Engineering Design Handbook. Army Weapon Systems Analysis. Part 2

DTIC Science & Technology

1979-10-01

EXPERIMENTAL DESIGN ............................... ............ 41-3 41-5 RESULTS OF THE ASARS lIX SIMULATIONS ........................... 41-4 41-6 LATIN...sciences and human factors engineering fields utilizing experimental methodology and multi-variable statistical techniques drawn from experimental ...randomly to grenades for the test design . The nine experimental types of hand grenades (first’ nine in Table 33-2) had a "pip" on their spherical

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.

21 CFR 170.22 - Safety factors to be considered.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Safety factors to be considered. 170.22 Section 170.22 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... experimental animals. ...

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.

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...

EXPERIMENTAL METHODOLOGIES AND PRELIMINARY TRANSFER FACTOR DATA FOR ESTIMATION OF DERMAL EXPOSURES TO PARTICLES

EPA Science Inventory

Developmental efforts and experimental data are described that focused on quantifying the transfer of particles on a mass basis from indoor surfaces to human skin. Methods were developed that utilized a common fluorescein-tagged Arizona Test Dust (ATD) as a possible surrogate ...

Featured Article: Serum [Met5]-enkephalin levels are reduced in multiple sclerosis and restored by low-dose naltrexone.

PubMed

Ludwig, Michael D; Zagon, Ian S; McLaughlin, Patricia J

2017-09-01

Low-dose naltrexone is a widely used off-label therapeutic prescribed for a variety of immune-related disorders. The mechanism underlying low-dose naltrexone's efficacy for fatigue, Crohn's disease, fibromyalgia, and multiple sclerosis is, in part, intermittent blockade of opioid receptors followed by upregulation of endogenous opioids. Short, intermittent blockade by naltrexone specifically blocks the opioid growth factor receptor resulting in biofeedback events that increase production of the endogenous opioid growth factor (OGF) (chemically termed [Met 5 ]-enkephalin) facilitating interactions between opioid growth factor and opioid growth factor receptor that ultimately, result in inhibited cell proliferation. Preclinical studies have reported that enkephalin levels are deficient in animal models of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. Our hypothesis is that serum enkephalin levels are diminished in humans with multiple sclerosis and experimental autoimmune encephalomyelitis mice, and that change in serum opioid growth factor levels may serve as a reasonable candidate biomarker for the onset of experimental autoimmune encephalomyelitis and response to therapy. To address this, we designed a two-part study to measure endogenous opioids in multiple sclerosis patients, and to investigate the temporal pattern of decline in serum enkephalin concentrations in mice with chronic progressive experimental autoimmune encephalomyelitis and treated with low-dose naltrexone. For comparison, we investigated whether low-dose naltrexone exposure in normal mice also resulted in altered enkephalin levels. In both animal models, we monitored tactile and heat sensitivity, as well as differential white blood cell counts as indicators of inflammation. Serum [Met 5 ]-enkephalin levels were lower in humans with multiple sclerosis relative to non-multiple sclerosis patients, and low-dose naltrexone restored their levels. In experimental autoimmune encephalomyelitis mice, [Met 5 ]-enkephalin levels were depressed prior to the appearance of clinical disease, and were restored with low-dose naltrexone treatment. Low-dose naltrexone therapy had no effect on serum [Met 5 ]-enkephalin or β-endorphin in normal mice. Thus, [Met 5 ]-enkephalin (i.e. opioid growth factor) may be a reasonable candidate biomarker for multiple sclerosis, and may signal new pathways for treatment of autoimmune disorders. Impact statement This report presents human and animal data identifying a novel biomarker for the onset and progression of multiple sclerosis (MS). Humans diagnosed with MS have reduced serum levels of OGF (i.e. [Met 5 ]-enkephalin) relative to non-MS neurologic patients, and low-dose naltrexone (LDN) therapy restored their enkephalin levels. Serum OGF levels were reduced in mice immunized with MOG 35-55 prior to any clinical behavioral sign of experimental autoimmune encephalomyelitis, and LDN therapy restored their serum OGF levels. β-endorphin concentrations were not altered by LDN in humans or mice. Thus, blood levels of OGF may serve as a new, selective biomarker for the progression of MS, as well as response to therapy.

[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.

