The effect of oxygen tension on human articular chondrocyte matrix synthesis: Integration of experimental and computational approaches

PubMed Central

Li, S; Oreffo, ROC; Sengers, BG; Tare, RS

2014-01-01

Significant oxygen gradients occur within tissue engineered cartilaginous constructs. Although oxygen tension is an important limiting parameter in the development of new cartilage matrix, its precise role in matrix formation by chondrocytes remains controversial, primarily due to discrepancies in the experimental setup applied in different studies. In this study, the specific effects of oxygen tension on the synthesis of cartilaginous matrix by human articular chondrocytes were studied using a combined experimental-computational approach in a “scaffold-free” 3D pellet culture model. Key parameters including cellular oxygen uptake rate were determined experimentally and used in conjunction with a mathematical model to estimate oxygen tension profiles in 21-day cartilaginous pellets. A threshold oxygen tension (pO2 ≈ 8% atmospheric pressure) for human articular chondrocytes was estimated from these inferred oxygen profiles and histological analysis of pellet sections. Human articular chondrocytes that experienced oxygen tension below this threshold demonstrated enhanced proteoglycan deposition. Conversely, oxygen tension higher than the threshold favored collagen synthesis. This study has demonstrated a close relationship between oxygen tension and matrix synthesis by human articular chondrocytes in a “scaffold-free” 3D pellet culture model, providing valuable insight into the understanding and optimization of cartilage bioengineering approaches. Biotechnol. Bioeng. 2014;111: 1876–1885. PMID:24668194

Humans and monkeys use different strategies to solve the same short-term memory tasks.

PubMed

Wittig, John H; Morgan, Barak; Masseau, Evan; Richmond, Barry J

2016-11-01

The neural mechanisms underlying human working memory are often inferred from studies using old-world monkeys. Humans use working memory to selectively memorize important information. We recently reported that monkeys do not seem to use selective memorization under experimental conditions that are common in monkey research, but less common in human research. Here we compare the performance of humans and monkeys under the same experimental conditions. Humans selectively remember important images whereas monkeys largely rely on recency information from nonselective memorization. Working memory studies in old-world monkeys must be interpreted cautiously when making inferences about the mechanisms underlying human working memory. © 2016 Wittig, et al.; Published by Cold Spring Harbor Laboratory Press.

Service Learning as a Mechanism for Change in Attitudes and Perceptions of Human Services Students toward Substance-Dependent Mothers

ERIC Educational Resources Information Center

Hogan, Sean R.; Bailey, Caroline E.

2010-01-01

The purpose of the study was to explore the potential effectiveness of service learning as a pedagogical technique for providing substance abuse education to human services/social work students. Using a quasi-experimental design, the authors assigned 38 human services undergraduate students to experimental and comparison groups on the basis of…

A model of human event detection in multiple process monitoring situations

NASA Technical Reports Server (NTRS)

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

1978-01-01

It is proposed that human decision making in many multi-task situations might be modeled in terms of the manner in which the human detects events related to his tasks and the manner in which he allocates his attention among his tasks once he feels events have occurred. A model of human event detection performance in such a situation is presented. An assumption of the model is that, in attempting to detect events, the human generates the probability that events have occurred. Discriminant analysis is used to model the human's generation of these probabilities. An experimental study of human event detection performance in a multiple process monitoring situation is described and the application of the event detection model to this situation is addressed. The experimental study employed a situation in which subjects simulataneously monitored several dynamic processes for the occurrence of events and made yes/no decisions on the presence of events in each process. Input to the event detection model of the information displayed to the experimental subjects allows comparison of the model's performance with the performance of the subjects.

Gene Expression Analysis to Assess the Relevance of Rodent Models to Human Lung Injury.

PubMed

Sweeney, Timothy E; Lofgren, Shane; Khatri, Purvesh; Rogers, Angela J

2017-08-01

The relevance of animal models to human diseases is an area of intense scientific debate. The degree to which mouse models of lung injury recapitulate human lung injury has never been assessed. Integrating data from both human and animal expression studies allows for increased statistical power and identification of conserved differential gene expression across organisms and conditions. We sought comprehensive integration of gene expression data in experimental acute lung injury (ALI) in rodents compared with humans. We performed two separate gene expression multicohort analyses to determine differential gene expression in experimental animal and human lung injury. We used correlational and pathway analyses combined with external in vitro gene expression data to identify both potential drivers of underlying inflammation and therapeutic drug candidates. We identified 21 animal lung tissue datasets and three human lung injury bronchoalveolar lavage datasets. We show that the metasignatures of animal and human experimental ALI are significantly correlated despite these widely varying experimental conditions. The gene expression changes among mice and rats across diverse injury models (ozone, ventilator-induced lung injury, LPS) are significantly correlated with human models of lung injury (Pearson r = 0.33-0.45, P < 1E -16 ). Neutrophil signatures are enriched in both animal and human lung injury. Predicted therapeutic targets, peptide ligand signatures, and pathway analyses are also all highly overlapping. Gene expression changes are similar in animal and human experimental ALI, and provide several physiologic and therapeutic insights to the disease.

Proceedings of the Second Workshop on Numerical Analysis of Human and Surrogate Response to Accelerative Loading

DTIC Science & Technology

2018-02-01

Dissection  2 primary experimental loading cases Tissue-Level Characterization Quasi -Static Bending (Hueur et al., 2006) High-Rate Combined...Yang Hybrid III Crash-Dummy Lower Ext. under High Speed Vertical Loading: A Combined Experimental and Computational Study Wayne State 14:05...25 Tusit Weerasooriya Mechanical Response of Human and Animal Bones: Overview of ARL Experimental Research ARL 11:50 Wayne Chen

Modeling aspects of human memory for scientific study.

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

Caudell, Thomas P.; Watson, Patrick; McDaniel, Mark A.

Working with leading experts in the field of cognitive neuroscience and computational intelligence, SNL has developed a computational architecture that represents neurocognitive mechanisms associated with how humans remember experiences in their past. The architecture represents how knowledge is organized and updated through information from individual experiences (episodes) via the cortical-hippocampal declarative memory system. We compared the simulated behavioral characteristics with those of humans measured under well established experimental standards, controlling for unmodeled aspects of human processing, such as perception. We used this knowledge to create robust simulations of & human memory behaviors that should help move the scientific community closermore » to understanding how humans remember information. These behaviors were experimentally validated against actual human subjects, which was published. An important outcome of the validation process will be the joining of specific experimental testing procedures from the field of neuroscience with computational representations from the field of cognitive modeling and simulation.« less

Uterus transplantation: Experimental animal models and recent experience in humans

PubMed Central

Şahin, Sadık; Selçuk, Selçuk; Eroğlu, Mustafa; Karateke, Ateş

2015-01-01

Uterus transplantation has been considered as an alternative management modality in the last few years for adoption or gestational surrogacy for women with absence of uterus due to congenital or acquired reasons. Surrogacy is legal in only a few countries because of ethical, social and legal issues. Up to date, a total of 11 uterus transplantation cases have been reported in which uteri were harvested from ten live donors and one donor with brain death. After unsuccessful attempt of first uterus transplantation, many studies have been conducted in animals and these experimental models enabled our knowledge to increase on this topic. First experimental studies were performed in rodents; later uterus transplantation was accomplished in sheep, pigs and rabbits. Recently, researches in non-human primates have led the experience regarding transplantation technique and success to improve. In this review, we reviewed the experimental animal researches in the area of uterus transplantation and recent experience in humans. PMID:28913039

Genetics of hypertension: discoveries from the bench to human populations

PubMed Central

Franceschini, Nora

2013-01-01

Hypertension is a complex trait that is influenced by both heritable and environmental factors. The search for genes accounting for the susceptibility to hypertension has driven parallel efforts in human research and in research using experimental animals in controlled environmental settings. Evidence from rodent models of genetic hypertension and human Mendelian forms of hypertension and hypotension have yielded mechanistic insights into the pathways that are perturbed in blood pressure homeostasis, most of which converge at the level of renal sodium reabsorption. However, the bridging of evidence from these very diverse approaches to identify mechanisms underlying hypertension susceptibility and the translation of these findings to human populations and public health remain a challenge. Furthermore, findings from genome-wide association studies still require functional validation in experimental models. In this review, we highlight results and implications from key studies in experimental and clinical hypertension to date. PMID:24133117

Using entropy measures to characterize human locomotion.

PubMed

Leverick, Graham; Szturm, Tony; Wu, Christine Q

2014-12-01

Entropy measures have been widely used to quantify the complexity of theoretical and experimental dynamical systems. In this paper, the value of using entropy measures to characterize human locomotion is demonstrated based on their construct validity, predictive validity in a simple model of human walking and convergent validity in an experimental study. Results show that four of the five considered entropy measures increase meaningfully with the increased probability of falling in a simple passive bipedal walker model. The same four entropy measures also experienced statistically significant increases in response to increasing age and gait impairment caused by cognitive interference in an experimental study. Of the considered entropy measures, the proposed quantized dynamical entropy (QDE) and quantization-based approximation of sample entropy (QASE) offered the best combination of sensitivity to changes in gait dynamics and computational efficiency. Based on these results, entropy appears to be a viable candidate for assessing the stability of human locomotion.

The Effect of Constructivist Instruction on Prospective Teachers' Attitudes toward Human Rights Education

ERIC Educational Resources Information Center

Gundogdu, Kerim

2010-01-01

Introduction: This study investigates the effect of employing constructivist methods and materials on the attitudes of prospective teachers' (psychological counseling students) toward human rights education. Method: The research employed a quasi-experimental pre test-post test control group design. The experimental group, consisted of 23 male and…

Magnetoacoustic imaging of human liver tumor with magnetic induction

NASA Astrophysics Data System (ADS)

Hu, Gang; Cressman, Erik; He, Bin

2011-01-01

Magnetoacoustic tomography with magnetic induction (MAT-MI) is an imaging technique under development to achieve imaging of electrical impedance contrast in biological tissues with spatial resolution close to ultrasound imaging. However, previously reported MAT-MI experimental results are obtained either from low salinity gel phantoms, or from normal animal tissue samples. In this study, we report the experimental study on the performance of the MAT-MI imaging method for imaging in vitro human liver tumor tissue. The present promising experimental results suggest the feasibility of MAT-MI to image electrical impedance contrast between the cancerous tissue and its surrounding normal tissues.

Gut Microbiome Standardization in Control and Experimental Mice.

PubMed

McCoy, Kathy D; Geuking, Markus B; Ronchi, Francesca

2017-04-03

Mouse models are used extensively to study human health and to investigate the mechanisms underlying human disease. In the past, most animal studies were performed without taking into consideration the impact of the microbiota. However, the microbiota that colonizes all body surfaces, including the gastrointestinal tract, respiratory tract, genitourinary tract, and skin, heavily impacts nearly every aspect of host physiology. When performing studies utilizing mouse models it is critical to understand that the microbiome is heavily impacted by environmental factors, including (but not limited to) food, bedding, caging, and temperature. In addition, stochastic changes in the microbiota can occur over time that also play a role in shaping microbial composition. These factors lead to massive variability in the composition of the microbiota between animal facilities and research institutions, and even within a single facility. Lack of experimental reproducibility between research groups has highlighted the necessity for rigorously controlled experimental designs in order to standardize the microbiota between control and experimental animals. Well controlled experiments are mandatory in order to reduce variability and allow correct interpretation of experimental results, not just of host-microbiome studies but of all mouse models of human disease. The protocols presented are aimed to design experiments that control the microbiota composition between different genetic strains of experimental mice within an animal unit. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

The Infant Gut Microbiome: Evidence for Obesity Risk and Dietary Intervention

PubMed Central

Koleva, Petya T.; Bridgman, Sarah L.; Kozyrskyj, Anita L.

2015-01-01

Increasing globally, particularly in children, obesity is a serious public health issue and risk factor for overweight and metabolic disease in later life. Both in experimental animal and human studies, advances in gene sequencing technologies have yielded intriguing possibilities for the role of the gut microbiome in later development of overweight status. Before translating study findings into practice, we must first reconcile inconsistencies between animal experimentation, and human adult and infant studies. Recent evidence for associations with gut microbiota and infant weight gain or child weight status, implicate Bacteroides and Lactobacillus species. Dietary manipulation with human milk and pre/probiotic formulations holds promise for preventing obesity. PMID:25835047

A review of studies on the effects of ultraviolet irradiation on the resistance to infections: evidence from rodent infection models and verification by experimental and observational human studies.

PubMed

Termorshuizen, F; Garssen, J; Norval, M; Koulu, L; Laihia, J; Leino, L; Jansen, C T; De Gruijl, F; Gibbs, N K; De Simone, C; Van Loveren, H

2002-02-01

Recent studies on the immunosuppressive effects of ultraviolet radiation (UVR) and the related resistance to infections in rodents and humans are presented. The waveband dependency of trans-to-cis isomerisation of urocanic acid in the stratum corneum and the role of DNA damage in UVR-induced erythema and immunosuppression were investigated to further elucidate the underlying mechanisms. Furthermore, human experimental studies on UVR-induced immunomodulation were performed. It appeared that the doses needed to suppress various immune parameters in humans (e.g. NK activity, contact hypersensitivity) were higher than those needed in experiments in rodents. Still, extrapolation of experimental animal data to the human situation showed that UVR may impair the resistance to different systemic infections at relevant outdoor doses. In observational human studies we aimed to substantiate the relevance of UVR for infections in humans. It was shown that sunny season was associated with a slightly retarded but clinically non-relevant antibody response to hepatitis B vaccination. Furthermore, sunny season appeared to be associated with a small decline in the number of CD4+ T-helper cells in a cohort of HIV-infected persons and a higher recurrence of herpes simplex and herpes zoster in a cohort of renal transplant recipients. However, in a study among young children a higher exposure to solar UVR was associated with a lower occurrence of upper respiratory tract symptoms. As disentangling the effects of UVR from other relevant factors is often impossible in observational studies, concise quantitative risk estimations for the human situation cannot be given at present.

The neuropathology observed in wild-type mice inoculated with human poliovirus mirrors human paralytic poliomyelitis.

PubMed

Ford, Dayton J; Ropka, Stacie L; Collins, George H; Jubelt, Burk

2002-09-01

Human paralytic poliomyelitis results from the destruction of spinal cord anterior horn motor neurons by human poliovirus (PV). CNS disease pathology similar to human poliomyelitis has been observed in experimentally infected chimpanzees, monkeys and wild-type mice. In this study we present a detailed examination of the clinical and histopathological features in the wild-type mouse after intracranial (i.c.) and novel intramuscular (i.m.) injection of poliovirus. Either route of poliovirus administration results in a clinical disease characterized predominately by flaccid paralysis. The observed histopathological features are compared with the histopathology reported for human paralytic poliomyelitis, experimentally infected chimpanzees, monkeys and transgenic mice expressing the human poliovirus receptor (hPVR). The observation of flaccid paralysis and anterior horn motor neuron destruction mirrors what is observed in human paralytic poliomyelitis. Our results suggest that the neuropathology observed in the wild-type mouse model is similar to what has been observed in both the human disease and in other experimental animal models, with the possible exception of the transgenic mouse model. The observed neuropathology of the wild-type mouse model more closely reflects what has been observed in human poliomyelitis, as well as in experimentally infected chimpanzees and monkeys, than does the hPVR transgenic mouse model. The previously reported poliovirus-induced white matter demyelinating disease was not observed.

INTEGRATING EPIDEMIOLOGY AND TOXICOLOGY IN NEUROTOXICITY RISK ASSESSMENT.

EPA Science Inventory

Neurotoxicity risk assessments depend on the best available scientific information, including data from animal toxicity, human experimental studies and human epidemiology studies. There are several factors to consider when evaluating the comparability of data from studies. Reg...

[Study of the relationship between human quality and reliability].

PubMed

Long, S; Wang, C; Wang, L i; Yuan, J; Liu, H; Jiao, X

1997-02-01

To clarify the relationship between human quality and reliability, 1925 experiments in 20 subjects were carried out to study the relationship between disposition character, digital memory, graphic memory, multi-reaction time and education level and simulated aircraft operation. Meanwhile, effects of task difficulty and enviromental factor on human reliability were also studied. The results showed that human quality can be predicted and evaluated through experimental methods. The better the human quality, the higher the human reliability.

Renal denervation and hypertension - The need to investigate unintended effects and neural control of the human kidney.

PubMed

Grisk, Olaf

2017-05-01

Increased renal sympathetic nerve activity (RSNA) is present in human and experimental forms of arterial hypertension. Experimental denervation studies showed that renal nerves contribute to the development of hypertension. Clinical trials provided equivocal results on the antihypertensive efficacy of renal denervation in patients spurring discussions on technical aspects of renal denervation and further research on the role of renal nerves for the regulation of kidney function as well as the pathophysiology of hypertension. This review summarizes recent findings on adrenoceptor expression and function in the human kidney, adrenoceptor-dependent regulation of sodium chloride transport in the distal nephron, experimental data on chronic RSNA and the development of high arterial pressure and consequences of renal denervation that may limit its antihypertensive efficacy. Future research needs to reduce the gap between our knowledge on neural control of renal function in animals vs. humans to facilitate translation of experimental animal data to humans. More experimental studies on the temporal relationship between RSNA and arterial pressure in the chronic setting are needed to better define the pathogenetic role of heightened RSNA in different forms of arterial hypertension in order to improve the rational basis for renal denervation in antihypertensive therapy. Finally, research on unintended consequences of renal denervation including but not limited to reinnervation and denervation supersensitivity needs to be intensified to further assess the potential of renal denervation to slow the progression of renal disease and hypertension. Copyright © 2016 Elsevier B.V. All rights reserved.

The ethics of human volunteer studies involving experimental exposure to pesticides: unanswered dilemmas

PubMed Central

2010-01-01

The controversy about the use of data from human volunteer studies involving experimental exposure to pesticides as part of regulatory risk assessment has been widely discussed, but the complex and interrelated scientific and ethical issues remain largely unresolved. This discussion paper, generated by authors who comprised a workgroup of the ICOH Scientific Committee on Rural Health, reviews the use of human experimental studies in regulatory risk assessment for pesticides with a view to advancing the debate as to when, if ever, such studies might be ethically justifiable. The discussion is based on three elements: (a) a review of discussion papers on the topic of human testing of pesticides and the positions adopted by regulatory agencies in developed countries; (b) an analysis of published and unpublished studies involving human testing with pesticides, both in the peer-reviewed literature and in the JMPR database; and (c) application of an ethical analysis to the problem. The paper identifies areas of agreement which include general principles that may provide a starting point on which to base criteria for judgements as to the ethical acceptability of such studies. However, the paper also highlights ongoing unresolved differences of opinion inherent in ethical analysis of contentious issues, which we propose should form a starting point for further debate and the development of guidelines to achieve better resolution of this matter. PMID:20718963

Experimental design and quantitative analysis of microbial community multiomics.

PubMed

Mallick, Himel; Ma, Siyuan; Franzosa, Eric A; Vatanen, Tommi; Morgan, Xochitl C; Huttenhower, Curtis

2017-11-30

Studies of the microbiome have become increasingly sophisticated, and multiple sequence-based, molecular methods as well as culture-based methods exist for population-scale microbiome profiles. To link the resulting host and microbial data types to human health, several experimental design considerations, data analysis challenges, and statistical epidemiological approaches must be addressed. Here, we survey current best practices for experimental design in microbiome molecular epidemiology, including technologies for generating, analyzing, and integrating microbiome multiomics data. We highlight studies that have identified molecular bioactives that influence human health, and we suggest steps for scaling translational microbiome research to high-throughput target discovery across large populations.

Human primordial germ cell formation is diminished by exposure to environmental toxicants acting through the AHR signaling pathway.

PubMed

Kee, Kehkooi; Flores, Martha; Cedars, Marcelle I; Reijo Pera, Renee A

2010-09-01

Historically, effects of environmental toxicants on human development have been deduced via epidemiological studies because direct experimental analysis has not been possible. However, in recent years, the derivation of human pluripotent stem cells has provided a potential experimental system to directly probe human development. Here, we used human embryonic stem cells (hESCs) to study the effect of environmental toxicants on human germ cell development, with a focus on differentiation of the founding population of primordial germ cells (PGCs), which will go on to form the oocytes of the adult. We demonstrate that human PGC numbers are specifically reduced by exposure to polycyclic aromatic hydrocarbons (PAHs), a group of toxicants common in air pollutants released from gasoline combustion or tobacco smoke. Further, we demonstrate that the adverse effects of PAH exposure are mediated through the aromatic hydrocarbon receptor (AHR) and BAX pathway. This study demonstrates the utility of hESCs as a model system for direct examination of the molecular and genetic pathways of environmental toxicants on human germ cell development.

Measuring Human Performance on Clustering Problems: Some Potential Objective Criteria and Experimental Research Opportunities

ERIC Educational Resources Information Center

Brusco, Michael J.

2007-01-01

The study of human performance on discrete optimization problems has a considerable history that spans various disciplines. The two most widely studied problems are the Euclidean traveling salesperson problem and the quadratic assignment problem. The purpose of this paper is to outline a program of study for the measurement of human performance on…

Diet composition as a source of variation in experimental animal models of cancer cachexia.

PubMed

Giles, Kaitlin; Guan, Chen; Jagoe, Thomas R; Mazurak, Vera

2016-05-01

A variety of experimental animal models are used extensively to study mechanisms underlying cancer cachexia, and to identify potential treatments. The important potential confounding effect of dietary composition and intake used in many preclinical studies of cancer cachexia is frequently overlooked. Dietary designs applied in experimental studies should maximize the applicability to human cancer cachexia, meeting the essential requirements of the species used in the study, matched between treatment and control groups as well as also being generally similar to human consumption. A literature review of scientific studies using animal models of cancer and cancer cachexia with dietary interventions was performed. Studies that investigated interventions using lipid sources were selected as the focus of discussion. The search revealed a number of nutrient intervention studies (n = 44), with the majority including n-3 fatty acids (n = 16), mainly eicosapentaenoic acid and/or docosahexaenoic acid. A review of the literature revealed that the majority of studies do not provide information about dietary design; food intake or pair-feeding is rarely reported. Further, there is a lack of standardization in dietary design, content, source, and overall composition in animal models of cancer cachexia. A model is proposed with the intent of guiding dietary design in preclinical studies to enable comparisons of dietary treatments within the same study, translation across different study designs, as well as application to human nutrient intakes. The potential for experimental endpoints to be affected by variations in food intake, macronutrient content, and diet composition is likely. Diet content and composition should be reported, and food intake assessed. Minimum standards for diet definition in cachexia studies would improve reproducibility of pre-clinical studies and aid the interpretation and translation of results to humans with cancer.

Diet composition as a source of variation in experimental animal models of cancer cachexia

PubMed Central

Giles, Kaitlin; Guan, Chen; Jagoe, Thomas R.

2015-01-01

Abstract Background A variety of experimental animal models are used extensively to study mechanisms underlying cancer cachexia, and to identify potential treatments. The important potential confounding effect of dietary composition and intake used in many preclinical studies of cancer cachexia is frequently overlooked. Dietary designs applied in experimental studies should maximize the applicability to human cancer cachexia, meeting the essential requirements of the species used in the study, matched between treatment and control groups as well as also being generally similar to human consumption. Methods A literature review of scientific studies using animal models of cancer and cancer cachexia with dietary interventions was performed. Studies that investigated interventions using lipid sources were selected as the focus of discussion. Results The search revealed a number of nutrient intervention studies (n = 44), with the majority including n‐3 fatty acids (n = 16), mainly eicosapentaenoic acid and/or docosahexaenoic acid. A review of the literature revealed that the majority of studies do not provide information about dietary design; food intake or pair‐feeding is rarely reported. Further, there is a lack of standardization in dietary design, content, source, and overall composition in animal models of cancer cachexia. A model is proposed with the intent of guiding dietary design in preclinical studies to enable comparisons of dietary treatments within the same study, translation across different study designs, as well as application to human nutrient intakes. Conclusion The potential for experimental endpoints to be affected by variations in food intake, macronutrient content, and diet composition is likely. Diet content and composition should be reported, and food intake assessed. Minimum standards for diet definition in cachexia studies would improve reproducibility of pre‐clinical studies and aid the interpretation and translation of results to humans with cancer. PMID:27493865

Modal analysis of human body vibration model for Indian subjects under sitting posture.

PubMed

Singh, Ishbir; Nigam, S P; Saran, V H

2015-01-01

Need and importance of modelling in human body vibration research studies are well established. The study of biodynamic responses of human beings can be classified into experimental and analytical methods. In the past few decades, plenty of mathematical models have been developed based on the diverse field measurements to describe the biodynamic responses of human beings. In this paper, a complete study on lumped parameter model derived from 50th percentile anthropometric data for a seated 54- kg Indian male subject without backrest support under free un-damped conditions has been carried out considering human body segments to be of ellipsoidal shape. Conventional lumped parameter modelling considers the human body as several rigid masses interconnected by springs and dampers. In this study, concept of mass of interconnecting springs has been incorporated and eigenvalues thus obtained are found to be closer to the values reported in the literature. Results obtained clearly establish decoupling of vertical and fore-and-aft oscillations. The mathematical modelling of human body vibration studies help in validating the experimental investigations for ride comfort of a sitting subject. This study clearly establishes the decoupling of vertical and fore-and-aft vibrations and helps in better understanding of possible human response to single and multi-axial excitations.

Intracochlear pressure measurements to study bone conduction transmission: State-of-the art and proof of concept of the experimental Procedure

NASA Astrophysics Data System (ADS)

Borgers, Charlotte; van Wieringen, Astrid; D'hondt, Christiane; Verhaert, Nicolas

2018-05-01

The cochlea is the main contributor in bone conduction perception. Measurements of differential pressure in the cochlea give a good estimation of the cochlear input provided by bone conduction stimulation. Recent studies have proven the feasibility of intracochlear pressure measurements in chinchillas and in human temporal bones to study bone conduction. However, similar measurements in fresh-frozen whole human cadaveric heads could give a more realistic representation of the five different transmission pathways of bone conduction to the cochlea compared to human temporal bones. The aim of our study is to develop and validate a framework for intracochlear pressure measurements to evaluate different aspects of bone conduction in whole human cadaveric heads. A proof of concept describing our experimental setup is provided together with the procedure. Additionally, we also present a method to fix the stapes footplate in order to simulate otosclerosis in human temporal bones. The effectiveness of this method is verified by some preliminary results.

Experimental evidence of human recreational disturbance effects on bird-territory establishment.

PubMed

Bötsch, Yves; Tablado, Zulima; Jenni, Lukas

2017-07-12

The worldwide increase in human outdoor activities raises concerns for wildlife. Human disturbances, even at low levels, are likely to impact species during sensitive periods of the annual cycle. However, experimental studies during the putative sensitive period of territory establishment of birds which not only investigate low disturbance levels, but which also exclude the effect of habitat modification (e.g. walking trails) are lacking. Here, we experimentally disturbed birds in forest plots by walking through twice a day during territory establishment. Later we compared the breeding bird community of experimentally disturbed plots with that of undisturbed control plots. We discovered that the number of territories (-15.0%) and species richness (-15.2%) in disturbed plots were substantially reduced compared with control plots. Species most affected included those sensitive to human presence (assessed by flight-initiation distances), open-cup nesters and above-ground foragers. Long-distance migrants, however, were unaffected due to their arrival after experimental disturbance took place. These findings highlight how territory establishment is a sensitive period for birds, when even low levels of human recreation may be perceived as threatening, and alter settlement decisions. This can have important implications for the conservation of species, which might go unnoticed when focusing only on already established birds. © 2017 The Author(s).

Part 2. Comparison of emergency washing solutions in 70% hydrofluoric acid-burned human skin in an established ex vivo explants model

PubMed Central

Burgher, François; Mathieu, Laurence; Lati, Elian; Gasser, Philippe; Peno-Mazzarino, Laurent; Blomet, Joël; Hall, Alan H; Maibach, Howard I

2011-01-01

Background: Hydrofluoric acid (HF) is a small and partially dissociated acid (pKa 3.2), able to deeply penetrate into human skin in addition to the corrosiveness of the hydrogen ion (H+) and the toxicity of the fluoride ion (F-). However, there has been a lack of experimental studies to objectively characterize the results of human HF skin exposure decontamination. Methodology/principal findings: A previously established experimental method using a human skin explants ex vivo model (Part 1. Experimental 70% hydrofluoric acid (HF) burns: Histological observations in an established human skin explants ex vivo model) described the lesions that appeared following 70% HF penetration. Within 5min, 70% HF penetrates to the dermis. Using the same experimental conditions, a comparison study of two different washing protocols was performed: water + topical calcium gluconate (CaG) versus Hexafluorine®. In these conditions, washing for 15min with running tap water followed by topical CaG ointment only delayed burn onset, while severe tissue damage appeared later. In contrast, after washing with Hexafluorine® over 10 min, no histological lesions developed. These results are in accordance with the results of accidental human industrial case reports. Conclusion/significance: Amphoteric and hypertonic Hexafluorine® can deactivate H+ and chelate F- ions. Based on these results, it should be considered as a promising first-aid decontamination solution to prevent or minimize significant local and systemic consequences of concentrated HF skin exposures. PMID:21083510

Cadmium osteotoxicity in experimental animals: Mechanisms and relationship to human exposures

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

Bhattacharyya, Maryka H.

Extensive epidemiological studies have recently demonstrated increased cadmium exposure correlating significantly with decreased bone mineral density and increased fracture incidence in humans at lower exposure levels than ever before evaluated. Studies in experimental animals have addressed whether very low concentrations of dietary cadmium can negatively impact the skeleton. This overview evaluates results in experimental animals regarding mechanisms of action on bone and the application of these results to humans. Results demonstrate that long-term dietary exposures in rats, at levels corresponding to environmental exposures in humans, result in increased skeletal fragility and decreased mineral density. Cadmium-induced demineralization begins soon after exposure,more » within 24 h of an oral dose to mice. In bone culture systems, cadmium at low concentrations acts directly on bone cells to cause both decreases in bone formation and increases in bone resorption, independent of its effects on kidney, intestine, or circulating hormone concentrations. Results from gene expression microarray and gene knock-out mouse models provide insight into mechanisms by which cadmium may affect bone. Application of the results to humans is considered with respect to cigarette smoke exposure pathways and direct vs. indirect effects of cadmium. Clearly, understanding the mechanism(s) by which cadmium causes bone loss in experimental animals will provide insight into its diverse effects in humans. Preventing bone loss is critical to maintaining an active, independent lifestyle, particularly among elderly persons. Identifying environmental factors such as cadmium that contribute to increased fractures in humans is an important undertaking and a first step to prevention.« less

16 CFR 1702.10 - Human experimental data involving the testing of human subjects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Human experimental data involving the testing of human subjects. 1702.10 Section 1702.10 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION... PACKAGING ACT REQUIREMENTS; PETITION PROCEDURES AND REQUIREMENTS § 1702.10 Human experimental data involving...

16 CFR 1702.10 - Human experimental data involving the testing of human subjects.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Human experimental data involving the testing of human subjects. 1702.10 Section 1702.10 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION... PACKAGING ACT REQUIREMENTS; PETITION PROCEDURES AND REQUIREMENTS § 1702.10 Human experimental data involving...

16 CFR 1702.10 - Human experimental data involving the testing of human subjects.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Human experimental data involving the testing of human subjects. 1702.10 Section 1702.10 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION... PACKAGING ACT REQUIREMENTS; PETITION PROCEDURES AND REQUIREMENTS § 1702.10 Human experimental data involving...

16 CFR 1702.10 - Human experimental data involving the testing of human subjects.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Human experimental data involving the testing of human subjects. 1702.10 Section 1702.10 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION... PACKAGING ACT REQUIREMENTS; PETITION PROCEDURES AND REQUIREMENTS § 1702.10 Human experimental data involving...

Improving the physiological realism of experimental models.

PubMed

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

2016-04-06

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

An experimental design for quantification of cardiovascular responses to music stimuli in humans.

PubMed

Chang, S-H; Luo, C-H; Yeh, T-L

2004-01-01

There have been several researches on the relationship between music and human physiological or psychological responses. However, there are cardiovascular index factors that have not been explored quantitatively due to the qualitative nature of acoustic stimuli. This study proposes and demonstrates an experimental design for quantification of cardiovascular responses to music stimuli in humans. The system comprises two components: a unit for generating and monitoring quantitative acoustic stimuli and a portable autonomic nervous system (ANS) analysis unit for quantitative recording and analysis of the cardiovascular responses. The experimental results indicate that the proposed system can exactly achieve the goal of full control and measurement for the music stimuli, and also effectively support many quantitative indices of cardiovascular response in humans. In addition, the analysis results are discussed and predicted in the future clinical research.

Modeling the propagation of electromagnetic waves over the surface of the human body

NASA Astrophysics Data System (ADS)

Vendik, I. B.; Vendik, O. G.; Kirillov, V. V.; Pleskachev, V. V.; Tural'chuk, P. A.

2016-12-01

The results of modeling and an experimental study of electromagnetic (EM) waves in microwave range propagating along the surface of the human body have been presented. The parameters of wave propagation, such as the attenuation and phase velocity, have also been investigated. The calculation of the propagation of EM waves by the numerical method FDTD (finite difference time domain), as well as the use of the analytical model of the propagation of the EM wave along flat and curved surfaces has been fulfilled. An experimental study on a human body has been conducted. It has been shown that creeping waves are slow and exhibit a noticeable dispersion, while the surface waves are dispersionless and propagate at the speed of light in free space. A comparison of the results of numerical simulation, analytical calculation, and experimental investigations at a frequency of 2.55 GHz has been carried out.

Ethical Considerations in Human Movement Research.

ERIC Educational Resources Information Center

Olivier, Steve

1995-01-01

Highlights ethical issues for human subject research, identifying principles that form the construct of a code of research ethics and evaluating against this construct past human experimentation and current research in human movement studies. The efficacy of legislation and self-regulation is examined. Particular attention is given to the context…

A review on human reinstatement studies: an overview and methodological challenges

PubMed Central

Haaker, Jan; Golkar, Armita; Hermans, Dirk

2014-01-01

In human research, studies of return of fear (ROF) phenomena, and reinstatement in particular, began only a decade ago and recently are more widely used, e.g., as outcome measures for fear/extinction memory manipulations (e.g., reconsolidation). As reinstatement research in humans is still in its infancy, providing an overview of its stability and boundary conditions and summarizing methodological challenges is timely to foster fruitful future research. As a translational endeavor, clarifying the circumstances under which (experimental) reinstatement occurs may offer a first step toward understanding relapse as a clinical phenomenon and pave the way for the development of new pharmacological or behavioral ways to prevent ROF. The current state of research does not yet allow pinpointing these circumstances in detail and we hope this review will aid the research field to advance in this direction. As an introduction, we begin with a synopsis of rodent work on reinstatement and theories that have been proposed to explain the findings. The review however mainly focuses on reinstatement in humans. We first describe details and variations of the experimental setup in reinstatement studies in humans and give a general overview of results. We continue with a compilation of possible experimental boundary conditions and end with the role of individual differences and behavioral and/or pharmacological manipulations. Furthermore, we compile important methodological and design details on the published studies in humans and end with open research questions and some important methodological and design recommendations as a guide for future research. PMID:25128533

16 CFR § 1702.10 - Human experimental data involving the testing of human subjects.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Human experimental data involving the testing of human subjects. § 1702.10 Section § 1702.10 Commercial Practices CONSUMER PRODUCT SAFETY... PREVENTION PACKAGING ACT REQUIREMENTS; PETITION PROCEDURES AND REQUIREMENTS § 1702.10 Human experimental data...

Differential Use of Attentional and Visual Communicative Signaling by Orangutans (Pongo pygmaeus) and Gorillas (Gorilla gorilla) in Response to the Attentional Status of a Human

PubMed Central

POSS, SARAH R.; KUHAR, CHRIS; STOINSKI, TARA S.; HOPKINS, WILLIAM D.

2007-01-01

In this study we investigated the communicative abilities of 10 orangutans (Pongo pygmaeus) and seven western lowland gorillas (Gorilla gorilla gorilla), and particularly focused on their sensitivity to the attentional state of a human experimenter when choosing from a repertoire of both auditory and visual communication strategies. In experiment 1 a banana was placed in front of the subject's cage and a human experimenter was either present or absent. The subject's behavior was recorded for 60 sec. Both gorillas and orangutans gestured (t(16)= −3.58, P<.005) and vocalized (t(16) = −2.47, P<.05) more when the experimenter was present. In experiment 2 a human experimenter held a banana in front of the subject's cage and was oriented either toward or away from the subject. Again the subject's behavior was recorded for 60 sec. In this experiment both gorillas and orangutans gestured significantly more frequently (t(16) = 3.40, P<.005) when the experimenter was oriented toward them. In addition, gorillas and orangutans used other forms of visual communication signals, such as lip pout (t(16) = 3.66, P<.005), barter/trade (t(16) = 2.31, P<.05), and body present (t(16) = 2.31, P<.05) significantly more when an experimenter was facing them. The overall results indicate that both gorillas and orangutans are sensitive to the attentional state of a human experimenter and use appropriate communicative signals to gain that individual's attention. These results are also similar to previous findings on communicative behaviors in chimpanzees. PMID:16967515

Differential use of attentional and visual communicative signaling by orangutans (Pongo pygmaeus) and gorillas (Gorilla gorilla) in response to the attentional status of a human.

PubMed

Poss, Sarah R; Kuhar, Chris; Stoinski, Tara S; Hopkins, William D

2006-10-01

In this study we investigated the communicative abilities of 10 orangutans (Pongo pygmaeus) and seven western lowland gorillas (Gorilla gorilla gorilla), and particularly focused on their sensitivity to the attentional state of a human experimenter when choosing from a repertoire of both auditory and visual communication strategies. In experiment 1 a banana was placed in front of the subject's cage and a human experimenter was either present or absent. The subject's behavior was recorded for 60 sec. Both gorillas and orangutans gestured (t(16)=-3.58, P<.005) and vocalized (t(16)=-2.47, P<.05) more when the experimenter was present. In experiment 2 a human experimenter held a banana in front of the subject's cage and was oriented either toward or away from the subject. Again the subject's behavior was recorded for 60 sec. In this experiment both gorillas and orangutans gestured significantly more frequently (t(16)=3.40, P<.005) when the experimenter was oriented toward them. In addition, gorillas and orangutans used other forms of visual communication signals, such as lip pout (t(16)=3.66, P<.005), barter/trade (t(16)=2.31, P<.05), and body present (t(16)=2.31, P<.05) significantly more when an experimenter was facing them. The overall results indicate that both gorillas and orangutans are sensitive to the attentional state of a human experimenter and use appropriate communicative signals to gain that individual's attention. These results are also similar to previous findings on communicative behaviors in chimpanzees.

Statistical modelling of networked human-automation performance using working memory capacity.

PubMed

Ahmed, Nisar; de Visser, Ewart; Shaw, Tyler; Mohamed-Ameen, Amira; Campbell, Mark; Parasuraman, Raja

2014-01-01

This study examines the challenging problem of modelling the interaction between individual attentional limitations and decision-making performance in networked human-automation system tasks. Analysis of real experimental data from a task involving networked supervision of multiple unmanned aerial vehicles by human participants shows that both task load and network message quality affect performance, but that these effects are modulated by individual differences in working memory (WM) capacity. These insights were used to assess three statistical approaches for modelling and making predictions with real experimental networked supervisory performance data: classical linear regression, non-parametric Gaussian processes and probabilistic Bayesian networks. It is shown that each of these approaches can help designers of networked human-automated systems cope with various uncertainties in order to accommodate future users by linking expected operating conditions and performance from real experimental data to observable cognitive traits like WM capacity. Practitioner Summary: Working memory (WM) capacity helps account for inter-individual variability in operator performance in networked unmanned aerial vehicle supervisory tasks. This is useful for reliable performance prediction near experimental conditions via linear models; robust statistical prediction beyond experimental conditions via Gaussian process models and probabilistic inference about unknown task conditions/WM capacities via Bayesian network models.

Comparative Pathology of Hepatitis A Virus and Hepatitis E Virus Infection.

PubMed

Cullen, John M; Lemon, Stanley M

2018-04-30

Hepatitis A virus (HAV) and hepatitis E virus (HEV) cause acute, self-limiting hepatic infections that are usually spread by the fecal-oral route in humans. Naturally occurring and experimental infections are possible in a variety of nonhuman primates and, in the case of HEV, a number of other species. Many advances in understanding the pathogenesis of these viruses have come from studies in experimental animals. In general, animals infected with these viruses recapitulate the histologic lesions seen in infected humans, but typically with less severe clinical and histopathological manifestations. This review describes the histopathologic changes associated with HAV and HEV infection in humans and experimental animals. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Buprenorphine During Pregnancy Reduces Neonate Distress

MedlinePlus

... supported clinical trial, the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, has found buprenorphine to be ... to the two medications. They surmise that the experimental treatment protocols may have moved patients from morphine ...

A comparison of human exposures to fiberglass with those used in a recent rat chronic inhalation study.

PubMed

Hesterberg, T W; Hart, G A

1994-12-01

In a recent rat inhalation study, 2 years of exposure to high concentrations of fiberglass (FG) resulted in no treatment-related fibrosis or thoracic tumors. To determine the relevancy of this study for human risk assessment, it is important to compare the rat experimental exposure levels with those of humans. Data on human exposures were taken from several studies and included FG manufacturing, installation and removal, and ambient air. FG levels in the rat aerosol were 200,000-fold higher than indoor air, > 2000-fold higher than during FG insulation manufacturing, and > 1000-fold higher than FG batt installation. The rat aerosol was 30-fold more concentrated than the highest human exposure (blowing installation of unbound FG). Rat FG lung burden also vastly exceeded that of FG workers, which was not significantly elevated above nonworker levels. The amount of fibers/mg dry lung for the rat after lifetime exposure was > 4000-fold greater than for the FG worker, average exposure 11 years. Aerosol and lung fiber dimensions in the rat study were comparable to those of human exposures. From these comparisons, it can be concluded that the exposure level in the rat inhalation study was sufficiently, if not excessively, high in comparison to human exposures. Increasing the experimental exposure in the rat studies would not serve to mirror human environmental or occupational exposures.

EXPERIMENTAL APPROACHES TO EVALUATING THE ROLE OF ENVIRONMENTAL FACTORS IN THE DEVELOPMENT OF CARDIOVASCULAR DISEASE

EPA Science Inventory

Epidemiologic studies have suggested factors in drinking water influence on the human cardiovascular system. A clear identification of the factors involved requires more invasive techniques and more strict experimental controls than can usually be applied in epidemiologic studies...

Automation effects in a multiloop manual control system

NASA Technical Reports Server (NTRS)

Hess, R. A.; Mcnally, B. D.

1986-01-01

An experimental and analytical study was undertaken to investigate human interaction with a simple multiloop manual control system in which the human's activity was systematically varied by changing the level of automation. The system simulated was the longitudinal dynamics of a hovering helicopter. The automation-systems-stabilized vehicle responses from attitude to velocity to position and also provided for display automation in the form of a flight director. The control-loop structure resulting from the task definition can be considered a simple stereotype of a hierarchical control system. The experimental study was complemented by an analytical modeling effort which utilized simple crossover models of the human operator. It was shown that such models can be extended to the description of multiloop tasks involving preview and precognitive human operator behavior. The existence of time optimal manual control behavior was established for these tasks and the role which internal models may play in establishing human-machine performance was discussed.

The philosophy of scientific experimentation: a review

PubMed Central

2009-01-01

Practicing and studying automated experimentation may benefit from philosophical reflection on experimental science in general. This paper reviews the relevant literature and discusses central issues in the philosophy of scientific experimentation. The first two sections present brief accounts of the rise of experimental science and of its philosophical study. The next sections discuss three central issues of scientific experimentation: the scientific and philosophical significance of intervention and production, the relationship between experimental science and technology, and the interactions between experimental and theoretical work. The concluding section identifies three issues for further research: the role of computing and, more specifically, automating, in experimental research, the nature of experimentation in the social and human sciences, and the significance of normative, including ethical, problems in experimental science. PMID:20098589

Experimental and numerical study of physiological responses in hot environments.

PubMed

Yang, Jie; Weng, Wenguo; Zhang, Baoting

2014-10-01

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

Cross-study projections of genomic biomarkers: an evaluation in cancer genomics.

PubMed

Lucas, Joseph E; Carvalho, Carlos M; Chen, Julia Ling-Yu; Chi, Jen-Tsan; West, Mike

2009-01-01

Human disease studies using DNA microarrays in both clinical/observational and experimental/controlled studies are having increasing impact on our understanding of the complexity of human diseases. A fundamental concept is the use of gene expression as a "common currency" that links the results of in vitro controlled experiments to in vivo observational human studies. Many studies--in cancer and other diseases--have shown promise in using in vitro cell manipulations to improve understanding of in vivo biology, but experiments often simply fail to reflect the enormous phenotypic variation seen in human diseases. We address this with a framework and methods to dissect, enhance and extend the in vivo utility of in vitro derived gene expression signatures. From an experimentally defined gene expression signature we use statistical factor analysis to generate multiple quantitative factors in human cancer gene expression data. These factors retain their relationship to the original, one-dimensional in vitro signature but better describe the diversity of in vivo biology. In a breast cancer analysis, we show that factors can reflect fundamentally different biological processes linked to molecular and clinical features of human cancers, and that in combination they can improve prediction of clinical outcomes.

Improving the physiological realism of experimental models

PubMed Central

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

2016-01-01

The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide an in silico platform for drug screening. Ultimately, these models rely on the analysis and integration of experimental data. As such, the success of VPH depends on the availability of physiologically realistic experimental models (E-Models) of human organ function that can be parametrized to test the numerical models. Here, the current state of suitable E-models, ranging from in vitro non-human cell organelles to in vivo human organ systems, is discussed. Specifically, challenges and recent progress in improving the physiological realism of E-models that may benefit the VPH project are highlighted and discussed using examples from the field of research on cardiovascular disease, musculoskeletal disorders, diabetes and Parkinson's disease. PMID:27051507

Justice- and fairness-related behaviors in nonhuman primates.

PubMed

Brosnan, Sarah F

2013-06-18

A distinctive feature across human societies is our interest in justice and fairness. People will sometimes invest in extremely costly behavior to achieve fair outcomes for themselves and others. Why do people care so much about justice? One way to address this is comparatively, exploring behaviors related to justice and fairness in other species. In this paper, I review work exploring responses to inequity, prosocial behavior, and other relevant behaviors in nonhuman primates in an effort to understand both the potential evolutionary function of these behaviors and the social and ecological reasons for the individual differences in behavior. I also consider how these behaviors relate to human behavior, particularly in the case of experimental studies using games derived from experimental economics to compare nonhuman primates' responses to those of humans in similar experimental conditions. These results emphasize the importance of a comparative approach to better understand the function and diversity of human behavior.

Experimental investigation of biodynamic human body models subjected to whole-body vibration during a vehicle ride.

PubMed

Taskin, Yener; Hacioglu, Yuksel; Ortes, Faruk; Karabulut, Derya; Arslan, Yunus Ziya

2018-02-06

In this study, responses of biodynamic human body models to whole-body vibration during a vehicle ride were investigated. Accelerations were acquired from three different body parts, such as the head, upper torso and lower torso, of 10 seated passengers during a car ride while two different road conditions were considered. The same multipurpose vehicle was used during all experiments. Additionally, by two widely used biodynamic models in the literature, a set of simulations were run to obtain theoretical accelerations of the models and were compared with those obtained experimentally. To sustain a quantified comparison between experimental and theoretical approaches, the root mean square acceleration and acceleration spectral density were calculated. Time and frequency responses of the models demonstrated that neither of the models showed the best prediction performance of the human body behaviour in all cases, indicating that further models are required for better prediction of the human body responses.

Justice- and fairness-related behaviors in nonhuman primates

PubMed Central

Brosnan, Sarah F.

2013-01-01

A distinctive feature across human societies is our interest in justice and fairness. People will sometimes invest in extremely costly behavior to achieve fair outcomes for themselves and others. Why do people care so much about justice? One way to address this is comparatively, exploring behaviors related to justice and fairness in other species. In this paper, I review work exploring responses to inequity, prosocial behavior, and other relevant behaviors in nonhuman primates in an effort to understand both the potential evolutionary function of these behaviors and the social and ecological reasons for the individual differences in behavior. I also consider how these behaviors relate to human behavior, particularly in the case of experimental studies using games derived from experimental economics to compare nonhuman primates’ responses to those of humans in similar experimental conditions. These results emphasize the importance of a comparative approach to better understand the function and diversity of human behavior. PMID:23754407

Role of metabolism and viruses in aflatoxin-induced liver cancer

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

Groopman, John D.; Kensler, Thomas W.

The use of biomarkers in molecular epidemiology studies for identifying stages in the progression of development of the health effects of environmental agents has the potential for providing important information for critical regulatory, clinical and public health problems. Investigations of aflatoxins probably represent one of the most extensive data sets in the field and this work may serve as a template for future studies of other environmental agents. The aflatoxins are naturally occurring mycotoxins found on foods such as corn, peanuts, various other nuts and cottonseed and they have been demonstrated to be carcinogenic in many experimental models. As amore » result of nearly 30 years of study, experimental data and epidemiological studies in human populations, aflatoxin B{sub 1} was classified as carcinogenic to humans by the International Agency for Research on Cancer. The long-term goal of the research described herein is the application of biomarkers to the development of preventative interventions for use in human populations at high-risk for cancer. Several of the aflatoxin-specific biomarkers have been validated in epidemiological studies and are now being used as intermediate biomarkers in prevention studies. The development of these aflatoxin biomarkers has been based upon the knowledge of the biochemistry and toxicology of aflatoxins gleaned from both experimental and human studies. These biomarkers have subsequently been utilized in experimental models to provide data on the modulation of these markers under different situations of disease risk. This systematic approach provides encouragement for preventive interventions and should serve as a template for the development, validation and application of other chemical-specific biomarkers to cancer or other chronic diseases.« less

Experimental human influenza: observations from studies of influenza antivirals.

PubMed

Hayden, Frederick G

2012-01-01

Randomized, placebo-controlled trials have been conducted for nearly five decades in experimentally induced human influenza infections to assess the effectiveness, tolerability and pharmacological properties of influenza antivirals. The results of such studies have not only provided key proof-of-concept data to facilitate drug development but also contributed to our understanding of influenza pathogenesis and transmission. The lack of availability of contemporary, safety-tested virus inoculation pools in recent years needs to be resolved in order to avoid hindering the development of new drugs and vaccines.

An Experimental Study of the Emergence of Human Communication Systems

ERIC Educational Resources Information Center

Galantucci, Bruno

2005-01-01

The emergence of human communication systems is typically investigated via 2 approaches with complementary strengths and weaknesses: naturalistic studies and computer simulations. This study was conducted with a method that combines these approaches. Pairs of participants played video games requiring communication. Members of a pair were…

Analyzing Data from a Pretest-Posttest Control Group Design: The Importance of Statistical Assumptions

ERIC Educational Resources Information Center

Zientek, Linda; Nimon, Kim; Hammack-Brown, Bryn

2016-01-01

Purpose: Among the gold standards in human resource development (HRD) research are studies that test theoretically developed hypotheses and use experimental designs. A somewhat typical experimental design would involve collecting pretest and posttest data on individuals assigned to a control or experimental group. Data from such a design that…

Comparing the Hematopoetic Syndrome Time Course in the NHP Animal Model to Radiation Accident Cases From the Database Search.

PubMed

Graessle, Dieter H; Dörr, Harald; Bennett, Alexander; Shapiro, Alla; Farese, Ann M; MacVittie, Thomas J; Meineke, Viktor

2015-11-01

Since controlled clinical studies on drug administration for the acute radiation syndrome are lacking, clinical data of human radiation accident victims as well as experimental animal models are the main sources of information. This leads to the question of how to compare and link clinical observations collected after human radiation accidents with experimental observations in non-human primate (NHP) models. Using the example of granulocyte counts in the peripheral blood following radiation exposure, approaches for adaptation between NHP and patient databases on data comparison and transformation are introduced. As a substitute for studying the effects of administration of granulocyte-colony stimulating factor (G-CSF) in human clinical trials, the method of mathematical modeling is suggested using the example of G-CSF administration to NHP after total body irradiation.

Medical experimentation in the elderly.

PubMed

Bernstein, J E; Nelson, F K

1975-07-01

Participation in human experimental research constitutes a major problem for the geriatric subject. Because there is a high incidence of noncontagious disease in the elderly, they are the group most useful for the study of new therapeutic agents or procedures. However, normal aging processes, often coupled with disease of the central nervous system, render elderly persons less able to comprehend the nature and risks of such studies. These factors permit easy exploitation of geriatric subjects in medical experimentation, with possible exposure to a significant risk of serious drug reactions and unnecessary hospitalization. Recent federal regulations have given "special protections" to children, prisoners, and the mentally infirm in experimental research, to guard against abuse of their human rights. A basic requirement is that informed consent be carefully obtained and documented. Such "special protections" should now be extended to geriatric subjects so that there will be no further exploitation in the course of valid clinical research.

Coordination Mechanism in Fast Human Movements - Experimental and Modelling Studies. Volume 1.

DTIC Science & Technology

1982-02-01

journal, possible the Journal of Motor Behavior of Experimental Brain Research. I. Proposed Experimental Studies - Year 3 At the present time we are...stimulation regimens must be devised to produce sensory imparted learning which manipulates each of these brain control mechanisms. Following the...movement center in the brain , presumably via the pyramidal tract from the cerebellum to the brainstem and spinal cord (cf. Miles and Evarts, 1979

A review on human reinstatement studies: an overview and methodological challenges.

PubMed

Haaker, Jan; Golkar, Armita; Hermans, Dirk; Lonsdorf, Tina B

2014-09-01

In human research, studies of return of fear (ROF) phenomena, and reinstatement in particular, began only a decade ago and recently are more widely used, e.g., as outcome measures for fear/extinction memory manipulations (e.g., reconsolidation). As reinstatement research in humans is still in its infancy, providing an overview of its stability and boundary conditions and summarizing methodological challenges is timely to foster fruitful future research. As a translational endeavor, clarifying the circumstances under which (experimental) reinstatement occurs may offer a first step toward understanding relapse as a clinical phenomenon and pave the way for the development of new pharmacological or behavioral ways to prevent ROF. The current state of research does not yet allow pinpointing these circumstances in detail and we hope this review will aid the research field to advance in this direction. As an introduction, we begin with a synopsis of rodent work on reinstatement and theories that have been proposed to explain the findings. The review however mainly focuses on reinstatement in humans. We first describe details and variations of the experimental setup in reinstatement studies in humans and give a general overview of results. We continue with a compilation of possible experimental boundary conditions and end with the role of individual differences and behavioral and/or pharmacological manipulations. Furthermore, we compile important methodological and design details on the published studies in humans and end with open research questions and some important methodological and design recommendations as a guide for future research. © 2014 Haaker et al.; Published by Cold Spring Harbor Laboratory Press.

Using Complementary Learning Clusters in Studying Literature to Enhance Students' Medical Humanities Literacy, Critical Thinking, and English Proficiency.

PubMed

Liao, Hung-Chang; Wang, Ya-Huei

2016-04-01

This study examined whether students studying literature in complementary learning clusters would show more improvement in medical humanities literacy, critical thinking skills, and English proficiency compared to those in conventional learning clusters. Ninety-three students participated in the study (M age = 18.2 years, SD = 0.4; 36 men, 57 women). A quasi-experimental design was used over 16 weeks, with the control group (n = 47) working in conventional learning clusters and the experimental group (n = 46) working in complementary learning clusters. Complementary learning clusters were those in which individuals had complementary strengths enabling them to learn from and offer assistance to other cluster members, hypothetically facilitating the learning process. Measures included the Medical Humanities Literacy Scale, Critical Thinking Disposition Assessment, English proficiency tests, and Analytic Critical Thinking Scoring Rubric. The results showed that complementary learning clusters have the potential to improve students' medical humanities literacy, critical thinking skills, and English proficiency. © The Author(s) 2016.

Erythropoietin regulations in humans under different environmental and experimental conditions.

PubMed

Gunga, H-C; Kirsch, K A; Roecker, L; Kohlberg, E; Tiedemann, J; Steinach, M; Schobersberger, W

2007-09-30

In the adult human, the kidney is the main organ for the production and release of erythropoietin (EPO). EPO is stimulating erythropoiesis by increasing the proliferation, differentiation and maturation of the erythroid precursors. In the last decades, enormous efforts were made in the purification, molecular encoding and description of the EPO gene. This led to an incredible increase in the understanding of the EPO-feedback-regulation loop at a molecular level, especially the oxygen-dependent EPO gene expression, a key function in the regulation loop. However, studies in humans at a systemic level are still very scanty. Therefore, it is the purpose of the present review to report on the main recent investigations on EPO production and release in humans under different environmental and experimental conditions, including: (i) studies on EPO circadian, monthly and even annual variations, (ii) studies in connection with short-, medium- and long-term exercise at sea-level which will be followed (iii) by studies performed at moderate and high altitude.

Quantitative comparisons of the actute neurotoxicity of toulene in rats and humans.

EPA Science Inventory

The behavioral and neurophysiological effects of acute exposure to toluene are the most thoroughly explored of all the hydrocarbon solvents. Behavioral effects have been experimentally studied in humans and other species, for example, rats. The existence of both rat and human dos...

An Experiment in Teaching Human Ethology

ERIC Educational Resources Information Center

Barnett, S. A.

1977-01-01

Students of ethology are often confused about the validity of arguments based on comparisons of animal and human behavior. The problem can be dealt with purely theoretically or through observational or experimental studies of human behavior. Some results of using these two methods are described and discussed. (Author/MA)

Stochastic estimation of human shoulder impedance with robots: an experimental design.

PubMed

Park, Kyungbin; Chang, Pyung Hun

2011-01-01

Previous studies assumed the shoulder as a hinge joint during human arm impedance measurement. This is obviously a vast simplification since the shoulder is a complex of several joints with multiple degrees of freedom. In the present work, a practical methodology for more general and realistic estimation of human shoulder impedance is proposed and validated with a spring array. It includes a gravity compensation scheme, which is developed and used for the experiments with a spatial three degrees of freedom PUMA-type robot. The experimental results were accurate and reliable, and thus it has shown a strong potential of the proposed methodology in the estimation of human shoulder impedance. © 2011 IEEE

The impact of pesticides on oxidative stress level in human organism and their activity as an endocrine disruptor.

PubMed

Jabłońska-Trypuć, Agata; Wołejko, Elżbieta; Wydro, Urszula; Butarewicz, Andrzej

2017-07-03

Pesticides cause serious environmental and health problems both to humans and animals. The aim of this review is to discuss selected herbicides and fungicides regarding their mode of action and their influence on basic oxidative stress parameters and endocrine disruption properties tested in selected cell cultures in vitro. Because of numerous difficulties which animal studies are subject to, cell cultures are an excellent experimental model reflecting human exposure to different pesticides through all relevant routes. This experimental model can be used to monitor aggregate and cumulative pesticide exposures.

Early-Life Nutritional Programming of Type 2 Diabetes: Experimental and Quasi-Experimental Evidence.

PubMed

Vaiserman, Alexander M

2017-03-05

Consistent evidence from both experimental and human studies suggest that inadequate nutrition in early life can contribute to risk of developing metabolic disorders including type 2 diabetes (T2D) in adult life. In human populations, most findings supporting a causative relationship between early-life malnutrition and subsequent risk of T2D were obtained from quasi-experimental studies ('natural experiments'). Prenatal and/or early postnatal exposures to famine were demonstrated to be associated with higher risk of T2D in many cohorts around the world. Recent studies have highlighted the importance of epigenetic regulation of gene expression as a possible major contributor to the link between the early-life famine exposure and T2D in adulthood. Findings from these studies suggest that prenatal exposure to the famine may result in induction of persistent epigenetic changes that have adaptive significance in postnatal development but can predispose to metabolic disorders including T2D at the late stages of life. In this review, quasi-experimental data on the developmental programming of T2D are summarized and recent research findings on changes in DNA methylation that mediate these effects are discussed.

Early-Life Nutritional Programming of Type 2 Diabetes: Experimental and Quasi-Experimental Evidence

PubMed Central

Vaiserman, Alexander M.

2017-01-01

Consistent evidence from both experimental and human studies suggest that inadequate nutrition in early life can contribute to risk of developing metabolic disorders including type 2 diabetes (T2D) in adult life. In human populations, most findings supporting a causative relationship between early-life malnutrition and subsequent risk of T2D were obtained from quasi-experimental studies (‘natural experiments’). Prenatal and/or early postnatal exposures to famine were demonstrated to be associated with higher risk of T2D in many cohorts around the world. Recent studies have highlighted the importance of epigenetic regulation of gene expression as a possible major contributor to the link between the early-life famine exposure and T2D in adulthood. Findings from these studies suggest that prenatal exposure to the famine may result in induction of persistent epigenetic changes that have adaptive significance in postnatal development but can predispose to metabolic disorders including T2D at the late stages of life. In this review, quasi-experimental data on the developmental programming of T2D are summarized and recent research findings on changes in DNA methylation that mediate these effects are discussed. PMID:28273874

They See a Rat, We Seek a Cure for Diseases: The Current Status of Animal Experimentation in Medical Practice

PubMed Central

Kehinde, Elijah O.

