United States)); Allen, B.C. (Clement Assoc., Ruston, LA (United States))

    1993-02-01

    Trichloroethylene (TCE) is a widespread environmental pollutant. TCE is classified as a rodent carcinogen by the U.S. Environmental Protection Agency (EPA). Using the rodent cancer bioassay findings and estimates of metabolized dose, the SPA has estimated lifetime exposure cancer risks for humans that ingest TCE in drinking water or inhale TCE. In this study, a physiologically based pharmacokinetic (PB-PK) model for mice was used to simulate selected gavage and inhalation bioassays with TCE. Plausible dose-metrics thought to be linked with the mechanism of action for TCE carcinogenesis were selected. These dose-metrics, adjusted to reflect an average amount per day for a lifetime, were metabolism of TCE (AMET, mg/kg/day) and systemic concentration of TCA (AUCTCA, mg/L/day). These dose-metrics were then used in a linearized multistage model to estimate AMET and AUCTCA values that correspond to liver cancer risks of 1 in 1 million in mice. A human PB-PK model for TCE was then used to predict TCE concentrations in drinking water and air that would provide AMET and AUCTCA values equal to the predicted mice AMET and AUCTCA values that correspond to liver cancer risks of 1 in 1 million. For the dose-metrics, AMET and AUCTCA, the TCE concentrations in air wave 10.0 and 0.1 ppb TCE (continuous exposure), respectively, and in water, 7 and 4 [mu] TCE/L, respectively.

  3. Human-on-a-chip design strategies and principles for physiologically based pharmacokinetics/pharmacodynamics modeling.

    Science.gov (United States)

    Abaci, Hasan Erbil; Shuler, Michael L

    2015-04-01

    Advances in maintaining multiple human tissues on microfluidic platforms has led to a growing interest in the development of microphysiological systems for drug development studies. Determination of the proper design principles and scaling rules for body-on-a-chip systems is critical for their strategic incorporation into physiologically based pharmacokinetic (PBPK)/pharmacodynamic (PD) model-aided drug development. While the need for a functional design considering organ-organ interactions has been considered, robust design criteria and steps to build such systems have not yet been defined mathematically. In this paper, we first discuss strategies for incorporating body-on-a-chip technology into the current PBPK modeling-based drug discovery to provide a conceptual model. We propose two types of platforms that can be involved in the different stages of PBPK modeling and drug development; these are μOrgans-on-a-chip and μHuman-on-a-chip. Then we establish the design principles for both types of systems and develop parametric design equations that can be used to determine dimensions and operating conditions. In addition, we discuss the availability of the critical parameters required to satisfy the design criteria, consider possible limitations for estimating such parameter values and propose strategies to address such limitations. This paper is intended to be a useful guide to the researchers focused on the design of microphysiological platforms for PBPK/PD based drug discovery.

  4. Alliances in Human Biology: The Harvard Committee on Industrial Physiology, 1929-1939.

    Science.gov (United States)

    Oakes, Jason

    2015-08-01

    In 1929 the newly-reorganized Rockefeller Foundation funded the work of a cross-disciplinary group at Harvard University called the Committee on Industrial Physiology (CIP). The committee's research and pedagogical work was oriented towards different things for different members of the alliance. The CIP program included a research component in the Harvard Fatigue Laboratory and Elton May's interpretation of the Hawthorne Studies; a pedagogical aspect as part of Wallace Donham's curriculum for Harvard Business School; and Lawrence Henderson's work with the Harvard Pareto Circle, his course Sociology 23, and the Harvard Society of Fellows. The key actors within the CIP alliance shared a concern with training men for elite careers in government service, business leadership, and academic prominence. But the first communications between the CIP and the Rockefeller Foundation did not emphasize training in human biology. Instead, the CIP presented itself as a coordinating body that would be able to organize all the varied work going on at Harvard that did not fit easily into one department, and it was on this basis that the CIP became legible to the President of Harvard, A. Lawrence Lowell, and to Rockefeller's Division of Social Sciences. The members of the CIP alliance used the term human biology for this project of research, training and institutional coordination.

  5. Human physiological benefits of viewing nature: EEG responses to exact and statistical fractal patterns.

    Science.gov (United States)

    Hagerhall, C M; Laike, T; Küller, M; Marcheschi, E; Boydston, C; Taylor, R P

    2015-01-01

    Psychological and physiological benefits of viewing nature have been extensively studied for some time. More recently it has been suggested that some of these positive effects can be explained by nature's fractal properties. Virtually all studies on human responses to fractals have used stimuli that represent the specific form of fractal geometry found in nature, i.e. statistical fractals, as opposed to fractal patterns which repeat exactly at different scales. This raises the question of whether human responses like preference and relaxation are being driven by fractal geometry in general or by the specific form of fractal geometry found in nature. In this study we consider both types of fractals (statistical and exact) and morph one type into the other. Based on the Koch curve, nine visual stimuli were produced in which curves of three different fractal dimensions evolve gradually from an exact to a statistical fractal. The patterns were shown for one minute each to thirty-five subjects while qEEG was continuously recorded. The results showed that the responses to statistical and exact fractals differ, and that the natural form of the fractal is important for inducing alpha responses, an indicator of a wakefully relaxed state and internalized attention.

  6. Recapitulation of physiological spatiotemporal signals promotes in vitro formation of phenotypically stable human articular cartilage

    Science.gov (United States)

    Wei, Yiyong; Zhou, Bin; Bernhard, Jonathan; Robinson, Samuel; Burapachaisri, Aonnicha; Guo, X. Edward

    2017-01-01

    Standard isotropic culture fails to recapitulate the spatiotemporal gradients present during native development. Cartilage grown from human mesenchymal stem cells (hMSCs) is poorly organized and unstable in vivo. We report that human cartilage with physiologic organization and in vivo stability can be grown in vitro from self-assembling hMSCs by implementing spatiotemporal regulation during induction. Self-assembling hMSCs formed cartilage discs in Transwell inserts following isotropic chondrogenic induction with transforming growth factor β to set up a dual-compartment culture. Following a switch in the basal compartment to a hypertrophic regimen with thyroxine, the cartilage discs underwent progressive deep-zone hypertrophy and mineralization. Concurrent chondrogenic induction in the apical compartment enabled the maintenance of functional and hyaline cartilage. Cartilage homeostasis, chondrocyte maturation, and terminal differentiation markers were all up-regulated versus isotropic control groups. We assessed the in vivo stability of the cartilage formed under different induction regimens. Cartilage formed under spatiotemporal regulation in vitro resisted endochondral ossification, retained the expression of cartilage markers, and remained organized following s.c. implantation in immunocompromised mice. In contrast, the isotropic control groups underwent endochondral ossification. Cartilage formed from hMSCs remained stable and organized in vivo. Spatiotemporal regulation during induction in vitro recapitulated some aspects of native cartilage development, and potentiated the maturation of self-assembling hMSCs into stable and organized cartilage resembling the native articular cartilage. PMID:28228529

  7. Effects of foliage plants on human physiological and psychological responses at different temperatures

    Science.gov (United States)

    Jumeno, Desto; Matsumoto, Hiroshi

    2015-02-01

    Escalation of task demands and time pressures tends to make a worker run into work stress, which leads to mental fatigue and depression. The mental fatigue can be reduced when attention capacity is restored. Nature can serve as a source of fascination which can restore the attention capacity. People bring plants indoors so they can experience nature in their workplace. The stress and fatigue are also affected by air temperatures. The increase or decrease of temperatures from the comfort zone may induce the stress and fatigue. The objective of this study is to investigate the intervention of using foliage plants placed inside a building at different air temperature levels. The effects of foliage plants on human stress and fatigue were measured by human physiological responses such as heart rate, amylase level, electroencephalography (EEG), and the secondary task-reaction time. Several different tasks, namely typing, math and logical sequences are included in the investigation of these studies. Fifteen subjects, with the age ranged from 22 to 38 years old have participated in the study using within subject design. From the study, it is revealed that the presence of foliage plants at several temperatures have different effects on meditation, secondary task reaction time and typing accuracy. This study also revealed that the presence of plants on several types of tasks has different effects of attention which are useful for increasing work performance.

  8. A wireless capsule system with ASIC for monitoring the physiological signals of the human gastrointestinal tract.

    Science.gov (United States)

    Xu, Fei; Yan, Guozheng; Zhao, Kai; Lu, Li; Gao, Jinyang; Liu, Gang

    2014-12-01

    This paper presents the design of a wireless capsule system for monitoring the physiological signals of the human gastrointestinal (GI) tract. The primary components of the system include a wireless capsule, a portable data recorder, and a workstation. Temperature, pH, and pressure sensors; an RF transceiver; a controlling and processing application specific integrated circuit (ASIC); and batteries were applied in a wireless capsule. Decreasing capsule size, improving sensor precision, and reducing power needs were the primary challenges; these were resolved by employing micro sensors, optimized architecture, and an ASIC design that include power management, clock management, a programmable gain amplifier (PGA), an A/D converter (ADC), and a serial peripheral interface (SPI) communication unit. The ASIC has been fabricated in 0.18- μm CMOS technology with a die area of 5.0 mm × 5.0 mm. The wireless capsule integrating the ASIC controller measures Φ 11 mm × 26 mm. A data recorder and a workstation were developed, and 20 cases of human experiments were conducted in hospitals. Preprocessing in the workstation can significantly improve the quality of the data, and 76 original features were determined by mathematical statistics. Based on the 13 optimal features achieved in the evaluation of the features, the clustering algorithm can identify the patients who lack GI motility with a recognition rate reaching 83.3%.

  9. Muscle sympathetic nerve responses to physiological changes in prostaglandin production in humans

    Science.gov (United States)

    Doerzbacher, K. J.; Ray, C. A.

    2001-01-01

    Previous studies suggest that prostaglandins may contribute to exercise-induced increases in muscle sympathetic nerve activity (MSNA). To test this hypothesis, MSNA was measured at rest and during exercise before and after oral administration of ketoprofen, a cyclooxygenase inhibitor, or placebo. Twenty-one subjects completed two bouts of graded dynamic and isometric handgrip to fatigue. Each exercise bout was followed by 2 min of postexercise muscle ischemia. The second exercise bouts were performed after 60 min of rest in which 11 subjects were given ketoprofen (300 mg) and 10 subjects received a placebo. Ketoprofen significantly lowered plasma thromboxane B(2) in the drug group (from 36 +/- 6 to 22 +/- 3 pg/ml, P muscle ischemia. There was no relationship between thromboxane B(2) concentrations and MSNA or arterial pressure responses during both exercise modes. The data indicate that physiological increases or decreases in prostaglandins do not alter exercise-induced increases in MSNA and arterial pressure in humans. These findings suggest that contraction-induced metabolites other than prostaglandins mediate MSNA responses to exercise in humans.

  10. A Human Life-Stage Physiologically Based Pharmacokinetic and Pharmacodynamic Model for Chlorpyrifos: Development and Validation

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Jordan N.; Hinderliter, Paul M.; Timchalk, Charles; Bartels, M. J.; Poet, Torka S.

    2014-08-01

    Sensitivity to 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 computationally predict disposition of CPF 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, age-dependent body weight was calculated from a generalized Gompertz function, and compartments (liver, brain, fat, blood, diaphragm, rapid, and slow) were scaled based on body weight from polynomial functions on a fractional body weight basis. Blood flows among compartments were calculated as a constant flow per compartment volume. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Model simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ≥ 0.55 mg/kg of chlorpyrifos (significantly higher than environmental exposure levels), 6 mo 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 oral doses of chlorpyrifos. At lower doses that are more relevant to environmental exposures, the model predicts 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 CPF disposition and biological response over various postnatal life-stages.

  11. Psychological and physiological human responses to simulated and real environments: A comparison between Photographs, 360° Panoramas, and Virtual Reality.

    Science.gov (United States)

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

    NARCIS (Netherlands)

    Al-Subeihi, A.A.; Spenkelink, A.; Punt, A.; Boersma, M.G.; Bladeren, van P.J.; Rietjens, I.

    2012-01-01

    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 curr

  13. Physiologically based kinetic models for the alkenylbenzene elemicin in rat and human and possible implications for risk assessment.

    NARCIS (Netherlands)

    Berg, van den S.J.; Punt, A.; Soffers, A.E.M.F.; Vervoort, J.J.M.; Ngeleja, S.; Spenkelink, B.; Rietjens, I.M.C.M.

    2012-01-01

    The present study describes physiologically based kinetic (PBK) models for the alkenylbenzene elemicin (3,4,5-trimethoxyallylbenzene) in rat and human, based on the PBK models previously developed for the structurally related alkenylbenzenes estragole, methyleugenol, and safrole. Using the newly dev

  14. Active Learning and Flipped Classroom, Hand in Hand Approach to Improve Students Learning in Human Anatomy and Physiology

    Science.gov (United States)

    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…

  15. Academic Performance in Human Anatomy and Physiology Classes: A 2-Yr Study of Academic Motivation and Grade Expectation

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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…

  17. An Investigation into the Effects of a Modified Mastery Strategy on Achievement in a High School Human Physiology Unit.

    Science.gov (United States)

    Lueckemeyer, Cynthia L.; Chiappetta, Eugene L.

    1981-01-01

    Determined if modifying Bloom's mastery strategy improves science achievement during a six week human physiology unit. Findings indicate only a small degree of improvement in achievement of 185 students. Suggests that the approach employed in this study would be impractical for the biology classroom. (DS)

  18. Interteaching within a Human Physiology Course: A Comparison of First- and Second-Year Students' Learning Skills and Perceptions

    Science.gov (United States)

    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…

  19. Interteaching within a Human Physiology Course: A Comparison of First- and Second-Year Students' Learning Skills and Perceptions

    Science.gov (United States)

    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…

  20. Academic Performance in Human Anatomy and Physiology Classes: A 2-Yr Study of Academic Motivation and Grade Expectation

    Science.gov (United States)

    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…

  1. Physiologically based kinetic modeling of hesperidin metabolism and its use to predict in vivo effective doses in humans

    NARCIS (Netherlands)

    Boonpawa, Rungnapa; Spenkelink, Bert; Punt, Ans; Rietjens, Ivonne

    2017-01-01

    Scope: To develop a physiologically based kinetic (PBK) model that describes the absorption, distribution, metabolism, and excretion of hesperidin in humans, enabling the translation of in vitro concentration-response curves to in vivo dose-response curves. Methods and results: The PBK model for

  2. The menagerie of human lipocalins: a natural protein scaffold for molecular recognition of physiological compounds.

    Science.gov (United States)

    Schiefner, André; Skerra, Arne

    2015-04-21

    all higher organisms, physiologically important members of this family have long been known in the human body, for example with the plasma retinol-binding protein that serves for the transport of vitamin A. This prototypic human lipocalin was the first for which a crystal structure was solved. Notably, several other lipocalins were discovered and assigned to this protein class before the term itself became familiar, which explains their diverse names in the scientific literature. To date, up to 15 distinct members of the lipocalin family have been characterized in humans, and during the last two decades the three-dimensional structures of a dozen major subtypes have been elucidated. This Account presents a comprehensive overview of the human lipocalins, revealing common structural principles but also deviations that explain individual functional features. Taking advantage of modern methods for combinatorial protein design, lipocalins have also been employed as scaffolds for the construction of artifical binding proteins with novel ligand specificities, so-called Anticalins, hence opening perspectives as a new class of biopharmaceuticals for medical therapy.

  3. Ultrasensitive, passive and wearable sensors for monitoring human muscle motion and physiological signals.

    Science.gov (United States)

    Cai, Feng; Yi, Changrui; Liu, Shichang; Wang, Yan; Liu, Lacheng; Liu, Xiaoqing; Xu, Xuming; Wang, Li

    2016-03-15

    Flexible sensors have attracted more and more attention as a fundamental part of anthropomorphic robot research, medical diagnosis and physical health monitoring. Here, we constructed an ultrasensitive and passive flexible sensor with the advantages of low cost, lightness and wearability, electric safety and reliability. The fundamental mechanism of the sensor is based on triboelectric effect inducing electrostatic charges on the surfaces between two different materials. Just like a plate capacitor, current will be generated while the distance or size of the parallel capacitors changes caused by the small mechanical disturbance upon it and therefore the output current/voltage will be produced. Typically, the passive sensor unambiguously monitors muscle motions including hand motion from stretch-clench-stretch, mouth motion from open-bite-open, blink and respiration. Moreover, this sensor records the details of the consecutive phases in a cardiac cycle of the apex cardiogram, and identify the peaks including percussion wave, tidal wave and diastolic wave of the radial pulse wave. To record subtle human physiological signals including radial pulsilogram and apex cardiogram with excellent signal/noise ratio, stability and reproducibility, the sensor shows great potential in the applications of medical diagnosis and daily health monitoring.

  4. Non-genomic aldosterone action: from the cell membrane to human physiology.

    Science.gov (United States)

    Lösel, Ralf; Feuring, Martin; Wehling, Martin

    2002-12-01

    According to the traditional model, steroid hormones bind to intracellular receptors and subsequently modulate transcription and protein synthesis, thus triggering genomic events finally responsible for delayed effects. In addition, very rapid effects of steroids mainly affecting intracellular signaling have been widely recognized which are clearly incompatible with the genomic model. These rapid, non-genomic steroid actions are likely to be transmitted via specific membrane receptors. Evidences for non-genomic steroid effects and distinct receptors involved are now presented for all steroid groups including vitamin D(3) and thyroid hormones. Mechanisms of action are being studied with regard to signal perception and transduction involved, and for various steroids including aldosterone a patchy sketch of a membrane receptor/second messenger cascade shows up being not essentially dissimilar to cascades involved in catecholamine or peptide hormone action. Aside non-classical membrane receptors with a high affinity for aldosterone, these effects involve phospholipase C, phosphoinositide turnover, intracellular pH and calcium, protein kinase C and tyrosine kinases. Increasing evidence is being accumulated for rapid physiological responses in humans, e.g. at the level of circulatory or metabolic effects, rendering clinical significance to these rapid actions.

  5. Dental and Medical Students' Use and Perceptions of Learning Resources in a Human Physiology Course.

    Science.gov (United States)

    Tain, Monica; Schwartzstein, Richard; Friedland, Bernard; Park, Sang E

    2017-09-01

    The aim of this study was to determine the use and perceived utility of various learning resources available during the first-year Integrated Human Physiology course at the dental and medical schools at Harvard University. Dental and medical students of the Class of 2018 were surveyed anonymously online in 2015 regarding their use of 29 learning resources in this combined course. The learning resources had been grouped into four categories to discern frequency of use and perceived usefulness among the categories. The survey was distributed to 169 students, and 73 responded for a response rate of 43.2%. There was no significant difference among the learning resource categories in frequency of use; however, there was a statistically significant difference among categories in students' perceptions of usefulness. No correlation was found between frequency of use and perceived usefulness of each category. Students seemingly were not choosing the most useful resources for them. These results suggest that, in the current educational environment, where new technologies and self-directed learning are highly sought after, there remains a need for instructor-guided learning.

  6. GDF15 in the Physiological Human Pregnancy: Novel Data and A Systematic Review

    Directory of Open Access Journals (Sweden)

    Aleksandrova AA

    2015-10-01

    Full Text Available The involvement of GDF15 protein in modulating the processes of cellular migration and adhesion, tissue remodeling and inflammatory responses suggests that this factor may be of high importance for pregnancy establishment and its further maintenance. Analyzing pregnancy-associated dynamics of the factor confers a valuable addition to the case-control studies and can help advance our understanding of the fundamentals of the factor’s involvement in pregnancy. However, as seen from the systematic literature review presented in this paper, current data set significant questions on roles of GDF15 in pregnancy. Additionally, a significant controversy is seen in the literature regarding the gestational dynamics of GDF15. Thus, we tried to contribute to the field by assessing the dynamics of serum GDF15 protein in the course of the physiological human pregnancy. We found that serum maternal GDF15 levels increase by almost two orders of magnitude with progression of pregnancy from the mid-first trimester towards the early second trimester and then towards the term. These data were further compared with those found in the literature.

  7. Human physiology and psychology in space flight; Uchu hiko ni okeru ningen no seiri to shinri

    Energy Technology Data Exchange (ETDEWEB)

    Murai, T. [National Space Development Agency of Japan, Tokyo (Japan)

    1999-10-05

    Human beings' adaptation to space and the effects on them of a prolonged stay in space are discussed. Some effects may be detrimental to crewmen even when they are medically judged as 'normal' and 'adaptable.' Bone deliming, muscular atrophy, and hypodynamia may be physiologically 'normal' and 'adaptable' in the zero-gravity environment where no strength is required to hold a position or attitude, and they will not cause any serious problems if crewmen are to stay in the zero-gravity environment permanently. Astronauts work on conditions that they return to the earth, however, and they have to stand on their own legs when back on the ground. Such being the case, they in the space vehicle are forced to make efforts at having their bone density and muscular strength sustained. It is inevitable for a space station to be a closed, isolated system, and the crewmen have to live in multinational, multicultural, and multilingual circumstances in case the flight is an international project. They will be exposed to great social and psychological stresses, and their adaptability to such stresses presents an important task. (NEDO)

  8. Crystal Structure of Human Senescence Marker Protein 30: Insights Linking Structural, Enzymatic, and Physiological Functions

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborti, Subhendu; Bahnson, Brian J. (Delaware)

    2010-05-25

    Human senescence marker protein 30 (SMP30), which functions enzymatically as a lactonase, hydrolyzes various carbohydrate lactones. The penultimate step in vitamin-C biosynthesis is catalyzed by this enzyme in nonprimate mammals. It has also been implicated as an organophosphate hydrolase, with the ability to hydrolyze diisopropyl phosphofluoridate and other nerve agents. SMP30 was originally identified as an aging marker protein, whose expression decreased androgen independently in aging cells. SMP30 is also referred to as regucalcin and has been suggested to have functions in calcium homeostasis. The crystal structure of the human enzyme has been solved from X-ray diffraction data collected to a resolution of 1.4 {angstrom}. The protein has a 6-bladed {beta}-propeller fold, and it contains a single metal ion. Crystal structures have been solved with the metal site bound with either a Ca{sup 2+} or a Zn{sup 2+} atom. The catalytic role of the metal ion has been confirmed by mutagenesis of the metal coordinating residues. Kinetic studies using the substrate gluconolactone showed a k{sub cat} preference of divalent cations in the order Zn{sup 2+} > Mn{sup 2+} > Ca{sup 2+} > Mg{sup 2+}. Notably, the Ca{sup 2+} had a significantly higher value of K{sub d} compared to those of the other metal ions tested (566, 82, 7, and 0.6 {micro}m for Ca{sup 2+}, Mg{sup 2+}, Zn{sup 2+}, and Mn{sup 2+}, respectively), suggesting that the Ca{sup 2+}-bound form may be physiologically relevant for stressed cells with an elevated free calcium level.

  9. Directed migration of human bone marrow mesenchymal stem cells in a physiological direct current electric field

    Directory of Open Access Journals (Sweden)

    Z Zhao

    2011-11-01

    Full Text Available At sites of bone fracture, naturally-occurring electric fields (EFs exist during healing and may guide cell migration. In this study, we investigated whether EFs could direct the migration of bone marrow mesenchymal stem cells (BM-MSCs, which are known to be key players in bone formation. Human BM-MSCs were cultured in direct current EFs of 10 to 600 mV/mm. Using time-lapse microscopy, we demonstrated that an EF directed migration of BM-MSCs mainly to the anode. Directional migration occurred at a low threshold and with a physiological EF of ~25 mV/mm. Increasing the EF enhanced the MSC migratory response. The migration speed peaked at 300 mV/mm, at a rate of 42 ±1 µm/h, around double the control (no EF migration rate. MSCs showed sustained response to prolonged EF application in vitro up to at least 8 h. The electrotaxis of MSCs with either early (P3-P5 or late (P7-P10 passage was also investigated. Migration was passage-dependent with higher passage number showing reduced directed migration, within the range of passages examined. An EF of 200 mV/mm for 2 h did not affect cell senescence, phenotype, or osteogenic potential of MSCs, regardless of passage number within the range tested (P3-P10. Our findings indicate that EFs are a powerful cue in directing migration of human MSCs in vitro. An applied EF may be useful to control or enhance migration of MSCs during bone healing.

  10. Physiological HEPES buffer proposed as a calibrator for pH measurement in human blood.

    Science.gov (United States)

    Lang, W; Zander, R

    1999-05-01

    N-(2-hydroxyethyl)-piperazine-N'-2-ethanesulfonic acid, known as HEPES buffer, with pK in the physiological range was studied for use as an alternative to conventional phosphate buffer for the calibration of pH in modern clinical analyzers. In different series of aqueous equimolar HEPES buffer, pH was measured at 37 degrees C with a capillary glass electrode standardized previously using phosphate, and variations due to changes in total HEPES buffer concentration (0.025 to 0.320 mol/l), and NaCl (0 to 0.250 mol/l) were monitored. For 0.05 equimolar HEPES buffer without NaCl, the pH of 7.362+/-0.003 (n = 15) obtained coincided well with the reference pH (7.364) from the National Institute of Standards and Technology (NIST). In particular, in the preferred 0.05 equimolar HEPES buffer/0.110 mol/l NaCl, which is isotonic to human plasma (0.160 mol/l), and termed physiological HEPES buffer (PHB), the pH of 7.346+/-0.003 (n = 84) can be related to the calculated corresponding reference pH from NIST without liquid junction (7.374), and is also compatible with the pH measured in normal arterial blood, pH = 7.403+/-0.003 (n = 20). Hence, in the two-point calibration of clinical analyzers, PHB, which is defined operationally with respect to the glass electrode and to phosphate buffer, may be useful as a calibrator in the range of buffer adjustment control to meet the correct values for pH when measuring in blood. Whereas Na-HEPES salt is hygroscopic and does not meet the declared purity grade (> 99%), pure HEPES acid is non-hygroscopic and conforms to the manufacturer's purity grade (> or = 99%). Therefore, for easy preparation of PHB, HEPES acid is the preferred starting material.

  11. Advances in understanding of mammalian penile evolution, human penile anatomy and human erection physiology: clinical implications for physicians and surgeons.

    Science.gov (United States)

    Hsieh, Cheng-Hsing; Liu, Shih-Ping; Hsu, Geng-Long; Chen, Heng-Shuen; Molodysky, Eugen; Chen, Ying-Hui; Yu, Hong-Jeng

    2012-07-01

    Recent studies substantiate a model of the tunica albuginea of the corpora cavernosa as a bi-layered structure with a 360° complete inner circular layer and a 300° incomplete outer longitudinal coat spanning from the bulbospongiosus and ischiocavernosus proximally and extending continuously into the distal ligament within the glans penis. The anatomical location and histology of the distal ligament invites convincing parallels with the quadrupedal os penis and therefore constitutes potential evidence of the evolutionary process. In the corpora cavernosa, a chamber design is responsible for facilitating rigid erections. For investigating its venous factors exclusively, hemodynamic studies have been performed on both fresh and defrosted human male cadavers. In each case, a rigid erection was unequivocally attainable following venous removal. This clearly has significant ramifications in relation to penile venous surgery and its role in treating impotent patients. One deep dorsal vein, 2 cavernosal veins and 2 pairs of para-arterial veins (as opposed to 1 single vein) are situated between Buck's fascia and the tunica albuginea. These newfound insights into penile tunical, venous anatomy and erection physiology were inspired by and, in turn, enhance clinical applications routinely encountered by physicians and surgeons, such as penile morphological reconstruction, penile implantation and penile venous surgery.

  12. Validation of a Computational Platform for the Analysis of the Physiologic Mechanisms of a Human Experimental Model of Hemorrhage

    Science.gov (United States)

    2009-12-01

    physiologic functioning of a virtual subject is a special adaptation of an established computer model of human physiology ( Guyton /Coleman/Summers model...RL. Computer simulation studies and the scientific method. J Appl Anim Welf Sci 1998;1:119–31. [PubMed: 16363976] 3. Guyton AC, Montani J-P, Hall JE...1197388] 7. Guyton AC, Coleman TG, Granger HJ. Circulation: overall regulation. Annu Rev Physiol 1972;34:13–46. [PubMed: 4334846] 8. Guyton AC, Coleman

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

    Science.gov (United States)

    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.

  14. Using Stimulation of the Diving Reflex in Humans to Teach Integrative Physiology

    Science.gov (United States)

    Choate, Julia K.; Denton, Kate M.; Evans, Roger G.; Hodgson, Yvonne

    2014-01-01

    During underwater submersion, the body responds by conserving O[subscript 2] and prioritizing blood flow to the brain and heart. These physiological adjustments, which involve the nervous, cardiovascular, and respiratory systems, are known as the diving response and provide an ideal example of integrative physiology. The diving reflex can be…

  15. Review of the physiology of human thermal comfort while exercising in urban landscapes and implications for bioclimatic design

    Science.gov (United States)

    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.

  16. Review of the physiology of human thermal comfort while exercising in urban landscapes and implications for bioclimatic design.

    Science.gov (United States)

    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.

  17. Context-dependent effects of steroid chemosignals on human physiology and mood.

    Science.gov (United States)

    Jacob, S; Hayreh, D J; McClintock, M K

    We examined the physiological and psychological effects of nanomolar amounts of steroids applied directly under the nose (Delta4,16-androstadien-3-one and 1,3,5,(10),16-estratetraen-3-ol). These potential human chemosignals were not consciously discernible in a strong-odor carrier (clove oil and propylene glycol). In a double-blind, within-subject, repeated-measures experiment with 65 subjects, we demonstrated that both steroids produced sustained changes in digit skin temperature and palmar skin conductance (an indicator of sympathetic nervous system tone) while the subjects were completing psychological questionnaires or reading. These effects, however, did not follow the sex-stereotyped pattern predicted by a sex attractant function. Both androstadienone and estratetraenol raised the skin temperature of men's hands and lowered it in women. Likewise, each steroid increased skin conductance, with a significantly greater effect on women than men. Women's responses were observed only in the sessions run by the male tester, an effect that may or may not be solely attributable to tester sex. Men's responses, in contrast, were not affected by this difference in socioexperimental condition. Similarly, women experienced an immediate increase in positive mood only in the presence of the male tester, while men's responses were unaffected by this socioexperimental context. One source of this sex difference may be the fact that the majority of women were in the late follicular phase of their menstrual cycle. Although it is premature to classify these steroids as pheromones, our data suggest that they function as chemosignals that modulate autonomic nervous system tone as well as psychological state.

  18. A vision and strategy for the virtual physiological human: 2012 update.

    Science.gov (United States)

    Hunter, Peter; Chapman, Tara; Coveney, Peter V; de Bono, Bernard; Diaz, Vanessa; Fenner, John; Frangi, Alejandro F; Harris, Peter; Hose, Rod; Kohl, Peter; Lawford, Pat; McCormack, Keith; Mendes, Miriam; Omholt, Stig; Quarteroni, Alfio; Shublaq, Nour; Skår, John; Stroetmann, Karl; Tegner, Jesper; Thomas, S Randall; Tollis, Ioannis; Tsamardinos, Ioannis; van Beek, Johannes H G M; Viceconti, Marco

    2013-04-06

    European funding under Framework 7 (FP7) for the virtual physiological human (VPH) project has been in place now for 5 years. The VPH Network of Excellence (NoE) has been set up to help develop common standards, open source software, freely accessible data and model repositories, and various training and dissemination activities for the project. It is also working to coordinate the many clinically targeted projects that have been funded under the FP7 calls. An initial vision for the VPH was defined by the FP6 STEP project in 2006. In 2010, we wrote an assessment of the accomplishments of the first two years of the VPH in which we considered the biomedical science, healthcare and information and communications technology challenges facing the project (Hunter et al. 2010 Phil. Trans. R. Soc. A 368, 2595-2614 (doi:10.1098/rsta.2010.0048)). We proposed that a not-for-profit professional umbrella organization, the VPH Institute, should be established as a means of sustaining the VPH vision beyond the time-frame of the NoE. Here, we update and extend this assessment and in particular address the following issues raised in response to Hunter et al.: (i) a vision for the VPH updated in the light of progress made so far, (ii) biomedical science and healthcare challenges that the VPH initiative can address while also providing innovation opportunities for the European industry, and (iii) external changes needed in regulatory policy and business models to realize the full potential that the VPH has to offer to industry, clinics and society generally.

  19. Opportunities for learning in an introductory undergraduate human anatomy and physiology course

    Science.gov (United States)

    Montplaisir, Lisa Marie

    2003-10-01

    The purpose of this study was to explore the course conditions that support the development of meaningful student learning in an introductory undergraduate human anatomy and physiology course. The study was conducted during an 8-week summer-session at a small mid-western university. Classroom observations and taped recordings of class sessions were used to determine content episodes within the instructional unit, opportunities for learning created by the instructor, demonstrations of information processing by the students, and the ways in which the instructor used the Personal Response System (PRS). Student interviews were used to determine students' level of understanding of pre-test and post-test items. Student interviews and a questionnaire were used to determine students' perceptions of the PRS as a learning tool. Findings reveal that the instructor had different expectations of students when posing verbal questions in-class than he had when posing PRS questions. The use of verbal questions did not permit demonstrations of student understanding; however, the use of the PRS did result in demonstrations of student understanding. Questions posed via the use of the PRS were categorized according to cognitive level. The cognitive level of the questions increased with time over the instructional unit and within the content episodes. Students demonstrated deeper understanding of the topics after instruction than they did before instruction. Students reported more in-class thinking about the content, more discussion of the content with their neighbors, more regular class attendance, more opportunities for deeper learning, and a general preference for the PRS over traditional lectures. Findings of the study indicate that the instructional decisions about the use of questions influences the opportunities for students to process information and demonstrate their understanding of the content and that students valued these opportunities. A better understanding of the

  20. A New Approach to Teaching Human Cardiovascular Physiology Using Doppler Ultrasound.

    Science.gov (United States)

    Looker, T.

    1985-01-01

    Explains the principles of the Doppler ultrasound technique and reviews its potential applications to the teaching of cardiovascular physiology. Identifies the instrumentation needed for this technique; provides examples and illustrations of the waveforms from the ultrasound blood velocimeter. (ML)

  1. Human plasma concentrations of cytochrome P450 probes extrapolated from pharmacokinetics in cynomolgus monkeys using physiologically based pharmacokinetic modeling.

    Science.gov (United States)

    Shida, Satomi; Utoh, Masahiro; Murayama, Norie; Shimizu, Makiko; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-01-01

    1. Cynomolgus monkeys are widely used in preclinical studies as non-human primate species. Pharmacokinetics of human cytochrome P450 probes determined in cynomolgus monkeys after single oral or intravenous administrations were extrapolated to give human plasma concentrations. 2. Plasma concentrations of slowly eliminated caffeine and R-/S-warfarin and rapidly eliminated omeprazole and midazolam previously observed in cynomolgus monkeys were scaled to human oral biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model. Results of the simplified human PBPK models were consistent with reported experimental PK data in humans or with values simulated by a fully constructed population-based simulator (Simcyp). 3. Oral administrations of metoprolol and dextromethorphan (human P450 2D probes) in monkeys reportedly yielded plasma concentrations similar to their quantitative detection limits. Consequently, ratios of in vitro hepatic intrinsic clearances of metoprolol and dextromethorphan determined in monkeys and humans were used with simplified PBPK models to extrapolate intravenous PK in monkeys to oral PK in humans. 4. These results suggest that cynomolgus monkeys, despite their rapid clearance of some human P450 substrates, could be a suitable model for humans, especially when used in conjunction with simple PBPK models.

  2. Behavioural and physiological stress responses to environmental and human factors in different small mammal species: implications for their conservation

    OpenAIRE

    Navarro Castilla, Álvaro

    2016-01-01

    Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Wild animal populations are continuously subjected to periodic disturbances by environmental and anthropogenic causes. Thereby, in this doctoral thesis, we carried out different investigations to study the behavioural and physiological stress responses of several small mammal species to different environmental and human factors. Behavioral responses to predation ris...

  3. Species distribution and physiological characterization of Acinetobacter genospecies from healthy human skin of tribal population in India

    Directory of Open Access Journals (Sweden)

    Yavankar S

    2007-01-01

    Full Text Available Background: Various reports on distribution of Acinetobacter spp. from healthy human skin restricted to urban population. However, no such data is available from healthy human skin of tribal population not exposed to modern antibiotics during their life time. Purpose: Isolation, biotyping, distribution and physiological characterisation of Acinetobacter spp. from healthy human skin of tribal population. Methods: Tribal population of Toranmal area of Satpuda Ranges, Maharashtra, India were sampled for ten body sites. Tentative Acinetobacter isolates were confirmed to the genus level by chromosomal DNA transformation assay and to species level using Bouvet and Grimont system. Novel physiological characteristics like pH, temperature and salt tolerance were studied. All strains were screened for production of various enzymes. Results: One hundred and eighteen strains were isolated, which belonged to nine Acinetobacter genospecies. A. haemolyticus was most abundant followed by A. calcoaceticus and A. genospecies 1-3. Higher percentage of Acinetobacter was recovered from skin of nose, Pawara tribe and female volunteers. They showed wide variation in temperature, salt and pH tolerance. Most of the strains could produce enzymes viz, lipase, esterase, urease and amylase. Conclusions: Acinetobacter spp. belonging to nine genospecies were obtained in the present study. Physiological characteristics including high salt, temperature and acidic pH tolerance were helpful to differentiate between the commensal and pathogenic species of Acinetobacter genus.

  4. Knowledge on the subject of human physiology among Polish high school students--a cross-sectional study.

    Science.gov (United States)

    Zwinczewska, Helena; Rozwadowska, Joanna; Traczyk, Anna; Majda, Szymon; Wysocki, Michał; Grabowski, Kamil; Kopeć, Sylwia; Głowacki, Roman; Węgrzyn, Katarzyna; Tomaszewski, Krzysztof A; Walocha, Jerzy A

    2014-01-01

    In most cases the only knowledge an individual will receive with regards to their own body and its proper functioning is during their high school education. The aim of this study was to evaluate high school students' knowledge about basic physiology. The research was carried out in five, randomly chosen high schools in Krakow, Poland. Young people in the age of 17-19 years were asked to fill in the questionnaire designed by the authors. The first part of the survey included personal data. The second part contained 20 close-ended questions assessing students' knowledge about the basics of human physiology. Question difficulty varied from easy through average, and up to difficult. The maximum number of points to achieve was 20. One-thousand-and eighty-three (out of 1179 invited--91.86%) Polish high school students (63.25% female) filled in a 20-item questionnaire constructed by the authors regarding basic human physiology. The mean age of the group was 17.66 ± 0.80 years. The mean score among the surveyed was 10.15 ± 3.48 (range 0-20). Only 26.04% of students achieved a grade of 60% or more, and only one person obtained the highest possible score. Females achieved significantly better scores than males (10.49 ± 3.38 vs. 9.56 ± 3.56; p students did not know that mature red blood cells do not have cell nuclei and a similar number of them answered that humans have 500,000 erythrocytes in 1 mm3 of blood. Over 32% believed that plasma does not participate in the transport of respiratory gases, and 31% believed that endocrine glands secrete hormones within their immediate vicinity and into the blood. Our research has shown that young people, especially men, often lack basic physiological knowledge needed to make conscious and responsible decisions regarding their health. Our results suggest that more emphasis should be put on properly teaching human physiology in high school, especially to those students who do not plan a career in medicine-related fields. This study

  5. The purinergic component of human bladder smooth muscle cells’ proliferation and contraction under physiological stretch

    Energy Technology Data Exchange (ETDEWEB)

    Wazir, Romel; Luo, De-Yi; Tian, Ye; Yue, Xuan; Li, Hong; Wang, Kun-Jie, E-mail: kunjiewangatscu@163.com

    2013-07-26

    Highlights: •Stretch induces proliferation and contraction. •Optimum applied stretch in vitro is 5% and 10% equibiaxial stretching respectively. •Expression of P2X1 and P2X2 is upregulated after application of stretch. •P2X2 is possibly more susceptible to stretch related changes. •Purinoceptors functioning may explain conditions with atropine resistance. -- Abstract: Objective: To investigate whether cyclic stretch induces proliferation and contraction of human smooth muscle cells (HBSMCs), mediated by P2X purinoceptor 1 and 2 and the signal transduction mechanisms of this process. Methods: HBSMCs were seeded on silicone membrane and stretched under varying parameters; (equibiaxial elongation: 2.5%, 5%, 10%, 15%, 20%, 25%), (Frequency: 0.05 Hz, 0.1 Hz, 0.2 Hz, 0.5 Hz, 1 Hz). 5-Bromo-2-deoxyuridine assay was employed for proliferative studies. Contractility of the cells was determined using collagen gel contraction assay. After optimal physiological stretch was established; P2X1 and P2X2 were analyzed by real time polymerase chain reaction and Western Blot. Specificity of purinoceptors was maintained by employing specific inhibitors; (NF023 for P2X1, and A317491for P2X2), in some experiments. Results: Optimum proliferation and contractility were observed at 5% and 10% equibiaxial stretching respectively, applied at a frequency of 0.1 Hz; At 5% stretch, proliferation increased from 0.837 ± 0.026 (control) to 1.462 ± 0.023%, p < 0.05. Mean contraction at 10% stretching increased from 31.7 ± 2.3%, (control) to 78.28 ±1.45%, p < 0.05. Expression of P2X1 and P2X2 was upregulated after application of stretch. Inhibition had effects on proliferation (1.232 ± 0.051, p < 0.05 NF023) and (1.302 ± 0.021, p < 0.05 A314791) while contractility was markedly reduced (68.24 ± 2.31, p < 0.05 NF023) and (73.2 ± 2.87, p < 0.05 A314791). These findings shows that mechanical stretch can promote magnitude-dependent proliferative and contractile modulation of HBSMCs in

  6. Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functions

    Directory of Open Access Journals (Sweden)

    Siegmund Kimberly D

    2010-10-01

    Full Text Available Abstract Background It has been proposed that anatomical differences in human and great ape guts arose in response to species-specific diets and energy demands. To investigate functional genomic consequences of these differences, we compared their physiological levels of phytanic acid, a branched chain fatty acid that can be derived from the microbial degradation of chlorophyll in ruminant guts. Humans who accumulate large stores of phytanic acid commonly develop cerebellar ataxia, peripheral polyneuropathy, and retinitis pigmentosa in addition to other medical conditions. Furthermore, phytanic acid is an activator of the PPAR-alpha transcription factor that influences the expression of genes relevant to lipid metabolism. Results Despite their trace dietary phytanic acid intake, all great ape species had elevated red blood cell (RBC phytanic acid levels relative to humans on diverse diets. Unlike humans, chimpanzees showed sexual dimorphism in RBC phytanic acid levels, which were higher in males relative to females. Cultured skin fibroblasts from all species had a robust capacity to degrade phytanic acid. We provide indirect evidence that great apes, in contrast to humans, derive significant amounts of phytanic acid from the hindgut fermentation of plant materials. This would represent a novel reduction of metabolic activity in humans relative to the great apes. Conclusion We identified differences in the physiological levels of phytanic acid in humans and great apes and propose this is causally related to their gut anatomies and microbiomes. Phytanic acid levels could contribute to cross-species and sex-specific differences in human and great ape transcriptomes, especially those related to lipid metabolism. Based on the medical conditions caused by phytanic acid accumulation, we suggest that differences in phytanic acid metabolism could influence the functions of human and great ape nervous, cardiovascular, and skeletal systems.