Accessing key steps of human tumor progression in vivo by using an avian embryo model

NASA Astrophysics Data System (ADS)

Hagedorn, Martin; Javerzat, Sophie; Gilges, Delphine; Meyre, Aurélie; de Lafarge, Benjamin; Eichmann, Anne; Bikfalvi, Andreas

2005-02-01

Experimental in vivo tumor models are essential for comprehending the dynamic process of human cancer progression, identifying therapeutic targets, and evaluating antitumor drugs. However, current rodent models are limited by high costs, long experimental duration, variability, restricted accessibility to the tumor, and major ethical concerns. To avoid these shortcomings, we investigated whether tumor growth on the chick chorio-allantoic membrane after human glioblastoma cell grafting would replicate characteristics of the human disease. Avascular tumors consistently formed within 2 days, then progressed through vascular endothelial growth factor receptor 2-dependent angiogenesis, associated with hemorrhage, necrosis, and peritumoral edema. Blocking of vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor signaling pathways by using small-molecule receptor tyrosine kinase inhibitors abrogated tumor development. Gene regulation during the angiogenic switch was analyzed by oligonucleotide microarrays. Defined sample selection for gene profiling permitted identification of regulated genes whose functions are associated mainly with tumor vascularization and growth. Furthermore, expression of known tumor progression genes identified in the screen (IL-6 and cysteine-rich angiogenic inducer 61) as well as potential regulators (lumican and F-box-only 6) follow similar patterns in patient glioma. The model reliably simulates key features of human glioma growth in a few days and thus could considerably increase the speed and efficacy of research on human tumor progression and preclinical drug screening. angiogenesis | animal model alternatives | glioblastoma

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

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

Porous titanium and Ti-35Nb alloy: effects on gene expression of osteoblastic cells derived from human alveolar bone.

PubMed

do Prado, Renata Falchete; Rabêlo, Sylvia Bicalho; de Andrade, Dennia Perez; Nascimento, Rodrigo Dias; Henriques, Vinicius André Rodrigues; Carvalho, Yasmin Rodarte; Cairo, Carlos Alberto Alves; de Vasconcellos, Luana Marotta Reis

2015-11-01

Tests on titanium alloys that possess low elastic modulus, corrosion resistance and minimal potential toxicity are ongoing. This study aimed to evaluate the behavior of human osteoblastic cells cultured on dense and porous Titanium (Ti) samples comparing to dense and porous Ti-35 Niobium (Ti-35Nb) samples, using gene expression analysis. Scanning electronic microscopy confirmed surface porosity and pore interconnectivity and X-ray diffraction showed titanium beta-phase stabilization in Ti-35Nb alloy. There were no differences in expression of transforming growth factor-β, integrin-β1, alkaline phosphatase, osteopontin, macrophage colony stimulating factor, prostaglandin E synthase, and apolipoprotein E regarding the type of alloy, porosity and experimental period. The experimental period was a significant factor for the markers: bone sialoprotein II and interleukin 6, with expression increasing over time. Porosity diminished Runt-related transcription factor-2 (Runx-2) expression. Cells adhering to the Ti-35Nb alloy showed statistically similar expression to those adhering to commercially pure Ti grade II, for all the markers tested. In conclusion, the molecular mechanisms of interaction between human osteoblasts and the Ti-35Nb alloy follow the principal routes of osseointegration of commercially pure Ti grade II. Porosity impaired the route of transcription factor Runx-2.

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.

Simulated binding of transcription factors to active and inactive regions folds human chromosomes into loops, rosettes and topological domains

PubMed Central

Brackley, Chris A.; Johnson, James; Kelly, Steven; Cook, Peter R.; Marenduzzo, Davide

2016-01-01

Biophysicists are modeling conformations of interphase chromosomes, often basing the strengths of interactions between segments distant on the genetic map on contact frequencies determined experimentally. Here, instead, we develop a fitting-free, minimal model: bivalent or multivalent red and green ‘transcription factors’ bind to cognate sites in strings of beads (‘chromatin’) to form molecular bridges stabilizing loops. In the absence of additional explicit forces, molecular dynamic simulations reveal that bound factors spontaneously cluster—red with red, green with green, but rarely red with green—to give structures reminiscent of transcription factories. Binding of just two transcription factors (or proteins) to active and inactive regions of human chromosomes yields rosettes, topological domains and contact maps much like those seen experimentally. This emergent ‘bridging-induced attraction’ proves to be a robust, simple and generic force able to organize interphase chromosomes at all scales. PMID:27060145

[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.