2013-01-01

The objective of this review article was to examine current and prospective developments in the scientific use of laboratory animals, and to find out whether or not there are still valid scientific benefits of and justification for animal experimentation. The PubMed and Web of Science databases were searched using the following key words: animal models, basic research, pharmaceutical research, toxicity testing, experimental surgery, surgical simulation, ethics, animal welfare, benign, malignant diseases. Important relevant reviews, original articles and references from 1970 to 2012 were reviewed for data on the use of experimental animals in the study of diseases. The use of laboratory animals in scientific research continues to generate intense public debate. Their use can be justified today in the following areas of research: basic scientific research, use of animals as models for human diseases, pharmaceutical research and development, toxicity testing and teaching of new surgical techniques. This is because there are inherent limitations in the use of alternatives such as in vitro studies, human clinical trials or computer simulation. However, there are problems of transferability of results obtained from animal research to humans. Efforts are on-going to find suitable alternatives to animal experimentation like cell and tissue culture and computer simulation. For the foreseeable future, it would appear that to enable scientists to have a more precise understanding of human disease, including its diagnosis, prognosis and therapeutic intervention, there will still be enough grounds to advocate animal experimentation. However, efforts must continue to minimize or eliminate the need for animal testing in scientific research as soon as possible. PMID:24217224

They see a rat, we seek a cure for diseases: the current status of animal experimentation in medical practice.

PubMed

Kehinde, Elijah O

2013-01-01

The objective of this review article was to examine current and prospective developments in the scientific use of laboratory animals, and to find out whether or not there are still valid scientific benefits of and justification for animal experimentation. The PubMed and Web of Science databases were searched using the following key words: animal models, basic research, pharmaceutical research, toxicity testing, experimental surgery, surgical simulation, ethics, animal welfare, benign, malignant diseases. Important relevant reviews, original articles and references from 1970 to 2012 were reviewed for data on the use of experimental animals in the study of diseases. The use of laboratory animals in scientific research continues to generate intense public debate. Their use can be justified today in the following areas of research: basic scientific research, use of animals as models for human diseases, pharmaceutical research and development, toxicity testing and teaching of new surgical techniques. This is because there are inherent limitations in the use of alternatives such as in vitro studies, human clinical trials or computer simulation. However, there are problems of transferability of results obtained from animal research to humans. Efforts are on-going to find suitable alternatives to animal experimentation like cell and tissue culture and computer simulation. For the foreseeable future, it would appear that to enable scientists to have a more precise understanding of human disease, including its diagnosis, prognosis and therapeutic intervention, there will still be enough grounds to advocate animal experimentation. However, efforts must continue to minimize or eliminate the need for animal testing in scientific research as soon as possible. © 2013 S. Karger AG, Basel.

Human survivability of extreme impacts in free-fall.

DOT National Transportation Integrated Search

1963-08-01

Human deceleration tolerances beyond the limits imposed by voluntary experimental methods were studied by means of intensive case histories of 137 individuals who have survived extremely abrupt impacts in accidental, suicidal, and homicidal free-fall...

Fruit Flies Help Human Sleep Research

MedlinePlus

Skip Navigation Bar Home Current Issue Past Issues Fruit Flies Help Human Sleep Research Past Issues / Summer 2007 ... courtesy of NIGMS Neuroscientist Chiara Cirelli uses experimental fruit flies to study sleep. Although it may be tough ...

Leishmania infection: painful or painless?

PubMed

Borghi, Sergio M; Fattori, Victor; Conchon-Costa, Ivete; Pinge-Filho, Phileno; Pavanelli, Wander R; Verri, Waldiceu A

2017-02-01

The complex life cycle and immunopathological features underpinning the interaction of Leishmania parasites and their mammalian hosts poses frequent poorly explored and inconclusively resolved questions. The altered nociceptive signals over the course of leishmaniasis remain an intriguing issue for nociceptive and parasitology researchers. Experimental investigations have utilized behavioral, morphological, and neuro-immune approaches in the study of experimental cutaneous leishmaniasis (CL). The data generated indicates new venues for the study of the pathological characteristics of nociceptive processing in this parasitic disease. Leishmania-induced pain may be easily observed in mice and rats. However, nociceptive data is more complex in human investigations, including the occurrence of painless lesions in mucocutaneous and cutaneous leishmaniasis. Data from recent decades indicate that humans can also be affected by pain-related symptoms, often distinct from the region of body infection. The molecular and cellular mechanisms underlying such variable nociceptive states in humans during the course of leishmaniasis are an active area of research. The present article reviews nociception in leishmaniasis, including in experimental models of CL and clinical reports.

The Validity of Communication Experiments Using Human Subjects: A Review

ERIC Educational Resources Information Center

Rossiter, Charles M.

1976-01-01

Reviews sixty-eight experiments published in various journals in 1973 and 1974 and concludes that communication experimentation may be severely limited by the nature of the subjects studied and the inappropriate handling of experimental reactivity. (MH)

Sensing sociality in dogs: what may make an interactive robot social?

PubMed

Lakatos, Gabriella; Janiak, Mariusz; Malek, Lukasz; Muszynski, Robert; Konok, Veronika; Tchon, Krzysztof; Miklósi, A

2014-03-01

This study investigated whether dogs would engage in social interactions with an unfamiliar robot, utilize the communicative signals it provides and to examine whether the level of sociality shown by the robot affects the dogs' performance. We hypothesized that dogs would react to the communicative signals of a robot more successfully if the robot showed interactive social behaviour in general (towards both humans and dogs) than if it behaved in a machinelike, asocial way. The experiment consisted of an interactive phase followed by a pointing session, both with a human and a robotic experimenter. In the interaction phase, dogs witnessed a 6-min interaction episode between the owner and a human experimenter and another 6-min interaction episode between the owner and the robot. Each interaction episode was followed by the pointing phase in which the human/robot experimenter indicated the location of hidden food by using pointing gestures (two-way choice test). The results showed that in the interaction phase, the dogs' behaviour towards the robot was affected by the differential exposure. Dogs spent more time staying near the robot experimenter as compared to the human experimenter, with this difference being even more pronounced when the robot behaved socially. Similarly, dogs spent more time gazing at the head of the robot experimenter when the situation was social. Dogs achieved a significantly lower level of performance (finding the hidden food) with the pointing robot than with the pointing human; however, separate analysis of the robot sessions suggested that gestures of the socially behaving robot were easier for the dogs to comprehend than gestures of the asocially behaving robot. Thus, the level of sociality shown by the robot was not enough to elicit the same set of social behaviours from the dogs as was possible with humans, although sociality had a positive effect on dog-robot interactions.

Report on carcinogens monograph on cumene.

PubMed

2013-09-01

The National Toxicology Program conducted a cancer evaluation on cumene for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for cumene in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to cumene. This monograph provides an assessment of the available scientific information on cumene, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that cumene be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found that cumene exposure caused lung tumors in male and female mice and liver tumors in female mice. Several proposed mechanisms of carcinogenesis support the relevance to humans of the lung and liver tumors observed in experimental animals. Specifically, there is evidence that humans and experimental animals metabolize cumene through similar metabolic pathways. In addition, mutations of the K-ras oncogene and p53 tumor-suppressor gene observed in cumene-induced lung tumors in mice, along with altered expression of many other genes, resemble molecular alterations found in human lung and other cancers.

Human Behavior: Do Animals Have the Answer

ERIC Educational Resources Information Center

Trotter, Robert J.

1974-01-01

Results of psychological experiments usinganimals are presented. Use of the animal-human analogy to generalize these findings to humans is discussed. Ethological studies are interpreted in light of the total environment and situation involved. The completeness of the ethological model compared to the animal-experimental model is discussed. (LS)

Experimental cancer cachexia: Evolving strategies for getting closer to the human scenario.

PubMed

Penna, Fabio; Busquets, Sílvia; Argilés, Josep M

2016-06-01

Cancer cachexia is a frequent syndrome that dramatically affects patient quality of life, anti-cancer treatment effectiveness, and overall survival. To date, no effective treatment is available and most of the studies are performed in experimental models in order to uncover the underlying mechanisms and to design prospective therapeutic strategies. This review summarizes the most relevant information regarding the use of animal models for studying cancer cachexia. Technical limitations and degree of recapitulation of the features of human cachexia are highlighted, in order to help investigators choose the most suitable model according to study-specific endpoints. Copyright © 2015 Elsevier Ltd. All rights reserved.

Induction of peritoneal endometriosis in nude mice with use of human immortalized endometriosis epithelial and stromal cells: a potential experimental tool to study molecular pathogenesis of endometriosis in humans.

PubMed

Banu, Sakhila K; Starzinski-Powitz, Anna; Speights, V O; Burghardt, Robert C; Arosh, Joe A

2009-05-01

To determine whether a mixed population of immortalized human endometriosis epithelial and stromal cells is able to induce peritoneal endometriosis in nude mice. Prospective experimental study. Human immortalized endometriosis epithelial and stromal cells were xenografted into ovariectomized nude mice. Macroscopically, the number of induced endometriosis-like lesions and their color were determined. Microscopically, histomorphology of endometriosis glands and their structure were analyzed, and comparisons were made with tissue from spontaneous endometriosis in women. College of Veterinary Medicine and Biomedical Sciences, Texas A&M University. Seven ovariectomized nude mice. Minimal invasive procedures were performed to administer estrogen pellets and transplant immortalized human endometriosis epithelial and stromal cells into nude mice. Peritoneal endometriosis-like lesions induced in nude mice were characterized and compared with spontaneous peritoneal endometriosis in women. Xenografts of human immortalized endometriosis epithelial and stromal cells into the peritoneal cavity of the recipient nude mice are able to proliferate, attach, invade, reorganize, and establish peritoneal endometriosis. Endometriosis glands at different stages of growth were present in induced endometriosis-like lesions. Proliferating cell nuclear antigen, metalloproteinase 2, estrogen receptor-alpha, cyclooxygenase-2, and prostaglandin E(2) receptors EP2 and EP4 proteins were expressed in both endometriosis glandular epithelial and stromal cells of the induced endometriosis-like lesions. This xenograft model could be used as a potential experimental tool to understand the molecular and cellular aspects of the pathogenesis of endometriosis in humans.

HUMAN BODY SHAPE INDEX BASED ON AN EXPERIMENTALLY DERIVED MODEL OF HUMAN GROWTH

PubMed Central

Lebiedowska, Maria K.; Alter, Katharine E.; Stanhope, Steven J.

2009-01-01

Objectives To test the assumption of geometrically similar growth by developing experimentally derived models of human body growth during the age interval of 5–18 years; to use the derived growth models to establish a new Human Body Shape Index (HBSI) based on natural age related changes in HBS; and to compare various metrics of relative body weight (body mass index, ponderal index, HBSI) in a sample of 5–18 year old children. Study design Non-disabled Polish children (N=847) participated in this descriptive study. To model growth, the best fit between body height (H) and body mass (M) was calculated for each sex with the allometric equation M= miHχ. HBSI and HBSI were calculated separately for girls and boys, using sex-specific values for χ and a general HBSI from combined data. The customary body mass and ponderal indices were calculated and compared to HBSI values. Results The models of growth were M=13.11H2.84 (R2=.90) and M=13.64H2.68 (R2=.91) for girls and boys respectively. HBSI values contained less inherent variability and were influenced least by growth (age and height) than customary indices. Conclusion Age-related growth during childhood is sex-specific and not geometrically similar. Therefore, indices of human body shape formulated from experimentally derived models of human growth are superior to customary geometric similarity-based indices for the characterization of human body shape in children during the formative growth years. PMID:18154897

PLANT - An experimental task for the study of human problem solving in process control. [Production Levels and Network Troubleshooting

NASA Technical Reports Server (NTRS)

Morris, N. M.; Rouse, W. B.; Fath, J. L.

1985-01-01

An experimental tool for the investigation of human problem-solving behavior is introduced. Production Levels and Network Troubleshooting (PLANT) is a computer-based process-control task which may be used to provide opportunities for subjects to control a dynamic system and diagnose, repair, and compensate for system failures. The task is described in detail, and experiments which have been conducted using PLANT are briefly discussed.

Tech versus the Human Touch: Teacher Affect Is More Effective.

ERIC Educational Resources Information Center

Perry, Alan

2003-01-01

An experimental group studied Macbeth in an independent, constructivist setting using multimedia; the control group studied traditionally. Eleven of 23 experimental students and 2 of 21 in the traditional class failed. In an experiment with Hamlet, the results were reversed. Students were most successful when the teacher was actively involved,…

[Human milk for neonatal pain relief during ophthalmoscopy].

PubMed

Ribeiro, Laiane Medeiros; Castral, Thaíla Corrêa; Montanholi, Liciane Langona; Daré, Mariana Firmino; Silva, Aline Carolina de Araújo; Antonini, Sonir Roberto Rauber; Scochi, Carmen Gracinda Silvan

2013-10-01

Ophthalmoscopy performed for the early diagnosis of retinopathy of prematurity (ROP) is painful for preterm infants, thus necessitating interventions for minimizing pain. The present study aimed to establish the effectiveness of human milk, compared with sucrose, for pain relief in premature infants subjected to ophthalmoscopy for the early diagnosis of ROP. This investigation was a pilot, quasi-experimental study conducted with 14 premature infants admitted to the neonatal intensive care unit (NICU) of a university hospital. Comparison between the groups did not yield a statistically significant difference relative to the crying time, salivary cortisol, or heart rate (HR). Human milk appears to be as effective as sucrose in relieving acute pain associated with ophthalmoscopy. The study's limitations included its small sample size and lack of randomization. Experimental investigations with greater sample power should be performed to reinforce the evidence found in the present study.

[Are non-clinical studies predictive of adverse events in humans?].

PubMed

Claude, N

2007-09-01

The predictibility of adverse events induced by drugs in non-clinical safety studies performed on in vitro and/or in vivo models is a key point for the safety of humans exposed to pharmaceuticals. The strength and the weakness of animal studies to predict human toxicity were assessed by an international study on the concordance of the toxicity of 150 pharmaceuticals observed in humans with that observed in experimental animals. The results showed a good correlation (70% of the adverse events in humans were detected in animal studies) and an early time to first appearance of concordant animal toxicity: 94% were first observed in studies of 1 month or less in duration. The highest incidence of overall concordance was seen in hematological and cardiovascular adverse effects and the least was seen in cutaneous and ophthalmological adverse effects. These studies, scientifically and regulatory standardized, need, in some cases to be adapted to specific problems linked to sensitive populations (young, old or with a pathology which could be worsened by the drug), or specific pharmaceuticals (produced by biotechnology). Some severe adverse events are not detected in conventional animal models (immuno-allergy, idiosyncrasy). Taken together, these elements support the value of toxicology studies to predict many human toxic events associated with pharmaceuticals. Nevertheless, a part of human toxicity is not detected by these experimental approaches, and new tools developed through progress in biology and bio-informatics should reduce this uncertainly margin.

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

ERIC Educational Resources Information Center

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

2014-01-01

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

ELECTRORETINOGRAMS ARE ALTERED BY SUBCHRONIC TOLUENE EXPOSURE TO LONG EVANS RATS: EXPERIMENTAL EVIDENCE SUPPORTING OBSERVATIONS FROM STUDIES OF EXPOSED HUMANS

EPA Science Inventory

Impaired visual functions, including low contrast sensitivity and reduced color discrimination, have been reported in studies of humans chronically exposed to several volatile organic solvents. These reports remain controversial, however, in part due to a lack of confirmation fro...

Subchronic Toluene Exposure alters Retinal Function in Long Evans Rats: Experimental Evidence Supporting Observations from Studies of Exposed Humans.

EPA Science Inventory

Studies of humans chronically exposed to volatile organic solvents commonly report impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports have been controversial, however, in part due to a lack of confirmation from controlled...

Coordination Mechanism in Fast Human Movements. Experimental and Modelling Studies. Volume 1.

DTIC Science & Technology

1983-09-01

Electrical Stimulation and the Treatment of Flaccid Hemiparesis : A Report on Three Case Studies", W. Kroll, P. Lagasse, and W. Kilmer. Proc. Conf...Canadian Soc. for Biomechanics (Human Locomotion 2), Kingston, Ontario, September 1982. 5. " Hemiparesis of the Upper Limb and Functional Electrical

Inherited secondary nephrogenic diabetes insipidus: concentrating on humans.

PubMed

Bockenhauer, D; Bichet, D G

2013-04-15

The study of human physiology is paramount to understanding disease and developing rational and targeted treatments. Conversely, the study of human disease can teach us a lot about physiology. Investigations into primary inherited nephrogenic diabetes insipidus (NDI) have contributed enormously to our understanding of the mechanisms of urinary concentration and identified the vasopressin receptor AVPR2, as well as the water channel aquaporin-2 (AQP2), as key players in water reabsorption in the collecting duct. Yet, there are also secondary forms of NDI, for instance as a complication of lithium treatment. The focus of this review is secondary NDI associated with inherited human diseases, such as Bartter syndrome or apparent mineralocorticoid excess. Currently, the underlying pathophysiology of this inherited secondary NDI is unclear, but there appears to be true AQP2 deficiency. To better understand the underlying mechanism(s), collaboration between clinical and experimental physiologists is essential to further investigate these observations in appropriate experimental models.

Can prion diseases be transmitted between individuals via blood transfusion: evidence from sheep experiments.

PubMed

Hunter, N; Houston, F

2002-01-01

We have shown that it is possible to transmit bovine spongiform encephalitis (BSE) to a sheep by transfusion with whole blood taken from another sheep during the pre-clinical phase of an experimental BSE infection when the donor animal appears healthy. BSE and new variant Creutzfeld-Jakob disease (vCJD) in humans are caused by the same infectious agent and the sheep-BSE experimental model has similar pathogenesis, with involvement of the lymphoreticular system, to that of human vCJD. Although we have had only one case of positive transmission of BSE out of a total of 21 transfusions, our studies remain incomplete and further cases could occur. Our studies, however, reinforce the possibility that whole blood donated by pre-clinical vCJD-infected humans may represent a risk of spreading vCJD infection among the human population of the U.K.

Paths of Movement for Selected Body Segments During Typical Pilot Tasks

DTIC Science & Technology

1976-03-01

11 Scope ........... ...................... 12 Past Human Motion Investigations ........... ... 13 Experimental Techniques in Human...of.literature has been generated during the past few decades in the field of human-motion recording and analysis. However, in most of these studies body...to meet the COMBIMAN model requirements. Past Human Motion Investigations The 15th century artist-scientist, Leonardo da Vinci, is generally credited

Experimental and clinical evidence of antioxidant therapy in acute pancreatitis

PubMed Central

Esrefoglu, Mukaddes

2012-01-01

Oxidative stress has been shown to play an important role in the pathogenesis of acute pancreatitis (AP). Antioxidants, alone or in combination with conventional therapy, should improve oxidative-stress-induced organ damage and therefore accelerate the rate of recovery. In recent years, substantial amounts of data about the efficiency of antioxidants against oxidative damage have been obtained from experiments with rodents. Some of these antioxidants have been found beneficial in the treatment of AP in humans; however, at present there is insufficient clinical data to support the benefits of antioxidants, alone or in combination with conventional therapy, in the management of AP in humans. Conflicting results obtained from experimental animals and humans may represent distinct pathophysiological mechanisms mediating tissue injury in different species. Further detailed studies should be done to clarify the exact mechanisms of tissue injury in human AP. Herein I tried to review the existing experimental and clinical studies on AP in order to determine the efficiency of antioxidants. The use of antioxidant enriched nutrition is a potential direction of clinical research in AP given the lack of clues about the efficiency and safety of antioxidant usage in patients with AP. PMID:23112545

Recommendations for Improving Identification and Quantification in Non-Targeted, GC-MS-Based Metabolomic Profiling of Human Plasma

PubMed Central

Wang, Hanghang; Muehlbauer, Michael J.; O’Neal, Sara K.; Newgard, Christopher B.; Hauser, Elizabeth R.; Shah, Svati H.

2017-01-01

The field of metabolomics as applied to human disease and health is rapidly expanding. In recent efforts of metabolomics research, greater emphasis has been placed on quality control and method validation. In this study, we report an experience with quality control and a practical application of method validation. Specifically, we sought to identify and modify steps in gas chromatography-mass spectrometry (GC-MS)-based, non-targeted metabolomic profiling of human plasma that could influence metabolite identification and quantification. Our experimental design included two studies: (1) a limiting-dilution study, which investigated the effects of dilution on analyte identification and quantification; and (2) a concentration-specific study, which compared the optimal plasma extract volume established in the first study with the volume used in the current institutional protocol. We confirmed that contaminants, concentration, repeatability and intermediate precision are major factors influencing metabolite identification and quantification. In addition, we established methods for improved metabolite identification and quantification, which were summarized to provide recommendations for experimental design of GC-MS-based non-targeted profiling of human plasma. PMID:28841195

The Non-Human Primate Experimental Glaucoma Model

PubMed Central

Burgoyne, Claude F.

2015-01-01

The purpose of this report is to summarize the current strengths and weaknesses of the non-human primate (NHP) experimental glaucoma (EG) model through sections devoted to its history, methods, important findings, alternative optic neuropathy models and future directions. NHP EG has become well established for studying human glaucoma in part because the NHP optic nerve head (ONH) shares a close anatomic association with the human ONH and because it provides the only means of systematically studying the very earliest visual system responses to chronic IOP elevation, i.e. the conversion from ocular hypertension to glaucomatous damage. However, NHPs are impractical for studies that require large animal numbers, demonstrate spontaneous glaucoma only rarely, do not currently provide a model of the neuropathy at normal levels of IOP, and cannot easily be genetically manipulated, except through tissue-specific, viral vectors. The goal of this summary is to direct NHP EG and non-NHP EG investigators to the previous, current and future accomplishment of clinically relevant knowledge in this model. PMID:26070984

Human Thermal Model Evaluation Using the JSC Human Thermal Database

NASA Technical Reports Server (NTRS)

Bue, Grant; Makinen, Janice; Cognata, Thomas

2012-01-01

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

Social learning across species: horses (Equus caballus) learn from humans by observation.

PubMed

Schuetz, Aurelia; Farmer, Kate; Krueger, Konstanze

2017-05-01

This study examines whether horses can learn by observing humans, given that they identify individual humans and orientate on the focus of human attention. We tested 24 horses aged between 3 and 12. Twelve horses were tested on whether they would learn to open a feeding apparatus by observing a familiar person. The other 12 were controls and received exactly the same experimental procedure, but without a demonstration of how to operate the apparatus. More horses from the group with demonstration (8/12) reached the learning criterion of opening the feeder twenty times consecutively than horses from the control group (2/12), and younger horses seemed to reach the criterion more quickly. Horses not reaching the learning criteria approached the human experimenters more often than those that did. The results demonstrate that horses learn socially across species, in this case from humans.

Computational Model for Oxygen Transport and Consumption in Human Vitreous

PubMed Central

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

2013-01-01

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

Computational model for oxygen transport and consumption in human vitreous.

PubMed

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

2013-10-15

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

Numerical-experimental study of internal fixation system "Dufoo" for vertebral fractures.

PubMed

Nieto-Miranda, J Jesús; Faraón-Carbajal Romero, Manuel; Sánchez-Aguilar, Jons

2012-01-01

We describe a numerical experimental study of the stress generated by the internal fixation system "Dufoo" used in the treatment of vertebral fractures with the purpose of validating the numerical model of human lumbar vertebrae under the main physiological loads that the human body is exposed to in this area. The objective is to model and numerically simulate the elements of the musculoskeletal system to collect the stresses generated and other parameters that are difficult to measure experimentally in the thoracic lumbar vertebrae. We used an internal fixator "Dufoo" and vertebrae L2-L3-L4 specimens from pig and human. The system uses a total L3 corpectomy. The fixator acts as a mechanical bridge implant from L2 to L4. Numerical analysis was performed using the finite element method (FEM). For the experimental study, reflective photoelasticity and extensometry were used. Torsion and combined loads generate the main displacements and stresses in the study system, determining that the internal fixation carries out part of the function of the damaged organ structure when absorbing the stresses presented by applied loads. Numerical analysis allows great freedom in the management of the variables involved in the developed models using radiological images. Geometric models are obtained and are entered into FEM programs that allow testing using parameters that, under actual conditions, may not be easily carried out, allowing to comprehensively determine the biomechanical behavior of the coupled system of study.

Does renal ageing affect survival?

PubMed

Razzaque, M Shawkat

2007-10-01

The effects of ageing on progressive deterioration of renal function, both in human and experimental animals, are described elsewhere, but the effect of renal damage on overall survival and longevity is not yet clearly established. The wild-type animals of various genetic backgrounds, fed with regular diet, overtime develop severe age-associated nephropathy, that include but not limited to inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis. Such renal damage significantly reduces their survival. Reducing renal damage, either by caloric restriction or by suppressing growth hormone (GH)/insulin-like growth factor-1 (IGF-1) activity could significantly enhance the longevity of these animals. Available survival studies using experimental animals clearly suggest that kidney pathology is one of the important non-neoplastic lesions that could affect overall survival, and that restoration of renal function by preventing kidney damage could significantly extend longevity. Careful long-term studies are needed to determine the human relevance of these experimental studies.

Game-XP: Action Games as Experimental Paradigms for Cognitive Science.

PubMed

Gray, Wayne D

2017-04-01

Why games? How could anyone consider action games an experimental paradigm for Cognitive Science? In 1973, as one of three strategies he proposed for advancing Cognitive Science, Allen Newell exhorted us to "accept a single complex task and do all of it." More specifically, he told us that rather than taking an "experimental psychology as usual approach," we should "focus on a series of experimental and theoretical studies around a single complex task" so as to demonstrate that our theories of human cognition were powerful enough to explain "a genuine slab of human behavior" with the studies fitting into a detailed theoretical picture. Action games represent the type of experimental paradigm that Newell was advocating and the current state of programming expertise and laboratory equipment, along with the emergence of Big Data and naturally occurring datasets, provide the technologies and data needed to realize his vision. Action games enable us to escape from our field's regrettable focus on novice performance to develop theories that account for the full range of expertise through a twin focus on expertise sampling (across individuals) and longitudinal studies (within individuals) of simple and complex tasks. Copyright © 2017 Cognitive Science Society, Inc.

40 CFR 158.250 - Experimental use permit data requirements for human exposure.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Experimental use permit data requirements for human exposure. 158.250 Section 158.250 Protection of Environment ENVIRONMENTAL PROTECTION... Experimental use permit data requirements for human exposure. No data for applicator exposure and post...

40 CFR 158.250 - Experimental use permit data requirements for human exposure.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Experimental use permit data requirements for human exposure. 158.250 Section 158.250 Protection of Environment ENVIRONMENTAL PROTECTION... Experimental use permit data requirements for human exposure. No data for applicator exposure and post...

40 CFR 158.250 - Experimental use permit data requirements for human exposure.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Experimental use permit data requirements for human exposure. 158.250 Section 158.250 Protection of Environment ENVIRONMENTAL PROTECTION... Experimental use permit data requirements for human exposure. No data for applicator exposure and post...

40 CFR 158.250 - Experimental use permit data requirements for human exposure.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Experimental use permit data requirements for human exposure. 158.250 Section 158.250 Protection of Environment ENVIRONMENTAL PROTECTION... Experimental use permit data requirements for human exposure. No data for applicator exposure and post...

The use of MR B+1 imaging for validation of FDTD electromagnetic simulations of human anatomies.

PubMed

Van den Berg, Cornelis A T; Bartels, Lambertus W; van den Bergen, Bob; Kroeze, Hugo; de Leeuw, Astrid A C; Van de Kamer, Jeroen B; Lagendijk, Jan J W

2006-10-07

In this study, MR B(+)(1) imaging is employed to experimentally verify the validity of FDTD simulations of electromagnetic field patterns in human anatomies. Measurements and FDTD simulations of the B(+)(1) field induced by a 3 T MR body coil in a human corpse were performed. It was found that MR B(+)(1) imaging is a sensitive method to measure the radiofrequency (RF) magnetic field inside a human anatomy with a precision of approximately 3.5%. A good correlation was found between the B(+)(1) measurements and FDTD simulations. The measured B(+)(1) pattern for a human pelvis consisted of a global, diagonal modulation pattern plus local B(+)(1) heterogeneties. It is believed that these local B(+)(1) field variations are the result of peaks in the induced electric currents, which could not be resolved by the FDTD simulations on a 5 mm(3) simulation grid. The findings from this study demonstrate that B(+)(1) imaging is a valuable experimental technique to gain more knowledge about the dielectric interaction of RF fields with the human anatomy.

PBPK modeling for PFOS and PFOA: validation with human experimental data.

PubMed

Fàbrega, Francesc; Kumar, Vikas; Schuhmacher, Marta; Domingo, José L; Nadal, Martí

2014-10-15

In recent years, because of the potential human toxicity, concern on perfluoroalkyl substances (PFASs) has increased notably with special attention to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Unfortunately, there is currently an important knowledge gap on the burdens of these chemicals in most human tissues, as the reported studies have been mainly focused on plasma. In order to overcome these limitations, the use of physiologically-based pharmacokinetic (PBPK) models has been extended. The present study was aimed at testing an existing PBPK model for their predictability of PFOS and PFOA in a new case-study, and also to adapt it to estimate the PFAS content in human tissue compartments. Model validation was conducted by means of PFOA and PFOS concentrations in food and human drinking water from Tarragona County (Catalonia, Spain), and being the predicted results compared with those experimentally found in human tissues (blood, liver, kidney, liver and brain) of subjects from the same area of study. The use of human-derived partition coefficient (Pk) data was proven as more suitable for application to this PBPK model than rat-based Pk values. However, the uncertainty and variability of the data are still too high to get conclusive results. Consequently, further efforts should be carried out to reduce parametric uncertainty of PBPK models. More specifically, a deeper knowledge on the distribution of PFOA and PFOS within the human body should be obtained by enlarging the number of biological monitoring studies on PFASs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Plasmodium knowlesi: from severe zoonosis to animal model.

PubMed

Cox-Singh, Janet; Culleton, Richard

2015-06-01

Plasmodium knowlesi malaria is a newly described zoonosis in Southeast Asia. Similarly to Plasmodium falciparum, P. knowlesi can reach high parasitaemia in the human host and both species cause severe and fatal illness. Interpretation of host-parasite interactions in studies of P. knowlesi malaria adds a counterpoint to studies on P. falciparum. However, there is no model system for testing the resulting hypotheses on malaria pathophysiology or for developing new interventions. Plasmodium knowlesi is amenable to genetic manipulation in vitro and several nonhuman primate species are susceptible to experimental infection. Here, we make a case for drawing on P. knowlesi as both a human pathogen and an experimental model to lift the roadblock between malaria research and its translation into human health benefits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Studying the neurobiology of human social interaction: Making the case for ecological validity.

PubMed

Hogenelst, Koen; Schoevers, Robert A; aan het Rot, Marije

2015-01-01

With this commentary we make the case for an increased focus on the ecological validity of the measures used to assess aspects of human social functioning. Impairments in social functioning are seen in many types of psychopathology, negatively affecting the lives of psychiatric patients and those around them. Yet the neurobiology underlying abnormal social interaction remains unclear. As an example of human social neuroscience research with relevance to biological psychiatry and clinical psychopharmacology, this commentary discusses published experimental studies involving manipulation of the human brain serotonin system that included assessments of social behavior. To date, these studies have mostly been laboratory-based and included computer tasks, observations by others, or single-administration self-report measures. Most laboratory measures used so far inform about the role of serotonin in aspects of social interaction, but the relevance for real-life interaction is often unclear. Few studies have used naturalistic assessments in real life. We suggest several laboratory methods with high ecological validity as well as ecological momentary assessment, which involves intensive repeated measures in naturalistic settings. In sum, this commentary intends to stimulate experimental research on the neurobiology of human social interaction as it occurs in real life.

Asymmetry in scientific method and limits to cross-disciplinary dialogue: toward a shared language and science policy in pharmacogenomics and human disease genetics.

PubMed

Ozdemir, Vural; Williams-Jones, Bryn; Graham, Janice E; Preskorn, Sheldon H; Gripeos, Dimitrios; Glatt, Stephen J; Friis, Robert H; Reist, Christopher; Szabo, Sandor; Lohr, James B; Someya, Toshiyuki

2007-04-01

Pharmacogenomics is a hybrid field of experimental science at the intersection of human disease genetics and clinical pharmacology sharing applications of the new genomic technologies. But this hybrid field is not yet stable or fully integrated, nor is science policy in pharmacogenomics fully equipped to resolve the challenges of this emerging hybrid field. The disciplines of human disease genetics and clinical pharmacology contain significant differences in their scientific practices. Whereas clinical pharmacology originates as an experimental science, human disease genetics is primarily observational in nature. The result is a significant asymmetry in scientific method that can differentially impact the degree to which gene-environment interactions are discerned and, by extension, the study sample size required in each discipline. Because the number of subjects enrolled in observational genetic studies of diseases is characteristically viewed as an important criterion of scientific validity and reliability, failure to recognize discipline-specific requirements for sample size may lead to inappropriate dismissal or silencing of meritorious, although smaller-scale, craft-based pharmacogenomic investigations using an experimental study design. Importantly, the recognition that pharmacogenomics is an experimental science creates an avenue for systematic policy response to the ethical imperative to prospectively pursue genetically customized therapies before regulatory approval of pharmaceuticals. To this end, we discuss the critical role of interdisciplinary engagement between medical sciences, policy, and social science. We emphasize the need for development of shared standards across scientific, methodologic, and socioethical epistemologic divides in the hybrid field of pharmacogenomics to best serve the interests of public health.

[Effects of lycopene on the skeletal system].

PubMed

Sołtysiak, Patrycja; Folwarczna, Joanna

2015-02-21

Antioxidant substances of plant origin, such as lycopene, may favorably affect the skeletal system. Lycopene is a carotenoid pigment, responsible for characteristic red color of tomatoes. It is believed that lycopene may play a role in the prevention of various diseases; despite theoretical premises and results of experimental studies, the effectiveness of lycopene has not yet been clearly demonstrated in studies carried out in humans. The aim of the study was to present the current state of knowledge on the effects of lycopene on the osseous tissue in in vitro and in vivo experimental models and on the skeletal system in humans. Results of the studies indicate that lycopene may inhibit bone resorption. Favorable effects of high doses of lycopene on the rat skeletal system in experimental conditions, including the model of osteoporosis induced by estrogen deficiency, have been demonstrated. The few epidemiological and clinical studies, although not fully conclusive, suggest a possible beneficial effect of lycopene present in the diet on the skeletal system.

A combined experimental and numerical study on upper airway dosimetry of inhaled nanoparticles from an electrical discharge machine shop.

PubMed

Tian, Lin; Shang, Yidan; Chen, Rui; Bai, Ru; Chen, Chunying; Inthavong, Kiao; Tu, Jiyuan

2017-07-12

Exposure to nanoparticles in the workplace is a health concern to occupational workers with increased risk of developing respiratory, cardiovascular, and neurological disorders. Based on animal inhalation study and human lung tumor risk extrapolation, current authoritative recommendations on exposure limits are either on total mass or number concentrations. Effects of particle size distribution and the implication to regional airway dosages are not elaborated. Real time production of particle concentration and size distribution in the range from 5.52 to 98.2 nm were recorded in a wire-cut electrical discharge machine shop (WEDM) during a typical working day. Under the realistic exposure condition, human inhalation simulations were performed in a physiologically realistic nasal and upper airway replica. The combined experimental and numerical study is the first to establish a realistic exposure condition, and under which, detailed dose metric studies can be performed. In addition to mass concentration guided exposure limit, inhalation risks to nano-pollutant were reexamined accounting for the actual particle size distribution and deposition statistics. Detailed dosimetries of the inhaled nano-pollutants in human nasal and upper airways with respect to particle number, mass and surface area were discussed, and empirical equations were developed. An astonishing enhancement of human airway dosages were detected by current combined experimental and numerical study in the WEDM machine shop. Up to 33 folds in mass, 27 folds in surface area and 8 folds in number dosages were detected during working hours in comparison to the background dosimetry measured at midnight. The real time particle concentration measurement showed substantial emission of nano-pollutants by WEDM machining activity, and the combined experimental and numerical study provided extraordinary details on human inhalation dosimetry. It was found out that human inhalation dosimetry was extremely sensitive to real time particle concentration and size distribution. Averaged particle concentration over 24-h period will inevitably misrepresent the sensible information critical for realistic inhalation risk assessment. Particle size distribution carries very important information in determining human airway dosimetry. A pure number or mass concentration recommendation on the exposure limit at workplace is insufficient. A particle size distribution, together with the deposition equations, is critical to recognize the actual exposure risks. In addition, human airway dosimetry in number, mass and surface area varies significantly. A complete inhalation risk assessment requires the knowledge of toxicity mechanisms in response to each individual metric. Further improvements in these areas are needed.

Human Laboratory Paradigms in Alcohol Research

PubMed Central

Plebani, Jennifer G.; Ray, Lara A.; Morean, Meghan E.; Corbin, William R.; Mackillop, James; Amlung, Michael; King, Andrea C.

2014-01-01

Human laboratory studies have a long and rich history in the field of alcoholism. Human laboratory studies have allowed for advances in alcohol research in a variety of ways, including elucidating of the neurobehavioral mechanisms of risk, identifying phenotypically distinct sub-types of alcohol users, investigating of candidate genes underlying experimental phenotypes for alcoholism, and testing mechanisms of action of alcoholism pharmacotherapies on clinically-relevant translational phenotypes, such as persons exhibiting positive-like alcohol effects or alcohol craving. Importantly, the field of human laboratory studies in addiction has progressed rapidly over the past decade and has built upon earlier findings of alcohol's neuropharmacological effects to advancing translational research on alcoholism etiology and treatment. To that end, the new generation of human laboratory studies has focused on applying new methodologies, further refining alcoholism phenotypes, and translating these findings to studies of alcoholism genetics, medication development, and pharmacogenetics. The combination of experimental laboratory approaches with recent developments in neuroscience and pharmacology has been particularly fruitful in furthering our understanding of the impact of individual differences in alcoholism risk and in treatment response. This review of the literature focuses on human laboratory studies of subjective intoxication, alcohol craving, anxiety, and behavioral economics. Each section discusses opportunities for phenotype refinement under laboratory conditions, as well as its application to translational science of alcoholism. A summary and recommendations for future research are also provided. PMID:22309888

The application of heterogeneous cluster grouping to reflective writing for medical humanities literature study to enhance students' empathy, critical thinking, and reflective writing.

PubMed

Liao, Hung-Chang; Wang, Ya-Huei

2016-09-02

To facilitate interdisciplinary collaboration and to make connections between patients' diseases and their social/cultural contexts, the study examined whether the use of heterogeneous cluster grouping in reflective writing for medical humanities literature acquisition could have positive effects on medical university students in terms of empathy, critical thinking, and reflective writing. A 15-week quasi-experimental design was conducted to investigate the learning outcomes. After conducting cluster algorithms, heterogeneous learning clusters (experimental group; n = 43) and non-heterogeneous learning clusters (control group; n = 43) were derived for a medical humanities literature study. Before and after the intervention, an Empathy Scale in Patient Care (ES-PC), a critical thinking disposition assessment (CTDA-R), and a reflective writing test were administered to both groups. The findings showed that on the empathy scale, significant differences in the "behavioral empathy," "affective empathy," and overall sections existed between the post-test mean scores of the experimental group and those of the control group, but such differences did not exist in "intelligent empathy." Regarding critical thinking, there were significant differences in "systematicity and analyticity," "skepticism and well-informed," "maturity and skepticism," and overall sections. As for reflective writing, significant differences existed in "ideas," "voice and point of view," "critical thinking and representation," "depth of reflection on personal growth," and overall sections, but not in "focus and context structure" and "language and conventions." This study outlined an alternative for using heterogeneous cluster grouping in reflective writing about medical humanities literature to facilitate interdisciplinary cooperation to provide more humanizing medical care.

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

NASA Astrophysics Data System (ADS)

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

2004-04-01

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

A Mechanistic Model of Human Recall of Social Network Structure and Relationship Affect.

PubMed

Omodei, Elisa; Brashears, Matthew E; Arenas, Alex

2017-12-07

The social brain hypothesis argues that the need to deal with social challenges was key to our evolution of high intelligence. Research with non-human primates as well as experimental and fMRI studies in humans produce results consistent with this claim, leading to an estimate that human primary groups should consist of roughly 150 individuals. Gaps between this prediction and empirical observations can be partially accounted for using "compression heuristics", or schemata that simplify the encoding and recall of social information. However, little is known about the specific algorithmic processes used by humans to store and recall social information. We describe a mechanistic model of human network recall and demonstrate its sufficiency for capturing human recall behavior observed in experimental contexts. We find that human recall is predicated on accurate recall of a small number of high degree network nodes and the application of heuristics for both structural and affective information. This provides new insight into human memory, social network evolution, and demonstrates a novel approach to uncovering human cognitive operations.

VICTORIA Class Submarine Human-in-the-Loop Experimentation Plan

DTIC Science & Technology

2014-06-01

1472G. VICTORIA Class Submarine Human-in-the-Loop Experimentation Plan and Preliminary Results © Her Majesty the Queen in Right of...19 th International Command and Control Research and Technology Symposium Title: VICTORIA Class Submarine Human-in-the-Loop...TYPE 3. DATES COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE VICTORIA Class Submarine Human-in-the-Loop Experimentation Plan 5a. CONTRACT

New insights on therapeutic touch: a discussion of experimental methodology and design that resulted in significant effects on normal human cells and osteosarcoma.

PubMed

Monzillo, Eloise; Gronowicz, Gloria

2011-01-01

Our purpose is to discuss the study design and innovative approaches that led to finding significant effects of one energy medicine therapy, Therapeutic Touch (TT), on cells. In the original published studies, TT was shown to significantly increase human osteoblast DNA synthesis, differentiation, and mineralization; increase in a dose-dependent manner the growth of other human cell types; and decrease the differentiation and mineralization of a human osteosarcoma-derived cell line. A unique feature of the study's methodology and design that contributed to the success of the findings was that a basic level of skill and maturity of the TT practitioner was quantified for producing observable and replicable outcomes in a test administered to all TT practitioners. Only those practitioners that passed the test were selected for the study. (2) The practitioners were required to keep a journal, which appeared to promote their ability to stay centered and replicate their treatments over months of cell experimentation. (3) The origin of the cells that the practitioners were treating was explained to them, although they were blinded to cell type during the experiments. (4) Only early passage cells were used to maintain a stable cell phenotype. (5) Standard protocols for performing TT in the room were followed to ensure reproducible conditions. (6) Placebo controls and untreated controls were used for each experiment. (7) The principal investigator and technicians performing the assays were blinded as to the experimental groups, and all assays and procedures were well established in the laboratory prior to the start of the TT experiments. The absence of studies on the human biofield from mainstream scientific literature is also discussed by describing the difficulties encountered in publishing. These roadblocks contribute to our lack of understanding of the human biofield and energy medicine modalities in science. In conclusion, this report seeks to encourage well-designed, evidence-based studies on the human biofield and the therapeutic potential of the human biofield. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of geomagnetic activity variations on the physiological and psychological state of functionally healthy humans: Some results of Azerbaijani studies

NASA Astrophysics Data System (ADS)

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.

Dynamics of the brain: Mathematical models and non-invasive experimental studies

NASA Astrophysics Data System (ADS)

Toronov, V.; Myllylä, T.; Kiviniemi, V.; Tuchin, V. V.

2013-10-01

Dynamics is an essential aspect of the brain function. In this article we review theoretical models of neural and haemodynamic processes in the human brain and experimental non-invasive techniques developed to study brain functions and to measure dynamic characteristics, such as neurodynamics, neurovascular coupling, haemodynamic changes due to brain activity and autoregulation, and cerebral metabolic rate of oxygen. We focus on emerging theoretical biophysical models and experimental functional neuroimaging results, obtained mostly by functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS). We also included our current results on the effects of blood pressure variations on cerebral haemodynamics and simultaneous measurements of fast processes in the brain by near-infrared spectroscopy and a very novel functional MRI technique called magnetic resonance encephalography. Based on a rapid progress in theoretical and experimental techniques and due to the growing computational capacities and combined use of rapidly improving and emerging neuroimaging techniques we anticipate during next decade great achievements in the overall knowledge of the human brain.

The effects of organic chromium on adipose anatomical parts, using pig as experimental model.

PubMed

Untea, A E; Varzaru, I; Ropota, M; Panaite, T D; Cornescu, G M

2016-01-01

The aim of this study was to evaluate the influence of chromium supplements on the quality of protein and lipids of adipose anatomical parts using pig as experimental modelfor humans. An experiment was conducted on 18 fattening castrated TOPIGS male pigs, for 4 weeks, under experimental farm conditions. The source of Cr(III) was chromium . picolinate, a food supplement used in human nutrition, 200 µg.Cr per kg diet (El) and 400 µg.Cr per kg diet (E2). The analytic.data showed an improvement of the amino acids profile in belly and in ham samples. A significant decrease of fatty acids concentrations in belly samples was noticed. In conclusion, we observed a positive effect associated with the essential amino acids deposition and decreasing of fatty acids concentrations in tissues with high content offat, thus in human nutrition, chromium is used as a nutritional supplement most recommended in impaired carbohydrate metabolism.

Reconciled rat and human metabolic networks for comparative toxicogenomics and biomarker predictions

PubMed Central

Blais, Edik M.; Rawls, Kristopher D.; Dougherty, Bonnie V.; Li, Zhuo I.; Kolling, Glynis L.; Ye, Ping; Wallqvist, Anders; Papin, Jason A.

2017-01-01

The laboratory rat has been used as a surrogate to study human biology for more than a century. Here we present the first genome-scale network reconstruction of Rattus norvegicus metabolism, iRno, and a significantly improved reconstruction of human metabolism, iHsa. These curated models comprehensively capture metabolic features known to distinguish rats from humans including vitamin C and bile acid synthesis pathways. After reconciling network differences between iRno and iHsa, we integrate toxicogenomics data from rat and human hepatocytes, to generate biomarker predictions in response to 76 drugs. We validate comparative predictions for xanthine derivatives with new experimental data and literature-based evidence delineating metabolite biomarkers unique to humans. Our results provide mechanistic insights into species-specific metabolism and facilitate the selection of biomarkers consistent with rat and human biology. These models can serve as powerful computational platforms for contextualizing experimental data and making functional predictions for clinical and basic science applications. PMID:28176778

Modal Damping Ratio and Optimal Elastic Moduli of Human Body Segments for Anthropometric Vibratory Model of Standing Subjects.

PubMed

Gupta, Manoj; Gupta, T C

2017-10-01

The present study aims to accurately estimate inertial, physical, and dynamic parameters of human body vibratory model consistent with physical structure of the human body that also replicates its dynamic response. A 13 degree-of-freedom (DOF) lumped parameter model for standing person subjected to support excitation is established. Model parameters are determined from anthropometric measurements, uniform mass density, elastic modulus of individual body segments, and modal damping ratios. Elastic moduli of ellipsoidal body segments are initially estimated by comparing stiffness of spring elements, calculated from a detailed scheme, and values available in literature for same. These values are further optimized by minimizing difference between theoretically calculated platform-to-head transmissibility ratio (TR) and experimental measurements. Modal damping ratios are estimated from experimental transmissibility response using two dominant peaks in the frequency range of 0-25 Hz. From comparison between dynamic response determined form modal analysis and experimental results, a set of elastic moduli for different segments of human body and a novel scheme to determine modal damping ratios from TR plots, are established. Acceptable match between transmissibility values calculated from the vibratory model and experimental measurements for 50th percentile U.S. male, except at very low frequencies, establishes the human body model developed. Also, reasonable agreement obtained between theoretical response curve and experimental response envelop for average Indian male, affirms the technique used for constructing vibratory model of a standing person. Present work attempts to develop effective technique for constructing subject specific damped vibratory model based on its physical measurements.

A Comparative Study on the Teaching Effects of TRIZ Courses for the Humanities

ERIC Educational Resources Information Center

Luo, Lingling; Li, Peng; Zhang, Ping

2017-01-01

In order to test the feasibility of the curriculum system of TRIZ used in humanities and social science majors, this study will test whether it is effective to cultivate students' creativity and to train their ability to solve problems. This study designs the randomly experimental targets in the two control groups for pretest and post-test. This…

The influence of retraction agents on cytoskeleton reorganization and oxidative stress in primary human gingival fibroblasts (HGFs).

PubMed

Nowakowska, Danuta; Saczko, Jolanta; Bieżuńska-Kusiak, Katarzyna; Choromańska, Anna; Dubińska-Magiera, Magda; Ziętek, Marek; Kulbacka, Julita

2014-03-01

Contemporary gingival retraction chemicals are not without disagreeable side-effects; there appears to be no best gingival retraction agent. The aim of this research was to select the most biocompatible retraction agents based on examination of the parameters of oxidative stress in fibroblasts derived from human primary cell culture. In this in vitro study we evaluated parameters of oxidative stress after treatment with retraction agents. Visine, Afrin, Neosynephrin, Strazolin and Adrenaline were the commercial products studied as gingival retraction agents. Additionally we examined three experimental agents. We determined lipid peroxidation and protein damage and monitored changes in cellular cytoskeleton proteins. Proliferative and survival efficiency were also evaluated. Oxidative changes included by evaluated retraction agents were at the lowest level in the case of the experimental gels. Also cytoskeleton observations suggest that the experimental agents did not degrade the cellular structure of human gingival fibroblasts (HGFs). The current study was performed because of a need to project new nontoxic and save retraction agents for peridontological therapeutic usage. We suggest that the new investigational gels are most biocompatible with periodontal tissues and can be applied as new vasoconstrictor chemical retraction agents. Copyright © 2014 Elsevier Ltd. All rights reserved.

Generalization Gradients in Human Predictive Learning: Effects of Discrimination Training and within-Subjects Testing

ERIC Educational Resources Information Center

Vervliet, Bram; Iberico, Carlos; Vervoort, Ellen; Baeyens, Frank

2011-01-01

Generalization gradients have been investigated widely in animal conditioning experiments, but much less so in human predictive learning tasks. Here, we apply the experimental design of a recent study on conditioned fear generalization in humans (Lissek et al., 2008) to a predictive learning task, and examine the effects of a number of relevant…

'Goats that stare at men'--revisited: do dwarf goats alter their behaviour in response to eye visibility and head direction of a human?

PubMed

Nawroth, Christian; von Borell, Eberhard; Langbein, Jan

2016-05-01

Being able to recognise when one is being observed by someone else is thought to be adaptive during cooperative or competitive events. In particular for prey species, this ability should be of use in the context of predation. A previous study reported that goats (Capra aegagrus hircus) alter their behaviour according to the body and head orientation of a human experimenter. During a food anticipation task, an experimenter remained in a particular posture for 30 s before delivering a reward, and the goats' active anticipation and standing alert behaviour were analysed. To further evaluate the specific mechanisms at work, we here present two additional test conditions. In particular, we investigated the effects of the eye visibility and head orientation of a human experimenter on the behaviour of the goats (N = 7). We found that the level of the subjects' active anticipatory behaviour was highest in the conditions where the experimenter was directing his head and body towards the goat ('Control' and 'Eyes closed' conditions), but the anticipatory behaviour was significantly decreased when the body ('Head only') or the head and body of the experimenter were directed away from the subject ('Back' condition). For standing alert, we found no significant differences between the three conditions in which the experimenter was directing his head towards the subject ('Control', 'Eyes closed' and 'Head only'). This lack of differences in the expression of standing alert suggests that goats evaluate the direction of a human's head as an important cue in their anticipatory behaviour. However, goats did not respond to the visibility of the experimenter's eyes alone.

The analgesic effects of exogenous melatonin in humans.

PubMed

Andersen, Lars Peter Holst

2016-10-01

The hormone, melatonin is produced with circadian rhythm by the pineal gland in humans. The melatonin rhythm provides an endogenous synchronizer, modulating e.g. blood pressure, body temperature, cortisol rhythm, sleep-awake-cycle, immune function and anti-oxidative defence. Interestingly, a number of experimental animal studies demonstrate significant dose-dependent anti-nociceptive effects of exogenous melatonin. Similarly, recent experimental- and clinical studies in humans indicate significant analgesic effects. In study I, we systematically reviewed all randomized studies investigating clinical effects of perioperative melatonin. Meta-analyses demonstrated significant analgesic and anxiolytic effects of melatonin in surgical patients, equating reductions of 20 mm and 19 mm, respectively on a VAS, compared with placebo. Profound heterogeneity between the included studies was, however, present. In study II, we aimed to investigate the analgesic, anti-hyperalgesic and anti-inflammatory effects of exogenous melatonin in a validated human inflammatory pain model, the human burn model. The study was performed as a randomized, double blind placebo-controlled crossover study. Primary outcomes were pain during the burn injury and areas of secondary hyperalgesia. No significant effects of exogenous melatonin were observed with respect to primary or secondary outcomes, compared to placebo. Study III and IV estimated the pharmacokinetic variables of exogenous melatonin. Oral melatonin demonstrated a t max value of 41 minutes. Bioavailability of oral melatonin was only 3%. Elimination t 1/2 were approximately 45 minutes following both oral and intravenous administration, respectively. High-dose intravenous melatonin was not associated with increased sedation, in terms of simple reaction times, compared to placebo. Similarly, no other adverse effects were reported. In Study V, we aimed to re-analyse data obtained from a randomized analgesic drug trial by a selection of standard statistical test. Furthermore, we presented an integrated assessment method of longitudinally measured pain intensity and opioid consumption. Our analyses documented that the employed statistical method impacted the statistical significance of post-operative analgesic outcomes. Furthermore, the novel integrated assessment method combines two interdependent outcomes, lowers the risk of type 2 errors, increases the statistical power, and provides a more accurate description of post-operative analgesic efficacy. Exogenous melatonin may offer an effective and safe analgesic drug. At this moment, however, the results of human studies have been contradictory. High-quality randomized experimental- and clinical studies are still needed to establish a "genuine" analgesic effect of the drug in humans. Other perioperative effects of exogenous melatonin should also be investigated, before melatonin can be introduced for clinical routine use in surgical patients. Despite promising experimental and clinical findings, several unanswered questions also relate to optimal dosage, timing of administration and administration route of exogenous melatonin.

The study of human higher mental functions as they relate to neurophysiological processes and personal characteristics

NASA Astrophysics Data System (ADS)

Runnova, Anastasiya; Zhuravlev, Maxim; Kulanin, Roman; Protasov, Pavel; Hramov, Alexander; Koronovskii, Alexey

2018-02-01

In this paper we study the correlation between the neurophysiological processes and personal characteristics arising in the processes of human higher mental functions. We find that the activity of the brain correlates with the results of psychological tests (according to the Cattell test). Experimental studies and math processing are described for operation design with the registration of human multi-channel EEG data in two phases (the processes of passive wakefulness (background) and special psychological testing (active phase)).

Review of genotoxicity biomonitoring studies of glyphosate-based formulations

PubMed Central

Kier, Larry D.

2015-01-01

Abstract Human and environmental genotoxicity biomonitoring studies involving exposure to glyphosate-based formulations (GBFs) were reviewed to complement an earlier review of experimental genotoxicity studies of glyphosate and GBFs. The environmental and most of the human biomonitoring studies were not informative because there was either a very low frequency of GBF exposure or exposure to a large number of pesticides without analysis of specific pesticide effects. One pesticide sprayer biomonitoring study indicated there was not a statistically significant relationship between frequency of GBF exposure reported for the last spraying season and oxidative DNA damage. There were three studies of human populations in regions of GBF aerial spraying. One study found increases for the cytokinesis-block micronucleus endpoint but these increases did not show statistically significant associations with self-reported spray exposure and were not consistent with application rates. A second study found increases for the blood cell comet endpoint at high exposures causing toxicity. However, a follow-up to this study 2 years after spraying did not indicate chromosomal effects. The results of the biomonitoring studies do not contradict an earlier conclusion derived from experimental genotoxicity studies that typical GBFs do not appear to present significant genotoxic risk under normal conditions of human or environmental exposures. PMID:25687244

Conceptual beliefs about human values and their implications: human nature beliefs predict value importance, value trade-offs, and responses to value-laden rhetoric.

PubMed

Bain, Paul G; Kashima, Yoshihisa; Haslam, Nick

2006-08-01

Beliefs that may underlie the importance of human values were investigated in 4 studies, drawing on research that distinguishes natural-kind (natural), nominal-kind (conventional), and artifact (functional) beliefs. Values were best characterized by artifact and nominal-kind beliefs, as well as a natural-kind belief specific to the social domain, "human nature" (Studies 1 and 2). The extent to which values were considered central to human nature was associated with value importance in both Australia and Japan (Study 2), and experimentally manipulating human nature beliefs influenced value importance (Study 3). Beyond their association with importance, human nature beliefs predicted participants' reactions to value trade-offs (Study 1) and to value-laden rhetorical statements (Study 4). Human nature beliefs therefore play a central role in the psychology of values.

Biomechanical Modeling of the Human Head

DTIC Science & Technology

2017-10-03

between model predictions and experimental data. This report details model calibration for all materials identified in models of a human head and...14 3 Stress-strain data for the pia mater and dura mater (human subject); experimental data orig- inally presented in [28...treated as one material) based on a hyperelastic model and experimental data from [59] ............................................... 20 5 Comparison of

Suppression of in vitro murine T cell proliferation by human adipose tissue-derived mesenchymal stem cells is dependent mainly on cyclooxygenase-2 expression

PubMed Central

Kim, Jin-Hee; Lee, Yong-Taek; Hong, Jun Man

2013-01-01

Mesenchymal stem cells (MSCs) of human origin have been frequently applied to experimental animal models to evaluate their immunomodulatory functions. MSCs are known to be activated by cytokines from T cells, predominantly by interferon-γ (IFN-γ), in conjunction with other cytokines such as tumor necrosis factor-α (TNF-α) and interlukin-1β. Because IFN-γ is not cross-reactive between human and mouse species, the manner in which human MSCs administered in experimental animals are activated and stimulated to function has been questioned. In the present study, we established MSCs from human adipose tissue. They successfully suppressed the proliferation of not only human peripheral blood mononuclear cells but also mouse splenic T cells. When these human MSCs were stimulated with a culture supernatant of mouse T cells or recombinant murine TNF-α, they expressed cyclooxygenase-2 (COX-2), but not indoleamine 2,3-dioxygenase. The dominant role of COX-2 in suppressing mouse T cell proliferation was validated by the addition of COX-2 inhibitor in the co-culture, wherein the suppressed proliferation was almost completely recovered. In conclusion, human MSCs in a murine environment were activated, at least in part, by TNF-α and mainly used COX-2 as a tool for the suppression of in vitro T cell proliferation. These results should be considered when interpreting results for human MSCs in experimental animals. PMID:24386599

Aviation human-in-the-loop simulation studies : experimental planning, design, and data management.

DOT National Transportation Integrated Search

2014-01-01

Researchers from the NASAAmes Flight Cognition Laband the FAAs Aerospace Human Factors Research Lab at the Civil Aerospace Medical Instituteexamined task and workload management by single pilots in very light jets, also called entry-level jets.Thi...

Platelet-rich plasma in orthopedic therapy: a comparative systematic review of clinical and experimental data in equine and human musculoskeletal lesions.

PubMed

Brossi, Patrícia M; Moreira, Juliana J; Machado, Thaís S L; Baccarin, Raquel Y A

2015-04-22

This systematic review aimed to present and critically appraise the available information on the efficacy of platelet rich plasma (PRP) in equine and human orthopedic therapeutics and to verify the influence of study design and methodology on the assumption of PRP's efficacy. We searched Medline, PubMed, Embase, Bireme and Google Scholar without restrictions until July 2013. Randomized trials, human cohort clinical studies or case series with a control group on the use of PRP in tendons, ligaments or articular lesions were included. Equine clinical studies on the same topics were included independently of their design. Experimental studies relevant to the clarification of PRP's effects and mechanisms of action in tissues of interest, conducted in any animal species, were selected. This review included 123 studies. PRP's beneficial effects were observed in 46.7% of the clinical studies, while the absence of positive effects was observed in 43.3%. Among experimental studies, 73% yielded positive results, and 7.9% yielded negative results. The most frequent flaws in the clinical trials' designs were the lack of a true placebo group, poor product characterization, insufficient blinding, small sampling, short follow-up periods, and adoption of poor outcome measures. The methods employed for PRP preparation and administration and the selected outcome measures varied greatly. Poor study design was a common feature of equine clinical trials. From studies in which PRP had beneficial effects, 67.8% had an overall high risk of bias. From the studies in which PRP failed to exhibit beneficial effects, 67.8% had an overall low risk of bias. Most experimental studies revealed positive effects of PRP. Although the majority of equine clinical studies yielded positive results, the human clinical trials' results failed to corroborate these findings. In both species, beneficial results were more frequently observed in studies with a high risk of bias. The use of PRP in musculoskeletal lesions, although safe and promising, has still not shown strong evidence in clinical scenarios.