  7. Breath-based meditation: A mechanism to restore the physiological and cognitive reserves for optimal human performance.

    Science.gov (United States)

    Carter, Kirtigandha Salwe; Carter, Robert

    2016-04-16

    Stress can be associated with many physiological changes resulting in significant decrements in human performance. Due to growing interests in alternative and complementary medicine by Westerners, many of the traditions and holistic yogic breathing practices today are being utilized as a measure for healthier lifestyles. These state-of-the-art practices can have a significant impact on common mental health conditions such as depression and generalized anxiety disorder. However, the potential of yogic breathing on optimizing human performance and overall well-being is not well known. Breathing techniques such as alternate nostril, Sudarshan Kriya and bhastrika utilizes rhythmic breathing to guide practitioners into a deep meditative state of relaxation and promote self-awareness. Furthermore, yogic breathing is physiologically stimulating and can be described as a natural "technological" solution to optimize human performance which can be categorized into: (1) cognitive function (i.e., mind, vigilance); and (2) physical performance (i.e., cardiorespiratory, metabolism, exercise, whole body). Based on previous studies, we postulate that daily practice of breathing meditation techniques play a significant role in preserving the compensatory mechanisms available to sustain physiological function. This preservation of physiological function may help to offset the time associated with reaching a threshold for clinical expression of chronic state (i.e., hypertension, depression, dementia) or acute state (i.e., massive hemorrhage, panic attic) of medical conditions. However, additional rigorous biomedical research is needed to evaluate the physiological mechanisms of various forms of meditation (i.e., breath-based, mantra, mindfulness) on human performance. These efforts will help to define how compensatory reserve mechanisms of cardiovascular and immune systems are modulated by breath-based meditation. While it has been suggested that breath-based meditation is easier for

  8. A biomimetic physiological model for human adipose tissue by adipocytes and endothelial cell cocultures with spatially controlled distribution.

    Science.gov (United States)

    Yao, Rui; Du, Yanan; Zhang, Renji; Lin, Feng; Luan, Jie

    2013-08-01

    An in vitro model that recapitulates the characteristics of native human adipose tissue would largely benefit pathology studies and therapy development. In this paper, we fabricated a physiological model composed of both human adipocytes and endothelial cells with spatially controlled distribution that biomimics the structure and composition of human adipose tissue. Detailed studies into the cell-cell interactions between the adipocytes and endothelial cells revealed a mutual-enhanced effect which resembles the in vivo routine. Furthermore, comparisons between planar coculture and model coculture demonstrated improved adipocyte function as well as endothelial cell proliferation under the same conditions. This research provided a reliable model for human adipose tissue development studies and potential obesity-related therapy development.

  9. Physiological level Production of Antigen-Specific Human Immunoglobulin in Cloned Transchromosomic Cattle

    OpenAIRE

    Akiko Sano; Hiroaki Matsushita; Hua Wu; Jin-An Jiao; Poothappillai Kasinathan; Eddie J. Sullivan; Zhongde Wang; Yoshimi Kuroiwa

    2013-01-01

    Therapeutic human polyclonal antibodies (hpAbs) derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human...

  10. Using stimulation of the diving reflex in humans to teach integrative physiology.

    Science.gov (United States)

    Choate, Julia K; Denton, Kate M; Evans, Roger G; Hodgson, Yvonne

    2014-12-01

    During underwater submersion, the body responds by conserving O2 and prioritizing blood flow to the brain and heart. These physiological adjustments, which involve the nervous, cardiovascular, and respiratory systems, are known as the diving response and provide an ideal example of integrative physiology. The diving reflex can be stimulated in the practical laboratory setting using breath holding and facial immersion in water. Our undergraduate physiology students complete a laboratory class in which they investigate the effects of stimulating the diving reflex on cardiovascular variables, which are recorded and calculated with a Finapres finger cuff. These variables include heart rate, cardiac output, stroke volume, total peripheral resistance, and arterial pressures (mean, diastolic, and systolic). Components of the diving reflex are stimulated by 1) facial immersion in cold water (15°C), 2) breathing with a snorkel in cold water (15°C), 3) facial immersion in warm water (30°C), and 4) breath holding in air. Statistical analysis of the data generated for each of these four maneuvers allows the students to consider the factors that contribute to the diving response, such as the temperature of the water and the location of the sensory receptors that initiate the response. In addition to providing specific details about the equipment, protocols, and learning outcomes, this report describes how we assess this practical exercise and summarizes some common student misunderstandings of the essential physiological concepts underlying the diving response.

  11. Ultrastructural and physiological changes induced by different stress conditions on the human parasite Trypanosoma cruzi.

    Science.gov (United States)

    Pérez-Morales, Deyanira; Hernández, Karla Daniela Rodríguez; Martínez, Ignacio; Agredano-Moreno, Lourdes Teresa; Jiménez-García, Luis Felipe; Espinoza, Bertha

    2017-01-01

    Trypanosoma cruzi is the etiological agent of Chagas disease. The life cycle of this protozoan parasite is digenetic because it alternates its different developmental forms through two hosts, a vector insect and a vertebrate host. As a result, the parasites are exposed to sudden and drastic environmental changes causing cellular stress. The stress response to some types of stress has been studied in T. cruzi, mainly at the molecular level; however, data about ultrastructure and physiological state of the cells in stress conditions are scarce or null. In this work, we analyzed the morphological, ultrastructural, and physiological changes produced on T. cruzi epimastigotes when they were exposed to acid, nutritional, heat, and oxidative stress. Clear morphological changes were observed, but the physiological conditions varied depending on the type of stress. The maintenance of the physiological state was severely affected by heat shock, acidic, nutritional, and oxidative stress. According to the surprising observed growth recovery after damage by stress alterations, different adaptations from the parasite to these harsh conditions were suggested. Particular cellular death pathways are discussed.

  12. Ethanol co-administration moderates 3,4-methylenedioxymethamphetamine effects on human physiology

    NARCIS (Netherlands)

    Dumont, G.J.H.; Kramers, C.; Sweep, F.C.G.J.; Willemsen, J.J.; Touw, D.J.; Schoemaker, R.C.; Van Gerven, J.M.A.; Buitelaar, J.K.; Verkes, R.J.

    2010-01-01

    Alcohol is frequently used in combination with 3,4- methylenedioxymethamphetamine (MDMA). Both drugs affect cardiovascular function, hydration and temperature regulation, but may have partly opposing effects. The present study aims to assess the acute physiologic effects of (co-) administration of M

  13. Physiological roles of semenogelin I and zinc in sperm motility and semen coagulation on ejaculation in humans.

    Science.gov (United States)

    Yoshida, Kaoru; Kawano, Natsuko; Yoshiike, Miki; Yoshida, Manabu; Iwamoto, Teruaki; Morisawa, Masaaki

    2008-03-01

    At ejaculation, human sperm are considered to be mechanically trapped and become immotile in the semen coagulum by binding to semenogelins (Sgs) from the seminal vesicle and zinc ions from the prostate. However, the physiological combined roles of the protein and heavy metal on sperm motility are unknown. Here, we have first demonstrated that Sg I alone, which does not form the semen coagulum without zinc, is an inhibitor of the motility of intact human sperm at physiological concentration. On the other hand, zinc ions alone had no effect on sperm motility, but confer recovery of sperm motility that has been inhibited by Sg I at a concentration equal to or less than 1 mg/ml. These observations suggest that the roles played by Sg I and zinc on sperm motility are not mechanical but physiological. Quartz crystal microbalance analysis suggests that the sperm extract first bind to Sg I and then zinc ions which subsequently increase the protein accumulation, suggesting that Sgs inhibit sperm motility by directly binding to the sperm surface. Further accumulation of Sg I mediated by zinc ions may entrap the quiescent sperm at semen ejaculation.

  14. Physiological Information Database (PID)

    Science.gov (United States)

    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...

  15. Physiological effects in aromatherapy

    OpenAIRE

    2004-01-01

    The effects of aromas on humans are divided into physiological and psychological effects. The physiological effect acts directly on the physical organism, the psychological effect acts via the sense of smell or olfactory system, which in turn may cause a physiological effect. This paper reviews on the physiological effects which are used for the evaluation of the effects of aromas. Physiological parameters, i.e. heart rate blood pressure, electrodermal activity, electroencephalogram, slow pot...

  16. A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen.

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Coppé

    Full Text Available Cellular senescence irreversibly arrests cell proliferation in response to oncogenic stimuli. Human cells develop a senescence-associated secretory phenotype (SASP, which increases the secretion of cytokines and other factors that alter the behavior of neighboring cells. We show here that "senescent" mouse fibroblasts, which arrested growth after repeated passage under standard culture conditions (20% oxygen, do not express a human-like SASP, and differ from similarly cultured human cells in other respects. However, when cultured in physiological (3% oxygen and induced to senesce by radiation, mouse cells more closely resemble human cells, including expression of a robust SASP. We describe two new aspects of the human and mouse SASPs. First, cells from both species upregulated the expression and secretion of several matrix metalloproteinases, which comprise a conserved genomic cluster. Second, for both species, the ability to promote the growth of premalignant epithelial cells was due primarily to the conserved SASP factor CXCL-1/KC/GRO-alpha. Further, mouse fibroblasts made senescent in 3%, but not 20%, oxygen promoted epithelial tumorigenesis in mouse xenographs. Our findings underscore critical mouse-human differences in oxygen sensitivity, identify conditions to use mouse cells to model human cellular senescence, and reveal novel conserved features of the SASP.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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.

  19. A review of human physiological and performance changes associated with desynchronosis of biological rhythms

    Science.gov (United States)

    Winget, C. M.; Deroshia, C. W.; Markley, C. L.; Holley, D. C.

    1984-01-01

    This review discusses the effects, in the aerospace environment, of alterations in approximately 24-h periodicities (circadian rhythms) upon physiological and psychological functions and possible therapies for desynchronosis induced by such alterations. The consequences of circadian rhythm alteration resulting from shift work, transmeridian flight, or altered day lengths are known as desynchronosis, dysrhythmia, dyschrony, jet lag, or jet syndrome. Considerable attention is focused on the ability to operate jet aircraft and manned space vehicles. The importance of environmental cues, such as light-dark cycles, which influence physiological and psychological rhythms is discussed. A section on mathematical models is presented to enable selection and verification of appropriate preventive and corrective measures and to better understand the problem of dysrhythmia.

  20. Human plasma concentrations of herbicidal carbamate molinate extrapolated from the pharmacokinetics established in in vivo experiments with chimeric mice with humanized liver and physiologically based pharmacokinetic modeling.

    Science.gov (United States)

    Yamashita, Masanao; Suemizu, Hiroshi; Murayama, Norie; Nishiyama, Sayako; Shimizu, Makiko; Yamazaki, Hiroshi

    2014-10-01

    To predict concentrations in humans of the herbicidal carbamate molinate, used exclusively in rice cultivation, a forward dosimetry approach was carried out using data from lowest-observed-adverse-effect-level doses orally administered to rats, wild type mice, and chimeric mice with humanized liver and from in vitro human and rodent experiments. Human liver microsomes preferentially mediated hydroxylation of molinate, but rat livers additionally produced molinate sulfoxide and an unidentified metabolite. Adjusted animal biomonitoring equivalents for molinate and its primary sulfoxide from animal studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and human metabolic data with a simple physiologically based pharmacokinetic (PBPK) model. The slower disposition of molinate and accumulation of molinate sulfoxide in humans were estimated by modeling after single and multiple doses compared with elimination in rodents. The results from simplified PBPK modeling in combination with chimeric mice with humanized liver suggest that ratios of estimated parameters of molinate sulfoxide exposure in humans to those in rats were three times as many as general safety factor of 10 for species difference in toxicokinetics. Thus, careful regulatory decision is needed when evaluating the human risk resulting from exposure to low doses of molinate and related carbamates based on data obtained from rats.

  1. Study on Effect of Plants in office on Human Physiological/Psychological Responses

    OpenAIRE

    2016-01-01

    Some offices have indoor environmental quality (IEQ) related problems such as space, indoor air quality (IAQ), office workers' thermal comfort, productivity and mental stress. As is well known, some foliage plants have effects of humidity control and VOC removal from indoor air, improvement of productivity and reducing workers' mental stress as well. The objective of this study is to examine the effect of indoor plants on physiological/psychological responses, and to demonstrate the mental he...

  2. [Recognition of commensal microflora by pattern recognition receptors in human physiology and pathology].

    Science.gov (United States)

    Bondarenko, V M; Likhoded, V G

    2012-01-01

    Contemporary data on the interaction of commensal microflora and Toll-like pattern recognition receptors are presented. These receptors recognize normal intestine microflora in physiological conditions, and this interaction is necessary for the maintenance of homeostasis and damage reparation of the intestine, for the induction of heat shock cytoprotective proteins. As a side effect in disruption of immunologic tolerance and misbalance of protective immunological mechanisms, multiorgan pathologic changes of organs and tissues may develop, including chronic inflammation processes of various localization.

  3. Ethanol co-administration moderates 3,4-methylenedioxymethamphetamine effects on human physiology.

    Science.gov (United States)

    Dumont, G J H; Kramers, C; Sweep, F C G J; Willemsen, J J; Touw, D J; Schoemaker, R C; van Gerven, J M A; Buitelaar, J K; Verkes, R J

    2010-02-01

    Alcohol is frequently used in combination with 3,4-methylenedioxymethamphetamine (MDMA). Both drugs affect cardiovascular function, hydration and temperature regulation, but may have partly opposing effects. The present study aims to assess the acute physiologic effects of (co-) administration of MDMA and ethanol over time. A four-way, double blind, randomized, crossover, placebo-controlled study in 16 healthy volunteers (9 male and 7 female) between the ages of 18 and 29. MDMA (100 mg) was given orally and blood ethanol concentration was maintained at pseudo-steady state levels of 0.6 per thousand by a three-hour 10% intravenous ethanol clamp. Cardiovascular function, temperature and hydration measures were recorded throughout the study days. Ethanol did not significantly affect physiologic function, with the exception of a short lasting increase in heart rate. MDMA potently increased heart rate and blood pressure and induced fluid retention as well as an increase in temperature. Co-administration of ethanol with MDMA did not affect cardiovascular function compared to the MDMA alone condition, but attenuated the effects of MDMA on fluid retention and showed a trend for attenuation of MDMA-induced temperature increase. In conclusion, co-administration of ethanol and MDMA did not exacerbate physiologic effects compared to all other drug conditions, and moderated some effects of MDMA alone.

  4. Human Blood Concentrations of Cotinine, a Biomonitoring Marker for Tobacco Smoke, Extrapolated from Nicotine Metabolism in Rats and Humans and Physiologically Based Pharmacokinetic Modeling

    Directory of Open Access Journals (Sweden)

    Masato Kitajima

    2010-09-01

    Full Text Available The present study defined a simplified physiologically based pharmacokinetic (PBPK model for nicotine and its primary metabolite cotinine in humans, based on metabolic parameters determined in vitro using relevant liver microsomes, coefficients derived in silico, physiological parameters derived from the literature, and an established rat PBPK model. The model consists of an absorption compartment, a metabolizing compartment, and a central compartment for nicotine and three equivalent compartments for cotinine. Evaluation of a rat model was performed by making comparisons with predicted concentrations in blood and in vivo experimental pharmacokinetic values obtained from rats after oral treatment with nicotine (1.0 mg/kg, a no-observed-adverse-effect level for 14 days. Elimination rates of nicotine in vitro were established from data from rat liver microsomes and from human pooled liver microsomes. Human biomonitoring data (17 ng nicotine and 150 ng cotinine per mL plasma 1 h after smoking from pooled five male Japanese smokers (daily intake of 43 mg nicotine by smoking revealed that these blood concentrations could be calculated using a human PBPK model. These results indicate that a simplified PBPK model for nicotine/cotinine is useful for a forward dosimetry approach in humans and for estimating blood concentrations of other related compounds resulting from exposure to low chemical doses.

  5. Control Strategy for Anaesthetic Drug Dosage with Interaction Among Human Physiological Organs Using Optimal Fractional Order PID Controller

    CERN Document Server

    Das, Saptarshi; Maharatna, Koushik

    2016-01-01

    In this paper, an efficient control strategy for physiological interaction based anaesthetic drug infusion model is explored using the fractional order (FO) proportional integral derivative (PID) controllers. The dynamic model is composed of several human organs by considering the brain response to the anaesthetic drug as output and the drug infusion rate as the control input. Particle Swarm Optimisation (PSO) is employed to obtain the optimal set of parameters for PID/FOPID controller structures. With the proposed FOPID control scheme much less amount of drug-infusion system can be designed to attain a specific anaesthetic target and also shows high robustness for +/-50% parametric uncertainty in the patient's brain model.

  6. Human control of an inverted pendulum: is continuous control necessary? Is intermittent control effective? Is intermittent control physiological?

    Science.gov (United States)

    Loram, Ian D; Gollee, Henrik; Lakie, Martin; Gawthrop, Peter J

    2011-01-15

    Human motor control is often explained in terms of engineering 'servo' theory. Recently, continuous, optimal control using internal models has emerged as a leading paradigm for voluntary movement. However, these engineering paradigms are designed for high band-width, inflexible, consistent systems whereas human control is low bandwidth and flexible using noisy sensors and actuators. By contrast, engineering intermittent control was designed for bandwidth-limited applications. Our general interest is whether intermittent rather than continuous control is generic to human motor control. Currently, it would be assumed that continuous control is the superior and physiologically natural choice for controlling unstable loads, for example as required for maintaining human balance. Using visuo-manual tracking of an unstable load, we show that control using gentle, intermittent taps is entirely natural and effective. The gentle tapping method resulted in slightly superior position control and velocity minimisation, a reduced feedback time delay, greater robustness to changing actuator gain and equal or greater linearity with respect to the external disturbance. Control was possible with a median contact rate of 0.8±0.3 s(-1). However, when optimising position or velocity regulation, a modal contact rate of 2 s(-1) was observed. This modal rate was consistent with insignificant disturbance-joystick coherence beyond 1-2 Hz in both tapping and continuous contact methods. For this load, these results demonstrate a motor control process of serial ballistic trajectories limited to an optimum rate of 2 s(-1). Consistent with theoretical reasoning, our results suggest that intermittent open loop action is a natural consequence of human physiology.

  7. Accelerated generation of human induced pluripotent stem cells with retroviral transduction and chemical inhibitors under physiological hypoxia.

    Science.gov (United States)

    Shimada, Hidenori; Hashimoto, Yoshiya; Nakada, Akira; Shigeno, Keiji; Nakamura, Tatsuo

    2012-01-13

    Induced pluripotent stem (iPS) cells are generated from somatic cells by the forced expression of a defined set of pluripotency-associated transcription factors. Human iPS cells can be propagated indefinitely, while maintaining the capacity to differentiate into all cell types in the body except for extra-embryonic tissues. This technology not only represents a new way to use individual-specific stem cells for regenerative medicine but also constitutes a novel method to obtain large amounts of disease-specific cells for biomedical research. Despite their great potential, the long reprogramming process (up to 1month) remains one of the most significant challenges facing standard virus-mediated methodology. In this study, we report the accelerated generation of human iPS cells from adipose-derived stem (ADS) cells, using a new combination of chemical inhibitors under a setting of physiological hypoxia in conjunction with retroviral transduction of Oct4, Sox2, Klf4, and L-Myc. Under optimized conditions, we observed human embryonic stem (ES)-like cells as early as 6 days after the initial retroviral transduction. This was followed by the emergence of fully reprogrammed cells bearing Tra-1-81-positive and DsRed transgene-silencing properties on day 10. The resulting cell lines resembled human ES cells in many respects including proliferation rate, morphology, pluripotency-associated markers, global gene expression patterns, genome-wide DNA methylation states, and the ability to differentiate into all three of the germ layers, both in vitro and in vivo. Our method, when combined with chemical inhibitors under conditions of physiological hypoxia, offers a powerful tool for rapidly generating bona fide human iPS cells and facilitates the application of iPS cell technology to biomedical research.

  8. You are not what you eat during physiological stress: Isotopic evaluation of human hair.

    Science.gov (United States)

    D'Ortenzio, Lori; Brickley, Megan; Schwarcz, Henry; Prowse, Tracy

    2015-07-01

    Variation in δ(13) C and δ(15) N values can be assessed to understand not only diet, but also the influence of physiological factors on an individual. The metabolic balance of an individual can impact isotopic signals in tissues that are forming during the periods of metabolic stress. Fluctuating δ(15) N values are associated with physiological stressors that alter an individual's metabolism such as infection, injury, or pregnancy. This study examines variation in δ(13) C and δ(15) N values along sequentially segmented hair in both modern and archaeological individuals. Subjects with an observable skeletal pathology, known chronic illness, or evidence of pregnancy were compared with controls exhibiting no evidence of physiological stress. The results on hair samples from individuals from 19(th) century Belleville, Ontario, four modern cadavers (two with cancer and two sudden deaths), and two living pregnant women indicate that δ(15) N values are approximately 1‰ higher in individuals with a pathological condition (e.g., infection, fracture, or cancer) and are 1‰ lower during pregnancy, whereas δ(13) C values show less variability. Higher nitrogen values may represent the recycling of nitrogen derived from the breakdown of existing proteins in the body (catabolism), whereas lower δ(15) N values are related to increased utilization of dietary and urea nitrogen for tissue synthesis during pregnancy. These findings suggest that short-term fluctuations of δ(15) N values may be the result of changes in an individual's metabolic balance, and that metabolic imbalance poses a confounding factor to ancient dietary studies when using rapidly growing tissues such as hair.

  9. Anorexia in human and experimental animal models: physiological aspects related to neuropeptides.

    Science.gov (United States)

    Yoshimura, Mitsuhiro; Uezono, Yasuhito; Ueta, Yoichi

    2015-09-01

    Anorexia, a loss of appetite for food, can be caused by various physiological and pathophysiological conditions. In this review, firstly, clinical aspects of anorexia nervosa are summarized in brief. Secondly, hypothalamic neuropeptides responsible for feeding regulation in each hypothalamic nucleus are discussed. Finally, three different types of anorexigenic animal models; dehydration-induced anorexia, cisplatin-induced anorexia and cancer anorexia-cachexia, are introduced. In conclusion, hypothalamic neuropeptides may give us novel insight to understand and find effective therapeutics strategy essential for various kinds of anorexia.

  10. Narrative review: the role of leptin in human physiology: emerging clinical applications.

    Science.gov (United States)

    Kelesidis, Theodore; Kelesidis, Iosif; Chou, Sharon; Mantzoros, Christos S

    2010-01-19

    Leptin is a hormone secreted by adipose tissue in direct proportion to amount of body fat. The circulating leptin levels serve as a gauge of energy stores, thereby directing the regulation of energy homeostasis, neuroendocrine function, and metabolism. Persons with congenital deficiency are obese, and treatment with leptin results in dramatic weight loss through decreased food intake and possible increased energy expenditure. However, most obese persons are resistant to the weight-reducing effects of leptin. Recent studies suggest that leptin is physiologically more important as an indicator of energy deficiency, rather than energy excess, and may mediate adaptation by driving increased food intake and directing neuroendocrine function to converse energy, such as inducing hypothalamic hypogonadism to prevent fertilization. Current studies investigate the role of leptin in weight-loss management because persons who have recently lost weight have relative leptin deficiency that may drive them to regain weight. Leptin deficiency is also evident in patients with diet- or exercise-induced hypothalamic amenorrhea and lipoatrophy. Replacement of leptin in physiologic doses restores ovulatory menstruation in women with hypothalamic amenorrhea and improves metabolic dysfunction in patients with lipoatrophy, including lipoatrophy associated with HIV or highly active antiretroviral therapy. The applications of leptin continue to grow and will hopefully soon be used therapeutically.

  11. Social relationships and physiological determinants of longevity across the human life span.

    Science.gov (United States)

    Yang, Yang Claire; Boen, Courtney; Gerken, Karen; Li, Ting; Schorpp, Kristen; Harris, Kathleen Mullan

    2016-01-19

    Two decades of research indicate causal associations between social relationships and mortality, but important questions remain as to how social relationships affect health, when effects emerge, and how long they last. Drawing on data from four nationally representative longitudinal samples of the US population, we implemented an innovative life course design to assess the prospective association of both structural and functional dimensions of social relationships (social integration, social support, and social strain) with objectively measured biomarkers of physical health (C-reactive protein, systolic and diastolic blood pressure, waist circumference, and body mass index) within each life stage, including adolescence and young, middle, and late adulthood, and compare such associations across life stages. We found that a higher degree of social integration was associated with lower risk of physiological dysregulation in a dose-response manner in both early and later life. Conversely, lack of social connections was associated with vastly elevated risk in specific life stages. For example, social isolation increased the risk of inflammation by the same magnitude as physical inactivity in adolescence, and the effect of social isolation on hypertension exceeded that of clinical risk factors such as diabetes in old age. Analyses of multiple dimensions of social relationships within multiple samples across the life course produced consistent and robust associations with health. Physiological impacts of structural and functional dimensions of social relationships emerge uniquely in adolescence and midlife and persist into old age.

  12. Heparin and Related Substances: Physiology and Pathophysiology in General and in Human Reproduction - Part 1

    Directory of Open Access Journals (Sweden)

    Würfel W

    2016-01-01

    Full Text Available Although heparin is usually associated with blood clotting and thrombosis prevention, its anti-coagulatory properties play an extremely significant role in clinical routine. However, it appears to have little importance in rheological homeostatis, particularly since heparin and related substances can also be found in simpler organisms without clotting mechanisms. In fact, heparin and heparan sulfate glycans are proteoglycans that have a long history in the development of species. Accordingly, their primary effects are electrostatic, not receptor-mediated, and they exhibit binding via their pronounced electronegativity. They exist in free form and as membrane-bound molecules. In physiological terms, heparin and heparinoids are immunological co-factors involved in inflammation and wound healing; they play significant roles in embryo development and organogenesis, serve as “homing factors,” and are involved at various points in carcinogenesis. They show diverse interactions with cytokines, growth factors and other mediators that are important in the implantation process and its control and continue to be so throughout pregnancy. It can be assumed that reproduction is a key focus of physiological functions; this would explain why heparin is so effective above and beyond its anti-coagulatory effects, e.g. in treating anti-phospholipid syndrome. To date no clear confirmation of the existence of a heparin deficiency syndrome has been possible, although initial results from studies concerning the general administration of heparin during pregnancy point in this direction

  13. Interaction between Fibrinogen and Insulin-Like Growth Factor-Binding Protein-1 in Human Plasma under Physiological Conditions.

    Science.gov (United States)

    Gligorijević, N; Nedić, O

    2016-02-01

    Fibrinogen is a plasma glycoprotein and one of the principle participants in blood coagulation. It interacts with many proteins during formation of a blood clot, including insulin-like growth factors (IGFs) and their binding proteins (IGFBP). Fibrinogen complexes were found as minor fractions in fibrinogen preparations independently of the coagulation process, and their presence influences the kinetics of polymerization. The idea of this work was to investigate whether fibrinogen in human plasma interacts with IGFBPs independently of the tissue injury or coagulation process. The results have shown that fibrinogen forms complexes with IGFBP-1 under physiological conditions. Several experimental approaches have confirmed that complexes are co-isolated with fibrinogen from plasma, they are relatively stable, and they appear as a general feature of human plasma. Several other experiments excluded the possibility that alpha-2 macroglobulin/IGFBP-1 complexes or IGFBP-1 oligomers contributed to IGFBP-1 immunoreactivity. The role of fibrinogen/IGFBP-1 complexes is still unknown. Further investigation in individuals expressing both impaired glucose control and coagulopathy could contribute to identification and understanding of their possible physiological role.

  14. Retracted: Physiologically based pharmacokinetic predictions of intestinal BCRP-mediated effect of telmisartan on the pharmacokinetics of rosuvastatin in humans.

    Science.gov (United States)

    Bae, Soo Hyeon; Park, Wan-Su; Han, Seunghoon; Park, Gab-Jin; Lee, Jongtae; Hong, Taegon; Jeon, Sangil; Yim, Dong-Seok

    2017-07-01

    'Physiologically based pharmacokinetic predictions of intestinal BCRP-mediated effect of telmisartan on the pharmacokinetics of rosuvastatin in humans' by Soo Hyeon Bae, Wan-Su Park, Seunghoon Han, Gab-jin Park, Jongtae Lee, Taegon Hong, Sangil Jeon and Dong-Seok Yim The above article, published online on 06 February 2017 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, K. Sandy Pang, and John Wiley & Sons, Ltd. The authors retracted the paper due to errors associated with use of log D vs. log P of telmisartan as inputs of the PBPK model. The authors concluded that there are too many changes in the article to be resolved by an Erratum, and had requested a retraction. Reference Bae, S. H., Park, W.-S., Han, S., Park, G., Lee, J., Hong, T., Jeon, S., and Yim, D.-S. (2016) Physiologically based pharmacokinetic predictions of intestinal BCRP-mediated effect of telmisartan on the pharmacokinetics of rosuvastatin in humans. Biopharm. Drug Dispos., doi: 10.1002/bdd.2060. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Differentiation of human adipocytes at physiological oxygen levels results in increased adiponectin secretion and isoproterenol-stimulated lipolysis.

    Science.gov (United States)

    Famulla, Susanne; Schlich, Raphaela; Sell, Henrike; Eckel, Jürgen

    2012-07-01

    Adipose tissue (AT) hypoxia occurs in obese humans and mice. Acute hypoxia in adipocytes causes dysregulation of adipokine secretion with an increase in inflammatory factors and diminished adiponectin release. O2 levels in humans range between 3 and 11% revealing that conventional in vitro culturing at ambient air and acute hypoxia treatment (1% O2) are performed under non-physiological conditions. In this study, we mimicked physiological conditions by differentiating human primary adipocytes under 10% or 5% O2 in comparison to 21% O2. Induction of differentiation markers was comparable between all three conditions. Adipokine release by adipocytes differentiated at lower oxygen levels was altered, with a marked upregulation of adiponectin, IL-6 and DPP4 secretion, and reduced leptin levels compared with adipocytes differentiated at 21% O2. Isoproterenol-induced lipolysis was significantly elevated in adipocytes differentiated at 10% and 5% compared with 21% O2. This effect was accompanied by increased protein expression of β-1 and -2 adrenergic receptor, HSL and perilipin. Conditioned medium (CM) of adipocytes differentiated at the three different conditions was generated for stimulation of human skeletal muscle cells (SkMC) or smooth muscle cells (SMC). CM-induced insulin resistance in SkMC was comparable for the different CMs. However, the SMC proliferative effect of CM from adipocytes differentiated at 10% O2 was significantly reduced compared with 21% O2. This study demonstrates that oxygen levels during adipogenesis are important factors altering adipocyte functionality such as adipokine release, in particular adiponectin secretion, as well as the hormone-induced lipolytic pathway.

  16. In vivo optical imaging of physiological responses to photostimulation in human photoreceptors

    CERN Document Server

    Hillmann, Dierck; Pfäffle, Clara; Sudkamp, Helge; Franke, Gesa; Hüttmann, Gereon

    2016-01-01

    Non-invasive functional imaging of molecular and cellular processes of vision is expected to have immense impact on research and clinical diagnostics. Although suitable intrinsic optical signals (IOS) have been observed ex vivo and in immobilized animals in vivo, it was so far not possible to obtain convincing IOS of photoreceptor activity in humans in vivo. Here, we observed spatially and temporally clearly resolved changes in the optical path length of the photoreceptor outer segment as response to an optical stimulus in living human. To obtain these changes, we evaluated phase data of a parallelized and computationally aberration-corrected optical coherence tomography (OCT) system. The non-invasive detection of optical path length changes shows the neuronal photoreceptor activity of single cones in living human retina, and, more importantly, it provides a new diagnostic option in ophthalmology and neurology and could give new insights into visual phototransduction in humans.

  17. Physiological Function and Transplantation of Scaffold-Free and Vascularized Human Cardiac Muscle Tissue

    National Research Council Canada - National Science Library

    K. R. Stevens; K. L. Kreutziger; S. K. Dupras; F. S. Korte; M. Regnier; V. Muskheli; M. B. Nourse; K. Bendixen; H. Reinecke; C. E. Murry; William A. Catterall

    2009-01-01

    Success of human myocardial tissue engineering for cardiac repair has been limited by adverse effects of scaffold materials, necrosis at the tissue core, and poor survival after transplantation due to ischemie injury...

  18. Physiological Adaptation of the Bacterium Lactococcus lactis in Response to the Production of Human CFTR

    NARCIS (Netherlands)

    Steen, Anton; Wiederhold, Elena; Gandhi, Tejas; Breitling, Rainer; Slotboom, Dirk Jan

    2011-01-01

    Biochemical and biophysical characterization of CFTR (the cystic fibrosis transmembrane conductance regulator) is thwarted by difficulties to obtain sufficient quantities of correctly folded and functional protein. Here we have produced human CFTR in the prokaryotic expression host Lactococcus lacti

  19. Physiological level production of antigen-specific human immunoglobulin in cloned transchromosomic cattle.

    Science.gov (United States)

    Sano, Akiko; Matsushita, Hiroaki; Wu, Hua; Jiao, Jin-An; Kasinathan, Poothappillai; Sullivan, Eddie J; Wang, Zhongde; Kuroiwa, Yoshimi

    2013-01-01

    Therapeutic human polyclonal antibodies (hpAbs) derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH) and kappa-chain (hIGK) germline loci (named as κHAC) are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO). However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM) and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ) in the pre-B cell receptor (pre-BCR) complex, we partially replaced (bovinized) the hIgM constant domain with the counterpart of bovine IgM (bIgM) that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO), the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype) in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG) can be produced from such Tc cattle.

  20. Physiological level production of antigen-specific human immunoglobulin in cloned transchromosomic cattle.

    Directory of Open Access Journals (Sweden)

    Akiko Sano

    Full Text Available Therapeutic human polyclonal antibodies (hpAbs derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc cattle carrying a human artificial chromosome (HAC comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH and kappa-chain (hIGK germline loci (named as κHAC are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO. However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ in the pre-B cell receptor (pre-BCR complex, we partially replaced (bovinized the hIgM constant domain with the counterpart of bovine IgM (bIgM that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO, the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG can be produced from such Tc cattle.

  1. Physiological Reactivity to Psychological Stress in Human Pregnancy: Current Knowledge and Future Directions

    Science.gov (United States)

    Christian, Lisa M.

    2012-01-01

    Cardiovascular and neuroendocrine reactivity to acute stress are important predictors of health outcomes in non-pregnant populations. Greater magnitude and duration of physiological responses have been associated with increased risk of hypertensive disorders and diabetes, greater susceptibility to infectious illnesses, suppression of cell-mediated immunity as well as risk for depression and anxiety disorders. Stress reactivity during pregnancy has unique implications for maternal health, birth outcomes, and fetal development. However, as compared to the larger literature, our understanding of the predictors and consequences of exaggerated stress reactivity in pregnancy is limited. This paper reviews the current state of this literature with an emphasis on gaps in knowledge and future directions. PMID:22800930

  2. Physiological, biochemical, anthropometric and biomechanical influences on exercise economy in humans

    DEFF Research Database (Denmark)

    Lundby, Carsten; Montero, David; Gehrig, Saskia

    2017-01-01

    ) or protein content (UCP3 and MFN2 expression) explained variation in cycling and running EE among subjects. In contrast, biomechanical variables related to vertical displacement correlated well with running EE, but were not significant when taking body weight into account. Thus, running EE and body weight......Inter-individual variation in running and cycling exercise economy (EE) remains unexplained although studied for more than a century. This study is the first to comprehensively evaluate the importance of biochemical, structural, physiological, anthropometric, and biomechanical influences on running...... and cycling EE within a single study. In 22 healthy males (VO2 max range 45.5 to 72.1 ml.min(-1) .kg(-1) ) no factor related to skeletal muscle structure (% slow twitch fibre content, number of capillaries per fibre), mitochondrial properties (volume density, oxidative capacity, or mitochondrial efficiency...

  3. Sex differences in self-reported and physiological response to oral cocaine and placebo in humans.

    Science.gov (United States)

    Singha, A K; McCance-Katz, E F; Petrakis, I; Kosten, T R; Oliveto, A

    2000-11-01

    Self-report and physiological data from 27 male and 8 female cocaine-abusing volunteers exposed to cocaine (80 mg/70 kg p.o.) and placebo were examined for sex differences in their responses. Females reported significantly greater baseline ratings on the Pentobarbital-Chlorpromazine-Alcohol Group (PCAG) (sedation) and Lysergic Acid Diethylamide (LSD) (dysphoria) subscales of the Addiction Research Center Inventory-Short Form (ARCI) relative to males. In addition, females reported significantly greater ratings on the Visual Analogs Scales (VAS) Bad Drug Effects and Anxious/Nervous scales relative to males, regardless of drug. Cocaine produced greater increase in systolic blood pressure in males following cocaine, whereas females showed greater increases following placebo. These results suggest that a placebo control is necessary to determine sex differences in response to an active drug.

  4. Outdoor thermal physiology along human pathways: a study using a wearable measurement system

    Science.gov (United States)

    Nakayoshi, Makoto; Kanda, Manabu; Shi, Rui; de Dear, Richard

    2015-05-01

    An outdoor summer study on thermal physiology along subjects' pathways was conducted in a Japanese city using a unique wearable measurement system that measures all the relevant thermal variables: ambient temperature, humidity, wind speed ( U) and short/long-wave radiation ( S and L), along with some physio-psychological parameters: skin temperature ( T skin), pulse rate, subjective thermal sensation and state of body motion. U, S and L were measured using a globe anemo-radiometer adapted use with pedestrian subjects. The subjects were 26 healthy Japanese adults (14 males, 12 females) ranging from 23 to 74 years in age. Each subject wore a set of instruments that recorded individual microclimate and physiological responses along a designated pedestrian route that traversed various urban textures. The subjects experienced varying thermal environments that could not be represented by fixed-point routine observational data. S fluctuated significantly reflecting the mixture of sunlit/shade distributions within complex urban morphology. U was generally low within urban canyons due to drag by urban obstacles such as buildings but the subjects' movements enhanced convective heat exchanges with the atmosphere, leading to a drop in T skin. The amount of sweating increased as standard effective temperature (SET*) increased. A clear dependence of sweating on gender and body size was found; males sweated more than females; overweight subjects sweated more than standard/underweight subjects. T skin had a linear relationship with SET* and a similarly clear dependence on gender and body size differences. T skin of the higher-sweating groups was lower than that of the lower-sweating groups, reflecting differences in evaporative cooling by perspiration.

  5. Human factors approach to evaluate the user interface of physiologic monitoring.

    Science.gov (United States)

    Fidler, Richard; Bond, Raymond; Finlay, Dewar; Guldenring, Daniel; Gallagher, Anthony; Pelter, Michele; Drew, Barbara; Hu, Xiao

    2015-01-01

    As technology infiltrates more of our personal and professional lives, user expectations for intuitive design have driven many consumer products, while medical equipment continues to have high training requirements. Not much is known about the usability and user experience associated with hospital monitoring equipment. This pilot project aimed to better understand and describe the user interface interaction and user experience with physiologic monitoring technology. This was a prospective, descriptive, mixed-methods quality improvement project to analyze perceptions and task analyses of physiologic monitors. Following a survey of practice patterns and perceived abilities to accomplish key tasks, 10 voluntary experienced physician and nurse subjects were asked to perform a series of tasks in 7 domains of monitor operations on GE Monitoring equipment in a single institution. For each task analysis, data were collected on time to complete the task, the number of button pushes or clicks required to accomplish the task, economy of motion, and observed errors. Although 60% of the participants reported incorporating monitoring data into patient care, 80% of participants preferred to receive monitoring data at the point of care (bedside). Average perceived central station usability is 5.3 out of 10 (ten is easiest). High variability exists in monitoring station interaction performance among those participating in this project. Alarms were almost universally silenced without cognitive recognition of the alarm state. Education related to monitoring operations appeared largely absent in this sample. Most users perceived the interface to not be intuitive, complaining of multiple layers and steps for data retrieval. These clinicians report real-time monitoring helpful for abrupt changes in condition like arrhythmias; however, reviewing alarms is not prioritized as valuable due to frequent false alarms. Participants requested exporting monitoring data to electronic medical

  6. Modulation of extracellular matrix genes reflects the magnitude of physiological adaptation to aerobic exercise training in humans

    Directory of Open Access Journals (Sweden)

    Greenhaff Paul L

    2005-09-01

    these ECM genes may be critical for physiological adaptation to exercise in humans. In addition, we show that, without careful demonstration of physiological adaptation, conclusions derived from gene expression profiling of human skeletal muscle following exercise may be of limited value. We propose that future studies should (a investigate the mechanisms that underlie the apparent link between physiological adaptation and gene expression and (b use the genes profiled in this paper as candidates for population genetic studies.

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

    Science.gov (United States)

    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

  8. A primary human macrophage-enteroid co-culture model to investigate mucosal gut physiology and host-pathogen interactions

    Science.gov (United States)

    Noel, Gaelle; Baetz, Nicholas W.; Staab, Janet F.; Donowitz, Mark; Kovbasnjuk, Olga; Pasetti, Marcela F.; Zachos, Nicholas C.