TRANSFORMING GROWTH FACTOR BETA1 IS EXPRESSED IN THE JEJUNUM AFTER EXPERIMENTAL HUMAN CRYPTOSPORIDIUM PARVUM INFECTION IN HUMANS. (R828035)

EPA Science Inventory

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

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

Numerical Calculation of Internal Human Body Resistances at Power Frequency, and Comparison of them with Experimental Ones

NASA Astrophysics Data System (ADS)

Tarao, Hiroo; Hayashi, Noriyuki; Hamamoto, Isao; Isaka, Katsuo

A numerical method, which is newly developed here, is used in order to calculate internal body resistances in a voxelized biological model. By using this method, the internal resistances of an anatomical human model were calculated for the two current paths: 1400 Ω for a hand to foot, and 1500 Ω for a hand to hand. They are compared with experimental ones (500 ∼ 600 Ω for the hand to foot and 500 ∼ 700 Ω for the hand to hand), resulting in the conclusion that the numerical values of the internal resistance are twice or three times higher than the experimental ones. While there is the discrepancy between the calculated and measured results in the absolute values, the profiles of their relative values along the current paths showed good agreement. This implies that the factors such as the anisotropy of muscle conductivity and the difference between in vivo and in vitro conductivities need to be considered. In fact, in consideration of those factors, the calculated results approached the experimental ones.

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

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.

Prebiotics and the absorption of minerals: a review of experimental and human data

USDA-ARS?s Scientific Manuscript database

Dietary factors, including calcium and vitamin D intake, absorption, and status, lifestyle factors including physical activity, and genetics interact to determine peak bone mass. The current recommended dietary intake of calcium (adequate intake, AI) of 1300 mg/day in the United States for adolescen...

Protection of Brain Injury by Amniotic Mesenchymal Stromal Cell-Secreted Metabolites.

PubMed

Pischiutta, Francesca; Brunelli, Laura; Romele, Pietro; Silini, Antonietta; Sammali, Eliana; Paracchini, Lara; Marchini, Sergio; Talamini, Laura; Bigini, Paolo; Boncoraglio, Giorgio B; Pastorelli, Roberta; De Simoni, Maria-Grazia; Parolini, Ornella; Zanier, Elisa R

2016-11-01

To define the features of human amniotic mesenchymal stromal cell secretome and its protective properties in experimental models of acute brain injury. Prospective experimental study. Laboratory research. C57Bl/6 mice. Mice subjected to sham or traumatic brain injury by controlled cortical impact received human amniotic mesenchymal stromal cells or phosphate-buffered saline infused intracerebroventricularly or intravenously 24 hours after injury. Organotypic cortical brain slices exposed to ischemic injury by oxygen-glucose deprivation were treated with human amniotic mesenchymal stromal cells or with their secretome (conditioned medium) in a transwell system. Traumatic brain injured mice receiving human amniotic mesenchymal stromal cells intravenously or intracerebroventricularly showed early and lasting functional and anatomical brain protection. cortical slices injured by oxigen-glucose deprivation and treated with human amniotic mesenchymal stromal cells or conditioned medium showed comparable protective effects (neuronal rescue, promotion of M2 microglia polarization, induction of trophic factors) indicating that the exposure of human amniotic mesenchymal stromal cells to the injured tissue is not necessary for the release of bioactive factors. Using sequential size-exclusion and gel-filtration chromatography, we identified a conditioned medium subfraction, which specifically displays these highly protective properties and we found that this fraction was rich in bioactive molecules with molecular weight smaller than 700 Da. Quantitative RNA analysis and mass spectrometry-based peptidomics showed that the active factors are not proteins or RNAs. The metabolomic profiling of six metabolic classes identified a list of molecules whose abundance was selectively elevated in the active conditioned medium fraction. Human amniotic mesenchymal stromal cell-secreted factors protect the brain after acute injury. Importantly, a fraction rich in metabolites, and containing neither proteic nor ribonucleic molecules was protective. This study indicates the profiling of protective factors that could be useful in cell-free therapeutic approaches for acute brain injury.

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.

Augmentation of Antitumor T-Cell Responses by Increasing APC T-Cell C5a/C3a-C5aR/C3aR Interactions

DTIC Science & Technology

2013-03-01

the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. The Journal of experimental medicine . 1984;160(5...cell immunity. The Journal of experimental medicine . 2005;201(10):1523-30. PubMed PMID: 15883171. 3. Vogel CW, Wilkie SD, Morgan AC. In vivo studies...with covalent conjugates of cobra venom factor and monoclonal antibodies to human tumors. Haematology and blood transfusion. 1985;29:514- 7. Epub