Alzheimer’s Disease: Experimental Models and Reality

PubMed Central

Drummond, Eleanor

2017-01-01

Experimental models of Alzheimer’s disease (AD) are critical to gaining a better understanding of pathogenesis and to assess the potential of novel therapeutic approaches. The most commonly used experimental animal models are transgenic mice that overexpress human genes associated with familial AD (FAD) that result in the formation of amyloid plaques. However, AD is defined by the presence and interplay of both amyloid plaques and neurofibrillary tangle pathology. The track record of success in AD clinical trials thus far has been very poor. In part, this high failure rate has been related to the premature translation of highly successful results in animal models that mirror only limited aspects of AD pathology to humans. A greater understanding of the strengths and weakness of each of the various models and the use of more than one model to evaluate potential therapies would help enhance the success of therapy translation from preclinical studies to patients. In this review we summarize the pathological features and limitations of the major experimental models of AD including transgenic mice, transgenic rats, various physiological models of sporadic AD and in vitro human cell culture models. PMID:28025715

Remembrance of Things Future: Prospective Memory in Laboratory, Workplace, and Everyday Settings

NASA Technical Reports Server (NTRS)

Dismukes, R. Key

2010-01-01

In this review, oriented to the human factors community, I will summarize and provide a perspective on recent research and theory on prospective memory. This will not be an exhaustive review of literature, which is already available in two excellent recent books that provide a wealth of detail on the current state of experimental research (Kliegel, McCaniel, & Einstein, 2008; McDaniel & Einstein, 2007; also see Brandimonte, Einstein, & McDaniel, 1996, for a still relevant overview of the field as it was emerging). Rather, I will explore the limits of existing experimental paradigms and theory, Vvilich, in my opinion, fail to capture some critical aspects of performance outside the laboratory. I will also review the relatively few studies in workplace and everyday settings and will discuss several studies that attempt to bridge between the bulk of experimental studies and these few naturalistic studies. Finally, I will describe countermeasures that can reduce vulnerability to forgetting to perform intended tasks, and I will propose a research agenda that would extend existing experimental and theoretical approaches and would support human factors practitioners by generating information on a wide range of issues relevant to prospective memory performance in natural settings.

The Biological Effects of Quadripolar Radiofrequency Sequential Application: A Human Experimental Study

PubMed Central

Cornaglia, Antonia Icaro; Faga, Angela; Scevola, Silvia

2014-01-01

Abstract Objective: An experimental study was conducted to assess the effectiveness and safety of an innovative quadripolar variable electrode configuration radiofrequency device with objective measurements in an ex vivo and in vivo human experimental model. Background data: Nonablative radiofrequency applications are well-established anti-ageing procedures for cosmetic skin tightening. Methods: The study was performed in two steps: ex vivo and in vivo assessments. In the ex vivo assessments the radiofrequency applications were performed on human full-thickness skin and subcutaneous tissue specimens harvested during surgery for body contouring. In the in vivo assessments the applications were performed on two volunteer patients scheduled for body contouring surgery at the end of the study. The assessment methods were: clinical examination and medical photography, temperature measurement with thermal imaging scan, and light microscopy histological examination. Results: The ex vivo assessments allowed for identification of the effective safety range for human application. The in vivo assessments allowed for demonstration of the biological effects of sequential radiofrequency applications. After a course of radiofrequency applications, the collagen fibers underwent an immediate heat-induced rearrangement and were partially denaturated and progressively metabolized by the macrophages. An overall thickening and spatial rearrangement was appreciated both in the collagen and elastic fibers, the latter displaying a juvenile reticular pattern. A late onset in the macrophage activation after sequential radiofrequency applications was appreciated. Conclusions: Our data confirm the effectiveness of sequential radiofrequency applications in obtaining attenuation of the skin wrinkles by an overall skin tightening. PMID:25244081

The biological effects of quadripolar radiofrequency sequential application: a human experimental study.

PubMed

Nicoletti, Giovanni; Cornaglia, Antonia Icaro; Faga, Angela; Scevola, Silvia

2014-10-01

An experimental study was conducted to assess the effectiveness and safety of an innovative quadripolar variable electrode configuration radiofrequency device with objective measurements in an ex vivo and in vivo human experimental model. Nonablative radiofrequency applications are well-established anti-ageing procedures for cosmetic skin tightening. The study was performed in two steps: ex vivo and in vivo assessments. In the ex vivo assessments the radiofrequency applications were performed on human full-thickness skin and subcutaneous tissue specimens harvested during surgery for body contouring. In the in vivo assessments the applications were performed on two volunteer patients scheduled for body contouring surgery at the end of the study. The assessment methods were: clinical examination and medical photography, temperature measurement with thermal imaging scan, and light microscopy histological examination. The ex vivo assessments allowed for identification of the effective safety range for human application. The in vivo assessments allowed for demonstration of the biological effects of sequential radiofrequency applications. After a course of radiofrequency applications, the collagen fibers underwent an immediate heat-induced rearrangement and were partially denaturated and progressively metabolized by the macrophages. An overall thickening and spatial rearrangement was appreciated both in the collagen and elastic fibers, the latter displaying a juvenile reticular pattern. A late onset in the macrophage activation after sequential radiofrequency applications was appreciated. Our data confirm the effectiveness of sequential radiofrequency applications in obtaining attenuation of the skin wrinkles by an overall skin tightening.

Alu repeat discovery and characterization within human genomes

PubMed Central

Hormozdiari, Fereydoun; Alkan, Can; Ventura, Mario; Hajirasouliha, Iman; Malig, Maika; Hach, Faraz; Yorukoglu, Deniz; Dao, Phuong; Bakhshi, Marzieh; Sahinalp, S. Cenk; Eichler, Evan E.

2011-01-01

Human genomes are now being rapidly sequenced, but not all forms of genetic variation are routinely characterized. In this study, we focus on Alu retrotransposition events and seek to characterize differences in the pattern of mobile insertion between individuals based on the analysis of eight human genomes sequenced using next-generation sequencing. Applying a rapid read-pair analysis algorithm, we discover 4342 Alu insertions not found in the human reference genome and show that 98% of a selected subset (63/64) experimentally validate. Of these new insertions, 89% correspond to AluY elements, suggesting that they arose by retrotransposition. Eighty percent of the Alu insertions have not been previously reported and more novel events were detected in Africans when compared with non-African samples (76% vs. 69%). Using these data, we develop an experimental and computational screen to identify ancestry informative Alu retrotransposition events among different human populations. PMID:21131385

Reconstructed human epidermis: A model to study the barrier function

NASA Astrophysics Data System (ADS)

Barbotteau, Y.; Gontier, E.; Barberet, P.; Cappadoro, M.; De Wever, B.; Habchi, C.; Incerti, S.; Mavon, A.; Moretto, P.; Pouthier, T.; Smith, R. W.; Ynsa, M. D.

2005-04-01

The use of in vitro reconstructed human epidermis (RHE) by the cosmetic and pharmaceutical industries is increasing because of its similar physiological mechanisms to native human skin. With the advent of ethic laws on animal experimentation, RHE provides an helpful alternative for the test of formulations. The aim of this study is to check that the RHE mineral status is comparable to that of human native skin by investigating the elemental distributions in the epidermis strata. In addition, possible deleterious effects of the transport on the epidermis ionic content were studied by nuclear microscopy.

Clay Modeling as a Method to Learn Human Muscles: A Community College Study

ERIC Educational Resources Information Center

Motoike, Howard K.; O'Kane, Robyn L.; Lenchner, Erez; Haspel, Carol

2009-01-01

The efficacy of clay modeling compared with cat dissection for human muscle identification was examined over two semesters at LaGuardia Community College in Queens, NY. The 181 students in 10 sections in this study were randomly distributed into control (cat dissection) and experimental (clay modeling) groups, and the results of the muscle…

Devising and Interdisciplinary Teaching: A Case Study in Collaboration between Theatre and Humanities Courses

ERIC Educational Resources Information Center

Mahoney, Kristin; Brown, Rich

2013-01-01

We use an experimental course collaboration that occurred in the winter of 2012 as a case study for an approach to interdisciplinary collaboration between Theatre and Humanities courses, and we argue that the theatre methodology of "devising" can serve as a particularly rich locus for collaboration between Theatre students and other…

Integrative analyses shed new light on human ribosomal protein gene regulation

PubMed Central

Li, Xin; Zheng, Yiyu; Hu, Haiyan; Li, Xiaoman

2016-01-01

Ribosomal protein genes (RPGs) are important house-keeping genes that are well-known for their coordinated expression. Previous studies on RPGs are largely limited to their promoter regions. Recent high-throughput studies provide an unprecedented opportunity to study how human RPGs are transcriptionally modulated and how such transcriptional regulation may contribute to the coordinate gene expression in various tissues and cell types. By analyzing the DNase I hypersensitive sites under 349 experimental conditions, we predicted 217 RPG regulatory regions in the human genome. More than 86.6% of these computationally predicted regulatory regions were partially corroborated by independent experimental measurements. Motif analyses on these predicted regulatory regions identified 31 DNA motifs, including 57.1% of experimentally validated motifs in literature that regulate RPGs. Interestingly, we observed that the majority of the predicted motifs were shared by the predicted distal and proximal regulatory regions of the same RPGs, a likely general mechanism for enhancer-promoter interactions. We also found that RPGs may be differently regulated in different cells, indicating that condition-specific RPG regulatory regions still need to be discovered and investigated. Our study advances the understanding of how RPGs are coordinately modulated, which sheds light to the general principles of gene transcriptional regulation in mammals. PMID:27346035

Integrative analyses shed new light on human ribosomal protein gene regulation.

PubMed

Li, Xin; Zheng, Yiyu; Hu, Haiyan; Li, Xiaoman

2016-06-27

Ribosomal protein genes (RPGs) are important house-keeping genes that are well-known for their coordinated expression. Previous studies on RPGs are largely limited to their promoter regions. Recent high-throughput studies provide an unprecedented opportunity to study how human RPGs are transcriptionally modulated and how such transcriptional regulation may contribute to the coordinate gene expression in various tissues and cell types. By analyzing the DNase I hypersensitive sites under 349 experimental conditions, we predicted 217 RPG regulatory regions in the human genome. More than 86.6% of these computationally predicted regulatory regions were partially corroborated by independent experimental measurements. Motif analyses on these predicted regulatory regions identified 31 DNA motifs, including 57.1% of experimentally validated motifs in literature that regulate RPGs. Interestingly, we observed that the majority of the predicted motifs were shared by the predicted distal and proximal regulatory regions of the same RPGs, a likely general mechanism for enhancer-promoter interactions. We also found that RPGs may be differently regulated in different cells, indicating that condition-specific RPG regulatory regions still need to be discovered and investigated. Our study advances the understanding of how RPGs are coordinately modulated, which sheds light to the general principles of gene transcriptional regulation in mammals.

Theoretical and Experimental Estimations of Volumetric Inductive Phase Shift in Breast Cancer Tissue

NASA Astrophysics Data System (ADS)

González, C. A.; Lozano, L. M.; Uscanga, M. C.; Silva, J. G.; Polo, S. M.

2013-04-01

Impedance measurements based on magnetic induction for breast cancer detection has been proposed in some studies. This study evaluates theoretical and experimentally the use of a non-invasive technique based on magnetic induction for detection of patho-physiological conditions in breast cancer tissue associated to its volumetric electrical conductivity changes through inductive phase shift measurements. An induction coils-breast 3D pixel model was designed and tested. The model involves two circular coils coaxially centered and a human breast volume centrally placed with respect to the coils. A time-harmonic numerical simulation study addressed the effects of frequency-dependent electrical properties of tumoral tissue on the volumetric inductive phase shift of the breast model measured with the circular coils as inductor and sensor elements. Experimentally; five female volunteer patients with infiltrating ductal carcinoma previously diagnosed by the radiology and oncology departments of the Specialty Clinic for Women of the Mexican Army were measured by an experimental inductive spectrometer and the use of an ergonomic inductor-sensor coil designed to estimate the volumetric inductive phase shift in human breast tissue. Theoretical and experimental inductive phase shift estimations were developed at four frequencies: 0.01, 0.1, 1 and 10 MHz. The theoretical estimations were qualitatively in agreement with the experimental findings. Important increments in volumetric inductive phase shift measurements were evident at 0.01MHz in theoretical and experimental observations. The results suggest that the tested technique has the potential to detect pathological conditions in breast tissue associated to cancer by non-invasive monitoring. Further complementary studies are warranted to confirm the observations.

Experimental study of the constituents of space wash water

NASA Technical Reports Server (NTRS)

Putnam, D. F.; Colombo, G. V.

1975-01-01

This report presents experimental data, obtained under controlled conditions, which quantify the various constituents of human origin that may be expected in space wash water. The experiments were conducted with a simulated crew of two male and two female subjects. The data show that the expected wash water contaminants originating from human secretions are substantially lower than theoretical projections indicated. The data presented are immediately useful and may have considerable impact on the tradeoff comparisons among various unit processes and systems under consideration by NASA for recycling space wash water.

Proceedings of the Symposium on Psychology in the Department of Defense (8th) Held in Colorado Springs, Colorado on 21-23 April 1982

DTIC Science & Technology

1982-12-01

readily visible but still represent low level flight. 33 Experimental Design and Pc,cedures. The experimental design used in this study was a 3 X 2...October 1979. Winer, B.J. Statistical principles in experimental design . New York: McGraw-Hill, 1971. 47 NONTRADITIONAL ADMISSIONS FACTORS: THE SPECIAL...Quasi- Experimental Designs for Research. Chicago: Rand McNally, 1963. R.C. Carter and H. Sbisa. Human Performance tests for repeated measurements

ATTEMPTS TO ESTABLISH EXPERIMENTAL CYCLOSPORA CAYETANENSIS INFECTION IN LABORATORY ANIMALS

EPA Science Inventory

Attempts were made to develop an animal model for Cyclospora cayetanensis to identify a practical laboratory host for studying human cyclosporiasis. Oocysts collected from stool of infected humans in the United States, Haiti, Guatemala, Peru and Nepal were held in potassium dich...

Brown Adipose Reporting Criteria in Imaging STudies (BARCIST 1.0): Recommendations for Standardized FDG-PET/CT Experiments in Humans

PubMed Central

Chen, Kong Y.; Laughlin, Maren R.; Haft, Carol R.; Hu, Houchun Harry; Bredella, Miriam A.; Enerbäck, Sven; Kinahan, Paul E.; van Marken Lichtenbelt, Wouter; Lin, Frank I.; Sunderland, John J.; Virtanen, Kirsi A.; Wahl, Richard L.

2016-01-01

Human brown adipose tissue (BAT) presence, metabolic activity and estimated mass are typically measured by imaging [18F]fluorodeoxyglucose (FDG) uptake in response to cold exposure in regions of the body expected to contain BAT, using positron emission tomography combined with x-ray computed tomography (FDG-PET/CT). Efforts to describe the epidemiology and biology of human BAT are hampered by diverse experimental practices, making it difficult to directly compare results among laboratories. An expert panel was assembled by the National Institute of Diabetes and Digestive and Kidney Diseases on November 4, 2014 to discuss minimal requirements for conducting FDG-PET/CT experiments of human BAT, data analysis, and publication of results. This resulted in Brown Adipose Reporting Criteria in Imaging STudies (BARCIST 1.0). Since there are no fully-validated best practices at this time, panel recommendations are meant to enhance comparability across experiments, but not to constrain experimental design or the questions that can be asked. PMID:27508870

Prelinguistic human infants and great apes show different communicative strategies in a triadic request situation.

PubMed

Gretscher, Heinz; Tempelmann, Sebastian; Haun, Daniel B M; Liebal, Katja; Kaminski, Juliane

2017-01-01

In the present research, we investigate the communicative strategies of 20 month old human infants and great apes when requesting rewards from a human experimenter. Infants and apes both adapted their signals to the attentional state of the experimenter as well as to the location of the reward. Yet, while infants frequently positioned themselves in front of the experimenter and pointed towards a distant reward, apes either remained in the experimenter's line of sight and pointed towards him or moved out of sight and pointed towards the reward. Further, when pointing towards a reward that was placed at a distance from the experimenter, only the infants, and not the apes, took the experimenter's attentional state into account. These results demonstrate that prelinguistic human infants and nonhuman apes use different means when guiding others' attention to a location; indicating that differing cognitive mechanisms may underlie their pointing gestures.

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

PubMed

Oesch, F; Fabian, E; Landsiedel, Robert

2018-06-18

Studies on the metabolic fate of medical drugs, skin care products, cosmetics and other chemicals intentionally or accidently applied to the human skin have become increasingly important in order to ascertain pharmacological effectiveness and to avoid toxicities. The use of freshly excised human skin for experimental investigations meets with ethical and practical limitations. Hence information on xenobiotic-metabolizing enzymes (XME) in the experimental systems available for pertinent studies compared with native human skin has become crucial. This review collects available information of which-taken with great caution because of the still very limited data-the most salient points are: in the skin of all animal species and skin-derived in vitro systems considered in this review cytochrome P450 (CYP)-dependent monooxygenase activities (largely responsible for initiating xenobiotica metabolism in the organ which provides most of the xenobiotica metabolism of the mammalian organism, the liver) are very low to undetectable. Quite likely other oxidative enzymes [e.g. flavin monooxygenase, COX (cooxidation by prostaglandin synthase)] will turn out to be much more important for the oxidative xenobiotic metabolism in the skin. Moreover, conjugating enzyme activities such as glutathione transferases and glucuronosyltransferases are much higher than the oxidative CYP activities. Since these conjugating enzymes are predominantly detoxifying, the skin appears to be predominantly protected against CYP-generated reactive metabolites. The following recommendations for the use of experimental animal species or human skin in vitro models may tentatively be derived from the information available to date: for dermal absorption and for skin irritation esterase activity is of special importance which in pig skin, some human cell lines and reconstructed skin models appears reasonably close to native human skin. With respect to genotoxicity and sensitization reactive-metabolite-reducing XME in primary human keratinocytes and several reconstructed human skin models appear reasonably close to human skin. For a more detailed delineation and discussion of the severe limitations see the Conclusions section in the end of this review.

Experimental Studies in a Reconfigurable C4 Test-bed for Network Enabled Capability

DTIC Science & Technology

2006-06-01

Cross1, Dr R. Houghton1, and Mr R. McMaster1 Defence Technology Centre for Human factors Integration (DTC HFI ) BITlab, School of Engineering and Design...NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Defence Technology Centre for Human factors Integration (DTC HFI ) BITlab, School of...studies into NEC by the Human Factors Integration Defence Technology Centre ( HFI -DTC). DEVELOPMENT OF THE TESTBED In brief, the C4 test-bed

Experimental Human Cell and Tissue Models of Pemphigus

PubMed Central

van der Wier, Gerda; Pas, Hendri H.; Jonkman, Marcel F.

2010-01-01

Pemphigus is a chronic mucocutaneous autoimmune bullous disease that is characterized by loss of cell-cell contact in skin and/or mucous membranes. Past research has successfully identified desmosomes as immunological targets and has demonstrated that acantholysis is initiated through direct binding of IgG. The exact mechanisms of acantholysis, however, are still missing. Experimental model systems have contributed considerably to today's knowledge and are still a favourite tool of research. In this paper we will describe to what extent human cell and tissue models represent the in vivo situation, for example, organ cultures of human skin, keratinocyte cultures, and human skin grafted on mice and, furthermore, how suitable they are to study the pathogenesis of pemphigus. Organ cultures closely mimic the architecture of the epidermis but are less suitable to answer posed biochemical questions. Cultured keratinocyte monolayers are convenient in this respect, but their desmosomal make-up in terms of adhesion molecules does not exactly reflect the in vivo situation. Reconstituted skin is a relatively new model that approaches organ culture. In models of human skin grafted on mice, acantholysis can be studied in actual human skin but now with all the advantages of an animal model. PMID:20585596

Exercise-induced neuroplasticity in human Parkinson's disease: What is the evidence telling us?

PubMed

Hirsch, Mark A; Iyer, Sanjay S; Sanjak, Mohammed

2016-01-01

While animal models of exercise and PD have pushed the field forward, few studies have addressed exercise-induced neuroplasticity in human PD. As a first step toward promoting greater international collaboration on exercise-induced neuroplasticity in human PD, we present data on 8 human PD studies (published between 2008 and 2015) with 144 adults with PD of varying disease severity (Hoehn and Yahr stage 1 to stage 3), using various experimental (e.g., randomized controlled trial) and quasi-experimental designs on the effects of cognitive and physical activity on brain structure or function in PD. We focus on plasticity mechanisms of intervention-induced increases in maximal corticomotor excitability, exercise-induced changes in voxel-based gray matter volume changes and increases in exercise-induced serum levels of brain derived neurotrophic factor (BDNF). Finally, we provide a future perspective for promoting international, collaborative research on exercise-induced neuroplasticity in human PD. An emerging body of evidence suggests exercise triggers several plasticity related events in the human PD brain including corticomotor excitation, increases and decreases in gray matter volume and changes in BDNF levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

Vertical transmission of learned signatures in a wild parrot

PubMed Central

Berg, Karl S.; Delgado, Soraya; Cortopassi, Kathryn A.; Beissinger, Steven R.; Bradbury, Jack W.

2012-01-01

Learned birdsong is a widely used animal model for understanding the acquisition of human speech. Male songbirds often learn songs from adult males during sensitive periods early in life, and sing to attract mates and defend territories. In presumably all of the 350+ parrot species, individuals of both sexes commonly learn vocal signals throughout life to satisfy a wide variety of social functions. Despite intriguing parallels with humans, there have been no experimental studies demonstrating learned vocal production in wild parrots. We studied contact call learning in video-rigged nests of a well-known marked population of green-rumped parrotlets (Forpus passerinus) in Venezuela. Both sexes of naive nestlings developed individually unique contact calls in the nest, and we demonstrate experimentally that signature attributes are learned from both primary care-givers. This represents the first experimental evidence for the mechanisms underlying the transmission of a socially acquired trait in a wild parrot population. PMID:21752824

Human Thermal Model Evaluation Using the JSC Human Thermal Database

NASA Technical Reports Server (NTRS)

Cognata, T.; Bue, G.; Makinen, J.

2011-01-01

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

Air ions and respiratory function outcomes: a comprehensive review

PubMed Central

2013-01-01

Background From a mechanistic or physical perspective there is no basis to suspect that electric charges on clusters of air molecules (air ions) would have beneficial or deleterious effects on respiratory function. Yet, there is a large lay and scientific literature spanning 80 years that asserts exposure to air ions affects the respiratory system and has other biological effects. Aims This review evaluates the scientific evidence in published human experimental studies regarding the effects of exposure to air ions on respiratory performance and symptoms. Methods We identified 23 studies (published 1933–1993) that met our inclusion criteria. Relevant data pertaining to study population characteristics, study design, experimental methods, statistical techniques, and study results were assessed. Where relevant, random effects meta-analysis models were utilized to quantify similar exposure and outcome groupings. Results The included studies examined the therapeutic benefits of exposure to negative air ions on respiratory outcomes, such as ventilatory function and asthmatic symptoms. Study specific sample sizes ranged between 7 and 23, and studies varied considerably by subject characteristics (e.g., infants with asthma, adults with emphysema), experimental method, outcomes measured (e.g., subjective symptoms, sensitivity, clinical pulmonary function), analytical design, and statistical reporting. Conclusions Despite numerous experimental and analytical differences across studies, the literature does not clearly support a beneficial role in exposure to negative air ions and respiratory function or asthmatic symptom alleviation. Further, collectively, the human experimental studies do not indicate a significant detrimental effect of exposure to positive air ions on respiratory measures. Exposure to negative or positive air ions does not appear to play an appreciable role in respiratory function. PMID:24016271

Human Health Effects of Biphenyl: Key Findings and Scientific Issues.

PubMed

Li, Zheng; Hogan, Karen A; Cai, Christine; Rieth, Susan

2016-06-01

In support of the Integrated Risk Information System (IRIS), the U.S. Environmental Protection Agency (EPA) has evaluated the human health hazards of biphenyl exposure. We review key findings and scientific issues regarding expected human health effects of biphenyl. Scientific literature from 1926 through September 2012 was critically evaluated to identify potential human health hazards associated with biphenyl exposure. Key issues related to the carcinogenicity and noncancer health hazards of biphenyl were examined based on evidence from experimental animal bioassays and mechanistic studies. Systematic consideration of experimental animal studies of oral biphenyl exposure took into account the variety of study designs (e.g., study sizes, exposure levels, and exposure durations) to reconcile differing reported results. The available mechanistic and toxicokinetic evidence supports the hypothesis that male rat urinary bladder tumors arise through urinary bladder calculi formation but is insufficient to hypothesize a mode of action for liver tumors in female mice. Biphenyl and its metabolites may induce genetic damage, but a role for genotoxicity in biphenyl-induced carcinogenicity has not been established. The available health effects data for biphenyl provides suggestive evidence for carcinogenicity in humans, based on increased incidences of male rat urinary bladder tumors at high exposure levels and on female mouse liver tumors. Kidney toxicity is also a potential human health hazard of biphenyl exposure. Li Z, Hogan KA, Cai C, Rieth S. 2016. Human health effects of biphenyl: key findings and scientific issues. Environ Health Perspect 124:703-712; http://dx.doi.org/10.1289/ehp.1509730.

Do young toddlers act on their social preferences?

PubMed

Dahl, Audun; Schuck, Rachel K; Campos, Joseph J

2013-10-01

From preschool age to adulthood, most humans prefer to help someone who has treated others well over helping someone who has treated others badly. Researchers have recently made opposing predictions about whether such observation-based preferential helping is present when children begin to help in the second year of life. In the present study, 84 toddlers (16-27 months) observed 1 experimenter (antisocial) take a ball from, and 1 experimenter (prosocial) return a ball to, a neutral experimenter. In subsequent tests, children could help either the antisocial or the prosocial experimenter. Only the oldest children showed a significant preference for helping the prosocial agent first. Most children in all age groups were willing to help both experimenters when given multiple opportunities to help. Across age groups, children who looked longer at the continuation of the antisocial interaction were more likely to help the prosocial agent. These findings suggest that social evaluations do affect toddlers' helping behavior but that interactions between human agents may be difficult to evaluate for very young children.

40 CFR 158.2083 - Experimental use permit biochemical pesticides human health assessment data requirements table.

Code of Federal Regulations, 2013 CFR

2013-07-01

... pesticides human health assessment data requirements table. 158.2083 Section 158.2083 Protection of... Biochemical Pesticides § 158.2083 Experimental use permit biochemical pesticides human health assessment data... determine the human health assessment data requirements for a particular biochemical pesticide product. (2...

40 CFR 158.2083 - Experimental use permit biochemical pesticides human health assessment data requirements table.

Code of Federal Regulations, 2014 CFR

2014-07-01

... pesticides human health assessment data requirements table. 158.2083 Section 158.2083 Protection of... Biochemical Pesticides § 158.2083 Experimental use permit biochemical pesticides human health assessment data... determine the human health assessment data requirements for a particular biochemical pesticide product. (2...

40 CFR 158.2083 - Experimental use permit biochemical pesticides human health assessment data requirements table.

Code of Federal Regulations, 2012 CFR

2012-07-01

... pesticides human health assessment data requirements table. 158.2083 Section 158.2083 Protection of... Biochemical Pesticides § 158.2083 Experimental use permit biochemical pesticides human health assessment data... determine the human health assessment data requirements for a particular biochemical pesticide product. (2...

40 CFR 158.2083 - Experimental use permit biochemical pesticides human health assessment data requirements table.

Code of Federal Regulations, 2010 CFR

2010-07-01

... pesticides human health assessment data requirements table. 158.2083 Section 158.2083 Protection of... Biochemical Pesticides § 158.2083 Experimental use permit biochemical pesticides human health assessment data... determine the human health assessment data requirements for a particular biochemical pesticide product. (2...

40 CFR 158.2083 - Experimental use permit biochemical pesticides human health assessment data requirements table.

Code of Federal Regulations, 2011 CFR

2011-07-01

... pesticides human health assessment data requirements table. 158.2083 Section 158.2083 Protection of... Biochemical Pesticides § 158.2083 Experimental use permit biochemical pesticides human health assessment data... determine the human health assessment data requirements for a particular biochemical pesticide product. (2...

TOLUENE EXPERIMENTAL EXPOSURES IN HUMANS: PHARMACOKINETICS AND BEHAVIOR

EPA Science Inventory

Toluene Experimental Exposures in Humans:
Pharmacokinetics and Behavioral Effects
(Ongoing Research)

Vernon A. Benignus1, Philip J. Bushnell2 and William K. Boyes2

Human subjects will be exposed to 250 and 500 ppm toluene for one hour in the Human St...

A meta-analysis of factors affecting trust in human-robot interaction.

PubMed

Hancock, Peter A; Billings, Deborah R; Schaefer, Kristin E; Chen, Jessie Y C; de Visser, Ewart J; Parasuraman, Raja

2011-10-01

We evaluate and quantify the effects of human, robot, and environmental factors on perceived trust in human-robot interaction (HRI). To date, reviews of trust in HRI have been qualitative or descriptive. Our quantitative review provides a fundamental empirical foundation to advance both theory and practice. Meta-analytic methods were applied to the available literature on trust and HRI. A total of 29 empirical studies were collected, of which 10 met the selection criteria for correlational analysis and 11 for experimental analysis. These studies provided 69 correlational and 47 experimental effect sizes. The overall correlational effect size for trust was r = +0.26,with an experimental effect size of d = +0.71. The effects of human, robot, and environmental characteristics were examined with an especial evaluation of the robot dimensions of performance and attribute-based factors. The robot performance and attributes were the largest contributors to the development of trust in HRI. Environmental factors played only a moderate role. Factors related to the robot itself, specifically, its performance, had the greatest current association with trust, and environmental factors were moderately associated. There was little evidence for effects of human-related factors. The findings provide quantitative estimates of human, robot, and environmental factors influencing HRI trust. Specifically, the current summary provides effect size estimates that are useful in establishing design and training guidelines with reference to robot-related factors of HRI trust. Furthermore, results indicate that improper trust calibration may be mitigated by the manipulation of robot design. However, many future research needs are identified.

Facilitating healthcare decisions by assessing the certainty in the evidence from preclinical animal studies

PubMed Central

Hooijmans, Carlijn R.; de Vries, Rob B. M.; Ritskes-Hoitinga, Merel; Rovers, Maroeska M.; Leeflang, Mariska M.; IntHout, Joanna; Wever, Kimberley E.; Hooft, Lotty; de Beer, Hans; Kuijpers, Ton; Macleod, Malcolm R.; Sena, Emily S.; ter Riet, Gerben; Morgan, Rebecca L.; Thayer, Kristina A.; Rooney, Andrew A.; Guyatt, Gordon H.; Schünemann, Holger J.

2018-01-01

Laboratory animal studies are used in a wide range of human health related research areas, such as basic biomedical research, drug research, experimental surgery and environmental health. The results of these studies can be used to inform decisions regarding clinical research in humans, for example the decision to proceed to clinical trials. If the research question relates to potential harms with no expectation of benefit (e.g., toxicology), studies in experimental animals may provide the only relevant or controlled data and directly inform clinical management decisions. Systematic reviews and meta-analyses are important tools to provide robust and informative evidence summaries of these animal studies. Rating how certain we are about the evidence could provide important information about the translational probability of findings in experimental animal studies to clinical practice and probably improve it. Evidence summaries and certainty in the evidence ratings could also be used (1) to support selection of interventions with best therapeutic potential to be tested in clinical trials, (2) to justify a regulatory decision limiting human exposure (to drug or toxin), or to (3) support decisions on the utility of further animal experiments. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach is the most widely used framework to rate the certainty in the evidence and strength of health care recommendations. Here we present how the GRADE approach could be used to rate the certainty in the evidence of preclinical animal studies in the context of therapeutic interventions. We also discuss the methodological challenges that we identified, and for which further work is needed. Examples are defining the importance of consistency within and across animal species and using GRADE’s indirectness domain as a tool to predict translation from animal models to humans. PMID:29324741

Facilitating healthcare decisions by assessing the certainty in the evidence from preclinical animal studies.

PubMed

Hooijmans, Carlijn R; de Vries, Rob B M; Ritskes-Hoitinga, Merel; Rovers, Maroeska M; Leeflang, Mariska M; IntHout, Joanna; Wever, Kimberley E; Hooft, Lotty; de Beer, Hans; Kuijpers, Ton; Macleod, Malcolm R; Sena, Emily S; Ter Riet, Gerben; Morgan, Rebecca L; Thayer, Kristina A; Rooney, Andrew A; Guyatt, Gordon H; Schünemann, Holger J; Langendam, Miranda W

2018-01-01

Laboratory animal studies are used in a wide range of human health related research areas, such as basic biomedical research, drug research, experimental surgery and environmental health. The results of these studies can be used to inform decisions regarding clinical research in humans, for example the decision to proceed to clinical trials. If the research question relates to potential harms with no expectation of benefit (e.g., toxicology), studies in experimental animals may provide the only relevant or controlled data and directly inform clinical management decisions. Systematic reviews and meta-analyses are important tools to provide robust and informative evidence summaries of these animal studies. Rating how certain we are about the evidence could provide important information about the translational probability of findings in experimental animal studies to clinical practice and probably improve it. Evidence summaries and certainty in the evidence ratings could also be used (1) to support selection of interventions with best therapeutic potential to be tested in clinical trials, (2) to justify a regulatory decision limiting human exposure (to drug or toxin), or to (3) support decisions on the utility of further animal experiments. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach is the most widely used framework to rate the certainty in the evidence and strength of health care recommendations. Here we present how the GRADE approach could be used to rate the certainty in the evidence of preclinical animal studies in the context of therapeutic interventions. We also discuss the methodological challenges that we identified, and for which further work is needed. Examples are defining the importance of consistency within and across animal species and using GRADE's indirectness domain as a tool to predict translation from animal models to humans.

Assessing the True Intraocular Pressure in the Non-human Primate.

PubMed

McAllister, Faith; Harwerth, Ronald; Patel, Nimesh

2018-02-01

For glaucoma patients, high intraocular pressure (IOP) is a risk factor for progressive neuropathy. Similarly, animal models used to study the disease are based on an experimental elevation of IOP. Thus, accurate IOP measurements are important in characterizing experimental models and resulting effects. The purpose of the present study was to investigate IOP measurements in a non-human primate model of experimental glaucoma by comparing clinical tonometry (Tono-Pen and TonoVet) to the true IOP from intracameral manometry. A total of 17 rhesus macaque eyes from 12 animals were used for this study. Eleven eyes had no previous experimental intervention, whereas six eyes were at varying stages of laser-induced experimental glaucoma. IOPs were adjusted by inserting a needle in the anterior chamber that was attached to a pressure transducer and syringe pump system. The anterior chamber IOP was adjusted to values between 10 and 50 mmHg and corresponding measures with Tono-Pen and TonoVet were taken. The IOPs by TonoVet and Tono-Pen were linearly related over the range of pressures tested (slope = 0.68 normal/healthy and 0.72 experimental glaucoma). For the most, TonoVet measures overestimated IOP at all anterior chamber pressure settings (mean difference of 3.17 mmHg, 95% CI 12.53 to -4.74 normal and 3.90 mmHg, 95% CI 12.90 to -6.53 experimental glaucoma). In contrast, Tono-Pen measures overestimated IOP at lower IOPs and underestimated at higher IOP (slope = -0.26 normal and -0.21 experimental glaucoma). The TonoVet and Tono-Pen tonometers that are often used to assess IOP in both clinical and experimental settings generally reflect the status of IOP, but the results from this study suggest that the instruments need calibration with true anterior chamber pressure for accurate measures in experimental models of glaucoma.

AfterMath: the work of proof in the age of human-machine collaboration.

PubMed

Dick, Stephanie

2011-09-01

During the 1970s and 1980s, a team of Automated Theorem Proving researchers at the Argonne National Laboratory near Chicago developed the Automated Reasoning Assistant, or AURA, to assist human users in the search for mathematical proofs. The resulting hybrid humans+AURA system developed the capacity to make novel contributions to pure mathematics by very untraditional means. This essay traces how these unconventional contributions were made and made possible through negotiations between the humans and the AURA at Argonne and the transformation in mathematical intuition they produced. At play in these negotiations were experimental practices, nonhumans, and nonmathematical modes of knowing. This story invites an earnest engagement between historians of mathematics and scholars in the history of science and science studies interested in experimental practice, material culture, and the roles of nonhumans in knowledge making.

Simulated sudden increase in geomagnetic activity and its effect on heart rate variability: Experimental verification of correlation studies.

PubMed

Caswell, Joseph M; Singh, Manraj; Persinger, Michael A

2016-08-01

Previous research investigating the potential influence of geomagnetic factors on human cardiovascular state has tended to converge upon similar inferences although the results remain relatively controversial. Furthermore, previous findings have remained essentially correlational without accompanying experimental verification. An exception to this was noted for human brain activity in a previous study employing experimental simulation of sudden geomagnetic impulses in order to assess correlational results that had demonstrated a relationship between geomagnetic perturbations and neuroelectrical parameters. The present study employed the same equipment in a similar procedure in order to validate previous findings of a geomagnetic-cardiovascular dynamic with electrocardiography and heart rate variability measures. Results indicated that potential magnetic field effects on frequency components of heart rate variability tended to overlap with previous correlational studies where low frequency power and the ratio between low and high frequency components of heart rate variability appeared affected. In the present study, a significant increase in these particular parameters was noted during geomagnetic simulation compared to baseline recordings. Copyright © 2016 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

NovelFam3000 – Uncharacterized human protein domains conserved across model organisms

PubMed Central

Kemmer, Danielle; Podowski, Raf M; Arenillas, David; Lim, Jonathan; Hodges, Emily; Roth, Peggy; Sonnhammer, Erik LL; Höög, Christer; Wasserman, Wyeth W

2006-01-01

Background Despite significant efforts from the research community, an extensive portion of the proteins encoded by human genes lack an assigned cellular function. Most metazoan proteins are composed of structural and/or functional domains, of which many appear in multiple proteins. Once a domain is characterized in one protein, the presence of a similar sequence in an uncharacterized protein serves as a basis for inference of function. Thus knowledge of a domain's function, or the protein within which it arises, can facilitate the analysis of an entire set of proteins. Description From the Pfam domain database, we extracted uncharacterized protein domains represented in proteins from humans, worms, and flies. A data centre was created to facilitate the analysis of the uncharacterized domain-containing proteins. The centre both provides researchers with links to dispersed internet resources containing gene-specific experimental data and enables them to post relevant experimental results or comments. For each human gene in the system, a characterization score is posted, allowing users to track the progress of characterization over time or to identify for study uncharacterized domains in well-characterized genes. As a test of the system, a subset of 39 domains was selected for analysis and the experimental results posted to the NovelFam3000 system. For 25 human protein members of these 39 domain families, detailed sub-cellular localizations were determined. Specific observations are presented based on the analysis of the integrated information provided through the online NovelFam3000 system. Conclusion Consistent experimental results between multiple members of a domain family allow for inferences of the domain's functional role. We unite bioinformatics resources and experimental data in order to accelerate the functional characterization of scarcely annotated domain families. PMID:16533400

Experimental sheep BSE prions generate the vCJD phenotype when serially passaged in transgenic mice expressing human prion protein.

PubMed

Joiner, Susan; Asante, Emmanuel A; Linehan, Jacqueline M; Brock, Lara; Brandner, Sebastian; Bellworthy, Susan J; Simmons, Marion M; Hope, James; Collinge, John; Wadsworth, Jonathan D F

2018-03-15

The epizootic prion disease of cattle, bovine spongiform encephalopathy (BSE), causes variant Creutzfeldt-Jakob disease (vCJD) in humans following dietary exposure. While it is assumed that all cases of vCJD attributed to a dietary aetiology are related to cattle BSE, sheep and goats are susceptible to experimental oral challenge with cattle BSE prions and farmed animals in the UK were undoubtedly exposed to BSE-contaminated meat and bone meal during the late 1980s and early 1990s. Although no natural field cases of sheep BSE have been identified, it cannot be excluded that some BSE-infected sheep might have entered the European human food chain. Evaluation of the zoonotic potential of sheep BSE prions has been addressed by examining the transmission properties of experimental brain isolates in transgenic mice that express human prion protein, however to-date there have been relatively few studies. Here we report that serial passage of experimental sheep BSE prions in transgenic mice expressing human prion protein with methionine at residue 129 produces the vCJD phenotype that mirrors that seen when the same mice are challenged with vCJD prions from patient brain. These findings are congruent with those reported previously by another laboratory, and thereby strongly reinforce the view that sheep BSE prions could have acted as a causal agent of vCJD within Europe. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Comprehension and utilisation of pointing gestures and gazing in dog-human communication in relatively complex situations.

PubMed

Lakatos, Gabriella; Gácsi, Márta; Topál, József; Miklósi, Adám

2012-03-01

The aim of the present investigation was to study the visual communication between humans and dogs in relatively complex situations. In the present research, we have modelled more lifelike situations in contrast to previous studies which often relied on using only two potential hiding locations and direct association between the communicative signal and the signalled object. In Study 1, we have provided the dogs with four potential hiding locations, two on each side of the experimenter to see whether dogs are able to choose the correct location based on the pointing gesture. In Study 2, dogs had to rely on a sequence of pointing gestures displayed by two different experimenters. We have investigated whether dogs are able to recognise an 'indirect signal', that is, a pointing toward a pointer. In Study 3, we have examined whether dogs can understand indirect information about a hidden object and direct the owner to the particular location. Study 1 has revealed that dogs are unlikely to rely on extrapolating precise linear vectors along the pointing arm when relying on human pointing gestures. Instead, they rely on a simple rule of following the side of the human gesturing. If there were more targets on the same side of the human, they showed a preference for the targets closer to the human. Study 2 has shown that dogs are able to rely on indirect pointing gestures but the individual performances suggest that this skill may be restricted to a certain level of complexity. In Study 3, we have found that dogs are able to localise the hidden object by utilising indirect human signals, and they are able to convey this information to their owner.

BioQ: tracing experimental origins in public genomic databases using a novel data provenance model.

PubMed

Saccone, Scott F; Quan, Jiaxi; Jones, Peter L

2012-04-15

Public genomic databases, which are often used to guide genetic studies of human disease, are now being applied to genomic medicine through in silico integrative genomics. These databases, however, often lack tools for systematically determining the experimental origins of the data. We introduce a new data provenance model that we have implemented in a public web application, BioQ, for assessing the reliability of the data by systematically tracing its experimental origins to the original subjects and biologics. BioQ allows investigators to both visualize data provenance as well as explore individual elements of experimental process flow using precise tools for detailed data exploration and documentation. It includes a number of human genetic variation databases such as the HapMap and 1000 Genomes projects. BioQ is freely available to the public at http://bioq.saclab.net.

Evolutionary foundations of human prosocial sentiments

PubMed Central

Silk, Joan B.; House, Bailey R.

2011-01-01

A growing body of evidence shows that humans are remarkably altruistic primates. Food sharing and division of labor play an important role in all human societies, and cooperation extends beyond the bounds of close kinship and networks of reciprocating partners. In humans, altruism is motivated at least in part by empathy and concern for the welfare of others. Although altruistic behavior is well-documented in other primates, the range of altruistic behaviors in other primate species, including the great apes, is much more limited than it is in humans. Moreover, when altruism does occur among other primates, it is typically limited to familiar group members—close kin, mates, and reciprocating partners. This suggests that there may be fundamental differences in the social preferences that motivate altruism across the primate order, and there is currently considerable interest in how we came to be such unusual apes. A body of experimental studies designed to examine the phylogenetic range of prosocial sentiments and behavior is beginning to shed some light on this issue. In experimental settings, chimpanzees and tamarins do not consistently take advantage of opportunities to deliver food rewards to others, although capuchins and marmosets do deliver food rewards to others in similar kinds of tasks. Although chimpanzees do not satisfy experimental criteria for prosociality in food delivery tasks, they help others complete tasks to obtain a goal. Differences in performance across species and differences in performance across tasks are not yet fully understood and raise new questions for further study. PMID:21690372

Apes' and Children's Understanding of Cooperative and Competitive Motives in a Communicative Situation

ERIC Educational Resources Information Center

Herrmann, Esther; Tomasello, Michael

2006-01-01

Chimpanzees ("Pan troglodytes") and bonobos ("Pan paniscus") (Study 1) and 18- and 24-month-old human children (Study 2) participated in a novel communicative task. A human experimenter (E) hid food or a toy in one of two opaque containers before gesturing towards the reward's location in one of two ways. In the Informing condition, she attempted…

The 3R principle and the use of non-human primates in the study of neurodegenerative diseases: the case of Parkinson's disease.

PubMed

Vitale, Augusto; Manciocco, Arianna; Alleva, Enrico

2009-01-01

The aim of this paper is to offer an ethical perspective on the use of non-human primates in neurobiological studies, using the Parkinson's disease (PD) as an important case study. We refer, as theoretical framework, to the 3R principle, originally proposed by Russell and Burch [Russell, W.M.S., Burch, R.L., 1959. The Principles of Humane Experimental Technique. Universities Federation for Animal Welfare Wheathampstead, England (reprinted in 1992)]. Then, the use of non-human primates in the study of PD will be discussed in relation to the concepts of Replacement, Reduction, and Refinement. Replacement and Reduction result to be the more problematic concept to be applied, whereas Refinement offers relatively more opportunities of improvement. However, although in some cases the 3R principle shows its applicative limits, its value, as conceptual and inspirational tool remains extremely valuable. It suggests to the researchers a series of questions, both theoretical and methodological, which can have the results of improving the quality of life on the experimental models, the quality of the scientific data, and the public perception from the non-scientist community.

[Comparative pathology of early stress-induced changes in the duodenal mucosa in laboratory rats and in humans].

PubMed

Peychl, L; Brejcha, A

2003-01-01

Our presentation comprises results of two studies: The first was an experimental investigation of 60 Wistar-strain rats used in a toxicological study. The other part analysed stress changes in the duodenal mucosa in the human autopsy material. Both humans and rats had been exposed to stress and showed similar histological changes. In the rats the same duodenal lesions were present both in the test group and the control animals in the toxicological study. Lesions consisted of oedema of the duodenal villi and erosions in the tips of the villi. We believe that in the experimental group the stress was caused by restraining the animals by daily introduction of the gastric metallic tube, by taking blood from the retrobulbar plexus, and by anaesthesia. The autopsy study comprised 35 cases displaying congestion and macroscopically recognizable multifocal bleeding into the duodenal mucosal folds. The microscopic investigation revealed bleeding into the mucosal villi and small erosions. In some cases there were cuneiform mucosal infarcts extending into the submucosa. In the humans, severe cardiovascular diseases and circulatory disturbances represented the main causes of the stress. Local hypoxia and gastric juice acidity were involved in the pathogenesis of the duodenal mucosal changes.

Identification of antipsychotic drug fluspirilene as a potential p53-MDM2 inhibitor: a combined computational and experimental study

NASA Astrophysics Data System (ADS)

Patil, Sachin P.; Pacitti, Michael F.; Gilroy, Kevin S.; Ruggiero, John C.; Griffin, Jonathan D.; Butera, Joseph J.; Notarfrancesco, Joseph M.; Tran, Shawn; Stoddart, John W.

2015-02-01

The inhibition of tumor suppressor p53 protein due to its direct interaction with oncogenic murine double minute 2 (MDM2) protein, plays a central role in almost 50 % of all human tumor cells. Therefore, pharmacological inhibition of the p53-binding pocket on MDM2, leading to p53 activation, presents an important therapeutic target against these cancers expressing wild-type p53. In this context, the present study utilized an integrated virtual and experimental screening approach to screen a database of approved drugs for potential p53-MDM2 interaction inhibitors. Specifically, using an ensemble rigid-receptor docking approach with four MDM2 protein crystal structures, six drug molecules were identified as possible p53-MDM2 inhibitors. These drug molecules were then subjected to further molecular modeling investigation through flexible-receptor docking followed by Prime/MM-GBSA binding energy analysis. These studies identified fluspirilene, an approved antipsychotic drug, as a top hit with MDM2 binding mode and energy similar to that of a native MDM2 crystal ligand. The molecular dynamics simulations suggested stable binding of fluspirilene to the p53-binding pocket on MDM2 protein. The experimental testing of fluspirilene showed significant growth inhibition of human colon tumor cells in a p53-dependent manner. Fluspirilene also inhibited growth of several other human tumor cell lines in the NCI60 cell line panel. Taken together, these computational and experimental data suggest a potentially novel role of fluspirilene in inhibiting the p53-MDM2 interaction. It is noteworthy here that fluspirilene has a long history of safe human use, thus presenting immediate clinical potential as a cancer therapeutic. Furthermore, fluspirilene could also serve as a structurally-novel lead molecule for the development of more potent, small-molecule p53-MDM2 inhibitors against several types of cancer. Importantly, the combined computational and experimental screening protocol presented in this study may also prove useful for screening other commercially-available compound databases for identification of novel, small molecule p53-MDM2 inhibitors.

Human Health Effects of Trichloroethylene: Key Findings and Scientific Issues

PubMed Central

Jinot, Jennifer; Scott, Cheryl Siegel; Makris, Susan L.; Cooper, Glinda S.; Dzubow, Rebecca C.; Bale, Ambuja S.; Evans, Marina V.; Guyton, Kathryn Z.; Keshava, Nagalakshmi; Lipscomb, John C.; Barone, Stanley; Fox, John F.; Gwinn, Maureen R.; Schaum, John; Caldwell, Jane C.

2012-01-01

Background: In support of the Integrated Risk Information System (IRIS), the U.S. Environmental Protection Agency (EPA) completed a toxicological review of trichloroethylene (TCE) in September 2011, which was the result of an effort spanning > 20 years. Objectives: We summarized the key findings and scientific issues regarding the human health effects of TCE in the U.S. EPA’s toxicological review. Methods: In this assessment we synthesized and characterized thousands of epidemiologic, experimental animal, and mechanistic studies, and addressed several key scientific issues through modeling of TCE toxicokinetics, meta-analyses of epidemiologic studies, and analyses of mechanistic data. Discussion: Toxicokinetic modeling aided in characterizing the toxicological role of the complex metabolism and multiple metabolites of TCE. Meta-analyses of the epidemiologic data strongly supported the conclusions that TCE causes kidney cancer in humans and that TCE may also cause liver cancer and non-Hodgkin lymphoma. Mechanistic analyses support a key role for mutagenicity in TCE-induced kidney carcinogenicity. Recent evidence from studies in both humans and experimental animals point to the involvement of TCE exposure in autoimmune disease and hypersensitivity. Recent avian and in vitro mechanistic studies provided biological plausibility that TCE plays a role in developmental cardiac toxicity, the subject of substantial debate due to mixed results from epidemiologic and rodent studies. Conclusions: TCE is carcinogenic to humans by all routes of exposure and poses a potential human health hazard for noncancer toxicity to the central nervous system, kidney, liver, immune system, male reproductive system, and the developing embryo/fetus. PMID:23249866

Interim report on intrathoracic radiotherapy of human small-cell lung carcinoma in nude mice with Re-188-RC-160, a radiolabeled somatostatin analogue

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

Zamora, P.O.; Bender, H.; Biersack, H.J.

1995-07-01

The purpose of this study was to evaluate the therapeutic efficacy of Re-188-RC-160 in experimental models of human small cell lung carcinomas which mimic the clinical presentation. In the experimental model, cells from the human small cell lung carcinoma cell line NCI-H69 cells were inoculated into the thoracic cavity of athymic mice and rats. Subsequently, the biodistribution of Re-188-RC-160 after injection into the pleural cavity, a radiolabeled somatostatin analogue, was monitored as was the effect on the subsequent growth of tumors. The results presented here, and which are a part of a larger series of studies, suggest that Re-188-RC-160 canmore » be effectively used in this animal model to restrict the growth of small cell lung carcinoma in the thoracic cavity.« less

Experimental Vaccine for Mosquito-Borne Chikungunya Virus Rates Well in Clinical Study | Frederick National Laboratory for Cancer Research

Cancer.gov

An experimental vaccine for mosquito-borne chikungunya virus, which spread to the U.S. this year, appears to be safe and well-tolerated while offering protection against the virus, according to the results of a first-in-human clinical trial. The vacc

Ecological research at the Blacks Mountain Experimental Forest in northeastern California

Treesearch

William W. Oliver

2000-01-01

At Blacks Mountain Experimental Forest in northeastern California, an interdisciplinary team of scientists developed and implemented a research project to study how forest structural complexity affects the health and vigor of interior ponderosa pine (Pinus ponderosa Dougl. ex Laws.) ecosystems, the ecosystem's resilience to natural and human-caused disturbances,...

Experimental Starvation in Man

DTIC Science & Technology

1945-10-15

and Problems A. Edema ..................... 37 B. Dental Effects. ...... , ......... 38 C. Specific Vitamin Nutrition ..... ...... 38 VII...experimental study on human starvation and nutritional rehabilitation. Thirty-four young men, previously normal and well-nourished, have completed six months of...anthropometric characteristics. The character of the diet and the extent of the nutritional deficit have been calculated to be representative of moderately

Use of electronic nose technology to identify cattle experimentally infected with Mycobacterium bovis: A pilot study

USDA-ARS?s Scientific Manuscript database

Electronic nose technology has historically been utilized for the detection of volatile organic compounds (VOCs) and semi-volatile compounds in air, soil, water, and for quality control in food, beverage and cosmetic industries. Breath analysis has been used experimentally in humans and animals to ...

New Experimental Models of Diabetic Nephropathy in Mice Models of Type 2 Diabetes: Efforts to Replicate Human Nephropathy

PubMed Central

Soler, María José; Riera, Marta; Batlle, Daniel

2012-01-01

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. The use of experimental models of DN has provided valuable information regarding many aspects of DN, including pathophysiology, progression, implicated genes, and new therapeutic strategies. A large number of mouse models of diabetes have been identified and their kidney disease was characterized to various degrees. Most experimental models of type 2 DN are helpful in studying early stages of DN, but these models have not been able to reproduce the characteristic features of more advanced DN in humans such as nodules in the glomerular tuft or glomerulosclerosis. The generation of new experimental models of DN created by crossing, knockdown, or knockin of genes continues to provide improved tools for studying DN. These models provide an opportunity to search for new mechanisms involving the development of DN, but their shortcomings should be recognized as well. Moreover, it is important to recognize that the genetic background has a substantial effect on the susceptibility to diabetes and kidney disease development in the various models of diabetes. PMID:22461787

Simulation of bone-conducted sound transmission in a three-dimensional finite-element model of a human skull

NASA Astrophysics Data System (ADS)

Chang, You; Kim, Namkeun; Stenfelt, Stefan

2015-12-01

Bone conduction (BC) is the transmission of sound to the inner ear through the bones of the skull. This type of transmission is used in humans fitted with BC hearing aids as well as to classify between conductive and sensorineural hearing losses. The objective of the present study is to develop a finite-element (FE) model of the human skull based on cryosectional images of a female cadaver head in order to gain better understanding of the sound transmission. Further, the BC behavior was validated in terms of sound transmission against experimental data published in the literature. Results showed the responses of the simulated skull FE model were consistent with the experimentally reported data.

Protecting human subjects in research.

PubMed

Orticio, Lily P

2009-01-01

The quest for advancing scientific knowledge through human experimentations using vulnerable groups is traced back to ancient history, when Herophilus performed vivisections on prisoners. The violation of the rights of human subjects through the 20th century led to the formulation of the Nuremberg Code in 1947 and the Declaration of Helsinki in 1964. In the United States, the most infamous was the Tuskegee public health study that resulted in the enactment of the National Research Act that authorized the creation of the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research in 1974. In spite of existing federal regulations, the system of protecting human subjects is still flawed. Transparency of conflict ofinterest, clarity, and strict adherence to institutional guidelines are critical in safeguarding the rights and safety of human subjects and the integrity of research. Education on ethics and emerging complex ethical issues, global awareness, and governmental cooperation and sanctions are important steps in addressing the inadequacies in protecting the most vulnerable populations in experimentations worldwide. Investigators must always remember that the primary safeguards of protecting human life rest in their hands.

The use of nonhuman primates in research on seasonal, pandemic and avian influenza, 1893–2014

PubMed Central

Davis, A. Sally; Taubenberger, Jeffery K.; Bray, Mike

2015-01-01

Attempts to reproduce the features of human influenza in laboratory animals date from the early 1890s, when Richard Pfeiffer inoculated apes with bacteria recovered from influenza patients and produced a mild respiratory illness. Numerous studies employing nonhuman primates (NHPs) were performed during the 1918 pandemic and the following decade. Most used bacterial preparations to infect animals, but some sought a filterable agent for the disease. Since the viral etiology of influenza was established in the early 1930s, studies in NHPs have been supplemented by a much larger number of experiments in mice, ferrets and human volunteers. However, the emergence of a novel swine-origin H1N1 influenza virus in 1976 and the highly pathogenic H5N1 avian influenza virus in 1997 stimulated an increase in NHP research, because these agents are difficult to study in naturally infected patients and cannot be administered to human volunteers. In this paper, we review the published literature on the use of NHPs in influenza research from 1893 through the end of 2014. The first section summarizes observational studies of naturally occurring influenza-like syndromes in wild and captive primates, including serologic investigations. The second provides a chronological account of experimental infections of NHPs, beginning with Pfeiffer’s study and covering all published research on seasonal and pandemic influenza viruses, including vaccine and antiviral drug testing. The third section reviews experimental infections of NHPs with avian influenza viruses that have caused disease in humans since 1997. The paper concludes with suggestions for further studies to more clearly define and optimize the role of NHPs as experimental animals for influenza research. PMID:25746173

The use of nonhuman primates in research on seasonal, pandemic and avian influenza, 1893-2014.

PubMed

Davis, A Sally; Taubenberger, Jeffery K; Bray, Mike

2015-05-01

Attempts to reproduce the features of human influenza in laboratory animals date from the early 1890s, when Richard Pfeiffer inoculated apes with bacteria recovered from influenza patients and produced a mild respiratory illness. Numerous studies employing nonhuman primates (NHPs) were performed during the 1918 pandemic and the following decade. Most used bacterial preparations to infect animals, but some sought a filterable agent for the disease. Since the viral etiology of influenza was established in the early 1930s, studies in NHPs have been supplemented by a much larger number of experiments in mice, ferrets and human volunteers. However, the emergence of a novel swine-origin H1N1 influenza virus in 1976 and the highly pathogenic H5N1 avian influenza virus in 1997 stimulated an increase in NHP research, because these agents are difficult to study in naturally infected patients and cannot be administered to human volunteers. In this paper, we review the published literature on the use of NHPs in influenza research from 1893 through the end of 2014. The first section summarizes observational studies of naturally occurring influenza-like syndromes in wild and captive primates, including serologic investigations. The second provides a chronological account of experimental infections of NHPs, beginning with Pfeiffer's study and covering all published research on seasonal and pandemic influenza viruses, including vaccine and antiviral drug testing. The third section reviews experimental infections of NHPs with avian influenza viruses that have caused disease in humans since 1997. The paper concludes with suggestions for further studies to more clearly define and optimize the role of NHPs as experimental animals for influenza research. Published by Elsevier B.V.

A QUANTITATIVE COMPARISON OF THE EFFECTS OF ACUTE INHALED TOLUENE IN HUMAN RATS

EPA Science Inventory

The effects of acute exposure to toluene have been explored more thoroughly than other hydrocarbon solvents. These effects have been experimentally studied in humans and other species, e.g., rats, as well as in a number of in vitro preparations. The existence ofdosimetric and eff...

Conducting Studies of Transfer of Learning: A Practical Guide

DTIC Science & Technology

1982-01-01

X) = percent transfer (If learning C where: Kall aicrage of grades assigned to experimental :.ttmdents for p~erformlanlce in the aircraft. an average...effectiveness. Human Factors. 1971 . 13(6). 561-567. Roscoe, S.N. A little more on incremental transfer effectiveness. Human Factors. 1972, 14(4), 363-364

Debriefing after Human Patient Simulation and Nursing Students' Learning

ERIC Educational Resources Information Center

Benhuri, Gloria

2014-01-01

Human Patient Simulation (HPS) exercises with life-like computerized manikins provide clinical experiences for nursing students in a safe environment followed by debriefing that promotes learning. Quantitative research in techniques to support learning from debriefing is limited. The purpose of the quantitative quasi-experimental study using a…

[Testing of the effect of classic conditioning stimuli in human experiment by means of the transfer of control paradigm].

PubMed

Wolter, J

1999-01-01

Pavlovian conditioning in animals is often evaluated by means of transfer of control experiments. With human subjects, however, only very few studies have been conducted and the outcomes were often not in accordance with theoretical explanations based on studies with animals. A theoretical framework is presented that tries to integrate the results of the human conditioning paradigm and the animal conditioning paradigm as well, with reference to the well-known Yerkes-Dodson law. The experimental study with human subjects (N = 24) confirmed the predictions out of this framework, when a procedure similar to animal research is applied.

A biorobotic model of the human larynx.

PubMed

Manti, M; Cianchetti, M; Nacci, A; Ursino, F; Laschi, C

2015-08-01

This work focuses on a physical model of the human larynx that replicates its main components and functions. The prototype reproduces the multilayer vocal folds and the ab/adduction movements. In particular, the vocal folds prototype is made with soft materials whose mechanical properties have been obtained to be similar to the natural tissue in terms of viscoelasticity. A computational model was used to study fluid-structure interaction between vocal folds and the airflow. This tool allowed us to make a comparison between theoretical and experimental results. Measurements were performed with this prototype in an experimental platform comprising a controlled air flow, pressure sensors and a high-speed camera for measuring vocal fold vibrations. Data included oscillation frequency at the onset pressure and glottal width. Results show that the combination between vocal fold geometry, mechanical properties and dimensions exhibits an oscillation frequency close to that of the human vocal fold. Moreover, computational results show a high correlation with the experimental one.