    2017-01-01

    Integration of the intestinal epithelium and the mucosal immune system is critical for gut homeostasis. The intestinal epithelium is a functional barrier that secludes luminal content, senses changes in the gut microenvironment, and releases immune regulators that signal underlying immune cells. However, interactions between epithelial and innate immune cells to maintain barrier integrity and prevent infection are complex and poorly understood. We developed and characterized a primary human macrophage-enteroid co-culture model for in-depth studies of epithelial and macrophage interactions. Human intestinal stem cell-derived enteroid monolayers co-cultured with human monocyte-derived macrophages were used to evaluate barrier function, cytokine secretion, and protein expression under basal conditions and following bacterial infection. Macrophages enhanced barrier function and maturity of enteroid monolayers as indicated by increased transepithelial electrical resistance and cell height. Communication between the epithelium and macrophages was demonstrated through morphological changes and cytokine production. Intraepithelial macrophage projections, efficient phagocytosis, and stabilized enteroid barrier function revealed a coordinated response to enterotoxigenic and enteropathogenic E. coli infections. In summary, we have established the first primary human macrophage-enteroid co-culture system, defined conditions that allow for a practical and reproducible culture model, and demonstrated its suitability to study gut physiology and host responses to enteric pathogens. PMID:28345602

  9. Physiologically based kinetic models for the alkenylbenzene elemicin in rat and human and possible implications for risk assessment.

    Science.gov (United States)

    van den Berg, Suzanne J P L; Punt, Ans; Soffers, Ans E M F; Vervoort, Jacques; Ngeleja, Stephen; Spenkelink, Bert; Rietjens, Ivonne M C M

    2012-11-19

    The present study describes physiologically based kinetic (PBK) models for the alkenylbenzene elemicin (3,4,5-trimethoxyallylbenzene) in rat and human, based on the PBK models previously developed for the structurally related alkenylbenzenes estragole, methyleugenol, and safrole. Using the newly developed models, the level of metabolic activation of elemicin in rat and human was predicted to obtain insight in species differences in the bioactivation of elemicin and read across to the other methoxy allylbenzenes, estragole and methyleugenol. Results reveal that the differences between rat and human in the formation of the proximate carcinogenic metabolite 1'-hydroxyelemicin and the ultimate carcinogenic metabolite 1'-sulfoxyelemicin are limited (rat and human liver. The insights thus obtained were used to perform a risk assessment for elemicin using the margin of exposure (MOE) approach and read across to the other methoxy allylbenzene derivatives for which in vivo animal tumor data are available. This reveals that elemicin poses a lower priority for risk management as compared to its structurally related analogues estragole and methyleugenol. Altogether, the results obtained indicate that PBK modeling provides an important insight in the occurrence of species differences in the metabolic activation of elemicin. Moreover, they provide an example of how PBK modeling can facilitate a read across in risk assessment from compounds for which in vivo toxicity studies are available to a compound for which only limited toxicity data have been described, thus contributing to the development of alternatives for animal testing.

  10. Accelerated generation of human induced pluripotent stem cells with retroviral transduction and chemical inhibitors under physiological hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, Hidenori [Department of Bioartificial Organs, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507 (Japan); Hashimoto, Yoshiya [Department of Biomaterials, Osaka Dental University, 8-1, Hanazonocho, Kuzuha, Hirakatashi, Osaka 573-1121 (Japan); Nakada, Akira; Shigeno, Keiji [Department of Bioartificial Organs, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507 (Japan); Nakamura, Tatsuo, E-mail: nakamura@frontier.kyoto-u.ac.jp [Department of Bioartificial Organs, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507 (Japan)

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Very rapid generation of human iPS cells under optimized conditions. Black-Right-Pointing-Pointer Five chemical inhibitors under hypoxia boosted reprogramming. Black-Right-Pointing-Pointer We performed genome-wide DNA methylation analysis. -- Abstract: Induced pluripotent stem (iPS) cells are generated from somatic cells by the forced expression of a defined set of pluripotency-associated transcription factors. Human iPS cells can be propagated indefinitely, while maintaining the capacity to differentiate into all cell types in the body except for extra-embryonic tissues. This technology not only represents a new way to use individual-specific stem cells for regenerative medicine but also constitutes a novel method to obtain large amounts of disease-specific cells for biomedical research. Despite their great potential, the long reprogramming process (up to 1 month) remains one of the most significant challenges facing standard virus-mediated methodology. In this study, we report the accelerated generation of human iPS cells from adipose-derived stem (ADS) cells, using a new combination of chemical inhibitors under a setting of physiological hypoxia in conjunction with retroviral transduction of Oct4, Sox2, Klf4, and L-Myc. Under optimized conditions, we observed human embryonic stem (ES)-like cells as early as 6 days after the initial retroviral transduction. This was followed by the emergence of fully reprogrammed cells bearing Tra-1-81-positive and DsRed transgene-silencing properties on day 10. The resulting cell lines resembled human ES cells in many respects including proliferation rate, morphology, pluripotency-associated markers, global gene expression patterns, genome-wide DNA methylation states, and the ability to differentiate into all three of the germ layers, both in vitro and in vivo. Our method, when combined with chemical inhibitors under conditions of physiological hypoxia, offers a powerful tool for rapidly

  11. Report: NIA Workshop on Measures of Physiologic Resiliencies in Human Aging.

    Science.gov (United States)

    Hadley, Evan C; Kuchel, George A; Newman, Anne B

    2017-07-01

    Resilience, the ability to resist or recover from adverse effects of a stressor, is of widespread interest in social, psychologic, biologic, and medical research and particularly salient as the capacity to respond to stressors becomes diminished with aging. To date, research on human resilience responses to and factors influencing these responses has been limited. The National Institute on Aging convened a workshop in August 2015 on needs for research to improve measures to predict and assess resilience in human aging. Effects of aging-related factors in impairing homeostatic responses were developed from examples illustrating multiple determinants of clinical resilience outcomes. Research directions were identified by workshop participants. Research needs identified included expanded uses of clinical data and specimens in predicting or assessing resilience, and contributions from epidemiological studies in identifying long-term predictors. Better measures, including simulation tests, are needed to assess resilience and its determinants. Mechanistic studies should include exploration of influences of biologic aging processes on human resiliencies. Important resource and infrastructure needs include consensus phenotype definitions of specific resiliencies, capacity to link epidemiological and clinical resilience data, sensor technology to capture responses to stressors, better laboratory animal models of human resiliencies, and new analytic methods to understand the effects of multiple determinants of stress responses. Extending the focus of care and research to improving the capacity to respond to stressors could benefit older adults in promoting a healthier life span.

  12. Regulation of lipid deposition in farm animals: Parallels between agriculture and human physiology.

    Science.gov (United States)

    Bergen, Werner G; Brandebourg, Terry D

    2016-06-01

    For many years, clinically oriented scientists and animal scientists have focused on lipid metabolism and fat deposition in various fat depots. While dealing with a common biology across species, the goals of biomedical and food animals lipid metabolism research differ in emphasis. In humans, mechanisms and regulation of fat synthesis, accumulation of fat in regional fat depots, lipid metabolism and dysmetabolism in adipose, liver and cardiac tissues have been investigated. Further, energy balance and weight control have also been extensively explored in humans. Finally, obesity and associated maladies including high cholesterol and atherosclerosis, cardiovascular disease, insulin resistance, hypertension, metabolic syndrome and health outcomes have been widely studied. In food animals, the emphasis has been on regulation of fatty acid synthesis and lipid deposition in fat depots and deposition of intramuscular fat. For humans, understanding the regulation of energy balance and body weight and of prevention or treatment of obesity and associated maladies have been important clinical outcomes. In production of food animals lowering fat content in muscle foods while enhancing intramuscular fat (marbling) have been major targets. In this review, we summarize how our laboratories have addressed the goal of providing lean but yet tasty and juicy muscle food products to consumers. In addition, we here describe efforts in the development of a new porcine model to study regulation of fat metabolism and obesity. Commonalities and differences in regulation of lipid metabolism between humans, rodents and food animals are emphasized throughout this review.

  13. Microbial Eco-Physiology of the human intestinal tract: a flow cytometric approach

    NARCIS (Netherlands)

    Amor, Ben K.

    2004-01-01

    This thesis describes a multifaceted approach to further enhance our view of the complex human intestinal microbial ecosystem. This approach combines me advantages of flow cyrometry (FCM), a single cell and high-throughput technology, and molecular techniques that have proven themselves to be invalu

  14. A brief review of the recent evolution of the human mouth in physiological and nutritional contexts.

    Science.gov (United States)

    Lucas, Peter W; Ang, Kai Yang; Sui, Zhongquan; Agrawal, Kalpana R; Prinz, Jonathan F; Dominy, Nathaniel J

    2006-08-30

    One of the defining characteristics of humans, one that could also explain our species' success, is probably our ability to cook food. A brief review of the literature suggests several adaptations of the mouth can be interpreted to support this. All probably enhance the efficiency of the physical treatment of food in the mouth.

  15. Microbial Eco-Physiology of the human intestinal tract: a flow cytometric approach

    NARCIS (Netherlands)

    Amor, Ben K.

    2004-01-01

    This thesis describes a multifaceted approach to further enhance our view of the complex human intestinal microbial ecosystem. This approach combines me advantages of flow cyrometry (FCM), a single cell and high-throughput technology, and molecular techniques that have proven themselves to be

  16. Microbial Eco-Physiology of the human intestinal tract: a flow cytometric approach

    NARCIS (Netherlands)

    Amor, Ben K.

    2004-01-01

    This thesis describes a multifaceted approach to further enhance our view of the complex human intestinal microbial ecosystem. This approach combines me advantages of flow cyrometry (FCM), a single cell and high-throughput technology, and molecular techniques that have proven themselves to be invalu

  17. Biomechanics of red blood cells in human spleen and consequences for physiology and disease

    Science.gov (United States)

    Pivkin, Igor V.; Peng, Zhangli; Karniadakis, George E.; Buffet, Pierre A.; Dao, Ming; Suresh, Subra

    2016-01-01

    Red blood cells (RBCs) can be cleared from circulation when alterations in their size, shape, and deformability are detected. This function is modulated by the spleen-specific structure of the interendothelial slit (IES). Here, we present a unique physiological framework for development of prognostic markers in RBC diseases by quantifying biophysical limits for RBCs to pass through the IES, using computational simulations based on dissipative particle dynamics. The results show that the spleen selects RBCs for continued circulation based on their geometry, consistent with prior in vivo observations. A companion analysis provides critical bounds relating surface area and volume for healthy RBCs beyond which the RBCs fail the “physical fitness test” to pass through the IES, supporting independent experiments. Our results suggest that the spleen plays an important role in determining distributions of size and shape of healthy RBCs. Because mechanical retention of infected RBC impacts malaria pathogenesis, we studied key biophysical parameters for RBCs infected with Plasmodium falciparum as they cross the IES. In agreement with experimental results, surface area loss of an infected RBC is found to be a more important determinant of splenic retention than its membrane stiffness. The simulations provide insights into the effects of pressure gradient across the IES on RBC retention. By providing quantitative biophysical limits for RBCs to pass through the IES, the narrowest circulatory bottleneck in the spleen, our results offer a broad approach for developing quantitative markers for diseases such as hereditary spherocytosis, thalassemia, and malaria. PMID:27354532

  18. Differentiation induced by physiological and pharmacological stimuli leads to increased antigenicity of human neuroblastoma cells

    Institute of Scientific and Technical Information of China (English)

    Lena-Maria Carlson; Sven P(a)hlman; Anna De Geer; Per Kogner; Jelena Levitskaya

    2008-01-01

    Sympathetic neuronal differentiation is associated with favorable prognosis of neuroblastoma (NB), the most common extra-cranial solid tumor of early childhood. Differentiation agents have proved useful in clinical protocols of NB treatment, but using them as a sole treatment is not sufficient to induce tumor elimination in patients. Therefore, complementary approaches, such as immunotherapy, are warranted. Here we demonstrate that differentiation of NB cell lines and ex vivo isolated tumor cells in response to physiological or pharmacological stimuli is associated with acquisition of increased antigenicity. This manifests as increased expression of surface major histocompatibility class I complexes and ICAM-1 molecules and translates into increased sensitivity of NB cells to lysis by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. The latter is paralleled by enhanced ability of differentiated cells to form immune conjugates and bind increased amounts of granzyme B to the cell surface. We demonstrate, for the first time, that, regardless of the stimulus applied, the differentiation state in NBs is associated with increased tumor antigenicity that enables more efficient elimination of tumor cells by cytotoxic lymphocytes and paves the way for combined application of differentiation-inducing agents and immunotherapy as an auxiliary approach in NB patients.

  19. Human Serum Albumin Increases the Stability of Green Tea Catechins in Aqueous Physiological Conditions.

    Directory of Open Access Journals (Sweden)

    Angelo Zinellu

    Full Text Available Epicatechin (EC, epigallocatechin (EGC, epicatechingallate (ECG and epigallocatechingallate (EGCG are antioxidants present in the green tea, a widely used beverage whose health benefits are largely recognized. Nevertheless, major physicochemical limitations, such as the high instability of catechins, pose important questions concerning their potential pharmacological use. Recent studies indicate that binding of catechins with plasmatic proteins may modulate their plasma concentration, tissue delivery and biological activity. After 5 minutes of incubation with HSA both ECG and EGCG were fully bound to HSA, while after 48h incubation only 41% of EC and 70% of EGC resulted linked. HSA had a strong stabilizing effect on all catechins, which could be found in solution between 29 and 85% even after 48h of incubation. In the absence of HSA, EGC and EGCG disappeared in less than 24h, while ECG and EC were found after 48h at 5 and 50%, respectively. The stabilizing effect of HSA toward EGCG, obtained in aqueous physiological conditions, resulted stronger in comparison to cysteine and HCl, previously reported to stabilize this polyphenol. Because of the multitude of contradictory data concerning in vivo and in vitro antioxidant-based experimentations, we believe our work may shed some light on this debated field of research.

  20. Human Serum Albumin Increases the Stability of Green Tea Catechins in Aqueous Physiological Conditions.

    Science.gov (United States)

    Zinellu, Angelo; Sotgia, Salvatore; Scanu, Bastianina; Forteschi, Mauro; Giordo, Roberta; Cossu, Annalisa; Posadino, Anna Maria; Carru, Ciriaco; Pintus, Gianfranco

    2015-01-01

    Epicatechin (EC), epigallocatechin (EGC), epicatechingallate (ECG) and epigallocatechingallate (EGCG) are antioxidants present in the green tea, a widely used beverage whose health benefits are largely recognized. Nevertheless, major physicochemical limitations, such as the high instability of catechins, pose important questions concerning their potential pharmacological use. Recent studies indicate that binding of catechins with plasmatic proteins may modulate their plasma concentration, tissue delivery and biological activity. After 5 minutes of incubation with HSA both ECG and EGCG were fully bound to HSA, while after 48h incubation only 41% of EC and 70% of EGC resulted linked. HSA had a strong stabilizing effect on all catechins, which could be found in solution between 29 and 85% even after 48h of incubation. In the absence of HSA, EGC and EGCG disappeared in less than 24h, while ECG and EC were found after 48h at 5 and 50%, respectively. The stabilizing effect of HSA toward EGCG, obtained in aqueous physiological conditions, resulted stronger in comparison to cysteine and HCl, previously reported to stabilize this polyphenol. Because of the multitude of contradictory data concerning in vivo and in vitro antioxidant-based experimentations, we believe our work may shed some light on this debated field of research.

  1. The resonant component of human physiological hand tremor is altered by slow voluntary movements.

    Science.gov (United States)

    Lakie, Martin; Vernooij, Carlijn A; Osborne, Timothy M; Reynolds, Raymond F

    2012-05-15

    Limb resonance imparts a characteristic spectrum to hand tremor. Movement will alter the resonance. We have examined the consequences of this change. Rectified forearm extensor muscle EMG and physiological hand tremor were recorded. In postural conditions the EMG spectrum is relatively flat whereas the acceleration spectrum is sharply peaked. Consequently, the gain between EMG and acceleration is maximal at the frequency where the tremor is largest (∼8 Hz). The shape of the gain curve implies mechanical resonance. Substantial alterations in posture do not significantly change the characteristics of the tremor or the shape or size of the gain curve. By contrast, slow or moderately paced voluntary wrist flexion–extension movements dramatically increase the hand tremor size and lower its peak frequency. These changes in size and frequency of the tremor cannot be attributed to changes in the EMG. Instead they reflect a very large change in the size and shape of the gain curve relating EMG to acceleration. The gain becomes larger and the peak moves to a lower frequency (∼6 Hz). We suggest that a movement-related (thixotropic) alteration in resonant properties of the wrist provides a simple explanation for these changes. The mechanism is illustrated by a model. Our new findings confirm that resonance plays a major role in wrist tremor. We also demonstrate that muscles operate very differently under postural and dynamic conditions. The different coupling between EMG and movement in posture and when moving must pose a considerable challenge for neural predictive control of skeletal muscles.

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

    Science.gov (United States)

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

    2013-01-01

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

  3. A study of student perceptions of learning transfer from a human anatomy and physiology course in an allied health program

    Science.gov (United States)

    Harrell, Leigh S.

    The purpose of this study was two-fold. First the study was designed to determine student perceptions regarding the perceived degree of original learning from a human anatomy and physiology course, and the student perception of the use of the knowledge in an allied health program. Second, the intention of the study was to establish student beliefs on the characteristics of the transfer of learning including those factors which enhance learning transfer and those that serve as barriers to learning transfer. The study participants were those students enrolled in any allied health program at a community college in a Midwest state, including: nursing, radiology, surgical technology, health information technology, and paramedic. Both quantitative and qualitative data were collected and analyzed from the responses to the survey. A sub-group of participants were chosen to participate in semi-structured formal interviews. From the interviews, additional qualitative data were gathered. The data collected through the study demonstrated student perception of successful transfer experiences. The students in the study were able to provide specific examples of learning transfer experienced from the human anatomy and physiology course in their allied health program. Findings also suggested students who earned higher grades in the human anatomy and physiology course perceived greater understanding and greater use of the course's learning objectives in their allied health program. The study found the students believed the following learning activities enhances the transfer of learning: (1) Providing application of the information or skills being learned during the instruction of the course content enhances the transfer of learning. (2) Providing resource materials and activities which allow the students to practice the content being taught facilitates the transfer of learning. The students made the following recommendations to remove barriers to the transfer of learning: (1

  4. Verification of impact of morning showering and mist sauna bathing on human physiological functions and work efficiency during the day

    Science.gov (United States)

    Lee, Soomin; Fujimura, Hiroko; Shimomura, Yoshihiro; Katsuura, Tetsuo

    2015-09-01

    Recently, a growing number in Japan are switching to taking baths in the morning (morning bathing). However, the effects of the morning bathing on human physiological functions and work efficiency have not yet been revealed. Then, we hypothesized that the effect of morning bathing on physiological functions would be different from those of night bathing. In this study, we measured the physiological functions and work efficiency during the day following the morning bathing (7:10-7:20) including showering, mist sauna bathing, and no bathing as a control. Ten male healthy young adults participated in this study as the subjects. We evaluated the rectal temperature (Tre), skin temperature (Tsk), heart rate (HR), heart rate variability (HRV), blood pressure (BP), the relative power density of the alpha wave (α-wave ratio) of electroencephalogram, alpha attenuation coefficient (AAC), and the error rate of the task performance. As a result, we found that the HR after the mist sauna bathing was significantly lower than those after no bathing rest 3 (11:00). Furthermore, we verified that the α-wave ratio of the Pz after the mist sauna bathing was significantly lower than those after no bathing during the task 6 (15:00). On the other hand, the α-wave ratio of the Pz after the mist sauna bathing was significantly higher than those after showering during the rest 3 (11:00). Tsk after the mist sauna bathing was higher than those after the showering at 9:00 and 15:00. In addition, the error rate of the task performance after the mist sauna bathing was lower than those after no bathing and showering at 14:00. This study concludes that a morning mist sauna is safe and maintains both skin temperature compared to other bathing methods. Moreover, it is presumed that the morning mist sauna bathing improves work efficiency comparing other bathing methods during the task period of the day following the morning bathing.

  5. Interteaching within a human physiology course: a comparison of first- and second-year students' learning skills and perceptions.

    Science.gov (United States)

    Byrne, Bruce; Guy, Richard

    2016-09-01

    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 completed a previous physiology course. Active learning, where students were required to engage with course material in a self-directed manner before tutorials and to identify areas of difficulty and discuss these within tutorial sessions, was a central component of the study. The second-year students adapted quickly to the novel approach, as indicated by stable levels of perceived difficulty and understanding. In contrast, the first-year students demonstrated a decrease in perceived difficulty and an increase in perceived individual understanding throughout the study. These results notwithstanding, there was a consistent low level of interest for both years but no significant difference between the first- and second-year individual and group learning skills by the end of the study, as measured by their performance in the tutorials. Overall, the results were encouraging, with both years achieving a reasonably high learning skill level (average: ∼70%) within the interteaching environment. The improvement of active learning shown by the first-year students may have compensated, to some extent, for the prior learning advantage of the second-year students, since both groups achieved similar marks in the written components of final exams for both interteaching modules.

  6. The Role of Gap Junction Channels During Physiologic and Pathologic Conditions of the Human Central Nervous System

    Science.gov (United States)

    Basilio, Daniel; Sáez, Juan C.; Orellana, Juan A.; Raine, Cedric S.; Bukauskas, Feliksas; Bennett, Michael V. L.; Berman, Joan W.

    2013-01-01

    Gap junctions (GJs) are expressed in most cell types of the nervous system, including neuronal stem cells, neurons, astrocytes, oligodendrocytes, cells of the blood brain barrier (endothelial cells and astrocytes) and under inflammatory conditions in microglia/macrophages. GJs connect cells by the docking of two hemichannels, one from each cell with each hemichannel being formed by 6 proteins named connexins (Cx). Unapposed hemichannels (uHC) also can be open on the surface of the cells allowing the release of different intracellular factors to the extracellular space. GJs provide a mechanism of cell-to-cell communication between adjacent cells that enables the direct exchange of intracellular messengers, such as calcium, nucleotides, IP3, and diverse metabolites, as well as electrical signals that ultimately coordinate tissue homeostasis, proliferation, differentiation, metabolism, cell survival and death. Despite their essential functions in physiological conditions, relatively little is known about the role of GJs and uHC in human diseases, especially within the nervous system. The focus of this review is to summarize recent findings related to the role of GJs and uHC in physiologic and pathologic conditions of the central nervous system. PMID:22438035

  7. The role of gap junction channels during physiologic and pathologic conditions of the human central nervous system.

    Science.gov (United States)

    Eugenin, Eliseo A; Basilio, Daniel; Sáez, Juan C; Orellana, Juan A; Raine, Cedric S; Bukauskas, Feliksas; Bennett, Michael V L; Berman, Joan W

    2012-09-01

    Gap junctions (GJs) are expressed in most cell types of the nervous system, including neuronal stem cells, neurons, astrocytes, oligodendrocytes, cells of the blood brain barrier (endothelial cells and astrocytes) and under inflammatory conditions in microglia/macrophages. GJs connect cells by the docking of two hemichannels, one from each cell with each hemichannel being formed by 6 proteins named connexins (Cx). Unapposed hemichannels (uHC) also can be open on the surface of the cells allowing the release of different intracellular factors to the extracellular space. GJs provide a mechanism of cell-to-cell communication between adjacent cells that enables the direct exchange of intracellular messengers, such as calcium, nucleotides, IP(3), and diverse metabolites, as well as electrical signals that ultimately coordinate tissue homeostasis, proliferation, differentiation, metabolism, cell survival and death. Despite their essential functions in physiological conditions, relatively little is known about the role of GJs and uHC in human diseases, especially within the nervous system. The focus of this review is to summarize recent findings related to the role of GJs and uHC in physiologic and pathologic conditions of the central nervous system.

  8. Long-term neural and physiological phenotyping of a single human.

    Science.gov (United States)

    Poldrack, Russell A; Laumann, Timothy O; Koyejo, Oluwasanmi; Gregory, Brenda; Hover, Ashleigh; Chen, Mei-Yen; Gorgolewski, Krzysztof J; Luci, Jeffrey; Joo, Sung Jun; Boyd, Ryan L; Hunicke-Smith, Scott; Simpson, Zack Booth; Caven, Thomas; Sochat, Vanessa; Shine, James M; Gordon, Evan; Snyder, Abraham Z; Adeyemo, Babatunde; Petersen, Steven E; Glahn, David C; Reese Mckay, D; Curran, Joanne E; Göring, Harald H H; Carless, Melanie A; Blangero, John; Dougherty, Robert; Leemans, Alexander; Handwerker, Daniel A; Frick, Laurie; Marcotte, Edward M; Mumford, Jeanette A

    2015-12-09

    Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of brain function over this timescale in healthy individuals are unknown. Here, as a proof of concept to address this question, we present the MyConnectome project. An intensive phenome-wide assessment of a single human was performed over a period of 18 months, including functional and structural brain connectivity using magnetic resonance imaging, psychological function and physical health, gene expression and metabolomics. A reproducible analysis workflow is provided, along with open access to the data and an online browser for results. We demonstrate dynamic changes in brain connectivity over the timescales of days to months, and relations between brain connectivity, gene expression and metabolites. This resource can serve as a testbed to study the joint dynamics of human brain and metabolic function over time, an approach that is critical for the development of precision medicine strategies for brain disorders.

  9. Differential role of Hedgehog signaling in human pancreatic (patho-) physiology: An up to date review

    OpenAIRE

    Klieser, Eckhard; SWIERCZYNSKI, STEFAN; Mayr, Christian; Jäger, Tarkan; Schmidt, Johanna; Neureiter, Daniel; KIESSLICH, TOBIAS; Illig, Romana

    2016-01-01

    Since the discovery of the Hedgehog (Hh) pathway in drosophila melanogaster, our knowledge of the role of Hh in embryonic development, inflammation, and cancerogenesis in humans has dramatically increased over the last decades. This is the case especially concerning the pancreas, however, real therapeutic breakthroughs are missing until now. In general, Hh signaling is essential for pancreatic organogenesis, development, and tissue maturation. In the case of acute pancreatitis, Hh has a prote...

  10. Electron Pathways through Erythrocyte Plasma Membrane in Human Physiology and Pathology: Potential Redox Biomarker?

    Directory of Open Access Journals (Sweden)

    Elena Matteucci

    2007-01-01

    Full Text Available Erythrocytes are involved in the transport of oxygen and carbon dioxide in the body. Since pH is the influential factor in the Bohr-Haldane effect, pHi is actively maintained via secondary active transports Na+/H+ exchange and HC3 -/Cl- anion exchanger. Because of the redox properties of the iron, hemoglobin generates reactive oxygen species and thus, the human erythrocyte is constantly exposed to oxidative damage. Although the adult erythrocyte lacks protein synthesis and cannot restore damaged proteins, it is equipped with high activity of protective enzymes. Redox changes in the cell initiate various signalling pathways. Plasma membrane oxido-reductases (PMORs are transmembrane electron transport systems that have been found in the membranes of all cells and have been extensively characterized in the human erythrocyte. Erythrocyte PMORs transfer reducing equivalents from intracellular reductants to extracellular oxidants, thus their most important role seems to be to enable the cell respond to changes in intra- and extra-cellular redox environments.So far the activity of erythrocyte PMORs in disease states has not been systematically investigated. This review summarizes present knowledge on erythrocyte electron transfer activity in humans (health, type 1 diabetes, diabetic nephropathy, and chronic uremia and hypothesizes an integrated model of the functional organization of erythrocyte plasma membrane where electron pathways work in parallel with transport metabolons to maintain redox homeostasis.

  11. Electron Pathways through Erythrocyte Plasma Membrane in Human Physiology and Pathology: Potential Redox Biomarker?

    Science.gov (United States)

    Matteucci, Elena; Giampietro, Ottavio

    2007-09-17

    Erythrocytes are involved in the transport of oxygen and carbon dioxide in the body. Since pH is the influential factor in the Bohr-Haldane effect, pHi is actively maintained via secondary active transports Na(+)/H(+) exchange and HC(3) (-)/Cl(-) anion exchanger. Because of the redox properties of the iron, hemoglobin generates reactive oxygen species and thus, the human erythrocyte is constantly exposed to oxidative damage. Although the adult erythrocyte lacks protein synthesis and cannot restore damaged proteins, it is equipped with high activity of protective enzymes. Redox changes in the cell initiate various signalling pathways. Plasma membrane oxido-reductases (PMORs) are transmembrane electron transport systems that have been found in the membranes of all cells and have been extensively characterized in the human erythrocyte. Erythrocyte PMORs transfer reducing equivalents from intracellular reductants to extracellular oxidants, thus their most important role seems to be to enable the cell respond to changes in intra- and extra-cellular redox environments.So far the activity of erythrocyte PMORs in disease states has not been systematically investigated. This review summarizes present knowledge on erythrocyte electron transfer activity in humans (health, type 1 diabetes, diabetic nephropathy, and chronic uremia) and hypothesizes an integrated model of the functional organization of erythrocyte plasma membrane where electron pathways work in parallel with transport metabolons to maintain redox homeostasis.

  12. Design of wearable hybrid generator for harvesting heat energy from human body depending on physiological activity

    Science.gov (United States)

    Kim, Myoung-Soo; Kim, Min-Ki; Kim, Kyongtae; Kim, Yong-Jun

    2017-09-01

    We developed a prototype of a wearable hybrid generator (WHG) that is used for harvesting the heat energy of the human body. This WHG is constructed by integrating a thermoelectric generator (TEG) in a circular mesh polyester knit fabric, circular-shaped pyroelectric generator (PEG), and quick sweat-pickup/dry-fabric. The fabric packaging enables the TEG part of the WHG to generate energy steadily while maintaining a temperature difference in extreme temperature environments. Moreover, when the body sweats, the evaporation heat of the sweat leads to thermal fluctuations in the WHG. This phenomenon further leads to an increase in the output power of the WHG. These characteristics of the WHG make it possible to produce electrical energy steadily without reduction in the conversion efficiency, as both TEG and PEG use the same energy source of the human skin and the ambient temperature. Under a temperature difference of ˜6.5 °C and temperature change rate of ˜0.62 °C s-1, the output power and output power density of the WHG, respectively, are ˜4.5 nW and ˜1.5 μW m-2. Our hybrid approach will provide a framework to enhance the output power of the wearable generators that harvest heat energy from human body in various environments.

  13. Effects of blue pulsed light on human physiological functions and subjective evaluation

    Directory of Open Access Journals (Sweden)

    Katsuura Tetsuo

    2012-09-01

    Full Text Available Abstract Background It has been assumed that light with a higher irradiance of pulsed blue light has a much greater influence than that of light with a lower irradiance of steady blue light, although they have the same multiplication value of irradiance and duration. We examined the non-visual physiological effects of blue pulsed light, and determined whether it is sensed visually as being blue. Findings Seven young male volunteers participated in the study. We placed a circular screen (diameter 500 mm in front of the participants and irradiated it using blue and/or white light-emitting diodes (LEDs, and we used halogen lamps as a standard illuminant. We applied three steady light conditions of white LED (F0, blue LED + white LED (F10, and blue LED (F100, and a blue pulsed light condition of a 100-μs pulse width with a 10% duty ratio (P10. The irradiance of all four conditions at the participant's eye level was almost the same, at around 12 μW/cm2. We measured their pupil diameter, recorded electroencephalogram readings and Kwansei Gakuin Sleepiness Scale score, and collected subjective evaluations. The subjective bluish score under the F100 condition was significantly higher than those under other conditions. Even under the P10 condition with a 10% duty ratio of blue pulsed light and the F10 condition, the participant did not perceive the light as bluish. Pupillary light response under the P10 pulsed light condition was significantly greater than under the F10 condition, even though the two conditions had equal blue light components. Conclusions The pupil constricted under the blue pulsed light condition, indicating a non-visual effect of the lighting, even though the participants did not perceive the light as bluish.

  14. Ape conservation physiology: fecal glucocorticoid responses in wild Pongo pygmaeus morio following human visitation.

    Directory of Open Access Journals (Sweden)

    Michael P Muehlenbein

    , preliminary results in these wild habituated orangutans suggest that low levels of predictable disturbance can likely result in low physiological impact on these animals.

  15. Physical activity and exercise in the regulation of human adipose tissue physiology.

    Science.gov (United States)

    Thompson, Dylan; Karpe, Fredrik; Lafontan, Max; Frayn, Keith

    2012-01-01

    Physical activity and exercise are key components of energy expenditure and therefore of energy balance. Changes in energy balance alter fat mass. It is therefore reasonable to ask: What are the links between physical activity and adipose tissue function? There are many complexities. Physical activity is a multifaceted behavior of which exercise is just one component. Physical activity influences adipose tissue both acutely and in the longer term. A single bout of exercise stimulates adipose tissue blood flow and fat mobilization, resulting in delivery of fatty acids to skeletal muscles at a rate well-matched to metabolic requirements, except perhaps in vigorous intensity exercise. The stimuli include adrenergic and other circulating factors. There is a period following an exercise bout when fatty acids are directed away from adipose tissue to other tissues such as skeletal muscle, reducing dietary fat storage in adipose. With chronic exercise (training), there are changes in adipose tissue physiology, particularly an enhanced fat mobilization during acute exercise. It is difficult, however, to distinguish chronic "structural" changes from those associated with the last exercise bout. In addition, it is difficult to distinguish between the effects of training per se and negative energy balance. Epidemiological observations support the idea that physically active people have relatively low fat mass, and intervention studies tend to show that exercise training reduces fat mass. A much-discussed effect of exercise versus calorie restriction in preferentially reducing visceral fat is not borne out by meta-analyses. We conclude that, in addition to the regulation of fat mass, physical activity may contribute to metabolic health through beneficial dynamic changes within adipose tissue in response to each activity bout.

  16. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.

    Science.gov (United States)

    Miller, Walter L; Auchus, Richard J

    2011-02-01

    Steroidogenesis entails processes by which cholesterol is converted to biologically active steroid hormones. Whereas most endocrine texts discuss adrenal, ovarian, testicular, placental, and other steroidogenic processes in a gland-specific fashion, steroidogenesis is better understood as a single process that is repeated in each gland with cell-type-specific variations on a single theme. Thus, understanding steroidogenesis is rooted in an understanding of the biochemistry of the various steroidogenic enzymes and cofactors and the genes that encode them. The first and rate-limiting step in steroidogenesis is the conversion of cholesterol to pregnenolone by a single enzyme, P450scc (CYP11A1), but this enzymatically complex step is subject to multiple regulatory mechanisms, yielding finely tuned quantitative regulation. Qualitative regulation determining the type of steroid to be produced is mediated by many enzymes and cofactors. Steroidogenic enzymes fall into two groups: cytochrome P450 enzymes and hydroxysteroid dehydrogenases. A cytochrome P450 may be either type 1 (in mitochondria) or type 2 (in endoplasmic reticulum), and a hydroxysteroid dehydrogenase may belong to either the aldo-keto reductase or short-chain dehydrogenase/reductase families. The activities of these enzymes are modulated by posttranslational modifications and by cofactors, especially electron-donating redox partners. The elucidation of the precise roles of these various enzymes and cofactors has been greatly facilitated by identifying the genetic bases of rare disorders of steroidogenesis. Some enzymes not principally involved in steroidogenesis may also catalyze extraglandular steroidogenesis, modulating the phenotype expected to result from some mutations. Understanding steroidogenesis is of fundamental importance to understanding disorders of sexual differentiation, reproduction, fertility, hypertension, obesity, and physiological homeostasis.

  17. Ape conservation physiology: fecal glucocorticoid responses in wild Pongo pygmaeus morio following human visitation.

    Science.gov (United States)

    Muehlenbein, Michael P; Ancrenaz, Marc; Sakong, Rosman; Ambu, Laurentius; Prall, Sean; Fuller, Grace; Raghanti, Mary Ann

    2012-01-01

    in these wild habituated orangutans suggest that low levels of predictable disturbance can likely result in low physiological impact on these animals.

  18. Two distinct interneuron circuits in human motor cortex are linked to different subsets of physiological and behavioral plasticity.

    Science.gov (United States)

    Hamada, Masashi; Galea, Joseph M; Di Lazzaro, Vincenzo; Mazzone, Paolo; Ziemann, Ulf; Rothwell, John C

    2014-09-17

    How does a single brain region participate in multiple behaviors? Here we argue that two separate interneuron circuits in the primary motor cortex (M1) contribute differently to two varieties of physiological and behavioral plasticity. To test this in human brain noninvasively, we used transcranial magnetic stimulation (TMS) of M1 hand area to activate two independent sets of synaptic inputs to corticospinal neurons by changing the direction of current induced in the brain: posterior-to-anterior current (PA inputs) and anterior-to-posterior current (AP inputs). We demonstrate that excitability changes produced by repetitive activation of AP inputs depend on cerebellar activity and selectively alter model-based motor learning. In contrast, the changes observed with repetitive stimulation of PA inputs are independent of cerebellar activity and specifically modulate model-free motor learning. The findings are highly suggestive that separate circuits in M1 subserve different forms of motor learning.

  19. The Circulatory and Metabolic Responses to Hypoxia in Humans – With Special Reference to Adipose Tissue Physiology and Obesity

    Science.gov (United States)

    Heinonen, Ilkka H. A.; Boushel, Robert; Kalliokoski, Kari K.

    2016-01-01

    Adipose tissue metabolism and circulation play an important role in human health. It is well-known that adipose tissue mass is increased in response to excess caloric intake leading to obesity and further to local hypoxia and inflammatory signaling. Acute exercise increases blood supply to adipose tissue and mobilization of fat stores for energy. However, acute exercise during systemic hypoxia reduces subcutaneous blood flow in healthy young subjects, but the response in overweight or obese subjects remains to be investigated. Emerging evidence also indicates that exercise training during hypoxic exposure may provide additive benefits with respect to many traditional cardiovascular risk factors as compared to exercise performed in normoxia, but unfavorable effects of hypoxia have also been documented. These topics will be covered in this brief review dealing with hypoxia and adipose tissue physiology. PMID:27621722

  20. Human-derived physiological heat shock protein 27 complex protects brain after focal cerebral ischemia in mice.

    Directory of Open Access Journals (Sweden)

    Shinichiro Teramoto

    Full Text Available Although challenging, neuroprotective therapies for ischemic stroke remain an interesting strategy for countering ischemic injury and suppressing brain tissue damage. Among potential neuroprotective molecules, heat shock protein 27 (HSP27 is a strong cell death suppressor. To assess the neuroprotective effects of HSP27 in a mouse model of transient middle cerebral artery occlusion, we purified a "physiological" HSP27 (hHSP27 from normal human lymphocytes. hHSP27 differed from recombinant HSP27 in that it formed dimeric, tetrameric, and multimeric complexes, was phosphorylated, and contained small amounts of αβ-crystallin and HSP20. Mice received intravenous injections of hHSP27 following focal cerebral ischemia. Infarct volume, neurological deficit scores, physiological parameters, and immunohistochemical analyses were evaluated 24 h after reperfusion. Intravenous injections of hHSP27 1 h after reperfusion significantly reduced infarct size and improved neurological deficits. Injected hHSP27 was localized in neurons on the ischemic side of the brain. hHSP27 suppressed neuronal cell death resulting from cytochrome c-mediated caspase activation, oxidative stress, and inflammatory responses. Recombinant HSP27 (rHSP27, which was artificially expressed and purified from Escherichia coli, and dephosphorylated hHSP27 did not have brain protective effects, suggesting that the phosphorylation of hHSP27 may be important for neuroprotection after ischemic insults. The present study suggests that hHSP27 with posttranslational modifications provided neuroprotection against ischemia/reperfusion injury and that the protection was mediated through the inhibition of apoptosis, oxidative stress, and inflammation. Intravenously injected human HSP27 should be explored for the treatment of acute ischemic strokes.

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

    Energy Technology Data Exchange (ETDEWEB)

    Redding, Laurel E.; Sohn, Michael D.; McKone, Thomas E.; Wang, Shu-Li; Hsieh, Dennis P. H.; Yang, Raymond S. H.

    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 compare 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.

  2. An examination of the effects of various noise on physiological sensibility responses by using human EEG

    Energy Technology Data Exchange (ETDEWEB)

    Cho, W. H.; Lee, J. K.; Son, T. Y.; Hwang, S. H.; Choi, H. [Sungkyunkwan University, Suwon (Korea, Republic of); Lee, M. S. [Hyundai Motor Company, Hwaseong (Korea, Republic of)

    2013-12-15

    This study investigated human stress levels based on electroencephalogram (EEG) data and carried out a subjective evaluation analysis about noise. Visual information is very important for finding human's emotional state. And relatively more previous works have been done than those using auditory stimulus. Since there are fewer previous works, we thought that using auditory stimulus is good choice for our study. Twelve human subjects were exposed to classic piano, ocean wave, army alarm, ambulance, and mosquito noises. We used two groups of comfortable and uncomfortable noises are to see the difference between the definitely different two groups to confirm usefulness of using this setting of experiment. EEG data were collected during the experimental session. The subjects were tested in a soundproof chamber and asked to minimize blinking, head movement, and swallowing during the experiment. The total time of the noise experiment included the time of the relaxation phase, during which the subjects relaxed in silence for 10 minutes. The relaxation phase was followed by a 20 -second noise exposure. The alpha band activities of the subjects were significantly decreased for the ambulance and mosquito noises, as it compared to the classic piano and ocean wave noises. The alpha band activities of the subjects decreased by 12.8 ± 2.3% for the ocean wave noise, decreased by 32.0 ± 5.4% for the army alarm noise, decreased by 34.5 ± 6.7% for the ambulance noise and decreased by 58.3 ± 9.1% for the mosquito noise compared to that of classic piano. On the other hand, their beta band activities were significantly increased for the ambulance and mosquito noises as it compared to classic piano and ocean wave. The beta band activities of the subjects increased by 7.9 ± 1.7% for the ocean wave noise, increased by 20.6 ± 5.3% for the army alarm noise, increased by 48.0 ± 7.5% for the ambulance noise and increased by 61.9 ± 11.2% for the mosquito noise, as it is compared

  3. Sensory and Physiological Effects on Humans of Combined Exposures to Air Temperatures and Volatile Organic Compounds

    DEFF Research Database (Denmark)

    Mølhave, Lars; Liu, Zunyong; Jørgensen, Anne Hempel

    1993-01-01

    Ten healthy humans were exposed to combinations of volatile organic compounds (VOCs) and air temperature (0 mg/m3 and 10 mg/m3 of a mixture of 22 volatile organic compounds and 18, 22 and 26° C). Previously demonstrated effects of VOCs and thermal exposures were replicated. For the first time nasal...... cross-sectional areas and nasal volumes, as measured by acoustic rhinometry, were shown to decrease with decreasing temperature and increasing VOC exposure. Temperature and pollutant exposures affected air quality, the need for more ventilation, skin humidity on the forehead, sweating, acute sensory...