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

Nature and Nurture: the complex genetics of myopia and refractive error

PubMed Central

Wojciechowski, Robert

2010-01-01

The refractive errors, myopia and hyperopia, are optical defects of the visual system that can cause blurred vision. Uncorrected refractive errors are the most common causes of visual impairment worldwide. It is estimated that 2.5 billion people will be affected by myopia alone with in the next decade. Experimental, epidemiological and clinical research has shown that refractive development is influenced by both environmental and genetic factors. Animal models have demonstrated that eye growth and refractive maturation during infancy are tightly regulated by visually-guided mechanisms. Observational data in human populations provide compelling evidence that environmental influences and individual behavioral factors play crucial roles in myopia susceptibility. Nevertheless, the majority of the variance of refractive error within populations is thought to be due to hereditary factors. Genetic linkage studies have mapped two dozen loci, while association studies have implicated more than 25 different genes in refractive variation. Many of these genes are involved in common biological pathways known to mediate extracellular matrix composition and regulate connective tissue remodeling. Other associated genomic regions suggest novel mechanisms in the etiology of human myopia, such as mitochondrial-mediated cell death or photoreceptor-mediated visual signal transmission. Taken together, observational and experimental studies have revealed the complex nature of human refractive variation, which likely involves variants in several genes and functional pathways. Multiway interactions between genes and/or environmental factors may also be important in determining individual risks of myopia, and may help explain the complex pattern of refractive error in human populations. PMID:21155761

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

Evaluation and optimization of hepatocyte culture media factors by design of experiments (DoE) methodology

PubMed Central

Dong, Jia; Lübberstedt, Marc; Urbaniak, Thomas; Nüssler, Andreas K.N.; Knobeloch, Daniel; Gerlach, Jörg C.; Zeilinger, Katrin

2008-01-01

Optimization of cell culture media based on statistical experimental design methodology is a widely used approach for improving cultivation conditions. We applied this methodology to refine the composition of an established culture medium for growth of a human hepatoma cell line, C3A. A selection of growth factors and nutrient supplements were systematically screened according to standard design of experiments (DoE) procedures. The results of the screening indicated that the medium additives hepatocyte growth factor, oncostatin M, and fibroblast growth factor 4 significantly influenced the metabolic activities of the C3A cell line. Surface response methodology revealed that the optimum levels for these factors were 30 ng/ml for hepatocyte growth factor and 35 ng/ml for oncostatin M. Additional experiments on primary human hepatocyte cultures showed high variance in metabolic activities between cells from different individuals, making determination of optimal levels of factors more difficult. Still, it was possible to conclude that hepatocyte growth factor, epidermal growth factor, and oncostatin M had decisive effects on the metabolic functions of primary human hepatocytes. PMID:19003182

Evaluation and optimization of hepatocyte culture media factors by design of experiments (DoE) methodology.

PubMed

Dong, Jia; Mandenius, Carl-Fredrik; Lübberstedt, Marc; Urbaniak, Thomas; Nüssler, Andreas K N; Knobeloch, Daniel; Gerlach, Jörg C; Zeilinger, Katrin

2008-07-01

Optimization of cell culture media based on statistical experimental design methodology is a widely used approach for improving cultivation conditions. We applied this methodology to refine the composition of an established culture medium for growth of a human hepatoma cell line, C3A. A selection of growth factors and nutrient supplements were systematically screened according to standard design of experiments (DoE) procedures. The results of the screening indicated that the medium additives hepatocyte growth factor, oncostatin M, and fibroblast growth factor 4 significantly influenced the metabolic activities of the C3A cell line. Surface response methodology revealed that the optimum levels for these factors were 30 ng/ml for hepatocyte growth factor and 35 ng/ml for oncostatin M. Additional experiments on primary human hepatocyte cultures showed high variance in metabolic activities between cells from different individuals, making determination of optimal levels of factors more difficult. Still, it was possible to conclude that hepatocyte growth factor, epidermal growth factor, and oncostatin M had decisive effects on the metabolic functions of primary human hepatocytes.

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.

Experimental system for the control of surgically induced infections

NASA Technical Reports Server (NTRS)

Tevebaugh, M. D.

1971-01-01

The development tests to be performed on the experimental system are described in detail. The test equipment, conditions, and procedures are given. The portable clean room tests include assembly, collapsability, portability, and storage; laminar flow rate; static pressure; air flow pattern; and electrostatic buildup. The other tests are on the ventilation system, human factors evaluation, electrical subsystem, and material compatibility.

Basins of attraction in human balance

NASA Astrophysics Data System (ADS)

Smith, Victoria A.; Lockhart, Thurmon E.; Spano, Mark L.