An investigation of thermal comfort inside an automobile during the heating period.

PubMed

Kaynakli, Omer; Kilic, Muhsin

2005-05-01

This paper describes a combined theoretical and experimental study of thermal comfort during the heating period inside an automobile. To investigate the effects of thermal conditions on the human physiology and thermal comfort during the heating period, temperature, humidity and air velocity were measured at a number of points inside the automobile, so thermal conditions were accurately determined. The human body was divided into 16 sedentary segments, and the change of temperature was observed both experimentally and theoretically. During transient conditions of the heating period, heat and mass transfer between the human body and the interior environment of an automobile were simulated by a computational model, and predictions were compared with the measured data. It is shown that there is a good agreement between the model predictions and experimental results. By means of the present model, the effects of the fast transient conditions of the heating period on the sensible and latent heat transfer from the body, body segments skin temperatures and thermal sensation were investigated in detail.

Epstein-Barr virus latency switch in human B-cells: a physico-chemical model.

PubMed

Werner, Maria; Ernberg, Ingemar; Zou, Jiezhi; Almqvist, Jenny; Aurell, Erik

2007-08-31

The Epstein-Barr virus is widespread in all human populations and is strongly associated with human disease, ranging from infectious mononucleosis to cancer. In infected cells the virus can adopt several different latency programs, affecting the cells' behaviour. Experimental results indicate that a specific genetic switch between viral latency programs, reprograms human B-cells between proliferative and resting states. Each of these two latency programs makes use of a different viral promoter, Cp and Qp, respectively. The hypothesis tested in this study is that this genetic switch is controlled by both human and viral transcription factors; Oct-2 and EBNA-1. We build a physico-chemical model to investigate quantitatively the dynamical properties of the promoter regulation and experimentally examine protein level variations between the two latency programs. Our experimental results display significant differences in EBNA-1 and Oct-2 levels between resting and proliferating programs. With the model we identify two stable latency programs, corresponding to a resting and proliferating cell. The two programs differ in robustness and transcriptional activity. The proliferating state is markedly more stable, with a very high transcriptional activity from its viral promoter. We predict the promoter activities to be mutually exclusive in the two different programs, and our relative promoter activities correlate well with experimental data. Transitions between programs can be induced, by affecting the protein levels of our transcription factors. Simulated time scales are in line with experimental results. We show that fundamental properties of the Epstein-Barr virus involvement in latent infection, with implications for tumor biology, can be modelled and understood mathematically. We conclude that EBNA-1 and Oct-2 regulation of Cp and Qp is sufficient to establish mutually exclusive expression patterns. Moreover, the modelled genetic control predict both mono- and bistable behavior and a considerable difference in transition dynamics, based on program stability and promoter activities. Both these phenomena we hope can be further investigated experimentally, to increase the understanding of this important switch. Our results also stress the importance of the little known regulation of human transcription factor Oct-2.

Recent studies on the developing human hepatocellular carcinoma.

PubMed

Gerber, M A

1986-01-01

From our knowledge of characteristic phenotypic changes of the preneoplastic lesions during the stepwise evolution of hepatocellular carcinoma (HCC) in experimental models, we are now beginning to define the structural, histochemical, biochemical, antigenic and molecular properties of early HCC and of the putative preneoplastic changes in human liver. Histological, ultrastructural, morphometric and immunohistochemical studies suggest that adenomatous nodules of regenerating and hyperplastic hepatocytes are more likely to represent direct precursors of HCC than dysplastic hepatocytes. Histochemical and immunomorphological investigations show appreciable functional and phenotypic heterogeneity of human HCC as previously recognized in experimental hepatocarcinogenesis. Studies of altered expression of oncogenes in the regenerating liver and HCC are beginning to define the molecular mechanisms in cell growth and malignant transformation. Although integration of Hepadna viral DNA sequences frequently occurs during persistent infection in man and animals, the exact mechanism of viral oncogenesis remains to be elucidated. It is likely that the development of monoclonal antibodies to surface antigens on transformed hepatocytes will be useful for exploring lineage relationships between the cell populations involved in hepatocarcinogenesis.

Man is not a big rat: concerns with traditional human risk assessment of phthalates based on their anti-androgenic effects observed in the rat foetus.

PubMed

Habert, René; Livera, Gabriel; Rouiller-Fabre, Virginie

2014-01-01

Phthalates provide one of the most documented example evidencing how much we must be cautious when using the traditional paradigm based on extrapolation of experimental data from rodent studies for human health risk assessment of endocrine disruptors (EDs). Since foetal testis is known as one of the most sensitive targets of EDs, phthalate risk assessment is routinely based on the capacity of such compounds to decrease testosterone production by the testis or to impair masculinization in the rat during foetal life. In this paper, the well-established inhibiting effects of phthalates of the foetal Leydig cells function in the rat are briefly reviewed. Then, data obtained in humans and other species are carefully analysed. Already in January 2009, using the organotypic culture system named Fetal Testis Assay (FeTA) that we developed, we reported that phthalates might not affect testosterone production in human foetal testes. Several recent experimental studies using xenografts confirm the absence of detectable anti-androgenic effect of phthalates in the human foetal testes. Epidemiological studies led to contradictory results. Altogether, these findings suggest that phthalates effects on foetal Leydig cells are largely species-specific. Consequently, the phthalate threshold doses that disturb foetal steroidogenesis in rat testes and that are presently used to define the acceptable daily intake levels for human health protection must be questioned. This does not mean that phthalates are safe because these compounds have many deleterious effects upon germ cell development that may be common to the different studied species including human. More generally, the identification of common molecular, cellular or/and phenotypic targets in rat and human testes should precede the choice of the toxicological endpoint in rat to accurately assess the safety threshold of any ED in humans.

Reducing variation in a rabbit vaccine safety study with particular emphasis on housing conditions and handling.

PubMed

Verwer, Cynthia M; van der Ark, Arno; van Amerongen, Geert; van den Bos, Ruud; Hendriksen, Coenraad F M

2009-04-01

This paper describes the results of a study of the effects of modified housing conditions, conditioning and habituation on humans using a rabbit model for monitoring whole-cell pertussis vaccine (pWCV)-induced adverse effects. The study has been performed with reference to previous vaccine safety studies of pWCV in rabbits in which results were difficult to interpret due to the large variation in experimental outcome, especially in the key parameter deep-body temperature (T(b)). Certain stressful laboratory conditions, as well as procedures involving humans, e.g. blood sampling, inoculation and cage-cleaning, were hypothesized to cause this large variation. The results of this study show that under modified housing conditions rabbits have normal circadian body temperatures. This allowed discrimination of pWCV-induced adverse effects in which handled rabbits tended to show a dose-related increase in temperature after inoculation with little variance, whereas non-handled rabbits did not. Effects of experimental and routine procedures on body temperature were significantly reduced under modified conditions and were within the normal T(b) range. Handled animals reacted less strongly and with less variance to experimental procedures, such as blood sampling, injection and cage-cleaning, than non-handled rabbits. Overall, handling had a positive effect on the behaviour of the animals. Data show that the housing modifications have provided a more robust model for monitoring pWCV adverse effects. Furthermore, conditioning and habituation of rabbits to humans reduce the variation in experimental outcome, which might allow for a reduction in the number of animals used. In addition, this also reduces distress and thus contributes to refining this animal model.

Observational studies as human experimentation: the uranium mining experience in the Navajo Nation (1947-66).

PubMed

Moure-Eraso, R

1999-01-01

This article evaluates how an observational epidemiologic study of federal agencies in uranium miners became an experiment of opportunity for radiation effects. Navajo miners and communities suffered environmental exposures caused by the practices of uranium mining and milling in the Navajo reservation during the 1947 to 1966 period. A historical review of the state-of-the-art knowledge of the health effects of uranium mining and milling during the years prior to 1947 was conducted. Contemporary prevention and remediation practices also were assessed. An appraisal of the summary of findings of a comprehensive evaluation of radiation human experimentation conducted by the U.S. federal government in 1995-96 (ACHRE) demonstrates that uranium miners, including Navajo miners, were the single group that was put more seriously at risk of harm from radiation exposures, with inadequate disclosure and often with fatal consequences. Uranium miners were unwilling and unaware victims of human experimentation to evaluate the health effects of radiation. The failure of the State and U.S. Governments to issue regulations or demand installation of known mine-dust exposure control measures caused widespread environmental damage in the Navajo Nation.

Effect of Lipid Bilayer on Human Islet Amyloid Polypeptide Self Assembly

NASA Astrophysics Data System (ADS)

Chiu, Chi-Cheng; Singh, Sadanand; de Pablo, Juan J.

2012-02-01

Aggregates of human islet amyloid polypeptides (hIAPP, also known as human amylin) are commonly found in the pancreatic β-cells of type II diabetes patients. Experimental studies have shown that small aggregates of hIAPP, that arise during the assembly process, lead to membrane leakage and are highly cytotoxic. Due to the fast assembly kinetics, it is difficult to study the early aggregation of hIAPP experimentally. In this work, we use molecular simulation with a coarse grained (CG) model to investigate the oligomerization of hIAPP with and without the presence of lipid bilayers. We develop a CG protein model that reproduces the three thremodynamically stable structures of hIAPP, namely α-helix, β-hairpin, and unstructured coil, and the corresponding free energy differences calculated by atomistic molecular simulations. The aggregated structure of hIAPP also agrees with that proposed by NMR experiments. We further investigate the assembly of hIAPP in the presence of a lipid bilayer and its effect on the membrane leakage. Comparing our results with the mechanism proposed based on experimental data provides a better understanding of the origins of hIAPP self assembly and its toxicity.

Comparison of experimental models for predicting laser-tissue interaction from 3.8-micron lasers

NASA Astrophysics Data System (ADS)

Williams, Piper C. M.; Winston, Golda C. H.; Randolph, Don Q.; Neal, Thomas A.; Eurell, Thomas E.; Johnson, Thomas E.

2004-07-01

The purpose of this study was to evaluate the laser-tissue interactions of engineered human skin and in-vivo pig skin following exposure to a single 3.8 micron laser light pulse. The goal of the study was to determine if these tissues shared common histologic features following laser exposure that might prove useful in developing in-vitro and in-vivo experimental models to predict the bioeffects of human laser exposure. The minimum exposure required to produce gross morphologic changes following a four microsecond, pulsed skin exposure for both models was determined. Histology was used to compare the cellular responses of the experimental models following laser exposure. Eighteen engineered skin equivalents (in-vitro model), were exposed to 3.8 micron laser light and the tissue responses compared to equivalent exposures made on five Yorkshire pigs (in-vivo model). Representative biopsies of pig skin were taken for histologic evaluation from various body locations immediately, one hour, and 24 hours following exposure. The pattern of epithelial changes seen following in-vitro laser exposure of the engineered human skin and in-vivo exposure of pig skin indicated a common histologic response for this particular combination of laser parameters.

Recent mouse and rat methods for the study of experimental oral candidiasis.

PubMed

Costa, Anna C B P; Pereira, Cristiane A; Junqueira, Juliana C; Jorge, Antonio O C

2013-07-01

The Candida genus expresses virulence factors that, when combined with immunosuppression and other risk factors, can cause different manifestations of oral candidiasis. The treatment of mucosal infections caused by Candida and the elucidation of the disease process have proven challenging. Therefore, the study of experimentally induced oral candidiasis in rats and mice is useful to clarify the etiopathology of this condition, improve diagnosis, and search for new therapeutic options because the disease process in these animals is similar to that of human candidiasis lesions. Here, we describe and discuss new studies involving rat and mouse models of oral candidiasis with respect to methods for inducing experimental infection, methods for evaluating the development of experimental candidiasis, and new treatment strategies for oral candidiasis.

[Methodological approaches to the experimental study of the impact of environmental pollution on the human body].

PubMed

Sosedova, L M

2014-01-01

In the materials there are presented features of methodological approaches in the performing of experimental studies concerning of the investigation of the impacts of environmental factors on the human body. There were shown the results of our experiments performed at the Institute, in the modeling of biological effects of antimicrobial nanobiocomposites with nanosilver particles, toxic encephalopathy, in the study of the combined effect of the factors of biological and chemical nature. There was proved the importance of intracellular of proteomics in the assessment of the effects of the action of nanoparticles and nanomaterials on the body. There were revealed key parts of progredient course of mercury poisoning in the long-term. The special section is presented by the study of long-term effects of anthropogenic environmental factors on subsequent generations. There are presented results witnessing to a deterioration of the functional state of the central nervous system in rats in the first and second generations, whose parents were exposed to neurotoxicants. There was proved the aggravating role of prenatal hypoxia in the development of toxicity in rats in sexually mature age. Experimental biomodeling is aimed at sighting of pathogenetically substantiated treatment and preventive measures: initially, in experimental conditions, and in the future in the rehabilitation of sick or injured patients.

Experimental study and constitutive modeling of the viscoelastic mechanical properties of the human prolapsed vaginal tissue.

PubMed

Peña, Estefania; Calvo, B; Martínez, M A; Martins, P; Mascarenhas, T; Jorge, R M N; Ferreira, A; Doblaré, M

2010-02-01

In this paper, the viscoelastic mechanical properties of vaginal tissue are investigated. Using previous results of the authors on the mechanical properties of biological soft tissues and newly experimental data from uniaxial tension tests, a new model for the viscoelastic mechanical properties of the human vaginal tissue is proposed. The structural model seems to be sufficiently accurate to guarantee its application to prediction of reliable stress distributions, and is suitable for finite element computations. The obtained results may be helpful in the design of surgical procedures with autologous tissue or prostheses.

A roadmap to computational social neuroscience.

PubMed

Tognoli, Emmanuelle; Dumas, Guillaume; Kelso, J A Scott

2018-02-01

To complement experimental efforts toward understanding human social interactions at both neural and behavioral levels, two computational approaches are presented: (1) a fully parameterizable mathematical model of a social partner, the Human Dynamic Clamp which, by virtue of experimentally controlled interactions between Virtual Partners and real people, allows for emergent behaviors to be studied; and (2) a multiscale neurocomputational model of social coordination that enables exploration of social self-organization at all levels-from neuronal patterns to people interacting with each other. These complementary frameworks and the cross product of their analysis aim at understanding the fundamental principles governing social behavior.

Numerical evaluation of heating in the human head due to magnetic resonance imaging (MRI)

NASA Astrophysics Data System (ADS)

Nguyen, Uyen; Brown, Steve; Chang, Isaac; Krycia, Joe; Mirotznik, Mark S.

2003-06-01

In this paper we present a numerical model for evaluating tissue heating during magnetic resonance imaging (MRI). Our method, which included a detailed anatomical model of a human head, calculated both the electromagnetic power deposition and the associated temperature elevations during a MRI head examination. Numerical studies were conducted using a realistic birdcage coil excited at frequencies ranging from 63 MHz to 500 MHz. The model was validated both experimentally and analytically. The experimental validation was performed at the MR test facility located at the FDA's Center for Devices and Radiological Health (CDRH).

Experimental semiotics: a review.

PubMed

Galantucci, Bruno; Garrod, Simon

2011-01-01

In the last few years a new line of research has appeared in the literature. This line of research, which may be referred to as experimental semiotics (ES; Galantucci, 2009; Galantucci and Garrod, 2010), focuses on the experimental investigation of novel forms of human communication. In this review we will (a) situate ES in its conceptual context, (b) illustrate the main varieties of studies thus far conducted by experimental semioticians, (c) illustrate three main themes of investigation which have emerged within this line of research, and (d) consider implications of this work for cognitive neuroscience.

Experimental Semiotics: A Review

PubMed Central

Galantucci, Bruno; Garrod, Simon

2010-01-01

In the last few years a new line of research has appeared in the literature. This line of research, which may be referred to as experimental semiotics (ES; Galantucci, 2009; Galantucci and Garrod, 2010), focuses on the experimental investigation of novel forms of human communication. In this review we will (a) situate ES in its conceptual context, (b) illustrate the main varieties of studies thus far conducted by experimental semioticians, (c) illustrate three main themes of investigation which have emerged within this line of research, and (d) consider implications of this work for cognitive neuroscience. PMID:21369364

Do dogs follow behavioral cues from an unreliable human?

PubMed

Takaoka, Akiko; Maeda, Tomomi; Hori, Yusuke; Fujita, Kazuo

2015-03-01

Dogs are known to consistently follow human pointing gestures. In this study, we asked whether dogs "automatically" do this or whether they flexibly adjust their behavior depending upon the reliability of the pointer, demonstrated in an immediately preceding event. We tested pet dogs in a version of the object choice task in which a piece of food was hidden in one of the two containers. In Experiment 1, Phase 1, an experimenter pointed at the baited container; the second container was empty. In Phase 2, after showing the contents of both containers to the dogs, the experimenter pointed at the empty container. In Phase 3, the procedure was exactly as in Phase 1. We compared the dogs' responses to the experimenter's pointing gestures in Phases 1 and 3. Most dogs followed pointing in Phase 1, but many fewer did so in Phase 3. In Experiment 2, dogs followed a new experimenter's pointing in Phase 3 following replication of procedures of Phases 1 and 2 in Experiment 1. This ruled out the possibility that dogs simply lost motivation to participate in the task in later phases. These results suggest that not only dogs are highly skilled at understanding human pointing gestures, but also they make inferences about the reliability of a human who presents cues and consequently modify their behavior flexibly depending on the inference.

Importance of the brow in facial expressiveness during human communication.

PubMed

Neely, John Gail; Lisker, Paul; Drapekin, Jesse

2014-03-01

The objective of this study was to evaluate laterality and upper/lower face dominance of expressiveness during prescribed speech using a unique validated image subtraction system capable of sensitive and reliable measurement of facial surface deformation. Observations and experiments of central control of facial expressions during speech and social utterances in humans and animals suggest that the right mouth moves more than the left during nonemotional speech. However, proficient lip readers seem to attend to the whole face to interpret meaning from expressed facial cues, also implicating a horizontal (upper face-lower face) axis. Prospective experimental design. Experimental maneuver: recited speech. image-subtraction strength-duration curve amplitude. Thirty normal human adults were evaluated during memorized nonemotional recitation of 2 short sentences. Facial movements were assessed using a video-image subtractions system capable of simultaneously measuring upper and lower specific areas of each hemiface. The results demonstrate both axes influence facial expressiveness in human communication; however, the horizontal axis (upper versus lower face) would appear dominant, especially during what would appear to be spontaneous breakthrough unplanned expressiveness. These data are congruent with the concept that the left cerebral hemisphere has control over nonemotionally stimulated speech; however, the multisynaptic brainstem extrapyramidal pathways may override hemiface laterality and preferentially take control of the upper face. Additionally, these data demonstrate the importance of the often-ignored brow in facial expressiveness. Experimental study. EBM levels not applicable.

Mechanical characterization of human red blood cells under different osmotic conditions by robotic manipulation with optical tweezers.

PubMed

Tan, Youhua; Sun, Dong; Wang, Jinzhi; Huang, Wenhao

2010-07-01

The physiological functions of human red blood cells (RBCs) play a crucial role to human health and are greatly influenced by their mechanical properties. Any alteration of the cell mechanics may cause human diseases. The osmotic condition is an important factor to the physiological environment, but its effect on RBCs has been little studied. To investigate this effect, robotic manipulation technology with optical tweezers is utilized in this paper to characterize the mechanical properties of RBCs in different osmotic conditions. The effectiveness of this technology is demonstrated first in the manipulation of microbeads. Then the optical tweezers are used to stretch RBCs to acquire the force-deformation relationships. To extract cell properties from the experimental data, a mechanical model is developed for RBCs in hypotonic conditions by extending our previous work , and the finite element model is utilized for RBCs in isotonic and hypertonic conditions. Through comparing the modeling results to the experimental data, the shear moduli of RBCs in different osmotic solutions are characterized, which shows that the cell stiffness increases with elevated osmolality. Furthermore, the property variation and potential biomedical significance of this study are discussed. In conclusion, this study indicates that the osmotic stress has a significant effect on the cell properties of human RBCs, which may provide insight into the pathology analysis and therapy of some human diseases.

Studying semblances of a true killer: experimental model of human ventricular fibrillation.

PubMed

Nair, K; Farid, T; Masse, S; Umapathy, K; Watkins, S; Poku, K; Asta, J; Kusha, M; Sevaptsidis, E; Jacob, J; Floras, J S; Nanthakumar, K

2012-04-01

It is unknown whether ventricular fibrillation (VF) studied in experimental models represents in vivo human VF. First, we examined closed chest in vivo VF induced at defibrillation threshold testing (DFT) in four patients with ischemic cardiomyopathy pretransplantation. We examined VF in these same four hearts in an ex vivo human Langendorff posttransplantation. VF from DFT was compared with VF from the electrodes from a similar region in the right ventricular endocardium in the Langendorff using two parameters: the scale distribution width (extracted from continuous wavelet transform) and VF mean cycle length (CL). In a second substudy group where multielectrode phase mapping could be performed, we examined early VF intraoperatively (in vivo open chest condition) in three patients with left ventricular cardiomyopathy. We investigated early VF in the hearts of three patients in an ex vivo Langendorff and compared findings with intraoperative VF using two metrics: dominant frequency (DF) assessed by the Welch periodogram and the number of phase singularities (lasting >480 ms). Wavelet analysis (P = 0.9) and VF CL were similar between the Langendorff and the DFT groups (225 ± 13, 218 ± 24 ms; P = 0.9), indicating that wave characteristics and activation rate of VF was comparable between the two models. Intraoperative DF was slower but comparable with the Langendorff DF over the endocardium (4.6 ± 0.1, 5.0 ± 0.4 Hz; P = 0.9) and the epicardium (4.5 ± 0.2, 5.2 ± 0.4 Hz; P = 0.9). Endocardial phase singularity number (9.6 ± 5, 12.1 ± 1; P = 0.6) was lesser in number but comparable between in vivo and ex vivo VF. VF dynamics in the limited experimental human studies approximates human in vivo VF.

A Decade in the MIST: Learnings from Investigations of Drug Metabolites in Drug Development under the "Metabolites in Safety Testing" Regulatory Guidance.

PubMed

Schadt, Simone; Bister, Bojan; Chowdhury, Swapan K; Funk, Christoph; Hop, Cornelis E C A; Humphreys, W Griffith; Igarashi, Fumihiko; James, Alexander D; Kagan, Mark; Khojasteh, S Cyrus; Nedderman, Angus N R; Prakash, Chandra; Runge, Frank; Scheible, Holger; Spracklin, Douglas K; Swart, Piet; Tse, Susanna; Yuan, Josh; Obach, R Scott

2018-06-01

Since the introduction of metabolites in safety testing (MIST) guidance by the Food and Drug Administration in 2008, major changes have occurred in the experimental methods for the identification and quantification of metabolites, ways to evaluate coverage of metabolites, and the timing of critical clinical and nonclinical studies to generate this information. In this cross-industry review, we discuss how the increased focus on human drug metabolites and their potential contribution to safety and drug-drug interactions has influenced the approaches taken by industry for the identification and quantitation of human drug metabolites. Before the MIST guidance was issued, the method of choice for generating comprehensive metabolite profile was radio chromatography. The MIST guidance increased the focus on human drug metabolites and their potential contribution to safety and drug-drug interactions and led to changes in the practices of drug metabolism scientists. In addition, the guidance suggested that human metabolism studies should also be accelerated, which has led to more frequent determination of human metabolite profiles from multiple ascending-dose clinical studies. Generating a comprehensive and quantitative profile of human metabolites has become a more urgent task. Together with technological advances, these events have led to a general shift of focus toward earlier human metabolism studies using high-resolution mass spectrometry and to a reduction in animal radiolabel absorption/distribution/metabolism/excretion studies. The changes induced by the MIST guidance are highlighted by six case studies included herein, reflecting different stages of implementation of the MIST guidance within the pharmaceutical industry. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Animal rights and animal experimentation. Implications for physicians.

PubMed Central

Gelpi, A. P.

1991-01-01

Practicing physicians are just becoming aware of the animal rights movement, which during the 1980s spawned numerous acts of violence against research facilities throughout the United States. The animal rightists are challenging physicians to show moral justification for the human exploitation of nature and the world of subhuman species. They have aroused public interest in animal welfare, sparked protective legislation for experimental animals, and indirectly encouraged the creation of committees to oversee the conduct of animal experimentation and the conditions of animal confinement. This controversy has necessitated a closer look at the questions of animal experimentation and animal rights against the backdrop of human experimentation and human rights. Physicians and specialists in animal care seek to alleviate suffering and anxiety, and, as moderates, they may be able to bring both sides of the animal rights controversy together in a spirit of mutual tolerance and in the common cause of promoting both human and animal welfare. PMID:1949772

Rapid Industrial Development, Competition, and Relative Economic Status: A Study in Human Ecology. Working Paper RID 73.10.

ERIC Educational Resources Information Center

Summers, Gene F.; Clemente, Frank

The document has 3 goals (1) to examine the distribution of economic benefits of industrial development as reflected by the concept of competition in human ecology; (2) to provide an empirical test of the ecological model, and (3) to relate the findings to public policy. Two Illinois study areas were identified. First, as an experimental region,…

[327] Biomedical Research Deferred in the Aftermath of the Apollo Fire: Impact to Progress in Human Spaceflight

NASA Technical Reports Server (NTRS)

Charles, John B.

2017-01-01

Before Apollo fire, early Apollo missions were expected to continue pattern established in Gemini program of accommodating significant scientific and biological experimentation, including human biomedical studies, during flights. Apollo1 and Apollo2, both 2-week engineering test flights, were to carry almost as many biomedical studies as Gemini 7, a 2-week medical test mission.

Solidarity with Animals: Assessing a Relevant Dimension of Social Identification with Animals.

PubMed

Amiot, Catherine E; Bastian, Brock

2017-01-01

Interactions with animals are pervasive in human life, a fact that is reflected in the burgeoning field of human-animal relations research. The goal of the current research was to examine the psychology of our social connection with other animals, by specifically developing a measure of solidarity with animals. In 8 studies using correlational, experimental, and longitudinal designs, solidarity with animals predicted more positive attitudes and behaviors toward animals, over and above existing scales of identification, and even when this implied a loss of resources and privileges for humans relative to animals. Solidarity with animals also displayed predicted relationships with relevant variables (anthropomorphism, empathy). Pet owners and vegetarians displayed higher levels of solidarity with animals. Correlational and experimental evidence confirmed that human-animal similarity heightens solidarity with animals. Our findings provide a useful measure that can facilitate important insights into the nature of our relationships with animals.

Solidarity with Animals: Assessing a Relevant Dimension of Social Identification with Animals

PubMed Central

Amiot, Catherine E.; Bastian, Brock

2017-01-01

Interactions with animals are pervasive in human life, a fact that is reflected in the burgeoning field of human-animal relations research. The goal of the current research was to examine the psychology of our social connection with other animals, by specifically developing a measure of solidarity with animals. In 8 studies using correlational, experimental, and longitudinal designs, solidarity with animals predicted more positive attitudes and behaviors toward animals, over and above existing scales of identification, and even when this implied a loss of resources and privileges for humans relative to animals. Solidarity with animals also displayed predicted relationships with relevant variables (anthropomorphism, empathy). Pet owners and vegetarians displayed higher levels of solidarity with animals. Correlational and experimental evidence confirmed that human-animal similarity heightens solidarity with animals. Our findings provide a useful measure that can facilitate important insights into the nature of our relationships with animals. PMID:28045909

Experimental econophysics: Complexity, self-organization, and emergent properties

NASA Astrophysics Data System (ADS)

Huang, J. P.

2015-03-01

Experimental econophysics is concerned with statistical physics of humans in the laboratory, and it is based on controlled human experiments developed by physicists to study some problems related to economics or finance. It relies on controlled human experiments in the laboratory together with agent-based modeling (for computer simulations and/or analytical theory), with an attempt to reveal the general cause-effect relationship between specific conditions and emergent properties of real economic/financial markets (a kind of complex adaptive systems). Here I review the latest progress in the field, namely, stylized facts, herd behavior, contrarian behavior, spontaneous cooperation, partial information, and risk management. Also, I highlight the connections between such progress and other topics of traditional statistical physics. The main theme of the review is to show diverse emergent properties of the laboratory markets, originating from self-organization due to the nonlinear interactions among heterogeneous humans or agents (complexity).

Which experimental systems should we use for human microbiome science?

PubMed

Douglas, Angela E

2018-03-01

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

Report on carcinogens monograph on 1-bromopropane.

PubMed

2013-09-01

The National Toxicology Program conducted a cancer evaluation on 1 bromopropane for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for 1 bromopropane in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to 1-bromopropane. This monograph provides an assessment of the available scientific information on 1 bromopropane, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that 1 bromopropane be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found inhalation exposure to 1-bromopropane caused skin tumors in male rats, large intestine tumors in female and male rats, and lung tumors in female mice. Also noted was that 1 bromopropane, either directly or via reactive metabolites, caused molecular alterations that typically are associated with carcinogenesis, including genotoxicity, oxidative stress, and glutathione depletion. These alterations, observed in mainly in vitro and toxicity studies in rodents, are relevant to possible mechanisms of human carcinogenicity and support the relevance of the cancer studies in experimental animals to humans.

A combination of experimental measurement, constitutive damage model, and diffusion tensor imaging to characterize the mechanical properties of the human brain.

PubMed

Karimi, Alireza; Rahmati, Seyed Mohammadali; Razaghi, Reza

2017-09-01

Understanding the mechanical properties of the human brain is deemed important as it may subject to various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the frontal lobe of the human brain. The constrained nonlinear minimization method was employed to identify the brain coefficients according to the axial and transversal compressive data. The pseudo-elastic damage model data was also well compared with that of the experimental data and it not only up to the primary loading but also the discontinuous softening could well address the mechanical behavior of the brain tissue.

Simulations of light effects on the human circadian pacemaker: implications for assessment of intrinsic period

NASA Technical Reports Server (NTRS)

Klerman, E. B.; Dijk, D. J.; Kronauer, R. E.; Czeisler, C. A.

1996-01-01

The sensitivity of the human circadian system to light has been the subject of considerable debate. Using computer simulations of a recent quantitative model for the effects of light on the human circadian system, we investigated these effects of light during different experimental protocols. The results of the simulations indicate that the nonuniform distribution over the circadian cycle of exposure to ordinary room light seen in classical free-run studies, in which subjects select their exposure to light and darkness, can result in an observed period of approximately 25 h, even when the intrinsic period of the subject's endogenous circadian pacemaker is much closer to 24 h. Other simulation results suggest that accurate assessment of the true intrinsic period of the human circadian pacemaker requires low ambient light intensities (approximately 10-15 lx) during scheduled wake episodes, desynchrony of the imposed light-dark cycle from the endogenous circadian oscillator, and a study length of at least 20 days. Although these simulations await further experimental substantiation, they highlight the sensitivity to light of the human circadian system and the potential confounding influence of light on the assessment of the intrinsic period of the circadian pacemaker.

Anti-aging effects of vitamin C on human pluripotent stem cell-derived cardiomyocytes.

PubMed

Kim, Yoon Young; Ku, Seung-Yup; Huh, Yul; Liu, Hung-Ching; Kim, Seok Hyun; Choi, Young Min; Moon, Shin Yong

2013-10-01

Human pluripotent stem cells (hPSCs) have arisen as a source of cells for biomedical research due to their developmental potential. Stem cells possess the promise of providing clinicians with novel treatments for disease as well as allowing researchers to generate human-specific cellular metabolism models. Aging is a natural process of living organisms, yet aging in human heart cells is difficult to study due to the ethical considerations regarding human experimentation as well as a current lack of alternative experimental models. hPSC-derived cardiomyocytes (CMs) bear a resemblance to human cardiac cells and thus hPSC-derived CMs are considered to be a viable alternative model to study human heart cell aging. In this study, we used hPSC-derived CMs as an in vitro aging model. We generated cardiomyocytes from hPSCs and demonstrated the process of aging in both human embryonic stem cell (hESC)- and induced pluripotent stem cell (hiPSC)-derived CMs. Aging in hESC-derived CMs correlated with reduced membrane potential in mitochondria, the accumulation of lipofuscin, a slower beating pattern, and the downregulation of human telomerase RNA (hTR) and cell cycle regulating genes. Interestingly, the expression of hTR in hiPSC-derived CMs was not significantly downregulated, unlike in hESC-derived CMs. In order to delay aging, vitamin C was added to the cultured CMs. When cells were treated with 100 μM of vitamin C for 48 h, anti-aging effects, specifically on the expression of telomere-related genes and their functionality in aging cells, were observed. Taken together, these results suggest that hPSC-derived CMs can be used as a unique human cardiomyocyte aging model in vitro and that vitamin C shows anti-aging effects in this model.

Investigation of crew restraint system biomechanics. Report for May 79-Mar 81

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

Phillips, N.S.; Thomson, R.A.; Fiscus, I.B.

1982-05-01

Experimental data were collected and analyses were performed to study the influence of the dynamic mechanical properties of restraint system components on human response to impact and restraint system haulback. Tests were accomplished to isolate the characteristics of the restraint system and the human body. Three restraint webbing materials were studied at varied strain rates. A pyrotechnically powered inertia reel was tested, but could not be analytically modeled successfully. Analytical models of the human and restraint system were used to study the influence of restraint material properties changes on human response parameters. An analytical model of a rhesus monkey wasmore » also used to study the efficacy of animal tests and scaling techniques to evaluate restraint systems for human use applications.« less

Who is healthy? Aspects to consider when including healthy volunteers in QST--based studies-a consensus statement by the EUROPAIN and NEUROPAIN consortia.

PubMed

Gierthmühlen, Janne; Enax-Krumova, Elena K; Attal, Nadine; Bouhassira, Didier; Cruccu, Giorgio; Finnerup, Nanna B; Haanpää, Maija; Hansson, Per; Jensen, Troels S; Freynhagen, Rainer; Kennedy, Jeffrey D; Mainka, Tina; Rice, Andrew S C; Segerdahl, Märta; Sindrup, Søren H; Serra, Jordi; Tölle, Thomas; Treede, Rolf-Detlef; Baron, Ralf; Maier, Christoph

2015-11-01

Clinical and human experimental pain studies often include so-called "healthy" controls in investigations of sensory abnormalities, using quantitative sensory testing (QST) as an outcome measure. However, the criteria for what is considered "healthy" vary among the different studies and between study centers and investigators, partly explaining the high variability of the results. Therefore, several aspects should be considered during inclusion of healthy volunteers in QST-based trials to have homogenous groups of healthy controls with less variability between human experimental studies, so that results are less likely to be false negative or false positive because of subject-related factors. The EUROPAIN and NEUROPAIN consortia aimed to define factors influencing the variability in selection of healthy subjects in QST-based studies before the start of both projects and to give recommendations how to minimize it based on the current literature and expertise of the participants. The present suggestions for inclusion criteria of healthy volunteers into QST-based trials describe a 2-level approach including standardized questionnaires enabling the collection of relevant information on sociodemographic data, medical history, current health status, coping strategies in dealing with pain, and the motivation of the volunteer to participate in the study. These suggestions are believed to help researchers interpret their results in comparison with others and improve the quality of clinical studies including healthy volunteers as controls or in human experimental pain studies. They aim to reduce any confounding factors. Furthermore, the acquired information will allow post hoc analyses of variance for different potential influencing factors.

Human Health Effects of Biphenyl: Key Findings and Scientific Issues

PubMed Central

Li, Zheng; Hogan, Karen A.; Cai, Christine; Rieth, Susan

2015-01-01

Background: In support of the Integrated Risk Information System (IRIS), the U.S. Environmental Protection Agency (EPA) has evaluated the human health hazards of biphenyl exposure. Objectives: We review key findings and scientific issues regarding expected human health effects of biphenyl. Methods: Scientific literature from 1926 through September 2012 was critically evaluated to identify potential human health hazards associated with biphenyl exposure. Key issues related to the carcinogenicity and noncancer health hazards of biphenyl were examined based on evidence from experimental animal bioassays and mechanistic studies. Discussion: Systematic consideration of experimental animal studies of oral biphenyl exposure took into account the variety of study designs (e.g., study sizes, exposure levels, and exposure durations) to reconcile differing reported results. The available mechanistic and toxicokinetic evidence supports the hypothesis that male rat urinary bladder tumors arise through urinary bladder calculi formation but is insufficient to hypothesize a mode of action for liver tumors in female mice. Biphenyl and its metabolites may induce genetic damage, but a role for genotoxicity in biphenyl-induced carcinogenicity has not been established. Conclusions: The available health effects data for biphenyl provides suggestive evidence for carcinogenicity in humans, based on increased incidences of male rat urinary bladder tumors at high exposure levels and on female mouse liver tumors. Kidney toxicity is also a potential human health hazard of biphenyl exposure. Citation: Li Z, Hogan KA, Cai C, Rieth S. 2016. Human health effects of biphenyl: key findings and scientific issues. Environ Health Perspect 124:703–712; http://dx.doi.org/10.1289/ehp.1509730 PMID:26529796

Human Factors Engineering Bibliographic Series. Volume 5, 1967 Literature

DTIC Science & Technology

1976-03-01

8217aining progracus designed to In- crease arn strength. There were 26 subects In each group. those In the experimental group, static and dyl’sic... experimental design over more usual classical procedures are Swq* gested.a’ 32,258 Cohen. 1t.l. CONTINUOUS VERSUS Tti. VISUAL FEEDSAX INl PRISM... experimental study was :?arformeed to evaluate, singly &no In combination, the effective- ness of a is-hr. training progrm and a set of visual aids designed to

Phase II Clinical Trial of Intraoral Grafting of Human Tissue Engineered Oral Mucosa

DTIC Science & Technology

2017-10-01

experimental arm subject in the small defect study. A protocol amendment in early 2017revised the study inclusionary criteria to include all non ...construed as an official Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE...group phase II study to assess the safety and efficacy for use of human EVPOME for soft tissue intraoral grafting procedures compared to the “gold

Meta-T: TetrisⓇ as an experimental paradigm for cognitive skills research.

PubMed

Lindstedt, John K; Gray, Wayne D

2015-12-01

Studies of human performance in complex tasks using video games are an attractive prospect, but many existing games lack a comprehensive way to modify the game and track performance beyond basic levels of analysis. Meta-T provides experimenters a tool to study behavior in a dynamic task environment with time-stressed decision-making and strong perceptual-motor elements, offering a host of experimental manipulations with a robust and detailed logging system for all user events, system events, and screen objects. Its experimenter-friendly interface provides control over detailed parameters of the task environment without need for programming expertise. Support for eye-tracking and computational cognitive modeling extend the paradigm's scope.

Compressive mechanical characterization of non-human primate spinal cord white matter.

PubMed

Jannesar, Shervin; Allen, Mark; Mills, Sarah; Gibbons, Anne; Bresnahan, Jacqueline C; Salegio, Ernesto A; Sparrey, Carolyn J

2018-05-02

The goal of developing computational models of spinal cord injury (SCI) is to better understand the human injury condition. However, finite element models of human SCI have used rodent spinal cord tissue properties due to a lack of experimental data. Central nervous system tissues in non human primates (NHP) closely resemble that of humans and therefore, it is expected that material constitutive models obtained from NHPs will increase the fidelity and the accuracy of human SCI models. Human SCI most often results from compressive loading and spinal cord white matter properties affect FE predicted patterns of injury; therefore, the objectives of this study were to characterize the unconfined compressive response of NHP spinal cord white matter and present an experimentally derived, finite element tractable constitutive model for the tissue. Cervical spinal cords were harvested from nine male adult NHPs (Macaca mulatta). White matter biopsy samples (3 mm in diameter) were taken from both lateral columns of the spinal cord and were divided into four strain rate groups for unconfined dynamic compression and stress relaxation (post-mortem <1-hour). The NHP spinal cord white matter compressive response was sensitive to strain rate and showed substantial stress relaxation confirming the viscoelastic behavior of the material. An Ogden 1st order model best captured the non-linear behavior of NHP white matter in a quasi-linear viscoelastic material model with 4-term Prony series. This study is the first to characterize NHP spinal cord white matter at high (>10/sec) strain rates typical of traumatic injury. The finite element derived material constitutive model of this study will increase the fidelity of SCI computational models and provide important insights for transferring pre-clinical findings to clinical treatments. Spinal cord injury (SCI) finite element (FE) models provide an important tool to bridge the gap between animal studies and human injury, assess injury prevention technologies (e.g. helmets, seatbelts), and provide insight into the mechanisms of injury. Although, FE model outcomes depend on the assumed material constitutive model, there is limited experimental data for fresh spinal cords and all was obtained from rodent, porcine or bovine tissues. Central nervous system tissues in non human primates (NHP) more closely resemble humans. This study characterizes fresh NHP spinal cord material properties at high strains rates and large deformations typical of SCI for the first time. A constitutive model was defined that can be readily implemented in finite strain FE analysis of SCI. Copyright © 2018. Published by Elsevier Ltd.

Chlorophenol sorption on multi-walled carbon nanotubes: DFT modeling and structure-property relationship analysis.

PubMed

Watkins, Marquita; Sizochenko, Natalia; Moore, Quentarius; Golebiowski, Marek; Leszczynska, Danuta; Leszczynski, Jerzy

2017-02-01

The presence of chlorophenols in drinking water can be hazardous to human health. Understanding the mechanisms of adsorption under specific experimental conditions would be beneficial when developing methods to remove toxic substances from drinking water during water treatment in order to limit human exposure to these contaminants. In this study, we investigated the sorption of chlorophenols on multi-walled carbon nanotubes using a density functional theory (DFT) approach. This was applied to study selected interactions between six solvents, five types of nanotubes, and six chlorophenols. Experimental data were used to construct structure-adsorption relationship (SAR) models that describe the recovery process. Specific interactions between solvents and chlorophenols were taken into account in the calculations by using novel specific mixture descriptors.

Review of Ginkgo biloba-induced toxicity, from experimental studies to human case reports.

PubMed

Mei, Nan; Guo, Xiaoqing; Ren, Zhen; Kobayashi, Daisuke; Wada, Keiji; Guo, Lei

2017-01-02

Ginkgo biloba seeds and leaves have been used as a traditional herbal remedy for thousands of years, and its leaf extract has been consumed as a botanical dietary supplement for decades. Ginkgo biloba extract is a complex mixture with numerous components, including flavonol glycosides and terpene lactones, and is one of the most widely sold botanical dietary supplements worldwide. Concerns about potential health risks for the general population have been raised because of the widespread human exposure to Ginkgo biloba and its potential toxic and carcinogenic activities in rodents. The National Toxicology Program conducted 2-year gavage studies on one Ginkgo biloba leaf extract and concluded that there was clear evidence of carcinogenic activity of this extract in mice based on an increased incidence of hepatocellular carcinoma and hepatoblastoma. Recently, Ginkgo biloba leaf extract has been classified as a possible human carcinogen (Group 2B) by the International Agency for Research on Cancer. This review presents updated information on the toxicological effects from experimental studies both in vitro and in vivo to human case reports (caused by ginkgo seeds or leaves), and also summarizes the negative results from relatively large clinical trials.

Gene Expression Changes Induced by PPAR Gamma Agonists in Animal and Human Liver

PubMed Central

Rogue, Alexandra; Spire, Catherine; Brun, Manuel; Claude, Nancy; Guillouzo, André

2010-01-01

Thiazolidinediones are a class of Peroxisome Proliferator Activated Receptor γ (PPARγ) agonists that reduce insulin resistance in type 2 diabetic patients. Although no detectable hepatic toxicity has been evidenced in animal studies during preclinical trials, these molecules have nevertheless induced hepatic adverse effects in some treated patients. The mechanism(s) of hepatotoxicity remains equivocal. Several studies have been conducted using PCR analysis and microarray technology to identify possible target genes and here we review the data obtained from various in vivo and in vitro experimental models. Although PPARγ is expressed at a much lower level in liver than in adipose tissue, PPARγ agonists exert various PPARγ-dependent effects in liver in addition to PPARγ-independent effects. Differences in effects are dependent on the choice of agonist and experimental conditions in rodent animal studies and in rodent and human liver cell cultures. These effects are much more pronounced in obese and diabetic liver. Moreover, our own recent studies have shown major interindividual variability in the response of primary human hepatocyte populations to troglitazone treatment, supporting the occurrence of hepatotoxicity in only some individuals. PMID:20981297

The Teaching Brain

ERIC Educational Resources Information Center

Battro, Antonio M.

2010-01-01

Animals cannot teach as humans do. Therefore, we lack the experimental support of animal studies that are so important to understand the evolution of our basic learning skills but are useless to explore the development of the teaching skills, unique to humans. And most important: children teach! We have at least two new challenges in our Mind,…

How to Bootstrap a Human Communication System

ERIC Educational Resources Information Center

Fay, Nicolas; Arbib, Michael; Garrod, Simon

2013-01-01

How might a human communication system be bootstrapped in the absence of conventional language? We argue that motivated signs play an important role (i.e., signs that are linked to meaning by structural resemblance or by natural association). An experimental study is then reported in which participants try to communicate a range of pre-specified…

Habituation as a Determinant of Human Food Intake

ERIC Educational Resources Information Center

Epstein, Leonard H.; Temple, Jennifer L.; Roemmich, James N.; Bouton, Mark E.

2009-01-01

Research has shown that animals and humans habituate on a variety of behavioral and physiological responses to repeated presentations of food cues, and habituation is related to amount of food consumed and cessation of eating. The purpose of this article is to provide an overview of experimental paradigms used to study habituation, integrate a…

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

PubMed Central

2013-01-01

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

BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity.

PubMed

Arts, Rob J W; Moorlag, Simone J C F M; Novakovic, Boris; Li, Yang; Wang, Shuang-Yin; Oosting, Marije; Kumar, Vinod; Xavier, Ramnik J; Wijmenga, Cisca; Joosten, Leo A B; Reusken, Chantal B E M; Benn, Christine S; Aaby, Peter; Koopmans, Marion P; Stunnenberg, Hendrik G; van Crevel, Reinout; Netea, Mihai G

2018-01-10

The tuberculosis vaccine bacillus Calmette-Guérin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide epigenetic reprograming of monocytes and protected against experimental infection with an attenuated yellow fever virus vaccine strain. Epigenetic reprogramming was accompanied by functional changes indicative of trained immunity. Reduction of viremia was highly correlated with the upregulation of IL-1β, a heterologous cytokine associated with the induction of trained immunity, but not with the specific IFNγ response. The importance of IL-1β for the induction of trained immunity was validated through genetic, epigenetic, and immunological studies. In conclusion, BCG induces epigenetic reprogramming in human monocytes in vivo, followed by functional reprogramming and protection against non-related viral infections, with a key role for IL-1β as a mediator of trained immunity responses. Copyright © 2017 Elsevier Inc. All rights reserved.

Global Human Footprint on the Linkage between Biodiversity and Ecosystem Functioning in Reef Fishes

PubMed Central

Mora, Camilo; Aburto-Oropeza, Octavio; Ayala Bocos, Arturo; Ayotte, Paula M.; Banks, Stuart; Bauman, Andrew G.; Beger, Maria; Bessudo, Sandra; Booth, David J.; Brokovich, Eran; Brooks, Andrew; Chabanet, Pascale; Cinner, Joshua E.; Cortés, Jorge; Cruz-Motta, Juan J.; Cupul Magaña, Amilcar; DeMartini, Edward E.; Edgar, Graham J.; Feary, David A.; Ferse, Sebastian C. A.; Friedlander, Alan M.; Gaston, Kevin J.; Gough, Charlotte; Graham, Nicholas A. J.; Green, Alison; Guzman, Hector; Hardt, Marah; Kulbicki, Michel; Letourneur, Yves; López Pérez, Andres; Loreau, Michel; Loya, Yossi; Martinez, Camilo; Mascareñas-Osorio, Ismael; Morove, Tau; Nadon, Marc-Olivier; Nakamura, Yohei; Paredes, Gustavo; Polunin, Nicholas V. C.; Pratchett, Morgan S.; Reyes Bonilla, Héctor; Rivera, Fernando; Sala, Enric; Sandin, Stuart A.; Soler, German; Stuart-Smith, Rick; Tessier, Emmanuel; Tittensor, Derek P.; Tupper, Mark; Usseglio, Paolo; Vigliola, Laurent; Wantiez, Laurent; Williams, Ivor; Wilson, Shaun K.; Zapata, Fernando A.

2011-01-01

Difficulties in scaling up theoretical and experimental results have raised controversy over the consequences of biodiversity loss for the functioning of natural ecosystems. Using a global survey of reef fish assemblages, we show that in contrast to previous theoretical and experimental studies, ecosystem functioning (as measured by standing biomass) scales in a non-saturating manner with biodiversity (as measured by species and functional richness) in this ecosystem. Our field study also shows a significant and negative interaction between human population density and biodiversity on ecosystem functioning (i.e., for the same human density there were larger reductions in standing biomass at more diverse reefs). Human effects were found to be related to fishing, coastal development, and land use stressors, and currently affect over 75% of the world's coral reefs. Our results indicate that the consequences of biodiversity loss in coral reefs have been considerably underestimated based on existing knowledge and that reef fish assemblages, particularly the most diverse, are greatly vulnerable to the expansion and intensity of anthropogenic stressors in coastal areas. PMID:21483714

Effect of Gravity on the Mammalian Cell Deformation

NASA Technical Reports Server (NTRS)

Hung, R. J.; Tsao, Y.; Gonda, Steven

1995-01-01

The effect of human cell immersed in culture liquid under a micro-gravity environment has been investigated. The study is based on the numerical simulation of the configuration of human cell affected by the time dependent variation of gravity acceleration ranging from 10(exp -3) to 2 g(sub o) (g(sub o) = 9.81 m/s(exp 2)) in 15 seconds. Both the free floating cell and the cell contacted to the upper and lower inclined walls imposed by the time-dependent reduced gravity acceleration are considered in this study. The results show that the cell configuration changes from spherical to horizontally elongated ellipsoid for both the free floating cell and the cell sitting on the lower inclined wall while the cell configuration varies from spherical to vertically elongated ellipsoid for the cell hanging to the upper inclined wall when the gravity acceleration increases. Experimental observations, carried out of human cells exposed to the variation of gravity levels, show that the results of experimental observations agree exactly with the theoretical model computation described in this paper. These results sre significant for humans exposed to the micro-gravity environment.

In vivo experience with peroral endoscopic myotomy: An essential activity for developing the technique in humans.

PubMed

Peñaloza-Ramírez, A; Suárez-Correa, J; Báez-Blanco, J; Sabogal-Gómez, C; Kuan-Casas, H; Sánchez-Pignalosa, C; Aponte-Ordóñez, P

Achalasia is the most widely studied esophageal motility disorder. No treatment has achieved completely satisfactory results. The laparoscopic Heller esophagomyotomy is currently the most accepted technique. With the advent of minimally invasive surgery, the appearance of peroral endoscopic myotomy (POEM) has promising results. The primary aim of our study was to perform peroral endoscopic esophagomyotomy in animal experimentation models to perfect the technique and later apply it to humans. The secondary aims were to evaluate the intraoperative and postoperative complications and to describe the anatomopathologic findings. An experimental study was conducted on 8 live porcine models that were followed for 30 days to identify postoperative complications. Necropsy was then performed to evaluate the histopathologic findings. The international requirements and regulations for animal experimentation were met. The technique was carried out in all the models. There was one intraoperative death. Pneumothorax was observed in 50% of the units in experimentation and subcutaneous cervical emphysema in 75%, with no significant clinical repercussions. Histologic muscle layer (myotomy) involvement was above the gastroesophageal junction in 87% of the cases and below it in 25%. Peroral endoscopic esophagomyotomy is a feasible, albeit complex, procedure that requires advanced training, and thus should be performed in highly specialized centers. Specific skills in advanced therapeutic endoscopic procedures of this type must continue to be developed through continuing education (ideally in in vivo models), to then be performed on humans. Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Comprehension of human pointing gestures in young human-reared wolves (Canis lupus) and dogs (Canis familiaris).

PubMed

Virányi, Zsófia; Gácsi, Márta; Kubinyi, Eniko; Topál, József; Belényi, Beatrix; Ujfalussy, Dorottya; Miklósi, Adám

2008-07-01

Dogs have a remarkable skill to use human-given cues in object-choice tasks, but little is known to what extent their closest wild-living relative, the wolf can achieve this performance. In Study 1, we compared wolf and dog pups hand-reared individually and pet dogs of the same age in their readiness to form eye-contact with a human experimenter in an object-choice task and to follow her pointing gesture. The results showed that dogs already at 4 months of age use momentary distal pointing to find hidden food even without intensive early socialization. Wolf pups, on the contrary, do not attend to this subtle pointing. Accordingly in Studies 2 and 3, these wolves were tested longitudinally with this and four other (easier) human-given cues. This revealed that wolves socialized at a comparable level to dogs are able to use simple human-given cues spontaneously if the human's hand is close to the baited container (e.g. touching, proximal pointing). Study 4 showed that wolves can follow also momentary distal pointing similarly to dogs if they have received extensive formal training. Comparing the wolves to naïve pet dogs of the same age revealed that during several months of formal training wolves can reach the level of dogs in their success of following momentary distal pointing in parallel with improving their readiness to form eye-contact with a human experimenter. We assume that the high variability in the wolves' communicative behaviour might have provided a basis for selection during the course of domestication of the dog.

Systematic analysis of video data from different human-robot interaction studies: a categorization of social signals during error situations.

PubMed

Giuliani, Manuel; Mirnig, Nicole; Stollnberger, Gerald; Stadler, Susanne; Buchner, Roland; Tscheligi, Manfred

2015-01-01

Human-robot interactions are often affected by error situations that are caused by either the robot or the human. Therefore, robots would profit from the ability to recognize when error situations occur. We investigated the verbal and non-verbal social signals that humans show when error situations occur in human-robot interaction experiments. For that, we analyzed 201 videos of five human-robot interaction user studies with varying tasks from four independent projects. The analysis shows that there are two types of error situations: social norm violations and technical failures. Social norm violations are situations in which the robot does not adhere to the underlying social script of the interaction. Technical failures are caused by technical shortcomings of the robot. The results of the video analysis show that the study participants use many head movements and very few gestures, but they often smile, when in an error situation with the robot. Another result is that the participants sometimes stop moving at the beginning of error situations. We also found that the participants talked more in the case of social norm violations and less during technical failures. Finally, the participants use fewer non-verbal social signals (for example smiling, nodding, and head shaking), when they are interacting with the robot alone and no experimenter or other human is present. The results suggest that participants do not see the robot as a social interaction partner with comparable communication skills. Our findings have implications for builders and evaluators of human-robot interaction systems. The builders need to consider including modules for recognition and classification of head movements to the robot input channels. The evaluators need to make sure that the presence of an experimenter does not skew the results of their user studies.

Experimental Quasi-Microwave Whole-Body Averaged SAR Estimation Method Using Cylindrical-External Field Scanning

NASA Astrophysics Data System (ADS)

Kawamura, Yoshifumi; Hikage, Takashi; Nojima, Toshio

The aim of this study is to develop a new whole-body averaged specific absorption rate (SAR) estimation method based on the external-cylindrical field scanning technique. This technique is adopted with the goal of simplifying the dosimetry estimation of human phantoms that have different postures or sizes. An experimental scaled model system is constructed. In order to examine the validity of the proposed method for realistic human models, we discuss the pros and cons of measurements and numerical analyses based on the finite-difference time-domain (FDTD) method. We consider the anatomical European human phantoms and plane-wave in the 2GHz mobile phone frequency band. The measured whole-body averaged SAR results obtained by the proposed method are compared with the results of the FDTD analyses.

Human motor unit recordings: origins and insight into the integrated motor system.

PubMed

Duchateau, Jacques; Enoka, Roger M

2011-08-29

Soon after Edward Liddell [1895-1981] and Charles Sherrington [1857-1952] introduced the concept of a motor unit in 1925 and the necessary technology was developed, the recording of single motor unit activity became feasible in humans. It was quickly discovered by Edgar Adrian [1889-1977] and Detlev Bronk [1897-1975] that the force exerted by muscle during voluntary contractions was the result of the concurrent recruitment of motor units and modulation of the rate at which they discharged action potentials. Subsequent studies found that the relation between discharge frequency and motor unit force was characterized by a sigmoidal function. Based on observations on experimental animals, Elwood Henneman [1915-1996] proposed a "size principle" in 1957 and most studies in humans focussed on validating this concept during various types of muscle contractions. By the end of the 20th C, the experimental evidence indicated that the recruitment order of human motor units was determined primarily by motoneuron size and that the occasional changes in recruitment order were not an intended strategy of the central nervous system. Fundamental knowledge on the function of Sherrington's "common final pathway" was expanded with observations on motor unit rotation, minimal and maximal discharge rates, discharge variability, and self-sustained firing. Despite the great amount of work on characterizing motor unit activity during the first century of inquiry, however, many basic questions remain unanswered and these limit the extent to which findings on humans and experimental animals can be integrated and generalized to all movements. 2011 Elsevier B.V. All rights reserved.

A Tool for Investigating Asthma and COPD Exacerbations: A Newly Manufactured and Well Characterised GMP Wild-Type Human Rhinovirus for Use in the Human Viral Challenge Model

PubMed Central

Fullen, Daniel J.; Murray, Bryan; Mori, Julie; Catchpole, Andrew; Borley, Daryl W.; Murray, Edward J.; Balaratnam, Ganesh; Gilbert, Anthony; Mann, Alex; Hughes, Fiona; Lambkin-Williams, Rob

2016-01-01

Background Human Rhinovirus infection is an important precursor to asthma and chronic obstructive pulmonary disease exacerbations and the Human Viral Challenge model may provide a powerful tool in studying these and other chronic respiratory diseases. In this study we have reported the production and human characterisation of a new Wild-Type HRV-16 challenge virus produced specifically for this purpose. Methods and Stock Development A HRV-16 isolate from an 18 year old experimentally infected healthy female volunteer (University of Virginia Children’s Hospital, USA) was obtained with appropriate medical history and consent. We manufactured a new HRV-16 stock by minimal passage in a WI-38 cell line under Good Manufacturing Practice conditions. Having first subjected the stock to rigorous adventitious agent testing and determining the virus suitability for human use, we conducted an initial safety and pathogenicity clinical study in adult volunteers in our dedicated clinical quarantine facility in London. Human Challenge and Conclusions In this study we have demonstrated the new Wild-Type HRV-16 Challenge Virus to be both safe and pathogenic, causing an appropriate level of disease in experimentally inoculated healthy adult volunteers. Furthermore, by inoculating volunteers with a range of different inoculum titres, we have established the minimum inoculum titre required to achieve reproducible disease. We have demonstrated that although inoculation titres as low as 1 TCID50 can produce relatively high infection rates, the optimal titre for progression with future HRV challenge model development with this virus stock was 10 TCID50. Studies currently underway are evaluating the use of this virus as a challenge agent in asthmatics. Trial Registration ClinicalTrials.gov NCT02522832 PMID:27936016

Thermodynamic Modeling and Analysis of Human Stress Response

NASA Technical Reports Server (NTRS)

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

1999-01-01

A novel approach based on the second law of thermodynamics is developed to investigate the psychophysiology and quantify human stress level. Two types of stresses (thermal and mental) are examined. A Unified Stress Response Theory (USRT) is developed under the new proposed field of study called Engineering Psychophysiology. The USRT is used to investigate both thermal and mental stresses from a holistic (human body as a whole) and thermodynamic viewpoint. The original concepts and definitions are established as postulates which form the basis for thermodynamic approach to quantify human stress level. An Objective Thermal Stress Index (OTSI) is developed by applying the second law of thermodynamics to the human thermal system to quantify thermal stress or dis- comfort in the human body. The human thermal model based on finite element method is implemented. It is utilized as a "Computational Environmental Chamber" to conduct series of simulations to examine the human thermal stress responses under different environmental conditions. An innovative hybrid technique is developed to analyze human thermal behavior based on series of human-environment interaction simulations. Continuous monitoring of thermal stress is demonstrated with the help of OTSI. It is well established that the human thermal system obeys the second law of thermodynamics. Further, the OTSI is validated against the experimental data. Regarding mental stress, an Objective Mental Stress Index (OMSI) is developed by applying the Maxwell relations of thermodynamics to the combined thermal and cardiovascular system in the human body. The OMSI is utilized to demonstrate the technique of monitoring mental stress continuously and is validated with the help of series of experimental studies. Although the OMSI indicates the level of mental stress, it provides a strong thermodynamic and mathematical relationship between activities of thermal and cardiovascular systems of the human body.

Neurophysiologic measures of auditory function in fish consumers: associations with long chain polyunsaturated fatty acids and methylmercury.