  4. Binaural beat technology in humans: a pilot study to assess neuropsychologic, physiologic, and electroencephalographic effects.

    Science.gov (United States)

    Wahbeh, Helané; Calabrese, Carlo; Zwickey, Heather; Zajdel, Dan

    2007-03-01

    When two auditory stimuli of different frequency are presented to each ear, binaural beats are perceived by the listener. The binaural beat frequency is equal to the difference between the frequencies applied to each ear. Our primary objective was to assess whether steady-state entrainment of electroencephalographic activity to the binaural beat occurs when exposed to a specific binaural beat frequency as has been hypothesized. Our secondary objective was to gather preliminary data on neuropsychologic and physiologic effects of binaural beat technology. A randomized, blinded, placebo-controlled crossover experiment in 4 healthy adult subjects. Subjects were randomized to experimental auditory stimulus of 30 minutes of binaural beat at 7 Hz (carrier frequencies: 133 Hz L; 140 Hz R) with an overlay of pink noise resembling the sound of rain on one session and control stimuli of the same overlay without the binaural beat carrier frequencies on the other session. Data were collected during two separate sessions 1 week apart. Neuropsychologic and blood pressure data were collected before and after the intervention; electroencephalographic data were collected before, during, and after listening to either binaural beats or control. Neuropsychologic measures included State Trait Anxiety Inventory, Profile of Mood States, Rey Auditory Verbal List Test, Stroop Test, and Controlled Oral Word Association Test. Spectral and coherence analysis was performed on the electroencephalogram (EEG), and all measures were analyzed for changes between sessions with and without binaural beat stimuli. There were no significant differences between the experimental and control conditions in any of the EEG measures. There was an increase of the Profile of Mood States depression subscale in the experimental condition relative to the control condition (p = 0.02). There was also a significant decrease in immediate verbal memory recall (p = 0.03) in the experimental condition compared to control

  5. Species distribution and physiological characterization of Acinetobacter genospecies from healthy human skin of tribal population in India

    OpenAIRE

    Yavankar S; Pardesi K; Chopade B

    2007-01-01

    Background: Various reports on distribution of Acinetobacter spp. from healthy human skin restricted to urban population. However, no such data is available from healthy human skin of tribal population not exposed to modern antibiotics during their life time. Purpose: Isolation, biotyping, distribution and physiological characterisation of Acinetobacter spp. from healthy human skin of tribal population. Methods: Tribal population of Toranmal area of Satpuda Ranges, Maharashtra, India...

  6. Atrial natriuretic peptide contributes to physiological control of lipid mobilization in humans.

    Science.gov (United States)

    Moro, Cedric; Crampes, Francois; Sengenes, Coralie; De Glisezinski, Isabelle; Galitzky, Jean; Thalamas, Claire; Lafontan, Max; Berlan, Michel

    2004-05-01

    In humans, lipid mobilization is considered to depend mainly on sympathetic nervous system activation and catecholamine action. A contribution of ANP was hypothesized because we have previously shown that atrial natriuretic peptide (ANP) is a lipolytic agent on isolated human fat cells. Control of lipid-mobilizing mechanisms was investigated using in situ microdialysis in subcutaneous adipose tissue (SCAT) in healthy young men during two successive exercise bouts performed at 35% and 60% peak oxygen consumption (VO2max) after placebo or acute oral tertatolol (nonselective beta-antagonist) treatment. In placebo-treated subjects, infusion of propranolol in the probe (100 micromol/l) only partially reduced (40%) the increment in extracellular glycerol concentration (EGC) promoted by exercise. Moreover, oral beta-adrenergic receptor blockade did not prevent exercise-induced lipid mobilization in SCAT while exerting fat cell beta-adrenergic receptor blockade. Exercise-induced increase in plasma ANP was potently amplified by oral tertatolol. A positive correlation was found between EGC and plasma ANP levels but also between extracellular cGMP (i.e., index of ANP-mediated lipolysis) and EGC. Thus, we demonstrate that exercise-induced lipid mobilization resistant to local propranolol and lipid-mobilizing action observed under oral beta-blockade is related to the action of ANP. Oral beta-adrenergic receptor blockade, which potentiates exercise-induced ANP release by the heart, may contribute to lipid mobilization in SCAT. The potential relevance of an ANP-related lipid-mobilizing pathway is discussed.

  7. Physiological and Molecular Genetic Effects of Time-Varying Electromagnetic Fields on Human Neuronal Cells

    Science.gov (United States)

    Goodwin, Thomas J.

    2003-01-01

    The present investigation details the development of model systems for growing two- and three-dimensional human neural progenitor cells within a culture medium facilitated by a time-varying electromagnetic field (TVEMF). The cells and culture medium are contained within a two- or three-dimensional culture vessel, and the electromagnetic field is emitted from an electrode or coil. These studies further provide methods to promote neural tissue regeneration by means of culturing the neural cells in either configuration. Grown in two dimensions, neuronal cells extended longitudinally, forming tissue strands extending axially along and within electrodes comprising electrically conductive channels or guides through which a time-varying electrical current was conducted. In the three-dimensional aspect, exposure to TVEMF resulted in the development of three-dimensional aggregates, which emulated organized neural tissues. In both experimental configurations, the proliferation rate of the TVEMF cells was 2.5 to 4.0 times the rate of the non-waveform cells. Each of the experimental embodiments resulted in similar molecular genetic changes regarding the growth potential of the tissues as measured by gene chip analyses, which measured more than 10,000 human genes simultaneously.

  8. Olfactory receptors modulate physiological processes in human airway smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Benjamin Kalbe

    2016-08-01

    Full Text Available Pathophysiological mechanisms in human airway smooth muscle cells (HASMCs significantly contribute to the progression of chronic inflammatory airway diseases with limited therapeutic options, such as severe asthma and COPD. These abnormalities include the contractility and hyperproduction of inflammatory proteins. To develop therapeutic strategies, key pathological mechanisms and putative clinical targets need to be identified. In the present study, we demonstrated that the human olfactory receptors (ORs OR1D2 and OR2AG1 are expressed at the RNA and protein levels in HASMCs. Using fluorometric calcium imaging, specific agonists for OR2AG1 and OR1D2 were identified to trigger transient Ca2+ increases in HASMCs via a cAMP-dependent signal transduction cascade. Furthermore, the activation of OR2AG1 via amyl butyrate inhibited the histamine-induced contraction of HASMCs, whereas the stimulation of OR1D2 with bourgeonal led to an increase in cell contractility. In addition, OR1D2 activation induced the secretion of IL-8 and GM-CSF. Both effects were inhibited by the specific OR1D2 antagonist undecanal. We herein provide the first evidence to show that ORs are functionally expressed in HASMCs and regulate pathophysiological processes. Therefore, ORs might be new therapeutic targets for these diseases, and blocking ORs could be an auspicious strategy for the treatment of early-stage chronic inflammatory lung diseases.

  9. A metabolic system-wide characterisation of the pig: a model for human physiology.

    Science.gov (United States)

    Merrifield, Claire A; Lewis, Marie; Claus, Sandrine P; Beckonert, Olaf P; Dumas, Marc-Emmanuel; Duncker, Swantje; Kochhar, Sunil; Rezzi, Serge; Lindon, John C; Bailey, Mick; Holmes, Elaine; Nicholson, Jeremy K

    2011-09-01

    The pig is a single-stomached omnivorous mammal and is an important model of human disease and nutrition. As such, it is necessary to establish a metabolic framework from which pathology-based variation can be compared. Here, a combination of one and two-dimensional (1)H and (13)C nuclear magnetic resonance spectroscopy (NMR) and high-resolution magic angle spinning (HR-MAS) NMR was used to provide a systems overview of porcine metabolism via characterisation of the urine, serum, liver and kidney metabolomes. The metabolites observed in each of these biological compartments were found to be qualitatively comparable to the metabolic signature of the same biological matrices in humans and rodents. The data were modelled using a combination of principal components analysis and Venn diagram mapping. Urine represented the most metabolically distinct biological compartment studied, with a relatively greater number of NMR detectable metabolites present, many of which are implicated in gut-microbial co-metabolic processes. The major inter-species differences observed were in the phase II conjugation of extra-genomic metabolites; the pig was observed to conjugate p-cresol, a gut microbial metabolite of tyrosine, with glucuronide rather than sulfate as seen in man. These observations are important to note when considering the translatability of experimental data derived from porcine models.

  10. Long-term neural and physiological phenotyping of a single human

    Science.gov (United States)

    Poldrack, Russell A.; Laumann, Timothy O.; Koyejo, Oluwasanmi; Gregory, Brenda; Hover, Ashleigh; Chen, Mei-Yen; Gorgolewski, Krzysztof J.; Luci, Jeffrey; Joo, Sung Jun; Boyd, Ryan L.; Hunicke-Smith, Scott; Simpson, Zack Booth; Caven, Thomas; Sochat, Vanessa; Shine, James M.; Gordon, Evan; Snyder, Abraham Z.; Adeyemo, Babatunde; Petersen, Steven E.; Glahn, David C.; Reese Mckay, D.; Curran, Joanne E.; Göring, Harald H. H.; Carless, Melanie A.; Blangero, John; Dougherty, Robert; Leemans, Alexander; Handwerker, Daniel A.; Frick, Laurie; Marcotte, Edward M.; Mumford, Jeanette A.

    2015-01-01

    Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of brain function over this timescale in healthy individuals are unknown. Here, as a proof of concept to address this question, we present the MyConnectome project. An intensive phenome-wide assessment of a single human was performed over a period of 18 months, including functional and structural brain connectivity using magnetic resonance imaging, psychological function and physical health, gene expression and metabolomics. A reproducible analysis workflow is provided, along with open access to the data and an online browser for results. We demonstrate dynamic changes in brain connectivity over the timescales of days to months, and relations between brain connectivity, gene expression and metabolites. This resource can serve as a testbed to study the joint dynamics of human brain and metabolic function over time, an approach that is critical for the development of precision medicine strategies for brain disorders. PMID:26648521

  11. [Heat exchange between human body and environment (theoretical bases of physiological measurement and evaluation)].

    Science.gov (United States)

    Pezzagno, G

    1999-01-01

    In the first part of this report the theory of the heat exchange between human body and external environment is developed. In particular, the problems concerning energy expenditure and heat production [metabolic heat] during physical activity, the heat exchange between internal organs and body surface, and its elimination are considered. Proposal of heat exchange equations (in case of conduction, convection, evaporation, radiation transport) are made, and the involved parameters and constants are indicated. Some pages are devoted to heat exchange through the lung and to "perspiratio insensibilis". In the second part the problems concerning the wellbeing and the thermal discomfort are discussed. A description of some widely employed indices of thermal stress, strain and comfort concludes the report [P4SR index, HSI index, ITS index, TTL index, HR index, WBGT index, TE indices]. In the end, the Fanger equations of thermal comfort are presented and discussed.

  12. Human placental extract mediated inhibition of proteinase K: implications of heparin and glycoproteins in wound physiology.

    Science.gov (United States)

    Sharma, Kanika; Mukherjee, Chaitali; Roy, Siddhartha; De, Debashree; Bhattacharyya, Debasish

    2014-09-01

    Efficient debridement of the wound bed following the removal of microbial load prevents its progression into a chronic wound. Bacterial infection and excessive proteolysis characterize impaired healing and therefore, their inhibition might restore the disturbed equilibrium in the healing process. Human placental extract exhibits reversible, non-competitive inhibition towards Proteinase K, a microbial protease, by stabilizing it against auto-digestion. Scattering and fluorescence studies followed by biochemical analysis indicated the involvement of a glycan moiety. Surface plasmon resonance demonstrated specific interaction of heparin with Proteinase K having Kd in μM range. Further, Proteinase K contains sequence motifs similar to other heparin-binding proteins. Molecular docking revealed presence of clefts suitable for binding of heparin-derived oligosaccharides. Comprehensive analysis of this inhibitory property of placental extract partly explains its efficacy in curing wounds with common bacterial infections.

  13. Physiological Roles of Platelet-activating Factor in Mammalian and Human Reproduction

    Institute of Scientific and Technical Information of China (English)

    Jiu-ming ZHU; Joe B. MASSEY; William E. ROUDEBUSH

    2005-01-01

    This review described origination, biosynthesis and functions of platelet-activat-ing factor (PAF) in the reproductive system of mammals and human beings. The articlemainly focused on biological roles of the phospholipid mediator in sperm fertilizationand embryonic implantation. As an autocrine product of sperm and embryos, PAFmarkedly stimulates sperm motility and fertilization and serves as a capacitationfactor in a ligand-receptor manner. After fertilization, embryo-derived PAF improvesits own development, especially from fertilized ova to blastocyst stage and is thoughtto act as an embryo growth factor in the same manner as on sperm. Its mechanism ofaction was also clarified. At the end, it was presented some advances in its clinicalapplication, followed by discussion of some issues possibly concerning in its currentapplication.

  14. Vascular hyperpolarization in human physiology and cardiovascular risk conditions and disease.

    Science.gov (United States)

    Schinzari, F; Tesauro, M; Cardillo, C

    2017-01-01

    Hyperpolarization causing smooth muscle relaxation contributes to the maintenance of vascular homeostasis, particularly in small-calibre arteries and arterioles. It may also become a compensatory vasodilator mechanism upregulated in states with impaired nitric oxide (NO) availability. Bioassay of vascular hyperpolarization in the human circulation has been hampered by the complexity of mechanisms involved and the limited availability of investigational tools. Firm evidence, however, supports the notion that hyperpolarization participates in the regulation of resting vasodilator tone and vascular reactivity in healthy subjects. In addition, an enhanced endothelium-derived hyperpolarization contributes to both resting and agonist-stimulated vasodilation in a variety of cardiovascular risk conditions and disease. Thus, hyperpolarization mediated by epoxyeicosatrienoic acids (EETs) and H2 O2 has been observed in coronary arterioles of patients with coronary artery disease. Similarly, ouabain-sensitive and EETs-mediated hyperpolarization has been observed to compensate for NO deficiency in patients with essential hypertension. Moreover, in non-hypertensive patients with multiple cardiovascular risk factors and in hypercholesterolaemia, KCa channel-mediated vasodilation appears to be activated. A novel paradigm establishes that perivascular adipose tissue (PVAT) is an additional regulator of vascular tone/function and endothelium is not the only agent in vascular hyperpolarization. Indeed, some PVAT-derived relaxing substances, such as adiponectin and angiotensin 1-7, may exert anticontractile and vasodilator actions by the opening of KCa channels in smooth muscle cells. Conversely, PVAT-derived factors impair coronary vasodilation via differential inhibition of some K(+) channels. In view of adipose tissue abnormalities occurring in human obesity, changes in PVAT-dependent hyperpolarization may be relevant for vascular dysfunction also in this condition.

  15. Analysis of Cap-binding Proteins in Human Cells Exposed to Physiological Oxygen Conditions.

    Science.gov (United States)

    Timpano, Sara; Melanson, Gaelan; Evagelou, Sonia L; Guild, Brianna D; Specker, Erin J; Uniacke, James

    2016-12-28

    Translational control is a focal point of gene regulation, especially during periods of cellular stress. Cap-dependent translation via the eIF4F complex is by far the most common pathway to initiate protein synthesis in eukaryotic cells, but stress-specific variations of this complex are now emerging. Purifying cap-binding proteins with an affinity resin composed of Agarose-linked m(7)GTP (a 5' mRNA cap analog) is a useful tool to identify factors involved in the regulation of translation initiation. Hypoxia (low oxygen) is a cellular stress encountered during fetal development and tumor progression, and is highly dependent on translation regulation. Furthermore, it was recently reported that human adult organs have a lower oxygen content (physioxia 1-9% oxygen) that is closer to hypoxia than the ambient air where cells are routinely cultured. With the ongoing characterization of a hypoxic eIF4F complex (eIF4F(H)), there is increasing interest in understanding oxygen-dependent translation initiation through the 5' mRNA cap. We have recently developed a human cell culture method to analyze cap-binding proteins that are regulated by oxygen availability. This protocol emphasizes that cell culture and lysis be performed in a hypoxia workstation to eliminate exposure to oxygen. Cells must be incubated for at least 24 hr for the liquid media to equilibrate with the atmosphere within the workstation. To avoid this limitation, pre-conditioned media (de-oxygenated) can be added to cells if shorter time points are required. Certain cap-binding proteins require interactions with a second base or can hydrolyze the m(7)GTP, therefore some cap interactors may be missed in the purification process. Agarose-linked to enzymatically resistant cap analogs may be substituted in this protocol. This method allows the user to identify novel oxygen-regulated translation factors involved in cap-dependent translation.

  16. A network biology approach to understanding the importance of chameleon proteins in human physiology and pathology.

    Science.gov (United States)

    Bahramali, Golnaz; Goliaei, Bahram; Minuchehr, Zarrin; Marashi, Sayed-Amir

    2017-02-01

    Chameleon proteins are proteins which include sequences that can adopt α-helix-β-strand (HE-chameleon) or α-helix-coil (HC-chameleon) or β-strand-coil (CE-chameleon) structures to operate their crucial biological functions. In this study, using a network-based approach, we examined the chameleon proteins to give a better knowledge on these proteins. We focused on proteins with identical chameleon sequences with more than or equal to seven residues long in different PDB entries, which adopt HE-chameleon, HC-chameleon, and CE-chameleon structures in the same protein. One hundred and ninety-one human chameleon proteins were identified via our in-house program. Then, protein-protein interaction (PPI) networks, Gene ontology (GO) enrichment, disease network, and pathway enrichment analyses were performed for our derived data set. We discovered that there are chameleon sequences which reside in protein-protein interaction regions between two proteins critical for their dual function. Analysis of the PPI networks for chameleon proteins introduced five hub proteins, namely TP53, EGFR, HSP90AA1, PPARA, and HIF1A, which were presented in four PPI clusters. The outcomes demonstrate that the chameleon regions are in critical domains of these proteins and are important in the development and treatment of human cancers. The present report is the first network-based functional study of chameleon proteins using computational approaches and might provide a new perspective for understanding the mechanisms of diseases helping us in developing new medical therapies along with discovering new proteins with chameleon properties which are highly important in cancer.

  17. Metaplasticity in human primary somatosensory cortex: effects on physiology and tactile perception.

    Science.gov (United States)

    Jones, Christina B; Lulic, Tea; Bailey, Aaron Z; Mackenzie, Tanner N; Mi, Yi Qun; Tommerdahl, Mark; Nelson, Aimee J

    2016-05-01

    Theta-burst stimulation (TBS) over human primary motor cortex evokes plasticity and metaplasticity, the latter contributing to the homeostatic balance of excitation and inhibition. Our knowledge of TBS-induced effects on primary somatosensory cortex (SI) is limited, and it is unknown whether TBS induces metaplasticity within human SI. Sixteen right-handed participants (6 females, mean age 23 yr) received two TBS protocols [continuous TBS (cTBS) and intermittent TBS (iTBS)] delivered in six different combinations over SI in separate sessions. TBS protocols were delivered at 30 Hz and were as follows: a single cTBS protocol, a single iTBS protocol, cTBS followed by cTBS, iTBS followed by iTBS, cTBS followed by iTBS, and iTBS followed by cTBS. Measures included the amplitudes of the first and second somatosensory evoked potentials (SEPs) via median nerve stimulation, their paired-pulse ratio (PPR), and temporal order judgment (TOJ). Dependent measures were obtained before TBS and at 5, 25, 50, and 90 min following stimulation. Results indicate similar effects following cTBS and iTBS; increased amplitudes of the second SEP and PPR without amplitude changes to SEP 1, and impairments in TOJ. Metaplasticity was observed such that TOJ impairments following a single cTBS protocol were abolished following consecutive cTBS protocols. Additionally, consecutive iTBS protocols altered the time course of effects when compared with a single iTBS protocol. In conclusion, 30-Hz cTBS and iTBS protocols delivered in isolation induce effects consistent with a TBS-induced reduction in intracortical inhibition within SI. Furthermore, cTBS- and iTBS-induced metaplasticity appear to follow homeostatic and nonhomeostatic rules, respectively.

  18. Metaplasticity in human primary somatosensory cortex: effects on physiology and tactile perception

    Science.gov (United States)

    Jones, Christina B.; Lulic, Tea; Bailey, Aaron Z.; Mackenzie, Tanner N.; Mi, Yi Qun; Tommerdahl, Mark

    2016-01-01

    Theta-burst stimulation (TBS) over human primary motor cortex evokes plasticity and metaplasticity, the latter contributing to the homeostatic balance of excitation and inhibition. Our knowledge of TBS-induced effects on primary somatosensory cortex (SI) is limited, and it is unknown whether TBS induces metaplasticity within human SI. Sixteen right-handed participants (6 females, mean age 23 yr) received two TBS protocols [continuous TBS (cTBS) and intermittent TBS (iTBS)] delivered in six different combinations over SI in separate sessions. TBS protocols were delivered at 30 Hz and were as follows: a single cTBS protocol, a single iTBS protocol, cTBS followed by cTBS, iTBS followed by iTBS, cTBS followed by iTBS, and iTBS followed by cTBS. Measures included the amplitudes of the first and second somatosensory evoked potentials (SEPs) via median nerve stimulation, their paired-pulse ratio (PPR), and temporal order judgment (TOJ). Dependent measures were obtained before TBS and at 5, 25, 50, and 90 min following stimulation. Results indicate similar effects following cTBS and iTBS; increased amplitudes of the second SEP and PPR without amplitude changes to SEP 1, and impairments in TOJ. Metaplasticity was observed such that TOJ impairments following a single cTBS protocol were abolished following consecutive cTBS protocols. Additionally, consecutive iTBS protocols altered the time course of effects when compared with a single iTBS protocol. In conclusion, 30-Hz cTBS and iTBS protocols delivered in isolation induce effects consistent with a TBS-induced reduction in intracortical inhibition within SI. Furthermore, cTBS- and iTBS-induced metaplasticity appear to follow homeostatic and nonhomeostatic rules, respectively. PMID:26984422

  19. Symbioses: a key driver of insect physiological processes, ecological interactions, evolutionary diversification, and impacts on humans.

    Science.gov (United States)

    Klepzig, K D; Adams, A S; Handelsman, J; Raffa, K F

    2009-02-01

    Symbiosis is receiving increased attention among all aspects of biology because of the unifying themes it helps construct across ecological, evolutionary, developmental, semiochemical, and pest management theory. Insects show a vast array of symbiotic relationships with a wide diversity of microorganisms. These relationships may confer a variety of benefits to the host (macrosymbiont), such as direct or indirect nutrition, ability to counter the defenses of plant or animal hosts, protection from natural enemies, improved development and reproduction, and communication. Benefits to the microsymbiont (including a broad range of fungi, bacteria, mites, nematodes, etc.) often include transport, protection from antagonists, and protection from environmental extremes. Symbiotic relationships may be mutualistic, commensal, competitive, or parasitic. In many cases, individual relationships may include both beneficial and detrimental effects to each partner during various phases of their life histories or as environmental conditions change. The outcomes of insect-microbial interactions are often strongly mediated by other symbionts and by features of the external and internal environment. These outcomes can also have important effects on human well being and environmental quality, by affecting agriculture, human health, natural resources, and the impacts of invasive species. We argue that, for many systems, our understanding of symbiotic relationships will advance most rapidly where context dependency and multipartite membership are integrated into existing conceptual frameworks. Furthermore, the contribution of entomological studies to overall symbiosis theory will be greatest where preoccupation with strict definitions and artificial boundaries is minimized, and integration of emerging molecular and quantitative techniques is maximized. We highlight symbiotic relations involving bark beetles to illustrate examples of the above trends.

  20. Acute physiological effects of glucocorticoids on fuel metabolism in humans are permissive but not direct.

    Science.gov (United States)

    Stimson, Roland H; Anderson, Anna J; Ramage, Lynne E; Macfarlane, David P; de Beaux, Andrew C; Mole, Damian J; Andrew, Ruth; Walker, Brian R

    2017-06-01

    The effects of glucocorticoids on fuel metabolism are complex. Acute glucocorticoid excess promotes lipolysis but chronic glucocorticoid excess causes visceral fat accumulation. We hypothesized that interactions between cortisol and insulin and adrenaline account for these conflicting results. We tested the effect of cortisol on lipolysis and glucose production with and without insulin and adrenaline in humans both in vivo and in vitro. A total of 20 healthy men were randomized to low and high insulin groups (both n = 10). Subjects attended on 3 occasions and received low (c. 150 nM), medium (c. 400 nM) or high (c. 1400 nM) cortisol infusion in a randomized crossover design. Deuterated glucose and glycerol were infused intravenously along with a pancreatic clamp (somatostatin with replacement of glucagon, insulin and growth hormone) and adrenaline. Subcutaneous adipose tissue was obtained for analysis. In parallel, the effect of cortisol on lipolysis was tested in paired primary cultures of human subcutaneous and visceral adipocytes. In vivo, high cortisol increased lipolysis only in the presence of high insulin and/or adrenaline but did not alter glucose kinetics. High cortisol increased adipose mRNA levels of ATGL, HSL and CGI-58 and suppressed G0S2. In vitro, high cortisol increased lipolysis in the presence of insulin in subcutaneous, but not visceral, adipocytes. The acute lipolytic effects of cortisol require supraphysiological concentrations, are dependent on insulin and adrenaline and are observed only in subcutaneous adipose tissue. The resistance of visceral adipose tissue to cortisol's lipolytic effects may contribute to the central fat accumulation observed with chronic glucocorticoid excess. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  1. Physiologically relevant plasma d,l-homocysteine concentrations mobilize Cd from human serum albumin.

    Science.gov (United States)

    Sagmeister, Peter; Gibson, Matthew A; McDade, Kyle H; Gailer, Jürgen

    2016-08-01

    Although low-level chronic exposure of humans to cadmium (Cd(2+)) can result in a variety of adverse health effects, little is known about the role that its interactions with plasma proteins and small molecular weight (SMW) ligands in the bloodstream may play in delivering this metal to its target organs. To gain insight, a Cd-human serum albumin (HSA) 1:1 (molar ratio) complex was analyzed by size exclusion chromatography (SEC) coupled on-line to a flame atomic absorption spectrometer (FAAS). Using a phosphate buffered saline (PBS)-buffer mobile phase, the stability of the Cd-HSA complex was investigated in the presence of 2.0mM of SMW ligands, including taurine, acetaminophen, l-methionine, l-cysteine (Cys), d,l-homocysteine (hCys) or l-cysteine methyl-ester (Cys-Me). While taurine, acetaminophen and l-methionine did not affect its integrity, Cys, hCys and Cys-Me completely abstracted Cd from HSA. Subsequent investigations into the effect of 1.5, 1.0 and 0.5mM Cys and hCys on the integrity of the Cd-HSA complex revealed clear differences with regard to the nature of the eluting SMW-Cd species between these structurally related endogenous thiols. Interestingly, the Cd-specific chromatograms that were obtained for 0.5mM hCys revealed the elution of an apparent mixture of the parent Cd-HSA complex with a significant contribution of a structurally uncharacterized CdxhCysy species. Since this hCys concentration is encountered in blood plasma of hyperhomocysteinemia patients and since previous studies by others have revealed that a SH-containing carrier mediates the uptake of Cd into hepatocytes, our results suggest that plasma hCys may play a role in the toxicologically relevant translocation of Cd from the bloodstream to mammalian target organs.

  2. Physiological properties of neurons derived from human embryonic stem cells using a dibutyryl cyclic AMP-based protocol.

    Science.gov (United States)

    Belinsky, Glenn S; Moore, Anna R; Short, Shaina M; Rich, Matthew T; Antic, Srdjan D

    2011-10-01

    Neurons derived from human embryonic stem cells hold promise for the therapy of neurological diseases. Quality inspection of human embryonic stem cell-derived neurons has often been based on immunolabeling for neuronal markers. Here we put emphasis on their physiological properties. Electrophysiological measurements were carried out systematically at different stages of neuronal in vitro development, including the very early stage, neuroepithelial rosettes. Developing human neurons are able to generate action potentials (APs) as early as 10 days after the start of differentiation. Tyrosine hydroxylase (TH)-positive (putative dopaminergic, DA) neurons tend to aggregate into clumps, and their overall yield per coverslip is relatively low (8.3%) because of areas void of DA neurons. On the same in vitro day, neighboring neurons can be in very different stages of differentiation, including repetitive AP firing, single full-size AP, and abortive AP. Similarly, the basic electrophysiological parameters (resting membrane potential, input resistance, peak sodium, and peak potassium currents) are scattered in a wide range. Visual appearance of differentiating neurons, and number of primary and secondary dendrites cannot be used to predict the peak sodium current or AP firing properties of cultured neurons. Approximately 13% of neurons showed evidence of hyperpolarization-induced current (I(h)), a characteristic of DA neurons; however, no neurons with repetitive APs showed I(h). The electrophysiological measurements thus indicate that a standard DA differentiation (dibutyryl cyclic AMP-based) protocol, applied for 2-5 weeks, produces a heterogeneous ensemble of mostly immature neurons. The overall quality of human neurons under present conditions (survival factors were not used) begins to deteriorate after 12 days of differentiation.

  3. Nasal Physiology

    Science.gov (United States)

    ... Caregivers Contact ARS HOME ANATOMY Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure ... Patient Education About this Website Font Size + - Home > ANATOMY > Nasal Physiology Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy ...

  4. Light Modulates Metabolic Pathways and Other Novel Physiological Traits in the Human Pathogen Acinetobacter baumannii.

    Science.gov (United States)

    Müller, Gabriela L; Tuttobene, Marisel; Altilio, Matías; Martínez Amezaga, Maitena; Nguyen, Meaghan; Cribb, Pamela; Cybulski, Larisa E; Ramírez, María Soledad; Altabe, Silvia; Mussi, María Alejandra

    2017-05-15

    Light sensing in chemotrophic bacteria has been relatively recently ascertained. In the human pathogen Acinetobacter baumannii, light modulates motility, biofilm formation, and virulence through the blue-light-sensing-using flavin (BLUF) photoreceptor BlsA. In addition, light can induce a reduction in susceptibility to certain antibiotics, such as minocycline and tigecycline, in a photoreceptor-independent manner. In this work, we identified new traits whose expression levels are modulated by light in this pathogen, which comprise not only important determinants related to pathogenicity and antibiotic resistance but also metabolic pathways, which represents a novel concept for chemotrophic bacteria. Indeed, the phenylacetic acid catabolic pathway and trehalose biosynthesis were modulated by light, responses that completely depend on BlsA. We further show that tolerance to some antibiotics and modulation of antioxidant enzyme levels are also influenced by light, likely contributing to bacterial persistence in adverse environments. Also, we present evidence indicating that surfactant production is modulated by light. Finally, the expression of whole pathways and gene clusters, such as genes involved in lipid metabolism and genes encoding components of the type VI secretion system, as well as efflux pumps related to antibiotic resistance, was differentially induced by light. Overall, our results indicate that light modulates global features of the A. baumannii lifestyle.IMPORTANCE The discovery that nonphototrophic bacteria respond to light constituted a novel concept in microbiology. In this context, we demonstrated that light could modulate aspects related to bacterial virulence, persistence, and resistance to antibiotics in the human pathogen Acinetobacter baumannii In this work, we present the novel finding that light directly regulates metabolism in this chemotrophic bacterium. Insights into the mechanism show the involvement of the photoreceptor BlsA. In

  5. Physiological and pharmacological characterization of transmembrane acid extruders in cultured human umbilical artery smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Gunng-Shinng Chen

    2015-01-01

    Full Text Available Background: Intracellular pH (pH i is a pivotal factor for cellular functions and homeostasis. Apart from passive intracellular buffering capacity, active transmembrane transporters responsible for kinetic changes of pH i impacts. Acid extrusion transporters such as Na + /H + exchanger (NHE and Na + /HCO3− cotransporter (NBC have been found to be activated when cells are in an acidic condition in different cell types. However, such far, the pH i regulators have not been characterized in human umbilical artery smooth muscle cells (HUASMCs. Materials and Methods: We, therefore, investigated the mechanism of pH i recovery from intracellular acidosis, induced by NH 4 Cl-prepulse, using pH-sensitive fluorescence dye: 2′,7′-bis(2-carboxethyl-5(6-carboxy-fluorescein in HUASMCs. Cultured HUASMCs were derived from the segments of the human umbilical artery that were obtained from women undergoing children delivery. Results: The resting pH i is 7.23 ± 0.03 when cells in HEPES (nominally HCO 3− -free buffered solution. The resting pH i is higher as 7.27 ± 0.03 when cells in CO 2 /HCO3− -buffered solution. In HEPES-buffered solution, a pH i recovery following induced intracellular acidosis could be inhibited completely by 30 μM HOE 694 (a specific NHE inhibitor or by removing [Na +]o . In 5% CO2/HCO3− -buffered solution, 30 μM HOE 694 slowed the pH i recovery from the induced intracellular acidosis only. On the contrary, HOE 694 adding together with 0.2 mM 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (a specific NBC inhibitor or removal of [Na +]o entirely blocked the acid extrusion. By using Western blot technique, we demonstrated that four different isoforms of NBC, that is, SLC4A8 (NBCBE, SLC4A7 (NBCn1, SLC4A5 (NBCe2 and SLC4A4 (NBCe1, co-exist in the HUASMCs. Conclusions: We demonstrate, for the 1 st time, that apart from the housekeeping NHE1, another Na + couple HCO3− -transporter, that is, NBC, functionally coexists to

  6. Physiological effects in aromatherapy

    Directory of Open Access Journals (Sweden)

    Tapanee Hongratanaworakit

    2004-01-01

    Full Text Available The effects of aromas on humans are divided into physiological and psychological effects. The physiological effect acts directly on the physical organism, the psychological effect acts via the sense of smell or olfactory system, which in turn may cause a physiological effect. This paper reviews on the physiological effects which are used for the evaluation of the effects of aromas. Physiological parameters, i.e. heart rate blood pressure, electrodermal activity, electroencephalogram, slow potential brain waves (contingent negativevariation, and eye blink rate or pupil functions, are used as indices for the measurement of the aroma effects

  7. Differential role of Hedgehog signaling in human pancreatic (patho-) physiology: An up to date review.

    Science.gov (United States)

    Klieser, Eckhard; Swierczynski, Stefan; Mayr, Christian; Jäger, Tarkan; Schmidt, Johanna; Neureiter, Daniel; Kiesslich, Tobias; Illig, Romana

    2016-05-15

    Since the discovery of the Hedgehog (Hh) pathway in drosophila melanogaster, our knowledge of the role of Hh in embryonic development, inflammation, and cancerogenesis in humans has dramatically increased over the last decades. This is the case especially concerning the pancreas, however, real therapeutic breakthroughs are missing until now. In general, Hh signaling is essential for pancreatic organogenesis, development, and tissue maturation. In the case of acute pancreatitis, Hh has a protective role, whereas in chronic pancreatitis, Hh interacts with pancreatic stellate cells, leading to destructive parenchym fibrosis and atrophy, as well as to irregular tissue remodeling with potency of initiating cancerogenesis. In vitro and in situ analysis of Hh in pancreatic cancer revealed that the Hh pathway participates in the development of pancreatic precursor lesions and ductal adenocarcinoma including critical interactions with the tumor microenvironment. The application of specific inhibitors of components of the Hh pathway is currently subject of ongoing clinical trials (phases 1 and 2). Furthermore, a combination of Hh pathway inhibitors and established chemotherapeutic drugs could also represent a promising therapeutic approach. In this review, we give a structured survey of the role of the Hh pathway in pancreatic development, pancreatitis, pancreatic carcinogenesis and pancreatic cancer as well as an overview of current clinical trials concerning Hh pathway inhibitors and pancreas cancer.

  8. Perspectives for induced pluripotent stem cell technology: new insights into human physiology involved in somatic mosaicism.

    Science.gov (United States)

    Nagata, Naoki; Yamanaka, Shinya

    2014-01-31

    Induced pluripotent stem cell technology makes in vitro reprogramming of somatic cells from individuals with various genetic backgrounds possible. By applying this technology, it is possible to produce pluripotent stem cells from biopsy samples of arbitrarily selected individuals with various genetic backgrounds and to subsequently maintain, expand, and stock these cells. From these induced pluripotent stem cells, target cells and tissues can be generated after certain differentiation processes. These target cells/tissues are expected to be useful in regenerative medicine, disease modeling, drug screening, toxicology testing, and proof-of-concept studies in drug development. Therefore, the number of publications concerning induced pluripotent stem cells has recently been increasing rapidly, demonstrating that this technology has begun to infiltrate many aspects of stem cell biology and medical applications. In this review, we discuss the perspectives of induced pluripotent stem cell technology for modeling human diseases. In particular, we focus on the cloning event occurring through the reprogramming process and its ability to let us analyze the development of complex disease-harboring somatic mosaicism.

  9. The delicate balance between secreted protein folding and endoplasmic reticulum-associated degradation in human physiology.

    Science.gov (United States)

    Guerriero, Christopher J; Brodsky, Jeffrey L

    2012-04-01

    Protein folding is a complex, error-prone process that often results in an irreparable protein by-product. These by-products can be recognized by cellular quality control machineries and targeted for proteasome-dependent degradation. The folding of proteins in the secretory pathway adds another layer to the protein folding "problem," as the endoplasmic reticulum maintains a unique chemical environment within the cell. In fact, a growing number of diseases are attributed to defects in secretory protein folding, and many of these by-products are targeted for a process known as endoplasmic reticulum-associated degradation (ERAD). Since its discovery, research on the mechanisms underlying the ERAD pathway has provided new insights into how ERAD contributes to human health during both normal and diseases states. Links between ERAD and disease are evidenced from the loss of protein function as a result of degradation, chronic cellular stress when ERAD fails to keep up with misfolded protein production, and the ability of some pathogens to coopt the ERAD pathway. The growing number of ERAD substrates has also illuminated the differences in the machineries used to recognize and degrade a vast array of potential clients for this pathway. Despite all that is known about ERAD, many questions remain, and new paradigms will likely emerge. Clearly, the key to successful disease treatment lies within defining the molecular details of the ERAD pathway and in understanding how this conserved pathway selects and degrades an innumerable cast of substrates.

  10. Nodal recovery, dual pathway physiology, and concealed conduction determine complex AV dynamics in human atrial tachyarrhythmias.

    Science.gov (United States)

    Masè, Michela; Glass, Leon; Disertori, Marcello; Ravelli, Flavia

    2012-11-15

    The genesis of complex ventricular rhythms during atrial tachyarrhythmias in humans is not fully understood. To clarify the dynamics of atrioventricular (AV) conduction in response to a regular high-rate atrial activation, 29 episodes of spontaneous or pacing-induced atrial flutter (AFL), covering a wide range of atrial rates (cycle lengths from 145 to 270 ms), were analyzed in 10 patients. AV patterns were identified by applying firing sequence and surrogate data analysis to atrial and ventricular activation series, whereas modular simulation with a difference-equation AV node model was used to correlate the patterns with specific nodal properties. AV node response at high atrial rate was characterized by 1) AV patterns of decreasing conduction ratios at the shortening of atrial cycle length (from 236.3 ± 32.4 to 172.6 ± 17.8 ms) according to a Farey sequence ordering (conduction ratio from 0.34 ± 0.12 to 0.23 ± 0.06; P AV block patterns occurring during regular atrial tachyarrhythmias. The characterization of AV nodal function during different AFL forms constitutes an intermediate step toward the understanding of complex ventricular rhythms during atrial fibrillation.

  11. [The physiological importance of prostaglandins in the mechanism of human labor].

    Science.gov (United States)

    Husslein, P

    1982-10-29

    Recent results indicate that prostaglandins play a major role in the mechanism of human labor. There are, however, no systematic studies on the role of prostaglandins in various forms of induction of labor. In the present study the concentration of 13,14-dihydro,15-ketoprostaglandin F2 (PGFM) in the maternal peripheral plasma was determined in labor of spontaneous onset, in labor after induction with oxytocin and in labor after induction by artificial rupture of membranes (ARM). In an additional group of women PGFM was determined before and immediately after delivery to get an insight into the mechanism of placental separation. In labor of spontaneous onset PGFM concentration increased significantly. In labour induced by oxytocin PGFM levels rose only in those women in whom induction of labor was successful. In induction of labor by ARM, PGFM level also increased in all women in whom induction was successful. At the time of placental separation PGFM concentration in the maternal blood increased dramatically. From the result of this study it is concluded that the increase of prostaglandin F synthesis is a necessary prerequisite for vaginal delivery and that prostaglandins are of major importance in the mechanism of placental separation and expulsion.

  12. A BRIEF HISTORY OF HUMAN POWERED FLIGHT: FROM PHYSIOLOGY TO PHILOSOPHY

    Directory of Open Access Journals (Sweden)

    Pietro Enrico di Prampero

    2010-01-01

    Full Text Available The development of a scientific theory (T can be separated into successive phases: i Fantasy, to conceive T ii Analysis to couch T into formal language iii Action, to apply in practice the predictions of T. The history of human powered flight, in which case the three phases are stretched over several thousand years, allow us to better appreciate their intrinsic characteristics. Fantasy, dating back to the myth of Ikarus, must be experimentally testable, as indeed were Daedalus’ wings. Analysis must state in quantitative terms the laws governing the matter at stake. Action, from Leonardo’s unsuccessful attempts to the crossings of the British Channel in 1979 and of the arm of the sea separating Crete from mainland Greece in 1988, has the aim of shaping the world according to our will. The kernel of any “proper” T is a formal system wherein a set of operational rules allows us to manipulate a set of symbols, representing the objects of T, on the bases of a limited number of axioms. In such formal systems, “theorem” is a string of symbols that can be arrived at in a finite number of steps from the axioms, applying the canonical operational rules. However, as Kurt Gödel showed in 1931, it is possible to demonstrate that, within a sufficiently powerful formal system, there exists demonstrably true strings of symbols that are not theorems. Thus, even in an ultra-powerful theory of everything, there will still be truths that can not be arrived at within the theory.