2017-12-01

Falls are a recognized risk factor for unintentional injuries among older adults, accounting for a large proportion of fractures, emergency department visits, and urgent hospitalizations. Human balance and gait research traditionally uses linear or qualitative tests to assess and describe human motion; however, human motion is neither a simple nor a linear process. The objective of this research is to identify and to learn more about what factors affect balance using nonlinear dynamical techniques, such as basin boundaries. Human balance data was collected using dual force plates for leans using only ankle movements as well as for unrestricted leans. Algorithms to describe the basin boundary were created and compared based on how well each method encloses the experimental data points as well as captures the differences between the two leaning conditions.

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.

Oral cancer.

PubMed

Gerson, S J

1990-01-01

In the U.S. oral cancer accounts for 2.1% of all cancers and 1% of cancer deaths. Two to three times as many males as females are affected. Blacks have more intra-oral cancer than whites, and their incidence and mortality rates have increased in recent years. The etiologic process very likely involves several factors. The major etiologic agents are tobacco (all types) and alcoholic beverages. Herpes simplex virus, human papilloma virus, and Candida have been implicated. Host factors include poor state of dentition, nutritional aberrations, cirrhosis of liver, lichen planus, and immunologic impairmant. Cellular changes include amplification of some oncogenes, alterations in antigen expression, production of gamma-glutamyl transpeptidase, and disturbance of keratin and involucrin production. Experimentally, cancer is readily produced on the hamster cheek pouch and rat oral mucosa. Unlike oral cancer in humans, most experimental lesions are exophytic, and they rarely metastasize.

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

Escherichia coli global gene expression in urine from women with urinary tract infection.

PubMed

Hagan, Erin C; Lloyd, Amanda L; Rasko, David A; Faerber, Gary J; Mobley, Harry L T

2010-11-11

Murine models of urinary tract infection (UTI) have provided substantial data identifying uropathogenic E. coli (UPEC) virulence factors and assessing their expression in vivo. However, it is unclear how gene expression in these animal models compares to UPEC gene expression during UTI in humans. To address this, we used a UPEC strain CFT073-specific microarray to measure global gene expression in eight E. coli isolates monitored directly from the urine of eight women presenting at a clinic with bacteriuria. The resulting gene expression profiles were compared to those of the same E. coli isolates cultured statically to exponential phase in pooled, sterilized human urine ex vivo. Known fitness factors, including iron acquisition and peptide transport systems, were highly expressed during human UTI and support a model in which UPEC replicates rapidly in vivo. While these findings were often consistent with previous data obtained from the murine UTI model, host-specific differences were observed. Most strikingly, expression of type 1 fimbrial genes, which are among the most highly expressed genes during murine experimental UTI and encode an essential virulence factor for this experimental model, was undetectable in six of the eight E. coli strains from women with UTI. Despite the lack of type 1 fimbrial expression in the urine samples, these E. coli isolates were generally capable of expressing type 1 fimbriae in vitro and highly upregulated fimA upon experimental murine infection. The findings presented here provide insight into the metabolic and pathogenic profile of UPEC in urine from women with UTI and represent the first transcriptome analysis for any pathogenic E. coli during a naturally occurring infection in humans.

Estrogen in cardiovascular disease during systemic lupus erythematosus.

PubMed

Gilbert, Emily L; Ryan, Michael J

2014-12-01

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that disproportionately affects women during their childbearing years. Cardiovascular disease is the leading cause of mortality in this patient population at an age when women often have low cardiovascular risk. Hypertension is a major cardiovascular disease risk factor, and its prevalence is markedly increased in women with SLE. Estrogen has traditionally been implicated in SLE disease progression because of the prevalence of the disease in women; however, its role in cardiovascular risk factors such as hypertension is unclear. The objective of this review is to discuss evidence for the role of estrogen in both human and murine SLE with emphasis on the effect of estrogen on cardiovascular risk factors, including hypertension. PubMed was used to search for articles with terms related to estradiol and SLE. The references of retrieved publications were also reviewed. The potential permissive role of estrogen in SLE development is supported by studies from experimental animal models of lupus in which early removal of estrogen or its effects leads to attenuation of SLE disease parameters, including autoantibody production and renal injury. However, data about the role of estrogens in human SLE are much less clear, with most studies not reaching firm conclusions about positive or negative outcomes after hormonal manipulations involving estrogen during SLE (ie, oral contraceptives, hormone therapy). Significant gaps in knowledge remain about the effect of estrogen on cardiovascular risk factors during SLE. Studies in women with SLE were not designed to determine the effect of estrogen or hormone therapy on blood pressure even though hypertension is highly prevalent, and risk of premature ovarian failure could necessitate use of hormone therapy in women with SLE. Recent evidence from an experimental animal model of lupus found that estrogen may protect against cardiovascular risk factors in adulthood. In addition, increasing evidence suggests that estrogen may have distinct temporal effects on cardiovascular risk factors during SLE. Data from experimental models of lupus suggest that estrogens may have an important permissive role for developing SLE early in life. However, their role in adulthood remains unclear, particularly for the effect on cardiovascular disease and its risk factors. Additional work is needed to understand the effect of estrogens in human SLE, and preclinical studies in experimental models of SLE may contribute important mechanistic insight to further advance the field. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