PubMed

Dziorny, Adam C; Orlando, Mark S; Strain, J J; Davidson, Philip W; Myers, Gary J

2013-09-01

Determining if associations exist between child neurodevelopment and environmental exposures, especially low level or background ones, is challenging and dependent upon being able to measure specific and sensitive endpoints. Psychometric or behavioral measures of CNS function have traditionally been used in such studies, but do have some limitations. Auditory neurophysiologic measures examine different nervous system structures and mechanisms, have fewer limitations, can more easily be quantified, and might be helpful additions to testing. To date, their use in human epidemiological studies has been limited. We reviewed the use of auditory brainstem responses (ABR) and otoacoustic emissions (OAE) in studies designed to determine the relationship of exposures to methyl mercury (MeHg) and nutrients from fish consumption with neurological development. We included studies of experimental animals and humans in an effort to better understand the possible benefits and risks of fish consumption. We reviewed the literature on the use of ABR and OAE to measure associations with environmental exposures that result from consuming a diet high in fish. We focused specifically on long chain polyunsaturated fatty acids (LCPUFA) and MeHg. We performed a comprehensive review of relevant studies using web-based search tools and appropriate search terms. Gestational exposure to both LCPUFA and MeHg has been reported to influence the developing auditory system. In experimental studies supplemental LCPUFA is reported to prolong ABR latencies and human studies also suggest an association. Experimental studies of acute and gestational MeHg exposure are reported to prolong ABR latencies and impair hair cell function. In humans, MeHg exposure is reported to prolong ABR latencies, but the impact on hair cell function is unknown. The auditory system can provide objective measures and may be useful in studying exposures to nutrients and toxicants and whether they are associated with children's neurodevelopment. Copyright © 2012 Elsevier Inc. All rights reserved.

Drosophila as a screening tool to study human neurodegenerative diseases.

PubMed

Lenz, Sarah; Karsten, Peter; Schulz, Jörg B; Voigt, Aaron

2013-11-01

In an aging society, research involving neurodegenerative disorders is of paramount importance. Over the past few years, research on Alzheimer's and Parkinson's diseases has made tremendous progress. Experimental studies, however, rely mostly on transgenic animal models, preferentially using mice. Although experiments on mice have enormous advantages, they also have some inherent limitations, some of which can be overcome by the use of Drosophila melanogaster as an experimental animal. Among the major advantages of using the fly is its small genome, which can also be modified very easily. The fact that its genome lends itself to diverse alterations (e. g. mutagenesis, transposons) has made the fly a useful organism to perform large-scale and genome-wide screening approaches. This has opened up an entirely new field of experimental research aiming to elucidate genetic interactions and screen for modifiers of disease processes in vivo. Here, we provide a brief overview of how flies can be used to analyze molecular mechanisms underlying human neurodegenerative diseases. © 2013 International Society for Neurochemistry.

Collective movements of pedestrians: How we can learn from simple experiments with non-human (ant) crowds

PubMed Central

Sarvi, Majid

2017-01-01

Introduction Understanding collective behavior of moving organisms and how interactions between individuals govern their collective motion has triggered a growing number of studies. Similarities have been observed between the scale-free behavioral aspects of various systems (i.e. groups of fish, ants, and mammals). Investigation of such connections between the collective motion of non-human organisms and that of humans however, has been relatively scarce. The problem demands for particular attention in the context of emergency escape motion for which innovative experimentation with panicking ants has been recently employed as a relatively inexpensive and non-invasive approach. However, little empirical evidence has been provided as to the relevance and reliability of this approach as a model of human behaviour. Methods This study explores pioneer experiments of emergency escape to tackle this question and to connect two forms of experimental observations that investigate the collective movement at macroscopic level. A large number of experiments with human and panicking ants are conducted representing the escape behavior of these systems in crowded spaces. The experiments share similar architectural structures in which two streams of crowd flow merge with one another. Measures such as discharge flow rates and the probability distribution of passage headways are extracted and compared between the two systems. Findings Our findings displayed an unexpected degree of similarity between the collective patterns emerged from both observation types, particularly based on aggregate measures. Experiments with ants and humans commonly indicated how significantly the efficiency of motion and the rate of discharge depend on the architectural design of the movement environment. Practical applications Our findings contribute to the accumulation of evidence needed to identify the boarders of applicability of experimentation with crowds of non-human entities as models of human collective motion as well as the level of measurements (i.e. macroscopic or microscopic) and the type of contexts at which reliable inferences can be drawn. This particularly has implications in the context of experimenting evacuation behaviour for which recruiting human subjects may face ethical restrictions. The findings, at minimum, offer promise as to the potential benefit of piloting such experiments with non-human crowds, thereby forming better-informed hypotheses. PMID:28854221

Collective movements of pedestrians: How we can learn from simple experiments with non-human (ant) crowds.

PubMed

Shahhoseini, Zahra; Sarvi, Majid

2017-01-01

Understanding collective behavior of moving organisms and how interactions between individuals govern their collective motion has triggered a growing number of studies. Similarities have been observed between the scale-free behavioral aspects of various systems (i.e. groups of fish, ants, and mammals). Investigation of such connections between the collective motion of non-human organisms and that of humans however, has been relatively scarce. The problem demands for particular attention in the context of emergency escape motion for which innovative experimentation with panicking ants has been recently employed as a relatively inexpensive and non-invasive approach. However, little empirical evidence has been provided as to the relevance and reliability of this approach as a model of human behaviour. This study explores pioneer experiments of emergency escape to tackle this question and to connect two forms of experimental observations that investigate the collective movement at macroscopic level. A large number of experiments with human and panicking ants are conducted representing the escape behavior of these systems in crowded spaces. The experiments share similar architectural structures in which two streams of crowd flow merge with one another. Measures such as discharge flow rates and the probability distribution of passage headways are extracted and compared between the two systems. Our findings displayed an unexpected degree of similarity between the collective patterns emerged from both observation types, particularly based on aggregate measures. Experiments with ants and humans commonly indicated how significantly the efficiency of motion and the rate of discharge depend on the architectural design of the movement environment. Our findings contribute to the accumulation of evidence needed to identify the boarders of applicability of experimentation with crowds of non-human entities as models of human collective motion as well as the level of measurements (i.e. macroscopic or microscopic) and the type of contexts at which reliable inferences can be drawn. This particularly has implications in the context of experimenting evacuation behaviour for which recruiting human subjects may face ethical restrictions. The findings, at minimum, offer promise as to the potential benefit of piloting such experiments with non-human crowds, thereby forming better-informed hypotheses.

Recent mouse and rat methods for the study of experimental oral candidiasis

PubMed Central

Costa, Anna CBP; Pereira, Cristiane A; Junqueira, Juliana C; Jorge, Antonio OC

2013-01-01

The Candida genus expresses virulence factors that, when combined with immunosuppression and other risk factors, can cause different manifestations of oral candidiasis. The treatment of mucosal infections caused by Candida and the elucidation of the disease process have proven challenging. Therefore, the study of experimentally induced oral candidiasis in rats and mice is useful to clarify the etiopathology of this condition, improve diagnosis, and search for new therapeutic options because the disease process in these animals is similar to that of human candidiasis lesions. Here, we describe and discuss new studies involving rat and mouse models of oral candidiasis with respect to methods for inducing experimental infection, methods for evaluating the development of experimental candidiasis, and new treatment strategies for oral candidiasis. PMID:23715031

Using Empowering Processes to Create Empowered Outcomes through the Family Development Credential Program: An Empirical Study of Change in Human Service Workers

ERIC Educational Resources Information Center

Hewitt, Nicole M.

2010-01-01

This study employed a quasi-experimental non-equivalent control group design with pretest and posttest. Two waves of data were collected from a non-random sample of 180 human service professionals in Western and Central Pennsylvania using two research instruments: the Social Work Empowerment Scale and the Conditions of Work Effectiveness-II Scale.…

Investigating the Awareness and Knowledge of Secondary School Students about the Effects of Allergic Pollen on Human Health: A Case of Burdur Province

ERIC Educational Resources Information Center

Tuzlak, Kadir

2016-01-01

The overall objective of this study is to increase the awareness of secondary school students of the effects of pollen allergy on human health by mapping allergic pollens appearing in Burdur atmosphere. This study is a pre-test and post-test experimental design. Mix method is applied thus. Both qualitative and quantitative data are gathered. The…

Gut microbiomes and their metabolites shape human and animal health.

PubMed

Park, Woojun

2018-03-01

The host genetic background, complex surrounding environments, and gut microbiome are very closely linked to human and animal health and disease. Although significant correlations between gut microbiota and human and animal health have been revealed, the specific roles of each gut bacterium in shaping human and animal health and disease remain unclear. However, recent omics-based studies using experimental animals and surveys of gut microbiota from unhealthy humans have provided insights into the relationships among microbial community, their metabolites, and human and animal health. This editorial introduces six review papers that provide new discoveries of disease-associated microbiomes and suggest possible microbiome-based therapeutic approaches to human disease.

Helping Survivors of Human Trafficking: A Systematic Review of Exit and Postexit Interventions.

PubMed

Dell, Nathaniel A; Maynard, Brandy R; Born, Kara R; Wagner, Elizabeth; Atkins, Bonnie; House, Whitney

2017-01-01

Human trafficking is a global problem and results in deleterious psychological, social, and physical effects on the lives of those who are trafficked; however, it is not clear how to best intervene with survivors. The purpose of this review was to synthesize the evidence of exit and postexit intervention programs for survivors of human trafficking to inform practice and research. Systematic review methods were used to search, select, and extract data from published and unpublished experimental, quasi-experimental, and preexperimental studies that assessed the effects of any exit or postexit interventions for victims of human trafficking. The authors searched eight databases, reviewed bibliographies, and conducted forward citation searches from relevant reports and prior reviews to find studies authored between 2005 and 2015. The search yielded six eligible studies that included 155 female and 6 male survivors from four countries. Interventions were diverse, with three using a trauma-informed approach. Authors measured a myriad of outcomes, including mental health, social network, community reintegration, and employment; however, the quality of most studies was poor. Evidence of effects of exit and postexit interventions is sparse, and much of the research is poorly designed and executed; however, the needs of trafficking survivors are complex and effective interventions are desperately needed. Implications for practice and research are discussed.

Extending the boundaries of the Declaration of Helsinki: a case study of an unethical experiment in a non-medical setting

PubMed Central

Richter, E.; Barach, P.; Berman, T.; Ben-David, G; Weinberger, Z.

2001-01-01

To examine the ethical issues involved in governmental decisions with potential health risks, we review the history of the decision to raise the interurban speed limit in Israel in light of its impact on road death and injury. In 1993, the Israeli Ministry of Transportation initiated an "experiment" to raise the interurban speed limit from 90 to 100 kph. The "experiment" did not include a protocol and did not specify cut-off points for early termination in the case of adverse results. After the raise in the speed limit, the death toll on interurban roads rose as a result of a sudden increase in speeds and case fatality rates. The committee's decision is a case study in unfettered human experimentation and public health risks when the setting is non-medical and lacks a defined ethical framework. The case study states the case for extending Helsinki type safeguards to experimentation in non-medical settings. Key Words: Declaration of Helsinki • human experimentation • speed limit PMID:11314157

Modelling Human Regulatory Variation in Mouse: Finding the Function in Genome-Wide Association Studies and Whole-Genome Sequencing

PubMed Central

Schmouth, Jean-François; Bonaguro, Russell J.; Corso-Diaz, Ximena; Simpson, Elizabeth M.

2012-01-01

An increasing body of literature from genome-wide association studies and human whole-genome sequencing highlights the identification of large numbers of candidate regulatory variants of potential therapeutic interest in numerous diseases. Our relatively poor understanding of the functions of non-coding genomic sequence, and the slow and laborious process of experimental validation of the functional significance of human regulatory variants, limits our ability to fully benefit from this information in our efforts to comprehend human disease. Humanized mouse models (HuMMs), in which human genes are introduced into the mouse, suggest an approach to this problem. In the past, HuMMs have been used successfully to study human disease variants; e.g., the complex genetic condition arising from Down syndrome, common monogenic disorders such as Huntington disease and β-thalassemia, and cancer susceptibility genes such as BRCA1. In this commentary, we highlight a novel method for high-throughput single-copy site-specific generation of HuMMs entitled High-throughput Human Genes on the X Chromosome (HuGX). This method can be applied to most human genes for which a bacterial artificial chromosome (BAC) construct can be derived and a mouse-null allele exists. This strategy comprises (1) the use of recombineering technology to create a human variant–harbouring BAC, (2) knock-in of this BAC into the mouse genome using Hprt docking technology, and (3) allele comparison by interspecies complementation. We demonstrate the throughput of the HuGX method by generating a series of seven different alleles for the human NR2E1 gene at Hprt. In future challenges, we consider the current limitations of experimental approaches and call for a concerted effort by the genetics community, for both human and mouse, to solve the challenge of the functional analysis of human regulatory variation. PMID:22396661

What experimental experience affects dogs' comprehension of human communicative actions?

PubMed

Hauser, Marc D; Comins, Jordan A; Pytka, Lisa M; Cahill, Donal P; Velez-Calderon, Sofia

2011-01-01

Studies of dogs report that individuals reliably respond to the goal-directed communicative actions (e.g., pointing) of human experimenters. All of these studies use some version of a multi-trial approach, thereby allowing for the possibility of rapid learning within an experimental session. The experiments reported here ask whether dogs can respond correctly to a communicative action based on only a single presentation, thereby eliminating the possibility of learning within the experimental context. We tested 173 dogs. For each dog reaching our test criteria, we used a single presentation of six different goal-directed actions within a session, asking whether they correctly follow to a target goal (container with concealed food) a (1) distal hand point, (2) step toward one container, (3) hand point to one container followed by step toward the other, (4) step toward one container and point to the other, (5) distal foot point with the experimenter's hands free, and (6) distal foot point with the experimenter's hands occupied. Given only a single presentation, dogs selected the correct container when the experimenter hand pointed, foot pointed with hands occupied, or stepped closer to the target container, but failed on the other actions, despite using the same method. The fact that dogs correctly followed foot pointing with hands occupied, but not hands free, suggests that they are sensitive to environmental constraints, and use this information to infer rational, goal-directed action. We discuss these results in light of the role of experience in recognizing communicative gestures, as well as the significance of coding criteria for studies of canine competence. Copyright © 2010 Elsevier B.V. All rights reserved.

[Contribution of animal experimentation to pharmacology].

PubMed

Sassard, Jean; Hamon, Michel; Galibert, Francis

2009-11-01

Animal experimentation is of considerable importance in pharmacology and cannot yet be avoided when studying complex, highly integrated physiological functions. The use of animals has been drastically reduced in the classical phases of pharmacological research, for example when comparing several compounds belonging to the same pharmacological class. However, animal experiments remain crucial for generating and validating new therapeutic concepts. Three examples of such research, conducted in strict ethical conditions, will be used to illustrate the different ways in which animal experimentation has contributed to human therapeutics.

Experimental endometriosis: the nude mouse as a xenographic host.

PubMed

Bruner-Tran, Kaylon L; Webster-Clair, Deborah; Osteen, Kevin G

2002-03-01

Endometriosis is a complex disease that can develop as a consequence of retrograde menstruation, occurring in association with the cyclic loss of endometrial tissue in primates and humans. In addition, progression of disease parallels a woman's exposure to ovarian steroids, rarely occurring prior to menarche and generally resolving following menopause. Because of the cost of developing primate models to study endometriosis, numerous small animal models have been established to approach various elements related to the pathophysiology of this disease. Our laboratory has developed an experimental endometriosis model using nude mice as a xenographic host for human tissues. Our goal is to approach the basic cellular mechanisms of estrogen and progesterone action that link these hormones to the development or prevention of endometriosis. In our initial studies, we have sought to understand steroid-associated regulation of matrix metalloproteinases (MMPs) with regard to the development of experimental endometriosis. Using both short-term organ cultures and nude mice as xenographic hosts of human tissue, we have demonstrated a critical role of progesterone and progesterone-associated cytokines in preventing the initial establishment of experimental disease. Women with endometriosis appear to lack normal endometrial responsiveness to progesterone, resulting in altered expression of several MMPs and an enhanced ability of these tissues to establish ectopic lesions in nude mice. Developing a better understanding of the impairments in the normal endometrial physiology of women with endometriosis should aid in the development of better treatment or diagnostic strategies.

Population and clinical genetics of human transposable elements in the (post) genomic era

PubMed Central

Rishishwar, Lavanya; Wang, Lu; Clayton, Evan A.; Mariño-Ramírez, Leonardo; McDonald, John F.; Jordan, I. King

2017-01-01

ABSTRACT Recent technological developments—in genomics, bioinformatics and high-throughput experimental techniques—are providing opportunities to study ongoing human transposable element (TE) activity at an unprecedented level of detail. It is now possible to characterize genome-wide collections of TE insertion sites for multiple human individuals, within and between populations, and for a variety of tissue types. Comparison of TE insertion site profiles between individuals captures the germline activity of TEs and reveals insertion site variants that segregate as polymorphisms among human populations, whereas comparison among tissue types ascertains somatic TE activity that generates cellular heterogeneity. In this review, we provide an overview of these new technologies and explore their implications for population and clinical genetic studies of human TEs. We cover both recent published results on human TE insertion activity as well as the prospects for future TE studies related to human evolution and health. PMID:28228978

Optimal control model predictions of system performance and attention allocation and their experimental validation in a display design study

NASA Technical Reports Server (NTRS)

Johannsen, G.; Govindaraj, T.

1980-01-01

The influence of different types of predictor displays in a longitudinal vertical takeoff and landing (VTOL) hover task is analyzed in a theoretical study. Several cases with differing amounts of predictive and rate information are compared. The optimal control model of the human operator is used to estimate human and system performance in terms of root-mean-square (rms) values and to compute optimized attention allocation. The only part of the model which is varied to predict these data is the observation matrix. Typical cases are selected for a subsequent experimental validation. The rms values as well as eye-movement data are recorded. The results agree favorably with those of the theoretical study in terms of relative differences. Better matching is achieved by revised model input data.

Pressure Dynamic Characteristics of Pressure Controlled Ventilation System of a Lung Simulator

PubMed Central

Shi, Yan; Ren, Shuai; Cai, Maolin; Xu, Weiqing; Deng, Qiyou

2014-01-01

Mechanical ventilation is an important life support treatment of critically ill patients, and air pressure dynamics of human lung affect ventilation treatment effects. In this paper, in order to obtain the influences of seven key parameters of mechanical ventilation system on the pressure dynamics of human lung, firstly, mechanical ventilation system was considered as a pure pneumatic system, and then its mathematical model was set up. Furthermore, to verify the mathematical model, a prototype mechanical ventilation system of a lung simulator was proposed for experimental study. Last, simulation and experimental studies on the air flow dynamic of the mechanical ventilation system were done, and then the pressure dynamic characteristics of the mechanical system were obtained. The study can be referred to in the pulmonary diagnostics, treatment, and design of various medical devices or diagnostic systems. PMID:25197318

Weight-of-evidence evaluation of short-term ozone exposure and cardiovascular effects.

PubMed

Goodman, Julie E; Prueitt, Robyn L; Sax, Sonja N; Lynch, Heather N; Zu, Ke; Lemay, Julie C; King, Joseph M; Venditti, Ferdinand J

2014-10-01

There is a relatively large body of research on the potential cardiovascular (CV) effects associated with short-term ozone exposure (defined by EPA as less than 30 days in duration). We conducted a weight-of-evidence (WoE) analysis to assess whether it supports a causal relationship using a novel WoE framework adapted from the US EPA's National Ambient Air Quality Standards causality framework. Specifically, we synthesized and critically evaluated the relevant epidemiology, controlled human exposure, and experimental animal data and made a causal determination using the same categories proposed by the Institute of Medicine report Improving the Presumptive Disability Decision-making Process for Veterans ( IOM 2008). We found that the totality of the data indicates that the results for CV effects are largely null across human and experimental animal studies. The few statistically significant associations reported in epidemiology studies of CV morbidity and mortality are very small in magnitude and likely attributable to confounding, bias, or chance. In experimental animal studies, the reported statistically significant effects at high exposures are not observed at lower exposures and thus not likely relevant to current ambient ozone exposures in humans. The available data also do not support a biologically plausible mechanism for CV effects of ozone. Overall, the current WoE provides no convincing case for a causal relationship between short-term exposure to ambient ozone and adverse effects on the CV system in humans, but the limitations of the available studies preclude definitive conclusions regarding a lack of causation. Thus, we categorize the strength of evidence for a causal relationship between short-term exposure to ozone and CV effects as "below equipoise."

Identification of stable reference genes in differentiating human pluripotent stem cells.

PubMed

Holmgren, Gustav; Ghosheh, Nidal; Zeng, Xianmin; Bogestål, Yalda; Sartipy, Peter; Synnergren, Jane

2015-06-01

Reference genes, often referred to as housekeeping genes (HKGs), are frequently used to normalize gene expression data based on the assumption that they are expressed at a constant level in the cells. However, several studies have shown that there may be a large variability in the gene expression levels of HKGs in various cell types. In a previous study, employing human embryonic stem cells (hESCs) subjected to spontaneous differentiation, we observed that the expression of commonly used HKG varied to a degree that rendered them inappropriate to use as reference genes under those experimental settings. Here we present a substantially extended study of the HKG signature in human pluripotent stem cells (hPSC), including nine global gene expression datasets from both hESC and human induced pluripotent stem cells, obtained during directed differentiation toward endoderm-, mesoderm-, and ectoderm derivatives. Sets of stably expressed genes were compiled, and a handful of genes (e.g., EID2, ZNF324B, CAPN10, and RABEP2) were identified as generally applicable reference genes in hPSCs across all cell lines and experimental conditions. The stability in gene expression profiles was confirmed by reverse transcription quantitative PCR analysis. Taken together, the current results suggest that differentiating hPSCs have a distinct HKG signature, which in some aspects is different from somatic cell types, and underscore the necessity to validate the stability of reference genes under the actual experimental setup used. In addition, the novel putative HKGs identified in this study can preferentially be used for normalization of gene expression data obtained from differentiating hPSCs. Copyright © 2015 the American Physiological Society.

Human factors requirements for telerobotic command and control: The European Space Agency experimental programme

NASA Technical Reports Server (NTRS)

Stone, Robert J.

1991-01-01

Space Telerobotics research, performed under contract to the European Space Agency (ESA), concerning the execution of human factors experiments, and ultimately leading to the development of a telerobotics test bed, has been carried out since 1985 by a British Consortium consisting of British Aerospace, the United Kingdom Atomic Energy Authority and, more recently, the UK National Advanced Robotics Research Centre. The principal aim of the first study of the series was to derive preliminary requirements for a teleoperation servicing system, with reference to two mission model scenarios. The first scenario introduced the problem of communications time delays, and their likely effect on the ground-based operator in control of a manipulator system on board an unmanned servicing vehicle in Low Earth Orbit. In the second scenario, the operator was located on the NASA Orbiter aft flight deck, supervising the control of a prototype manipulator in the 'servicing' of an experimental payload in the cargo bay area. Human factors analyses centered on defining the requirements for the teleoperator workstation, such as identifying basic ergonomic requirements for workstation and panel layouts, defining teleoperation strategies, developing alphanumeric and graphic screen formats for the supervision or direct control of the manipulator, and the potential applications of expert system technology. The second study for ESA involved an experimental appraisal of some of the important issues highlighted in the first study, for which relevant human factors data did not exist. Of central importance during the second study was the issue of communications time delays and their effect on the manual control of a teleoperated manipulator from a ground-based command and control station.

BioQ: tracing experimental origins in public genomic databases using a novel data provenance model

PubMed Central

Saccone, Scott F.; Quan, Jiaxi; Jones, Peter L.

2012-01-01

Motivation: Public genomic databases, which are often used to guide genetic studies of human disease, are now being applied to genomic medicine through in silico integrative genomics. These databases, however, often lack tools for systematically determining the experimental origins of the data. Results: We introduce a new data provenance model that we have implemented in a public web application, BioQ, for assessing the reliability of the data by systematically tracing its experimental origins to the original subjects and biologics. BioQ allows investigators to both visualize data provenance as well as explore individual elements of experimental process flow using precise tools for detailed data exploration and documentation. It includes a number of human genetic variation databases such as the HapMap and 1000 Genomes projects. Availability and implementation: BioQ is freely available to the public at http://bioq.saclab.net Contact: ssaccone@wustl.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:22426342

Methodological quality of quantitative lesbian, gay, bisexual, and transgender nursing research from 2000 to 2010.

PubMed

Johnson, Michael; Smyer, Tish; Yucha, Carolyn

2012-01-01

The purpose of this study was to evaluate the methodological quality of quantitative lesbian, gay, bisexual, and transgender nursing research from 2000 to 2010. Using a key word search in Cumulative Index to Nursing and Allied Health Literature, 188 studies were identified and 40 met the criteria, which included descriptive, experimental, quasi-experimental, or observational (case control, cohort, and cross-sectional) design. The methodological quality of these studies was similar to that reported for medical and nursing educational research. The foci of these lesbian, gay, bisexual, and transgender studies were biased toward human immunodeficiency virus, acquired immunodeficiency syndrome, and sexually transmitted diseases, and 58.5% of the funded research was related to human immunodeficiency virus or acquired immunodeficiency syndrome. To provide evidence-based health care to these populations, an understanding of the current state of research is crucial.

Antitumor Efficacy Testing in Rodents

PubMed Central

2008-01-01

The preclinical research and human clinical trials necessary for developing anticancer therapeutics are costly. One contributor to these costs is preclinical rodent efficacy studies, which, in addition to the costs associated with conducting them, often guide the selection of agents for clinical development. If inappropriate or inaccurate recommendations are made on the basis of these preclinical studies, then additional costs are incurred. In this commentary, I discuss the issues associated with preclinical rodent efficacy studies. These include the identification of proper preclinical efficacy models, the selection of appropriate experimental endpoints, and the correct statistical evaluation of the resulting data. I also describe important experimental design considerations, such as selecting the drug vehicle, optimizing the therapeutic treatment plan, properly powering the experiment by defining appropriate numbers of replicates in each treatment arm, and proper randomization. Improved preclinical selection criteria can aid in reducing unnecessary human studies, thus reducing the overall costs of anticancer drug development. PMID:18957675

Human body shape index based on an experimentally derived model of human growth.

PubMed

Lebiedowska, Maria K; Alter, Katharine E; Stanhope, Steven J

2008-01-01

To test the assumption of geometrically similar growth by developing experimentally derived models of human body growth during the age interval of 5 to 18 years; to use these derived growth models to establish a new human body shape index (HBSI) based on natural age-related changes in human body shape (HBS); and to compare various metrics of relative body weight (body mass index [BMI], ponderal index [PI], and HBSI) in a sample of 5- to 18-year-old children. Nondisabled Polish children (n = 847) participated in this descriptive study. To model growth, the best fit between body height (H) and body mass (M) was calculated for each sex using the allometric equation M = m(i) H(chi). HBSI was calculated separately for girls and boys, using sex-specific values for chi and a general HBSI from combined data. The customary BMI and PI were calculated and compared with HBSI values. The models of growth were M = 13.11H(2.84) (R2 = 0.90) for girls and M = 13.64H(2.68) (R2 = 0.91) for boys. HBSI values contained less inherent variability and were less influenced by growth (age and height) compared with BMI and PI. Age-related growth during childhood is sex-specific and not geometrically similar. Therefore, indices of HBS formulated from experimentally derived models of human growth are superior to customary geometric similarity-based indices for characterizing HBS in children during the formative growth years.

Effect of Abdominal Loading Location on Liver Motion: Experimental Assessment using Ultrafast Ultrasound Imaging and Simulation with a Human Body Model.

PubMed

Le Ruyet, Anicet; Berthet, Fabien; Rongiéras, Frédéric; Beillas, Philippe

2016-11-01

A protocol based on ultrafast ultrasound imaging was applied to study the in situ motion of the liver while the abdomen was subjected to compressive loading at 3 m/s by a hemispherical impactor or a seatbelt. The loading was applied to various locations between the lower abdomen and the mid thorax while feature points inside the liver were followed on the ultrasound movie (2000 frames per second). Based on tests performed on five post mortem human surrogates (including four tested in the current study), trends were found between the loading location and feature point trajectory parameters such as the initial angle of motion or the peak displacement in the direction of impact. The impactor tests were then simulated using the GHBMC M50 human body model that was globally scaled to the dimensions of each surrogate. Some of the experimental trends observed could be reproduced in the simulations (e.g. initial angle) while others differed more widely (e.g. final caudal motion). The causes for the discrepancies need to be further investigated. The liver strain energy density predicted by the model was also widely affected by the impact location. Experimental and simulation results both highlight the importance of the liver position with respect to the impactor when studying its response in situ.

Experimental metagenomics and ribosomal profiling of the human skin microbiome.

PubMed

Ferretti, Pamela; Farina, Stefania; Cristofolini, Mario; Girolomoni, Giampiero; Tett, Adrian; Segata, Nicola

2017-03-01

The skin is the largest organ in the human body, and it is populated by a large diversity of microbes, most of which are co-evolved with the host and live in symbiotic harmony. There is increasing evidence that the skin microbiome plays a crucial role in the defense against pathogens, immune system training and homoeostasis, and microbiome perturbations have been associated with pathological skin conditions. Studying the skin resident microbial community is thus essential to better understand the microbiome-host crosstalk and to associate its specific configurations with cutaneous diseases. Several community profiling approaches have proved successful in unravelling the composition of the skin microbiome and overcome the limitations of cultivation-based assays, but these tools remain largely inaccessible to the clinical and medical dermatology communities. The study of the skin microbiome is also characterized by specific technical challenges, such as the low amount of microbial biomass and the extensive human DNA contamination. Here, we review the available community profiling approaches to study the skin microbiome, specifically focusing on the practical experimental and analytical tools necessary to generate and analyse skin microbiome data. We describe all the steps from the initial samples collection to the final data interpretation, with the goal of enabling clinicians and researchers who are not familiar with the microbiome field to perform skin profiling experiments. © 2016 The Authors. Experimental Dermatology Published by John Wiley & Sons Ltd.

Study on contraction and relaxation of experimentally denervated and immobilized muscles: Comparison with dystrophic muscles

NASA Technical Reports Server (NTRS)

Takamori, M.; Tsujihata, M.; Mori, M.; Hazama, R.; Ide, Y.

1980-01-01

The contraction-relaxation mechanism of experimentally denervated and immobilized muscles of the rabbit is examined. Results are compared with those of human dystrophic muscles, in order to elucidate the role and extent of the neurotrophic factor, and the role played by the intrinsic activity of muscle in connection with pathogenesis and pathophysiology of this disease.

Prison Education and Rehabilitation: Illusion or Reality? A Case Study of an Experimental Program.

ERIC Educational Resources Information Center

Lewis, Morgan V.; And Others

A review of the literature, covering a variety of theories as to the causes of criminal behavior in young people and barriers to their rehabilitation, lays the groundwork for a report of an experimental program using the humanities to assist in the rehabilitation of young criminal offenders, at the State Correctional Institution at Camp Hill, Pa.…

Probing the inhibitory potency of epigallocatechin gallate against human γB-crystallin aggregation: Spectroscopic, microscopic and simulation studies

NASA Astrophysics Data System (ADS)

Chaudhury, Susmitnarayan; Dutta, Anirudha; Bag, Sudipta; Biswas, Pranandita; Das, Amit Kumar; Dasgupta, Swagata

2018-03-01

Aggregation of human ocular lens proteins, the crystallins is believed to be one of the key reasons for age-onset cataract. Previous studies have shown that human γD-crystallin forms amyloid like fibres under conditions of low pH and elevated temperature. In this article, we have investigated the aggregation propensity of human γB-crystallin in absence and presence of epigallocatechin gallate (EGCG), in vitro, when exposed to stressful conditions. We have used different spectroscopic and microscopic techniques to elucidate the inhibitory effect of EGCG towards aggregation. The experimental results have been substantiated by molecular dynamics simulation studies. We have shown that EGCG possesses inhibitory potency against the aggregation of human γB-crystallin at low pH and elevated temperature.

Experimental evaluation of a miniature MR device for a wide range of human perceivable haptic sensations

NASA Astrophysics Data System (ADS)

Yang, Tae-Heon; Koo, Jeong-Hoi

2017-12-01

Humans can experience a realistic and vivid haptic sensations by the sense of touch. In order to have a fully immersive haptic experience, both kinaesthetic and vibrotactile information must be presented to human users. Currently, little haptic research has been performed on small haptic actuators that can covey both vibrotactile feedback based on the frequency of vibrations up to the human-perceivable limit and multiple levels of kinaesthetic feedback rapidly. Therefore, this study intends to design a miniature haptic device based on MR fluid and experimentally evaluate its ability to convey vibrotactile feedback up to 300 Hz along with kinaesthetic feedback. After constructing a prototype device, a series of testing was performed to evaluate its performance of the prototype using an experimental setup, consisting of a precision dynamic mechanical analyzer and an accelerometer. The kinaesthetic testing results show that the prototype device can provide the force rate up to 89% at 5 V (360 mA), which can be discretized into multiple levels of ‘just noticeable difference’ force rate, indicating that the device can convey a wide range of kinaesthetic sensations. To evaluate the high frequency vibrotactile feedback performance of the device, its acceleration responses were measured and processed using the FFT analysis. The results indicate that the device can convey high frequency vibrotactile sensations up to 300 Hz with the sufficiently large intensity of accelerations that human can feel.

Experimental and natural infections in MyD88- and IRAK-4-deficient mice and humans

PubMed Central

von Bernuth, Horst; Picard, Capucine; Puel, Anne; Casanova, Jean-Laurent

2013-01-01

Most Toll-like-receptors (TLRs) and interleukin-1 receptors (IL-1Rs) signal via myeloid differentiation primary response 88 (MyD88) and interleukin-1 receptor-associated kinase 4 (IRAK-4). The combined roles of these two receptor families in the course of experimental infections have been assessed in MyD88- and IRAK-4-deficient mice for almost fifteen years. These animals have been shown to be susceptible to 46 pathogens: 27 bacteria, 8 viruses, 7 parasites, and 4 fungi. Humans with inborn MyD88 or IRAK-4 deficiency were first identified in 2003. They suffer from naturally occurring life-threatening infections caused by a small number of bacterial species, although the incidence and severity of these infections decrease with age. Mouse TLR- and IL-1R-dependent immunity mediated by MyD88 and IRAK-4 seems to be vital to combat a wide array of experimentally administered pathogens at most ages. By contrast, human TLR- and IL-1R-dependent immunity mediated by MyD88 and IRAK-4 seems to be effective in the natural setting against only a few bacteria and is most important in infancy and early childhood. The roles of TLRs and IL-1Rs in protective immunity deduced from studies in mutant mice subjected to experimental infections should therefore be reconsidered in the light of findings for natural infections in humans carrying mutations as discussed in this review. PMID:23255009

Intervention Research and Its Influence on Nonintervention Research in Human Resource Development

ERIC Educational Resources Information Center

Park, Sunyoung; Chae, Chungil

2017-01-01

Purpose: The purpose of this paper is to identify how intervention research weighed in nonintervention research in the field of human resource development (HRD) by examining the number, citation frequency and use of experimental studies in HRD academic journals. Design/methodology/approach: A total of 2,700 articles published between 1990 and 2014…

Gambling, games of skill and human ecology: a pilot study by a multidimensional analysis approach.

PubMed

Valera, Luca; Giuliani, Alessandro; Gizzi, Alessio; Tartaglia, Francesco; Tambone, Vittoradolfo

2015-01-01

The present pilot study aims at analyzing the human activity of playing in the light of an indicator of human ecology (HE). We highlighted the four essential anthropological dimensions (FEAD), starting from the analysis of questionnaires administered to actual gamers. The coherence between theoretical construct and observational data is a remarkable proof-of-concept of the possibility of establishing an experimentally motivated link between a philosophical construct (coming from Huizinga's Homo ludens definition) and actual gamers' motivation pattern. The starting hypothesis is that the activity of playing becomes ecological (and thus not harmful) when it achieves the harmony between the FEAD, thus realizing HE; conversely, it becomes at risk of creating some form of addiction, when destroying FEAD balance. We analyzed the data by means of variable clustering (oblique principal components) so to experimentally verify the existence of the hypothesized dimensions. The subsequent projection of statistical units (gamers) on the orthogonal space spanned by principal components allowed us to generate a meaningful, albeit preliminary, clusterization of gamer profiles.

Comparison of protocols for measuring and calculating postmortem submersion intervals for human analogs in fresh water.

PubMed

Humphreys, Michael K; Panacek, Edward; Green, William; Albers, Elizabeth

2013-03-01

Protocols for determining postmortem submersion interval (PMSI) have long been problematic for forensic investigators due to the wide variety of factors affecting the rate of decomposition of submerged carrion. Likewise, it has been equally problematic for researchers to develop standardized experimental protocols to monitor underwater decomposition without artificially affecting the decomposition rate. This study compares two experimental protocols: (i) underwater in situ evaluation with photographic documentation utilizing the Heaton et al. total aquatic decomposition (TAD) score and (ii) weighing the carrion before and after submersion. Complete forensic necropsies were performed as a control. Perinatal piglets were used as human analogs. The results of this study indicate that in order to objectively measure decomposition over time, the human analog should be examined at depth using the TAD scoring system rather than utilizing a carrion weight evaluation. The acquired TAD score can be used to calculate an approximate PMSI. © 2012 American Academy of Forensic Sciences.

Generic aspects of the airborne spread of human pathogens indoors and emerging air decontamination technologies.

PubMed

Ijaz, M Khalid; Zargar, Bahram; Wright, Kathryn E; Rubino, Joseph R; Sattar, Syed A

2016-09-02

Indoor air can be an important vehicle for a variety of human pathogens. This review provides examples of airborne transmission of infectious agents from experimental and field studies and discusses how airborne pathogens can contaminate other parts of the environment to give rise to secondary vehicles leading air-surface-air nexus with possible transmission to susceptible hosts. The following groups of human pathogens are covered because of their known or potential airborne spread: vegetative bacteria (staphylococci and legionellae), fungi (Aspergillus, Penicillium, and Cladosporium spp and Stachybotrys chartarum), enteric viruses (noro- and rotaviruses), respiratory viruses (influenza and coronaviruses), mycobacteria (tuberculous and nontuberculous), and bacterial spore formers (Clostridium difficile and Bacillus anthracis). An overview of methods for experimentally generating and recovering airborne human pathogens is included, along with a discussion of factors that influence microbial survival in indoor air. Available guidelines from the U.S. Environmental Protection Agency and other global regulatory bodies for the study of airborne pathogens are critically reviewed with particular reference to microbial surrogates that are recommended. Recent developments in experimental facilities to contaminate indoor air with microbial aerosols are presented, along with emerging technologies to decontaminate indoor air under field-relevant conditions. Furthermore, the role that air decontamination may play in reducing the contamination of environmental surfaces and its combined impact on interrupting the risk of pathogen spread in both domestic and institutional settings is discussed. Copyright © 2016. Published by Elsevier Inc.

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

PubMed Central

2014-01-01

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

Attentional shifts between surfaces: effects on detection and early brain potentials.

PubMed

Pinilla, T; Cobo, A; Torres, K; Valdes-Sosa, M

2001-06-01

Two consecutive events transforming the same illusory surface in transparent motion (brief changes in direction) can be discriminated with ease, but a prolonged interference ( approximately 500 ms) on the discrimination of the second event arises when different surfaces are concerned [Valdes-Sosa, M., Cobo, A., & Pinilla, T. (2000). Attention to object files defined by transparent motion. Journal of Experimental Psychology: Human Perception and Performance, 26(2), 488-505]. Here we further characterise this phenomenon and compare it to the attentional blink AB [Shapiro, K.L., Raymond, J.E., & Arnell, K.M. (1994). Attention to visual pattern information produces the attentional blink in RSVP. Journal of Experimental Psychology: Human Perception and Performance, 20, 357-371]. Similar to the AB, reduced sensitivity (d') was found in the two-surface condition. However, the two-surface cost was associated with a reduced N1 brain response in contrast to reports for AB [Vogel, E.K., Luck, S.J., & Shapiro, K. (1998). Electrophysiological evidence for a postperceptual locus of suppression during the attentional blink. Journal of Experimental Psychology: Human Perception and Performance, 24(6), 1656-1674]. The results from this study indicate that the two-surface cost corresponds to competitive effects in early vision. Reasons for the discrepancy with the AB study are considered.

Allium sativum L. Improves Visual Memory and Attention in Healthy Human Volunteers

PubMed Central

Tasnim, Sara; Haque, Parsa Sanjana; Bari, Md. Sazzadul; Hossain, Md. Monir; Islam, Sardar Mohd. Ashraful; Shahriar, Mohammad; Bhuiyan, Mohiuddin Ahmed; Bin Sayeed, Muhammad Shahdaat

2015-01-01

Studies have shown that Allium sativum L. (AS) protects amyloid-beta peptide-induced apoptosis, prevents oxidative insults to neurons and synapses, and thus prevent Alzheimer's disease progression in experimental animals. However, there is no experimental evidence in human regarding its putative role in memory and cognition. We have studied the effect of AS consumption by healthy human volunteers on visual memory, verbal memory, attention, and executive function in comparison to control subjects taking placebo. The study was conducted over five weeks and twenty volunteers of both genders were recruited and divided randomly into two groups: A (AS) and B (placebo). Both groups participated in the 6 computerized neuropsychological tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) twice: at the beginning and after five weeks of the study. We found statistically significant difference (p < 0.05) in several parameters of visual memory and attention due to AS ingestion. We also found statistically nonsignificant (p > 0.05) beneficial effects on verbal memory and executive function within a short period of time among the volunteers. Study for a longer period of time with patients suffering from neurodegenerative diseases might yield more relevant results regarding the potential therapeutic role of AS. PMID:26351508

Fracture characterization of human cortical bone under mode II loading using the end-notched flexure test.

PubMed

Silva, F G A; de Moura, M F S F; Dourado, N; Xavier, J; Pereira, F A M; Morais, J J L; Dias, M I R; Lourenço, P J; Judas, F M

2017-08-01

Fracture characterization of human cortical bone under mode II loading was analyzed using a miniaturized version of the end-notched flexure test. A data reduction scheme based on crack equivalent concept was employed to overcome uncertainties on crack length monitoring during the test. The crack tip shear displacement was experimentally measured using digital image correlation technique to determine the cohesive law that mimics bone fracture behavior under mode II loading. The developed procedure was validated by finite element analysis using cohesive zone modeling considering a trapezoidal with bilinear softening relationship. Experimental load-displacement curves, resistance curves and crack tip shear displacement versus applied displacement were used to validate the numerical procedure. The excellent agreement observed between the numerical and experimental results reveals the appropriateness of the proposed test and procedure to characterize human cortical bone fracture under mode II loading. The proposed methodology can be viewed as a novel valuable tool to be used in parametric and methodical clinical studies regarding features (e.g., age, diseases, drugs) influencing bone shear fracture under mode II loading.

A Viscoelastic Constitutive Model Can Accurately Represent Entire Creep Indentation Tests of Human Patella Cartilage

PubMed Central

Pal, Saikat; Lindsey, Derek P.; Besier, Thor F.; Beaupre, Gary S.

2013-01-01

Cartilage material properties provide important insights into joint health, and cartilage material models are used in whole-joint finite element models. Although the biphasic model representing experimental creep indentation tests is commonly used to characterize cartilage, cartilage short-term response to loading is generally not characterized using the biphasic model. The purpose of this study was to determine the short-term and equilibrium material properties of human patella cartilage using a viscoelastic model representation of creep indentation tests. We performed 24 experimental creep indentation tests from 14 human patellar specimens ranging in age from 20 to 90 years (median age 61 years). We used a finite element model to reproduce the experimental tests and determined cartilage material properties from viscoelastic and biphasic representations of cartilage. The viscoelastic model consistently provided excellent representation of the short-term and equilibrium creep displacements. We determined initial elastic modulus, equilibrium elastic modulus, and equilibrium Poisson’s ratio using the viscoelastic model. The viscoelastic model can represent the short-term and equilibrium response of cartilage and may easily be implemented in whole-joint finite element models. PMID:23027200

Pesticides, chemical and industrial exposures in relation to systemic lupus erythematosus

PubMed Central

Parks, Christine G.; De Roos, Anneclaire J.

2013-01-01

Growing evidence suggests exposure to chemicals and industrial pollutants may increase risk of SLE. Here we review research on SLE associations with occupational and industrial exposures, primarily drawing on studies in human populations and summarizing epidemiologic research published in the past decade. The association of occupational silica exposure with SLE is well established, but key questions remain, including the required dose and susceptibility factors, and SLE risk due to other silicate exposures. Research on SLE and other exposures is less well developed, though several potential associations merit further consideration due to the consistency of preliminary human findings, experimental animal research, and biologic plausibility. These include pesticides and solvents, for which experimental findings also support investigation of specific agents, including organochlorines and trichloroethylene. Experimental findings and biologic plausibility suggest research on SLE and occupational exposure to hydrocarbons (i.e., mineral oils) is warranted, especially given the widespread exposures in the population. Experimental and limited human findings support further investigation of SLE related to mercury exposure, especially in dental occupations. Research on environmental risk factors in risk-enriched cohorts (family based) is recommended, as is further investigation of exposures in relation to intermediate markers of effect (e.g., antinuclear antibodies), clinical features (e.g., nephritis) and outcomes. PMID:24763537

Size of Human Figure Drawings as Influenced by Instructions for "Sexy" versus "Average" Drawings and by the Status of the Experimenter.

ERIC Educational Resources Information Center

Duffy, Karen G.; And Others

1982-01-01

Investigated the effects of experimenter status and sex and instructional set on the size of "sexy" and "average" human figure drawings by students. Results showed no effects for experimenter status or sex. "Sexy" drawings were consistently drawn larger than "average" drawings and male figures were drawn…

Shoe-Floor Interactions in Human Walking With Slips: Modeling and Experiments.

PubMed

Trkov, Mitja; Yi, Jingang; Liu, Tao; Li, Kang

2018-03-01

Shoe-floor interactions play a crucial role in determining the possibility of potential slip and fall during human walking. Biomechanical and tribological parameters influence the friction characteristics between the shoe sole and the floor and the existing work mainly focus on experimental studies. In this paper, we present modeling, analysis, and experiments to understand slip and force distributions between the shoe sole and floor surface during human walking. We present results for both soft and hard sole material. The computational approaches for slip and friction force distributions are presented using a spring-beam networks model. The model predictions match the experimentally observed sole deformations with large soft sole deformation at the beginning and the end stages of the stance, which indicates the increased risk for slip. The experiments confirm that both the previously reported required coefficient of friction (RCOF) and the deformation measurements in this study can be used to predict slip occurrence. Moreover, the deformation and force distribution results reported in this study provide further understanding and knowledge of slip initiation and termination under various biomechanical conditions.

Biospecimen Reporting for Improved Study Quality

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

Moore, Ph.D., Helen M.; Kelly, Ph.D., Andrea B.; Jewell, Ph.D., Scott D.

Human biospecimens are subjected to collection, processing, and storage that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research that uses human tissues, it is crucial that information on the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality (BRISQ) recommendations outlined herein are intended to applymore » to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The BRISQ guidelines are proposed as an important and timely resource tool to strengthen communication and publications on biospecimen-related research and to help reassure patient contributors and the advocacy community that their contributions are valued and respected.« less

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

PubMed

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

2013-02-01

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

Comparative theoretical and experimental study on novel tri-quinoline system and its anticancer studies

NASA Astrophysics Data System (ADS)

Gayathri, Kasirajan; Radhika, Ramachandran; Shankar, Ramasamy; Malathi, Mahalingam; Savithiri, Krishnaswamy; Sparkes, Hazel A.; Howard, Judith A. K.; Mohan, Palathurai Subramaniam

2017-04-01

A novel compound 2-chloro-3,6-bis-(quinolin-8-yloxymethyl)-quinoline 3 bearing a tri-quinoline moiety has been synthesized from 2-chloro-3,6-dimethyl quinoline 1 and 8-hydroxy quinoline 2 using dry acetone and K2CO3 as a base. 3 has been characterized by using FT-IR, FT-Raman, UV-Vis, 1H NMR, 13C NMR spectra and single crystal X-ray diffraction methods. We have also made a combined experimental and theoretical study on the molecular structure, vibrational spectra, NMR, FT-IR, FT-Raman and UV-Vis spectra of 2-chloro-3,6-bis-(quinolin-8-yloxymethyl)-quinoline. The theoretical studies of the title compound have been evaluated by using density functional theory calculations using B3LYP/6-31+G(d,p) and M06-2X/6-31+G(d,p) level of theories. The calculated theoretical values were found to be in good agreement with the experimental findings. The single crystal structure 3 crystallized in the orthorhombic space group Pna21. The compound 3 exhibits higher cytotoxicity in human cervical cancer cell lines (HeLa) than human breast cancer cell lines (MCF7).

3D virtual human atria: A computational platform for studying clinical atrial fibrillation

PubMed Central

Aslanidi, Oleg V; Colman, Michael A; Stott, Jonathan; Dobrzynski, Halina; Boyett, Mark R; Holden, Arun V; Zhang, Henggui

2011-01-01

Despite a vast amount of experimental and clinical data on the underlying ionic, cellular and tissue substrates, the mechanisms of common atrial arrhythmias (such as atrial fibrillation, AF) arising from the functional interactions at the whole atria level remain unclear. Computational modelling provides a quantitative framework for integrating such multi-scale data and understanding the arrhythmogenic behaviour that emerges from the collective spatio-temporal dynamics in all parts of the heart. In this study, we have developed a multi-scale hierarchy of biophysically detailed computational models for the human atria – 3D virtual human atria. Primarily, diffusion tensor MRI reconstruction of the tissue geometry and fibre orientation in the human sinoatrial node (SAN) and surrounding atrial muscle was integrated into the 3D model of the whole atria dissected from the Visible Human dataset. The anatomical models were combined with the heterogeneous atrial action potential (AP) models, and used to simulate the AP conduction in the human atria under various conditions: SAN pacemaking and atrial activation in the normal rhythm, break-down of regular AP wave-fronts during rapid atrial pacing, and the genesis of multiple re-entrant wavelets characteristic of AF. Contributions of different properties of the tissue to the mechanisms of the normal rhythm and AF arrhythmogenesis are investigated and discussed. The 3D model of the atria itself was incorporated into the torso model to simulate the body surface ECG patterns in the normal and arrhythmic conditions. Therefore, a state-of-the-art computational platform has been developed, which can be used for studying multi-scale electrical phenomena during atrial conduction and arrhythmogenesis. Results of such simulations can be directly compared with experimental electrophysiological and endocardial mapping data, as well as clinical ECG recordings. More importantly, the virtual human atria can provide validated means for directly dissecting 3D excitation propagation processes within the atrial walls from an in vivo whole heart, which are beyond the current technical capabilities of experimental or clinical set-ups. PMID:21762716

Experimental Models of Vaginal Candidiasis and Their Relevance to Human Candidiasis

PubMed Central

Sobel, Jack D.

2016-01-01

Vulvovaginal candidiasis (VVC) is a high-incidence disease seriously affecting the quality of life of women worldwide, particularly in its chronic, recurrent forms (RVVC), and with no definitive cure or preventive measure. Experimental studies in currently used rat and mouse models of vaginal candidiasis have generated a large mass of data on pathogenicity determinants and inflammation and immune responses of potential importance for the control of human pathology. However, reflection is necessary about the relevance of these rodent models to RVVC. Here we examine the chemical, biochemical, and biological factors that determine or contrast the forms of the disease in rodent models and in women and highlight the differences between them. We also appeal for approaches to improve or replace the current models in order to enhance their relevance to human infection. PMID:26883592

Modulation of the malignant phenotype with the urokinase-type plasminogen activator and the type I plasminogen activator inhibitor.

PubMed

Sordat, B; Reiter, L; Cajot, J F

1990-12-02

Gene transfer techniques were utilized to evaluate the role of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) in enhancing or preventing the expression of the invasive malignant phenotype, respectively. Mouse L-cell transfectants expressing human uPA or human PAI-1 as well as mouse B16 transfectants expressing mouse uPA or human PAI-1 were generated. These transfectants were tested using a variety of experimental methods including smooth muscle cell matrix solubilization in vitro, lung colony formation in vivo and co-cultures of antagonist-expressing cells in vitro. Results from these studies provide direct evidence for an enhancing role of uPA in malignant invasion and experimental metastasis and for a modulatory role of PAI-1 in tumor cell-mediated breakdown of extracellular matrices.

Quantifying Astronaut Tasks: Robotic Technology and Future Space Suit Design

NASA Technical Reports Server (NTRS)

Newman, Dava

2003-01-01

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

Immune reactions and allergy in experimental anisakiasis

PubMed Central

Lee, Haneul Nari

2006-01-01

The third-stage larvae (L3) of the parasitic nematode, Anisakis simplex, have been implicated in the induction of hyperimmune allergic reactions in orally infected humans. In this work, we have conducted a review of an investigation into immune reactions occurring in animals experimentally infected with A. simplex L3. The patterns of serum antibody productions in the experimental animals against excretory-secretory products (ESP) of A. simplex L3 contributed to our current knowledge regarding specific humoral immune reactions in humans. In our review, we were able to determine that L3 infection of experimental animals may constitute a good model system for further exploration of immune mechanisms and allergy in anisakiasis of humans. PMID:17170569

Role of non-human primates in malaria vaccine development: Memorandum from a WHO Meeting*

PubMed Central

1988-01-01

This Memorandum discusses the coordination and standardization of malaria vaccine research in non-human primates to encourage optimum use of the available animals in experiments that are fully justified both scientifically and ethically. The requirements for experimentation in non-human primates, the availability of suitable animals for malaria vaccine studies, and the criteria for testing candidate vaccines are considered. The policy and legislation relevant to the use of non-human primates in biomedical research are also briefly discussed. The Memorandum concludes with eight recommendations. PMID:3266112

The prediction of biogenic magnetic nanoparticles biomineralization in human tissues and organs

NASA Astrophysics Data System (ADS)

Medviediev, O.; Gorobets, O. Yu; Gorobets, S. V.; Yadrykhins'ky, V. S.

2017-10-01

In this study, human homologs of magnetosome island proteins basing on pairwise and multiple alignment of amino acid sequences were found. The expression levels of genes, which encode magnetosome island proteins of M. gryphiswaldense MSR-1, that were cultured under oxygen deficiency conditions and also under microaerobic conditions were compared to the expression levels of genes that encode the relevant homologs in human organism. The possibility of BMN biomineralization in human tissues and organs, in which BMN were not experimentally found before, was predicted.

Does testosterone affect lateralization of brain and behaviour? A meta-analysis in humans and other animal species.

PubMed

Pfannkuche, Kristina A; Bouma, Anke; Groothuis, Ton G G

2009-04-12

Lateralization of brain and behaviour has been the topic of research for many years in neuropsychology, but the factors guiding its development remain elusive. Based on sex differences in human lateralization, four hypotheses have been postulated that suggest a role for androgens, specifically testosterone. With the discovery that lateralization is a fundamental principle in the organization of brain and behaviour among vertebrates, it has now become possible to experimentally test such hypotheses in animal models. The use of different taxa, humans, other mammalian species and birds (with oestradiol and not testosterone involved in sexual differentiation in birds) facilitates to differentiate between the hypotheses. We used meta-analyses for analysing papers that provided sufficient information, and a semi-quantitative approach based on all relevant studies that we extracted from the literature. We tested the predictions of these hypotheses regarding strength and direction of lateralization for motor output, language and visuospatial cognition in these three taxa. We tested for sex differences and early organizational effects of testosterone (both correlative and experimental studies). We found sex differences in the direction of lateralization for non-human mammals (motor biases similar to humans) and in direction and strength in birds (visual cognitive tasks). However, the prediction that prenatal testosterone exposure affects the direction of lateralization was not supported for humans. In birds and non-human mammals, opposite trends were found, with the effect in non-human mammals being opposite to the expectation based on sex differences. None of the four hypotheses was sufficiently supported and more studies, testing a wider array of functions in different taxa while reporting the data more completely are needed.

The role of the placenta in drug transport and fetal drug exposure.

PubMed

Koren, Gideon; Ornoy, Asher

2018-04-01

It was assumed for decades that the human placenta serves as a barrier, protecting the fetus from exposure to xenobiotics circulating in the mother. The thalidomide disaster completely reversed this concept. The study of the human placenta is therefore critical to understanding the mechanisms by which xenobiotics reach the fetus and exert their effects. Areas covered: This review describes mechanisms by which drugs interact with the human placenta, and experimental methods to study these interactions in humans. We have selected three areas of current clinical interest, where the placenta exhibits critical role in drug transport: The ABC transporters, the placental handling of cancer therapeutic drugs and the interaction between the placenta and immunoglobulins. Expert commentary: The optimal model to predict drug transfer and transport from the mother to the fetus is the isolated human placental lobule perfused in vitro. Unlike subcellular preparations or tissue homogenates, data obtained from a perfused intact tissue, where structural integrity and cell-cell organization are maintained, more closely reflect the in vivo situation. Moreover, confounding metabolic and physiologic influences are minimized and the experimental conditions can be controlled. It is important to remember that due to significant differences in the function of the placenta in the first two months (histiotrophic nutrition) and later in pregnancy (hemotrophic nutrition) there might be differences in the transplacental transfer of drugs. While most of our knowledge comes from studies on term placentae, we are in need of studies on young placenta that functions during the period of organogenesis.

On the promotion of human flourishing

PubMed Central

VanderWeele, Tyler J.

2017-01-01

Many empirical studies throughout the social and biomedical sciences focus only on very narrow outcomes such as income, or a single specific disease state, or a measure of positive affect. Human well-being or flourishing, however, consists in a much broader range of states and outcomes, certainly including mental and physical health, but also encompassing happiness and life satisfaction, meaning and purpose, character and virtue, and close social relationships. The empirical literature from longitudinal, experimental, and quasiexperimental studies is reviewed in attempt to identify major determinants of human flourishing, broadly conceived. Measures of human flourishing are proposed. Discussion is given to the implications of a broader conception of human flourishing, and of the research reviewed, for policy, and for future research in the biomedical and social sciences. PMID:28705870

Computational Fluid Dynamics Modeling of Bacillus anthracis ...

EPA Pesticide Factsheets

Journal Article Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived from computed tomography (CT) or µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditions using average species-specific minute volumes. Four different exposure scenarios were modeled in the rabbit based upon experimental inhalation studies. For comparison, human simulations were conducted at the highest exposure concentration used during the rabbit experimental exposures. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Despite the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the upper conducting airways of the human at the same air concentration of anthrax spores. This greater deposition of spores in the upper airways in the human resulted in lower penetration and deposition in the tracheobronchial airways and the deep lung than that predict

THE EXPERIMENTAL INFECTION OF THE HUMAN BODY LOUSE, PEDICULUS HUMANUS CORPORIS, WITH MURINE AND EPIDEMIC LOUSE-BORNE TYPHUS STRAINS

PubMed Central

Snyder, J. C.; Wheeler, C. M.

1945-01-01

Experiments are described which demonstrate that human body lice (Pediculus humanus corporis), were infected experimentally with murine and epidemic louse-borne strains of typhus fever by feeding on suitably prepared rabbits. Details of the two methods of infection, the "bleb technique" and the "I.V. technique," are presented. It is concluded that the experimental infection of human lice with typhus can be accomplished very easily and rapidly with these methods. The possible applications of the method are discussed. PMID:19871482

Alcohol and Sexuality Research in the AIDS Era: Trends in Publication Activity, Target Populations and Research Design

PubMed Central

George, William H.

2009-01-01

Research addressing relationships between alcohol and human sexuality has proliferated, due in part to efforts to characterize alcohol's role in HIV risk behavior. This study provides a descriptive review of the alcohol–sexuality literature, using abstracts from 264 identified studies to estimate changes in publication activity, target populations, and the prevalence of HIV-related studies over time. We also examine methodological trends by estimating the prevalence of experimental vs. non-experimental studies. Findings show considerable increases in research activity and diversity of populations studied since the mid-1980's and highlight the emergence of HIV-related studies as a focal point of alcohol–sexuality research efforts. Results also demonstrate a substantial decline in the proportion of studies utilizing experimental methods, in part because of frequent use of non-experimental approaches in studies of alcohol and HIV risk behavior. We discuss implications and review the role of experiments in evaluating causal relationships between alcohol and sexual risk behavior. PMID:16897352

Alcohol and sexuality research in the AIDS era: trends in publication activity, target populations and research design.

PubMed

Hendershot, Christian S; George, William H

2007-03-01

Research addressing relationships between alcohol and human sexuality has proliferated, due in part to efforts to characterize alcohol's role in HIV risk behavior. This study provides a descriptive review of the alcohol-sexuality literature, using abstracts from 264 identified studies to estimate changes in publication activity, target populations, and the prevalence of HIV-related studies over time. We also examine methodological trends by estimating the prevalence of experimental vs. non-experimental studies. Findings show considerable increases in research activity and diversity of populations studied since the mid-1980's and highlight the emergence of HIV-related studies as a focal point of alcohol-sexuality research efforts. Results also demonstrate a substantial decline in the proportion of studies utilizing experimental methods, in part because of frequent use of non-experimental approaches in studies of alcohol and HIV risk behavior. We discuss implications and review the role of experiments in evaluating causal relationships between alcohol and sexual risk behavior.