  13. Physiological adaptation of the bacterium Lactococcus lactis in response to the production of human CFTR.

    Science.gov (United States)

    Steen, Anton; Wiederhold, Elena; Gandhi, Tejas; Breitling, Rainer; Slotboom, Dirk Jan

    2011-07-01

    Biochemical and biophysical characterization of CFTR (the cystic fibrosis transmembrane conductance regulator) is thwarted by difficulties to obtain sufficient quantities of correctly folded and functional protein. Here we have produced human CFTR in the prokaryotic expression host Lactococcus lactis. The full-length protein was detected in the membrane of the bacterium, but the yields were too low (proteins) for in vitro functional and structural characterization, and induction of the expression of CFTR resulted in growth arrest. We used isobaric tagging for relative and absolute quantitation based quantitative proteomics to find out why production of CFTR in L. lactis was problematic. Protein abundances in membrane and soluble fractions were monitored as a function of induction time, both in CFTR expression cells and in control cells that did not express CFTR. Eight hundred and forty six proteins were identified and quantified (35% of the predicted proteome), including 163 integral membrane proteins. Expression of CFTR resulted in an increase in abundance of stress-related proteins (e.g. heat-shock and cell envelope stress), indicating the presence of misfolded proteins in the membrane. In contrast to the reported consequences of membrane protein overexpression in Escherichia coli, there were no indications that the membrane protein insertion machinery (Sec) became overloaded upon CFTR production in L. lactis. Nutrients and ATP became limiting in the control cells as the culture entered the late exponential and stationary growth phases but this did not happen in the CFTR expressing cells, which had stopped growing upon induction. The different stress responses elicited in E. coli and L. lactis upon membrane protein production indicate that different strategies are needed to overcome low expression yields and toxicity.

  14. Mechanism and physiologic significance of the suppression of cholesterol esterification in human interstitial fluid

    Directory of Open Access Journals (Sweden)

    Norman Eric Miller

    2016-07-01

    Full Text Available Cholesterol esterification in high density lipoproteins (HDLs by lecithin:cholesterol acyltransferase (LCAT promotes unesterified cholesterol (UC transfer from red cell membranes to plasma in vitro. However, it does not explain the transfer of UC from most peripheral cells to interstitial fluid in vivo, as HDLs in afferent peripheral lymph are enriched in UC. Having already reported that the endogenous cholesterol esterification rate (ECER in lymph is only five per cent of that in plasma, we have now explored the underlying mechanism. In peripheral lymph from 20 healthy men, LCAT concentration, LCAT activity (assayed using an optimized substrate, and LCAT specific activity averaged respectively 11.8, 10.3, and 84.9 per cent of plasma values. When recombinant human LCAT was added to lymph, the increments in enzyme activity were similar to those when LCAT was added to plasma. Addition of apolipoprotein AI (apo AI, fatty acid-free albumin, Intralipid, or the d<1.006 g/ml plasma fraction had no effect on ECER. During incubation of lymph plus plasma, the ECER was similar to that observed with buffer plus plasma. When lymph was added to heat-inactivated plasma, the ECER was 11-fold greater than with lymph plus buffer. Addition of discoidal proteoliposomes of apo AI and phosphatidycholine (PC to lymph increased ECER ten-fold, while addition of apo AI/PC/UC discs did so by only six-fold. We conclude that the low ECER in lymph is due to a property of the HDLs, seemingly substrate inhibition of LCAT by excess cell-derived UC. This is reversed when lymph enters plasma, consequent upon redistribution of UC from lymph HDLs to plasma lipoproteins.

  15. Biological fractionation of stable Ca isotopes in Göttingen minipigs as a physiological model for Ca homeostasis in humans.

    Science.gov (United States)

    Heuser, Alexander; Eisenhauer, Anton; Scholz-Ahrens, Katharina E; Schrezenmeir, Jürgen

    2016-12-01

    In order to investigate fractionation of calcium (Ca) isotopes in vertebrates as a diagnostic tool to detect Ca metabolism dysfunction we analyzed the Ca isotopic composition (δ(44/40)Ca = [((44)Ca/(40)Ca)sample/((44)Ca/(40)Ca)reference]-1) of diet, faeces, blood, bones and urine from Göttingen minipigs, an animal model for human physiology. Samples of three groups were investigated: 1. control group (Con), 2. group with glucocorticosteroid induced osteoporosis (GIO) and 3. group with Ca and vitamin D deficiency induced osteomalacia (-CaD). In contrast to Con and GIO whose average δ(44/40)Cafaeces values (0.39 ± 0.13‰ and 0.28 ± 0.08‰, respectively) tend to be lower than their diet (0.47 ± 0.02‰), δ(44/40)Cafaeces of -CaD (-0.27 ± 0.21‰) was significantly lower than their δ(44/40)Cadiet (0.37 ± 0.03‰), but also lower than δ(44/40)Cafaeces of Con and GIO. We suggest that the low δ(44/40)Cafaeces of -CaD might be due to the contribution of isotopically light Ca from gastrointestinal fluids during gut passage. Assuming that this endogenous Ca source is a common physiologic feature, a fractionation during Ca absorption is also required for explaining δ(44/40)Cafaeces of Con and GIO. The δ(44/40)Caurine of all groups are high (>2.0‰) reflecting preferential renal reabsorption of light Ca isotopes. In Göttingen minipigs we found a Ca isotope fractionation between blood and bones (Δ(44/40)Cablood-bone) of 0.68 ± 0.15‰.

  16. Effects of acclimation to human interaction on performance, temperament, physiological responses, and pregnancy rates of Brahman-crossbred cows.

    Science.gov (United States)

    Cooke, R F; Arthington, J D; Araujo, D B; Lamb, G C

    2009-12-01

    The objective of this study was to evaluate, over 2 consecutive years, the effects of acclimation to human interaction on performance, temperament, plasma concentrations of hormones and metabolites, and pregnancy rates of Brahman-crossbred cows. A total of 160 Braford and 235 Brahman x British cows were assigned to the 2-yr study. Approximately 45 d after weaning (August 2006) in yr 1, cows were evaluated for BW, BCS, and temperament (chute score, pen score, and exit velocity), stratified by these measurements in addition to breed and age, and randomly allocated to 14 groups (Braford = 8; Brahman x British = 6). Groups were randomly assigned to the control or acclimation treatment. In yr 2, cows were reevaluated within 45 d after weaning (August 2007) for BW, BCS, and temperament, stratified, and divided into 14 groups similarly as in yr 1, but in such a way that cows received the same treatment assigned in yr 1. Cows were acclimated to human interaction from August to January, and the acclimation process consisted of the same person visiting groups twice weekly and offering approximately 0.05 kg of range cubes per cow (as-fed basis). In January of both years, cow temperament, BW, and BCS were reassessed and cows were exposed to a 90-d breeding season. Blood samples were collected at the beginning of the acclimation period (August) and breeding season (January) for determination of plasma cortisol, IGF-I, and acute phase proteins. A treatment x breed interaction was detected during yr 1 (P < 0.01) for pregnancy analysis because acclimated Braford cows conceived earlier and at a greater percentage (P < 0.01) compared with control cows. According to values obtained at the beginning of breeding and pooled across treatments and breeds, IGF-I concentrations and BCS affected quadratically (P < 0.05), and concentrations of ceruloplasmin and haptoglobin decreased linearly (P < 0.05), the probability of pregnancy during both years. Temperament and cortisol concentrations

  17. Acute exercise and physiological insulin induce distinct phosphorylation signatures on TBC1D1 and TBC1D4 in human skeletal muscle

    DEFF Research Database (Denmark)

    Treebak, Jonas Thue; Pehmøller, Christian; Kristensen, Jonas Møller

    2014-01-01

    We investigated the phosphorylation signatures of two Rab GTPase activating proteins TBC1D1 and TBC1D4 in human skeletal muscle in response to physical exercise and physiological insulin levels induced by a carbohydrate rich meal using a paired experimental design. Eight healthy male volunteers...... in response to physiological stimuli in human skeletal muscle and support the idea that Akt and AMPK are upstream kinases. TBC1D1 phosphorylation signatures were comparable between in vitro contracted mouse skeletal muscle and exercised human muscle, and we show that AMPK was regulating phosphorylation...... of these sites in mouse muscle. Contraction and exercise elicited a different phosphorylation pattern of TBC1D4 in mouse compared with human muscle, and although different circumstances in our experimental setup may contribute to this difference, the observation exemplifies that transferring findings between...

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

    Science.gov (United States)

    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…

  19. The Implementation of Clay Modeling and Rat Dissection into the Human Anatomy and Physiology Curriculum of a Large Urban Community College

    Science.gov (United States)

    Haspel, Carol; Motoike, Howard K.; Lenchner, Erez

    2014-01-01

    After a considerable amount of research and experimentation, cat dissection was replaced with rat dissection and clay modeling in the human anatomy and physiology laboratory curricula at La Guardia Community College (LAGCC), a large urban community college of the City University of New York (CUNY). This article describes the challenges faculty…

  20. The Implementation of Clay Modeling and Rat Dissection into the Human Anatomy and Physiology Curriculum of a Large Urban Community College

    Science.gov (United States)

    Haspel, Carol; Motoike, Howard K.; Lenchner, Erez

    2014-01-01

    After a considerable amount of research and experimentation, cat dissection was replaced with rat dissection and clay modeling in the human anatomy and physiology laboratory curricula at La Guardia Community College (LAGCC), a large urban community college of the City University of New York (CUNY). This article describes the challenges faculty…

  1. Expression of endogenic lectins and their glycoligands in the tear fluid, human corneal and conjunctival epithelium under physiological and disease conditions

    OpenAIRE

    Hrdličková, Enkela

    2016-01-01

    Purpose: Lectins play an important role in many biological processes. The aim of this work was to analyse mainly the expression of endogenic lectins, such as galectins and plant lectin, e.g. Dolichos biflorus agglutinin (DBA), and their glycoligands in the tear fluid, human corneal and conjunctival epithelium in physiological and disease conditions. Further, we studied the human natural antibody against Galα1,3Gal-R, which is mainly responsible for hyperacute rejection of xenografts transplan...

  2. Academic performance in human anatomy and physiology classes: a 2-yr study of academic motivation and grade expectation.

    Science.gov (United States)

    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.

  3. Do targeted written comments and the rubric method of delivery affect performance on future human physiology laboratory reports?

    Science.gov (United States)

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

    2016-09-01

    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 into four groups related to rubric delivery and targeted comments. All students received feedback via the same detailed grading rubric. At the end of the term, subjects provided consent and a self-assessment of their rubric viewing rate and preferences. There were no differences in laboratory report scores between groups (P = 0.86), although scores did improve over time (P < 0.01). Students receiving targeted comments self-reported viewing their rubric more often than students that received no comments (P = 0.02), but the viewing rate was independent of the rubric delivery method (P = 0.15). Subjects with high rubric viewing rates did not have higher laboratory report grades than subjects with low viewing rates (P = 0.64). When asked about their preference for the future, 43% of respondents preferred the same method again (electronic or paper rubric) and 25% had no preference. We conclude that although student laboratory report grades improved over time, the rate and degree of improvement were not related to rubric delivery method or to the inclusion of targeted comments.

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

    Science.gov (United States)

    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

  5. Support vector machines to detect physiological patterns for EEG and EMG-based human-computer interaction: a review

    Science.gov (United States)

    Quitadamo, L. R.; Cavrini, F.; Sbernini, L.; Riillo, F.; Bianchi, L.; Seri, S.; Saggio, G.

    2017-02-01

    Support vector machines (SVMs) are widely used classifiers for detecting physiological patterns in human-computer interaction (HCI). Their success is due to their versatility, robustness and large availability of free dedicated toolboxes. Frequently in the literature, insufficient details about the SVM implementation and/or parameters selection are reported, making it impossible to reproduce study analysis and results. In order to perform an optimized classification and report a proper description of the results, it is necessary to have a comprehensive critical overview of the applications of SVM. The aim of this paper is to provide a review of the usage of SVM in the determination of brain and muscle patterns for HCI, by focusing on electroencephalography (EEG) and electromyography (EMG) techniques. In particular, an overview of the basic principles of SVM theory is outlined, together with a description of several relevant literature implementations. Furthermore, details concerning reviewed papers are listed in tables and statistics of SVM use in the literature are presented. Suitability of SVM for HCI is discussed and critical comparisons with other classifiers are reported.

  6. Role of leptin in energy-deprivation states: normal human physiology and clinical implications for hypothalamic amenorrhoea and anorexia nervosa.

    Science.gov (United States)

    Chan, Jean L; Mantzoros, Christos S

    Leptin is an adipocyte-secreted hormone that plays a key part in energy homoeostasis. Advances in leptin physiology have established that the main role of this hormone is to signal energy availability in energy-deficient states. Studies in animals and human beings have shown that low concentrations of leptin are fully or partly responsible for starvation-induced changes in neuroendocrine axes, including low reproductive, thyroid, and insulin-like growth factor (IGF) hormones. Disease states such as exercise-induced hypothalamic amenorrhoea and anorexia nervosa are also associated with low concentrations of leptin and a similar spectrum of neuroendocrine abnormalities. We have recently shown in an interventional, proof-of-concept study that leptin can restore ovulatory menstrual cycles and improve reproductive, thyroid, and IGF hormones and bone markers in hypothalamic amenorrhoea. Further studies are warranted to establish the safety and effectiveness of leptin for the infertility and osteoporosis associated with hypothalamic amenorrhoea, and to clarify its role in anorexia nervosa.

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

    Science.gov (United States)

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

    Science.gov (United States)

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

    2009-10-01

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

  9. Patch clamp studies of human sperm under physiological ionic conditions reveal three functionally and pharmacologically distinct cation channels.

    Science.gov (United States)

    Mansell, S A; Publicover, S J; Barratt, C L R; Wilson, S M

    2014-05-01

    Whilst fertilizing capacity depends upon a K(+) conductance (GK) that allows the spermatozoon membrane potential (Vm) to be held at a negative value, the characteristics of this conductance in human sperm are virtually unknown. We therefore studied the biophysical/pharmacological properties of the K(+) conductance in spermatozoa from normal donors held under voltage/current clamp in the whole cell recording configuration. Our standard recording conditions were designed to maintain quasi-physiological, Na(+), K(+) and Cl(-) gradients. Experiments that explored the effects of ionic substitution/ion channel blockers upon membrane current/potential showed that resting Vm was dependent upon a hyperpolarizing K(+) current that flowed via channels that displayed only weak voltage dependence and limited (∼7-fold) K(+) versus Na(+) selectivity. This conductance was blocked by quinidine (0.3 mM), bupivacaine (3 mM) and clofilium (50 µM), NNC55-0396 (2 µM) and mibefradil (30 µM), but not by 4-aminopyridine (2 mM, 4-AP). Progesterone had no effect upon the hyperpolarizing K(+) current. Repolarization after a test depolarization consistently evoked a transient inward 'tail current' (ITail) that flowed via a second population of ion channels with poor (∼3-fold) K(+) versus Na(+) selectivity. The activity of these channels was increased by quinidine, 4-AP and progesterone. Vm in human sperm is therefore dependent upon a hyperpolarizing K(+) current that flows via channels that most closely resemble those encoded by Slo3. Although 0.5 µM progesterone had no effect upon these channels, this hormone did activate the pharmacologically distinct channels that mediate ITail. In conclusion, this study reveals three functionally and pharmacologically distinct cation channels: Ik, ITail, ICatSper.

  10. Physiological Acoustics

    Science.gov (United States)

    Young, Eric D.

    The analysis of physiological sound in the peripheral auditory system solves three important problems. First, sound energy impinging on the head must be captured and presented to the transduction apparatus in the ear as a suitable mechanical signal; second, this mechanical signal needs to be transduced into a neural representation that can be used by the brain; third, the resulting neural representation needs to be analyzed by central neurons to extract information useful to the animal. This chapter provides an overview of some aspects of the first two of these processes. The description is entirely focused on the mammalian auditory system, primarily on human hearing and on the hearing of a few commonly used laboratory animals (mainly rodents and carnivores). Useful summaries of non-mammalian hearing are available [1]. Because of the large size of the literature, review papers are referenced wherever possible.

  11. Physiology of sport.

    Science.gov (United States)

    Maughan, Ron

    2007-07-01

    The elite athlete represents the extreme of the human gene pool, where genetic endowment is developed by an intensive training programme. Sport encompasses many different activities, calling for different physical and mental attributes. Understanding the physiology of exercise provides insights into normal physiological function.

  12. Human exercise physiology

    DEFF Research Database (Denmark)

    Volianitis, Stefanos; Secher, Niels H.

    2009-01-01

    that relates to the occurrence of hypoxia/anoxia in the natural life of the animal. The hypoxic/anoxic performance of the heart muscle correlates positively with the glycolytic capacity relative to the aerobic capacity, and this performance also tends to be high in hearts having a low aerobic or maximal...

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

    Science.gov (United States)

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

    2011-01-01

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

  14. Detailed Physiologic Characterization Reveals Diverse Mechanisms for Novel Genetic Loci Regulating Glucose and Insulin Metabolism in Humans

    Science.gov (United States)

    Ingelsson, Erik; Langenberg, Claudia; Hivert, Marie-France; Prokopenko, Inga; Lyssenko, Valeriya; Dupuis, Josée; Mägi, Reedik; Sharp, Stephen; Jackson, Anne U.; Assimes, Themistocles L.; Shrader, Peter; Knowles, Joshua W.; Zethelius, Björn; Abbasi, Fahim A.; Bergman, Richard N.; Bergmann, Antje; Berne, Christian; Boehnke, Michael; Bonnycastle, Lori L.; Bornstein, Stefan R.; Buchanan, Thomas A.; Bumpstead, Suzannah J.; Böttcher, Yvonne; Chines, Peter; Collins, Francis S.; Cooper, Cyrus C.; Dennison, Elaine M.; Erdos, Michael R.; Ferrannini, Ele; Fox, Caroline S.; Graessler, Jürgen; Hao, Ke; Isomaa, Bo; Jameson, Karen A.; Kovacs, Peter; Kuusisto, Johanna; Laakso, Markku; Ladenvall, Claes; Mohlke, Karen L.; Morken, Mario A.; Narisu, Narisu; Nathan, David M.; Pascoe, Laura; Payne, Felicity; Petrie, John R.; Sayer, Avan A.; Schwarz, Peter E. H.; Scott, Laura J.; Stringham, Heather M.; Stumvoll, Michael; Swift, Amy J.; Syvänen, Ann-Christine; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Tönjes, Anke; Valle, Timo T.; Williams, Gordon H.; Lind, Lars; Barroso, Inês; Quertermous, Thomas; Walker, Mark; Wareham, Nicholas J.; Meigs, James B.; McCarthy, Mark I.; Groop, Leif; Watanabe, Richard M.; Florez, Jose C.

    2010-01-01

    OBJECTIVE Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084). RESULTS The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 × 10−71). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction. CONCLUSIONS Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes. PMID:20185807

  15. Bilirubin activates transcription of HIF-1α in human proximal tubular cells cultured in the physiologic oxygen content.

    Science.gov (United States)

    Kim, Sung Gyun; Ahn, Shin-Young; Lee, Eun Seong; Kim, Sejoong; Na, Ki Young; Chae, Dong-Wan; Chin, Ho Jun

    2014-09-01

    The expression of hypoxia-inducible factor (HIF) is influenced by reactive oxygen species (ROS). Effect of bilirubin on HIF-1 expression in proximal tubular cells was investigated under physiological oxygen concentration, which is relative hypoxic condition mimicking oxygen content in the medulla of renal tissue. The human kidney (HK2) cells were cultured in 5% oxygen with or without bilirubin. HIF-1α protein expression was increased by bilirubin treatment at 0.01-0.2 mg/dL concentration. The messenger RNA expression of HIF-1α was increased by 1.69±0.05 folds in the cells cultured with 0.1 mg/dL bilirubin, compared to the control cells. The inhibitors of PI3K/mTOR, PI3K/AKT, and ERK 1/2 pathways did not attenuate increased HIF-1α expression by bilirubin. HIF-1α expression decreased by 10 µM exogenous hydrogen peroxide (H2O2); scavenger of ROS with or without bilirubin in the HK2 cells increased HIF-1α concentration more than that in the cells without bilirubin. Exogenous H2O2 decreased the phosphorylation of P70S6 kinase, which was completely reversed by bilirubin treatment. Knockdown of NOX4 gene by small interfering RNA (siRNA) increased HIF-1α mRNA expression. In coonclusion, bilirubin enhances HIF-1α transcription as well as the up-regulation of HIF-1α protein translation through the attenuation of ROS and subunits of NADPH oxidase.

  16. AltitudeOmics: the integrative physiology of human acclimatization to hypobaric hypoxia and its retention upon reascent.

    Directory of Open Access Journals (Sweden)

    Andrew W Subudhi

    Full Text Available An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics project aimed to bridge this gap. Our goals were 1 to describe a phenotype for successful acclimatization and assess its retention and 2 use these findings as a foundation for companion mechanistic studies. Our approach was to characterize acclimatization by measuring changes in arterial oxygenation and hemoglobin concentration [Hb], acute mountain sickness (AMS, cognitive function, and exercise performance in 21 subjects as they acclimatized to 5260 m over 16 days. We then focused on the retention of acclimatization by having subjects reascend to 5260 m after either 7 (n = 14 or 21 (n = 7 days at 1525 m. At 16 days at 5260 m we observed: 1 increases in arterial oxygenation and [Hb] (compared to acute hypoxia: PaO2 rose 9±4 mmHg to 45±4 while PaCO2 dropped a further 6±3 mmHg to 21±3, and [Hb] rose 1.8±0.7 g/dL to 16±2 g/dL; 2 no AMS; 3 improved cognitive function; and 4 improved exercise performance by 8±8% (all changes p<0.01. Upon reascent, we observed retention of arterial oxygenation but not [Hb], protection from AMS, retention of exercise performance, less retention of cognitive function; and noted that some of these effects lasted for 21 days. Taken together, these findings reveal new information about retention of acclimatization, and can be used as a physiological foundation to explore the molecular mechanisms of acclimatization and its retention.

  17. Characterization of the interaction between human lactoferrin and lomefloxacin at physiological condition: Multi-spectroscopic and modeling description

    Energy Technology Data Exchange (ETDEWEB)

    Chamani, J., E-mail: Chamani@ibb.ut.ac.i [Department of Biology, Faculty of Science, Islamic Azad University-Mashhad Branch, Mashhad (Iran, Islamic Republic of); Tafrishi, N. [Department of Biology, Faculty of Science, Islamic Azad University-Mashhad Branch, Mashhad (Iran, Islamic Republic of); Momen-Heravi, M. [Department of Chemistry, Faculty of Science, Islamic Azad University-Mashhad Branch, Mashhad (Iran, Islamic Republic of)

    2010-07-15

    The interaction between lomefloxacin (LMF) and human lactoferrin (Hlf) was studied by using fluorescence, circular dichroism (CD) spectroscopic and molecular modeling measurements. By the fluorescence quenching results, it was found that the binding constant K{sub A}=8.69x10{sup 5} L mol{sup -1}, and number of binding sites n=1.75 at physiological condition. Experimental results observed showed that the binding of LMF to Hlf induced conformational changes of Hlf. The participation of tyrosyl and tryptophanyl residues of protein was also estimated in the drug-Hlf complex by synchronous fluorescence. The quantitative analysis data of far-UV CD spectra from that of the alpha-helix 37.4% in free Hlf to 30.2% in the LMF-Hlf complex further confirmed that secondary structure of the protein was changed by LMF. Near-UV CD showed perturbations around tryptophan and tyrosine residues which involves perturbations of tertiary structure. The thermodynamic parameters like, DELTAH{sup o} and DELTAS{sup o}, have been calculated to be 63.411 kJ mol{sup -1} and 231.104 J mol{sup -1} K{sup -1}, respectively. Thermodynamic analysis showed that hydrophobic interactions were the main force in the binding site but the hydrogen bonding and electrostatic interaction could not be excluded which in agreement with the result of molecular docking study. The distance r between donor and acceptor was obtained according to fluorescence resonance energy transfer (FRET) and found to be 1.78 nm. The interaction between LMF and Hlf has been verified as consistent with the static quenching procedure and the quenching mechanism is related to the energy transfer. Furthermore, the study of molecular modeling that LMF could bind to the alpha-helixes between Pro145-Asn152 and Phe167-Gln172 regions and hydrophobic interaction was the major acting force for the binding site, which was in agreement with the thermodynamic analysis.

  18. Human Cells Cultured under Physiological Oxygen Utilize Two Cap-binding Proteins to recruit Distinct mRNAs for Translation.

    Science.gov (United States)

    Timpano, Sara; Uniacke, James

    2016-05-13

    Translation initiation is a focal point of translational control and requires the binding of eIF4E to the 5' cap of mRNA. Under conditions of extreme oxygen depletion (hypoxia), human cells repress eIF4E and switch to an alternative cap-dependent translation mediated by a homolog of eIF4E, eIF4E2. This homolog forms a complex with the oxygen-regulated hypoxia-inducible factor 2α and can escape translation repression. This complex mediates cap-dependent translation under cell culture conditions of 1% oxygen (to mimic tumor microenvironments), whereas eIF4E mediates cap-dependent translation at 21% oxygen (ambient air). However, emerging evidence suggests that culturing cells in ambient air, or "normoxia," is far from physiological or "normal." In fact, oxygen in human tissues ranges from 1-11% or "physioxia." Here we show that two distinct modes of cap-dependent translation initiation are active during physioxia and act on separate pools of mRNAs. The oxygen-dependent activities of eIF4E and eIF4E2 are elucidated by observing their polysome association and the status of mammalian target of rapamycin complex 1 (eIF4E-dependent) or hypoxia-inducible factor 2α expression (eIF4E2-dependent). We have identified oxygen conditions where eIF4E is the dominant cap-binding protein (21% normoxia or standard cell culture conditions), where eIF4E2 is the dominant cap-binding protein (1% hypoxia or ischemic diseases and cancerous tumors), and where both cap-binding proteins act simultaneously to initiate the translation of distinct mRNAs (1-11% physioxia or during development and stem cell differentiation). These data suggest that the physioxic proteome is generated by initiating translation of mRNAs via two distinct but complementary cap-binding proteins.

  19. 人体生理反应与纺织品感觉评价%APPLICATIONS OF HUMAN PHYSIOLOGICAL RESPONSES IN THE SENSATIONAL EVALUATION OF TEXTILE FABRICS

    Institute of Scientific and Technical Information of China (English)

    潘志娟; 李栋高

    2001-01-01

    We introduced the applications of human physiological responses in the sensational evaluation of textile fabrics and analyzed the problems existing in the present researches. Better ways are suggested.%主要介绍了人体生理反应在纺织品感觉评价上的应用状况,分析了目前的研究中存在的问题并提出了有关的改进方案。

  20. The calculation of human toxicity thresholds of 2,3,7,8-TCDD; A Physiologically Based Pharmacokinetic modeling approach

    NARCIS (Netherlands)

    Zeilmaker MJ; van Eijkeren JCH; LBO

    1998-01-01

    Dit rapport beschrijft de toepassing van een 'Physiologically Based PharmacoKinetic' model (PBPK model) bij het berekenen van de verwachte 'No Adverse Effect Level' van 2,3,7,8-TetraChloroDibenzo-p-Dioxine (TCDD) bij de mens. Het model houdt rekening met variabiliteit en onzeker

  1. Central Respiratory Chemosensitivity and Cerebrovascular CO[subscript 2] Reactivity: A Rebreathing Demonstration Illustrating Integrative Human Physiology

    Science.gov (United States)

    MacKay, Christina M.; Skow, Rachel J.; Tymko, Michael M.; Boulet, Lindsey M.; Davenport, Margie H.; Steinback, Craig D.; Ainslie, Philip N.; Lemieux, Chantelle C. M.; Day, Trevor A.

    2016-01-01

    One of the most effective ways of engaging students of physiology and medicine is through laboratory demonstrations and case studies that combine 1) the use of equipment, 2) problem solving, 3) visual representations, and 4) manipulation and interpretation of data. Depending on the measurements made and the type of test, laboratory demonstrations…

  2. A microfluidic cell culture device (μFCCD) to culture epithelial cells with physiological and morphological properties that mimic those of the human intestine.

    Science.gov (United States)

    Chi, Meiying; Yi, Banya; Oh, Seunghan; Park, Dong-June; Sung, Jong Hwan; Park, Sungsu

    2015-01-01

    Physiological and morphological properties of the human intestine cannot be accurately mimicked in conventional culture devices such as well plates and petri dishes where intestinal epithelial cells form a monolayer with loose contacts among cells. Here, we report a novel microfluidic cell culture device (μFCCD) that can be used to culture cells as a human intestinal model. This device enables intestinal epithelial cells (Caco-2) to grow three-dimensionally on a porous membrane coated with fibronectin between two polydimethylsiloxane (PDMS) layers. Within 3 days, Caco-2 cells cultured in the μFCCD formed villi- and crypt-like structures with small intercellular spaces, while individual cells were tightly connected to one another through the expression of the tight junction protein occludin, and were covered with a secreted mucin, MUC-2. Caco-2 cells cultured in the μFCCD for 3 days were less susceptible to bacterial attack than those cultured in transwell plates for 21 days. μFCCD-cultured Caco-2 cells also displayed physiologically relevant absorption and paracellular transport properties. These results suggest that our intestinal model more accurately mimics the morphological and physiological properties of the intestine in vivo than the conventional transwell culture model.

  3. Fetal cardiovascular physiology.

    Science.gov (United States)

    Rychik, J

    2004-01-01

    The cardiovascular system of the fetus is physiologically different than the adult, mature system. Unique characteristics of the myocardium and specific channels of blood flow differentitate the physiology of the fetus from the newborn. Conditions of increased preload and afterload in the fetus, such as sacrococcygeal teratoma and twin-twin transfusion syndrome, result in unique and complex pathophysiological states. Echocardiography has improved our understanding of human fetal cadiovasvular physiology in the normal and diseased states, and has expanded our capability to more effectively treat these disease processes.

  4. Human plasma concentrations of five cytochrome P450 probes extrapolated from pharmacokinetics in dogs and minipigs using physiologically based pharmacokinetic modeling.

    Science.gov (United States)

    Shida, Satomi; Yamazaki, Hiroshi

    2016-09-01

    The pharmacokinetics of cytochrome P450 probes in humans can be extrapolated from corresponding data in cynomolgus monkeys using simplified physiologically based pharmacokinetic (PBPK) modeling. In the current study, despite some species difference in drug clearances, this modeling methodology was adapted to estimate human plasma concentrations of P450 probes based on data from commonly used medium-sized experimental animals, namely dogs and minipigs. Using known species allometric scaling factors and in vitro metabolic clearance data, the observed plasma concentrations of slowly eliminated caffeine and warfarin and rapidly eliminated omeprazole, metoprolol and midazolam in two young dogs were scaled to human oral monitoring equivalents. Using the same approach, the previously reported pharmacokinetics of the five P450 probes in minipigs was also scaled to human monitoring equivalents. The human plasma concentration profiles of the five P450 probes estimated by the simplified human PBPK models based on observed/reported pharmacokinetics in dogs/minipigs were consistent with previously published pharmacokinetic data in humans. These results suggest that dogs and minipigs, in addition to monkeys, could be suitable models for humans during research into new drugs, especially when used in combination with simple PBPK models.

  5. 医学生理学教学与人文教育的融合之策略%Practice of Medicinal Humanism Eeducation in Physiology Teaching

    Institute of Scientific and Technical Information of China (English)

    曾俊伟; 田虹; 刘晓红

    2013-01-01

    Nowadays, it is a very important problem about how to improving medical students' quality in humanities in contemporary medical education. Physiology is a basic course for medical education. This paper explore how to achieve the integration between humanistic quality in medical education and physiology teaching.%加强人文素质教育是当代医学教育面临的重要问题。生理学是医学教育中一门重要的基础学科,在生理学教学过程中,应从理论课程和实验课两方面着手进行人文教育,将医学生理学专业教学与人文素质教育有机融合起来。

  6. The role of glucagon-like peptide 1 in glucose homeostasis and in other aspects of human physiology.

    Science.gov (United States)

    Franek, Edward; Gajos, Grzegorz; Gumprecht, Janusz; Kretowski, Adam; Zahorska-Markiewicz, Barbara; Małecki, Maciej T

    2009-11-01

    This paper reviews the structure, function, and pathophysiology of glucagon-like peptide 1 (GLP-1). It describes the physiology and pathophysiology of the incretin axis, of which GLP-1 is a component, as well as the biosynthesis, secretion, activity, and degradation of this intestinal hormone. Effects of GLP-1 on the endocrine function of the pancreas, cardiovascular system, central nervous system, and on water-electrolyte balance have been also presented.

  7. Effects of thermal discomfort in an office on perceived air quality, SBS symptoms, physiological responses and human performance

    DEFF Research Database (Denmark)

    Lan, Li; Wargocki, Pawel; Wyon, David Peter

    2011-01-01

    °C) and while warm (at 30°C). Multiple physiological measurements and subjective assessment were made. The results show that when the subjects felt warm, they assessed the air quality to be worse, reported increased intensity of many sick building syndrome symptoms, expressed more negative mood......, and were less willing to exert effort. Task performance decreased when the subjects felt warm. Their heart rate, respiratory ventilation, and end-tidal partial pressure of carbon dioxide increased significantly, and their arterial oxygen saturation decreased. Tear film quality was found to be significantly...

  8. Intragastric formation and modulation of N-nitrosodimethylamine in a dynamic in vitro gastrointestinal model under human physiological conditions

    NARCIS (Netherlands)

    Krul, C.A.M.; Zeilmaker, M.J.; Schothorst, R.C.; Havenaar, R.

    2004-01-01

    Human exposure to carcinogenic N-alkylnitrosamines can occur exogenously via food consumption or endogenously by formation of these compounds through nitrosation of amine precursors. Information on the intragastric formation of NDMA from complex mixtures of precursors and inhibitors in humans is not

  9. Learning Outcomes and Student-Perceived Value of Clay Modeling and Cat Dissection in Undergraduate Human Anatomy and Physiology

    Science.gov (United States)

    DeHoff, Mary Ellen; Clark, Krista L.; Meganathan, Karthikeyan

    2011-01-01

    Alternatives and/or supplements to animal dissection are being explored by educators of human anatomy at different academic levels. Clay modeling is one such alternative that provides a kinesthetic, three-dimensional, constructive, and sensory approach to learning human anatomy. The present study compared two laboratory techniques, clay modeling…

  10. Learning Outcomes and Student-Perceived Value of Clay Modeling and Cat Dissection in Undergraduate Human Anatomy and Physiology

    Science.gov (United States)

    DeHoff, Mary Ellen; Clark, Krista L.; Meganathan, Karthikeyan

    2011-01-01

    Alternatives and/or supplements to animal dissection are being explored by educators of human anatomy at different academic levels. Clay modeling is one such alternative that provides a kinesthetic, three-dimensional, constructive, and sensory approach to learning human anatomy. The present study compared two laboratory techniques, clay modeling…

  11. From space to Earth: advances in human physiology from 20 years of bed rest studies (1986-2006).

    Science.gov (United States)

    Pavy-Le Traon, A; Heer, M; Narici, M V; Rittweger, J; Vernikos, J

    2007-09-01

    Bed rest studies of the past 20 years are reviewed. Head-down bed rest (HDBR) has proved its usefulness as a reliable simulation model for the most physiological effects of spaceflight. As well as continuing to search for better understanding of the physiological changes induced, these studies focused mostly on identifying effective countermeasures with encouraging but limited success. HDBR is characterised by immobilization, inactivity, confinement and elimination of Gz gravitational stimuli, such as posture change and direction, which affect body sensors and responses. These induce upward fluid shift, unloading the body's upright weight, absence of work against gravity, reduced energy requirements and reduction in overall sensory stimulation. The upward fluid shift by acting on central volume receptors induces a 10-15% reduction in plasma volume which leads to a now well-documented set of cardiovascular changes including changes in cardiac performance and baroreflex sensitivity that are identical to those in space. Calcium excretion is increased from the beginning of bed rest leading to a sustained negative calcium balance. Calcium absorption is reduced. Body weight, muscle mass, muscle strength is reduced, as is the resistance of muscle to insulin. Bone density, stiffness of bones of the lower limbs and spinal cord and bone architecture are altered. Circadian rhythms may shift and are dampened. Ways to improve the process of evaluating countermeasures--exercise (aerobic, resistive, vibration), nutritional and pharmacological--are proposed. Artificial gravity requires systematic evaluation. This review points to clinical applications of BR research revealing the crucial role of gravity to health.

  12. A Multi-Wavelength Opto-Electronic Patch Sensor to Effectively Detect Physiological Changes against Human Skin Types.

    Science.gov (United States)

    Yan, Liangwen; Hu, Sijung; Alzahrani, Abdullah; Alharbi, Samah; Blanos, Panagiotis

    2017-06-21

    Different skin pigments among various ethnic group people have an impact on spectrometric illumination on skin surface. To effectively capture photoplethysmographic (PPG) signals, a multi-wavelength opto-electronic patch sensor (OEPS) together with a schematic architecture of electronics were developed to overcome the drawback of present PPG sensor. To perform a better in vivo physiological measurement against skin pigments, optimal illuminations in OEPS, whose wavelength is compatible with a specific skin type, were optimized to capture a reliable physiological sign of heart rate (HR). A protocol was designed to investigate an impact of five skin types in compliance with Von Luschan's chromatic scale. Thirty-three healthy male subjects between the ages of 18 and 41 were involved in the protocol implemented by means of the OEPS system. The results show that there is no significant difference (p: 0.09, F = 3.0) in five group tests with the skin types across various activities throughout a series of consistent measurements. The outcome of the present study demonstrates that the OEPS, with its multi-wavelength illumination characteristics, could open a path in multiple applications of different ethnic groups with cost-effective health monitoring.

  13. Expression of calcitonin gene-related peptide-receptor component protein (CGRP-RCP) in human myometrium in differing physiological states and following misoprostol administration.

    Science.gov (United States)

    Goharkhay, Nina; Lu, Jing; Felix, Juan C; Wing, Deborah A

    2007-09-01

    Our objective was to assess relative expression levels of mRNA for calcitonin gene-related peptide-receptor component protein (CGRP-RCP) in human myometrium in various physiological states. Using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), we analyzed myometrial samples from 46 women (10 menopausal, 10 nongravid premenopausal, 19 gravidae, and 7 premenopausal misoprostol-treated nongravid women) for the specific expression of CGRP-RCP mRNA. The expression of CGRP-RCP was significantly increased in gravid compared with nongravid myometrium ( P RCP expression were found among the other study groups. We concluded that the increased mRNA expression CGRP-RCP in gravid myometrium supports the possibility of involvement of CGRP in the control of myometrial contractility. Additional studies are necessary to evaluate the exact mechanism of action of CGRP and CGRP-RCP in human myometrium.

  14. Relationship between Mood Change, Odour and Its Physiological Effects in Humans While Inhaling the Fragrances of Essential Oils as well as Linalool and Its Enantiomers

    Directory of Open Access Journals (Sweden)

    Tomomi Matumura

    2013-03-01

    Full Text Available Humans can detect and discriminate a vast number of odours. The number perceived as distinguishable is estimated to be more than ten thousand. Humans are capable of distinguishing even slight alterations in the structure of an odorous molecule. A pair of enantiomers of an odorant, which possess the same molecular structures except for the chiral position, can trigger profoundly different odour perceptions. How precisely can humans and their olfactory system detect and discriminate such a great variety of odours and such subtle differences in the molecular structures? In a series of studies, we have attempted to examine the relationship between mood change, odour and its physiological effects, by focusing on the possible verbal and non-verbal changes in humans induced by smelling the fragrances of essential oils as well as linalool and its enantiometric isomers. In this article, we provide an overview of our recent verbal and non-verbal studies. We then discuss how our findings may contribute to the assessment of psychophysiological responses of essential oils as well as how our research can contribute to the study of human chemoreception science, by shedding light on the sophistication of the olfactory system in its ability to detect and discriminate odors.

  15. Mathematical physiology

    CERN Document Server

    Sneyd, James

    2009-01-01

    There has been a long history of interaction between mathematics and physiology. This book looks in detail at a wide selection of mathematical models in physiology, showing how physiological problems can be formulated and studied mathematically, and how such models give rise to interesting and challenging mathematical questions. With its coverage of many recent models it gives an overview of the field, while many older models are also discussed, to put the modern work in context. In this second edition the coverage of basic principles has been expanded to include such topics as stochastic differential equations, Markov models and Gibbs free energy, and the selection of models has also been expanded to include some of the basic models of fluid transport, respiration/perfusion, blood diseases, molecular motors, smooth muscle, neuroendrocine cells, the baroreceptor loop, turboglomerular oscillations, blood clotting and the retina. Owing to this extensive coverage, the second edition is published in two volumes. ...

  16. A semi-physiological model of amyloid-β biosynthesis and clearance in human cerebrospinal fluid: a tool for alzheimer's disease research and drug development.

    Science.gov (United States)

    Haug, Karin G; Staab, Alexander; Dansirikul, Chantaratsamon; Lehr, Thorsten

    2013-07-01

    Stable isotope labeling kinetics (SILK) was successfully applied to quantify endogenous amyloid-β (Aβ) metabolism in human cerebrospinal fluid (CSF). A semi-physiological model describing Aβ biosynthesis and degradation in human CSF and the impact of the γ-secretase inhibitor semagacestat should be developed and validated based on digitized data from three published SILK studies. Aβ biosynthesis was adequately characterized by six transit compartments. At each transition step, a first-order degradation process was implemented. A two-compartment model best described semagacestat CSF concentration-time profiles. Semagacestat concentrations were linked to the Aβ production by an inhibitory Emax model. For model validation, three individual Aβ profiles from literature were successfully predicted. Model application demonstrated a 35% decreased Aβ elimination rate constant in Alzheimer's disease (AD) patients. Study design optimization revealed that SILK studies could be conducted with significant less sampling points compared to the standard protocol without losing information about the Aβ metabolism, if analyzed by the presented model. In conclusion, the analysis outlined the advantages and opportunities of integrating all available data and knowledge into a semi-physiological model. The model can serve as valuable tool for researchers and clinicians interested in the pathology of AD as well as in the development of new therapeutics for AD.