Estrogen in Cardiovascular Disease during Systemic Lupus Erythematosus

PubMed Central

Gilbert, Emily L.; Ryan, Michael J.

2015-01-01

Purpose Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that disproportionately affects women during their childbearing years. Cardiovascular disease is the leading cause of mortality in this patient population at an age when women often have low cardiovascular risk. Hypertension is a major cardiovascular disease risk factor, and its prevalence is markedly increased in women with SLE. Estrogen has traditionally been implicated in SLE disease progression because of the prevalence of the disease in women; however, its role in cardiovascular risk factors such as hypertension is unclear. The objective of this review is to discuss evidence for the role of estrogen in both human and murine SLE with emphasis on the effect of estrogen on cardiovascular risk factors, including hypertension. Methods PubMed was used to search for articles with terms related to estradiol and SLE. The references of retrieved publications were also reviewed. Findings The potential permissive role of estrogen in SLE development is supported by studies from experimental animal models of lupus in which early removal of estrogen or its effects leads to attenuation of SLE disease parameters, including autoantibody production and renal injury. However, data about the role of estrogens in human SLE are much less clear, with most studies not reaching firm conclusions about positive or negative outcomes after hormonal manipulations involving estrogen during SLE (ie, oral contraceptives, hormone therapy). Significant gaps in knowledge remain about the effect of estrogen on cardiovascular risk factors during SLE. Studies in women with SLE were not designed to determine the effect of estrogen or hormone therapy on blood pressure even though hypertension is highly prevalent, and risk of premature ovarian failure could necessitate use of hormone therapy in women with SLE. Recent evidence from an experimental animal model of lupus found that estrogen may protect against cardiovascular risk factors in adulthood. In addition, increasing evidence suggests that estrogen may have distinct temporal effects on cardiovascular risk factors during SLE. Implications Data from experimental models of lupus suggest that estrogens may have an important permissive role for developing SLE early in life. However, their role in adulthood remains unclear, particularly for the effect on cardiovascular disease and its risk factors. Additional work is needed to understand the effect of estrogens in human SLE, and preclinical studies in experimental models of SLE may contribute important mechanistic insight to further advance the field. PMID:25194860

21 CFR 170.22 - Safety factors to be considered.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES Food Additive Safety § 170.22 Safety factors to... be applied in determining whether the proposed use of a food additive will be safe: Except where... experimentation data to man of 100 to 1, will be used; that is, a food additive for use by man will not be granted...

21 CFR 170.22 - Safety factors to be considered.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES Food Additive Safety § 170.22 Safety factors to... be applied in determining whether the proposed use of a food additive will be safe: Except where... experimentation data to man of 100 to 1, will be used; that is, a food additive for use by man will not be granted...

21 CFR 170.22 - Safety factors to be considered.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES Food Additive Safety § 170.22 Safety factors to... be applied in determining whether the proposed use of a food additive will be safe: Except where... experimentation data to man of 100 to 1, will be used; that is, a food additive for use by man will not be granted...

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.

A musculoskeletal model of human locomotion driven by a low dimensional set of impulsive excitation primitives