Assisting at-risk community college students' acquisition of critical thinking learning strategies in human anatomy and physiology

NASA Astrophysics Data System (ADS)

Arburn, Theresa Morkovsky

1998-11-01

The purpose of this study was to investigate whether learning thinking strategies within the context of a community college course in Human Anatomy and Physiology would result in increased academic performance and the incidence of critical thinking skills. Included in the study sample were 68 community college students, many of whom would be categorized as "at-risk," who were enrolled in four sections of a Human Anatomy and Physiology class. Two of the class sections served as the experimental group and two sections served as the control group. During the course of one semester, members of the experimental group participated in the use of a student-generated questioning technique in conjunction with lecture presentations, while members of the control group did not. All students were pretested using the Learning and Study Strategies Inventory (LASSI) and the California Critical Thinking Skills Test (CCTST). Posttesting was completed using these same instruments and an end-of-course comprehensive examination. Analysis of data revealed no significant differences between the experimental and control groups with regard to their overall achievement, their ability to process information, or their demonstration of critical thinking. It was interesting to note, however, that members of the experimental group did exhibit a change in their ability to select main ideas, apply deductive reasoning, and use inference. While the use of thinking strategies within the context of the course did not effect a significant change in academic achievement or critical thinking among at-risk community college students, it should be noted that application of a non-lecture method of class participation had no negative impact on student performance. Whether more abstruse changes have occurred with regard to the acquisition of cognitive skills remains to be elucidated.

Human embryonic stem cell lines model experimental human cytomegalovirus latency.

PubMed

Penkert, Rhiannon R; Kalejta, Robert F

2013-05-28

Herpesviruses are highly successful pathogens that persist for the lifetime of their hosts primarily because of their ability to establish and maintain latent infections from which the virus is capable of productively reactivating. Human cytomegalovirus (HCMV), a betaherpesvirus, establishes latency in CD34(+) hematopoietic progenitor cells during natural infections in the body. Experimental infection of CD34(+) cells ex vivo has demonstrated that expression of the viral gene products that drive productive infection is silenced by an intrinsic immune defense mediated by Daxx and histone deacetylases through heterochromatinization of the viral genome during the establishment of latency. Additional mechanistic details about the establishment, let alone maintenance and reactivation, of HCMV latency remain scarce. This is partly due to the technical challenges of CD34(+) cell culture, most notably, the difficulty in preventing spontaneous differentiation that drives reactivation and renders them permissive for productive infection. Here we demonstrate that HCMV can establish, maintain, and reactivate in vitro from experimental latency in cultures of human embryonic stem cells (ESCs), for which spurious differentiation can be prevented or controlled. Furthermore, we show that known molecular aspects of HCMV latency are faithfully recapitulated in these cells. In total, we present ESCs as a novel, tractable model for studies of HCMV latency.

Experimental West Nile Virus Infection in Rabbits: An Alternative Model for Studying Induction of Disease and Virus Control

PubMed Central

Suen, Willy W.; Uddin, Muhammad J.; Wang, Wenqi; Brown, Vienna; Adney, Danielle R.; Broad, Nicole; Prow, Natalie A.; Bowen, Richard A.; Hall, Roy A.; Bielefeldt-Ohmann, Helle

2015-01-01

The economic impact of non-lethal human and equine West Nile virus (WNV) disease is substantial, since it is the most common presentation of the infection. Experimental infection with virulent WNV strains in the mouse and hamster models frequently results in severe neural infection and moderate to high mortality, both of which are not representative features of most human and equine infections. We have established a rabbit model for investigating pathogenesis and immune response of non-lethal WNV infection. Two species of rabbits, New Zealand White (Oryctolagus cuniculus) and North American cottontail (Sylvilagus sp.), were experimentally infected with virulent WNV and Murray Valley encephalitis virus strains. Infected rabbits exhibited a consistently resistant phenotype, with evidence of low viremia, minimal-absent neural infection, mild-moderate neuropathology, and the lack of mortality, even though productive virus replication occurred in the draining lymph node. The kinetics of anti-WNV neutralizing antibody response was comparable to that commonly seen in infected horses and humans. This may be explained by the early IFNα/β and/or γ response evident in the draining popliteal lymph node. Given this similarity to the human and equine disease, immunocompetent rabbits are, therefore, a valuable animal model for investigating various aspects of non-lethal WNV infections. PMID:26184326

Particle deposition in human respiratory system: deposition of concentrated hygroscopic aerosols.

PubMed

Varghese, Suresh K; Gangamma, S

2009-06-01

In the nearly saturated human respiratory tract, the presence of water-soluble substances in the inhaled aerosols can cause change in the size distribution of the particles. This consequently alters the lung deposition profiles of the inhaled airborne particles. Similarly, the presence of high concentration of hygroscopic aerosols also affects the water vapor and temperature profiles in the respiratory tract. A model is presented to analyze these effects in human respiratory system. The model solves simultaneously the heat and mass transfer equations to determine the size evolution of respirable particles and gas-phase properties within human respiratory tract. First, the model predictions for nonhygroscopic aerosols are compared with experimental results. The model results are compared with experimental results of sodium chloride particles. The model reproduces the major features of the experimental data. The water vapor profile is significantly modified only when a high concentration of particles is present. The model is used to study the effect of equilibrium assumptions on particle deposition. Simulations show that an infinite dilution solution assumption to calculate the saturation equilibrium over droplet could induce errors in estimating particle growth. This error is significant in the case of particles of size greater than 1 mum and at number concentrations higher than 10(5)/cm(3).

Chemical carcinogens and inhibitors of carcinogenesis in the human diet

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

Carr, B.I.

1985-01-01

The induction of cancer by chemicals as presently understood involves a series of steps, some of which require the passage of time. Many substances that are potent carcinogens in experimental animals are known to exist in nature and occur as part of the human diet. In addition, many of the substances that are known to inhibit experimental carcinogenesis also exist in the human diet. Thus, in addition to industrially produced carcinogens, humans can be presumed to have evolved in an environment that contains both carcinogens and anti-carcinogens. There is also a great deal of experimental and human epidemiologic data onmore » the influence of lipids, proteins and carbohydrates on cancer incidence rates; however, much of those data are confusing and conflicting.« less

Radiofrequency ablation of retained placenta accreta after conservative management: preliminary evaluation in the pregnant ewe and in normal human placenta in vitro.

PubMed

Morel, O; Monceau, E; Tran, N; Malartic, C; Morel, F; Barranger, E; Côté, J F; Gayat, E; Chavatte-Palmer, P; Cabrol, D; Tsatsaris, V

2009-06-01

To evaluate radiofrequency (RF) efficiency and safety for the ablation of retained placenta in humans, using a pregnant sheep model. Experimental study. Laboratory of Surgery School, Nancy, France. Three pregnant ewes/ten human placentas. Various RF procedures were tested in pregnant ewes on 50 placentomes (individual placental units). Reproducibility of the best procedure was then evaluated in a further 20 placentomes and on ten human term placentas in vitro after delivery. Placental tissues destruction, lesions' size, myometrial lesions. Low power (100 W) and low target temperatures (60 degrees C) lead to homogenous tissue destruction, without myometrial lesion. No significant difference was observed in terms of lesion size and procedure duration for in the placentomes of pregnant ewe in vivo and in human placentas in vitro. The diameter of the ablation could be correlated with the tines deployment. The placental tissue structure is very permissive to RF energy, which suggests that RF could be used for the ablation of retained placenta, providing optimal control of tissue destruction. These results call for further experimental evaluations.

She's not a person...she's just a woman! Infra-humanization and intimate partner violence.

PubMed

Baldry, Anna Costanza; Pacilli, Maria Giuseppina; Pagliaro, Stefano

2015-05-01

This article examines the association between a target's perceived humanness and individuals' willingness to provide help and support in cases of violence against women (VAW), specifically, intimate partner violence (IPV). In an experimental study, undergraduates read a fictitious article from a newspaper describing an IPV episode of a man hitting his wife and accusing her of cheating on him. According to the experimental condition, they then read that the victim either had or had not admitted the infidelity. Participants then judged the victim on an infra-humanization scale and expressed their willingness to provide help and support to the victim herself as if they were a neighbor witnessing the attack. Results showed that a victim admitting an affair with another man (admission condition) elicited lower perceived humanness and lower willingness to provide help than a victim denying such adultery (no admission condition). Moreover, targets' perceived humanness mediated the effect of contextual features on participants' willingness to provide help to the victim. Results are discussed in terms of victim blaming, and practical implications for prevention strategies are presented. © The Author(s) 2014.

The effect of cell phones on human health

NASA Astrophysics Data System (ADS)

Abu-Isbeih, Ibrahim N.; Saad, Dina

2011-10-01

The effect of cell phone radiation on human health is the subject of recent interest and study, as a result of the enormous increase in cell phone usage throughout the world. Cell phones use electromagnetic radiation in the microwave range, which some believe may be harmful to human health. Other digital wireless systems, such as data communication networks, produce similar radiation. The objective of this survey is to review the effects of cell phones on human health: A large body of research exists, both epidemiological and experimental, in non-human animals and in humans, of which the majority shows no definite causative relationship between exposure to cell phones and harmful biological effects in humans. This is often paraphrased simply as the balance of evidence showing no harm to humans from cell phones, although a significant number of individual studies do suggest such a relationship, or are inconclusive.

Quantitative comparisons of the acute neurotoxicity of toluene in rats and humans.

PubMed

Benignus, Vernon A; Boyes, William K; Kenyon, Elaina M; Bushnell, Philip J

2007-11-01

The behavioral and neurophysiological effects of acute exposure to toluene are the most thoroughly explored of all the hydrocarbon solvents. Behavioral effects have been experimentally studied in humans and other species, for example, rats. The existence of both rat and human dosimetric data offers the opportunity to quantitatively compare the relative sensitivity to acute toluene exposure. The purpose of this study was to fit dose-effect curves to existing data and to estimate the dose-equivalence equation (DEE) between rats and humans. The DEE gives the doses that produce the same magnitude of effect in the two species. Doses were brain concentrations of toluene estimated from physiologically based pharmacokinetic models. Human experiments measuring toluene effects on choice reaction time (CRT) were meta-analyzed. Rat studies employed various dependent variables: amplitude of visual-evoked potentials (VEPs), signal detection (SIGDET) accuracy (ACCU) and reaction time (RT), and escape-avoidance (ES-AV) behaviors. Comparison of dose-effect functions showed that human and rat sensitivity was practically the same for those two task regimens that exerted the least control over the behaviors being measured (VEP in rats and CRT in humans) and the sensitivity was progressively lower for SIGDET RT, SIGDET ACCU, and ES-AV behaviors in rats. These results suggested that the sensitivity to impairment by toluene depends on the strength of control over the measured behavior rather than on the species being tested. This interpretation suggests that (1) sensitivity to toluene would be equivalent in humans and rats if both species performed behaviors that were controlled to the same extent, (2) the most sensitive tests of neurobehavioral effects would be those in which least control is exerted on the behavior being measured, and (3) effects of toluene in humans may be estimated using the DEEs from rat studies despite differences in the amount of control exerted by the experimental regimen or differences in the behaviors under investigation.

Comparison of protocols for measuring cosmetic ingredient distribution in human and pig skin.

PubMed

Gerstel, D; Jacques-Jamin, C; Schepky, A; Cubberley, R; Eilstein, J; Grégoire, S; Hewitt, N; Klaric, M; Rothe, H; Duplan, H

2016-08-01

The Cosmetics Europe Skin Bioavailability and Metabolism Task Force aims to improve the measurement and prediction of the bioavailability of topically-exposed compounds for risk assessment. Key parameters of the experimental design of the skin penetration studies were compared. Penetration studies with frozen human and pig skin were conducted in two laboratories, according to the SCCS and OECD 428 guidelines. The disposition in skin was measured 24h after finite topical doses of caffeine, resorcinol and 7-ethoxycoumarin. The bioavailability distribution in skin layers of cold and radiolabelled chemicals were comparable. Furthermore, the distribution of each chemical was comparable in human and pig skin. The protocol was reproducible across the two laboratories. There were small differences in the amount of chemical detected in the skin layers, which were attributed to differences in washing procedures and anatomical sites of the skin used. In conclusion, these studies support the use of pig skin as an alternative source of skin should the availability of human skin become a limiting factor. If radiolabelled chemicals are not available, cold chemicals can be used, provided that the influence of chemical stability, reactivity or metabolism on the experimental design and the relevance of the data obtained is considered. Copyright © 2016. Published by Elsevier Ltd.

Heterogeneity of the gut microbiome in mice: guidelines for optimizing experimental design.

PubMed

Laukens, Debby; Brinkman, Brigitta M; Raes, Jeroen; De Vos, Martine; Vandenabeele, Peter

2016-01-01

Targeted manipulation of the gut flora is increasingly being recognized as a means to improve human health. Yet, the temporal dynamics and intra- and interindividual heterogeneity of the microbiome represent experimental limitations, especially in human cross-sectional studies. Therefore, rodent models represent an invaluable tool to study the host-microbiota interface. Progress in technical and computational tools to investigate the composition and function of the microbiome has opened a new era of research and we gradually begin to understand the parameters that influence variation of host-associated microbial communities. To isolate true effects from confounding factors, it is essential to include such parameters in model intervention studies. Also, explicit journal instructions to include essential information on animal experiments are mandatory. The purpose of this review is to summarize the factors that influence microbiota composition in mice and to provide guidelines to improve the reproducibility of animal experiments. © FEMS 2015.

Heterogeneity of the gut microbiome in mice: guidelines for optimizing experimental design

PubMed Central

Laukens, Debby; Brinkman, Brigitta M.; Raes, Jeroen; De Vos, Martine; Vandenabeele, Peter

2015-01-01

Targeted manipulation of the gut flora is increasingly being recognized as a means to improve human health. Yet, the temporal dynamics and intra- and interindividual heterogeneity of the microbiome represent experimental limitations, especially in human cross-sectional studies. Therefore, rodent models represent an invaluable tool to study the host–microbiota interface. Progress in technical and computational tools to investigate the composition and function of the microbiome has opened a new era of research and we gradually begin to understand the parameters that influence variation of host-associated microbial communities. To isolate true effects from confounding factors, it is essential to include such parameters in model intervention studies. Also, explicit journal instructions to include essential information on animal experiments are mandatory. The purpose of this review is to summarize the factors that influence microbiota composition in mice and to provide guidelines to improve the reproducibility of animal experiments. PMID:26323480

Social Learning and Culture in Child and Chimpanzee.

PubMed

Whiten, Andrew

2017-01-03

A few decades ago, we knew next to nothing about the behavior of our closest animal relative, the chimpanzee, but long-term field studies have since revealed an undreamed-of richness in the diversity of their cultural traditions across Africa. These discoveries have been complemented by a substantial suite of experimental studies, now bridging to the wild through field experiments. These field and experimental studies, particularly those in which direct chimpanzee-child comparisons have been made, delineate a growing set of commonalities between the phenomena of social learning and culture in the lives of chimpanzees and humans. These commonalities in social learning inform our understanding of the evolutionary roots of the cultural propensities the species share. At the same time, such comparisons throw into clearer relief the unique features of the distinctive human capacity for cumulative cultural evolution, and new research has begun to probe the key psychological attributes that may explain it.

SURVEYS OF RADIOACTIVITY IN HUMAN DIET AND EXPERIMENTAL STUDIES. Report for 1960

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

None

1961-11-16

Results are presented from a survey of Sr/sup 90/ in human diet in the United Kingdom during 1960. Data are included from a country-wide survey, which enabled the assessment of the mean ratio of Sr/sup 90/ to Ca in the average diet of the population, and local studies in areas where the quantity of Sr/sup 90/ was likely to exceed the average. Measurements were also made of Sr/sup 90/ in herbage and soil from representative pastures throughout the country, and Cs/sup 137/ in milk produced in the United Kingdom during 1960. Results are included from experimental studies of factors affectingmore » the passage of Sr/sup 90/ through food chains. Limited data are also included on Sr/sup 90/ in selected foods from Australia, the Republic of Ireland, and the Federation of Rhodesia and Nyasaland. (C.H.)« less

Experimental Studies on the Efficiency of Musical Emotions for the Reconciliation of Conceptual Dissonances

DTIC Science & Technology

2012-08-20

Final Report for AOARD Grant FA2386-11-1-4103 “Experimental studies on the efficiency of musical emotions for the reconciliation of conceptual...Performance: 01/09/2011 – 10/08/2012 Abstract: Debates on the origin and function of music have a long history. While some scientists argue that... music itself plays no adaptive role in human evolution, others suggest that music clearly has an evolutionary role, and point to music’s universality1

A pseudoreceptor modelling study of the varicella-zoster virus and human thymidine kinase binding sites

NASA Astrophysics Data System (ADS)

Greenidge, Paulette A.; Merz, Alfred; Folkers, Gerd

1995-12-01

A representative range of pyrimidine nucleoside analogues that are known to inhibit herpes simplex virus (HSV) replication have been used to construct receptor binding site models for the varicella-zoster virus (VZV), thymidine kinase (TK) and human TK1. Given a set of interacting ligands, superimposed in such a manner as to define a pharmacophore, the pseudoreceptor modelling technique Yak provides a means of building binding site models of macromolecules for which no three-dimensional experimental structures are available. Once the models have been evaluated by their ability to reproduce experimental binding data [Vedani et al., J. Am. Chem. Soc., 117 (1995) 4987], they can be used for predictive purposes. Calculated and experimental values of relative binding affinity are compared. Our models suggest that the substitution of one residue may be sufficient to determine ligand subtype affinity.

Determination of Important Nuclear Fragmentation Processes for Human Space Radiation Protection

NASA Technical Reports Server (NTRS)

Lin, Zi-Wei

2007-01-01

We present a semi-analytical method to determine which partial cross sections of nuclear fragmentations most affect the shielded dose equivalent due to exposure to galactic cosmic rays. The cross sections thus determined will require more theoretical and/or experimental studies in order for us to better predict, reduce and mitigate the radiation exposure in human space explorations.

Sexual transmission of Lyme disease: challenging the tickborne disease paradigm.

PubMed

Stricker, Raphael B; Middelveen, Marianne J

2015-01-01

Lyme disease caused by the spirochete Borrelia burgdorferi has become a major worldwide epidemic. In this article, we explore the clinical, epidemiological and experimental evidence for sexual transmission of Lyme disease in animal models and humans. Although the likelihood of sexual transmission of the Lyme spirochete remains speculative, the possibility of Lyme disease transmission via intimate human contact merits further study.

Responses to human intruders by birds nesting in colonies: Experimental results and management guidelines

USGS Publications Warehouse

Erwin, R.M.

1989-01-01

Colonies of nesting wading birds and seabirds were studied at coastal sites in Virginia and North Carolina to determine distances at which birds flushed in response to human intrusion. There were few statistically significant relationships between flushing distances and colony size. Similarly, there were few differences between responses during incubation compared to post-hatching periods.

Impact of Bisphenol A on the Cardiovascular System — Epidemiological and Experimental Evidence and Molecular Mechanisms

PubMed Central

Gao, Xiaoqian; Wang, Hong-Sheng

2014-01-01

Bisphenol A (BPA) is a ubiquitous plasticizing agent used in the manufacturing of polycarbonate plastics and epoxy resins. There is well-documented and broad human exposure to BPA. The potential risk that BPA poses to the human health has attracted much attention from regulatory agencies and the general public, and has been extensively studied. An emerging and rapidly growing area in the study of BPA’s toxicity is its impact on the cardiovascular (CV) system. Recent epidemiological studies have shown that higher urinary BPA concentration in humans is associated with various types of CV diseases, including angina, hypertension, heart attack and coronary and peripheral arterial disease. Experimental studies have demonstrated that acute BPA exposure promotes the development of arrhythmias in female rodent hearts. Chronic exposure to BPA has been shown to result in cardiac remodeling, atherosclerosis, and altered blood pressure in rodents. The underlying mechanisms may involve alteration of cardiac Ca2+ handling, ion channel inhibition/activation, oxidative stress, and genome/transcriptome modifications. In this review, we discuss these recent findings that point to the potential CV toxicity of BPA, and highlight the knowledge gaps in this growing research area. PMID:25153468

[Comparative studies of face recognition].

PubMed

Kawai, Nobuyuki

2012-07-01

Every human being is proficient in face recognition. However, the reason for and the manner in which humans have attained such an ability remain unknown. These questions can be best answered-through comparative studies of face recognition in non-human animals. Studies in both primates and non-primates show that not only primates, but also non-primates possess the ability to extract information from their conspecifics and from human experimenters. Neural specialization for face recognition is shared with mammals in distant taxa, suggesting that face recognition evolved earlier than the emergence of mammals. A recent study indicated that a social insect, the golden paper wasp, can distinguish their conspecific faces, whereas a closely related species, which has a less complex social lifestyle with just one queen ruling a nest of underlings, did not show strong face recognition for their conspecifics. Social complexity and the need to differentiate between one another likely led humans to evolve their face recognition abilities.

Components of plastic: experimental studies in animals and relevance for human health

PubMed Central

Talsness, Chris E.; Andrade, Anderson J. M.; Kuriyama, Sergio N.; Taylor, Julia A.; vom Saal, Frederick S.

2009-01-01

Components used in plastics, such as phthalates, bisphenol A (BPA), polybrominated diphenyl ethers (PBDE) and tetrabromobisphenol A (TBBPA), are detected in humans. In addition to their utility in plastics, an inadvertent characteristic of these chemicals is the ability to alter the endocrine system. Phthalates function as anti-androgens while the main action attributed to BPA is oestrogen-like activity. PBDE and TBBPA have been shown to disrupt thyroid hormone homeostasis while PBDEs also exhibit anti-androgen action. Experimental investigations in animals indicate a wide variety of effects associated with exposure to these compounds, causing concern regarding potential risk to human health. For example, the spectrum of effects following perinatal exposure of male rats to phthalates has remarkable similarities to the testicular dysgenesis syndrome in humans. Concentrations of BPA in the foetal mouse within the range of unconjugated BPA levels observed in human foetal blood have produced effects in animal experiments. Finally, thyroid hormones are essential for normal neurological development and reproductive function. Human body burdens of these chemicals are detected with high prevalence, and concentrations in young children, a group particularly sensitive to exogenous insults, are typically higher, indicating the need to decrease exposure to these compounds. PMID:19528057

The relevance of non-human primate and rodent malaria models for humans

PubMed Central

2011-01-01

At the 2010 Keystone Symposium on "Malaria: new approaches to understanding Host-Parasite interactions", an extra scientific session to discuss animal models in malaria research was convened at the request of participants. This was prompted by the concern of investigators that skepticism in the malaria community about the use and relevance of animal models, particularly rodent models of severe malaria, has impacted on funding decisions and publication of research using animal models. Several speakers took the opportunity to demonstrate the similarities between findings in rodent models and human severe disease, as well as points of difference. The variety of malaria presentations in the different experimental models parallels the wide diversity of human malaria disease and, therefore, might be viewed as a strength. Many of the key features of human malaria can be replicated in a variety of nonhuman primate models, which are very under-utilized. The importance of animal models in the discovery of new anti-malarial drugs was emphasized. The major conclusions of the session were that experimental and human studies should be more closely linked so that they inform each other, and that there should be wider access to relevant clinical material. PMID:21288352

Viral infections and breast cancer - A current perspective.

PubMed

Gannon, O M; Antonsson, A; Bennett, I C; Saunders, N A

2018-04-28

Sporadic human breast cancer is the most common cancer to afflict women. Since the discovery, decades ago, of the oncogenic mouse mammary tumour virus, there has been significant interest in the potential aetiologic role of infectious agents in sporadic human breast cancer. To address this, many studies have examined the presence of viruses (e.g. papillomaviruses, herpes viruses and retroviruses), endogenous retroviruses and more recently, microbes, as a means of implicating them in the aetiology of human breast cancer. Such studies have generated conflicting experimental and clinical reports of the role of infection in breast cancer. This review evaluates the current evidence for a productive oncogenic viral infection in human breast cancer, with a focus on the integration of sensitive and specific next generation sequencing technologies with pathogen discovery. Collectively, the majority of the recent literature using the more powerful next generation sequencing technologies fail to support an oncogenic viral infection being involved in disease causality in breast cancer. In balance, the weight of the current experimental evidence supports the conclusion that viral infection is unlikely to play a significant role in the aetiology of breast cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed

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

2011-05-01

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

A unified model of the excitability of mouse sensory and motor axons.

PubMed

Makker, Preet G S; Matamala, José Manuel; Park, Susanna B; Lees, Justin G; Kiernan, Matthew C; Burke, David; Moalem-Taylor, Gila; Howells, James

2018-06-19

Non-invasive nerve excitability techniques have provided valuable insight into the understanding of neurological disorders. The widespread use of mice in translational research on peripheral nerve disorders and by pharmaceutical companies during drug development requires valid and reliable models that can be compared to humans. This study established a novel experimental protocol that enables comparative assessment of the excitability properties of motor and sensory axons at the same site in mouse caudal nerve, compared the mouse data to data for motor and sensory axons in human median nerve at the wrist, and constructed a mathematical model of the excitability of mouse axons. In a separate study, ischaemia was employed as an experimental manoeuvre to test the translational utility of this preparation. The patterns of mouse sensory and motor excitability were qualitatively similar to human studies under normal and ischaemic conditions. The most conspicuous differences between mouse and human studies were observed in the recovery cycle and the response to hyperpolarization. Modelling showed that an increase in temperature in mouse axons could account for most of the differences in the recovery cycle. The modelling also suggested a larger hyperpolarization-activated conductance in mouse axons. The kinetics of this conductance appeared to be much slower raising the possibility that an additional or different hyperpolarization-activated cyclic-nucleotide gated (HCN) channel isoform underlies the accommodation to hyperpolarization in mouse axons. Given a possible difference in HCN isoforms, caution should be exercised in extrapolating from studies of mouse motor and sensory axons to human nerve disorders. This article is protected by copyright. All rights reserved.

Sutural growth restriction and modern human facial evolution: an experimental study in a pig model

PubMed Central

Holton, Nathan E; Franciscus, Robert G; Nieves, Mary Ann; Marshall, Steven D; Reimer, Steven B; Southard, Thomas E; Keller, John C; Maddux, Scott D

2010-01-01

Facial size reduction and facial retraction are key features that distinguish modern humans from archaic Homo. In order to more fully understand the emergence of modern human craniofacial form, it is necessary to understand the underlying evolutionary basis for these defining characteristics. Although it is well established that the cranial base exerts considerable influence on the evolutionary and ontogenetic development of facial form, less emphasis has been placed on developmental factors intrinsic to the facial skeleton proper. The present analysis was designed to assess anteroposterior facial reduction in a pig model and to examine the potential role that this dynamic has played in the evolution of modern human facial form. Ten female sibship cohorts, each consisting of three individuals, were allocated to one of three groups. In the experimental group (n = 10), microplates were affixed bilaterally across the zygomaticomaxillary and frontonasomaxillary sutures at 2 months of age. The sham group (n = 10) received only screw implantation and the controls (n = 10) underwent no surgery. Following 4 months of post-surgical growth, we assessed variation in facial form using linear measurements and principal components analysis of Procrustes scaled landmarks. There were no differences between the control and sham groups; however, the experimental group exhibited a highly significant reduction in facial projection and overall size. These changes were associated with significant differences in the infraorbital region of the experimental group including the presence of an infraorbital depression and an inferiorly and coronally oriented infraorbital plane in contrast to a flat, superiorly and sagittally infraorbital plane in the control and sham groups. These altered configurations are markedly similar to important additional facial features that differentiate modern humans from archaic Homo, and suggest that facial length restriction via rigid plate fixation is a potentially useful model to assess the developmental factors that underlie changing patterns in craniofacial form associated with the emergence of modern humans. PMID:19929910

Understanding of visual attention by adult humans (Homo sapiens): a partial replication of Povinelli, Bierschwale, and Cech (1999).

PubMed

Thomas, Emily; Murphy, Mary; Pitt, Rebecca; Rivers, Angela; Leavens, David A

2008-11-01

Povinelli, Bierschwale, and Cech (1999) reported that when tested on a visual attention task, the behavior of juvenile chimpanzees did not support a high-level understanding of visual attention. This study replicates their research using adult humans and aims to investigate the validity of their experimental design. Participants were trained to respond to pointing cues given by an experimenter, and then tested on their ability to locate hidden objects from visual cues. Povinelli et al.'s assertion that the generalization of pointing to gaze is indicative of a high-level framework was not supported by our findings: Training improved performance only on initial probe trials when the experimenter's gaze was not directed at the baited cup. Furthermore, participants performed above chance on such trials, the same result exhibited by chimpanzees and used as evidence by Povinelli et al. to support a low-level framework. These findings, together with the high performance of participants in an incongruent condition, in which the experimenter pointed to or gazed at an unbaited container, challenge the validity of their experimental design. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

A Discourse on Human Systems Integration

DTIC Science & Technology

2010-09-01

criterion for one of the study tasks. 2. Research Design This was a mixed methods study. The first-phase quantitative portion of the study...used a quasi-experimental, posttest-only with nonequivalent groups design . The independent variables were defined as follows: • The categorical... Research Design ...............................................................................287 3. Instruments

Experimental Reservoirs of Human Pathogens: The Vibrio Cholerae Paradigm (7th Annual SFAF Meeting, 2012)

ScienceCinema

Colwell, Rita

2018-05-14

Rita Colwell on "Experimental Reservoirs of Human Pathogens: The Vibrio cholerae paradigm" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

Experimental Reservoirs of Human Pathogens: The Vibrio Cholerae Paradigm (7th Annual SFAF Meeting, 2012)

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

Colwell, Rita

Rita Colwell on "Experimental Reservoirs of Human Pathogens: The Vibrio cholerae paradigm" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

An experimental paradigm for team decision processes

NASA Technical Reports Server (NTRS)

Serfaty, D.; Kleinman, D. L.

1986-01-01

The study of distributed information processing and decision making is presently hampered by two factors: (1) The inherent complexity of the mathematical formulation of decentralized problems has prevented the development of models that could be used to predict performance in a distributed environment; and (2) The lack of comprehensive scientific empirical data on human team decision making has hindered the development of significant descriptive models. As a part of a comprehensive effort to find a new framework for multihuman decision making problems, a novel experimental research paradigm was developed involving human terms in decision making tasks. Attempts to construct parts of an integrated model with ideas from queueing networks, team theory, distributed estimation and decentralized resource management are described.

Neurocognitive Effect of Nootropic Drug Brahmi (Bacopa monnieri) in Alzheimer's Disease

PubMed Central

Chaudhari, Kaustubh S.; Tiwari, Nishant R.; Tiwari, Rakesh R.; Sharma, Rohan S.

2017-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease of the elderly. The rapid increase in its incidence has necessitated development of newer drugs. Ayurvedic herbal medications are increasingly researched due to their biosafety profile and usefulness in cognitive impairment. In this article, we critically reviewed one such Medhya Rasayana (nootropic drug) Brahmi-derived from extract of Bacopa monnieri (EBm). Studies have shown that EBm promotes free radical scavenger mechanisms and protects cells in prefrontal cortex, hippocampus, and striatum against cytotoxicity and DNA damage implicated in AD. It also reduces lipoxygenase activity reducing lipid peroxidation, increases glutathione peroxidase and chelates iron. Administration of EBm was seen to protect the cholinergic neurons and reduce anticholinesterase activity comparable to donepezil, rivastigmine, and galantamine. It also reduces hippocampal β-amyloid deposition and stress-induced hippocampal damage. The neuroprotective effect of EBm is also due to nitric oxide-mediated cerebral vasodilation. EBm improved the total memory score and maximum improvement was seen in logical memory and paired associate learning in humans and reversed phenytoin-induced memory impairment in experimental model. EBm has not shown any serious clinical, neurological, hematological complications, or vital organs damage in experimental studies. Rats showed marked reduction in fertility; however, libido was unaffected. There is no experimental evidence of genotoxicity or teratogenesis by use of EBm. Mild nausea and gastrointestinal upset are seen in humans. Brahmi promises to be a novel agent in AD; however, further human trials are recommended to verify the efficacy and rule out any side effects as evidenced by the experimental models. PMID:28588366

Development of a quantitative validation method for forensic investigation of human spermatozoa using a commercial fluorescence staining kit (SPERM HY-LITER™ Express).

PubMed

Takamura, Ayari; Watanabe, Ken; Akutsu, Tomoko

2016-11-01

In investigations of sexual assaults, as well as in identifying a suspect, the detection of human sperm is important. Recently, a kit for fluorescent staining of human spermatozoa, SPERM HY-LITER™, has become available. This kit allows for microscopic observation of the heads of human sperm using an antibody tagged with a fluorescent dye. This kit is specific to human sperm and provides easy detection by luminescence. However, criteria need to be established to objectively evaluate the fluorescent signals and to evaluate the staining efficiency of this kit. These criteria will be indispensable for investigation of forensic samples. In the present study, the SPERM HY-LITER™ Express kit, which is an improved version of SPERM HY-LITER™, was evaluated using an image analysis procedure using Laplacian and Gaussian methods. This method could be used to automatically select important regions of fluorescence produced by sperm. The fluorescence staining performance was evaluated and compared under various experimental conditions, such as for aged traces and in combination with other chemical staining methods. The morphological characteristics of human sperm were incorporated into the criteria for objective identification of sperm, based on quantified features of the fluorescent spots. Using the criteria, non-specific or insignificant fluorescent spots were excluded, and the specificity of the kit for human sperm was confirmed. The image analysis method and criteria established in this study are universal and could be applied under any experimental conditions. These criteria will increase the reliability of operator judgment in the analysis of human sperm samples in forensics.

Demonstration of brain noise on human EEG signals in perception of bistable images

NASA Astrophysics Data System (ADS)

Grubov, Vadim V.; Runnova, Anastasiya E.; Kurovskaya, Maria K.; Pavlov, Alexey N.; Koronovskii, Alexey A.; Hramov, Alexander E.

2016-03-01

In this report we studied human brain activity in the case of bistable visual perception. We proposed a new approach for quantitative characterization of this activity based on analysis of EEG oscillatory patterns and evoked potentials. Accordingly to theoretical background, obtained experimental EEG data and results of its analysis we studied a characteristics of brain activity during decision-making. Also we have shown that decisionmaking process has the special patterns on the EEG data.

'Goats that stare at men': dwarf goats alter their behaviour in response to human head orientation, but do not spontaneously use head direction as a cue in a food-related context.

PubMed

Nawroth, Christian; von Borell, Eberhard; Langbein, Jan

2015-01-01

Recently, comparative research on the mechanisms and species-specific adaptive values of attributing attentive states and using communicative cues has gained increased interest, particularly in non-human primates, birds, and dogs. Here, we investigate these phenomena in a farm animal species, the dwarf goat (Capra aegagrus hircus). In the first experiment, we investigated the effects of different human head and body orientations, as well as human experimenter presence/absence, on the behaviour of goats in a food-anticipating paradigm. Over a 30-s interval, the experimenter engaged in one of four different postures or behaviours (head and body towards the subject-'Control', head to the side, head and body away from the subject, or leaving the room) before delivering a reward. We found that the level of subjects' active anticipatory behaviour was highest in the control condition and decreased with a decreasing level of attention paid to the subject by the experimenter. Additionally, goats 'stared' (i.e. stood alert) at the experimental set-up for significantly more time when the experimenter was present but paid less attention to the subject ('Head' and 'Back' condition) than in the 'Control' and 'Out' conditions. In a second experiment, the experimenter provided different human-given cues that indicated the location of a hidden food reward in a two-way object choice task. Goats were able to use both 'Touch' and 'Point' cues to infer the correct location of the reward but did not perform above the level expected by chance in the 'Head only' condition. We conclude that goats are able to differentiate among different body postures of a human, including head orientation; however, despite their success at using multiple physical human cues, they fail to spontaneously use human head direction as a cue in a food-related context.

Electrophysiological properties of computational human ventricular cell action potential models under acute ischemic conditions.

PubMed

Dutta, Sara; Mincholé, Ana; Quinn, T Alexander; Rodriguez, Blanca

2017-10-01

Acute myocardial ischemia is one of the main causes of sudden cardiac death. The mechanisms have been investigated primarily in experimental and computational studies using different animal species, but human studies remain scarce. In this study, we assess the ability of four human ventricular action potential models (ten Tusscher and Panfilov, 2006; Grandi et al., 2010; Carro et al., 2011; O'Hara et al., 2011) to simulate key electrophysiological consequences of acute myocardial ischemia in single cell and tissue simulations. We specifically focus on evaluating the effect of extracellular potassium concentration and activation of the ATP-sensitive inward-rectifying potassium current on action potential duration, post-repolarization refractoriness, and conduction velocity, as the most critical factors in determining reentry vulnerability during ischemia. Our results show that the Grandi and O'Hara models required modifications to reproduce expected ischemic changes, specifically modifying the intracellular potassium concentration in the Grandi model and the sodium current in the O'Hara model. With these modifications, the four human ventricular cell AP models analyzed in this study reproduce the electrophysiological alterations in repolarization, refractoriness, and conduction velocity caused by acute myocardial ischemia. However, quantitative differences are observed between the models and overall, the ten Tusscher and modified O'Hara models show closest agreement to experimental data. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

1-Amino-4-hydroxy-9,10-anthraquinone - An analogue of anthracycline anticancer drugs, interacts with DNA and induces apoptosis in human MDA-MB-231 breast adinocarcinoma cells: Evaluation of structure-activity relationship using computational, spectroscopic and biochemical studies.

PubMed

Mondal, Palash; Roy, Sanjay; Loganathan, Gayathri; Mandal, Bitapi; Dharumadurai, Dhanasekaran; Akbarsha, Mohammad A; Sengupta, Partha Sarathi; Chattopadhyay, Shouvik; Guin, Partha Sarathi

2015-12-01

The X-ray diffraction and spectroscopic properties of 1-amino-4-hydroxy-9,10-anthraquinone (1-AHAQ), a simple analogue of anthracycline chemotherapeutic drugs were studied by adopting experimental and computational methods. The optimized geometrical parameters obtained from computational methods were compared with the results of X-ray diffraction analysis and the two were found to be in reasonably good agreement. X-ray diffraction study, Density Functional Theory (DFT) and natural bond orbital (NBO) analysis indicated two types of hydrogen bonds in the molecule. The IR spectra of 1-AHAQ were studied by Vibrational Energy Distribution Analysis (VEDA) using potential energy distribution (PED) analysis. The electronic spectra were studied by TDDFT computation and compared with the experimental results. Experimental and theoretical results corroborated each other to a fair extent. To understand the biological efficacy of 1-AHAQ, it was allowed to interact with calf thymus DNA and human breast adino-carcinoma cell MDA-MB-231. It was found that the molecule induces apoptosis in this adinocarcinoma cell, with little, if any, cytotoxic effect in HBL-100 normal breast epithelial cell.

Laboratory production in vivo of infectious human papillomavirus type 11.

PubMed Central

Kreider, J W; Howett, M K; Leure-Dupree, A E; Zaino, R J; Weber, J A

1987-01-01

Human papillomaviruses (HPV) induce among patients natural lesions which produce small amounts of virus. Infection of human cell cultures does not lead to the multiplication of virus, which also does not replicate in experimental animals. We have developed a unique system for the laboratory production of HPV type 11 (HPV-11). Fragments of human neonatal foreskin were infected with an extract of naturally occurring human vulvar condylomata and grafted beneath the renal capsule of athymic mice. Later (3 to 5 months), condylomatous cysts developed from those grafts. Nuclei of koilocytotic cells contained large amounts of capsid antigen and intranuclear virions. The experimentally induced condylomata were homogenized, and the virions were extracted and used to infect another generation of human foreskin grafts in athymic mice. The HPV-11 DNA content and infectivity of the natural and experimental condylomata were similar. Extracts of experimental condylomata were subjected to differential ultracentrifugation and sedimentation in CsCl density gradients. A single, opalescent band was visible at a density of 1.34 g/ml. It contained HPV virions with HPV-11 DNA. This report is the first demonstration of the laboratory production of an HPV. Images PMID:3027386

Experimental intrauterine growth retardation.

PubMed

van Marthens, E; Harel, S; Zamenshof, S

1975-01-01

The effects of experimental intrauterine growth retardation on subsequent fetal development, especially with respect to brain development, were studied in a new animal model. The rabbit was chosen since it has a perinatal pattern of brain development similar to that of the human. Experimental ischemia was induced during the last trimester by ligation of spiral arterioles and the differential effects on fetal development at term (30th gestational day) are reported. Specific brain regions were examined for wet weight, total cell number (DNA) and total protein content. Highly significant decreases in all these parameters were found in both the cortex and cerebellum following experimental intrauterine growth retardation; these two organs were differentially affected. The prospects and advantages of using this animal model for the study of the postnatal "catch-up growth" are discussed.

A review and preliminary evaluation of methodological factors in performance assessments of time-varying aircraft noise effects

NASA Technical Reports Server (NTRS)

Coates, G. D.; Alluisi, E. A.

1975-01-01

The effects of aircraft noise on human performance is considered. Progress is reported in the following areas: (1) review of the literature to identify the methodological and stimulus parameters involved in the study of noise effects on human performance; (2) development of a theoretical framework to provide working hypotheses as to the effects of noise on complex human performance; and (3) data collection on the first of several experimental investigations designed to provide tests of the hypotheses.

New, More Authentic Model for AIDS Will Accelerate Studies | Poster

Cancer.gov

By Frank Blanchard, Staff Writer, and Jeff Lifson, Guest Writer Researchers are working to develop a more authentic animal model of human immunodeficiency virus (HIV) infection and AIDS that is expected to speed up studies of experimental treatments and vaccines.

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

PubMed Central

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

2016-01-01

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

Systemic effects of H2S inhalation at human equivalent dose of pathologic halitosis on rats.

PubMed

Yalçın Yeler, Defne; Aydin, Murat; Gül, Mehmet; Hocaoğlu, Turgay; Özdemir, Hakan; Koraltan, Melike

2017-10-01

Halitosis is composed by hundreds of toxic gases. It is still not clear whether halitosis gases self-inhaled by halitosis patients cause side effects. The aim of the study was to investigate the effect of H 2 S inhalation at a low concentration (human equivalent dose of pathologic halitosis) on rats. The threshold level of pathologic halitosis perceived by humans at 250 ppb of H 2 S was converted to rat equivalent concentration (4.15 ppm). In the experimental group, 8 rats were exposed to H 2 S via continuous inhalation but not the control rats. After 50 days, blood parameters were measured and tissue samples were obtained from the brain, kidney and liver and examined histopathologically to determine any systemic effect. While aspartate transaminase, creatine kinase-MB and lactate dehydrogenase levels were found to be significantly elevated, carbondioxide and alkaline phosphatase were decreased in experimental rats. Other blood parameters were not changed significantly. Experimental rats lost weight and became anxious. Histopathological examination showed mononuclear inflammatory cell invasion in the portal areas, nuclear glycogen vacuoles in the parenchymal area, single-cell necrosis in a few foci, clear expansion in the central hepatic vein and sinusoids, hyperplasia in Kupffer cells and potential fibrous tissue expansion in the portal areas in the experimental rats. However, no considerable histologic damage was observed in the brain and kidney specimens. It can be concluded that H 2 S inhalation equivalent to pathologic halitosis producing level in humans may lead to systemic effects, particularly heart or liver damage in rats.

75 FR 42087 - Science Advisory Board Staff Office; Request for Nominations of Experts for the SAB Hydraulic...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-20

... regarding trace organics and environmental monitoring; statistics, particularly regarding experimental design of field studies; human health effects and risk assessment; civil and environmental engineering...

An experimental study for determining human discomfort response to roll vibration

NASA Technical Reports Server (NTRS)

Leatherwood, J. D.; Dempsey, T. K.; Clevenson, S. A.

1976-01-01

An experimental study using a passenger ride quality apparatus (PRQA) was conducted to determine the subjective reactions of passengers to roll vibrations. The data obtained illustrate the effect upon human comfort of several roll-vibration parameters: namely, roll acceleration level, roll frequency, and seat location (i.e., distance from axis of rotation). Results of an analysis of variance indicated that seat location had no effect on discomfort ratings of roll vibrations. The effect of roll acceleration level was significant, and discomfort ratings increased markedly with increasing roll acceleration level at all roll frequencies investigated. Of particular interest, is the fact that the relationship between discomfort ratings and roll acceleration level was linear in nature. The effect of roll frequency also was significant as was the interaction between roll acceleration level and roll frequency.

Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human.

PubMed

Morgan, Michael M; Christie, MacDonald J

2011-10-01

Opioid agonists are the most effective treatment for pain, but their use is limited by side effects, tolerance and fears of addiction and dependence. A major goal of opioid research is to develop agonists that have high analgesic efficacy and a low profile for side effects, tolerance, addiction and dependence. Unfortunately, there is a serious lack of experimental data comparing the degree to which different opioids produce these effects in humans. In contrast, a wide range of experimental techniques from heterologous expression systems to behaviour assessment in whole animals have been developed to study these problems. The objective of this review is to describe and evaluate these techniques as they are used to study opioid efficacy, tolerance, addiction and dependence. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Sudden unexpected death in epilepsy genetics: Molecular diagnostics and prevention.

PubMed

Goldman, Alica M; Behr, Elijah R; Semsarian, Christopher; Bagnall, Richard D; Sisodiya, Sanjay; Cooper, Paul N

2016-01-01

Epidemiologic studies clearly document the public health burden of sudden unexpected death in epilepsy (SUDEP). Clinical and experimental studies have uncovered dynamic cardiorespiratory dysfunction, both interictally and at the time of sudden death due to epilepsy. Genetic analyses in humans and in model systems have facilitated our current molecular understanding of SUDEP. Many discoveries have been informed by progress in the field of sudden cardiac death and sudden infant death syndrome. It is becoming apparent that SUDEP genomic complexity parallels that of sudden cardiac death, and that there is a pauci1ty of analytically useful postmortem material. Because many challenges remain, future progress in SUDEP research, molecular diagnostics, and prevention rests in international, collaborative, and transdisciplinary dialogue in human and experimental translational research of sudden death. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Models and mechanisms of anxiety: evidence from startle studies

PubMed Central

Grillon, Christian

2009-01-01

Rationale Preclinical data indicates that threat stimuli elicit two classes of defensive behaviors, those that are associated with imminent danger and are characterized by avoidance or fight (fear), and those that are associated with temporally uncertain danger and are characterized by sustained apprehension and hypervigilance (anxiety). Objective To 1) review evidence for a distinction between fear and anxiety in animal and human experimental models using the startle reflex as an operational measure of aversive states, 2) describe experimental models of anxiety, as opposed to fear, in humans, 3) examine the relevance of these models to clinical anxiety. Results The distinction between phasic fear to imminent threat and sustained anxiety to temporally uncertain danger is suggested by psychopharmacological and behavioral evidence from ethological studies and can be traced back to distinct neuroanatomical systems, the amygdala and the bed nucleus of the stria terminalis. Experimental models of anxiety, not fear, are relevant to non-phobic anxiety disorders. Conclusions Progress in our understanding of normal and abnormal anxiety is critically dependent on our ability to model sustained aversive states to temporally uncertain threat. PMID:18058089

Whole parasite blood stage malaria vaccines: a convergence of evidence.

PubMed

McCarthy, James S; Good, Michael F

2010-01-01

There is a growing realization of the limitations of recombinant protein-based malaria vaccines. This, coupled with a better understanding of the protective immunity to malaria, both in animal models and in naturally exposed human populations and experimentally infected volunteers, as well as the increased capacity to manipulate parasites provides new impetus to evaluate whole blood stage parasite approaches to malaria vaccine development. In this review previous studies in rodents and primates of whole killed and attenuated blood stage vaccines, and recent work on the effect of genetically attenuated parasites on immunity in rodent models of blood stage immunity are discussed. The relationship between these findings and what is now known about protective immunity in human populations, specifically against the blood stages of the parasite lifecycle is discussed and recent findings from human experimental infection are be reviewed. Finally, the prospect for and impediments to the development whole blood stage parasites are reviewed.

THE INVOLVEMENT OF HUMAN MONOGENIC CARDIOMYOPATHY GENES IN EXPERIMENTAL POLYGENIC CARDIAC HYPERTROPHY.

PubMed

Prestes, Priscilla R; Marques, Francine Z; Lopez-Campos, Guillermo; Lewandowski, Paul; Delbridge, Lea M D; Charchar, Fadi J; Harrap, Stephen B

2018-05-18

Hypertrophic cardiomyopathy thickens heart muscles reducing functionality and increasing risk of cardiac disease and morbidity. Genetic factors are involved, but their contribution is poorly understood. We used the hypertrophic heart rat (HHR), a unique normotensive polygenic model of cardiac hypertrophy and heart failure to investigate the role of genes associated with monogenic human cardiomyopathy. We selected 42 genes involved in monogenic human cardiomyopathies to study: 1) DNA variants, by sequencing the whole-genome of 13-week old HHR and age-matched normal heart rat (NHR), its genetic control strain; 2) mRNA expression, by targeted RNA-sequencing in left ventricles of HHR and NHR at five ages (2-days old, 4-, 13-, 33- and 50-weeks old) compared to human idiopathic dilated data; and 3) microRNA expression, with rat microRNA microarrays in left ventricles of 2-days old HHR and age-matched NHR. We also investigated experimentally validated microRNA-mRNA interactions. Whole-genome sequencing revealed unique variants mostly located in non-coding regions of HHR and NHR. We found 29 genes differentially expressed in at least one age. Genes encoding desmoglein 2 (Dsg2) and transthyretin (Ttr) were significantly differentially expressed at all ages in the HHR, but only Ttr was also differentially expressed in human idiopathic cardiomyopathy. Lastly, only two microRNAs differentially expressed in the HHR were present in our comparison of validated microRNA-mRNA interactions. These two microRNAs interact with five of the genes studied. Our study shows that genes involved in monogenic forms of human cardiomyopathies may also influence polygenic forms of the disease.

Human versus animal: contrasting decomposition dynamics of mammalian analogues in experimental taphonomy.

PubMed

Stokes, Kathryn L; Forbes, Shari L; Tibbett, Mark

2013-05-01

Taphonomic studies regularly employ animal analogues for human decomposition due to ethical restrictions relating to the use of human tissue. However, the validity of using animal analogues in soil decomposition studies is still questioned. This study compared the decomposition of skeletal muscle tissues (SMTs) from human (Homo sapiens), pork (Sus scrofa), beef (Bos taurus), and lamb (Ovis aries) interred in soil microcosms. Fixed interval samples were collected from the SMT for microbial activity and mass tissue loss determination; samples were also taken from the underlying soil for pH, electrical conductivity, and nutrient (potassium, phosphate, ammonium, and nitrate) analysis. The overall patterns of nutrient fluxes and chemical changes in nonhuman SMT and the underlying soil followed that of human SMT. Ovine tissue was the most similar to human tissue in many of the measured parameters. Although no single analogue was a precise predictor of human decomposition in soil, all models offered close approximations in decomposition dynamics. © 2013 American Academy of Forensic Sciences.

Genetically diverse CC-founder mouse strains replicate the human influenza gene expression signature.

PubMed

Elbahesh, Husni; Schughart, Klaus

2016-05-19

Influenza A viruses (IAV) are zoonotic pathogens that pose a major threat to human and animal health. Influenza virus disease severity is influenced by viral virulence factors as well as individual differences in host response. We analyzed gene expression changes in the blood of infected mice using a previously defined set of signature genes that was derived from changes in the blood transcriptome of IAV-infected human volunteers. We found that the human signature was reproduced well in the founder strains of the Collaborative Cross (CC) mice, thus demonstrating the relevance and importance of mouse experimental model systems for studying human influenza disease.

Controlled human infection with RSV: The opportunities of experimental challenge.

PubMed

Habibi, Maximillian S; Chiu, Christopher

2017-01-11

Despite the recent explosion in RSV vaccine development, there remain substantial hurdles to overcome before licensing of effective vaccines will allow widespread use, particularly in high-risk populations. Incomplete understanding of mechanisms and correlates of protection against RSV mean that, for the time being, successful RSV vaccines must directly demonstrate efficacy, which necessitates large and costly clinical trials in naturally infected patients. To mitigate the risks inherent in progressing to these late-stage trials, experimental human RSV infection studies have recently been re-established, representing the interface between pre-clinical models and observational studies of patients. Not only can they be used for early proof-of-concept clinical trials to test vaccine efficacy, but human challenge studies also offer the potential to better understand protective immunity against RSV infection to improve vaccine design and delivery. In the past, controlled human infection studies with RSV have been instrumental in elucidating the influence of factors such as route of infection and type of inoculum on the course of disease. Recently, efficacy trials of novel RSV antiviral drugs have also been successfully undertaken. Now, with advances in technology, detailed investigations of human mucosal immunity in the RSV-infected airway are possible. These have indicated defects in RSV-induced humoral and CD8+ T cell immunity that may contribute to the recurrent symptomatic infection that occurs throughout life and should be circumvented by optimal vaccines. Here, we discuss the insights derived from RSV human challenge models; the major impediments to their more widespread uptake; and their potential benefit in accelerating vaccine development, including future directions to further enhance the relevance of these models to at-risk patient populations. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Psychophysiology of Delayed Extinction and Reconsideration in Humans

DTIC Science & Technology

2012-02-01

modify or block it. The aim of this project is to create an experimental assay in the form of an optimal Pavlovian differential fear conditioning ...The aim of this project is to create an experimental assay in the form of an optimal Pavlovian differential fear conditioning paradigm. Animal...open label study examining the relative efficacies of pharmacological and non- drug interventions within a fear conditioning paradigm. At the time of

Pathogen transmission in relation to duration of attachment by Ixodes scapularis ticks.

PubMed

Eisen, Lars

2018-03-01

The blacklegged tick, Ixodes scapularis, is the primary vector to humans in the eastern United States of the deer tick virus lineage of Powassan virus (Powassan virus disease); the protozoan parasite Babesia microti (babesiosis); and multiple bacterial disease agents including Anaplasma phagocytophilum (anaplasmosis), Borrelia burgdorferi and Borrelia mayonii (Lyme disease), Borrelia miyamotoi (relapsing fever-like illness, named Borrelia miyamotoi disease), and Ehrlichia muris eauclairensis (a minor causative agent of ehrlichiosis). With the notable exception of Powassan virus, which can be transmitted within minutes after attachment by an infected tick, there is no doubt that the risk of transmission of other I. scapularis-borne pathogens, including Lyme disease spirochetes, increases with the length of time (number of days) infected ticks are allowed to remain attached. This review summarizes data from experimental transmission studies to reinforce the important disease-prevention message that regular (at least daily) tick checks and prompt tick removal has strong potential to reduce the risk of transmission of I. scapularis-borne bacterial and parasitic pathogens from infected attached ticks. The most likely scenario for human exposure to an I. scapularis-borne pathogen is the bite by a single infected tick. However, recent reviews have failed to make a clear distinction between data based on transmission studies where experimental hosts were fed upon by a single versus multiple infected ticks. A summary of data from experimental studies on transmission of Lyme disease spirochetes (Bo. burgdorferi and Bo. mayonii) by I. scapularis nymphs indicates that the probability of transmission resulting in host infection, at time points from 24 to 72 h after nymphal attachment, is higher when multiple infected ticks feed together as compared to feeding by a single infected tick. In the specific context of risk for human infection, the most relevant experimental studies therefore are those where the probability of pathogen transmission at a given point in time after attachment was determined using a single infected tick. The minimum duration of attachment by single infected I. scapularis nymphs required for transmission to result in host infection is poorly defined for most pathogens, but experimental studies have shown that Powassan virus can be transmitted within 15 min of tick attachment and both A. phagocytophilum and Bo. miyamotoi within the first 24 h of attachment. There is no experimental evidence for transmission of Lyme disease spirochetes by single infected I. scapularis nymphs to result in host infection when ticks are attached for only 24 h (despite exposure of nearly 90 experimental rodent hosts across multiple studies) but the probability of transmission resulting in host infection appears to increase to approximately 10% by 48 h and reach 70% by 72 h for Bo. burgdorferi. Caveats to the results from experimental transmission studies, including specific circumstances (such as re-attachment of previously partially fed infected ticks) that may lead to more rapid transmission are discussed. Published by Elsevier GmbH.

Estrogen receptor β actions in the female cardiovascular system: A systematic review of animal and human studies.

PubMed

Muka, Taulant; Vargas, Kris G; Jaspers, Loes; Wen, Ke-xin; Dhana, Klodian; Vitezova, Anna; Nano, Jana; Brahimaj, Adela; Colpani, Veronica; Bano, Arjola; Kraja, Bledar; Zaciragic, Asija; Bramer, Wichor M; van Dijk, Gaby M; Kavousi, Maryam; Franco, Oscar H

2016-04-01

Five medical databases were searched for studies that assessed the role of ERβ in the female cardiovascular system and the influence of age and menopause on ERβ functioning. Of 9472 references, 88 studies met our inclusion criteria (71 animal model experimental studies, 15 human model experimental studies and 2 population based studies). ERβ signaling was shown to possess vasodilator and antiangiogenic properties by regulating the activity of nitric oxide, altering membrane ionic permeability in vascular smooth muscle cells, inhibiting vascular smooth muscle cell migration and proliferation and by regulating adrenergic control of the arteries. Also, a possible protective effect of ERβ signaling against left ventricular hypertrophy and ischemia/reperfusion injury via genomic and non-genomic pathways was suggested in 27 studies. Moreover, 5 studies reported that the vascular effects of ERβ may be vessel specific and may differ by age and menopause status. ERβ seems to possess multiple functions in the female cardiovascular system. Further studies are needed to evaluate whether isoform-selective ERβ-ligands might contribute to cardiovascular disease prevention. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A porcine model: surgical anatomy of the orbit for maxillofacial surgery.

PubMed

Kyllar, Michal; Štembírek, Jan; Danek, Zdenek; Hodan, Radek; Stránský, Jiří; Machoň, Vladimír; Foltán, René

2016-04-01

Due to its similarity to humans, the pig has proven to be a suitable biomodel for both research purposes and for training medical professionals, particularly in surgical specializations. For example, new implant materials have been tested on pig jaws and pigs have also been used in the development of new surgical techniques. For optimizing the effectiveness of such research or training, detailed data on the anatomy of their particular features are needed. At present, however, only limited information related to surgical and imaging anatomy of the facial and orbital areas of the pig and its comparison to human structures from the experimental surgery point of view is available in the literature. The aim of this study was to obtain such data and to compare the morphological structures of the porcine and human orbital regions and to lay down the foundation for practical use in experimental surgery. Ten pig heads were examined using computed tomography (CT) and magnetic resonance imaging (MRI) and, subsequently, a dissection of the orbit was carried out. Attention was focused on the structure of the orbit (floor, rim and nerves) frequently affected by pathological processes in humans (such as trauma, infection or tumours) and which consequently are frequently the subject of maxillofacial surgery. The porcine orbit is suitable for use in experimental medicine. However, if used in experiments, its anatomical peculiarities must be taken into consideration. Our study presents a foundation of basic knowledge for researchers who plan to use the pig as a biomedical model to investigate alternative treatments in the head region. © The Author(s) 2015.

Chimeric mice with humanized liver: Application in drug metabolism and pharmacokinetics studies for drug discovery.

PubMed

Naritomi, Yoichi; Sanoh, Seigo; Ohta, Shigeru

2018-02-01

Predicting human drug metabolism and pharmacokinetics (PK) is key to drug discovery. In particular, it is important to predict human PK, metabolite profiles and drug-drug interactions (DDIs). Various methods have been used for such predictions, including in vitro metabolic studies using human biological samples, such as hepatic microsomes and hepatocytes, and in vivo studies using experimental animals. However, prediction studies using these methods are often inconclusive due to discrepancies between in vitro and in vivo results, and interspecies differences in drug metabolism. Further, the prediction methods have changed from qualitative to quantitative to solve these issues. Chimeric mice with humanized liver have been developed, in which mouse liver cells are mostly replaced with human hepatocytes. Since human drug metabolizing enzymes are expressed in the liver of these mice, they are regarded as suitable models for mimicking the drug metabolism and PK observed in humans; therefore, these mice are useful for predicting human drug metabolism and PK. In this review, we discuss the current state, issues, and future directions of predicting human drug metabolism and PK using chimeric mice with humanized liver in drug discovery. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Translational overview of cytokine inhibition in acute myocardial infarction and chronic heart failure.

PubMed

Hartman, Minke H T; Groot, Hilde E; Leach, Irene Mateo; Karper, Jacco C; van der Harst, Pim

2018-02-15

Many cytokines are currently under investigation as potential target to improve cardiac function and outcome in the setting of acute myocardial infarction (MI) or chronic heart failure (HF). Here we aim to provide a translational overview of cytokine inhibiting therapies tested in experimental models and clinical studies. In various experimental studies, inhibition of interleukin-1 (IL-1), -6 (IL-6), -8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), CC- and CXC chemokines, and tumor necrosis factor-α (TNF-α) had beneficial effects on cardiac function and outcome. On the other hand, neutral or even detrimental results have been reported for some (IL-1, IL-6, IL-8, and MCP-1). Ambivalence of cytokine function, differences in study designs, treatment regimens and chosen endpoints hamper the translation of experimental research into clinical practice. Human studies are currently limited to IL-1β inhibition, IL-1 receptor antagonists (IL-1RA), IL-6 receptor antagonists (IL-6RA) or TNF inhibition. Despite favorable effects on cardiovascular events observed in retrospective cohort studies of rheumatoid arthritis patients treated with TNF inhibition or IL-1RA, most prospective studies reported disappointing and inconsistent results. Smaller studies (n < 100) generally reported favorable results of anticytokine therapy on cardiac function, but only one of the larger studies (n > 100) evaluating IL-1β inhibition presented positive results on outcome. In conclusion, of the 10 anticytokine therapies tested in animals models beneficial effects have been reported in at least one setting. In larger clinical studies, findings were unsatisfactory in all but one. Many anticytokine therapies with promising animal experimental data continue to require further evaluation in humans. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Experimental study showed that adding fortifier and extra-hydrolysed proteins to preterm infant mothers' milk increased osmolality.