  17. A YAP/TAZ-miR-130/301 molecular circuit exerts systems-level control of fibrosis in a network of human diseases and physiologic conditions

    Science.gov (United States)

    Bertero, Thomas; Cottrill, Katherine A.; Annis, Sofia; Bhat, Balkrishen; Gochuico, Bernadette R.; Osorio, Juan C.; Rosas, Ivan; Haley, Kathleen J.; Corey, Kathleen E.; Chung, Raymond T.; Nelson Chau, B.; Chan, Stephen Y.

    2015-01-01

    The molecular origins of fibrosis affecting multiple tissue beds remain incompletely defined. Previously, we delineated the critical role of the control of extracellular matrix (ECM) stiffening by the mechanosensitive microRNA-130/301 family, as activated by the YAP/TAZ co-transcription factors, in promoting pulmonary hypertension (PH). We hypothesized that similar mechanisms may dictate fibrosis in other tissue beds beyond the pulmonary vasculature. Employing an in silico combination of microRNA target prediction, transcriptomic analysis of 137 human diseases and physiologic states, and advanced gene network modeling, we predicted the microRNA-130/301 family as a master regulator of fibrotic pathways across a cohort of seemingly disparate diseases and conditions. In two such diseases (pulmonary fibrosis and liver fibrosis), inhibition of microRNA-130/301 prevented the induction of ECM modification, YAP/TAZ, and downstream tissue fibrosis. Thus, mechanical forces act through a central feedback circuit between microRNA-130/301 and YAP/TAZ to sustain a common fibrotic phenotype across a network of human physiologic and pathophysiologic states. Such re-conceptualization of interconnections based on shared systems of disease and non-disease gene networks may have broad implications for future convergent diagnostic and therapeutic strategies. PMID:26667495

  18. Genus-Wide Comparative Genomics of Malassezia Delineates Its Phylogeny, Physiology, and Niche Adaptation on Human Skin

    NARCIS (Netherlands)

    Wu, Guangxi; Zhao, He; Li, Chenhao; Rajapakse, Menaka Priyadarsani; Wong, Wing Cheong; Xu, Jun; Saunders, Charles W; Reeder, Nancy L; Reilman, Raymond A; Scheynius, Annika; Sun, Sheng; Billmyre, Blake Robert; Li, Wenjun; Averette, Anna Floyd; Mieczkowski, Piotr; Heitman, Joseph; Theelen, Bart; Schröder, Markus S; De Sessions, Paola Florez; Butler, Geraldine; Maurer-Stroh, Sebastian; Boekhout, Teun; Nagarajan, Niranjan; Dawson, Thomas L

    2015-01-01

    Malassezia is a unique lipophilic genus in class Malasseziomycetes in Ustilaginomycotina, (Basidiomycota, fungi) that otherwise consists almost exclusively of plant pathogens. Malassezia are typically isolated from warm-blooded animals, are dominant members of the human skin mycobiome and are

  19. Network physiology reveals relations between network topology and physiological function

    OpenAIRE

    Bashan, Amir; Bartsch, Ronny P.; Kantelhardt, Jan W.; Havlin, Shlomo; Ivanov, Plamen Ch.

    2012-01-01

    The human organism is an integrated network where complex physiological systems, each with its own regulatory mechanisms, continuously interact, and where failure of one system can trigger a breakdown of the entire network. Identifying and quantifying dynamical networks of diverse systems with different types of interactions is a challenge. Here we develop a framework to probe interactions among diverse systems, and we identify a physiological network. We find that each physiological state is...

  20. Identification of the Learning Styles in the Students of Exercise Physiology in the Rehabilitation and Human Development Faculty

    Directory of Open Access Journals (Sweden)

    Jorge Enrique Correa Bautista

    2006-10-01

    Full Text Available The object of this study is to identify the learningstyles (LS used by the students of the subjectof physiology of the exercise of the program ofRecibido: Marzo 13 de 2006.Aceptado: Junio 2 de 2006.* Fisioterapeuta. Candidato a Magíster en Fisiología.Profesor de carrera.Artículo originalPhysiotherapy, with the purpose of establishinga direct relationship later on between the learningstyles and the possible pedagogic strategiesthat but they favor the compression of the physiologyof the exercise 48 subject of second andthird year of career they were interviewed throughthe instrument standardized compound number(CHAEA. This study carried out an analysis descriptiveand of typical deviation of the data. Theywere differences statistically significant in thestyles of active and reflexive learning, in frontof the Theoretical and pragmatic styles what putsin evidence the necessity to generate pedagogicstrategies inside the subject that this chord withthe tendency of the active and reflexive learningof the students.

  1. Physiological and serological variation in S. mitis biovar 1 from the human oral cavity during the first year of life

    Science.gov (United States)

    Kirchherr, Jennifer L.; Bowden, George H.; Cole, Michael F.; Kawamura, Yoshiaki; Richmond, Dorothy A.; Sheridan, Michael J.; Wirth, Katherine A.

    2007-01-01

    SUMMARY Objective The purpose of the study was to explore the physiological and antigenic diversity of a large number of S. mitis biovar 1 isolates in order to begin to determine whether these properties contribute to species persistence. Design S. mitis biovar 1 was collected from four infants from birth to one year of age. At each of 8–9 visits 60 isolates each were obtained from the cheeks, tongue and incisors (once erupted) yielding 4,440 in total. These were tested for production of neuraminidase, β1-N-acetylglucosaminidase, β1-N-acetylgalactosaminidase, IgA1 protease, and amylase-binding. Antigenic diversity was examined by ELISA and Western immunoblotting using antisera raised against S. mitis biovar 1 NCTC 12261T and SK145. Results 3,330 (75%) of the isolates were identified as S. mitis biovar 1 and 3,144 (94.4%) could be divided into four large phenotypic groups based on glycosidase production. 54% of the isolates produced IgA1 protease, but production was disproportionate among the phenotypes. Between 1/3 to 1/2 of the strains of each phenotype bound salivary α-amylase. Antisera against strains NCTC 12261T and SK145 displayed different patterns of reactivity with randomly selected representatives of the four phenotypes. Conclusions S. mitis biovar 1 is physiologically and antigenically diverse, properties which could aid strains in avoiding host immunity and promote re-colonization of a habitat or transfer to a new habitat. PMID:17045561

  2. Reproductive physiology

    Science.gov (United States)

    Gee, G.F.; Russman, S.E.; Ellis, David H.; Gee, George F.; Mirande, Claire M.

    1996-01-01

    Conclusions: Although the general pattern of avian physiology applies to cranes, we have identified many physiological mechanisms (e.g., effects of disturbance) that need further study. Studies with cranes are expensive compared to those done with domestic fowl because of the crane's larger size, low reproductive rate, and delayed sexual maturity. To summarize, the crane reproductive system is composed of physiological and anatomical elements whose function is controlled by an integrated neural-endocrine system. Males generally produce semen at a younger age than when females lay eggs. Eggs are laid in clutches of two (1 to 3), and females will lay additional clutches if the preceding clutches are removed. Both sexes build nests and incubate the eggs. Molt begins during incubation and body molt may be completed annually in breeding pairs. However, remiges are replaced sequentially over 2 to 3 years, or abruptly every 2 to 3 years in other species. Most immature birds replace their juvenal remiges over a 2 to 3 year period. Stress interferes with reproduction in cranes by reducing egg production or terminating the reproductive effort. In other birds, stress elevates corticosterone levels and decreases LHRH release. We know little about the physiological response of cranes to stress.

  3. Exercise physiology

    DEFF Research Database (Denmark)

    Kiens, Bente; Richter, Erik; Wojtaszewski, Jørgen

    2014-01-01

    The passing of Professor Bengt Saltin on September 12, 2014 truly marks the end of an era. As editor of the Journal of Applied Physiology and one of Bengt’s many collaborators and colleagues, I wanted the Journal to celebrate his many seminal contributions by means of an Editorial. Professor Bent...

  4. Procedures of Exercise Physiology Laboratories

    Science.gov (United States)

    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. Use of physiologically based kinetic (PBK) modeling to study interindividual human variation and species differences in plasma concentrations of quercetin and its metabolites.

    Science.gov (United States)

    Boonpawa, Rungnapa; Moradi, Nooshin; Spenkelink, Albertus; Rietjens, Ivonne M C M; Punt, Ans

    2015-12-15

    Biological activities of flavonoids in vivo ultimately depend on the systemic bioavailability of the aglycones and their metabolites. We aimed to develop physiologically based kinetic (PBK) models to predict plasma concentrations of the flavonoid quercetin and its metabolites in individual human subjects and to define species differences compared with male rat. The human models were developed based on in vitro metabolic parameters derived from incubations with pooled and 20 individual human tissue fractions and by fitting kinetic parameters to available in vivo data. The outcomes obtained were compared to a previously developed model for quercetin and its metabolites formation in male rat. Quercetin-3'-O-glucuronide was predicted to be the major circulating metabolite in 19 out of 20 individuals, while in male rat di- and tri-conjugates of quercetin containing a glucuronic acid, sulfate and/or methyl moieties are the major metabolites. Significant species differences occur in major circulating metabolites of quercetin suggesting that rat is not an adequate model to study effects of quercetin in man. The defined PBK models can be used to guide the experimental design of in vitro experiments with flavonoids, especially to better take into account the relevance of metabolism and the contribution of metabolites to the biological activity in humans.

  6. Molecular, physiological, and motor performance defects in DMSXL mice carrying >1,000 CTG repeats from the human DM1 locus.

    Directory of Open Access Journals (Sweden)

    Aline Huguet

    Full Text Available Myotonic dystrophy type 1 (DM1 is caused by an unstable CTG repeat expansion in the 3'UTR of the DM protein kinase (DMPK gene. DMPK transcripts carrying CUG expansions form nuclear foci and affect splicing regulation of various RNA transcripts. Furthermore, bidirectional transcription over the DMPK gene and non-conventional RNA translation of repeated transcripts have been described in DM1. It is clear now that this disease may involve multiple pathogenic pathways including changes in gene expression, RNA stability and splicing regulation, protein translation, and micro-RNA metabolism. We previously generated transgenic mice with 45-kb of the DM1 locus and >300 CTG repeats (DM300 mice. After successive breeding and a high level of CTG repeat instability, we obtained transgenic mice carrying >1,000 CTG (DMSXL mice. Here we described for the first time the expression pattern of the DMPK sense transcripts in DMSXL and human tissues. Interestingly, we also demonstrate that DMPK antisense transcripts are expressed in various DMSXL and human tissues, and that both sense and antisense transcripts accumulate in independent nuclear foci that do not co-localize together. Molecular features of DM1-associated RNA toxicity in DMSXL mice (such as foci accumulation and mild missplicing, were associated with high mortality, growth retardation, and muscle defects (abnormal histopathology, reduced muscle strength, and lower motor performances. We have found that lower levels of IGFBP-3 may contribute to DMSXL growth retardation, while increased proteasome activity may affect muscle function. These data demonstrate that the human DM1 locus carrying very large expansions induced a variety of molecular and physiological defects in transgenic mice, reflecting DM1 to a certain extent. As a result, DMSXL mice provide an animal tool to decipher various aspects of the disease mechanisms. In addition, these mice can be used to test the preclinical impact of systemic

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

    Science.gov (United States)

    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.

  8. Molecular, physiological, and motor performance defects in DMSXL mice carrying >1,000 CTG repeats from the human DM1 locus.

    Science.gov (United States)

    Huguet, Aline; Medja, Fadia; Nicole, Annie; Vignaud, Alban; Guiraud-Dogan, Céline; Ferry, Arnaud; Decostre, Valérie; Hogrel, Jean-Yves; Metzger, Friedrich; Hoeflich, Andreas; Baraibar, Martin; Gomes-Pereira, Mário; Puymirat, Jack; Bassez, Guillaume; Furling, Denis; Munnich, Arnold; Gourdon, Geneviève

    2012-01-01

    Myotonic dystrophy type 1 (DM1) is caused by an unstable CTG repeat expansion in the 3'UTR of the DM protein kinase (DMPK) gene. DMPK transcripts carrying CUG expansions form nuclear foci and affect splicing regulation of various RNA transcripts. Furthermore, bidirectional transcription over the DMPK gene and non-conventional RNA translation of repeated transcripts have been described in DM1. It is clear now that this disease may involve multiple pathogenic pathways including changes in gene expression, RNA stability and splicing regulation, protein translation, and micro-RNA metabolism. We previously generated transgenic mice with 45-kb of the DM1 locus and >300 CTG repeats (DM300 mice). After successive breeding and a high level of CTG repeat instability, we obtained transgenic mice carrying >1,000 CTG (DMSXL mice). Here we described for the first time the expression pattern of the DMPK sense transcripts in DMSXL and human tissues. Interestingly, we also demonstrate that DMPK antisense transcripts are expressed in various DMSXL and human tissues, and that both sense and antisense transcripts accumulate in independent nuclear foci that do not co-localize together. Molecular features of DM1-associated RNA toxicity in DMSXL mice (such as foci accumulation and mild missplicing), were associated with high mortality, growth retardation, and muscle defects (abnormal histopathology, reduced muscle strength, and lower motor performances). We have found that lower levels of IGFBP-3 may contribute to DMSXL growth retardation, while increased proteasome activity may affect muscle function. These data demonstrate that the human DM1 locus carrying very large expansions induced a variety of molecular and physiological defects in transgenic mice, reflecting DM1 to a certain extent. As a result, DMSXL mice provide an animal tool to decipher various aspects of the disease mechanisms. In addition, these mice can be used to test the preclinical impact of systemic therapeutic

  9. The Importance of the Ionic Product for Water to Understand the Physiology of the Acid-Base Balance in Humans

    OpenAIRE

    Adeva-Andany, María M.; Natalia Carneiro-Freire; Cristóbal Donapetry-García; Eva Rañal-Muíño; Yosua López-Pereiro

    2014-01-01

    Human plasma is an aqueous solution that has to abide by chemical rules such as the principle of electrical neutrality and the constancy of the ionic product for water. These rules define the acid-base balance in the human body. According to the electroneutrality principle, plasma has to be electrically neutral and the sum of its cations equals the sum of its anions. In addition, the ionic product for water has to be constant. Therefore, the plasma concentration of hydrogen ions depends on th...

  10. Interleukin-15 plays a central role in human kidney physiology and cancer through the γc signaling pathway.

    Directory of Open Access Journals (Sweden)

    Julien Giron-Michel

    Full Text Available The ability of Interleukin-15 (IL-15 to activate many immune antitumor mechanisms renders the cytokine a good candidate for the therapy of solid tumors, particularly renal cell carcinoma. Although IL-15 is being currently used in clinical trials, the function of the cytokine on kidney's components has not been extensively studied; we thus investigated the role of IL-15 on normal and tumor renal epithelial cells. Herein, we analyzed the expression and the biological functions of IL-15 in normal renal proximal tubuli (RPTEC and in their neoplastic counterparts, the renal clear cell carcinomas (RCC. This study shows that RPTEC express a functional heterotrimeric IL-15Rαβγc complex whose stimulation with physiologic concentrations of rhIL-15 is sufficient to inhibit epithelial mesenchymal transition (EMT commitment preserving E-cadherin expression. Indeed, IL-15 is not only a survival factor for epithelial cells, but it can also preserve the renal epithelial phenotype through the γc-signaling pathway, demonstrating that the cytokine possess a wide range of action in epithelial homeostasis. In contrast, in RCC in vitro and in vivo studies reveal a defect in the expression of γc-receptor and JAK3 associated kinase, which strongly impacts IL-15 signaling. Indeed, in the absence of the γc/JAK3 couple we demonstrate the assembly of an unprecedented functional high affinity IL-15Rαβ heterodimer, that in response to physiologic concentrations of IL-15, triggers an unbalanced signal causing the down-regulation of the tumor suppressor gene E-cadherin, favoring RCC EMT process. Remarkably, the rescue of IL-15/γc-dependent signaling (STAT5, by co-transfecting γc and JAK3 in RCC, inhibits EMT reversion. In conclusion, these data highlight the central role of IL-15 and γc-receptor signaling in renal homeostasis through the control of E-cadherin expression and preservation of epithelial phenotype both in RPTEC (up-regulation and RCC (down-regulation.

  11. The circulatory and metabolic responses to hypoxia in humans - with special reference to adipose tissue physiology and obesity

    NARCIS (Netherlands)

    I. Heinonen (Ilkka); R. Boushel (Robert); K.K. Kalliokoski (Kari)

    2016-01-01

    textabstractAdipose tissue metabolism and circulation play an important role in human health. It is well-known that adipose tissue mass is increased in response to excess caloric intake leading to obesity and further to local hypoxia and inflammatory signaling. Acute exercise increases blood supply

  12. Open-Box Muscle-Computer Interface: Introduction to Human-Computer Interactions in Bioengineering, Physiology, and Neuroscience Courses

    Science.gov (United States)

    Landa-Jiménez, M. A.; González-Gaspar, P.; Pérez-Estudillo, C.; López-Meraz, M. L.; Morgado-Valle, C.; Beltran-Parrazal, L.

    2016-01-01

    A Muscle-Computer Interface (muCI) is a human-machine system that uses electromyographic (EMG) signals to communicate with a computer. Surface EMG (sEMG) signals are currently used to command robotic devices, such as robotic arms and hands, and mobile robots, such as wheelchairs. These signals reflect the motor intention of a user before the…

  13. Open-Box Muscle-Computer Interface: Introduction to Human-Computer Interactions in Bioengineering, Physiology, and Neuroscience Courses

    Science.gov (United States)

    Landa-Jiménez, M. A.; González-Gaspar, P.; Pérez-Estudillo, C.; López-Meraz, M. L.; Morgado-Valle, C.; Beltran-Parrazal, L.

    2016-01-01

    A Muscle-Computer Interface (muCI) is a human-machine system that uses electromyographic (EMG) signals to communicate with a computer. Surface EMG (sEMG) signals are currently used to command robotic devices, such as robotic arms and hands, and mobile robots, such as wheelchairs. These signals reflect the motor intention of a user before the…

  14. Evaluation of the interindividual human variation in bioactivation of methyleugenol using physiologically based kinetic modeling and Monte Carlo simulations

    Energy Technology Data Exchange (ETDEWEB)

    Al-Subeihi, Ala' A.A., E-mail: subeihi@yahoo.com [Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen (Netherlands); BEN-HAYYAN-Aqaba International Laboratories, Aqaba Special Economic Zone Authority (ASEZA), P. O. Box 2565, Aqaba 77110 (Jordan); Alhusainy, Wasma; Kiwamoto, Reiko; Spenkelink, Bert [Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen (Netherlands); Bladeren, Peter J. van [Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen (Netherlands); Nestec S.A., Avenue Nestlé 55, 1800 Vevey (Switzerland); Rietjens, Ivonne M.C.M.; Punt, Ans [Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen (Netherlands)

    2015-03-01

    The present study aims at predicting the level of formation of the ultimate carcinogenic metabolite of methyleugenol, 1′-sulfooxymethyleugenol, in the human population by taking variability in key bioactivation and detoxification reactions into account using Monte Carlo simulations. Depending on the metabolic route, variation was simulated based on kinetic constants obtained from incubations with a range of individual human liver fractions or by combining kinetic constants obtained for specific isoenzymes with literature reported human variation in the activity of these enzymes. The results of the study indicate that formation of 1′-sulfooxymethyleugenol is predominantly affected by variation in i) P450 1A2-catalyzed bioactivation of methyleugenol to 1′-hydroxymethyleugenol, ii) P450 2B6-catalyzed epoxidation of methyleugenol, iii) the apparent kinetic constants for oxidation of 1′-hydroxymethyleugenol, and iv) the apparent kinetic constants for sulfation of 1′-hydroxymethyleugenol. Based on the Monte Carlo simulations a so-called chemical-specific adjustment factor (CSAF) for intraspecies variation could be derived by dividing different percentiles by the 50th percentile of the predicted population distribution for 1′-sulfooxymethyleugenol formation. The obtained CSAF value at the 90th percentile was 3.2, indicating that the default uncertainty factor of 3.16 for human variability in kinetics may adequately cover the variation within 90% of the population. Covering 99% of the population requires a larger uncertainty factor of 6.4. In conclusion, the results showed that adequate predictions on interindividual human variation can be made with Monte Carlo-based PBK modeling. For methyleugenol this variation was observed to be in line with the default variation generally assumed in risk assessment. - Highlights: • Interindividual human differences in methyleugenol bioactivation were simulated. • This was done using in vitro incubations, PBK modeling

  15. Development of a Combined In Vitro Physiologically Based Kinetic (PBK) and Monte Carlo Modelling Approach to Predict Interindividual Human Variation in Phenol-Induced Developmental Toxicity.

    Science.gov (United States)

    Strikwold, Marije; Spenkelink, Bert; Woutersen, Ruud A; Rietjens, Ivonne M C M; Punt, Ans

    2017-06-01

    With our recently developed in vitro physiologically based kinetic (PBK) modelling approach, we could extrapolate in vitro toxicity data to human toxicity values applying PBK-based reverse dosimetry. Ideally information on kinetic differences among human individuals within a population should be considered. In the present study, we demonstrated a modelling approach that integrated in vitro toxicity data, PBK modelling and Monte Carlo simulations to obtain insight in interindividual human kinetic variation and derive chemical specific adjustment factors (CSAFs) for phenol-induced developmental toxicity. The present study revealed that UGT1A6 is the primary enzyme responsible for the glucuronidation of phenol in humans followed by UGT1A9. Monte Carlo simulations were performed taking into account interindividual variation in glucuronidation by these specific UGTs and in the oral absorption coefficient. Linking Monte Carlo simulations with PBK modelling, population variability in the maximum plasma concentration of phenol for the human population could be predicted. This approach provided a CSAF for interindividual variation of 2.0 which covers the 99th percentile of the population, which is lower than the default safety factor of 3.16 for interindividual human kinetic differences. Dividing the dose-response curve data obtained with in vitro PBK-based reverse dosimetry, with the CSAF provided a dose-response curve that reflects the consequences of the interindividual variability in phenol kinetics for the developmental toxicity of phenol. The strength of the presented approach is that it provides insight in the effect of interindividual variation in kinetics for phenol-induced developmental toxicity, based on only in vitro and in silico testing. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Functional Integrity of the Chimeric (Humanized) Mouse Liver: Enzyme Zonation, Physiologic Spaces, and Hepatic Enzymes and Transporters.

    Science.gov (United States)

    Chow, Edwin C Y; Wang, Jason Z Ya; Quach, Holly P; Tang, Hui; Evans, David C; Li, Albert P; Silva, Jose; Pang, K Sandy

    2016-09-01

    Chimeric mouse liver models are useful in vivo tools for human drug metabolism studies; however, liver integrity and the microcirculation remain largely uninvestigated. Hence, we conducted liver perfusion studies to examine these attributes in FRGN [Fah(-/-), Rag2(-/-), and Il2rg(-/-), NOD strain] livers (control) and chimeric livers repopulated with mouse (mFRGN) or human (hFRGN) hepatocytes. In single-pass perfusion studies (2.5 ml/min), outflow dilution profiles of noneliminated reference indicators ((51)Cr-RBC, (125)I-albumin, (14)C-sucrose, and (3)H-water) revealed preservation of flow-limited distribution and reduced water and albumin spaces in hFRGN livers compared with FRGN livers, a view supported microscopically by tightly packed sinusoids. With prograde and retrograde perfusion of harmol (50 µM) in FRGN livers, an anterior sulfation (Sult1a1) over the posterior distribution of glucuronidation (Ugt1a1) activity was preserved, evidenced by the 42% lower sulfation-to-glucuronidation ratio (HS/HG) and 14% higher harmol extraction ratio (E) upon switching from prograde to retrograde flow. By contrast, zonation was lost in mFRGN and hFRGN livers, with HS/HG and E for both flows remaining unchanged. Remnant mouse genes persisted in hFRGN livers (10%-300% those of FRGN). When hFRGN livers were compared with human liver tissue, higher UGT1A1 and MRP2, lower MRP3, and unchanged SULT1A1 and MRP4 mRNA expression were observed. Total Sult1a1/SULT1A1 protein expression in hFRGN livers was higher than that of FRGN livers, consistent with higher harmol sulfate formation. The composite data on humanized livers suggest a loss of zonation, lack of complete liver humanization, and persistence of murine hepatocyte activities leading to higher sulfation.

  17. Importance of Physical and Physiological Parameters in Simulated Particle Transport in the Alveolar Zone of the Human Lung

    Directory of Open Access Journals (Sweden)

    Dogan Ciloglu

    2017-01-01

    Full Text Available The trajectory and deposition efficiency of micron-sized (1–5 µm particles, inhaled into the pulmonary system, are accurately determined with the aid of a newly developed model and modified simulation techniques. This alveolar model, which has a simple but physiologically appropriate geometry, and the utilized fluid structure interaction (FSI methods permit the precise simulation of tissue wall deformation and particle fluid interactions. The relation between tissue movement and airflow in the alveolated duct is solved by a two-way fluid structure interaction simulation technique, using ANSYS Workbench (Release 16.0, ANSYS INC., Pittsburgh, PA, USA, 2015. The dynamic transport of particles and their deposition are investigated as a function of aerodynamic particle size, tissue visco-elasticity, tidal breathing period, gravity orientation and particle–fluid interactions. It is found that the fluid flows and streamlines differ between the present flexible model and rigid models, and the two-way coupling particle trajectories vary relative to one-way particle coupling. In addition, the results indicate that modelling the two-way coupling particle system is important because the two-way discrete phase method (DPM approach despite its complexity provides more extensive particle interactions and is more reliable than transport results from the one-way DPM approach. The substantial difference between the results of the two approaches is likely due to particle–fluid interactions, which re-suspend the sediment particles in the airway stream and hence pass from the current generation.

  18. Physiologically-Relevant Modes of Membrane Interactions by the Human Antimicrobial Peptide, LL-37, Revealed by SFG Experiments

    Science.gov (United States)

    Ding, Bei; Soblosky, Lauren; Nguyen, Khoi; Geng, Junqing; Yu, Xinglong; Ramamoorthy, Ayyalusamy; Chen, Zhan

    2013-05-01

    Antimicrobial peptides (AMPs) could become the next generation antibiotic compounds which can overcome bacterial resistance by disrupting cell membranes and it is essential to determine the factors underlying its mechanism of action. Although high-resolution NMR and other biological studies have provided valuable insights, it has been a major challenge to follow the AMP-membrane interactions at physiologically-relevant low peptide concentrations. In this study, we demonstrate a novel approach to overcome this major limitation by performing Sum Frequency Generation (SFG) vibrational spectroscopic experiments on lipid bilayers containing an AMP, LL-37. Our results demonstrate the power of SFG to study non-linear helical peptides and also infer that lipid-peptide interaction and the peptide orientation depend on the lipid membrane composition. The observed SFG signal changes capture the aggregating process of LL-37 on membrane. In addition, our SFG results on cholesterol-containing lipid bilayers indicate the inhibition effect of cholesterol on peptide-induced membrane permeation process.

  19. The Use of Human Adipose-Derived Stem Cells in the Treatment of Physiological and Pathological Vulvar Dystrophies

    Directory of Open Access Journals (Sweden)

    Maria Giuseppina Onesti

    2016-01-01

    Full Text Available “Vulvar dystrophy” is characterized by chronic alterations of vulvar trophism, occurring in both physiological (menopause and pathological (lichen sclerosus, vulvar graft-versus-host disease conditions. Associated symptoms are itching, burning, dyspareunia and vaginal dryness. Current treatments often do not imply a complete remission of symptoms. Adipose-Derived Stem Cells (ADSCs injection represents a valid alternative therapy to enhance trophism and tone of dystrophic tissues. We evaluated efficacy of ADSCs-based therapy in the dystrophic areas. From February to April 2013 we enrolled 8 patients with vulvar dystrophy. A biopsy specimen was performed before and after treatment. Digital photographs were taken at baseline and during the follow-up. Pain was detected with Visual Analogue Scale and sexual function was evaluated with Female Sexual Function Index. All patients received 2 treatments in 3 months. Follow-up was at 1 week , 1 and 3 months, and 1 and 2 years. We obtained a significant vulvar trophism enhancement in all patients, who reported pain reduction and sexual function improvement. Objective exam with speculum was easy to perform after treatment. We believe ADSCs-based therapy finds its application in the treatment of vulvar dystrophies, since ADSCs could induce increased vascularization due to their angiogenic properties and tissue trophism improvement thanks to their eutrophic effect.

  20. Study on inter-ethnic human differences in bioactivation and detoxification of estragole using physiologically based kinetic modeling.

    Science.gov (United States)

    Ning, Jia; Louisse, Jochem; Spenkelink, Bert; Wesseling, Sebastiaan; Rietjens, Ivonne M C M

    2017-03-29

    Considering the rapid developments in food safety in the past decade in China, it is of importance to obtain insight into what extent safety and risk assessments of chemicals performed for the Caucasian population apply to the Chinese population. The aim of the present study was to determine physiologically based kinetic (PBK) modeling-based predictions for differences between Chinese and Caucasians in terms of metabolic bioactivation and detoxification of the food-borne genotoxic carcinogen estragole. The PBK models were defined based on kinetic constants for hepatic metabolism derived from in vitro incubations using liver fractions of the two ethnic groups, and used to evaluate the inter-ethnic differences in metabolic activation and detoxification of estragole. The models predicted that at realistic dietary intake levels, only 0.02% of the dose was converted to the ultimate carcinogenic metabolite 1'-sulfooxyestragole in Chinese subjects, whereas this amounted to 0.09% of the dose in Caucasian subjects. Detoxification of 1'-hydroxyestragole, mainly via conversion to 1'-oxoestragole, was similar within the two ethnic groups. The 4.5-fold variation in formation of the ultimate carcinogenic metabolite of estragole accompanied by similar rates of detoxification may indicate a lower risk of estragole for the Chinese population at similar levels of exposure. The study provides a proof of principle for how PBK modeling can identify differences in ethnic sensitivity and provide a more refined risk assessment for a specific ethnic group for a compound of concern.

  1. Reinforcing, subject-rated, performance and physiological effects of methylphenidate and d-amphetamine in stimulant abusing humans.

    Science.gov (United States)

    Stoops, William W; Glaser, Paul E A; Fillmore, Mark T; Rush, Craig R

    2004-12-01

    Methylphenidate has potential for abuse because it produces behavioural effects similar to those observed with other abused stimulants, such as d-amphetamine and cocaine. The aim of this study was to further characterize the abuse potential of oral methylphenidate relative to oral d-amphetamine. Ten drug-abusing volunteers were recruited to participate in this study, which consisted of seven dose conditions: methylphenidate (16, 32 and 48 mg), d-amphetamine (8, 16 and 24 mg) and placebo. The reinforcing effects of these drugs were assessed during a self-administration session (preceded by a sampling session for each condition) with a modified progressive-ratio procedure. Subject-rated, performance and physiological effects were assessed concurrently during both the sampling and self-administration sessions. The intermediate dose of methylphenidate and d-amphetamine increased responding significantly above placebo levels. Both methylphenidate and d-amphetamine produced dose-dependent increases in stimulant-like subject ratings (e.g. Active, Alert, or Energetic and High), but the effects of these drugs were not isomorphic. These findings are consistent with epidemiological data and previous findings from laboratory studies that suggest methylphenidate has at least some abuse potential.

  2. A novel initiation mechanism of death in Streptococcus pneumoniae induced by the human milk protein-lipid complex HAMLET and activated during physiological death.

    Science.gov (United States)

    Clementi, Emily A; Marks, Laura R; Duffey, Michael E; Hakansson, Anders P

    2012-08-03

    To cause colonization or infection, most bacteria grow in biofilms where differentiation and death of subpopulations is critical for optimal survival of the whole population. However, little is known about initiation of bacterial death under physiological conditions. Membrane depolarization has been suggested, but never shown to be involved, due to the difficulty of performing such studies in bacteria and the paucity of information that exists regarding ion transport mechanisms in prokaryotes. In this study, we performed the first extensive investigation of ion transport and membrane depolarization in a bacterial system. We found that HAMLET, a human milk protein-lipid complex, kills Streptococcus pneumoniae (the pneumococcus) in a manner that shares features with activation of physiological death from starvation. Addition of HAMLET to pneumococci dissipated membrane polarity, but depolarization per se was not enough to trigger death. Rather, both HAMLET- and starvation-induced death of pneumococci specifically required a sodium-dependent calcium influx, as shown using calcium and sodium transport inhibitors. This mechanism was verified under low sodium conditions, and in the presence of ionomycin or monensin, which enhanced pneumococcal sensitivity to HAMLET- and starvation-induced death. Pneumococcal death was also inhibited by kinase inhibitors, and indicated the involvement of Ser/Thr kinases in these processes. The importance of this activation mechanism was made evident, as dysregulation and manipulation of physiological death was detrimental to biofilm formation, a hallmark of bacterial colonization. Overall, our findings provide novel information on the role of ion transport during bacterial death, with the potential to uncover future antimicrobial targets.

  3. A Novel Initiation Mechanism of Death in Streptococcus pneumoniae Induced by the Human Milk Protein-Lipid Complex HAMLET and Activated during Physiological Death*

    Science.gov (United States)

    Clementi, Emily A.; Marks, Laura R.; Duffey, Michael E.; Hakansson, Anders P.

    2012-01-01

    To cause colonization or infection, most bacteria grow in biofilms where differentiation and death of subpopulations is critical for optimal survival of the whole population. However, little is known about initiation of bacterial death under physiological conditions. Membrane depolarization has been suggested, but never shown to be involved, due to the difficulty of performing such studies in bacteria and the paucity of information that exists regarding ion transport mechanisms in prokaryotes. In this study, we performed the first extensive investigation of ion transport and membrane depolarization in a bacterial system. We found that HAMLET, a human milk protein-lipid complex, kills Streptococcus pneumoniae (the pneumococcus) in a manner that shares features with activation of physiological death from starvation. Addition of HAMLET to pneumococci dissipated membrane polarity, but depolarization per se was not enough to trigger death. Rather, both HAMLET- and starvation-induced death of pneumococci specifically required a sodium-dependent calcium influx, as shown using calcium and sodium transport inhibitors. This mechanism was verified under low sodium conditions, and in the presence of ionomycin or monensin, which enhanced pneumococcal sensitivity to HAMLET- and starvation-induced death. Pneumococcal death was also inhibited by kinase inhibitors, and indicated the involvement of Ser/Thr kinases in these processes. The importance of this activation mechanism was made evident, as dysregulation and manipulation of physiological death was detrimental to biofilm formation, a hallmark of bacterial colonization. Overall, our findings provide novel information on the role of ion transport during bacterial death, with the potential to uncover future antimicrobial targets. PMID:22700972

  4. Physiological Parameters Database for Older Adults

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Physiological Parameters Database for Older Adults is available for download and contains physiological parameters values for healthy older human adults (age 60...

  5. Novel and existing data for a future physiological toxicokinetic model of ethylene and its metabolite ethylene oxide in mouse, rat, and human.

    Science.gov (United States)

    Filser, Johannes Georg; Artati, Anna; Li, Qiang; Pütz, Christian; Semder, Brigitte; Klein, Dominik; Kessler, Winfried

    2015-11-05

    The olefin ethylene is a ubiquitously found gas. It originates predominantly from plants, combustion processes and industrial sources. In mammals, inhaled ethylene is metabolized by cytochrome P450-dependent monooxygenases, particularly by cytochrome P450 2E1, to ethylene oxide, an epoxide that directly alkylates proteins and DNA. Ethylene oxide was mutagenic in vitro and in vivo in insects and mammals and carcinogenic in rats and mice. A physiological toxicokinetic model is a most useful tool for estimating the ethylene oxide burden in ethylene-exposed rodents and humans. The only published physiological toxicokinetic model for ethylene and metabolically produced ethylene oxide is discussed. Additionally, existing data required for the development of a future model and for testing its predictive accuracy are reviewed and extended by new gas uptake studies with ethylene and ethylene oxide in B6C3F1 mice and with ethylene in F344 rats. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  6. 基于LabVIEW的人体生理参数采集系统设计%Design of LabVIEW-based acquisition system for human physiological parameters

    Institute of Scientific and Technical Information of China (English)

    张凌飞; 王圣禹; 郑黄敏; 王雪梅

    2014-01-01

    In order to enable people to understand their own physiological parameters in time,a human physiological pa-rameter acquisition system based on virtual instrument was designed. The method to compile system software with LabVIEW, the system hardware composed of sensor,alignment circuit and data acquisition card as well as the method to display the temper-ature,pulse wave and heart rate on the PC screen are described in this paper briefly. Experimental results shows that this sys-tem achieves good effect.%为了使人们能更加及时地了解自己的一些生理参数,设计了一种基于虚拟仪器的人体生理参数采集系统。在此简单叙述了利用LabVIEW编写系统软件,由传感器、调理电路和数据采集卡构成系统硬件,并将采集到体温、脉搏波和心率显示在PC机上的原理和方法。通过实践,系统达到了较好的效果。

  7. Nitrogen Solubility in Adipose Tissues of Diving Animals: Implications for Human Divers and for Modeling Diving Physiology

    Science.gov (United States)

    2016-11-01

    in different locations, and even though manunalian and avian body core temperature is regulated to between 37-40 °C, the peripheral regions of the...adipose at different temperatures , because diving animals and humans may experience a range of water temperatures when diving to different depths or... body will experience temperatures along a gradient between core and ambient. Coupled with new knowledge of solubility in adipose tissue was the need

  8. Overexpression of human and fly frataxins in Drosophila provokes deleterious effects at biochemical, physiological and developmental levels.

    Directory of Open Access Journals (Sweden)

    Juan A Navarro

    Full Text Available BACKGROUND: Friedreich's ataxia (FA, the most frequent form of inherited ataxias in the Caucasian population, is caused by a reduced expression of frataxin, a highly conserved protein. Model organisms have contributed greatly in the efforts to decipher the function of frataxin; however, the precise function of this protein remains elusive. Overexpression studies are a useful approach to investigate the mechanistic actions of frataxin; however, the existing literature reports contradictory results. To further investigate the effect of frataxin overexpression, we analyzed the consequences of overexpressing human (FXN and fly (FH frataxins in Drosophila. METHODOLOGY/PRINCIPAL FINDINGS: We obtained transgenic flies that overexpressed human or fly frataxins in a general pattern and in different tissues using the UAS-GAL4 system. For both frataxins, we observed deleterious effects at the biochemical, histological and behavioral levels. Oxidative stress is a relevant factor in the frataxin overexpression phenotypes. Systemic frataxin overexpression reduces Drosophila viability and impairs the normal embryonic development of muscle and the peripheral nervous system. A reduction in the level of aconitase activity and a decrease in the level of NDUF3 were also observed in the transgenic flies that overexpressed frataxin. Frataxin overexpression in the nervous system reduces life span, impairs locomotor ability and causes brain degeneration. Frataxin aggregation and a misfolding of this protein have been shown not to be the mechanism that is responsible for the phenotypes that have been observed. Nevertheless, the expression of human frataxin rescues the aconitase activity in the fh knockdown mutant. CONCLUSION/SIGNIFICANCE: Our results provide in vivo evidence of a functional equivalence for human and fly frataxins and indicate that the control of frataxin expression is important for treatments that aim to increase frataxin levels.

  9. Overexpression of Human and Fly Frataxins in Drosophila Provokes Deleterious Effects at Biochemical, Physiological and Developmental Levels

    Science.gov (United States)

    Soriano, Sirena; Botella, José A.; Schneuwly, Stephan; Martínez-Sebastián, María J.; Moltó, María D.

    2011-01-01

    Background Friedreich's ataxia (FA), the most frequent form of inherited ataxias in the Caucasian population, is caused by a reduced expression of frataxin, a highly conserved protein. Model organisms have contributed greatly in the efforts to decipher the function of frataxin; however, the precise function of this protein remains elusive. Overexpression studies are a useful approach to investigate the mechanistic actions of frataxin; however, the existing literature reports contradictory results. To further investigate the effect of frataxin overexpression, we analyzed the consequences of overexpressing human (FXN) and fly (FH) frataxins in Drosophila. Methodology/Principal Findings We obtained transgenic flies that overexpressed human or fly frataxins in a general pattern and in different tissues using the UAS-GAL4 system. For both frataxins, we observed deleterious effects at the biochemical, histological and behavioral levels. Oxidative stress is a relevant factor in the frataxin overexpression phenotypes. Systemic frataxin overexpression reduces Drosophila viability and impairs the normal embryonic development of muscle and the peripheral nervous system. A reduction in the level of aconitase activity and a decrease in the level of NDUF3 were also observed in the transgenic flies that overexpressed frataxin. Frataxin overexpression in the nervous system reduces life span, impairs locomotor ability and causes brain degeneration. Frataxin aggregation and a misfolding of this protein have been shown not to be the mechanism that is responsible for the phenotypes that have been observed. Nevertheless, the expression of human frataxin rescues the aconitase activity in the fh knockdown mutant. Conclusion/Significance Our results provide in vivo evidence of a functional equivalence for human and fly frataxins and indicate that the control of frataxin expression is important for treatments that aim to increase frataxin levels. PMID:21779322

  10. Effects of geomagnetic activity variations on the physiological and psychological state of functionally healthy humans: Some results of Azerbaijani studies

    Science.gov (United States)

    Babayev, Elchin S.; Allahverdiyeva, Aysel A.

    There are collaborative and cross-disciplinary space weather studies in the Azerbaijan National Academy of Sciences conducted with purposes of revealing possible effects of solar, geomagnetic and cosmic ray variability on certain technological, biological and ecological systems. This paper describes some results of the experimental studies of influence of the periodical and aperiodical changes of geomagnetic activity upon human brain, human health and psycho-emotional state. It also covers the conclusions of studies on influence of violent solar events and severe geomagnetic storms of the solar cycle 23 on the mentioned systems in middle-latitude location. It is experimentally established that weak and moderate geomagnetic storms do not cause significant changes in the brain's bioelectrical activity and exert only stimulating influence while severe disturbances of geomagnetic conditions cause negative influence, seriously disintegrate brain's functionality, activate braking processes and amplify the negative emotional background of an individual. It is concluded that geomagnetic disturbances affect mainly emotional and vegetative spheres of human beings while characteristics reflecting personality properties do not undergo significant changes.

  11. Human biofluid concentrations of mono(2-ethylhexyl)phthalate extrapolated from pharmacokinetics in chimeric mice with humanized liver administered with di(2-ethylhexyl)phthalate and physiologically based pharmacokinetic modeling.