PubMed Central

Sartori, Massimo; Gizzi, Leonardo; Lloyd, David G.; Farina, Dario

2013-01-01

Human locomotion has been described as being generated by an impulsive (burst-like) excitation of groups of musculotendon units, with timing dependent on the biomechanical goal of the task. Despite this view being supported by many experimental observations on specific locomotion tasks, it is still unknown if the same impulsive controller (i.e., a low-dimensional set of time-delayed excitastion primitives) can be used as input drive for large musculoskeletal models across different human locomotion tasks. For this purpose, we extracted, with non-negative matrix factorization, five non-negative factors from a large sample of muscle electromyograms in two healthy subjects during four motor tasks. These included walking, running, sidestepping, and crossover cutting maneuvers. The extracted non-negative factors were then averaged and parameterized to obtain task-generic Gaussian-shaped impulsive excitation curves or primitives. These were used to drive a subject-specific musculoskeletal model of the human lower extremity. Results showed that the same set of five impulsive excitation primitives could be used to predict the dynamics of 34 musculotendon units and the resulting hip, knee and ankle joint moments (i.e., NRMSE = 0.18 ± 0.08, and R2 = 0.73 ± 0.22 across all tasks and subjects) without substantial loss of accuracy with respect to using experimental electromyograms (i.e., NRMSE = 0.16 ± 0.07, and R2 = 0.78 ± 0.18 across all tasks and subjects). Results support the hypothesis that biomechanically different motor tasks might share similar neuromuscular control strategies. This might have implications in neurorehabilitation technologies such as human-machine interfaces for the torque-driven, proportional control of powered prostheses and orthoses. In this, device control commands (i.e., predicted joint torque) could be derived without direct experimental data but relying on simple parameterized Gaussian-shaped curves, thus decreasing the input drive complexity and the number of needed sensors. PMID:23805099

A musculoskeletal model of human locomotion driven by a low dimensional set of impulsive excitation primitives.

PubMed

Sartori, Massimo; Gizzi, Leonardo; Lloyd, David G; Farina, Dario

2013-01-01

Human locomotion has been described as being generated by an impulsive (burst-like) excitation of groups of musculotendon units, with timing dependent on the biomechanical goal of the task. Despite this view being supported by many experimental observations on specific locomotion tasks, it is still unknown if the same impulsive controller (i.e., a low-dimensional set of time-delayed excitastion primitives) can be used as input drive for large musculoskeletal models across different human locomotion tasks. For this purpose, we extracted, with non-negative matrix factorization, five non-negative factors from a large sample of muscle electromyograms in two healthy subjects during four motor tasks. These included walking, running, sidestepping, and crossover cutting maneuvers. The extracted non-negative factors were then averaged and parameterized to obtain task-generic Gaussian-shaped impulsive excitation curves or primitives. These were used to drive a subject-specific musculoskeletal model of the human lower extremity. Results showed that the same set of five impulsive excitation primitives could be used to predict the dynamics of 34 musculotendon units and the resulting hip, knee and ankle joint moments (i.e., NRMSE = 0.18 ± 0.08, and R (2) = 0.73 ± 0.22 across all tasks and subjects) without substantial loss of accuracy with respect to using experimental electromyograms (i.e., NRMSE = 0.16 ± 0.07, and R (2) = 0.78 ± 0.18 across all tasks and subjects). Results support the hypothesis that biomechanically different motor tasks might share similar neuromuscular control strategies. This might have implications in neurorehabilitation technologies such as human-machine interfaces for the torque-driven, proportional control of powered prostheses and orthoses. In this, device control commands (i.e., predicted joint torque) could be derived without direct experimental data but relying on simple parameterized Gaussian-shaped curves, thus decreasing the input drive complexity and the number of needed sensors.

Guide to Instrumentation Literature

DTIC Science & Technology

1955-12-14

equipment design , 1287f]-040. 166 refs. 5059. A. Chapanis, W. Ro Garner and C& T. Morgan, Applied experImental psychology. Human factors in enginering...Complete details of the work are presented, including laboratory data, experimental procedures, and theoretical and mathematical analyses. Annual...Instrumentation . . . . . . ....... 16 2.3 Books * • • •••••••••.• 1 Automatic Control; Design ; lhteory; Servomechanisms; Applications . . . . . . . . . 18

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.

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

VISIONET: intuitive visualisation of overlapping transcription factor networks, with applications in cardiogenic gene discovery.

PubMed

Nim, Hieu T; Furtado, Milena B; Costa, Mauro W; Rosenthal, Nadia A; Kitano, Hiroaki; Boyd, Sarah E

2015-05-01

Existing de novo software platforms have largely overlooked a valuable resource, the expertise of the intended biologist users. Typical data representations such as long gene lists, or highly dense and overlapping transcription factor networks often hinder biologists from relating these results to their expertise. VISIONET, a streamlined visualisation tool built from experimental needs, enables biologists to transform large and dense overlapping transcription factor networks into sparse human-readable graphs via numerically filtering. The VISIONET interface allows users without a computing background to interactively explore and filter their data, and empowers them to apply their specialist knowledge on far more complex and substantial data sets than is currently possible. Applying VISIONET to the Tbx20-Gata4 transcription factor network led to the discovery and validation of Aldh1a2, an essential developmental gene associated with various important cardiac disorders, as a healthy adult cardiac fibroblast gene co-regulated by cardiogenic transcription factors Gata4 and Tbx20. We demonstrate with experimental validations the utility of VISIONET for expertise-driven gene discovery that opens new experimental directions that would not otherwise have been identified.