PubMed

Rosas, R; Sanz, M P; Fernández-Calle, P; Alcaide, M J; Montes, M T; Pastrana, N; Segovia, C; Omeñaca, F; Sáenz de Pipaón, M

2016-12-01

Measuring milk osmolality after adjustable fortification is clinically relevant, as values exceeding recommended safety thresholds might result in gastrointestinal consequences. The aim of this study was to evaluate the effect of four fortification levels and storage time on the osmolality of human milk. This was an experimental study using 71 spare samples of fresh breastmilk collected from 31 mothers of preterm infants. Osmolality was measured before and after adding commercial human milk fortifier containing dextrinomaltose and hydrolysed proteins at four different concentrations. Measurements were performed at various points during the 23 hours after fortification. The mean basal osmolality of the 71 human milk samples was 296 ± 14 milliosmoles (mOsm)/kg, and these remained stable over a period of 23 hours. Just after fortification, the four fortified formulas showed higher osmolalities than the nonfortified human milk, ranging between 384 ± 14 and 486 ± 15 mOsm/kg, respectively (p < 0.01). This osmolality increased significantly from 20 minutes to 23 hours after fortification (p < 0.05). Adding fortifier and extra-hydrolysed proteins to human preterm milk increased osmolality, and these osmolality levels also increased with time. We recommend evaluating the risk of hyperosmolality when a higher fortification level is needed, to avoid gastrointestinal problems. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Short-term fasting alters cytochrome P450-mediated drug metabolism in humans.

PubMed

Lammers, Laureen A; Achterbergh, Roos; de Vries, Emmely M; van Nierop, F Samuel; Klümpen, Heinz-Josef; Soeters, Maarten R; Boelen, Anita; Romijn, Johannes A; Mathôt, Ron A A

2015-06-01

Experimental studies indicate that short-term fasting alters drug metabolism. However, the effects of short-term fasting on drug metabolism in humans need further investigation. Therefore, the aim of this study was to evaluate the effects of short-term fasting (36 h) on P450-mediated drug metabolism. In a randomized crossover study design, nine healthy subjects ingested a cocktail consisting of five P450-specific probe drugs [caffeine (CYP1A2), S-warfarin (CYP2C9), omeprazole (CYP2C19), metoprolol (CYP2D6), and midazolam (CYP3A4)] on two occasions (control study after an overnight fast and after 36 h of fasting). Blood samples were drawn for pharmacokinetic analysis using nonlinear mixed effects modeling. In addition, we studied in Wistar rats the effects of short-term fasting on hepatic mRNA expression of P450 isoforms corresponding with the five studied P450 enzymes in humans. In the healthy subjects, short-term fasting increased oral caffeine clearance by 20% (P = 0.03) and decreased oral S-warfarin clearance by 25% (P < 0.001). In rats, short-term fasting increased mRNA expression of the orthologs of human CYP1A2, CYP2C19, CYP2D6, and CYP3A4 (P < 0.05), and decreased the mRNA expression of the ortholog of CYP2C9 (P < 0.001) compared with the postabsorptive state. These results demonstrate that short-term fasting alters cytochrome P450-mediated drug metabolism in a nonuniform pattern. Therefore, short-term fasting is another factor affecting cytochrome P450-mediated drug metabolism in humans. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Silica and lung cancer: a controversial issue.

PubMed

Pairon, J C; Brochard, P; Jaurand, M C; Bignon, J

1991-06-01

The role of crystalline silica in lung cancer has long been the subject of controversy. In this article, we review the main experimental and epidemiological studies dealing with this problem. Some evidence for a genotoxic potential of crystalline silica has been obtained in the rare in vitro studies published to date. In vivo studies have shown that crystalline silica is carcinogenic in the rat; the tumour types appear to vary according to the route of administration. In addition, an association between carcinogenic and fibrogenic potency has been observed in various animal species exposed to crystalline silica. An excess of lung cancer related to occupational exposure to crystalline silica is reported in many epidemiological studies, regardless of the presence of silicosis. However, most of these studies are difficult to interpret because they do not correctly take into account associated carcinogens such as tobacco smoke and other occupational carcinogens. An excess of lung cancer is generally reported in studies based on silicosis registers. Overall, experimental and human studies suggest an association between exposure to crystalline silica and an excess of pulmonary malignancies. Although the data available are not sufficient to establish a clear-cut causal relationship in humans, an association between the onset of pneumoconiosis and pulmonary malignancies is probable. In contrast, experimental observations have given rise to a pathophysiological mechanism that might account for a putative carcinogenic potency of crystalline silica.

A model of fluid and solute exchange in the human: validation and implications.

PubMed

Bert, J L; Gyenge, C C; Bowen, B D; Reed, R K; Lund, T

2000-11-01

In order to understand better the complex, dynamic behaviour of the redistribution and exchange of fluid and solutes administered to normal individuals or to those with acute hypovolemia, mathematical models are used in addition to direct experimental investigation. Initial validation of a model developed by our group involved data from animal experiments (Gyenge, C.C., Bowen, B.D., Reed, R.K. & Bert, J.L. 1999b. Am J Physiol 277 (Heart Circ Physiol 46), H1228-H1240). For a first validation involving humans, we compare the results of simulations with a wide range of different types of data from two experimental studies. These studies involved administration of normal saline or hypertonic saline with Dextran to both normal and 10% haemorrhaged subjects. We compared simulations with data including the dynamic changes in plasma and interstitial fluid volumes VPL and VIT respectively, plasma and interstitial colloid osmotic pressures PiPL and PiIT respectively, haematocrit (Hct), plasma solute concentrations and transcapillary flow rates. The model predictions were overall in very good agreement with the wide range of experimental results considered. Based on the conditions investigated, the model was also validated for humans. We used the model both to investigate mechanisms associated with the redistribution and transport of fluid and solutes administered following a mild haemorrhage and to speculate on the relationship between the timing and amount of fluid infusions and subsequent blood volume expansion.

Viscoelastic modeling and quantitative experimental characterization of normal and osteoarthritic human articular cartilage using indentation.

PubMed

Richard, F; Villars, M; Thibaud, S

2013-08-01

The viscoelastic behavior of articular cartilage changes with progression of osteoarthritis. The objective of this study is to quantify this progression and to propose a viscoelastic model of articular cartilage taking into account the degree of osteoarthritis that which be easily used in predictive numerical simulations of the hip joint behavior. To quantify the effects of osteoarthritis (OA) on the viscoelastic behavior of human articular cartilage, samples were obtained from the hip arthroplasty due to femoral neck fracture (normal cartilage) or advanced coxarthrosis (OA cartilage). Experimental data were obtained from instrumented indentation tests on unfrozen femoral cartilage collected and studied in the day following the prosthetic hip surgery pose. By using an inverse method coupled with a numerical modeling (FEM) of all experimental data of the indentation tests, the viscoelastic properties of the two states were quantified. Mean values of viscoelastic parameters were significantly lower for OA cartilage than normal (instantaneous and relaxed tension moduli, viscosity coefficient). Based on the results and in the thermodynamic framework, a constitutive viscoelastic model taking into account the degree of osteoarthritis as an internal variable of damage is proposed. The isotropic phenomenological viscoelastic model including degradation provides an accurate prediction of the mechanical response of the normal human cartilage and OA cartilage with advanced coxarthrosis but should be further validated for intermediate degrees of osteoarthritis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Economic Opportunities and Gender Differences in Human Capital: Experimental Evidence for India. NBER Working Paper No. 16021

ERIC Educational Resources Information Center

Jensen, Robert T.

2010-01-01

Gender differences in health and education are a concern for a number of developing countries. While standard theory predicts human capital should respond to market returns, social norms (e.g., disapproval of women working outside the home) may weaken or even sever this link for girls. Though many studies have examined the link between women's…

Innate immunity in Alzheimer's disease: the relevance of animal models?

PubMed

Franco Bocanegra, Diana K; Nicoll, James A R; Boche, Delphine

2018-05-01

The mouse is one of the organisms most widely used as an animal model in biomedical research, due to the particular ease with which it can be handled and reproduced in laboratory. As a member of the mammalian class, mice share with humans many features regarding metabolic pathways, cell morphology and anatomy. However, important biological differences between mice and humans exist and must be taken into consideration when interpreting research results, to properly translate evidence from experimental studies into information that can be useful for human disease prevention and/or treatment. With respect to Alzheimer's disease (AD), much of the experimental information currently known about this disease has been gathered from studies using mainly mice as models. Therefore, it is notably important to fully characterise the differences between mice and humans regarding important aspects of the disease. It is now widely known that inflammation plays an important role in the development of AD, a role that is not only a response to the surrounding pathological environment, but rather seems to be strongly implicated in the aetiology of the disease as indicated by the genetic studies. This review highlights relevant differences in inflammation and in microglia, the innate immune cell of the brain, between mice and humans regarding genetics and morphology in normal ageing, and the relationship of microglia with AD-like pathology, the inflammatory profile, and cognition. We conclude that some noteworthy differences exist between mice and humans regarding microglial characteristics, in distribution, gene expression, and states of activation. This may have repercussions in the way that transgenic mice respond to, and influence, the AD-like pathology. However, despite these differences, human and mouse microglia also show similarities in morphology and behaviour, such that the mouse is a suitable model for studying the role of microglia, as long as these differences are taken into consideration when delineating new strategies to approach the study of neurodegenerative diseases.

[Culture conditions for gametes and embryos: Which culture medium? Which impact on newborn?

PubMed

Koscinski, I; Merten, M; Kazdar, N; Guéant, J-L

2018-05-01

Many studies have examined the impact of cell/embryo culture media on the development of human embryo during IVF process, but few studies have followed up and compared the effects of these culture media on the developmental outcome of children conceived by IVF. As recurrent experimental evidence from animal studies suggests potential long-term effects of embryo culture media on the health outcome of IVF-conceived children, more studies are needed to clarify the role of the culture media and mechanisms underlying such effects. In human, however, the effects of culture media are difficult to pinpoint due to complications stem from both the influence of maternal nutrition during the gestational period and the parental genetic. Based on a simple review of the literature integrating animal experimentations and human clinic studies, we suggest that the composition of culture medium should be considered beyond the character of unique or sequential medium, corresponding to "let embryo choose" or "back to nature" respectively. Instead, we suggest that the main components of embryo culture media should be considered from the point of view of metabolic consequences and potential epigenetic effects. Given that energetic metabolites can regulate epigenetic machinery, we hypothesize that metabolic abnormalities linked to morphological abnormalities could reveal epigenetic defects in embryos. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Influence of Cultural, Organizational, and Automation Capability on Human Automation Trust: A Case Study of Auto-GCAS Experimental Test Pilots

NASA Technical Reports Server (NTRS)

Koltai, Kolina; Ho, Nhut; Masequesmay, Gina; Niedober, David; Skoog, Mark; Cacanindin, Artemio; Johnson, Walter; Lyons, Joseph

2014-01-01

This paper discusses a case study that examined the influence of cultural, organizational and automation capability upon human trust in, and reliance on, automation. In particular, this paper focuses on the design and application of an extended case study methodology, and on the foundational lessons revealed by it. Experimental test pilots involved in the research and development of the US Air Force's newly developed Automatic Ground Collision Avoidance System served as the context for this examination. An eclectic, multi-pronged approach was designed to conduct this case study, and proved effective in addressing the challenges associated with the case's politically sensitive and military environment. Key results indicate that the system design was in alignment with pilot culture and organizational mission, indicating the potential for appropriate trust development in operational pilots. These include the low-vulnerability/ high risk nature of the pilot profession, automation transparency and suspicion, system reputation, and the setup of and communications among organizations involved in the system development.

Type I interferons in tuberculosis: Foe and occasionally friend.

PubMed

Moreira-Teixeira, Lúcia; Mayer-Barber, Katrin; Sher, Alan; O'Garra, Anne

2018-05-07

Tuberculosis remains one of the leading causes of mortality worldwide, and, despite its clinical significance, there are still significant gaps in our understanding of pathogenic and protective mechanisms triggered by Mycobacterium tuberculosis infection. Type I interferons (IFN) regulate a broad family of genes that either stimulate or inhibit immune function, having both host-protective and detrimental effects, and exhibit well-characterized antiviral activity. Transcriptional studies have uncovered a potential deleterious role for type I IFN in active tuberculosis. Since then, additional studies in human tuberculosis and experimental mouse models of M. tuberculosis infection support the concept that type I IFN promotes both bacterial expansion and disease pathogenesis. More recently, studies in a different setting have suggested a putative protective role for type I IFN. In this study, we discuss the mechanistic and contextual factors that determine the detrimental versus beneficial outcomes of type I IFN induction during M. tuberculosis infection, from human disease to experimental mouse models of tuberculosis. © 2018 Moreira-Teixeira et al.

The Jeremiah Metzger lecture of The American Clinical and Climatological Association 1975. New genetic insight into old diseases.

PubMed Central

McKusick, V. A.

1976-01-01

With these three examples, examined in some detail, I have attempted to indicate new directions in medical genetics. Some of the recognizable generalities are the following: 1. With the application of cell culture techniques in the area called human somatic cell genetics, human genetics has become essentially an experimental science. Somaticcell studies have provided insight into genetic disorders that would not have been possible from studies in the whole organism. Even therapeutic possibilities can be explored. Somatic cell hyubridization has substituted for controlled matings in permitting linkage studies for mapping of the human chromosomes... Images Fig. 1 Fig. 8 Fig. 9 PMID:960419

Human skin volatiles: a review.

PubMed

Dormont, Laurent; Bessière, Jean-Marie; Cohuet, Anna

2013-05-01

Odors emitted by human skin are of great interest to biologists in many fields; applications range from forensic studies to diagnostic tools, the design of perfumes and deodorants, and the ecology of blood-sucking insect vectors of human disease. Numerous studies have investigated the chemical composition of skin odors, and various sampling methods have been used for this purpose. The literature shows that the chemical profile of skin volatiles varies greatly among studies, and the use of different sampling procedures is probably responsible for some of these variations. To our knowledge, this is the first review focused on human skin volatile compounds. We detail the different sampling techniques, each with its own set of advantages and disadvantages, which have been used for the collection of skin odors from different parts of the human body. We present the main skin volatile compounds found in these studies, with particular emphasis on the most frequently studied body regions, axillae, hands, and feet. We propose future directions for promising experimental studies on odors from human skin, particularly in relation to the chemical ecology of blood-sucking insects.

Relationships between gastric slow wave frequency, velocity, and extracellular amplitude studied by a joint experimental-theoretical approach.

PubMed

Wang, T H-H; Du, P; Angeli, T R; Paskaranandavadivel, N; Erickson, J C; Abell, T L; Cheng, L K; O'Grady, G

2018-01-01

Gastric slow wave dysrhythmias are accompanied by deviations in frequency, velocity, and extracellular amplitude, but the inherent association between these parameters in normal activity still requires clarification. This study quantified these associations using a joint experimental-theoretical approach. Gastric pacing was conducted in pigs with simultaneous high-resolution slow wave mapping (32-256 electrodes; 4-7.6 mm spacing). Relationships between period, velocity, and amplitude were quantified and correlated for each wavefront. Human data from two existing mapping control cohorts were analyzed to extract and correlate these same parameters. A validated biophysically based ICC model was also applied in silico to quantify velocity-period relationships during entrainment simulations and velocity-amplitude relationships from membrane potential equations. Porcine pacing studies identified positive correlations for velocity-period (0.13 mm s -1 per 1 s, r 2 =.63, P<.001) and amplitude-velocity (74 μV per 1 mm s -1 , r 2 =.21, P=.002). In humans, positive correlations were also quantified for velocity-period (corpus: 0.11 mm s -1 per 1 s, r 2 =.16, P<.001; antrum: 0.23 mm s -1 per 1 s, r 2 =.55; P<.001), and amplitude-velocity (94 μV per 1 mm s -1 , r 2 =.56; P<.001). Entrainment simulations matched the experimental velocity-period relationships and demonstrated dependence on the slow wave recovery phase. Simulated membrane potential relationships were close to these experimental results (100 μV per 1 mm s -1 ). These data quantify the relationships between slow wave frequency, velocity, and extracellular amplitude. The results from both human and porcine studies were in keeping with biophysical models, demonstrating concordance with ICC biophysics. These relationships are important in the regulation of gastric motility and will help to guide interpretations of dysrhythmias. © 2017 John Wiley & Sons Ltd.

Epistatically Interacting Substitutions Are Enriched during Adaptive Protein Evolution

PubMed Central

Gong, Lizhi Ian; Bloom, Jesse D.

2014-01-01

Most experimental studies of epistasis in evolution have focused on adaptive changes—but adaptation accounts for only a portion of total evolutionary change. Are the patterns of epistasis during adaptation representative of evolution more broadly? We address this question by examining a pair of protein homologs, of which only one is subject to a well-defined pressure for adaptive change. Specifically, we compare the nucleoproteins from human and swine influenza. Human influenza is under continual selection to evade recognition by acquired immune memory, while swine influenza experiences less such selection due to the fact that pigs are less likely to be infected with influenza repeatedly in a lifetime. Mutations in some types of immune epitopes are therefore much more strongly adaptive to human than swine influenza—here we focus on epitopes targeted by human cytotoxic T lymphocytes. The nucleoproteins of human and swine influenza possess nearly identical numbers of such epitopes. However, mutations in these epitopes are fixed significantly more frequently in human than in swine influenza, presumably because these epitope mutations are adaptive only to human influenza. Experimentally, we find that epistatically constrained mutations are fixed only in the adaptively evolving human influenza lineage, where they occur at sites that are enriched in epitopes. Overall, our results demonstrate that epistatically interacting substitutions are enriched during adaptation, suggesting that the prevalence of epistasis is dependent on the underlying evolutionary forces at play. PMID:24811236

The influence of essential oils on human attention. I: alertness.

PubMed

Ilmberger, J; Heuberger, E; Mahrhofer, C; Dessovic, H; Kowarik, D; Buchbauer, G

2001-03-01

Scientific research on the effects of essential oils on human behavior lags behind the promises made by popular aromatherapy. Nearly all aspects of human behavior are closely linked to processes of attention, the basic level being that of alertness, which ranges from sleep to wakefulness. In our study we measured the influence of essential oils and components of essential oils [peppermint, jasmine, ylang-ylang, 1,8-cineole (in two different dosages) and menthol] on this core attentional function, which can be experimentally defined as speed of information processing. Substances were administered by inhalation; levels of alertness were assessed by measuring motor and reaction times in a reaction time paradigm. The performances of the six experimental groups receiving substances (n = 20 in four groups, n = 30 in two groups) were compared with those of corresponding control groups receiving water. Between-group analysis, i.e. comparisons between experimental groups and their respective control groups, mainly did not reach statistical significance. However, within-group analysis showed complex correlations between subjective evaluations of substances and objective performance, indicating that effects of essentials oils or their components on basic forms of attentional behavior are mainly psychological.

Taenia solium: current understanding of laboratory animal models of taeniosis.

PubMed

Flisser, A; Avila, G; Maravilla, P; Mendlovic, F; León-Cabrera, S; Cruz-Rivera, M; Garza, A; Gómez, B; Aguilar, L; Terán, N; Velasco, S; Benítez, M; Jimenez-Gonzalez, D E

2010-03-01

Neurocysticercosis is a public health problem in many developing countries and is the most frequent parasitic disease of the brain. The human tapeworm carrier is the main risk factor for acquiring neurocysticercosis. Since the parasite lodges only in the human intestine, experimental models of Taenia solium taeniosis have been explored. Macaques, pigs, dogs, cats and rabbits are unsuccessful hosts even in immunodepressed status. By contrast, rodents are adequate hosts since tapeworms with mature, pregravid and, in some cases, gravid proglottids develop after infection. In this review, information that has been generated with experimental models of taeniosis due to T. solium is discussed. Initially, the use of the model for immunodiagnosis of human taeniosis and evaluation of intervention measures is summarized. Next, descriptions of tapeworms and comparison of hamsters, gerbils and other mammals as experimental models are discussed, as well as data on the humoral immune response, the inflammatory reaction and the production of cytokines associated to Th1 and Th2 responses in the intestinal mucosa. Finally, evaluation of protection induced against the development of tapeworms by recombinant T. solium calreticulin in hamsters is summarized and compared to other studies.

Malnutrition: A Deterrent to Human Progress

ERIC Educational Resources Information Center

Johnson, Nancy E.; Found, R. Elaine

1971-01-01

Authors discuss the effects of malnutrition on retardation of mental development and intellectual capacity. Research findings on undernourished experimental animals are cited as well as studies involving children suffering the effects of malnutrition in infancy. (Editor/LF)

Characterizing traffic under uncertain disruptions : an experimental approach.

DOT National Transportation Integrated Search

2013-03-01

The objective of the research is to study long-term traffic patterns under uncertain disruptions using : data collected from human subjects who simultaneously make route choices in controlled PC-based : laboratory experiments. Uncertain disruptions t...

Space weightlessness and hormonal changes in human subjects and experimental animals

NASA Technical Reports Server (NTRS)

Grindeland, R. E.

1982-01-01

Data from spaceflight and bed rest studies are briefly described and the difficulties in interpreting these results are discussed. Growth hormone, prolactin, adrenocorticotropic hormone, cortisol, insulin, aldosterone, and other hormones are addressed.

Outbreak of swine influenza in Argentina reveals a non-contemporary human H3N2 virus highly transmissible among pigs

PubMed Central

Cappuccio, Javier A.; Pena, Lindomar; Dibárbora, Marina; Rimondi, Agustina; Piñeyro, Pablo; Insarralde, Lucas; Quiroga, María A.; Machuca, Mariana; Craig, Maria I.; Olivera, Valeria; Chockalingam, Ashok; Perfumo, Carlos J.

2011-01-01

Sporadic outbreaks of human H3N2 influenza A virus (IAV) infections in swine populations have been reported in Asia, Europe and North America since 1970. In South America, serological surveys in pigs indicate that IAVs of the H3 and H1 subtypes are currently in circulation; however, neither virus isolation nor characterization has been reported. In November 2008, an outbreak of respiratory disease in pigs consistent with swine influenza virus (SIV) infection was detected in Argentina. The current study describes the clinical epidemiology, pathology, and molecular and biological characteristics of the virus. Phylogenetic analysis revealed that the virus isolate shared nucleotide identities of 96–98 % with H3N2 IAVs that circulated in humans from 2000 to 2003. Antigenically, sera from experimentally inoculated animals cross-reacted mainly with non-contemporary human-origin H3N2 influenza viruses. In an experimental infection in a commercial swine breed, the virus was of low virulence but was transmitted efficiently to contact pigs and caused severe disease when an infected animal acquired a secondary bacterial infection. This is the first report of a wholly human H3N2 IAV associated with clinical disease in pigs in South America. These studies highlight the importance of two-way transmission of IAVs and SIVs between pigs and humans, and call for enhanced influenza surveillance in the pig population worldwide. PMID:21849519

Group 2 ILCs: A way of enhancing immune protection against human helminths?

PubMed

Nausch, N; Mutapi, F

2018-02-01

Group 2 innate lymphoid cells (ILC2s) play crucial roles in type 2 immune responses associated with allergic and autoimmune diseases, viral and helminth infections and tissue homoeostasis. Experimental models show that in helminth infections ILC2s provide an early source of type 2 cytokines and therefore are essential for the induction of potentially protective type 2 responses. Much of our knowledge of ILC2s in helminth infections has come from experimental mouse models with very few studies analysing ILC2s in natural human infections. In attempts to harness knowledge from paradigms of the development of protective immunity in human helminth infections for vaccine development, the role of ILC2 cells could be pivotal. So far, potential vaccines against human helminth infections have failed to provide effective protection when evaluated in human studies. In addition to appropriate antigen selection, it is apparent that more detailed knowledge on mechanisms of induction and maintenance of protective immune responses is required. Therefore, there is need to understand how ILC2 cells induce type 2 responses and subsequently support the development of a protective immune response in the context of immunizations. Within this review, we summarize the current knowledge of the biology of ILC2s, discuss the importance of ILC2s in human helminth infections and explore how ILC2 responses could be boosted to efficiently induce protective immunity. © 2017 The Authors. Parasite Immunology Published by John Wiley & Sons Ltd.

Outbreak of swine influenza in Argentina reveals a non-contemporary human H3N2 virus highly transmissible among pigs.

PubMed

Cappuccio, Javier A; Pena, Lindomar; Dibárbora, Marina; Rimondi, Agustina; Piñeyro, Pablo; Insarralde, Lucas; Quiroga, María A; Machuca, Mariana; Craig, Maria I; Olivera, Valeria; Chockalingam, Ashok; Perfumo, Carlos J; Perez, Daniel R; Pereda, Ariel

2011-12-01

Sporadic outbreaks of human H3N2 influenza A virus (IAV) infections in swine populations have been reported in Asia, Europe and North America since 1970. In South America, serological surveys in pigs indicate that IAVs of the H3 and H1 subtypes are currently in circulation; however, neither virus isolation nor characterization has been reported. In November 2008, an outbreak of respiratory disease in pigs consistent with swine influenza virus (SIV) infection was detected in Argentina. The current study describes the clinical epidemiology, pathology, and molecular and biological characteristics of the virus. Phylogenetic analysis revealed that the virus isolate shared nucleotide identities of 96-98 % with H3N2 IAVs that circulated in humans from 2000 to 2003. Antigenically, sera from experimentally inoculated animals cross-reacted mainly with non-contemporary human-origin H3N2 influenza viruses. In an experimental infection in a commercial swine breed, the virus was of low virulence but was transmitted efficiently to contact pigs and caused severe disease when an infected animal acquired a secondary bacterial infection. This is the first report of a wholly human H3N2 IAV associated with clinical disease in pigs in South America. These studies highlight the importance of two-way transmission of IAVs and SIVs between pigs and humans, and call for enhanced influenza surveillance in the pig population worldwide.

Risk of chronic low-dose selenium overexposure in humans: insights from epidemiology and biochemistry.

PubMed

Vinceti, Marco; Maraldi, Tullia; Bergomi, Margherita; Malagoli, Carlotta

2009-01-01

The latest developments of epidemiologic and biochemical research suggest that current upper limits of intake for dietary selenium and for overall selenium exposure may be inadequate to protect human health. In particular, recent experimental and observational prospective studies indicate a diabetogenic effect of selenium at unexpectedly low levels of intake. Experimental evidence from laboratory studies and veterinary medicine appears to confirm previous epidemiologic observations that selenium overexposure is associated with an increased risk of amyotrophic lateral sclerosis, and a recent large trial indicated no beneficial effect in preventing prostate cancer. Moreover, the pro-oxidant properties of selenium species and the observation that the selenium-containing enzymes glutathione peroxidases are induced by oxidative stress imply that the increase in enzymatic activity induced by this metalloid may represent at least in part a compensatory response. Taken together, the data indicate that the upper safe limit of organic and inorganic selenium intake in humans may be lower than has been thought and that low-dose chronic overexposure to selenium may be considerably more widespread than supposed.

Comparison of probiotic lactobacilli and bifidobacteria effects, immune responses and rotavirus vaccines and infection in different host species

PubMed Central

Vlasova, Anastasia N.; Kandasamy, Sukumar; Chattha, Kuldeep S.; Rajashekara, Gireesh; Saif, Linda J.

2016-01-01

Different probiotic strains of Lactobacillus and Bifidobacterium genera possess significant and widely acknowledged health-promoting and immunomodulatory properties. They also provide an affordable means for prevention and treatment of various infectious, allergic and inflammatory conditions as demonstrated in numerous human and animal studies. Despite the ample evidence of protective effects of these probiotics against rotavirus (RV) infection and disease, the precise immune mechanisms of this protection remain largely undefined, because of limited mechanistic research possible in humans and investigated in the majority of animal models. Additionally, while most human clinical probiotic trials are well-standardized using the same strains, uniform dosages, regimens of the probiotic treatments and similar host age, animal studies often lack standardization, have variable experimental designs, and non-uniform and sometime limited selection of experimental variables or observational parameters. This review presents selected data on different probiotic strains of lactobacilli and bifidobacteria and summarizes the knowledge of their immunomodulatory properties and the associated protection against RV disease in diverse host species including neonates. PMID:26809484

Correlation between E-cadherin-regulated cell adhesion and human osteosarcoma MG-63 cell anoikis.

PubMed

Lin, Ding-Sheng; Cai, Le-Yi; Ding, Jian; Gao, Wei-Yang

2014-01-01

The aim of this study was to investigate the relationship between cell adhesion and anoikis evasion among human osteosarcoma cells (MG-63), and to further study the molecular mechanisms. Human osteosarcoma cells (MG-63) were assessed for apoptosis, and caspase-3, E-cadherin and β-catenin expression in EDTA and control non-EDTA groups. MG-63 cells were predominantly aggregated when in suspension, and the suspended cells were more dispersed in the EDTA group. Following culture in suspension for 24 h, 48 h, or 72 h, the rates of apoptosis were 34.88%±3.64%, 59.3%±7.22% and 78.5%±5.21% in the experimental group and 7.34%±2.13%, 14.7%±3.69%, and 21.4%±3.60% in the control group, respectively. Caspase-3 expression progressively increased and E-cadherin and β-catenin were decreased in the experimental group, whereas there was no change in the control group. MG-63 cells could avoid anoikis through cell adhesion, and E-cadherin might play a role in this process.

Approximate numerical abilities and mathematics: Insight from correlational and experimental training studies.

PubMed

Hyde, D C; Berteletti, I; Mou, Y

2016-01-01

Humans have the ability to nonverbally represent the approximate numerosity of sets of objects. The cognitive system that supports this ability, often referred to as the approximate number system (ANS), is present in early infancy and continues to develop in precision over the life span. It has been proposed that the ANS forms a foundation for uniquely human symbolic number and mathematics learning. Recent work has brought two types of evidence to bear on the relationship between the ANS and human mathematics: correlational studies showing individual differences in approximate numerical abilities correlate with individual differences in mathematics achievement and experimental studies showing enhancing effects of nonsymbolic approximate numerical training on exact, symbolic mathematical abilities. From this work, at least two accounts can be derived from these empirical data. It may be the case that the ANS and mathematics are related because the cognitive and brain processes responsible for representing numerical quantity in each format overlap, the Representational Overlap Hypothesis, or because of commonalities in the cognitive operations involved in mentally manipulating the representations of each format, the Operational Overlap hypothesis. The two hypotheses make distinct predictions for future work to test. © 2016 Elsevier B.V. All rights reserved.

Study on the interaction of antiviral drug 'Tenofovir' with human serum albumin by spectral and molecular modeling methods

NASA Astrophysics Data System (ADS)

Shahabadi, Nahid; Hadidi, Saba; Feizi, Foroozan

2015-03-01

This study was designed to examine the interaction of Tenofovir (Ten) with human serum albumin (HSA) under physiological conditions. The binding of drugs with human serum albumin is a crucial factor influencing the distribution and bioactivity of drugs in the body. To understand the action mechanisms between Ten and HSA, the binding of Ten with HSA was investigated by a combined experimental and computational approach. UV-vis results confirmed that Ten interacted with HSA to form a ground-state complex and values of the Stern-Volmer quenching constant indicate the presence of a static component in the quenching mechanism. As indicated by the thermodynamic parameters (positive ΔH and ΔS values), hydrophobic interaction plays a major role in the Ten-HSA complex. Through the site marker competitive experiment, Ten was confirmed to be located in site I of HSA. Furthermore, UV-vis absorption spectra, synchronous fluorescence spectrum and CD data were used to investigate the structural change of HSA molecules with addition of Ten, the results indicate that the secondary structure of HSA molecules was changed in the presence of Ten. The experimental results were in agreement with the results obtained via molecular docking study.

A review of critical factors for assessing the dermal absorption of metal oxide nanoparticles from sunscreens applied to humans, and a research strategy to address current deficiencies.

PubMed

Gulson, Brian; McCall, Maxine J; Bowman, Diana M; Pinheiro, Teresa

2015-11-01

Metal oxide nanoparticles in sunscreens provide broad-spectrum ultraviolet protection to skin. All studies to assess dermal penetration of nanoparticles have unanimously concluded that the overwhelming majority of nanoparticles remain on the outer surface of the skin. However, possibly due to many different experimental protocols in use, conclusions over the potential penetration to viable skin are mixed. Here, we review several factors that may influence experimental results for dermal penetration including the species studied (human, or animal model), size and coating of the metal oxide nanoparticles, composition of the sunscreen formulation, site of sunscreen application, dose and number of applications, duration of the study, types of biological samples analysed, methods for analysing samples, exposure to UV and skin flexing. Based on this information, we suggest an appropriate research agenda involving international collaboration that maximises the potential for dermal absorption of nanoparticles, and their detection, under normal conditions of sunscreen use by humans. If results from this research agenda indicate no absorption is observed, then concerns over adverse health effects from the dermal absorption of nanoparticles in sunscreens may be allayed.

Clinical pharmacology of analgesics assessed with human experimental pain models: bridging basic and clinical research

PubMed Central

Oertel, Bruno Georg; Lötsch, Jörn

2013-01-01

The medical impact of pain is such that much effort is being applied to develop novel analgesic drugs directed towards new targets and to investigate the analgesic efficacy of known drugs. Ongoing research requires cost-saving tools to translate basic science knowledge into clinically effective analgesic compounds. In this review we have re-examined the prediction of clinical analgesia by human experimental pain models as a basis for model selection in phase I studies. The overall prediction of analgesic efficacy or failure of a drug correlated well between experimental and clinical settings. However, correct model selection requires more detailed information about which model predicts a particular clinical pain condition. We hypothesized that if an analgesic drug was effective in an experimental pain model and also a specific clinical pain condition, then that model might be predictive for that particular condition and should be selected for development as an analgesic for that condition. The validity of the prediction increases with an increase in the numbers of analgesic drug classes for which this agreement was shown. From available evidence, only five clinical pain conditions were correctly predicted by seven different pain models for at least three different drugs. Most of these models combine a sensitization method. The analysis also identified several models with low impact with respect to their clinical translation. Thus, the presently identified agreements and non-agreements between analgesic effects on experimental and on clinical pain may serve as a solid basis to identify complex sets of human pain models that bridge basic science with clinical pain research. PMID:23082949

Optimizing methods and dodging pitfalls in microbiome research.

PubMed

Kim, Dorothy; Hofstaedter, Casey E; Zhao, Chunyu; Mattei, Lisa; Tanes, Ceylan; Clarke, Erik; Lauder, Abigail; Sherrill-Mix, Scott; Chehoud, Christel; Kelsen, Judith; Conrad, Máire; Collman, Ronald G; Baldassano, Robert; Bushman, Frederic D; Bittinger, Kyle

2017-05-05

Research on the human microbiome has yielded numerous insights into health and disease, but also has resulted in a wealth of experimental artifacts. Here, we present suggestions for optimizing experimental design and avoiding known pitfalls, organized in the typical order in which studies are carried out. We first review best practices in experimental design and introduce common confounders such as age, diet, antibiotic use, pet ownership, longitudinal instability, and microbial sharing during cohousing in animal studies. Typically, samples will need to be stored, so we provide data on best practices for several sample types. We then discuss design and analysis of positive and negative controls, which should always be run with experimental samples. We introduce a convenient set of non-biological DNA sequences that can be useful as positive controls for high-volume analysis. Careful analysis of negative and positive controls is particularly important in studies of samples with low microbial biomass, where contamination can comprise most or all of a sample. Lastly, we summarize approaches to enhancing experimental robustness by careful control of multiple comparisons and to comparing discovery and validation cohorts. We hope the experimental tactics summarized here will help researchers in this exciting field advance their studies efficiently while avoiding errors.

[Analysis of heavy-metal-mediated disease and development of a novel remediation system based on fieldwork and experimental research].

PubMed

Yajima, Ichiro; Zou, Cunchao; Li, Xiang; Nakano, Chizuru; Omata, Yasuhiro; Kumasaka, Mayuko Y

2015-01-01

Heavy-metal pollution occurs in various environments, including water, air and soil, and has serious effects on human health. Since heavy-metal pollution in drinking water causes various diseases including skin cancer, it has become a global problem worldwide. However, there is limited information on the mechanism of development of heavy-metal-mediated disease. We performed both fieldwork and experimental studies to elucidate the levels of heavy-metal pollution and mechanisms of development of heavy-metal-related disease and to develop a novel remediation system. Our fieldwork in Bangladesh, Vietnam and Malaysia demonstrated that drinking well water in these countries was polluted with high concentrations of several heavy metals including arsenic, barium, iron and manganese. Our experimental studies based on the data from our fieldwork demonstrated that these heavy metals caused skin cancer and hearing loss. Further experimental studies resulted in the development of a novel remediation system with which toxic heavy metals were absorbed from polluted drinking water. Implementation of both fieldwork and experimental studies is important for prediction, prevention and therapy of heavy-metal-mediated diseases.

Nicotinamide treatment ameliorates the course of experimental colitis mediated by enhanced neutrophil-specific antibacterial clearance.

PubMed

Bettenworth, Dominik; Nowacki, Tobias M; Ross, Matthias; Kyme, Pierre; Schwammbach, Daniela; Kerstiens, Linda; Thoennissen, Gabriela B; Bokemeyer, Carsten; Hengst, Karin; Berdel, Wolfgang E; Heidemann, Jan; Thoennissen, Nils H

2014-07-01

In previous studies, we could show that the B vitamin nicotinamide (NAM) enhanced antimicrobial activity of neutrophils. Here, we assessed the effects of NAM in two models of experimental colitis. Colitis was induced in C57BL/6 mice either by oral infection with Citrobacter rodentium or by DSS (dextran sodium sulphate) administration, and animals were systemically treated with NAM. Ex vivo bacterial clearance was assessed in murine and human whole blood, as well as isolated human neutrophils. In C. rodentium-induced colitis, NAM treatment resulted in markedly decreased systemic bacterial invasion, histological damage and increased fecal clearance of C. rodentium by up to 600-fold. In contrast, NAM had no effect when administered to neutrophil-depleted mice. Ex vivo stimulation of isolated human neutrophils, as well as murine and human whole blood with NAM led to increased clearance of C. rodentium and enhanced expression of antimicrobial peptides in neutrophils. Moreover, NAM treatment significantly ameliorated the course of DSS colitis, as assessed by body weight, histological damage and myeloperoxidase activity. Pharmacological application of NAM mediates beneficial effects in bacterial and chemically induced colitis. Future studies are needed to explore the clinical potential of NAM in the context of intestinal bacterial infections and human inflammatory bowel disease (IBD). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Music Performance As an Experimental Approach to Hyperscanning Studies

PubMed Central

Acquadro, Michaël A. S.; Congedo, Marco; De Riddeer, Dirk

2016-01-01

Humans are fundamentally social and tend to create emergent organizations when interacting with each other; from dyads to families, small groups, large groups, societies, and civilizations. The study of the neuronal substrate of human social behavior is currently gaining momentum in the young field of social neuroscience. Hyperscanning is a neuroimaging technique by which we can study two or more brains simultaneously while participants interact with each other. The aim of this article is to discuss several factors that we deem important in designing hyperscanning experiments. We first review hyperscanning studies performed by means of electroencephalography (EEG) that have been relying on a continuous interaction paradigm. Then, we provide arguments for favoring ecological paradigms, for studying the emotional component of social interactions and for performing longitudinal studies, the last two aspects being largely neglected so far in the hyperscanning literature despite their paramount importance in social sciences. Based on these premises, we argue that music performance is a suitable experimental setting for hyperscanning and that for such studies EEG is an appropriate choice as neuroimaging modality. PMID:27252641

Evolution of the human hand: approaches to acquiring, analysing and interpreting the anatomical evidence

PubMed Central

MARZKE, MARY W.; MARZKE, R. F.

2000-01-01

The discovery of fossil hand bones from an early human ancestor at Olduvai Gorge in 1960, at the same level as primitive stone tools, generated a debate about the role of tools in the evolution of the human hand that has raged to the present day. Could the Olduvai hand have made the tools? Did the human hand evolve as an adaptation to tool making and tool use? The debate has been fueled by anatomical studies comparing living and fossil human and nonhuman primate hands, and by experimental observations. These have assessed the relative abilities of apes and humans to manufacture the Oldowan tools, but consensus has been hampered by disagreements about how to translate experimental data from living species into quantitative models for predicting the performance of fossil hands. Such models are now beginning to take shape as new techniques are applied to the capture, management and analysis of data on kinetic and kinematic variables ranging from hand joint structure, muscle mechanics, and the distribution and density of bone to joint movements and muscle recruitment during manipulative behaviour. The systematic comparative studies are highlighting a functional complex of features in the human hand facilitating a distinctive repertoire of grips that are apparently more effective for stone tool making than grips characterising various nonhuman primate species. The new techniques are identifying skeletal variables whose form may provide clues to the potential of fossil hominid hands for one-handed firm precision grips and fine precision manoeuvering movements, both of which are essential for habitual and effective tool making and tool use. PMID:10999274

Human Gut Microbiome: Function Matters.

PubMed

Heintz-Buschart, Anna; Wilmes, Paul

2017-11-22

The human gut microbiome represents a complex ecosystem contributing essential functions to its host. Recent large-scale metagenomic studies have provided insights into its structure and functional potential. However, the functional repertoire which is actually contributed to human physiology remains largely unexplored. Here, by leveraging recent omics datasets, we challenge current assumptions regarding key attributes of the functional gut microbiome, in particular with respect to its variability. We further argue that the closing of existing gaps in functional knowledge should be addressed by a most-wanted gene list, the development and application of molecular and cellular high-throughput measurements, the development and sensible use of experimental models, as well as the direct study of observable molecular effects in the human host. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evolution and the psychology of intergroup conflict: the male warrior hypothesis.

PubMed

McDonald, Melissa M; Navarrete, Carlos David; Van Vugt, Mark

2012-03-05

The social science literature contains numerous examples of human tribalism and parochialism-the tendency to categorize individuals on the basis of their group membership, and treat ingroup members benevolently and outgroup members malevolently. We hypothesize that this tribal inclination is an adaptive response to the threat of coalitional aggression and intergroup conflict perpetrated by 'warrior males' in both ancestral and modern human environments. Here, we describe how male coalitional aggression could have affected the social psychologies of men and women differently and present preliminary evidence from experimental social psychological studies testing various predictions from the 'male warrior' hypothesis. Finally, we discuss the theoretical implications of our research for studying intergroup relations both in humans and non-humans and discuss some practical implications.

Alarmins S100A8/S100A9 aggravate osteophyte formation in experimental osteoarthritis and predict osteophyte progression in early human symptomatic osteoarthritis.

PubMed

Schelbergen, R F P; de Munter, W; van den Bosch, M H J; Lafeber, F P J G; Sloetjes, A; Vogl, T; Roth, J; van den Berg, W B; van der Kraan, P M; Blom, A B; van Lent, P L E M

2016-01-01

Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (OA). In the current study, we investigated whether S100A8 and S100A9 are involved in osteophyte formation during experimental OA and whether S100A8/A9 predicts osteophyte progression in early human OA. OA was elicited in S100A9-/- mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN neoepitope was measured histologically. Chondrogenesis was induced in murine mesenchymal stem cells in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA participants of the Cohort Hip and Cohort Knee (CHECK) cohort study and osteophytes measured after 2 and 5 years. Osteophyte size was drastically reduced in S100A9-/- mice in ligaments and at medial femur and tibia on days 21 and 42 of collagenase-induced OA, in which synovial activation is high. In contrast, osteophyte size was not reduced in S100A9-/- mice during destabilised medial meniscus OA, in which synovial activation is scant. S100A8 increased expression and activation of matrix metalloproteinases during micromass chondrogenesis, thereby possibly increasing cartilage matrix remodelling allowing for larger osteophytes. Interestingly, early symptomatic OA participants of the CHECK study with osteophyte progression after 2 and 5 years had elevated S100A8/A9 plasma levels at baseline, while C-reactive protein, erythrocyte sedimentation rate and cartilage oligomeric matrix protein were not elevated at baseline. S100A8/A9 aggravate osteophyte formation in experimental OA with high synovial activation and may be used to predict osteophyte progression in early symptomatic human OA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The CD8 T cell in multiple sclerosis: suppressor cell or mediator of neuropathology?

PubMed

Johnson, Aaron J; Suidan, Georgette L; McDole, Jeremiah; Pirko, Istvan

2007-01-01

Multiple sclerosis (MS) is the most common human demyelinating disease of the central nervous system. It is universally accepted that the immune system plays a major role in the pathogenesis of MS. For decades, CD4 T cells have been considered the predominant mediator of neuropathology in MS. This perception was largely due to the similarity between MS and CD4 T-cell-driven experimental allergic encephalomyelitis, the most commonly studied murine model of MS. Over the last decade, several new observations in MS research imply an emerging role for CD8 T cells in neuropathogenesis. In certain experimental autoimmune encephalomyelitis (EAE) models, CD8 T cells are considered suppressors of pathology, whereas in other EAE models, neuropathology can be exacerbated by adoptive transfer of CD8 T cells. Studies using the Theiler's murine encephalomyelitis virus (TMEV) model have demonstrated preservation of motor function and axonal integrity in animals deficient in CD8 T cells or their effector molecules. CD8 T cells have also been demonstrated to be important regulators of blood-brain barrier permeability. There is also an emerging role for CD8 T cells in human MS. Human genetic studies reveal an important role for HLA class I molecules in MS susceptibility. In addition, neuropathologic studies demonstrate that CD8 T cells are the most numerous inflammatory infiltrate in MS lesions at all stages of lesion development. CD8 T cells are also capable of damaging neurons and axons in vitro. In this chapter, we discuss the neuropathologic, genetic, and experimental evidence for a critical role of CD8 T cells in the pathogenesis of MS and its most frequently studied animal models. We also highlight important new avenues for future research.

Practical training on porcine hearts enhances students' knowledge of human cardiac anatomy.

PubMed

Musumeci, Giuseppe; Loreto, Carla; Mazzone, Venera; Szychlinska, Marta Anna; Castrogiovanni, Paola; Castorina, Sergio

2014-05-01

Historically, cadavers have been used for the study of anatomy. Nowadays, the territorial and legal limitations of this approach have led to the introduction of alternative teaching methods such as the use of practical exercise consisting of dissection and observation of animal organs. The aim of this study was to evaluate the use of practical training on animal organs compared with the traditional method of anatomy teaching, based on the dissection of human cadavers. In this study, we seek to demonstrate the usefulness of practical exercise on animal organs. This practical training was held a week after the series of lectures, thus leaving time for the students to learn and understand the topics discussed. Immediately after the lecture, all of the students completed a preliminary test to assess the immediate effect of the lecture. Immediately before the practical exercise, both control and experimental groups completed a second test to assess the effectiveness of personal study. Immediately after practical training, a third test was completed by the experimental group and the control group (no practical activity on animal organs) to highlight the added value of hands-on practice in addition to the lecture. Data obtained from statistical analysis showed a p<0.05 (control group vs. experimental group) only for the third test as expected, highlighting significant differences in anatomy learning between control and experimental groups. Thus, the results of this study emphasize the utility of practical training on animal organs in learning and understanding anatomy, considering the limitations of the use of cadavers. Copyright © 2014 Elsevier GmbH. All rights reserved.

Human Visual System as a Double-Slit Single Photon Interference Sensor: A Comparison between Modellistic and Biophysical Tests

PubMed Central

Pizzi, Rita; Wang, Rui; Rossetti, Danilo

2016-01-01

This paper describes a computational approach to the theoretical problems involved in the Young's single-photon double-slit experiment, focusing on a simulation of this experiment in the absence of measuring devices. Specifically, the human visual system is used in place of a photomultiplier or similar apparatus. Beginning with the assumption that the human eye perceives light in the presence of very few photons, we measure human eye performance as a sensor in a double-slit one-photon-at-a-time experimental setup. To interpret the results, we implement a simulation algorithm and compare its results with those of human subjects under identical experimental conditions. In order to evaluate the perceptive parameters exactly, which vary depending on the light conditions and on the subject’s sensitivity, we first review the existing literature on the biophysics of the human eye in the presence of a dim light source, and then use the known values of the experimental variables to set the parameters of the computational simulation. The results of the simulation and their comparison with the experiment involving human subjects are reported and discussed. It is found that, while the computer simulation indicates that the human eye has the capacity to detect the corpuscular nature of photons under these conditions, this was not observed in practice. The possible reasons for the difference between theoretical prediction and experimental results are discussed. PMID:26816029

Histologic evaluation of human pulp tissue after orthodontic intrusion.

PubMed

Lazzaretti, Dieison Nardi; Bortoluzzi, Gianna Steffens; Torres Fernandes, Lauren Fioreze; Rodriguez, Rubens; Grehs, Renésio Armindo; Martins Hartmann, Mateus Silveira

2014-10-01

The forces applied during orthodontic treatment bring about effects on the teeth and surrounding tissues. The aim of this study was to evaluate the possible changes in the human pulpal tissue resulting from orthodontic intrusion in a 21-day period using histologic examination. The sample consisted of 17 young individuals of both sexes between the ages of 12 and 19 years. A total of 34 premolars were evaluated with orthodontic indication of extraction. Because it is a split-mouth study, in each patient, intrusion force of 60 g was applied randomly on 1 of the dental elements experimental group for 21 days. The counterpart control group received no force. After extractions, these dental elements were fixed in 10% formaldehyde, processed automatically, submitted to histotechnical preparation, and stained with hematoxylin-eosin for analysis under optical microscope. The paired Fisher exact test (P ≤ .05) showed a significant increase of fibrous tissue in the experimental group. The nonparametric paired Wilcoxon test (P ≤ .05) showed a significant increase in the number of pulpal nodules in the elements of the experimental group and showed no difference in the number of blood vessels between the groups. Large-caliber vessels and congested elements were observed in 8 of the experimental group elements. The orthodontic intrusion force, in these conditions, caused vascular changes in the pulpal tissue and also increased the presence of fibrosis and the number of pulp calcifications in the experimental elements. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Controlling attentional priority by preventing changes in oculomotor programs: a job for the premotor cortex?

PubMed

Michael, G A; Kleitz, C; Sellal, F; Hirsch, E; Marescaux, C

2001-01-01

Abruptly presented items capture attention automatically so they constitute the first items to be examined [Yantis and Jonides, Journal of Experimental Psychology: Human Perception and Performance, 1984;10:601; Jonids and Yantis, Perception and Psychophysics, 1988;43:346; Theeuwes, Perception and Psychophysics, 1992;51:599; Theeuwes, Journal of Experimental Psychology: Human Perception and Performance, 1994;20:799]. This attentional priority can be controlled in a top-down manner by directing attention towards the locus of interest [Yantis and Johnson, Journal of Experimental Psychology: Human Perception and Performance, 1990;16:812; Theeuwes. Perception and Psychophysics, 1991;49:83; Miller, Perception and Psychophysics, 1989;45:567; Folk et al., Journal of Experimental Psychology: Human Perception and Performance, 1992; 18:1030]. The premotor theory of attention [Rizzolatti et al., Neuropsychologia 1987;25:31; Rizzolatti et al., Attention and Performance XV, 1994, p. 231] assumes that the mechanism responsible for the attentional shifts is strictly linked to that responsible for eye movements, and several studies [Corbetta et al., Society of Neuroscience Abstracts 1997;23:122.12; Nobre et al., Brain 1997;120:515; Theeuwes et al., Journal of Experimental Psychology: Human Perception and Performance, 1999;25:1595] suggested that the premotor cortex plays a role in the control of attention. However, the nature of this involvement is still unclear. We have been asking a patient (RJ) with a damage of the right premotor cortex to decide whether a target had a discontinuity on its right or left side. The absolute location of the target was pre-cued. In Section 2, an interference was observed when a sudden onset occurred in the visual space, suggesting that RJ was not able to control attentional capture. The possibility to attribute this interference to an insufficient focalization of attention or a grouping effect were discarded by Sections 3 and 4, respectively. Section 5 revealed that this interference followed exclusively the onset occurring in the hemifield opposite the one containing the target (meridian effect [Rizzolatti et al., Neuropsychologia 1987;25:31]). The results suggest that the control of attentional capture may be achieved by keeping constant the parameters of the appropriate oculomotor program.

The Evolution of a Connectionist Model of Situated Human Language Understanding

NASA Astrophysics Data System (ADS)

Mayberry, Marshall R.; Crocker, Matthew W.

The Adaptive Mechanisms in Human Language Processing (ALPHA) project features both experimental and computational tracks designed to complement each other in the investigation of the cognitive mechanisms that underlie situated human utterance processing. The models developed in the computational track replicate results obtained in the experimental track and, in turn, suggest further experiments by virtue of behavior that arises as a by-product of their operation.

Role of Poultry in the Spread of Novel H7N9 Influenza Virus in China

PubMed Central

Pantin-Jackwood, Mary J.; Miller, Patti J.; Spackman, Erica; Swayne, David E.; Susta, Leonardo; Costa-Hurtado, Mar

2014-01-01

ABSTRACT The recent outbreak of H7N9 influenza in China has resulted in many human cases with a high fatality rate. Poultry are the likely source of infection for humans on the basis of sequence analysis and virus isolations from live bird markets, but it is not clear which species of birds are most likely to be infected and shedding levels of virus sufficient to infect humans. Intranasal inoculation of chickens, Japanese quail, pigeons, Pekin ducks, Mallard ducks, Muscovy ducks, and Embden geese with 106 50% egg infective doses of the A/Anhui/1/2013 virus resulted in infection but no clinical disease signs. Virus shedding was much higher and prolonged in quail and chickens than in the other species. Quail effectively transmitted the virus to direct contacts, but pigeons and Pekin ducks did not. In all species, virus was detected at much higher titers from oropharyngeal swabs than cloacal swabs. The hemagglutinin gene from samples collected from selected experimentally infected birds was sequenced, and three amino acid differences were commonly observed when the sequence was compared to the sequence of A/Anhui/1/2013: N123D, N149D, and L217Q. Leucine at position 217 is highly conserved for human isolates and is associated with α2,6-sialic acid binding. Different amino acid combinations were observed, suggesting that the inoculum had viral subpopulations that were selected after passage in birds. These experimental studies corroborate the finding that certain poultry species are reservoirs of the H7N9 influenza virus and that the virus is highly tropic for the upper respiratory tract, so testing of bird species should preferentially be conducted with oropharyngeal swabs for the best sensitivity. IMPORTANCE The recent outbreak of H7N9 influenza in China has resulted in a number of human infections with a high case fatality rate. The source of the viral outbreak is suspected to be poultry, but definitive data on the source of the infection are not available. This study provides experimental data to show that quail and chickens are susceptible to infection, shed large amounts of virus, and are likely important in the spread of the virus to humans. Other poultry species can be infected and shed virus but are less likely to play a role of transmitting the virus to humans. Pigeons were previously suggested to be a possible source of the virus because of isolation of the virus from several pigeons in poultry markets in China, but experimental studies show that they are generally resistant to infection and are unlikely to play a role in the spread of the virus. PMID:24574407

Genetic variability of Taenia solium cysticerci recovered from experimentally infected pigs and from naturally infected pigs using microsatellite markers

PubMed Central

Eguiluz, María; Roncal, Elisa; Quiñones-García, Stefany; Clipman, Steven J.; Calcina, Juan; Gavidia, Cesar M.; Sheen, Patricia; Garcia, Hector H.; Gilman, Robert H.; Gonzalez, Armando E.; Zimic, Mirko

2017-01-01

The adult Taenia solium, the pork tapeworm, usually lives as a single worm in the small intestine of humans, its only known definitive host. Mechanisms of genetic variation in T. solium are poorly understood. Using three microsatellite markers previously reported [1], this study explored the genetic variability of T. solium from cysts recovered from experimentally infected pigs. It then explored the genetic epidemiology and transmission in naturally infected pigs and adult tapeworms recovered from human carriers from an endemic rural community in Peru. In an initial study on experimental infection, two groups of three piglets were each infected with proglottids from one of two genetically different tapeworms for each of the microsatellites. After 7 weeks, pigs were slaughtered and necropsy performed. Thirty-six (92.3%) out of 39 cysts originated from one tapeworm, and 27 (100%) out of 27 cysts from the other had exactly the same genotype as the parental tapeworm. This suggests that the microsatellite markers may be a useful tool for studying the transmission of T. solium. In the second study, we analyzed the genetic variation of T. solium in cysts recovered from eight naturally infected pigs, and from adult tapeworms recovered from four human carriers; they showed genetic variability. Four pigs had cysts with only one genotype, and four pigs had cysts with two different genotypes, suggesting that multiple infections of genetically distinct parental tapeworms are possible. Six pigs harbored cysts with a genotype corresponding to one of the identified tapeworms from the human carriers. In the dendrogram, cysts appeared to cluster within the corresponding pigs as well as with the geographical origin, but this association was not statistically significant. We conclude that genotyping of microsatellite size polymorphisms is a potentially important tool to trace the spread of infection and pinpoint sources of infection as pigs spread cysts with a shared parental genotype. PMID:29284011

Genetic variability of Taenia solium cysticerci recovered from experimentally infected pigs and from naturally infected pigs using microsatellite markers.

PubMed

Pajuelo, Mónica J; Eguiluz, María; Roncal, Elisa; Quiñones-García, Stefany; Clipman, Steven J; Calcina, Juan; Gavidia, Cesar M; Sheen, Patricia; Garcia, Hector H; Gilman, Robert H; Gonzalez, Armando E; Zimic, Mirko

2017-12-01

The adult Taenia solium, the pork tapeworm, usually lives as a single worm in the small intestine of humans, its only known definitive host. Mechanisms of genetic variation in T. solium are poorly understood. Using three microsatellite markers previously reported [1], this study explored the genetic variability of T. solium from cysts recovered from experimentally infected pigs. It then explored the genetic epidemiology and transmission in naturally infected pigs and adult tapeworms recovered from human carriers from an endemic rural community in Peru. In an initial study on experimental infection, two groups of three piglets were each infected with proglottids from one of two genetically different tapeworms for each of the microsatellites. After 7 weeks, pigs were slaughtered and necropsy performed. Thirty-six (92.3%) out of 39 cysts originated from one tapeworm, and 27 (100%) out of 27 cysts from the other had exactly the same genotype as the parental tapeworm. This suggests that the microsatellite markers may be a useful tool for studying the transmission of T. solium. In the second study, we analyzed the genetic variation of T. solium in cysts recovered from eight naturally infected pigs, and from adult tapeworms recovered from four human carriers; they showed genetic variability. Four pigs had cysts with only one genotype, and four pigs had cysts with two different genotypes, suggesting that multiple infections of genetically distinct parental tapeworms are possible. Six pigs harbored cysts with a genotype corresponding to one of the identified tapeworms from the human carriers. In the dendrogram, cysts appeared to cluster within the corresponding pigs as well as with the geographical origin, but this association was not statistically significant. We conclude that genotyping of microsatellite size polymorphisms is a potentially important tool to trace the spread of infection and pinpoint sources of infection as pigs spread cysts with a shared parental genotype.

In vitro and in vivo studies on antitumor effects of gossypol on human stomach adenocarcinoma (AGS) cell line and MNNG induced experimental gastric cancer

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

Gunassekaran, G.R., E-mail: gunassekaran@yahoo.co.in; Kalpana Deepa Priya, D.; Gayathri, R.

2011-08-12

Highlights: {yields} Gossypol is a well known polyphenolic compound used for anticancer studies but we are the first to report that gossypol has antitumor effect on MNNG induced gastric cancer in experimental animal models. {yields} Our study shows that gossypol inhibits the proliferation of AGS (human gastric adenocarcinoma) cell line. {yields} In animal models, gossypol extends the survival of cancer bearing animals and also protects the cells from carcinogenic effect. {yields} So we suggest that gossypol would be a potential chemotherapeutic and chemopreventive agent for gastric cancer. -- Abstract: The present study has evaluated the chemopreventive effects of gossypol onmore » N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis and on human gastric adenocarcinoma (AGS) cell line. Gossypol, C{sub 30}H{sub 30}O{sub 8}, is a polyphenolic compound that has anti proliferative effect and induces apoptosis in various cancer cells. The aim of this work was to delineate in vivo and in vitro anti-initiating mechanisms of orally administered gossypol in target (stomach) tissues and in human gastric adenocarcinoma (AGS) cell line. In vitro results prove that gossypol has potent cytotoxic effect and inhibit the proliferation of adenocarcinoma (AGS) cell line. In vivo results prove gossypol to be successful in prolonging the survival of MNNG induced cancer bearing animals and in delaying the onset of tumor in animals administrated with gossypol and MNNG simultaneously. Examination of the target (stomach) tissues in sacrificed experimental animals shows that administration of gossypol significantly reduces the level of tumor marker enzyme (carcino embryonic antigen) and pepsin. The level of Nucleic acid contents (DNA and RNA) significantly reduces, and the membrane damage of glycoprotein subsides, in the target tissues of cancer bearing animals, with the administration of gossypol. These data suggest that gossypol may create a beneficial effect in patients with gastric cancer.« less

Experimental Proteus mirabilis Burn Surface Infection

DTIC Science & Technology

1982-02-01

Reprinted from the Achie of Surgery ECTE February 1982, Volume 117 Copyright 19 2. American Medical Association MAY 2 8 1982 V0A Experimental Proteus ... mirabilis Burn Surface Infection Albert T. McManus, PhD; Charles G. McLeod, Jr, DVM; Arthur D. Mason, Jr, MD * We established a human burn Isolate of... Proteus mirabills as have examined human burn isolates from the genera an experimental pathogen. Infliction of a nonfatal scald injury Enterobacter

Establishment of a novel human medulloblastoma cell line characterized by highly aggressive stem-like cells.