    Science.gov (United States)

    Adachi, Koichiro; Suemizu, Hiroshi; Murayama, Norie; Shimizu, Makiko; Yamazaki, Hiroshi

    2015-05-01

    Di(2-ethylhexyl)phthalate (DEHP) is a reproductive toxicant in male rodents. The aim of the current study was to extrapolate the pharmacokinetics and toxicokinetics of mono(2-ethylhexyl)phthalate (MEHP, a primary metabolite of DEHP) in humans by using data from oral administration of DEHP to chimeric mice transplanted with human hepatocytes. MEHP and its glucuronide were detected in plasma from control mice and chimeric mice after single oral doses of 250mg DEHP/kg body weight. Biphasic plasma concentration-time curves of MEHP and its glucuronide were seen only in control mice. MEHP and its glucuronide were extensively excreted in urine within 24h in mice with humanized liver. In contrast, fecal excretion levels of MEHP glucuronide were high in control mice compared with those with humanized liver. Adjusted animal biomonitoring equivalents from chimeric mice studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model. Estimated urine MEHP concentrations in humans were consistent with reported concentrations. This research illustrates how chimeric mice transplanted with human hepatocytes in combination with a simple PBPK model can assist evaluations of pharmacokinetics or toxicokinetics of the primary or secondary metabolites of DEHP.

  12. Physiology of the fetal circulation.

    Science.gov (United States)

    Kiserud, Torvid

    2005-12-01

    Our understanding of fetal circulatory physiology is based on experimental animal data, and this continues to be an important source of new insight into developmental mechanisms. A growing number of human studies have investigated the human physiology, with results that are similar but not identical to those from animal studies. It is time to appreciate these differences and base more of our clinical approach on human physiology. Accordingly, the present review focuses on distributional patterns and adaptational mechanisms that were mainly discovered by human studies. These include cardiac output, pulmonary and placental circulation, fetal brain and liver, venous return to the heart, and the fetal shunts (ductus venosus, foramen ovale and ductus arteriosus). Placental compromise induces a set of adaptational and compensational mechanisms reflecting the plasticity of the developing circulation, with both short- and long-term implications. Some of these aspects have become part of the clinical physiology of today with consequences for surveillance and treatment.

  13. Olfaction: anatomy, physiology and behavior

    OpenAIRE

    Benignus, Vernon A.; Prah, James D.

    1982-01-01

    The anatomy, physiology and function of the olfactory system are reviewed, as are the normal effects of olfactory stimulation. It is speculated that olfaction may have important but unobtrusive effects on human behavior.

  14. 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.

    Science.gov (United States)

    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.

  15. 高校人体解剖生理学实验教学平台建设%Human anatomy physiology experiment teaching platform construction in university

    Institute of Scientific and Technical Information of China (English)

    邴杰

    2014-01-01

    Based on the teaching platform construction of the human anatomical physiology experiment at the college of life science of Beijing Normal University, introduced the platform construction in detail from the following three aspects:network classroom and interactive learning platform, virtual reality platform, multi-functional experimental platform construction. The aim is to integrate the educational and informationized teaching, virtual reality technology and multi-functional operating platform organically into the physical laboratory construction, and to create a vivid, three-dimensional, functional experimental platform of human anatomical physiology, and thus build up an experimental teaching platform which could promotes the students' all-round development with the combination of teaching and innovation and stimulates students’ enthusiasm, initiative and creativity for learning.%结合北京师范大学生命科学学院人体解剖生理学实验教学平台建设,从网络教室与交互式学习平台、虚拟现实平台、多功能实验操作平台建设三个方面进行详细介绍。旨在将教育信息化教学、虚拟现实技术与网络互联技术有机整合到实体实验室建设中,为学生打造一个集生动化、立体化、功能化于一体的人体解剖生理学实验平台,从而搭建促进学生全方位发展的教学与创新相结合的实验教学平台,激发学生的学习积极性、主动性和创造性。

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

    Science.gov (United States)

    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

  17. Physiology for engineers applying engineering methods to physiological systems

    CERN Document Server

    Chappell, Michael

    2016-01-01

    This book provides an introduction to qualitative and quantitative aspects of human physiology. It looks at biological and physiological processes and phenomena, including a selection of mathematical models, showing how physiological problems can be mathematically formulated and studied. It also illustrates how a wide range of engineering and physics topics, including electronics, fluid dynamics, solid mechanics and control theory can be used to describe and understand physiological processes and systems. Throughout the text there are introductions to measuring and quantifying physiological processes using both signal and imaging technologies. Physiology for Engineers describes the basic structure and models of cellular systems, the structure and function of the cardiovascular system, the electrical and mechanical activity of the heart and provides an overview of the structure and function of the respiratory and nervous systems. It also includes an introduction to the basic concepts and applications of reacti...

  18. Network Physiology reveals relations between network topology and physiological function

    CERN Document Server

    Bashan, Amir; Kantelhardt, Jan W; Havlin, Shlomo; Ivanov, Plamen Ch; 10.1038/ncomms1705

    2012-01-01

    The human organism is an integrated network where complex physiologic systems, each with its own regulatory mechanisms, continuously interact, and where failure of one system can trigger a breakdown of the entire network. Identifying and quantifying dynamical networks of diverse systems with different types of interactions is a challenge. Here, we develop a framework to probe interactions among diverse systems, and we identify a physiologic network. We find that each physiologic state is characterized by a specific network structure, demonstrating a robust interplay between network topology and function. Across physiologic states the network undergoes topological transitions associated with fast reorganization of physiologic interactions on time scales of a few minutes, indicating high network flexibility in response to perturbations. The proposed system-wide integrative approach may facilitate the development of a new field, Network Physiology.

  19. The human gut microbiome as source of innovation for health: Which physiological and therapeutic outcomes could we expect?

    Science.gov (United States)

    Doré, Joël; Multon, Marie-Christine; Béhier, Jehan-Michel

    2017-02-01

    From the moment of birth, each human being builds a microbe-host symbiosis which is key for the preservation of its health and well-being. This personal symbiotic coexistence is the result of progressive enrichments in microorganism diversity through external supplies. This diversity is nowadays massively overthrown by drastic changes related to clinical practice in birth management, environmental exposure, nutrition and healthcare behaviors. The last two generations have been the frame of massive modifications in life and food habits, with people being more and more sedentary, overfed and permeated with drugs and pollutants. We are now able to measure the impact of these changes on the gut microbiota diversity. Concomitantly, these modifications of lifestyle were associated with a dramatic increase in incidence of immune-mediated diseases including metabolic, allergic and inflammatory diseases and most likely neurodegenerative and psychiatric disorders. Microbiota is becoming a hot topic in the scientific community and in the mainstream media. The number of scientific publications increased by up to a factor three over the last five years, with gastrointestinal and metabolic diseases being the most productive areas. In the intellectual property landscape, the patent families on microbiota have more than doubled in the meantime. In parallel, funding either from National Institutes (e.g. from NIH which funds research mainly in the field of allergies, infections, cancer and cardiovascular diseases, from the White House which launched the national microbiome initiative) or by pharmaceutical companies follow the same trend, showing a boost and a strong support in the research field on microbiota. All major health players are investing in microbiome research as shown by the number of deals signed and by funding during 2015. The Giens round table addressed how the medicine of tomorrow, considering human beings as a human-microbe symbiotic supraorganism, could leverage

  20. Speckle shearing pattern interferometry to assess mechanical strain in the human mandible jaw bone under physiological stress

    Science.gov (United States)

    Moreno, V.; Vázquez-Vázquez, C.; Gallas, M.; Crespo, J.

    2011-05-01

    Electronic Speckle Pattern Interferometry (ESPI) has been used in experiments to measure displacement on the surface of bones undergoing external forces. However in order to asses directly the derivative of the displacements a related technique, Shearography, is used. This technique has been applied in biomechanical experiments although limited to small pieces of bone to determine their elastic properties. In this work we propose the use of Shearing Speckle Interferometry to evaluate the mechanical behaviour of the human mandible under compressive stress, simulating masticatory forces or impacts, in order to analyze the strain distribution on mandibular bone.

  1. Comparative analysis of human γD-crystallin aggregation under physiological and low pH conditions.

    Directory of Open Access Journals (Sweden)

    Josephine W Wu

    Full Text Available Cataract, a major cause of visual impairment worldwide, is the opacification of the eye's crystalline lens due to aggregation of the crystallin proteins. The research reported here is aimed at investigating the aggregating behavior of γ-crystallin proteins in various incubation conditions. Thioflavin T binding assay, circular dichroism spectroscopy, 1-anilinonaphthalene-8-sulfonic acid fluorescence spectroscopy, intrinsic (tryptophan fluorescence spectroscopy, light scattering, and electron microscopy were used for structural characterization. Molecular dynamics simulations and bioinformatics prediction were performed to gain insights into the γD-crystallin mechanisms of fibrillogenesis. We first demonstrated that, except at pH 7.0 and 37°C, the aggregation of γD-crystallin was observed to be augmented upon incubation, as revealed by turbidity measurements. Next, the types of aggregates (fibrillar or non-fibrillar aggregates formed under different incubation conditions were identified. We found that, while a variety of non-fibrillar, granular species were detected in the sample incubated under pH 7.0, the fibrillogenesis of human γD-crystallin could be induced by acidic pH (pH 2.0. In addition, circular dichroism spectroscopy, 1-anilinonaphthalene-8-sulfonic acid fluorescence spectroscopy, and intrinsic fluorescence spectroscopy were used to characterize the structural and conformational features in different incubation conditions. Our results suggested that incubation under acidic condition led to a considerable change in the secondary structure and an enhancement in solvent-exposure of the hydrophobic regions of human γD-crystallin. Finally, molecular dynamics simulations and bioinformatics prediction were performed to better explain the differences between the structures and/or conformations of the human γD-crystallin samples and to reveal potential key protein region involved in the varied aggregation behavior. Bioinformatics analyses

  2. Isolation of mesenchymal stem cells from human bone and long-term cultivation under physiologic oxygen conditions.

    Science.gov (United States)

    Klepsch, Sebastian; Jamnig, Angelika; Trimmel, Daniela; Schimke, Magdalena; Kapferer, Werner; Brunauer, Regina; Singh, Sarvpreet; Reitinger, Stephan; Lepperdinger, Günter

    2013-01-01

    Bone-derived stroma cells contain a rare subpopulation, which exhibits enhanced stemness characteristics. Therefore, this particular cell type is often attributed the mesenchymal stem cell (MSC). Due to their high proliferation potential, multipotential differentiation capacity, and immunosuppressive properties, MSCs are now widely appreciated for cell therapeutic applications in a multitude of clinical aspects. In line with this, maintenance of MSC stemness during isolation and culture expansion is considered pivot. Here, we provide step-by-step protocols which allow selection for, and in vitro propagation of high quality MSC from human bone.

  3. Capillary growth in human skeletal muscle: physiological factors and the balance between pro-angiogenic and angiostatic factors

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Hoier, Birgitte

    2014-01-01

    In human skeletal muscle, the capillary net readily adapts according to the level of muscular activity to allow for optimal diffusion conditions for oxygen from the blood to the muscle. Animal studies have demonstrated that stimulation of capillary growth in skeletal muscle can occur either...... by mechanical or by chemical signalling. Mechanical signals originate from shear stress forces on the endothelial cell layer induced by the blood flowing through the vessel, but include also mechanical stretch and compression of the vascular structures and the surrounding tissue, as the muscle contracts...

  4. Application of physiologically based pharmacokinetic modeling in predicting drug–drug interactions for sarpogrelate hydrochloride in humans

    Directory of Open Access Journals (Sweden)

    Min JS

    2016-09-01

    Full Text Available Jee Sun Min,1 Doyun Kim,1 Jung Bae Park,1 Hyunjin Heo,1 Soo Hyeon Bae,2 Jae Hong Seo,1 Euichaul Oh,1 Soo Kyung Bae1 1Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Bucheon, 2Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul, South Korea Background: Evaluating the potential risk of metabolic drug–drug interactions (DDIs is clinically important. Objective: To develop a physiologically based pharmacokinetic (PBPK model for sarpogrelate hydrochloride and its active metabolite, (R,S-1-{2-[2-(3-methoxyphenylethyl]-phenoxy}-3-(dimethylamino-2-propanol (M-1, in order to predict DDIs between sarpogrelate and the clinically relevant cytochrome P450 (CYP 2D6 substrates, metoprolol, desipramine, dextromethorphan, imipramine, and tolterodine. Methods: The PBPK model was developed, incorporating the physicochemical and pharmacokinetic properties of sarpogrelate hydrochloride, and M-1 based on the findings from in vitro and in vivo studies. Subsequently, the model was verified by comparing the predicted concentration-time profiles and pharmacokinetic parameters of sarpogrelate and M-1 to the observed clinical data. Finally, the verified model was used to simulate clinical DDIs between sarpogrelate hydrochloride and sensitive CYP2D6 substrates. The predictive performance of the model was assessed by comparing predicted results to observed data after coadministering sarpogrelate hydrochloride and metoprolol. Results: The developed PBPK model accurately predicted sarpogrelate and M-1 plasma concentration profiles after single or multiple doses of sarpogrelate hydrochloride. The simulated ratios of area under the curve and maximum plasma concentration of metoprolol in the presence of sarpogrelate hydrochloride to baseline were in good agreement with the observed ratios. The predicted fold-increases in the area under the curve ratios of metoprolol

  5. Network Physiology: Mapping Interactions Between Networks of Physiologic Networks

    Science.gov (United States)

    Ivanov, Plamen Ch.; Bartsch, Ronny P.

    The human organism is an integrated network of interconnected and interacting organ systems, each representing a separate regulatory network. The behavior of one physiological system (network) may affect the dynamics of all other systems in the network of physiologic networks. Due to these interactions, failure of one system can trigger a cascade of failures throughout the entire network. We introduce a systematic method to identify a network of interactions between diverse physiologic organ systems, to quantify the hierarchical structure and dynamics of this network, and to track its evolution under different physiologic states. We find a robust relation between network structure and physiologic states: every state is characterized by specific network topology, node connectivity and links strength. Further, we find that transitions from one physiologic state to another trigger a markedly fast reorganization in the network of physiologic interactions on time scales of just a few minutes, indicating high network flexibility in response to perturbations. This reorganization in network topology occurs simultaneously and globally in the entire network as well as at the level of individual physiological systems, while preserving a hierarchical order in the strength of network links. Our findings highlight the need of an integrated network approach to understand physiologic function, since the framework we develop provides new information which can not be obtained by studying individual systems. The proposed system-wide integrative approach may facilitate the development of a new field, Network Physiology.

  6. Associated expressions of FGFR-2 and FGFR-3: from mouse mammary gland physiology to human breast cancer.

    Science.gov (United States)

    Cerliani, Juan P; Vanzulli, Silvia I; Piñero, Cecilia Pérez; Bottino, María C; Sahores, Ana; Nuñez, Myriam; Varchetta, Romina; Martins, Rubén; Zeitlin, Eduardo; Hewitt, Stephen M; Molinolo, Alfredo A; Lanari, Claudia; Lamb, Caroline A

    2012-06-01

    Fibroblast growth factor receptors (FGFRs) are tyrosine kinase receptors which have been implicated in breast cancer. The aim of this study was to evaluate FGFR-1, -2, -3, and -4 protein expressions in normal murine mammary gland development, and in murine and human breast carcinomas. Using immunohistochemistry and Western blot, we report a hormonal regulation of FGFR during postnatal mammary gland development. Progestin treatment of adult virgin mammary glands resulted in changes in localization of FGFR-3 from the cytoplasm to the nucleus, while treatment with 17-β-estradiol induced changes in the expressions and/or localizations of FGFR-2 and -3. In murine mammary carcinomas showing different degrees of hormone dependence, we found progestin-induced increased expressions, mainly of FGFR-2 and -3. These receptors were constitutively activated in hormone-independent variants. We studied three luminal human breast cancer cell lines growing as xenografts, which particularly expressed FGFR-2 and -3, suggesting a correlation between hormonal status and FGFR expression. Most importantly, in breast cancer samples from 58 patients, we found a strong association (P FGFR-2 and -3 expressions and a weaker correlation of each receptor with estrogen receptor expression. FGFR-4 correlated with c-erbB2 over expression. We conclude that FGFR-2 and -3 may be mechanistically linked and can be potential targets for treatment of estrogen receptor-positive breast cancer patients.

  7. The Importance of the Ionic Product for Water to Understand the Physiology of the Acid-Base Balance in Humans

    Directory of Open Access Journals (Sweden)

    María M. Adeva-Andany

    2014-01-01

    Full Text Available Human plasma is an aqueous solution that has to abide by chemical rules such as the principle of electrical neutrality and the constancy of the ionic product for water. These rules define the acid-base balance in the human body. According to the electroneutrality principle, plasma has to be electrically neutral and the sum of its cations equals the sum of its anions. In addition, the ionic product for water has to be constant. Therefore, the plasma concentration of hydrogen ions depends on the plasma ionic composition. Variations in the concentration of plasma ions that alter the relative proportion of anions and cations predictably lead to a change in the plasma concentration of hydrogen ions by driving adaptive adjustments in water ionization that allow plasma electroneutrality while maintaining constant the ionic product for water. The accumulation of plasma anions out of proportion of cations induces an electrical imbalance compensated by a fall of hydroxide ions that brings about a rise in hydrogen ions (acidosis. By contrast, the deficiency of chloride relative to sodium generates plasma alkalosis by increasing hydroxide ions. The adjustment of plasma bicarbonate concentration to these changes is an important compensatory mechanism that protects plasma pH from severe deviations.

  8. The importance of the ionic product for water to understand the physiology of the acid-base balance in humans.

    Science.gov (United States)

    Adeva-Andany, María M; Carneiro-Freire, Natalia; Donapetry-García, Cristóbal; Rañal-Muíño, Eva; López-Pereiro, Yosua

    2014-01-01

    Human plasma is an aqueous solution that has to abide by chemical rules such as the principle of electrical neutrality and the constancy of the ionic product for water. These rules define the acid-base balance in the human body. According to the electroneutrality principle, plasma has to be electrically neutral and the sum of its cations equals the sum of its anions. In addition, the ionic product for water has to be constant. Therefore, the plasma concentration of hydrogen ions depends on the plasma ionic composition. Variations in the concentration of plasma ions that alter the relative proportion of anions and cations predictably lead to a change in the plasma concentration of hydrogen ions by driving adaptive adjustments in water ionization that allow plasma electroneutrality while maintaining constant the ionic product for water. The accumulation of plasma anions out of proportion of cations induces an electrical imbalance compensated by a fall of hydroxide ions that brings about a rise in hydrogen ions (acidosis). By contrast, the deficiency of chloride relative to sodium generates plasma alkalosis by increasing hydroxide ions. The adjustment of plasma bicarbonate concentration to these changes is an important compensatory mechanism that protects plasma pH from severe deviations.

  9. Occupational physiology

    CERN Document Server

    Toomingas, Allan; Tornqvist, Ewa Wigaeus

    2011-01-01

    In a clear and accessible presentation, Occupational Physiology focuses on important issues in the modern working world. Exploring major public health problems-such as musculoskeletal disorders and stress-this book explains connections between work, well-being, and health based on up-to-date research in the field. It provides useful methods for risk assessment and guidelines on arranging a good working life from the perspective of the working individual, the company, and society as a whole.The book focuses on common, stressful situations in different professions. Reviewing bodily demands and r

  10. Humans on the International Space Station-How Research, Operations, and International Collaboration are Leading to New Understanding of Human Physiology and Performance in Microgravity

    Science.gov (United States)

    Ronbinson, Julie A.; Harm, Deborah L.

    2009-01-01

    As the International Space Station (ISS) nears completion, and full international utilization is achieved, we are at a scientific crossroads. ISS is the premier location for research aimed at understanding the effects of microgravity on the human body. For applications to future human exploration, it is key for validation, quantification, and mitigation of a wide variety of spaceflight risks to health and human performance. Understanding and mitigating these risks is the focus of NASA s Human Research Program. However, NASA s approach to defining human research objectives is only one of many approaches within the ISS international partnership (including Roscosmos, the European Space Agency, the Canadian Space Agency, and the Japan Aerospace Exploration Agency). Each of these agencies selects and implements their own ISS research, with independent but related objectives for human and life sciences research. Because the science itself is also international and collaborative, investigations that are led by one ISS partner also often include cooperative scientists from around the world. The operation of the ISS generates significant additional data that is not directly linked to specific investigations. Such data comes from medical monitoring of crew members, life support and radiation monitoring, and from the systems that have been implemented to protect the health of the crew (such as exercise hardware). We provide examples of these international synergies in human research on ISS and highlight key early accomplishments that derive from these broad interfaces. Taken as a whole, the combination of diverse research objectives, operational data, international sharing of research resources on ISS, and scientific collaboration provide a robust research approach and capability that no one partner could achieve alone.

  11. Humans on the International Space Station-How Research, Operations, and International Collaboration are Leading to New Understanding of Human Physiology and Performance in Microgravity

    Science.gov (United States)

    Ronbinson, Julie A.; Harm, Deborah L.

    2009-01-01

    As the International Space Station (ISS) nears completion, and full international utilization is achieved, we are at a scientific crossroads. ISS is the premier location for research aimed at understanding the effects of microgravity on the human body. For applications to future human exploration, it is key for validation, quantification, and mitigation of a wide variety of spaceflight risks to health and human performance. Understanding and mitigating these risks is the focus of NASA s Human Research Program. However, NASA s approach to defining human research objectives is only one of many approaches within the ISS international partnership (including Roscosmos, the European Space Agency, the Canadian Space Agency, and the Japan Aerospace Exploration Agency). Each of these agencies selects and implements their own ISS research, with independent but related objectives for human and life sciences research. Because the science itself is also international and collaborative, investigations that are led by one ISS partner also often include cooperative scientists from around the world. The operation of the ISS generates significant additional data that is not directly linked to specific investigations. Such data comes from medical monitoring of crew members, life support and radiation monitoring, and from the systems that have been implemented to protect the health of the crew (such as exercise hardware). We provide examples of these international synergies in human research on ISS and highlight key early accomplishments that derive from these broad interfaces. Taken as a whole, the combination of diverse research objectives, operational data, international sharing of research resources on ISS, and scientific collaboration provide a robust research approach and capability that no one partner could achieve alone.

  12. HepatoNet1: a comprehensive metabolic reconstruction of the human hepatocyte for the analysis of liver physiology.

    Science.gov (United States)

    Gille, Christoph; Bölling, Christian; Hoppe, Andreas; Bulik, Sascha; Hoffmann, Sabrina; Hübner, Katrin; Karlstädt, Anja; Ganeshan, Ramanan; König, Matthias; Rother, Kristian; Weidlich, Michael; Behre, Jörn; Holzhütter, Herrmann-Georg

    2010-09-07

    We present HepatoNet1, the first reconstruction of a comprehensive metabolic network of the human hepatocyte that is shown to accomplish a large canon of known metabolic liver functions. The network comprises 777 metabolites in six intracellular and two extracellular compartments and 2539 reactions, including 1466 transport reactions. It is based on the manual evaluation of >1500 original scientific research publications to warrant a high-quality evidence-based model. The final network is the result of an iterative process of data compilation and rigorous computational testing of network functionality by means of constraint-based modeling techniques. Taking the hepatic detoxification of ammonia as an example, we show how the availability of nutrients and oxygen may modulate the interplay of various metabolic pathways to allow an efficient response of the liver to perturbations of the homeostasis of blood compounds.

  13. An aura of confusion: 'seeing auras-vital energy or human physiology?' Part 1 of a three part series.

    Science.gov (United States)

    Duerden, Tim

    2004-02-01

    The first of three papers that considers claims made for the perception or detection of vital energy. Many systems of Complementary and Alternative Medicine (CAM) assume the existence of a vital force that mediates therapeutic efficacy, for example chi or qi in Traditional Chinese medicine. Vital energy directly perceived or imaged that surrounds living organisms is frequently termed the aura. This paper aims to show how phenomena that arise as a consequence of the normal functioning of the human visual system can be inappropriately offered as support of claims for the direct perception of vital energy or the aura. Specifically, contrast and complementary colour phenomena, entoptic phenomena and the deformation phosphene, the 'flying corpuscle effect', the blind spot and the 'reverse telescope effect' are explained and discussed.

  14. Human Milk Cells Contain Numerous miRNAs that May Change with Milk Removal and Regulate Multiple Physiological Processes.

    Science.gov (United States)

    Alsaweed, Mohammed; Lai, Ching Tat; Hartmann, Peter E; Geddes, Donna T; Kakulas, Foteini

    2016-06-17

    Human milk (HM) is a complex biofluid conferring nutritional, protective and developmental components for optimal infant growth. Amongst these are maternal cells, which change in response to feeding and were recently shown to be a rich source of miRNAs. We used next generation sequencing to characterize the cellular miRNA profile of HM collected before and after feeding. HM cells conserved higher miRNA content than the lipid and skim HM fractions or other body fluids, in accordance with previous studies. In total, 1467 known mature and 1996 novel miRNAs were identified, with 89 high-confidence novel miRNAs. HM cell content was higher post-feeding (p milk components, with potential diagnostic value in lactation performance. They are also involved in the control of body fluid balance, thirst, appetite, immune response, and development, implicating their functional significance for the infant.

  15. Comparison of the physiological properties of human periodontal-masseteric reflex evoked by incisor and canine stimulation

    Directory of Open Access Journals (Sweden)

    Hiroko eOhmori

    2012-06-01

    Full Text Available Introduction: The present study was designed to clarify whether the bilateral cooperation in the human periodontal-masseteric reflex (PMR differs between central incisors and canines. Methods: Surface array electrodes were placed on the bilateral masseter muscles to simultaneously record the firing activities of single motor units from both sides in 7 healthy adults. During light clenching, mechanical stimulation was applied to the right maxillary central incisor and canine to evoke the PMR. Unitary activity was plotted with respect to the background activity and firing frequency. The slope of the regression line (sRL and the correlation coefficient (CC between the central incisor and canine and the lateral differences between these values were compared. Results: There were significant differences in the sRL and CC, as well as lateral differences, between the central incisor- and canine-driven PMR. Discussion: These results suggest that the PMR differs depending on both the tooth position and laterality.

  16. Human stefin B normal and patho-physiological role: molecular and cellular aspects of amyloid-type aggregation of certain EPM1 mutants.

    Directory of Open Access Journals (Sweden)

    Mira ePolajnar

    2012-08-01

    Full Text Available Epilepsies are characterised by abnormal electrophysiological activity of the brain. Among various types of inherited epilepsies different epilepsy syndromes, among them progressive myoclonus epilepsies with features of ataxia and neurodegeneration, are counted. The progressive myoclonus epilepsy of type 1 (EPM1, also known as Unverricht-Lundborg disease presents with features of cerebellar atrophy and increased oxidative stress. It has been found that EPM1 is caused by mutations in human cystatin B gene (human stefin B. We first describe the role of protein aggregation in other neurodegenerative conditions. Protein aggregates appear intraneurally but are also excreted, such as is the case with senile plaques of amyloid- β (Aβ that accumulate in the brain parenchyma and vessel walls. A common characteristic of such diseases is the change of the protein conformation towards β secondary structure that accounts for the strong tendency of such proteins to aggregate and form amyloid fibrils. Second, we describe the patho-physiology of EPM1 and the normal and aberrant roles of stefin B in a mouse model of the disease. Furthermore, we discuss how the increased protein aggregation observed with some of the mutants of human stefin B may relate to the neurodegeneration that occurs in rare EPM1 patients. Our hypothesis (Ceru et al., 2005 states that some of the EPM1 mutants of human stefin B may undergo aggregation in neural cells, thus gaining additional toxic function (apart from loss of normal function. Our in vitro experiments thus far have confirmed that 4 mutants undergo increased aggregation relative to the wild-type protein. It has been shown that the R68X mutant forms amyloid-fibrils very rapidly, even at neutral pH and forms perinuclear inclusions, whereas the G4R mutant exhibits a prolonged lag phase, during which the toxic prefibrillar aggregates accumulate and are scattered more diffusely over the cytoplasm. Initial experiments on the G50E

  17. A Physiological and Psychometric Evaluation of Human Subconscious Visual Response and Its Application in Health Promoting Lighting

    Science.gov (United States)

    Vartanian, Garen V.

    Subconscious vision is a recent focus of the vision science community, brought on by the discovery of a previously unknown photoreceptor in the retina dedicated to driving non-image-forming responses, intrinsically photosensitive retinal ganglion cells (ipRGCs). In addition to accepting inputs from rod and cone photoreceptors, ipRGCs contain their own photopigment, melanopsin, and are considered true photoreceptors. ipRGCs drive various non-image-forming photoresponses, including circadian photoentrainment, melatonin suppression, and pupil constriction. In order to understand more about ipRGC function in humans, we studied its sensitivity to light stimuli in the evening and day. First, we measured the sensitivity threshold of melatonin suppression at night. Using a protocol that enhances data precision, we have found the threshold for human melatonin suppression to be two orders of magnitude lower than previously reported. This finding has far-reaching implications since there is mounting evidence that nocturnal activation of the circadian system can be harmful. Paradoxically, ipRGCs are understimulated during the day. Optimizing daytime non-image-forming photostimulation has health benefits, such as increased alertness, faster reaction times, better sleep quality, and treatment of depression. In order to enhance ipRGC excitation, we aimed to circumvent adaptation (i.e. desensitization) of the photoresponse by using flickering instead of steady light. We find that properly timed flickering light enhances pupillary light reflex significantly when compared to steady light with 9-fold more energy density. Employing our findings, a new form of LED light is proposed to enhance subconscious visual responses at a typical indoor illuminance level. Using the silent substitution technique, a melanopsin-selective flicker is introduced into the light. A linear optimization algorithm is used to maximize the contrast of the subconscious, melanopsin-based response function while

  18. Differential role of Hedgehog signaling in human pancreatic(patho-) physiology:An up to date review

    Institute of Scientific and Technical Information of China (English)

    Eckhard Klieser; Stefan Swierczynski; Christian Mayr; Tarkan J?ger; Johanna Schmidt; Daniel Neureiter; Tobias Kiesslich; Romana Illig

    2016-01-01

    Since the discovery of the Hedgehog(Hh)pathway in drosophila melanogaster,our knowledge of the role of Hh in embryonic development,inflammation,and cancerogenesis in humans has dramatically increased over the last decades.This is the case especially concerning the pancreas,however,real therapeutic breakthroughs are missing until now.In general,Hh signaling is essential for pancreatic organogenesis,development,and tissue maturation.In the case of acute pancreatitis,Hh has a protective role,whereas in chronic pancreatitis,Hh interacts with pancreatic stellate cells,leading to destructive parenchym fibrosis and atrophy,as well as to irregular tissue remodeling with potency of initiating cancerogenesis.In vitro and in situ analysis of Hh in pancreatic cancer revealed that the Hh pathway participates in the development of pancreatic precursor lesions and ductal adenocarcinoma including critical interactions with the tumor microenvironment.The application of specific inhibitors of components of the Hh pathway is currently subject of ongoing clinical trials(phases 1 and 2).Furthermore,a combination of Hh pathway inhibitors and established chemotherapeutic drugs could also represent a promising therapeutic approach.In this review,we give a structured survey of the role of the Hh pathway in pancreatic development,pancreatitis,pancreatic carcinogenesis and pancreatic cancer as well as an overview of current clinical trials concerning Hh pathway inhibitors and pancreas cancer.

  19. Human Milk Cells Contain Numerous miRNAs that May Change with Milk Removal and Regulate Multiple Physiological Processes

    Directory of Open Access Journals (Sweden)

    Mohammed Alsaweed

    2016-06-01

    Full Text Available Human milk (HM is a complex biofluid conferring nutritional, protective and developmental components for optimal infant growth. Amongst these are maternal cells, which change in response to feeding and were recently shown to be a rich source of miRNAs. We used next generation sequencing to characterize the cellular miRNA profile of HM collected before and after feeding. HM cells conserved higher miRNA content than the lipid and skim HM fractions or other body fluids, in accordance with previous studies. In total, 1467 known mature and 1996 novel miRNAs were identified, with 89 high-confidence novel miRNAs. HM cell content was higher post-feeding (p < 0.05, and was positively associated with total miRNA content (p = 0.014 and species number (p < 0.001. This coincided with upregulation of 29 known and 2 novel miRNAs, and downregulation of 4 known and 1 novel miRNAs post-feeding, but no statistically significant change in expression was found for the remaining miRNAs. These findings suggest that feeding may influence the miRNA content of HM cells. The most highly and differentially expressed miRNAs were key regulators of milk components, with potential diagnostic value in lactation performance. They are also involved in the control of body fluid balance, thirst, appetite, immune response, and development, implicating their functional significance for the infant.

  20. Ex Vivo and in Silico Study of Human Common Carotid Arteries Pressure Response in Physiological and Inverted State

    Science.gov (United States)

    Piechna, A.; Cieślicki, K.; Lombarski, L.; Ciszek, B.

    2015-02-01

    Arterial walls are a multilayer structures with nonlinear material characteristics. Furthermore, residual stresses exist in unloaded state (zero-pressure condition) and they affect arterial behavior. To investigate these phenomena a number of theoretical and numerical studies were performed, however no experimental validation was proposed and realized yet. We cannot get rid of residual stresses without damaging the arterial segment. In this paper we propose a novel experiment to validate a numerical model of artery with residual stresses. The inspiration for our study originates from experiments made by Dobrin on dogs' arteries (1999). We applied the idea of turning the artery inside out. After such an operation the sequence of layer is reversed and the residual stresses are re-ordered. We performed several pressure-inflation tests on human Common Carotid Arteries (CCA) in normal and inverted configurations. The nonlinear responses of arterial behavior were obtained and compared to the numerical model. Computer simulations were carried out using the commercial software which applied the finite element method (FEM). Then, these results were discussed.

  1. The Application of Global Sensitivity Analysis in the Development of a Physiologically Based Pharmacokinetic Model for m-Xylene and Ethanol Co-Exposure in Humans

    Directory of Open Access Journals (Sweden)

    George D Loizou

    2015-06-01

    Full Text Available Global sensitivity analysis (SA was used during the development phase of a binary chemical physiologically based pharmacokinetic (PBPK model used for the analysis of m-xylene and ethanol co-exposure in humans. SA was used to identify those parameters which had the most significant impact on variability of venous blood and exhaled m-xylene and urinary excretion of the major metabolite of m-xylene metabolism, 3-methyl hippuric acid. This information informed the selection of parameters for estimation/calibration by fitting to measured biological monitoring (BM data in a Bayesian framework using Markov chain Monte Carlo (MCMC simulation. Data generated in controlled human studies were shown to be useful for investigating the structure and quantitative outputs of PBPK models as well as the biological plausibility and variability of parameters for which measured values were not available. This approach ensured that a priori knowledge in the form of prior distributions was ascribed only to those parameters that were identified as having the greatest impact on variability. This is an efficient approach which helps reduce computational cost.

  2. Evaluating functional roles of phase resetting in generation of adaptive human bipedal walking with a physiologically based model of the spinal pattern generator.

    Science.gov (United States)

    Aoi, Shinya; Ogihara, Naomichi; Funato, Tetsuro; Sugimoto, Yasuhiro; Tsuchiya, Kazuo

    2010-05-01

    The central pattern generators (CPGs) in the spinal cord strongly contribute to locomotor behavior. To achieve adaptive locomotion, locomotor rhythm generated by the CPGs is suggested to be functionally modulated by phase resetting based on sensory afferent or perturbations. Although phase resetting has been investigated during fictive locomotion in cats, its functional roles in actual locomotion have not been clarified. Recently, simulation studies have been conducted to examine the roles of phase resetting during human bipedal walking, assuming that locomotion is generated based on prescribed kinematics and feedback control. However, such kinematically based modeling cannot be used to fully elucidate the mechanisms of adaptation. In this article we proposed a more physiologically based mathematical model of the neural system for locomotion and investigated the functional roles of phase resetting. We constructed a locomotor CPG model based on a two-layered hierarchical network model of the rhythm generator (RG) and pattern formation (PF) networks. The RG model produces rhythm information using phase oscillators and regulates it by phase resetting based on foot-contact information. The PF model creates feedforward command signals based on rhythm information, which consists of the combination of five rectangular pulses based on previous analyses of muscle synergy. Simulation results showed that our model establishes adaptive walking against perturbing forces and variations in the environment, with phase resetting playing important roles in increasing the robustness of responses, suggesting that this mechanism of regulation may contribute to the generation of adaptive human bipedal locomotion.

  3. Response of soybean rhizosphere communities to human hygiene water addition as determined by community level physiological profiling (CLPP) and terminal restriction fragment length polymorphism (TRFLP) analysis

    Science.gov (United States)

    Kerkhof, L.; Santoro, M.; Garland, J.

    2000-01-01

    In this report, we describe an experiment conducted at Kennedy Space Center in the biomass production chamber (BPC) using soybean plants for purification and processing of human hygiene water. Specifically, we tested whether it was possible to detect changes in the root-associated bacterial assemblage of the plants and ultimately to identify the specific microorganism(s) which differed when plants were exposed to hygiene water and other hydroponic media. Plants were grown in hydroponics media corresponding to four different treatments: control (Hoagland's solution), artificial gray water (Hoagland's+surfactant), filtered gray water collected from human subjects on site, and unfiltered gray water. Differences in rhizosphere microbial populations in all experimental treatments were observed when compared to the control treatment using both community level physiological profiles (BIOLOG) and molecular fingerprinting of 16S rRNA genes by terminal restriction fragment length polymorphism analysis (TRFLP). Furthermore, screening of a clonal library of 16S rRNA genes by TRFLP yielded nearly full length SSU genes associated with the various treatments. Most 16S rRNA genes were affiliated with the Klebsiella, Pseudomonas, Variovorax, Burkholderia, Bordetella and Isosphaera groups. This molecular approach demonstrated the ability to rapidly detect and identify microorganisms unique to experimental treatments and provides a means to fingerprint microbial communities in the biosystems being developed at NASA for optimizing advanced life support operations.

  4. Response of soybean rhizosphere communities to human hygiene water addition as determined by community level physiological profiling (CLPP) and terminal restriction fragment length polymorphism (TRFLP) analysis

    Science.gov (United States)

    Kerkhof, L.; Santoro, M.; Garland, J.

    2000-01-01

    In this report, we describe an experiment conducted at Kennedy Space Center in the biomass production chamber (BPC) using soybean plants for purification and processing of human hygiene water. Specifically, we tested whether it was possible to detect changes in the root-associated bacterial assemblage of the plants and ultimately to identify the specific microorganism(s) which differed when plants were exposed to hygiene water and other hydroponic media. Plants were grown in hydroponics media corresponding to four different treatments: control (Hoagland's solution), artificial gray water (Hoagland's+surfactant), filtered gray water collected from human subjects on site, and unfiltered gray water. Differences in rhizosphere microbial populations in all experimental treatments were observed when compared to the control treatment using both community level physiological profiles (BIOLOG) and molecular fingerprinting of 16S rRNA genes by terminal restriction fragment length polymorphism analysis (TRFLP). Furthermore, screening of a clonal library of 16S rRNA genes by TRFLP yielded nearly full length SSU genes associated with the various treatments. Most 16S rRNA genes were affiliated with the Klebsiella, Pseudomonas, Variovorax, Burkholderia, Bordetella and Isosphaera groups. This molecular approach demonstrated the ability to rapidly detect and identify microorganisms unique to experimental treatments and provides a means to fingerprint microbial communities in the biosystems being developed at NASA for optimizing advanced life support operations.

  5. Low-frequency physiological activation of the vestibular utricle causes biphasic modulation of skin sympathetic nerve activity in humans.

    Science.gov (United States)

    Grewal, Tarandeep; Dawood, Tye; Hammam, Elie; Kwok, Kenny; Macefield, Vaughan G

    2012-07-01

    We have previously shown that sinusoidal galvanic vestibular stimulation, a means of selectively modulating vestibular afferent activity, can cause partial entrainment of sympathetic outflow to muscle and skin in human subjects. However, it influences the firing of afferents from the entire vestibular apparatus, including the semicircular canals. Here, we tested the hypothesis that selective stimulation of one set of otolithic organs-those located in the utricle, which are sensitive to displacement in the horizontal axis-could entrain sympathetic nerve activity. Skin sympathetic nerve activity (SSNA) was recorded via tungsten microelectrodes inserted into cutaneous fascicles of the common peroneal nerve in 10 awake subjects, seated (head vertical, eyes closed) on a motorised platform. Slow sinusoidal accelerations-decelerations (~4 mG) were applied in the X (antero-posterior) or Y (medio-lateral) direction at 0.08 Hz; composite movements in both directions were also applied. Subjects either reported feeling a vague sense of movement (with no sense of direction) or no movement at all. Nevertheless, cross-correlation analysis revealed a marked entrainment of SSNA for all types of movements: vestibular modulation was 97 ± 3 % for movements in the X axis and 91 ± 5 % for displacements in the Y axis. For each sinusoidal cycle, there were two major peaks of modulation-one associated with acceleration as the platform moved forward or to the side, and one associated with acceleration in the opposite direction. We interpret these observations as reflecting inertial displacement of the stereocilia within the utricle during acceleration, which causes a robust vestibulosympathetic reflex.

  6. Incorporation of Therapeutic Interventions in Physiologically Based Pharmacokinetic Modeling of Human Clinical Case Reports of Accidental or Intentional Overdosing with Ethylene Glycol

    Energy Technology Data Exchange (ETDEWEB)

    Corley, Rick A.; McMartin, K. E.

    2005-05-16

    Ethylene glycol is a high production volume chemical used in the manufacture of resins and fibers, antifreeze, deicing fluids, heat transfer and hydraulic fluids. Although occupational uses of ethylene glycol have not been associated with adverse effects, there are case reports where humans have either intentionally or accidentally ingested large quantities of ethylene glycol, primarily from antifreeze. The acute toxicity of ethylene glycol in humans and animals and can proceed through three stages, each associated with a different metabolite: central nervous system depression (ethylene glycol), cardiopulmonary effects associated with metabolic acidosis (glycolic acid) and ultimately renal toxicity (oxalic acid), depending upon the total amounts consumed and effectiveness of therapeutic interventions. A physiologically based pharmacokinetic (PBPK) model developed in a companion paper (Corley et al., 2004) was refined in this study to include clinically relevant treatment regimens for ethylene glycol poisoning such as hemodialysis or metabolic inhibition with either ethanol or fomepizole. Such modifications enabled the model to describe several human case reports which included analysis of ethylene glycol and/or glycolic acid. Such data and model simulations provide important confirmation that the PBPK model developed previously can adequately describe the pharmacokinetics of ethylene glycol in humans following low, occupational or environmentally relevant inhalation exposures, as well as massive oral doses even under conditions where treatments have been employed that markedly affect the disposition of ethylene glycol and glycolic acid. By integrating the case report data sets with controlled studies in this PBPK model, it was demonstrated that fomepizole, if administered early enough in a clinical situation, can be more effective than ethanol or hemodialysis in preventing the metabolism of ethylene glycol to more toxic metabolites. Hemodialysis remains an

  7. Metabolic profiling and flux analysis of MEL-2 human embryonic stem cells during exponential growth at physiological and atmospheric oxygen concentrations.

    Science.gov (United States)

    Turner, Jennifer; Quek, Lake-Ee; Titmarsh, Drew; Krömer, Jens O; Kao, Li-Pin; Nielsen, Lars; Wolvetang, Ernst; Cooper-White, Justin

    2014-01-01

    As human embryonic stem cells (hESCs) steadily progress towards regenerative medicine applications there is an increasing emphasis on the development of bioreactor platforms that enable expansion of these cells to clinically relevant numbers. Surprisingly little is known about the metabolic requirements of hESCs, precluding the rational design and optimisation of such platforms. In this study, we undertook an in-depth characterisation of MEL-2 hESC metabolic behaviour during the exponential growth phase, combining metabolic profiling and flux analysis tools at physiological (hypoxic) and atmospheric (normoxic) oxygen concentrations. To overcome variability in growth profiles and the problem of closing mass balances in a complex environment, we developed protocols to accurately measure uptake and production rates of metabolites, cell density, growth rate and biomass composition, and designed a metabolic flux analysis model for estimating internal rates. hESCs are commonly considered to be highly glycolytic with inactive or immature mitochondria, however, whilst the results of this study confirmed that glycolysis is indeed highly active, we show that at least in MEL-2 hESC, it is supported by the use of oxidative phosphorylation within the mitochondria utilising carbon sources, such as glutamine to maximise ATP production. Under both conditions, glycolysis was disconnected from the mitochondria with all of the glucose being converted to lactate. No difference in the growth rates of cells cultured under physiological or atmospheric oxygen concentrations was observed nor did this cause differences in fluxes through the majority of the internal metabolic pathways associated with biogenesis. These results suggest that hESCs display the conventional Warburg effect, with high aerobic activity despite high lactate production, challenging the idea of an anaerobic metabolism with low mitochondrial activity. The results of this study provide new insight that can be used in

  8. An Extended Minimal Physiologically Based Pharmacokinetic Model: Evaluation of Type II Diabetes Mellitus and Diabetic Nephropathy on Human IgG Pharmacokinetics in Rats.

    Science.gov (United States)

    Chadha, Gurkishan S; Morris, Marilyn E

    2015-11-01

    Although many studies have evaluated the effects of type 2 diabetes mellitus (T2DM) on the pharmacokinetics (PK) of low molecular weight molecules, there is limited information regarding effects on monoclonal antibodies. Our previous studies have reported significant increases in total (2-4 fold) and renal (100-300 fold) clearance of human IgG, an antibody isotype, in Zucker diabetic fatty (ZDF) rats. Pioglitazone treatment incompletely reversed the disease-related PK changes. The objective of this study was to construct a mechanistic model for simultaneous fitting plasma and urine data, to yield physiologically relevant PK parameters. We propose an extended minimal physiologically based PK (mPBPK) model specifically for IgG by classifying organs as either leaky or tight vascular tissues, and adding a kidney compartment. The model incorporates convection as the primary mechanism of IgG movement from plasma into tissues, interstitial fluid (ISF) in extravascular distribution space, and glomerular filtration rate (GFR), sieving coefficient and fraction reabsorbed in the kidney. The model captured the plasma and urine PK profiles well, and simulated concentrations in ISF. The model estimated a 2-4 fold increase in nonrenal clearance from plasma and 30-120 fold increase in renal clearance with T2DM, consistent with the experimental findings, and these differences in renal clearance were related to changes in GFR, sieving coefficient, and proximal tubular reabsorption. In conclusion, the mPBPK model offers a more relevant approach for analyzing plasma and urine IgG concentration-time data than conventional models and provides insight regarding alterations in distributional and elimination parameters occurring with T2DM.

  9. Carotid sinus physiology as affected by clothing pressure on human neck%颈部服装压对人体颈动脉窦生理的影响

    Institute of Scientific and Technical Information of China (English)

    吴志明; 赵敏; 陈星毅

    2011-01-01

    为研究人体颈部服装压对颈动脉窦生理的影响,选取15名青年女性为实验对象,测量其穿着不同领宽的针织高领衫时的服装压值.通过台阶实验,对人体在静止-运动-静止过程中心率和血压的变化进行客观评价.研究认为:服装压与心率、血压存在相关性,各项生理指标在颈部受压超过1.2kPa时呈明显下降趋势,运动状态受压对心血管系统造成的负面影响最为显著;不同穿着状态下,颈部受压对收缩压的影响显著于舒张压,颈部受压过大将影响人体在运动后的血压恢复.%A study of effect of clothing pressure on carotid sinus physiology selected fifteen females whose clothing pressure values when wearing knitted high collar shirts with different collar widths were measured. Data of heart rate and blood pressure of each subject were collected in static-dynamic-static state by step test for objective evaluation. The results showed that clothing pressure was correlated with heart rate and blood pressure, and all physiological indicators revealed a remarkable downward trend when the pressure on human neck exceeded 1.2 kPa. Pressure on the neck had the most significant negative impact on cardiovascular system while taking exercises. Pressure on the neck showed more significant effects on systolic blood pressure than on diastolic blood pressure in different wearing states,and overpressure on the neck would affect human blood pressure recovery after exercises.

  10. Physiologically relevant organs on chips.

    Science.gov (United States)

    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.

  11. Space Physiology within an Exercise Physiology Curriculum

    Science.gov (United States)

    Carter, Jason R.; West, John B.

    2013-01-01

    Compare and contrast strategies remain common pedagogical practices within physiological education. With the support of an American Physiological Society Teaching Career Enhancement Award, we have developed a junior- or senior-level undergraduate curriculum for exercise physiology that compares and contrasts the physiological adaptations of…

  12. Potassium physiology.

    Science.gov (United States)

    Thier, S O

    1986-04-25

    Potassium is the most abundant exchangeable cation in the body. It exists predominantly in the intracellular fluid at concentrations of 140 to 150 meq/liter and in the extracellular fluid at concentrations of 3.5 to 5 meq/liter. The maintenance of the serum potassium concentration is a complex bodily function and results from the balance between intake, excretion, and distribution between intracellular and extracellular space. Ingested potassium is virtually completely absorbed from and minimally excreted through the intestine under nonpathologic circumstances. Renal excretion of potassium, which is the major chronic protective mechanism against abnormalities in potassium balance, depends on filtration, reabsorption, and a highly regulated distal nephron secretory process. Factors regulating potassium secretion include prior potassium intake, intracellular potassium, delivery of sodium chloride and poorly reabsorbable anions to the distal nephron, the urine flow rate, hormones such as aldosterone and beta-catecholamines, and the integrity of the renal tubular cell. The maintenance of distribution between the inside and outside of cells depends on the integrity of the cell membrane and its pumps, osmolality, pH, and the hormones insulin, aldosterone, beta 2-catecholamines, alpha-catecholamines, and prostaglandins. Both distribution across cell membranes and/or renal excretion of potassium may be altered by pharmacologic agents such as diuretics, alpha- and beta-catechol antagonists and agonists, depolarizing agents, and digitalis. Problems with hypokalemia and hyperkalemia can be analyzed on the basis of potassium physiology and pharmacology; proper treatment depends on an accurate analysis.

  13. Tissue-specific gene expression templates for accurate molecular characterization of the normal physiological states of multiple human tissues with implication in development and cancer studies.

    Science.gov (United States)

    Hwang, Pei-Ing; Wu, Huan-Bin; Wang, Chin-Di; Lin, Bai-Ling; Chen, Cheng-Tao; Yuan, Shinsheng; Wu, Guani; Li, Ker-Chau

    2011-09-01

    To elucidate the molecular complications in many complex diseases, we argue for the priority to construct a model representing the normal physiological state of a cell/tissue. By analyzing three independent microarray datasets on normal human tissues, we established a quantitative molecular model GET, which consists of 24 tissue-specific Gene Expression Templates constructed from a set of 56 genes, for predicting 24 distinct tissue types under disease-free condition. 99.2% correctness was reached when a large-scale validation was performed on 61 new datasets to test the tissue-prediction power of GET. Network analysis based on molecular interactions suggests a potential role of these 56 genes in tissue differentiation and carcinogenesis.Applying GET to transcriptomic datasets produced from tissue development studies the results correlated well with developmental stages. Cancerous tissues and cell lines yielded significantly lower correlation with GET than the normal tissues. GET distinguished melanoma from normal skin tissue or benign skin tumor with 96% sensitivity and 89% specificity. These results strongly suggest that a normal tissue or cell may uphold its normal functioning and morphology by maintaining specific chemical stoichiometry among genes. The state of stoichiometry can be depicted by a compact set of representative genes such as the 56 genes obtained here. A significant deviation from normal stoichiometry may result in malfunction or abnormal growth of the cells.

  14. Solution structure of human plasma fibronectin using small-angle X-ray and neutron scattering at physiological pH and ionic strength

    Energy Technology Data Exchange (ETDEWEB)

    Sjoeberg, B.P.; Pap, S.; Osterlund, E.; Osterlund, K.; Vuento, M.; Kjems, J.

    1987-06-01

    Human plasma fibronectin has been investigated at physiological pH and ionic strength, by using small-angle X-ray and neutron scattering techniques. The results indicate that the molecule is disc shaped with an axial ratio of about 1:10. In fact, an ellipsoid of revolution with semiaxes a = 1.44 nm and b = c = 13.8 nm is in agreement with the experimental scattering data, and can also fully explain the rather extreme hydrodynamic parameters reported for fibronectin. The X-ray data gave a radius of gyration of 8.9 nm and a molecular weight of 510,000, whereas the neutron data gave slightly larger values, 9.5 nm and 530,000, respectively. From the volume of the best fitting ellipsoid we obtain a degree of hydration of 0.61 g H/sub 2/O/g protein (dry weight). Neutron data, recorded at different D/sub 2/O concentrations in the solvent, gave a match point of 43% D/sub 2/O, which indicates that approximately 80% of the hydrogens bound to oxygen and nitrogen are exchangeable.

  15. Prediction of Deoxypodophyllotoxin Disposition in Mouse, Rat, Monkey and Dog by Physiologically-based Pharmacokinetic Model and the Extrapolation to Human

    Directory of Open Access Journals (Sweden)

    Yang Chen

    2016-12-01

    Full Text Available Deoxypodophyllotoxin (DPT is a potential anti-tumor candidate prior to its clinical phase. The aim of the study was to develop a physiologically-based pharmacokinetic (PBPK model consisting of 13 tissue compartments to predict DPT disposition in mouse, rat, monkey and dog based on in vitro and in silico inputs. Since large interspecies difference was found in unbound fraction of DPT in plasma, we assumed that Kt:pl,u (unbound tissue-to-plasma concentration ratio was identical across species. The predictions of our model were then validated by in vivo data of corresponding preclinical species, along with visual predictive checks. Reasonable matches were found between observed and predicted plasma concentrations and pharmacokinetic parameters in all four animal species. The prediction in the related seven tissues of mouse was also desirable. We also attempted to predict human pharmacokinetic profile by both the developed PBPK model and interspecies allometric scaling across mouse, rat and monkey, while dog was excluded from the scaling. The two approaches reached similar results. We hope the study will help in the efficacy and safety assessment of DPT in future clinical studies and provide a reference to the preclinical screening of similar compounds by PBPK model.

  16. Tissue-specific gene expression templates for accurate molecular characterization of the normal physiological states of multiple human tissues with implication in development and cancer studies

    Directory of Open Access Journals (Sweden)

    Yuan Shinsheng

    2011-09-01

    Full Text Available Abstract Background To elucidate the molecular complications in many complex diseases, we argue for the priority to construct a model representing the normal physiological state of a cell/tissue. Results By analyzing three independent microarray datasets on normal human tissues, we established a quantitative molecular model GET, which consists of 24 tissue-specific Gene Expression Templates constructed from a set of 56 genes, for predicting 24 distinct tissue types under disease-free condition. 99.2% correctness was reached when a large-scale validation was performed on 61 new datasets to test the tissue-prediction power of GET. Network analysis based on molecular interactions suggests a potential role of these 56 genes in tissue differentiation and carcinogenesis. Applying GET to transcriptomic datasets produced from tissue development studies the results correlated well with developmental stages. Cancerous tissues and cell lines yielded significantly lower correlation with GET than the normal tissues. GET distinguished melanoma from normal skin tissue or benign skin tumor with 96% sensitivity and 89% specificity. Conclusions These results strongly suggest that a normal tissue or cell may uphold its normal functioning and morphology by maintaining specific chemical stoichiometry among genes. The state of stoichiometry can be depicted by a compact set of representative genes such as the 56 genes obtained here. A significant deviation from normal stoichiometry may result in malfunction or abnormal growth of the cells.

  17. Regulatory roles of the N-terminal domain based on crystal structures of human pyruvate dehydrogenase kinase 2 containing physiological and synthetic ligands.

    Science.gov (United States)

    Knoechel, Thorsten R; Tucker, Alec D; Robinson, Colin M; Phillips, Chris; Taylor, Wendy; Bungay, Peter J; Kasten, Shane A; Roche, Thomas E; Brown, David G

    2006-01-17

    Pyruvate dehydrogenase kinase (PDHK) regulates the activity of the pyruvate dehydrogenase multienzyme complex. PDHK inhibition provides a route for therapeutic intervention in diabetes and cardiovascular disorders. We report crystal structures of human PDHK isozyme 2 complexed with physiological and synthetic ligands. Several of the PDHK2 structures disclosed have C-terminal cross arms that span a large trough region between the N-terminal regulatory (R) domains of the PDHK2 dimers. The structures containing bound ATP and ADP demonstrate variation in the conformation of the active site lid, residues 316-321, which enclose the nucleotide beta and gamma phosphates at the active site in the C-terminal catalytic domain. We have identified three novel ligand binding sites located in the R domain of PDHK2. Dichloroacetate (DCA) binds at the pyruvate binding site in the center of the R domain, which together with ADP, induces significant changes at the active site. Nov3r and AZ12 inhibitors bind at the lipoamide binding site that is located at one end of the R domain. Pfz3 (an allosteric inhibitor) binds in an extended site at the other end of the R domain. We conclude that the N-terminal domain of PDHK has a key regulatory function and propose that the different inhibitor classes act by discrete mechanisms. The structures we describe provide insights that can be used for structure-based design of PDHK inhibitors.

  18. 论瑜伽练习对人体生理机能的功效%On Efficacy of Yoga on Human Physiology

    Institute of Scientific and Technical Information of China (English)

    施明雅

    2014-01-01

    瑜伽是一项可以全民健身的体育运动项目,它在练习时基本不受时间、场地和人数的限制,它不但可以强身健体,而且可以消除疲劳和紧张郁闷等负面情绪,是一项对身体很好的体育运动项目。练习者可根据自己的情况来选择练习内容,它是一项有着极高锻炼价值的运动项目,本文将通过文献资料法、访谈等方法对瑜伽练习对人体生理机能的功效进行分析。%Yoga is a nationwide body-building sports project, it does not in practice limited by the timing, venue and number, it will not only build stronger bodies, and can eliminate fatigue and tension depression and other negative emotions, is a very good sports on the body. Practitioner to select exercises depending on their content, of efficient training value significance it was one of the sport, this article through the literature, interviews and other methods of analysis of the effectiveness of Yoga training on physiological function of human body.

  19. Intraoperative engineering of osteogenic grafts combining freshly harvested, human adipose-derived cells and physiological doses of bone morphogenetic protein-2

    Directory of Open Access Journals (Sweden)

    A Mehrkens

    2012-09-01

    Full Text Available Engineered osteogenic constructs for bone repair typically involve complex and costly processes for cell expansion. Adipose tissue includes mesenchymal precursors in large amounts, in principle allowing for an intraoperative production of osteogenic grafts and their immediate implantation. However, stromal vascular fraction (SVF cells from adipose tissue were reported to require a molecular trigger to differentiate into functional osteoblasts. The present study tested whether physiological doses of recombinant human BMP-2 (rhBMP-2 could induce freshly harvested human SVF cells to generate ectopic bone tissue. Enzymatically dissociated SVF cells from 7 healthy donors (1 x 106 or 4 x 106 were immediately embedded in a fibrin gel with or without 250 ng rhBMP-2, mixed with porous silicated calcium-phosphate granules (Actifuse®, Apatech (final construct size: 0.1 cm3 and implanted ectopically for eight weeks in nude mice. In the presence of rhBMP-2, SVF cells not only supported but directly contributed to the formation of bone ossicles, which were not observed in control cell-free, rhBMP-2 loaded implants. In vitro analysis indicated that rhBMP-2 did not involve an increase in the percentage of SVF cells recruited to the osteogenic lineage, but rather induced a stimulation of the osteoblastic differentiation of the committed progenitors. These findings confirm the feasibility of generating fully osteogenic grafts using an easily accessible autologous cell source and low amounts of rhBMP-2, in a timing compatible with an intraoperative schedule. The study warrants further investigation at an orthotopic site of implantation, where the delivery of rhBMP-2 could be bypassed thanks to the properties of the local milieu.

  20. New Roles Assigned to the α1–β1 (and α2–β2 Interface of the Human Hemoglobin Molecule from Physiological to Cellular

    Directory of Open Access Journals (Sweden)

    Yoshiaki Sugawara

    2011-11-01

    Full Text Available Cellular life is reliant upon rapid and efficient responses to internal and external conditions. The basic molecular events associated with these processes are the structural transitions of the proteins (structural protein allostery involved. From this view, the human hemoglobin (Hb molecule (α2β2 holds a special position in this field. Hb has two types of αβ interface (i.e., α1β1 [and α2β2] and α1β2 [and α2β1]. The latter α1–β2 (and α2–β1 interface is known to be associated with cooperative O2 binding, and exhibits principal roles if the molecule goes from its deoxy to oxy quaternary structure. However, the role of the former α1–β1 (and α2–β2 interface has been unclear for a long time. In this regard, important and intriguing observations have been accumulating. A new role was attributed first as stabilizing the HbO2 tetramer against acidic autoxidation. That is, the α1–β1 (and α2–β2 interface produces a conformational constraint in the β chain whereby the distal (E7 histidine (His residue is tilted slightly away from the bound O2 so as to prevent proton-catalyzed displacement of O2– by a solvent water molecule. The β chains thus acquire pH-dependent delayed autoxidation in the HbO2 tetramer. The next role was suggested by our studies searching for similar phenomena in normal human erythrocytes under mild heating. Tilting of the distal (E7 His in turn triggered degradation of the Hb molecule to hemichrome, and subsequent clustering of Heinz bodies within the erythrocyte. As Heinz body-containing red cells become trapped in the spleen, it was demonstrated that the α1–β1 (and α2–β2 interface may exert delicate control of the fate (removal of its own erythrocyte. Herein we review and summarize the related results and current interpretation of the oxidative behavior of human Hb, emphasizing the correlation between hemichrome emergence and Heinz-body formation, and specifically discuss the new roles

  1. Brown Adipose Tissue in Human and Its Potential Physiological Significance%人体内褐色脂肪组织及其生理功能

    Institute of Scientific and Technical Information of China (English)

    李永国; 颜忠诚; 王德华

    2011-01-01

    Brown adipose tissue (BAT) plays an important role in nonshiverthing thermogenesis, thermoregulation and body mass regulation in small mammals. However, in human, the presence of brown adipose tissue was thought to be relevant only in infants, with negligible physiologic relevance in adult.Recently, using 18F-fluorodeoxyglucose ( 18 F-FDG) positron-emission tomographic and computed tomographic (PET-CT) scans showed that adults retain metabolically active BAT depots that can be induced in response to cold and sympathetic nervous system activation. These findings highlight BAT as a potential relevant target for pharmacological and gene expression manipulation to combat human obesity. We reviewed the recent research progresses of BAT in human and its potential functional significance.%褐色脂肪组织(brown adipose tissue,BAT)在小型哺乳动物的非颤抖性产热、体温调节以及体重维持等方面都具有重要的生理功能.在人类中,曾一度认为褐色脂肪组织只在新生儿中存在,在成人体中不存在或数量甚微而没有生理意义.随着医学科技的发展,2009年采用监测癌症及癌症转移的氟化脱氧葡萄糖正电子发射计算机断层显像技术-X射线断层显像技术(18F-FDG PET-CT)检测到在成年人体内也存在功能性的褐色脂肪组织,此发现颠覆了传统的观念,也为人类对抗肥胖提供了新靶标.本文就褐色脂肪组织在人类体内的存在及其潜在的生理意义进行了概述.

  2. Physiologically based pharmacokinetic-pharmacodynamic modeling to predict concentrations and actions of sodium-dependent glucose transporter 2 inhibitor canagliflozin in human intestines and renal tubules.

    Science.gov (United States)

    Mori, Kazumi; Saito, Ryuta; Nakamaru, Yoshinobu; Shimizu, Makiko; Yamazaki, Hiroshi

    2016-11-01

    Canagliflozin is a recently developed sodium-glucose cotransporter (SGLT) 2 inhibitor that promotes renal glucose excretion and is considered to inhibit renal SGLT2 from the luminal side of proximal tubules. Canagliflozin reportedly inhibits SGLT1 weakly and suppresses postprandial plasma glucose, suggesting that it also inhibits intestinal SGLT1. However, it is difficult to measure the drug concentrations of these assumed sites of action directly. The pharmacokinetic-pharmacodynamic (PK/PD) relationships of canagliflozin remain poorly characterized. Therefore, a physiologically based pharmacokinetic (PBPK) model of canagliflozin was developed based on clinical data from healthy volunteers and it was used to simulate luminal concentrations in intestines and renal tubules. In small intestine simulations, the inhibition ratios for SGLT1 were predicted to be 40%-60% after the oral administration of clinical doses (100-300 mg/day). In contrast, inhibition ratios of canagliflozin for renal SGLT2 and SGLT1 were predicted to be approximately 100% and 0.2%-0.4%, respectively. These analyses suggest that canagliflozin only inhibits SGLT2 in the kidney. Using the simulated proximal tubule luminal concentrations of canagliflozin, the urinary glucose excretion rates in canagliflozin-treated diabetic patients were accurately predicted using the renal glucose reabsorption model as a PD model. Because the simulation of canagliflozin pharmacokinetics was successful, this PBPK methodology was further validated by successfully simulating the pharmacokinetics of dapagliflozin, another SGLT2 inhibitor. The present results suggest the utility of this PBPK/PD model for predicting canagliflozin concentrations at target sites and help to elucidate the pharmacological effects of SGLT1/2 inhibition in humans. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Physiological observations validate finite element models for estimating subject-specific electric field distributions induced by transcranial magnetic stimulation of the human motor cortex.

    Science.gov (United States)

    Opitz, Alexander; Legon, Wynn; Rowlands, Abby; Bickel, Warren K; Paulus, Walter; Tyler, William J

    2013-11-01

    Recent evidence indicates subject-specific gyral folding patterns and white matter anisotropy uniquely shape electric fields generated by TMS. Current methods for predicting the brain regions influenced by TMS involve projecting the TMS coil position or center of gravity onto realistic head models derived from structural and functional imaging data. Similarly, spherical models have been used to estimate electric field distributions generated by TMS pulses delivered from a particular coil location and position. In the present paper we inspect differences between electric field computations estimated using the finite element method (FEM) and projection-based approaches described above. We then more specifically examined an approach for estimating cortical excitation volumes based on individualistic FEM simulations of electric fields. We evaluated this approach by performing neurophysiological recordings during MR-navigated motormapping experiments. We recorded motor evoked potentials (MEPs) in response to single pulse TMS using two different coil orientations (45° and 90° to midline) at 25 different locations (5×5 grid, 1cm spacing) centered on the hotspot of the right first dorsal interosseous (FDI) muscle in left motor cortex. We observed that motor excitability maps varied within and between subjects as a function of TMS coil position and orientation. For each coil position and orientation tested, simulations of the TMS-induced electric field were computed using individualistic FEM models and compared to MEP amplitudes obtained during our motormapping experiments. We found FEM simulations of electric field strength, which take into account subject-specific gyral geometry and tissue conductivity anisotropy, significantly correlated with physiologically observed MEP amplitudes (rmax=0.91, p=1.8×10(-5) rmean=0.81, p=0.01). These observations validate the implementation of individualistic FEM models to account for variations in gyral folding patterns and tissue

  4. Physiologically based pharmacokinetic modeling of human exposure to perfluorooctanoic acid suggests historical non drinking-water exposures are important for predicting current serum concentrations.

    Science.gov (United States)

    Worley, Rachel Rogers; Yang, Xiaoxia; Fisher, Jeffrey

    2017-09-01

    Manufacturing of perfluorooctanoic acid (PFOA), a synthetic chemical with a long half-life in humans, peaked between 1970 and 2002, and has since diminished. In the United States, PFOA is detected in the blood of >99% of people tested, but serum concentrations have decreased since 1999. Much is known about exposure to PFOA in drinking water; however, the impact of non-drinking water PFOA exposure on serum PFOA concentrations is not well characterized. The objective of this research is to apply physiologically based pharmacokinetic (PBPK) modeling and Monte Carlo analysis to evaluate the impact of historic non-drinking water PFOA exposure on serum PFOA concentrations. In vitro to in vivo extrapolation was utilized to inform descriptions of PFOA transport in the kidney. Monte Carlo simulations were incorporated to evaluate factors that account for the large inter-individual variability of serum PFOA concentrations measured in individuals from North Alabama in 2010 and 2016, and the Mid-Ohio River Valley between 2005 and 2008. Predicted serum PFOA concentrations were within two-fold of experimental data. With incorporation of Monte Carlo simulations, the model successfully tracked the large variability of serum PFOA concentrations measured in populations from the Mid-Ohio River Valley. Simulation of exposure in a population of 45 adults from North Alabama successfully predicted 98% of individual serum PFOA concentrations measured in 2010 and 2016, respectively, when non-drinking water ingestion of PFOA exposure was included. Variation in serum PFOA concentrations may be due to inter-individual variability in the disposition of PFOA and potentially elevated historical non-drinking water exposures. Published by Elsevier Inc.

  5. Application of the physiological and morphological parameters of the brazilian population sample to the mathematical model of the human respiratory tract; Aplicacao dos parametros fisiologicos e morfologicos de uma amostra da populacao brasileira no modelo matematico do trato respiratorio humano

    Energy Technology Data Exchange (ETDEWEB)

    Reis, Arlene Alves dos

    2005-07-01

    The Human Respiratory Tract Model proposed by the ICRP Publication 66 accounts for the morphology and physiology of the respiratory tract. The characteristics of air drawn into the lungs and exhaled are greatly influenced by the morphology of the respiratory tract, which causes numerous changes in pressure, flow rate, direction and humidity as air moves into and out of the lungs. Concerning the respiratory physiological parameters the breathing characteristics influence the volume, the inhalation rate of air and the portion that enters through the nose and the mouth. These characteristics are important to determine the fractional deposition. The model uses morphological and physiological parameters from the Caucasian man to establish deposition fractions in the respiratory tract regions. It is known that the morphology and physiology are influenced by environmental, occupational and economic conditions. The ICRP recommends, for a reliable evaluation of the regional deposition, the use of parameters from a local population when information is available. The main purpose of this study is to verify the influence in using the morphology and physiology parameters representative of a sample of the Brazilian population on the deposition model of the ICRP Publication 66. The morphological and physiological data were obtained from the literature. The software EXCEL for Windows (version 2000) was used in order to implement the deposition model and also to allow the changes in parameters of interest. Initially, the implemented model was checked using the parameters defined by the ICRP and the results of the fraction deposition in the respiratory tract compartments were compared. Finally, morphological and physiological parameters from Brazilian adult male were applied and the fractional deposition calculated. The results suggest a significant variation in fractional deposition when Brazilian parameters are applied in the model. (author)

  6. 医用镁合金降解及其对人体的影响%Medical magnesium alloy degradation and its impact on human physiology

    Institute of Scientific and Technical Information of China (English)

    高家诚; 胡德; 宋长江

    2012-01-01

    镁合金具有比高分子更高的强度、比陶瓷材料更好的韧性,与人体自然骨的密度、弹性模量和力学性能也更为接近。更重要的是,其植入人体后将会逐步腐蚀降解,既无毒副作用也无需二次手术,是一种极具潜质的新型可降解生物金属材料。但镁在人体生理环境中腐蚀速度太快,可能导致镁离子、氢气、局部pH值和腐蚀沉淀物在体内发生堆积,同时镁合金的机械完整性和力学性能也会因此丧失,达不到预期的治疗目的,甚至引起不良反应和治疗失败。从镁在人体的腐蚀机理和降解产物对人体造成的影响进行综述,并分析了镁合金在未来的发展方向和挑战。%Magnesium alloy has a higher strength than the polymer, better toughness than ceramic materials, and the density,elastic modulus and mechanical properties are also closer to the body's natural bone, More im- portantly, magnesium alloy can be corrossed and degradated after implanted into the human body,neither cause side effects do not need the second surgery, so it was considered as a great potential biodegradable materials. However,excessive corrosion rate of magnesium in the body's physiological environment will lead to magnesi- um ions, hydrogen and corrosion sediment accumulation in the body, the local pH value increased and the me- chanical structure was incomplete, reduce the treatment effect, and even cause adverse reactions and treatment failure. From the magnesium corrosion mechanism and degradation products in the human body impact were re- viewed and analyzed the magnesium alloy in the future development direction and challenges.

  7. Medical electronics and physiological measurement

    Science.gov (United States)

    Cochrane, T.

    1989-07-01

    This article describes some recent developments in physiological measurement since the last `special issue' in 1978. Nine examples are given covering mature applications, new techniques and some `ideas for the future'. The need for good scientists in this interesting and challenging area is stressed. Physiological measurement is challenging because human physiology is complex. The examples described in this article illustrate some areas where cooperation between basic scientists, engineers, clinicians and, not least, patients has led to remarkable advances in our understanding of man and his physiology. Many challenges still lie ahead. There is no doubt that good quality graduates, with fresh minds and fresh enthusiasm, are needed to build on the foundation that has already been laid.

  8. Research Progress of Acquisition Technology of Human Physiological Signals Based on Literature Novelty Search%基于文献查新探讨人体生理信号采集技术进展

    Institute of Scientific and Technical Information of China (English)

    尤惠霞; 谢雪玲; 吴雅云

    2013-01-01

    本文基于对同方中国知网和万方医学期刊两个数据库的文献查新,探讨人体生理信号采集技术及采集项目的研究进展情况,为本课题研究人员提供研究思路,避免重复性研究,推动该课题研究更深入发展。%This paper discussed the research progress about acquisition technologies and acquisition projects of human physiological signals based on literature novelty search of CNKI database and WanFang database, to provide research ideas for researchers so that they can avoid conducting repetitive researchs and promote further development of acquisition technologies and acquisition projects of human physiological signals.

  9. 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

    Science.gov (United States)

    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.

  10. Medical Study on Physiological Load in the Process of Human Movement%人体运动过程中的医学生理负荷的研究

    Institute of Scientific and Technical Information of China (English)

    刘宗祥

    2014-01-01

    This paper comprehensively analyzed the physiological load of relevant concepts, through the analysis of the sports staff feel physiological load situation, and combine the physiological load of heart rate index analysis of sports per-sonnel, the comprehensive analysis of heart rate on the basis of the index with the physiological load of exercise, is con-structed based on the index of heart rate level of sports physiological load evaluation, personnel movement can be ana-lyzed based on the assessment level, timely adjust the movement of physiological load, and prevent the occurrence of sports injury, improve the quality of movement.%通过人体运动过程中的生理负荷强度能够有效描述人体运动的状态,并且可反映人体对运动强度的适应情况。目前常用的生理负荷强度测量方法有心率、吸氧量、乳酸浓度以及呼吸频率等。通过全面分析了生理负荷的相关概念,利用运动人员的自我感觉分析生理负荷情况,并结合心率指标分析运动人员的生理负荷,在全面分析心率指标同运动生理负荷关系的基础上,构建了基于心率指标的运动生理负荷评估等级,基于该评估等级可分析运动人员的运动情况,及时调整运动人员的生理负荷,避免运动伤痛的发生,提高运动质量。

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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…

  13. Conservation physiology of animal migration.

    Science.gov (United States)

    Lennox, Robert J; Chapman, Jacqueline M; Souliere, Christopher M; Tudorache, Christian; Wikelski, Martin; Metcalfe, Julian D; Cooke, Steven J

    2016-01-01

    Migration is a widespread phenomenon among many taxa. This complex behaviour enables animals to exploit many temporally productive and spatially discrete habitats to accrue various fitness benefits (e.g. growth, reproduction, predator avoidance). Human activities and global environmental change represent potential threats to migrating animals (from individuals to species), and research is underway to understand mechanisms that control migration and how migration responds to modern challenges. Focusing on behavioural and physiological aspects of migration can help to provide better understanding, management and conservation of migratory populations. Here, we highlight different physiological, behavioural and biomechanical aspects of animal migration that will help us to understand how migratory animals interact with current and future anthropogenic threats. We are in the early stages of a changing planet, and our understanding of how physiology is linked to the persistence of migratory animals is still developing; therefore, we regard the following questions as being central to the conservation physiology of animal migrations. Will climate change influence the energetic costs of migration? Will shifting temperatures change the annual clocks of migrating animals? Will anthropogenic influences have an effect on orientation during migration? Will increased anthropogenic alteration of migration stopover sites/migration corridors affect the stress physiology of migrating animals? Can physiological knowledge be used to identify strategies for facilitating the movement of animals? Our synthesis reveals that given the inherent challenges of migration, additional stressors derived from altered environments (e.g. climate change, physical habitat alteration, light pollution) or interaction with human infrastructure (e.g. wind or hydrokinetic turbines, dams) or activities (e.g. fisheries) could lead to long-term changes to migratory phenotypes. However, uncertainty remains

  14. A Review of the Comparative Anatomy, Histology, Physiology and Pathology of the Nasal Cavity of Rats, Mice, Dogs and Non-human Primates. Relevance to Inhalation Toxicology and Human Health Risk Assessment.

    Science.gov (United States)

    Chamanza, R; Wright, J A

    2015-11-01

    There are many significant differences in the structural and functional anatomy of the nasal cavity of man and laboratory animals. Some of the differences may be responsible for the species-specific nasal lesions that are often observed in response to inhaled toxicants. This paper reviews the comparative anatomy, physiology and pathology of the nasal cavity of the rat, mouse, dog, monkey and man, highlighting factors that may influence the distribution of nasal lesions. Gross anatomical variations such as turbinate structure, folds or grooves on nasal walls, or presence or absence of accessory structures, may influence nasal airflow and species-specific uptake and deposition of inhaled material. In addition, interspecies variations in the morphological and biochemical composition and distribution of the nasal epithelium may affect the local tissue susceptibility and play a role in the development of species-specific nasal lesions. It is concluded that, while the nasal cavity of the monkey might be more similar to that of man, each laboratory animal species provides a model that responds in a characteristic and species-specific manner. Therefore for human risk assessment, careful consideration must be given to the anatomical differences between a given animal model and man.

  15. Development of Human Physiological Signals Generator Based on Virtual Instrument%基于虚拟仪器的人体生理信号发生器的研制

    Institute of Scientific and Technical Information of China (English)

    陆宏伟; 王春芳; 花有园; 田佳佳; 刘世海

    2013-01-01

    目的:基于虚拟仪器技术构建人体生理信号发生器.方法:利用MIT-BIH等标准数据库中大量免费的人体生理数据,通过NI公司的PCI数据采集卡(可实现模-数/数-模转换,本研究利用其数-模转换功能),利用LabVIEW编程实现模拟信号输出.采用NI-PCI 6221 DAQ卡,插入电脑PCI插槽构成系统硬件.系统软件先读入头文件,根据头文件各个字段设置相应变量,然后读入数据文件,根据文件格式进行解码,计算出相应数值发送给DAQ卡,输出模拟信号.DAQ卡的配置可通过LabVIEW自带的DAQ Assistant助手.结果:可准确输出心电、脑电、肌电、体温、呼吸、血压等多种人体生理信号,信号的幅值等参数可调.结论:利用虚拟仪器技术可简单灵活地输出多种人体生理参数,与其他只能重复输出相同波形且价格昂贵的模拟仪比,本研究的人体生理信号发生器具有很高的性价比.%Objective: A human physiological signals generator based on virtual instrument is developed. Methods: We utilize the PCI data acquisition card by NI corporation (which has both AD and DA functions, in this study we only use the DA function) and the PC as system's hardware, the master machine program developed with Lab VIEW environment as system's software. By utilizing the huge amount of freely accessible digital human physiological signals provided by MIT-BIH and other databases, the system can generate analog human physiological signals. The system's hardware is composed of NI-PCI 6221 DAQ card and the PC. Firstly, the software read the head file, and several variables were set according to the fields of the head file. Secondly, data file was read into the computer by decoding the file format. The configuration of the DAQ card was made by utilizing the DAQ assistant. Lastly, a figure was computed and sent to the DAQ card to output the analog signal. Results: The system can precisely generate many kinds of human physiological

  16. 人体解剖生理学课程引入虚拟现实技术的教改探索%Applying Virtual Reality Technology in"Human Anatomy ;and Physiology"

    Institute of Scientific and Technical Information of China (English)

    范敏; 戴培山

    2014-01-01

    "Human Anatomy and Physiology" is a course with many teaching contents, it contains complex anatomy structures. The course needs rich spatial imagination. It is very difficult for non-medical students in higher education institutions to under-stand human anatomy structure and physiology. In this paper, virtual reality technology was applied in "Human Anatomy and Physiology" teaching, and human eye, ear and cardiovascular system were taken as examples to show how to apply virtual real-ity technology in teaching. By contrast, we found that with its characters of intuitive and vivid, the virtual reality technology in creased students' interest in the course,improved the teaching effect.%人体解剖生理学课程教学内容多,涉及的人体结构复杂,需要较强的空间想象能力。非医学院校的学生理解人体解剖结构和生理功能比较困难。本文将虚拟现实技术引入到人体解剖生理学的教学当中,以人眼、耳和心血管系统的教学内容为例分析了如何在教学过程中引入虚拟现实技术。通过对比,我们发现虚拟现实技术利用其直观、形象的特点,增加了学生对课程的兴趣,提高了教学效果。

  17. Network Physiology: How Organ Systems Dynamically Interact.

    Science.gov (United States)

    Bartsch, Ronny P; Liu, Kang K L; Bashan, Amir; Ivanov, Plamen Ch

    2015-01-01

    We systematically study how diverse physiologic systems in the human organism dynamically interact and collectively behave to produce distinct physiologic states and functions. This is a fundamental question in the new interdisciplinary field of Network Physiology, and has not been previously explored. Introducing the novel concept of Time Delay Stability (TDS), we develop a computational approach to identify and quantify networks of physiologic interactions from long-term continuous, multi-channel physiological recordings. We also develop a physiologically-motivated visualization framework to map networks of dynamical organ interactions to graphical objects encoded with information about the coupling strength of network links quantified using the TDS measure. Applying a system-wide integrative approach, we identify distinct patterns in the network structure of organ interactions, as well as the frequency bands through which these interactions are mediated. We establish first maps representing physiologic organ network interactions and discover basic rules underlying the complex hierarchical reorganization in physiologic networks with transitions across physiologic states. Our findings demonstrate a direct association between network topology and physiologic function, and provide new insights into understanding how health and distinct physiologic states emerge from networked interactions among nonlinear multi-component complex systems. The presented here investigations are initial steps in building a first atlas of dynamic interactions among organ systems.

  18. Network Physiology: How Organ Systems Dynamically Interact.

    Directory of Open Access Journals (Sweden)

    Ronny P Bartsch

    Full Text Available We systematically study how diverse physiologic systems in the human organism dynamically interact and collectively behave to produce distinct physiologic states and functions. This is a fundamental question in the new interdisciplinary field of Network Physiology, and has not been previously explored. Introducing the novel concept of Time Delay Stability (TDS, we develop a computational approach to identify and quantify networks of physiologic interactions from long-term continuous, multi-channel physiological recordings. We also develop a physiologically-motivated visualization framework to map networks of dynamical organ interactions to graphical objects encoded with information about the coupling strength of network links quantified using the TDS measure. Applying a system-wide integrative approach, we identify distinct patterns in the network structure of organ interactions, as well as the frequency bands through which these interactions are mediated. We establish first maps representing physiologic organ network interactions and discover basic rules underlying the complex hierarchical reorganization in physiologic networks with transitions across physiologic states. Our findings demonstrate a direct association between network topology and physiologic function, and provide new insights into understanding how health and distinct physiologic states emerge from networked interactions among nonlinear multi-component complex systems. The presented here investigations are initial steps in building a first atlas of dynamic interactions among organ systems.

  19. 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

    Science.gov (United States)

    2003-12-01

    collective group of EEG, EMG and EOG measurements taken when studying sleep stages is referred to as Polysomnography (PSG). The physiologic sensor...AND OWL survey via web input forms. • The RESEARCH TEAM updates the ACTIGRAPH STATUS and PDA STATUS and assigns ACTIGRAPHs and PDAs to...LOG tables. The COLLECTED EQUIPMENT AND DATA are updated to ensure all equipment is accounted for and all available data have been collected from

  20. Development of clothing micro climate monitoring system for human physiological indexes%人体生理指标与服装微气候监测系统研发

    Institute of Scientific and Technical Information of China (English)

    洪岩; 杨敏; 陈雁

    2013-01-01

    This study is devoted to how to monitor human physiological indexes by observing the change of related indexes of the clothing micro climate monitoring system. Having analyzed the clothing which makes a person feel comfortable and enjoy good healthy as well as related physiological indexes, we investigated the rou