PubMed

Silva, Patrícia Benites Gonçalves da; Rodini, Carolina Oliveira; Kaid, Carolini; Nakahata, Adriana Miti; Pereira, Márcia Cristina Leite; Matushita, Hamilton; Costa, Silvia Souza da; Okamoto, Oswaldo Keith

2016-08-01

Medulloblastoma is a highly aggressive brain tumor and one of the leading causes of morbidity and mortality related to childhood cancer. These tumors display differential ability to metastasize and respond to treatment, which reflects their high degree of heterogeneity at the genetic and molecular levels. Such heterogeneity of medulloblastoma brings an additional challenge to the understanding of its physiopathology and impacts the development of new therapeutic strategies. This translational effort has been the focus of most pre-clinical studies which invariably employ experimental models using human tumor cell lines. Nonetheless, compared to other cancers, relatively few cell lines of human medulloblastoma are available in central repositories, partly due to the rarity of these tumors and to the intrinsic difficulties in establishing continuous cell lines from pediatric brain tumors. Here, we report the establishment of a new human medulloblastoma cell line which, in comparison with the commonly used and well-established cell line Daoy, is characterized by enhanced proliferation and invasion capabilities, stem cell properties, increased chemoresistance, tumorigenicity in an orthotopic metastatic model, replication of original medulloblastoma behavior in vivo, strong chromosome structural instability and deregulation of genes involved in neural development. These features are advantageous for designing biologically relevant experimental models in clinically oriented studies, making this novel cell line, named USP-13-Med, instrumental for the study of medulloblastoma biology and treatment.

Prolactin secretion patterns: basic mechanisms and clinical implications for reproduction.

PubMed

Egli, Marcel; Leeners, Brigitte; Kruger, Tillmann H C

2010-11-01

Prolactin (PRL) is one of the most versatile hormones in the mammalian body affecting reproductive, sexual, metabolic, immune, and other functions. It is therefore not surprising that the neural control of PRL secretion is complex, involving the coordinated actions of several hypothalamic nuclei. A plethora of experimental data exists on the hypothalamic control of hormone secretion under various physiological stimuli. There have been even mathematical models and computer studies published, which help to understand the complex hypothalamic-pituitary network. Nevertheless, the putative role of PRL for human reproduction still has to be clarified. Here, we review data on the underlying mechanisms controlling PRL secretion using both experimental and mathematical approaches. These investigations primarily focus on rhythmic secretion in rats during early pregnancy or pseudopregnancy, and they point to the important role of oxytocin as a crucial PRL-releasing factor. Recent data on human studies and their theoretical and clinical implications are reviewed as well. In particular, studies demonstrating a sustained PRL surge after sexual climax in males and females are presented, indicating possible implications for both sexual satiation and reproductive functions. Taking these data together, there is evidence for the hypothesis that the PRL surge induced by sexual activity, together with the altered PRL rhythmic pattern, is important for successful initialization of pregnancy not only in rodents but also possibly in humans. However, further investigations are needed to clarify such a role in humans.

Development of human epithelial cell systems for radiation risk assessment

NASA Astrophysics Data System (ADS)

Yang, C. H.; Craise, L. M.

1994-10-01

The most important health effect of space radiation for astronauts is cancer induction. For radiation risk assessment, an understanding of carcinogenic effect of heavy ions in human cells is most essential. In our laboratory, we have successfully developed a human mammary epithelial cell system for studying the neoplastic transformation in vitro. Growth variants were obtained from heavy ion irradiated immortal mammary cell line. These cloned growth variants can grow in regular tissue culture media and maintain anchorage dependent growth and density inhibition property. Upon further irradiation with high-LET radiation, transformed foci were found. Experimental results from these studies suggest that multiexposure of radiation is required to induce neoplastic transformation of human epithelial cells. This multihits requirement may be due to high genomic stability of human cells. These growth variants can be useful model systems for space flight experiments to determine the carcinogenic effect of space radiation in human epithelial cells.

Development of human epithelial cell systems for radiation risk assessment

NASA Technical Reports Server (NTRS)

Yang, C. H.; Craise, L. M.

1994-01-01

The most important health effect of space radiation for astronauts is cancer induction. For radiation risk assessment, an understanding of carcinogenic effect of heavy ions in human cells is most essential. In our laboratory, we have successfully developed a human mammary epithelial cell system for studying the neoplastic transformation in vitro. Growth variants were obtained from heavy ion irradiated immortal mammary cell line. These cloned growth variants can grow in regular tissue culture media and maintain anchorage dependent growth and density inhibition property. Upon further irradiation with high-Linear Energy Transfer (LET) radiation, transformed foci were found. Experimental results from these studies suggest that multiexposure of radiation is required to induce neoplastic tranformation of human epithelial cells. This multihits requirement may be due to high genomic stability of human cells. These growth variants can be useful model systems for space flight experiments to determine the carcinogenic effect of space radiation in human epithelial cells.

Identifying protein phosphorylation sites with kinase substrate specificity on human viruses.

PubMed

Bretaña, Neil Arvin; Lu, Cheng-Tsung; Chiang, Chiu-Yun; Su, Min-Gang; Huang, Kai-Yao; Lee, Tzong-Yi; Weng, Shun-Long

2012-01-01

Viruses infect humans and progress inside the body leading to various diseases and complications. The phosphorylation of viral proteins catalyzed by host kinases plays crucial regulatory roles in enhancing replication and inhibition of normal host-cell functions. Due to its biological importance, there is a desire to identify the protein phosphorylation sites on human viruses. However, the use of mass spectrometry-based experiments is proven to be expensive and labor-intensive. Furthermore, previous studies which have identified phosphorylation sites in human viruses do not include the investigation of the responsible kinases. Thus, we are motivated to propose a new method to identify protein phosphorylation sites with its kinase substrate specificity on human viruses. The experimentally verified phosphorylation data were extracted from virPTM--a database containing 301 experimentally verified phosphorylation data on 104 human kinase-phosphorylated virus proteins. In an attempt to investigate kinase substrate specificities in viral protein phosphorylation sites, maximal dependence decomposition (MDD) is employed to cluster a large set of phosphorylation data into subgroups containing significantly conserved motifs. The experimental human phosphorylation sites are collected from Phospho.ELM, grouped according to its kinase annotation, and compared with the virus MDD clusters. This investigation identifies human kinases such as CK2, PKB, CDK, and MAPK as potential kinases for catalyzing virus protein substrates as confirmed by published literature. Profile hidden Markov model is then applied to learn a predictive model for each subgroup. A five-fold cross validation evaluation on the MDD-clustered HMMs yields an average accuracy of 84.93% for Serine, and 78.05% for Threonine. Furthermore, an independent testing data collected from UniProtKB and Phospho.ELM is used to make a comparison of predictive performance on three popular kinase-specific phosphorylation site prediction tools. In the independent testing, the high sensitivity and specificity of the proposed method demonstrate the predictive effectiveness of the identified substrate motifs and the importance of investigating potential kinases for viral protein phosphorylation sites.

Reconstruction of Human Monte Carlo Geometry from Segmented Images

NASA Astrophysics Data System (ADS)

Zhao, Kai; Cheng, Mengyun; Fan, Yanchang; Wang, Wen; Long, Pengcheng; Wu, Yican

2014-06-01

Human computational phantoms have been used extensively for scientific experimental analysis and experimental simulation. This article presented a method for human geometry reconstruction from a series of segmented images of a Chinese visible human dataset. The phantom geometry could actually describe detailed structure of an organ and could be converted into the input file of the Monte Carlo codes for dose calculation. A whole-body computational phantom of Chinese adult female has been established by FDS Team which is named Rad-HUMAN with about 28.8 billion voxel number. For being processed conveniently, different organs on images were segmented with different RGB colors and the voxels were assigned with positions of the dataset. For refinement, the positions were first sampled. Secondly, the large sums of voxels inside the organ were three-dimensional adjacent, however, there were not thoroughly mergence methods to reduce the cell amounts for the description of the organ. In this study, the voxels on the organ surface were taken into consideration of the mergence which could produce fewer cells for the organs. At the same time, an indexed based sorting algorithm was put forward for enhancing the mergence speed. Finally, the Rad-HUMAN which included a total of 46 organs and tissues was described by the cuboids into the Monte Carlo Monte Carlo Geometry for the simulation. The Monte Carlo geometry was constructed directly from the segmented images and the voxels was merged exhaustively. Each organ geometry model was constructed without ambiguity and self-crossing, its geometry information could represent the accuracy appearance and precise interior structure of the organs. The constructed geometry largely retaining the original shape of organs could easily be described into different Monte Carlo codes input file such as MCNP. Its universal property was testified and high-performance was experimentally verified

First experience with x-ray dark-field radiography for human chest imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Noel, Peter B.; Willer, Konstantin; Fingerle, Alexander A.; Gromann, Lukas B.; De Marco, Fabio; Scherer, Kai H.; Herzen, Julia; Achterhold, Klaus; Gleich, Bernhard; Münzel, Daniela; Renz, Martin; Renger, Bernhard C.; Fischer, Florian; Braun, Christian; Auweter, Sigrid; Hellbach, Katharina; Reiser, Maximilian F.; Schröter, Tobias; Mohr, Jürgen; Yaroshenko, Andre; Maack, Hanns-Ingo; Pralow, Thomas; van der Heijden, Hendrik; Proksa, Roland; Köhler, Thomas; Wieberneit, Nataly; Rindt, Karsten; Rummeny, Ernst J.; Pfeiffer, Franz

2017-03-01

Purpose: To evaluate the performance of an experimental X-ray dark-field radiography system for chest imaging in humans and to compare with conventional diagnostic imaging. Materials and Methods: The study was institutional review board (IRB) approved. A single human cadaver (52 years, female, height: 173 cm, weight: 84 kg, chest circumference: 97 cm) was imaged within 24 hours post mortem on the experimental x-ray dark-field system. In addition, the cadaver was imaged on a clinical CT system to obtain a reference scan. The grating-based dark-field radiography setup was equipped with a set of three gratings to enable grating-based dark-field contrast x-ray imaging. The prototype operates at an acceleration voltage of up to 70 kVp and with a field-of-view large enough for clinical chest x-ray (>35 x 35 cm2). Results: It was feasible to extract x-ray dark-field signal of the whole human thorax, clearly demonstrating that human x-ray dark-field chest radiography is feasible. Lung tissue produced strong scattering, reflected in a pronounced x-ray dark-field signal. The ribcage and the backbone are less prominent than the lung but are also distinguishable. Finally, the soft tissue is not present in the dark-field radiography. The regions of the lungs affected by edema, as verified by CT, showed less dark-field signal compared to healthy lung tissue. Conclusion: Our results reveal the current status of translating dark-field imaging from a micro (small animal) scale to a macro (patient) scale. The performance of the experimental x-ray dark-field radiography setup offers, for the first time, obtaining multi-contrast chest x-ray images (attenuation and dark-field signal) from a human cadaver.

Orangutans (Pongo pygmaeus) and bonobos (Pan paniscus) point to inform a human about the location of a tool.

PubMed

Zimmermann, Felizitas; Zemke, Franziska; Call, Josep; Gómez, Juan Carlos

2009-03-01

Although pointing is not part of great apes' natural gestural repertoire, they can learn to point to food, in order to request it. To assess the flexibility with which they can use this gesture, one can vary the potential referent of the point. In two previous studies, three orangutans (two of them human-reared) have shown the ability to point to the location of a tool which a human experimenter needed in order to give them food. Here, we tested six orangutans and five bonobos using a set-up in which our subjects had to guide a human experimenter to the hiding place of a fork which was needed in order to retrieve a piece of food for the subject out of a vertical tube. We further examined the potential role of a competitive/deceptive context by varying the identity of the person responsible for hiding the tool. In addition, we implemented three different control conditions in which an object was hidden but it was not necessary to indicate its location to get the food. We found that the majority of subjects spontaneously guided the experimenter to the hiding place of the fork by pointing to it when it was necessary and they did so significantly less in control conditions. We did not find an effect of the person hiding the fork. Our results show that mother-reared orangutans and bonobos are able to point to inform a human about the location of an object that the human needs to procure food for the subject and that they can take into account whether it is relevant or not to do so.

Postural control during quiet bipedal standing in rats

PubMed Central

Sato, Yota; Fujiki, Soichiro; Sato, Yamato; Aoi, Shinya; Tsuchiya, Kazuo; Yanagihara, Dai

2017-01-01

The control of bipedal posture in humans is subject to non-ideal conditions such as delayed sensation and heartbeat noise. However, the controller achieves a high level of functionality by utilizing body dynamics dexterously. In order to elucidate the neural mechanism responsible for postural control, the present study made use of an experimental setup involving rats because they have more accessible neural structures. The experimental design requires rats to stand bipedally in order to obtain a water reward placed in a water supplier above them. Their motions can be measured in detail using a motion capture system and a force plate. Rats have the ability to stand bipedally for long durations (over 200 s), allowing for the construction of an experimental environment in which the steady standing motion of rats could be measured. The characteristics of the measured motion were evaluated based on aspects of the rats’ intersegmental coordination and power spectrum density (PSD). These characteristics were compared with those of the human bipedal posture. The intersegmental coordination of the standing rats included two components that were similar to that of standing humans: center of mass and trunk motion. The rats’ PSD showed a peak at approximately 1.8 Hz and the pattern of the PSD under the peak frequency was similar to that of the human PSD. However, the frequencies were five times higher in rats than in humans. Based on the analysis of the rats’ bipedal standing motion, there were some common characteristics between rat and human standing motions. Thus, using standing rats is expected to be a powerful tool to reveal the neural basis of postural control. PMID:29244818

Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line

PubMed Central

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

2016-01-01

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

Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line.

PubMed

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

2016-02-17

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

EXPERIMENTAL SUBCUTANEOUS CYSTICERCOSIS BY Taenia crassiceps IN BALB/c AND C57BL/6 MICE

PubMed Central

PEREIRA, Íria Márcia; LIMA, Sarah Buzaim; FREITAS, Aline de Araújo; VINAUD, Marina Clare; JUNIOR, Ruy de Souza LINO

2016-01-01

SUMMARY Human cysticercosis is one of the most severe parasitic infections affecting tissues. Experimental models are needed to understand the host-parasite dynamics involved throughout the course of the infection. The subcutaneous experimental model is the closest to what is observed in human cysticercosis that does not affect the central nervous system. The aim of this study was to evaluate macroscopically and microscopically the experimental subcutaneous cysticercosis caused by Taenia crassiceps cysticerci in BALB/c and C57BL/6 mice. Animals were inoculated in the dorsal subcutaneous region and macroscopic and microscopic aspects of the inflammatory process in the host-parasite interface were evaluated until 90 days after the inoculation (DAI). All the infected animals presented vesicles containing cysticerci in the inoculation site, which was translucent at 7 DAI and then remained opaque throughout the experimental days. The microscopic analysis showed granulation tissue in BALB/c mice since the acute phase of infection evolving to chronicity without cure, presenting 80% of larval stage cysticerci at 90 DAI. While C57BL/6 mice presented 67% of final stage cysticerci at 90 DAI, the parasites were surrounded by neutrophils evolving to the infection control. It is possible to conclude that the genetic features of susceptibility (BALB/c) or resistance (C57BL/6) were confirmed in an experimental subcutaneous model of cysticercosis. PMID:27410915

EXPERIMENTAL SUBCUTANEOUS CYSTICERCOSIS BY Taenia crassiceps IN BALB/c AND C57BL/6 MICE.

PubMed

Pereira, Íria Márcia; Lima, Sarah Buzaim; Freitas, Aline de Araújo; Vinaud, Marina Clare; Junior, Ruy de Souza Lino

2016-07-11

Human cysticercosis is one of the most severe parasitic infections affecting tissues. Experimental models are needed to understand the host-parasite dynamics involved throughout the course of the infection. The subcutaneous experimental model is the closest to what is observed in human cysticercosis that does not affect the central nervous system. The aim of this study was to evaluate macroscopically and microscopically the experimental subcutaneous cysticercosis caused by Taenia crassiceps cysticerci in BALB/c and C57BL/6 mice. Animals were inoculated in the dorsal subcutaneous region and macroscopic and microscopic aspects of the inflammatory process in the host-parasite interface were evaluated until 90 days after the inoculation (DAI). All the infected animals presented vesicles containing cysticerci in the inoculation site, which was translucent at 7 DAI and then remained opaque throughout the experimental days. The microscopic analysis showed granulation tissue in BALB/c mice since the acute phase of infection evolving to chronicity without cure, presenting 80% of larval stage cysticerci at 90 DAI. While C57BL/6 mice presented 67% of final stage cysticerci at 90 DAI, the parasites were surrounded by neutrophils evolving to the infection control. It is possible to conclude that the genetic features of susceptibility (BALB/c) or resistance (C57BL/6) were confirmed in an experimental subcutaneous model of cysticercosis.

B.M. Teplov as a Theoretician of Differential Psychology

ERIC Educational Resources Information Center

Nebylitsyn, V. D.

1974-01-01

Teplov's far-reaching ideas on the physiological mechanisms of human individual-psychological differences are presented; in particular, his use of "involuntary" experimental methods to study nervous-system types and the "combinability" of nervous-system characteristics. (CS)

Susceptibility of Legionella pneumophila to ofloxacin in vitro and in experimental Legionella pneumonia in guinea pigs.

PubMed Central

Saito, A; Sawatari, K; Fukuda, Y; Nagasawa, M; Koga, H; Tomonaga, A; Nakazato, H; Fujita, K; Shigeno, Y; Suzuyama, Y

1985-01-01

The antimicrobial activity of ofloxacin was tested against 15 standard strains and 37 clinical and environmental strains of Legionella pneumophila by agar dilution susceptibility studies with a new growth medium. The ofloxacin MICs were inoculum dependent and ranged from 0.03 to 0.125 microgram/ml. The antibacterial activities of other agents tested relative to ofloxacin were rifampin greater than ofloxacin greater than josamycin greater than pipemidic acid. Ofloxacin, at concentrations equal to or greater than 0.05 microgram/ml, inhibited the growth of L. pneumophila grown in human monocytes. The therapeutic efficacy of ofloxacin in experimental guinea pig L. pneumophila pneumonia was greater than that observed with erythromycin or josamycin therapy; it was less effective than was rifampin. Ofloxacin was very active against intracellular L. pneumophila in these experiments and should be studied in the therapy of human Legionnaires disease. PMID:3862361

Effects of titanium surface topography on morphology and in vitro activity of human gingival fibroblasts.

PubMed

Ramaglia, L; Capece, G; Di Spigna, G; Bruno, M P; Buonocore, N; Postiglione, L

2013-01-01

The aim of the present study was to evaluate in vitro the biological behavior of human gingival fibroblasts cultured on two different titanium surfaces. Titanium test disks were prepared with a machined, relatively smooth (S) surface or a rough surface (O) obtained by a double acid etching procedure. Primary cultures of human gingival fibroblasts were plated on the experimental titanium disks and cultured up to 14 days. Titanium disk surfaces were analysed by scanning electron microscopy (SEM). Cell proliferation and a quantitative analysis by ELISA in situ of ECM components as CoI, FN and TN were performed. Results have shown different effects of titanium surface microtopography on cell expression and differentiation. At 96 hours of culture on experimental surfaces human gingival fibroblasts displayed a favourable cell attachment and proliferation on both surfaces although showing some differences. Both the relatively smooth and the etched surfaces interacted actively with in vitro cultures of human gingival fibroblasts, promoting cell proliferation and differentiation. Results suggested that the microtopography of a double acid-etched rough surface may induce a greater Co I and FN production, thus conditioning in vivo the biological behaviour of human gingival fibroblasts during the process of peri-implant soft tissue healing.

Thirst-dependent risk preferences in monkeys identify a primitive form of wealth.

PubMed

Yamada, Hiroshi; Tymula, Agnieszka; Louie, Kenway; Glimcher, Paul W

2013-09-24

Experimental economic techniques have been widely used to evaluate human risk attitudes, but how these measured attitudes relate to overall individual wealth levels is unclear. Previous noneconomic work has addressed this uncertainty in animals by asking the following: (i) Do our close evolutionary relatives share both our risk attitudes and our degree of economic rationality? And (ii) how does the amount of food or water one holds (a nonpecuniary form of "wealth") alter risk attitudes in these choosers? Unfortunately, existing noneconomic studies have provided conflicting insights from an economic point of view. We therefore used standard techniques from human experimental economics to measure monkey risk attitudes for water rewards as a function of blood osmolality (an objective measure of how much water the subjects possess). Early in training, monkeys behaved randomly, consistently violating first-order stochastic dominance and monotonicity. After training, they behaved like human choosers--technically consistent in their choices and weakly risk averse (i.e., risk averse or risk neutral on average)--suggesting that well-trained monkeys can serve as a model for human choice behavior. As with attitudes about money in humans, these risk attitudes were strongly wealth dependent; as the animals became "poorer," risk aversion increased, a finding incompatible with some models of wealth and risk in human decision making.

Rumination, Age, and Years of Experience: A Predictive Study of Burnout

ERIC Educational Resources Information Center

McDuffy, Moriel S.

2016-01-01

This study used a non-experimental design to examine whether job satisfaction, rumination, age and years of experience predict burnout among human service workers serving high-risk populations. The study also used a stepwise regression to assess whether job satisfaction, rumination, age, or years of experience predict burnout equally. Burnout was…

Study of Personal and Social Adjustment Ability of the Disabled Pupils

ERIC Educational Resources Information Center

Ryabova, Natalia Vladimirovna; Parfyonova, Tatyana Aleksandrovna

2015-01-01

The article presents the results of experimental work aimed at studying personal and social adjustment of a child with disabilities. Analysis of domestic and foreign psychological and educational literature allowed us to determine the key concept of the study, namely "social and personal orientation", as a trait of a human's personality,…

Mycobacterium tuberculosis Coinfection Has No Impact on Plasmodium berghei ANKA-Induced Experimental Cerebral Malaria in C57BL/6 Mice.

PubMed

Blank, Jannike; Behrends, Jochen; Jacobs, Thomas; Schneider, Bianca E

2016-02-01

Cerebral malaria (CM) is the most severe complication of human infection with Plasmodium falciparum. The mechanisms predisposing to CM are still not fully understood. Proinflammatory immune responses are required for the control of blood-stage malaria infection but are also implicated in the pathogenesis of CM. A fine balance between pro- and anti-inflammatory immune responses is required for parasite clearance without the induction of host pathology. The most accepted experimental model to study human CM is Plasmodium berghei ANKA (PbANKA) infection in C57BL/6 mice that leads to the development of a complex neurological syndrome which shares many characteristics with the human disease. We applied this model to study the outcome of PbANKA infection in mice previously infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. Tuberculosis is coendemic with malaria in large regions in the tropics, and mycobacteria have been reported to confer some degree of unspecific protection against rodent Plasmodium parasites in experimental coinfection models. We found that concomitant M. tuberculosis infection did not change the clinical course of PbANKA-induced experimental cerebral malaria (ECM) in C57BL/6 mice. The immunological environments in spleen and brain did not differ between singly infected and coinfected animals; instead, the overall cytokine and T cell responses in coinfected mice were comparable to those in animals solely infected with PbANKA. Our data suggest that M. tuberculosis coinfection is not able to change the outcome of PbANKA-induced disease, most likely because the inflammatory response induced by the parasite rapidly dominates in mice previously infected with M. tuberculosis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Reconstruction of Tissue-Specific Metabolic Networks Using CORDA

PubMed Central

Schultz, André; Qutub, Amina A.

2016-01-01

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

Drosophila and experimental neurology in the post-genomic era.

PubMed

Shulman, Joshua M

2015-12-01

For decades, the fruit fly, Drosophila melanogaster, has been among the premiere genetic model systems for probing fundamental neurobiology, including elucidation of mechanisms responsible for human neurologic disorders. Flies continue to offer virtually unparalleled versatility and speed for genetic manipulation, strong genomic conservation, and a nervous system that recapitulates a range of cellular and network properties relevant to human disease. I focus here on four critical challenges emerging from recent advances in our understanding of the genomic basis of human neurologic disorders where innovative experimental strategies are urgently needed: (1) pinpointing causal genes from associated genomic loci; (2) confirming the functional impact of allelic variants; (3) elucidating nervous system roles for novel or poorly studied genes; and (4) probing network interactions within implicated regulatory pathways. Drosophila genetic approaches are ideally suited to address each of these potential translational roadblocks, and will therefore contribute to mechanistic insights and potential breakthrough therapies for complex genetic disorders in the coming years. Strategic collaboration between neurologists, human geneticists, and the Drosophila research community holds great promise to accelerate progress in the post-genomic era. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterizing human vestibular sensory epithelia for experimental studies: new hair bundles on old tissue and implications for therapeutic interventions in ageing

PubMed Central

Taylor, Ruth R.; Jagger, Daniel J.; Saeed, Shakeel R.; Axon, Patrick; Donnelly, Neil; Tysome, James; Moffatt, David; Irving, Richard; Monksfield, Peter; Coulson, Chris; Freeman, Simon R.; Lloyd, Simon K.; Forge, Andrew

2015-01-01

Balance disequilibrium is a significant contributor to falls in the elderly. The most common cause of balance dysfunction is loss of sensory cells from the vestibular sensory epithelia of the inner ear. However, inaccessibility of inner ear tissue in humans severely restricts possibilities for experimental manipulation to develop therapies to ameliorate this loss. We provide a structural and functional analysis of human vestibular sensory epithelia harvested at trans-labyrinthine surgery. We demonstrate the viability of the tissue and labeling with specific markers of hair cell function and of ion homeostasis in the epithelium. Samples obtained from the oldest patients revealed a significant loss of hair cells across the tissue surface, but we found immature hair bundles present in epithelia harvested from patients >60 years of age. These results suggest that the environment of the human vestibular sensory epithelium could be responsive to stimulation of developmental pathways to enhance hair cell regeneration, as has been demonstrated successfully in the vestibular organs of adult mice. PMID:25818177

Characterizing human vestibular sensory epithelia for experimental studies: new hair bundles on old tissue and implications for therapeutic interventions in ageing.

PubMed

Taylor, Ruth R; Jagger, Daniel J; Saeed, Shakeel R; Axon, Patrick; Donnelly, Neil; Tysome, James; Moffatt, David; Irving, Richard; Monksfield, Peter; Coulson, Chris; Freeman, Simon R; Lloyd, Simon K; Forge, Andrew

2015-06-01

Balance disequilibrium is a significant contributor to falls in the elderly. The most common cause of balance dysfunction is loss of sensory cells from the vestibular sensory epithelia of the inner ear. However, inaccessibility of inner ear tissue in humans severely restricts possibilities for experimental manipulation to develop therapies to ameliorate this loss. We provide a structural and functional analysis of human vestibular sensory epithelia harvested at trans-labyrinthine surgery. We demonstrate the viability of the tissue and labeling with specific markers of hair cell function and of ion homeostasis in the epithelium. Samples obtained from the oldest patients revealed a significant loss of hair cells across the tissue surface, but we found immature hair bundles present in epithelia harvested from patients >60 years of age. These results suggest that the environment of the human vestibular sensory epithelium could be responsive to stimulation of developmental pathways to enhance hair cell regeneration, as has been demonstrated successfully in the vestibular organs of adult mice. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

PERFLUORINATED COMPOUNDS: EMERGING POPs WITH POTENTIAL IMMUNOTOXICITY

PubMed Central

Corsini, Emanuela; Luebke, Robert W.; Germolec, Dori R.; DeWitt, Jamie C.

2015-01-01

Perfluorinated compounds (PFCs) have been recognized as an important class of environmental contaminants commonly detected in blood samples of both wildlife and humans. These compounds have been in use for more than 60 years as surface treatment chemicals, polymerization aids, and surfactants. They possess a strong carbon-fluorine bond, which leads to their environmental persistence. There is evidence from both epidemiology and laboratory studies that PFCs may be immunotoxic, affecting both cell-mediated and humoral immunity. Reported effects of PFCs include decreased spleen and thymus weights and cellularity, reduced antibody production, reduced survival after influenza infection, and altered cytokine production. Immunosuppression is a critical effect associated with exposure to PFCs, as it has been reported to reduce antibody responses to vaccination in children. Mounting evidence suggests that immunotoxicity in experimental animals can occur at serum concentrations below, within, or just above the reported range for highly exposed humans and wildlife. Considering bioaccumulation and exposure to multiple PFCs, the risk of immunotoxicity for humans and wildlife cannot be discounted. This review will discuss current and recently published work exploring the immunomodulatory effects of PFCs in experimental animals and humans. PMID:24503008

The cognitive cost of sleep lost

PubMed Central

McCoy, John G.; Strecker, Robert E.

2013-01-01

A substantial body of literature supports the intuitive notion that a good night’s sleep can facilitate human cognitive performance the next day. Deficits in attention, learning & memory, emotional reactivity, and higher-order cognitive processes, such as executive function and decision making, have all been documented following sleep disruption in humans. Thus, whilst numerous clinical and experimental studies link human sleep disturbance to cognitive deficits, attempts to develop valid and reliable rodent models of these phenomena are fewer, and relatively more recent. This review focuses primarily on the cognitive impairments produced by sleep disruption in rodent models of several human patterns of sleep loss/sleep disturbance. Though not an exclusive list, this review will focus on four specific types of sleep disturbance: total sleep deprivation, experimental sleep fragmentation, selective REM sleep deprivation, and chronic sleep restriction. The use of rodent models can provide greater opportunities to understand the neurobiological changes underlying sleep loss induced cognitive impairments. Thus, this review concludes with a description of recent neurobiological findings concerning the neuroplastic changes and putative brain mechanisms that may underlie the cognitive deficits produced by sleep disturbances. PMID:21875679

Autonomy in Materials Research: A Case Study in Carbon Nanotube Growth (Postprint)

DTIC Science & Technology

2016-10-21

built an Autonomous Research System (ARES)—an autonomous research robot capable of first-of-its-kind closed-loop iterative materials experimentation...ARES exploits advances in autonomous robotics , artificial intelligence, data sciences, and high-throughput and in situ techniques, and is able to...roles of humans and autonomous research robots , and for human-machine partnering. We believe autonomous research robots like ARES constitute a

Systematic review of community health impacts of mountaintop removal mining.

PubMed

Boyles, Abee L; Blain, Robyn B; Rochester, Johanna R; Avanasi, Raghavendhran; Goldhaber, Susan B; McComb, Sofie; Holmgren, Stephanie D; Masten, Scott A; Thayer, Kristina A

2017-10-01

The objective of this evaluation is to understand the human health impacts of mountaintop removal (MTR) mining, the major method of coal mining in and around Central Appalachia. MTR mining impacts the air, water, and soil and raises concerns about potential adverse health effects in neighboring communities; exposures associated with MTR mining include particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), metals, hydrogen sulfide, and other recognized harmful substances. A systematic review was conducted of published studies of MTR mining and community health, occupational studies of MTR mining, and any available animal and in vitro experimental studies investigating the effects of exposures to MTR-mining-related chemical mixtures. Six databases (Embase, PsycINFO, PubMed, Scopus, Toxline, and Web of Science) were searched with customized terms, and no restrictions on publication year or language, through October 27, 2016. The eligibility criteria included all human population studies and animal models of human health, direct and indirect measures of MTR-mining exposure, any health-related effect or change in physiological response, and any study design type. Risk of bias was assessed for observational and experimental studies using an approach developed by the National Toxicology Program (NTP) Office of Health Assessment and Translation (OHAT). To provide context for these health effects, a summary of the exposure literature is included that focuses on describing findings for outdoor air, indoor air, and drinking water. From a literature search capturing 3088 studies, 33 human studies (29 community, four occupational), four experimental studies (two in rat, one in vitro and in mice, one in C. elegans), and 58 MTR mining exposure studies were identified. A number of health findings were reported in observational human studies, including cardiopulmonary effects, mortality, and birth defects. However, concerns for risk of bias were identified, especially with respect to exposure characterization, accounting for confounding variables (such as socioeconomic status), and methods used to assess health outcomes. Typically, exposure was assessed by proximity of residence or hospital to coal mining or production level at the county level. In addition, assessing the consistency of findings was challenging because separate publications likely included overlapping case and comparison groups. For example, 11 studies of mortality were conducted with most reporting higher rates associated with coal mining, but many of these relied on the same national datasets and were unable to consider individual-level contributors to mortality such as poor socioeconomic status or smoking. Two studies of adult rats reported impaired microvascular and cardiac mitochondrial function after intratracheal exposure to PM from MTR-mining sites. Exposures associated with MTR mining included reports of PM levels that sometimes exceeded Environmental Protection Agency (EPA) standards; higher levels of dust, trace metals, hydrogen sulfide gas; and a report of increased public drinking water violations. This systematic review could not reach conclusions on community health effects of MTR mining because of the strong potential for bias in the current body of human literature. Improved characterization of exposures by future community health studies and further study of the effects of MTR mining chemical mixtures in experimental models will be critical to determining health risks of MTR mining to communities. Without such work, uncertainty will remain regarding the impact of these practices on the health of the people who breathe the air and drink the water affected by MTR mining. Published by Elsevier Ltd.

Human-robot interaction modeling and simulation of supervisory control and situational awareness during field experimentation with military manned and unmanned ground vehicles

NASA Astrophysics Data System (ADS)

Johnson, Tony; Metcalfe, Jason; Brewster, Benjamin; Manteuffel, Christopher; Jaswa, Matthew; Tierney, Terrance

2010-04-01

The proliferation of intelligent systems in today's military demands increased focus on the optimization of human-robot interactions. Traditional studies in this domain involve large-scale field tests that require humans to operate semiautomated systems under varying conditions within military-relevant scenarios. However, provided that adequate constraints are employed, modeling and simulation can be a cost-effective alternative and supplement. The current presentation discusses a simulation effort that was executed in parallel with a field test with Soldiers operating military vehicles in an environment that represented key elements of the true operational context. In this study, "constructive" human operators were designed to represent average Soldiers executing supervisory control over an intelligent ground system. The constructive Soldiers were simulated performing the same tasks as those performed by real Soldiers during a directly analogous field test. Exercising the models in a high-fidelity virtual environment provided predictive results that represented actual performance in certain aspects, such as situational awareness, but diverged in others. These findings largely reflected the quality of modeling assumptions used to design behaviors and the quality of information available on which to articulate principles of operation. Ultimately, predictive analyses partially supported expectations, with deficiencies explicable via Soldier surveys, experimenter observations, and previously-identified knowledge gaps.

Sex Differences in Androgen Regulation of Metabolism in Nonhuman Primates.

PubMed

True, Cadence; Abbott, David H; Roberts, Charles T; Varlamov, Oleg

2017-01-01

The in-depth characterization of sex differences relevant to human physiology requires the judicious use of a variety of animal models and human clinical data. Nonhuman primates (NHPs) represent an important experimental system that bridges rodent studies and clinical investigations. NHP studies have been especially useful in understanding the role of sex hormones in development and metabolism and also allow the elucidation of the effects of pertinent dietary influences on physiology pertinent to disease states such as obesity and diabetes. This chapter summarizes the current state of our understanding of androgen effects on male and female NHP metabolism relevant to hypogonadism in human males and polycystic ovary syndrome in human females. This review will also focus on the interaction between altered androgen levels and dietary restriction and excess, in particular the Western-style diet that underlies significant human pathophysiology.

SEX DIFFERENCES IN ANDROGEN REGULATION OF METABOLISM IN NONHUMAN PRIMATES

PubMed Central

True, Cadence; Abbott, David H.; Roberts, Charles T.; Varlamov, Oleg

2018-01-01

The in-depth characterization of sex differences relevant to human physiology requires the judicious use of a variety of animal models and human clinical data. Nonhuman primates (NHPs) represent an important experimental system that bridges rodent studies and clinical investigations. NHP studies have been especially useful in understanding the role of sex hormones in development and metabolism and also allow the elucidation of the effects of pertinent dietary influences on physiology pertinent to disease states such as obesity and diabetes. This chapter summarizes the current state of our understanding of androgen effects on male and female NHP metabolism relevant to hypogonadism in human males and polycystic ovary syndrome in human females, as well as the interaction between altered androgen levels and dietary restriction and excess, in particular the western-style diet that underlies significant human pathophysiology. PMID:29224110

Study of the neural dynamics for understanding communication in terms of complex hetero systems.

PubMed

Tsuda, Ichiro; Yamaguchi, Yoko; Hashimoto, Takashi; Okuda, Jiro; Kawasaki, Masahiro; Nagasaka, Yasuo

2015-01-01

The purpose of the research project was to establish a new research area named "neural information science for communication" by elucidating its neural mechanism. The research was performed in collaboration with applied mathematicians in complex-systems science and experimental researchers in neuroscience. The project included measurements of brain activity during communication with or without languages and analyses performed with the help of extended theories for dynamical systems and stochastic systems. The communication paradigm was extended to the interactions between human and human, human and animal, human and robot, human and materials, and even animal and animal. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Reciprocal transcriptional regulation of metabolic and signaling pathways correlates with disease severity in heart failure.

PubMed

Barth, Andreas S; Kumordzie, Ami; Frangakis, Constantine; Margulies, Kenneth B; Cappola, Thomas P; Tomaselli, Gordon F

2011-10-01

Systolic heart failure (HF) is a complex systemic syndrome that can result from a wide variety of clinical conditions and gene mutations. Despite phenotypic similarities, characterized by ventricular dilatation and reduced contractility, the extent of common and divergent gene expression between different forms of HF remains a matter of intense debate. Using a meta-analysis of 28 experimental (mouse, rat, dog) and human HF microarray studies, we demonstrate that gene expression changes are characterized by a coordinated and reciprocal regulation of major metabolic and signaling pathways. In response to a wide variety of stressors in animal models of HF, including ischemia, pressure overload, tachypacing, chronic isoproterenol infusion, Chagas disease, and transgenic mouse models, major metabolic pathways are invariably downregulated, whereas cell signaling pathways are upregulated. In contrast to this uniform transcriptional pattern that recapitulates a fetal gene expression program in experimental animal models of HF, human HF microarray studies displayed a greater heterogeneity, with some studies even showing upregulation of metabolic and downregulation of signaling pathways in end-stage human hearts. These discrepant results between animal and human studies are due to a number of factors, prominently cardiac disease and variable exposure to cold cardioplegic solution in nonfailing human samples, which can downregulate transcripts involved in oxidative phosphorylation (OXPHOS), thus mimicking gene expression patterns observed in failing samples. Additionally, β-blockers and ACE inhibitor use in end-stage human HF was associated with higher levels of myocardial OXPHOS transcripts, thus partially reversing the fetal gene expression pattern. In human failing samples, downregulation of metabolism was associated with hemodynamic markers of disease severity. Irrespective of the etiology, gene expression in failing myocardium is characterized by downregulation of metabolic transcripts and concomitant upregulation of cell signaling pathways. Gene expression changes along this metabolic-signaling axis in mammalian myocardium are a consistent feature in the heterogeneous transcriptional response observed in phenotypically similar models of HF.

Human beta-globin gene polymorphisms characterized in DNA extracted from ancient bones 12,000 years old.

PubMed

Béraud-Colomb, E; Roubin, R; Martin, J; Maroc, N; Gardeisen, A; Trabuchet, G; Goosséns, M

1995-12-01

Analyzing the nuclear DNA from ancient human bones is an essential step to the understanding of genetic diversity in current populations, provided that such systematic studies are experimentally feasible. This article reports the successful extraction and amplification of nuclear DNA from the beta-globin region from 5 of 10 bone specimens up to 12,000 years old. These have been typed for beta-globin frameworks by sequencing through two variable positions and for a polymorphic (AT) chi (T) gamma microsatellite 500 bp upstream of the beta-globin gene. These specimens of human remains are somewhat older than those analyzed in previous nuclear gene sequencing reports and considerably older than those used to study high-copy-number human mtDNA. These results show that the systematic study of nuclear DNA polymorphisms of ancient populations is feasible.

hPDI: a database of experimental human protein-DNA interactions.

PubMed

Xie, Zhi; Hu, Shaohui; Blackshaw, Seth; Zhu, Heng; Qian, Jiang

2010-01-15

The human protein DNA Interactome (hPDI) database holds experimental protein-DNA interaction data for humans identified by protein microarray assays. The unique characteristics of hPDI are that it contains consensus DNA-binding sequences not only for nearly 500 human transcription factors but also for >500 unconventional DNA-binding proteins, which are completely uncharacterized previously. Users can browse, search and download a subset or the entire data via a web interface. This database is freely accessible for any academic purposes. http://bioinfo.wilmer.jhu.edu/PDI/.

An Automated, Experimenter-Free Method for the Standardised, Operant Cognitive Testing of Rats

PubMed Central

Rivalan, Marion; Munawar, Humaira; Fuchs, Anna; Winter, York

2017-01-01

Animal models of human pathology are essential for biomedical research. However, a recurring issue in the use of animal models is the poor reproducibility of behavioural and physiological findings within and between laboratories. The most critical factor influencing this issue remains the experimenter themselves. One solution is the use of procedures devoid of human intervention. We present a novel approach to experimenter-free testing cognitive abilities in rats, by combining undisturbed group housing with automated, standardized and individual operant testing. This experimenter-free system consisted of an automated-operant system (Bussey-Saksida rat touch screen) connected to a home cage containing group living rats via an automated animal sorter (PhenoSys). The automated animal sorter, which is based on radio-frequency identification (RFID) technology, functioned as a mechanical replacement of the experimenter. Rats learnt to regularly and individually enter the operant chamber and remained there for the duration of the experimental session only. Self-motivated rats acquired the complex touch screen task of trial-unique non-matching to location (TUNL) in half the time reported for animals that were manually placed into the operant chamber. Rat performance was similar between the two groups within our laboratory, and comparable to previously published results obtained elsewhere. This reproducibility, both within and between laboratories, confirms the validity of this approach. In addition, automation reduced daily experimental time by 80%, eliminated animal handling, and reduced equipment cost. This automated, experimenter-free setup is a promising tool of great potential for testing a large variety of functions with full automation in future studies. PMID:28060883

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

PubMed

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

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

Dissecting the human immunologic memory for pathogens.

PubMed

Zielinski, Christina E; Corti, Davide; Mele, Federico; Pinto, Dora; Lanzavecchia, Antonio; Sallusto, Federica

2011-03-01

Studies on immunologic memory in animal models and especially in the human system are instrumental to identify mechanisms and correlates of protection necessary for vaccine development. In this article, we provide an overview of the cellular basis of immunologic memory. We also describe experimental approaches based on high throughput cell cultures, which we have developed to interrogate human memory T cells, B cells, and plasma cells. We discuss how these approaches can provide new tools and information for vaccine design, in a process that we define as 'analytic vaccinology'. © 2011 John Wiley & Sons A/S.

Standardised animal models of host microbial mutualism

PubMed Central

Macpherson, A J; McCoy, K D

2015-01-01

An appreciation of the importance of interactions between microbes and multicellular organisms is currently driving research in biology and biomedicine. Many human diseases involve interactions between the host and the microbiota, so investigating the mechanisms involved is important for human health. Although microbial ecology measurements capture considerable diversity of the communities between individuals, this diversity is highly problematic for reproducible experimental animal models that seek to establish the mechanistic basis for interactions within the overall host-microbial superorganism. Conflicting experimental results may be explained away through unknown differences in the microbiota composition between vivaria or between the microenvironment of different isolated cages. In this position paper, we propose standardised criteria for stabilised and defined experimental animal microbiotas to generate reproducible models of human disease that are suitable for systematic experimentation and are reproducible across different institutions. PMID:25492472

77 FR 23135 - 2,4-D; Order Denying NRDC's Petition To Revoke Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-18

... cannot be determined (``non-threshold effects''). Because EPA identified only threshold effect risks for... uncertainty or safety factors \\1\\ in conjunction with experimental toxicity data in assessing risk to humans... difference in sensitivity between humans and experimental animals (i.e., inter-species sensitivity) and...

40 CFR 158.220 - Experimental use permit data requirements for product performance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... pesticide product bears a claim to control pest microorganisms that pose a threat to human health and whose... PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Experimental Use Permits..., birds, bats, canids, and skunks) that may directly or indirectly transmit diseases to humans. However...

40 CFR 158.220 - Experimental use permit data requirements for product performance.

Code of Federal Regulations, 2012 CFR

2012-07-01

... pesticide product bears a claim to control pest microorganisms that pose a threat to human health and whose... PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Experimental Use Permits..., birds, bats, canids, and skunks) that may directly or indirectly transmit diseases to humans. However...

40 CFR 158.220 - Experimental use permit data requirements for product performance.

Code of Federal Regulations, 2011 CFR

2011-07-01

... pesticide product bears a claim to control pest microorganisms that pose a threat to human health and whose... PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Experimental Use Permits..., birds, bats, canids, and skunks) that may directly or indirectly transmit diseases to humans. However...

40 CFR 158.220 - Experimental use permit data requirements for product performance.

Code of Federal Regulations, 2013 CFR

2013-07-01

... pesticide product bears a claim to control pest microorganisms that pose a threat to human health and whose... PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Experimental Use Permits..., birds, bats, canids, and skunks) that may directly or indirectly transmit diseases to humans. However...

Human patient simulators and interactive case studies: a comparative analysis of learning outcomes and student perceptions.

PubMed

Howard, Valerie Michele; Ross, Carl; Mitchell, Ann M; Nelson, Glenn M

2010-01-01

Although human patient simulators provide an innovative teaching method for nursing students, they are quite expensive. To investigate the value of this expenditure, a quantitative, quasi-experimental, two-group pretest and posttest design was used to compare two educational interventions: human patient simulators and interactive case studies. The sample (N = 49) consisted of students from baccalaureate, accelerated baccalaureate, and diploma nursing programs. Custom-designed Health Education Systems, Inc examinations were used to measure knowledge before and after the implementation of the two educational interventions. Students in the human patient simulation group scored significantly higher than did those in the interactive case study group on the posttest Health Education Systems, Inc examination, and no significant difference was found in student scores among the three types of nursing programs that participated in the study. Data obtained from a questionnaire administered to participants indicated that students responded favorably to the use of human patient simulators as a teaching method.

[Some notes on the history of the experimental surgery laboratory. Reflections on its relevance in education and surgical research].

PubMed

de la Garza-Rodea, Anabel Sofía; Padilla-Sánchez, Luis; de la Garza-Aguilar, Javier; Neri-Vela, Rolando

2007-01-01

The progress of medicine has largely been due to research, and for surgery, in particular, the experimental surgical laboratory has been considered fundamental to the surgeon's education. In this study, a general view of experimental surgery is given in animal models based on bioethical norms as well as to design, create and apply different surgical procedures before performing in humans. Experimental surgery also facilitates surgical teaching and promotes the surgeon's scientific reasoning. Methods. This is a retrospective and descriptive study. Data were collected from direct and indirect sources of available publications on the historical, bioethical and educational aspects of medicine, focusing on surgery. The important facts corresponding to the field of experimental surgery and applicable in Mexico were selected. Concepts of experimental surgical models and of the experimental surgery laboratory were described. Bioethical considerations are emphasized for care of experimental animals. Finally, this work focuses on the importance of surgical experimentation in current and future development of the surgical researcher. Conclusions. Experimentation with animal models in a surgical laboratory is essential for surgical teaching and promotes development of the scientific thought in the surgeon. It is necessary for surgical research and is fundamental for making progress in surgery, treatment and medicine as science.

SOX2 and nestin expression in human melanoma: an immunohistochemical and experimental study

PubMed Central

Laga, Alvaro C.; Zhan, Qian; Weishaupt, Carsten; Ma, Jie; Frank, Markus H.; Murphy, George F.

2012-01-01

SOX2 is an embryonic neural crest stem-cell transcription factor recently shown to be expressed in human melanoma and to correlate with experimental tumor growth. SOX2 binds to an enhancer region of the gene that encodes for nestin, also a neural progenitor cell biomarker. To define further the potential relationship between SOX2 and nestin, we examined co-expression patterns in 135 melanomas and 37 melanocytic nevi. Immunohistochemical staining in 27 melanoma tissue sections showed an association between SOX2 positivity, spindle cell shape and a peripheral nestin distribution pattern. In contrast, SOX2-negative cells were predominantly epithelioid, and exhibited a cytoplasmic pattern for nestin. In tissue microarrays, co-expression correlated with tumor progression, with only 11% of nevi co-expressing SOX2 and nestin in contrast to 65% of metastatic melanomas, and preliminarily, with clinical outcome. Human melanoma lines that differentially expressed constitutive SOX2 revealed a positive correlation between SOX2 and nestin expression. Experimental melanomas grown from these respective cell lines in murine subcutis and dermis of xenografted human skin maintained the association between SOX2-positivity, spindle cell shape, and peripheral nestin distribution. Moreover, the cytoplasmic pattern of nestin distribution was observed in xenografts generated from SOX2-knockdown A2058 melanoma cells, in contrast to the periperhal nestin pattern seen in tumors grown from A2058 control cells transfected with non-target shRNA. In aggregate, these data further support a biologically significant linkage between SOX2 and nestin expression in human melanoma. PMID:21410764

In Vitro Experimental Model for the Long-Term Analysis of Cellular Dynamics During Bronchial Tree Development from Lung Epithelial Cells

PubMed Central

Maruta, Naomichi; Marumoto, Moegi

2017-01-01

Lung branching morphogenesis has been studied for decades, but the underlying developmental mechanisms are still not fully understood. Cellular movements dynamically change during the branching process, but it is difficult to observe long-term cellular dynamics by in vivo or tissue culture experiments. Therefore, developing an in vitro experimental model of bronchial tree would provide an essential tool for developmental biology, pathology, and systems biology. In this study, we succeeded in reconstructing a bronchial tree in vitro by using primary human bronchial epithelial cells. A high concentration gradient of bronchial epithelial cells was required for branching initiation, whereas homogeneously distributed endothelial cells induced the formation of successive branches. Subsequently, the branches grew in size to the order of millimeter. The developed model contains only two types of cells and it facilitates the analysis of lung branching morphogenesis. By taking advantage of our experimental model, we carried out long-term time-lapse observations, which revealed self-assembly, collective migration with leader cells, rotational motion, and spiral motion of epithelial cells in each developmental event. Mathematical simulation was also carried out to analyze the self-assembly process and it revealed simple rules that govern cellular dynamics. Our experimental model has provided many new insights into lung development and it has the potential to accelerate the study of developmental mechanisms, pattern formation, left–right asymmetry, and disease pathogenesis of the human lung. PMID:28471293

Maternal and fetal effects of chocolate consumption during pregnancy: a systematic review.

PubMed

Latif, Rabia

2018-03-13

The purpose of this review is to explore the effects of chocolate consumption during pregnancy on fetus and mother herself. Randomized controlled trials/quasi-experimental/observational/controlled before and after studies involving chocolate/cocoa/cacao consumption (irrespective of type or dose, composition, exposure period, and method of administration) among pregnant women/animals; and measuring any outcome (beneficial or harmful) related to fetus or mother after chocolate exposure were included. Databases searched were PubMed, Web of Science and Scopus; between April and May 2017. Risk of bias within each human randomized controlled trial (RCT) and animals' experimental studies was evaluated by "The Cochrane Collaboration's tool" and SYRCLE's tool respectively. Fourteen human studies including a total of 6639 participants and nine animal studies were selected. Outcome variables investigated in human studies were maternal blood pressure, fetal heart rate, and striae gravidarum. Animal studies explored chocolate-induced teratogenicity and fetal metabolic derangements. Ten out of these 23 studies reported chocolate to be "beneficial"; five studies reported adverse effects, whereas eight studies declared chocolate as "neutral". Maternal chocolate intake has acute stimulatory effects on fetal reactivity and chronic blood pressure reducing effect in mothers. Chocolate is nonteratogenic and does not affect reproductive indices. Metabolic derangements in offsprings born to chocolate fed dams have been reported. Pregnant females must be careful about consumption of cocoa and chocolate. Future studies should be planned, keeping in view heterogeneities identified across the selected studies in this review.

Neurochemical dynamics of acute orofacial pain in the human trigeminal brainstem nuclear complex.

PubMed

de Matos, Nuno M P; Hock, Andreas; Wyss, Michael; Ettlin, Dominik A; Brügger, Mike

2017-11-15

The trigeminal brainstem sensory nuclear complex is the first central relay structure mediating orofacial somatosensory and nociceptive perception. Animal studies suggest a substantial involvement of neurochemical alterations at such basal CNS levels in acute and chronic pain processing. Translating this animal based knowledge to humans is challenging. Human related examining of brainstem functions are challenged by MR related peculiarities as well as applicability aspects of experimentally standardized paradigms. Based on our experience with an MR compatible human orofacial pain model, the aims of the present study were twofold: 1) from a technical perspective, the evaluation of proton magnetic resonance spectroscopy at 3 T regarding measurement accuracy of neurochemical profiles in this small brainstem nuclear complex and 2) the examination of possible neurochemical alterations induced by an experimental orofacial pain model. Data from 13 healthy volunteers aged 19-46 years were analyzed and revealed high quality spectra with significant reductions in total N-acetylaspartate (N-acetylaspartate + N-acetylaspartylglutamate) (-3.7%, p = 0.009) and GABA (-10.88%, p = 0.041) during the pain condition. These results might reflect contributions of N-acetylaspartate and N-acetylaspartylglutamate in neuronal activity-dependent physiologic processes and/or excitatory neurotransmission, whereas changes in GABA might indicate towards a reduction in tonic GABAergic functioning during nociceptive signaling. Summarized, the present study indicates the applicability of 1 H-MRS to obtain neurochemical dynamics within the human trigeminal brainstem sensory nuclear complex. Further developments are needed to pave the way towards bridging important animal based knowledge with human research to understand the neurochemistry of orofacial nociception and pain. Copyright © 2017 Elsevier Inc. All rights reserved.

Stalking Antibiotic-Resistant Bacteria in Common Vegetables

ERIC Educational Resources Information Center

Brock, David; Boeke, Caroline; Josowitz, Rebecca; Loya, Katherine

2004-01-01

The study developed a simple experimental protocol for studying antibiotic resistant bacteria that will allow students to determine the proportion of such bacteria found on common fruit and vegetable crops. This protocol can open up the world of environmental science and show how human behavior can dramatically alter ecosystems.

Effects of suspended sulfates on human health.

PubMed Central

French, J G

1975-01-01

Recent evidence from epidemiologic studies conducted in several areas of the United States shows an association of excess risk of asthmatic attacks with elevated levels of suspended sulfates within specific temperature ranges. These findings are disscussed in the context of experimental animal studies which tend to support these observations. PMID:1157797

An Analysis of Student Choices in Medical Ethical Dilemmas.

ERIC Educational Resources Information Center

Woloshin, Phyllis Lerman

This report describes a study undertaken to assess student choices in medical ethical dilemmas. Medical ethical dilemmas are interpreted to include problems such as abortion, euthanasia, sterilization, experimentation on humans, allocation of scarce medical resources, and physician and health personnel training. The major purpose of the study was…

Session 6: Infant nutrition: future research developments in Europe EARNEST, the early nutrition programming project: EARly Nutrition programming - long-term Efficacy and Safety Trials and integrated epidemiological, genetic, animal, consumer and economic research.

PubMed

Fewtrell, M S

2007-08-01

Increasing evidence from lifetime experimental studies in animals and observational and experimental studies in human subjects suggests that pre- and postnatal nutrition programme long-term health. However, key unanswered questions remain on the extent of early-life programming in contemporary European populations, relevant nutritional exposures, critical time periods, mechanisms and the effectiveness of interventions to prevent or reverse programming effects. The EARly Nutrition programming - long-term Efficacy and Safety Trials and integrated epidemiological, genetic, animal, consumer and economic research (EARNEST) consortium brings together a multi-disciplinary team of scientists from European research institutions in an integrated programme of work that includes experimental studies in human subjects, modern prospective observational studies and mechanistic animal work including physiological studies, cell-culture models and molecular techniques. Theme 1 tests early nutritional programming of disease in human subjects, measuring disease markers in childhood and early adulthood in nineteen randomised controlled trials of nutritional interventions in pregnancy and infancy. Theme 2 examines associations between early nutrition and later outcomes in large modern European population-based prospective studies, with detailed measures of diet in pregnancy and early life. Theme 3 uses animal, cellular and molecular techniques to study lifetime effects of early nutrition. Biomedical studies are complemented by studies of the social and economic importance of programming (themes 4 and 5), and themes encouraging integration, communication, training and wealth creation. The project aims to: help formulate policies on the composition and testing of infant foods; improve the nutritional value of infant formulas; identify interventions to prevent and reverse adverse early nutritional programming. In addition, it has the potential to develop new products through industrial partnerships, generate information on the social and economic cost of programming in Europe and help maintain Europe's lead in this critical area of research.

Impact of suggestion on the human experimental model of cold hyperalgesia after topical application of high-concentration menthol [40%].

PubMed

Helfert, S; Reimer, M; Barnscheid, L; Hüllemann, P; Rengelshausen, J; Keller, T; Baron, R; Binder, A

2018-05-14

Human experimental pain models in healthy subjects offer unique possibilities to study mechanisms of pain within a defined setting of expected pain symptoms, signs and mechanisms. Previous trials in healthy subjects demonstrated that topical application of 40% menthol is suitable to induce cold hyperalgesia. The objective of this study was to evaluate the impact of suggestion on this experimental human pain model. The study was performed within a single-centre, randomized, placebo-controlled, double-blind, two-period crossover trial in a cohort of 16 healthy subjects. Subjects were tested twice after topical menthol application (40% dissolved in ethanol) and twice after ethanol (as placebo) application. In the style of a balanced placebo trial design, the subjects received during half of the testing the correct information about the applied substance (topical menthol or ethanol) and during half of the testing the incorrect information, leading to four tested conditions (treatment conditions: menthol-told-menthol and menthol-told-ethanol; placebo conditions: ethanol-told-menthol and ethanol-told-ethanol). Cold but not mechanical hyperalgesia was reliably induced by the model. The cold pain threshold decreased in both treatment conditions regardless whether true or false information was given. Minor suggestion effects were found in subjects with prior ethanol application. The menthol model is a reliable, nonsuggestible model to induce cold hyperalgesia. Mechanical hyperalgesia is not as reliable to induce. Cold hyperalgesia may be investigated under unbiased and suggestion-free conditions using the menthol model of pain. © 2018 European Pain Federation - EFIC®.

Evaluation of in vitro vs. in vivo methods for assessment of dermal absorption of organic flame retardants: a review.

PubMed

Abdallah, Mohamed Abou-Elwafa; Pawar, Gopal; Harrad, Stuart

2015-01-01

There is a growing interest to study human dermal exposure to a large number of chemicals, whether in the indoor or outdoor environment. Such studies are essential to predict the systemic exposure to xenobiotic chemicals for risk assessment purposes and to comply with various regulatory guidelines. However, very little is currently known about human dermal exposure to persistent organic pollutants. While recent pharmacokinetic studies have highlighted the importance of dermal contact as a pathway of human exposure to brominated flame retardants, risk assessment studies had to apply assumed values for percutaneous penetration of various flame retardants (FRs) due to complete absence of specific experimental data on their human dermal bioavailability. Therefore, this article discusses the current state-of-knowledge on the significance of dermal contact as a pathway of human exposure to FRs. The available literature on in vivo and in vitro methods for assessment of dermal absorption of FRs in human and laboratory animals is critically reviewed. Finally, a novel approach for studying human dermal absorption of FRs using in vitro three-dimensional (3D) human skin equivalent models is presented and the challenges facing future dermal absorption studies on FRs are highlighted. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ethics of animal research in human disease remediation, its institutional teaching; and alternatives to animal experimentation.

PubMed

Cheluvappa, Rajkumar; Scowen, Paul; Eri, Rajaraman

2017-08-01

Animals have been used in research and teaching for a long time. However, clear ethical guidelines and pertinent legislation were instated only in the past few decades, even in developed countries with Judeo-Christian ethical roots. We compactly cover the basics of animal research ethics, ethical reviewing and compliance guidelines for animal experimentation across the developed world, "our" fundamentals of institutional animal research ethics teaching, and emerging alternatives to animal research. This treatise was meticulously constructed for scientists interested/involved in animal research. Herein, we discuss key animal ethics principles - Replacement/Reduction/Refinement. Despite similar undergirding principles across developed countries, ethical reviewing and compliance guidelines for animal experimentation vary. The chronology and evolution of mandatory institutional ethical reviewing of animal experimentation (in its pioneering nations) are summarised. This is followed by a concise rendition of the fundamentals of teaching animal research ethics in institutions. With the advent of newer methodologies in human cell-culturing, novel/emerging methods aim to minimise, if not avoid the usage of animals in experimentation. Relevant to this, we discuss key extant/emerging alternatives to animal use in research; including organs on chips, human-derived three-dimensional tissue models, human blood derivates, microdosing, and computer modelling of various hues. © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.