Maternal hypothyroidism: An overview of current experimental models.

PubMed

Ghanbari, Mahboubeh; Ghasemi, Asghar

2017-10-15

Maternal hypothyroidism (MH) is the most common cause of transient congenital hypothyroidism. Different animal models are used for assessing developmental effects of MH in offspring. The severity and status of hypothyroidism in animal models must be a reflection of the actual conditions in humans. To obtain comparable results with different clinical conditions, which lead to MH in humans, several factors have been suggested for researchers to consider before designing the experimental models. Regarding development of fetal body systems during pregnancy, interference at different times provides different results and the appropriate time for induction of hypothyroidism should be selected based on accurate time of development of the system under assessment. Other factors that should be taken into consideration include, physiological and biochemical differences between humans and other species, thyroid hormone-independent effects of anti-thyroid drugs, circadian rhythms in TSH secretion, sex differences, physical and psychological stress. This review addresses essential guidelines for selecting and managing the optimal animal model for MH as well as discussing the pros and cons of currently used models. Copyright © 2017 Elsevier Inc. All rights reserved.

Human Factors Experimental Design and Analysis Reference

DTIC Science & Technology

2007-07-01

Equipment 1.4.5. Pretesting 1.5. Research Design Alternatives ………………………………………………………...30 1.6. Analyzing Results ……………………………………………………………………….31 1.7...46 2.1.1. Threats to Validity 2.1.2. Quantitative Research Approach 2.2. Experimental Design Alternatives...with a discussion of quantitative models in research that are used to predict human performance. Next empirical model building using polynomial

The Utilization of Navy People-Related RDT&E (Research, Development, Test, and Evaluation): Fiscal Year 1983.

DTIC Science & Technology

1984-06-01

emostraion. Tese eserch ool wee deignted and experimental demonstrations wre successfully con- for demonstrations. These research tools wre designated ...Topics 4.02 Instructional Systems Design Methodology Instructional Systems Development and Effectiveness Evaluation .................................... 1...6 53 0 0 67w Report Page 10.07 Human Performance Variables/Factors 10.08 Man-Machine Design Methodology Computer Assisted Methods for Human

Exploring the dynamics of collective cognition using a computational model of cognitive dissonance

NASA Astrophysics Data System (ADS)

Smart, Paul R.; Sycara, Katia; Richardson, Darren P.

2013-05-01

The socially-distributed nature of cognitive processing in a variety of organizational settings means that there is increasing scientific interest in the factors that affect collective cognition. In military coalitions, for example, there is a need to understand how factors such as communication network topology, trust, cultural differences and the potential for miscommunication affects the ability of distributed teams to generate high quality plans, to formulate effective decisions and to develop shared situation awareness. The current paper presents a computational model and associated simulation capability for performing in silico experimental analyses of collective sensemaking. This model can be used in combination with the results of human experimental studies in order to improve our understanding of the factors that influence collective sensemaking processes.

Comprehension of human pointing gestures in horses (Equus caballus).

PubMed

Maros, Katalin; Gácsi, Márta; Miklósi, Adám

2008-07-01

Twenty domestic horses (Equus caballus) were tested for their ability to rely on different human gesticular cues in a two-way object choice task. An experimenter hid food under one of two bowls and after baiting, indicated the location of the food to the subjects by using one of four different cues. Horses could locate the hidden reward on the basis of the distal dynamic-sustained, proximal momentary and proximal dynamic-sustained pointing gestures but failed to perform above chance level when the experimenter performed a distal momentary pointing gesture. The results revealed that horses could rely spontaneously on those cues that could have a stimulus or local enhancement effect, but the possible comprehension of the distal momentary pointing remained unclear. The results are discussed with reference to the involvement of various factors such as predisposition to read human visual cues, the effect of domestication and extensive social experience and the nature of the gesture used by the experimenter in comparative investigations.

Inhibition of plasma vasopressin after drinking in dehydrated humans

NASA Technical Reports Server (NTRS)

Geelen, G.; Keil, L. C.; Kravik, S. E.; Wade, C. E.; Thrasher, T. N.; Barnes, P. R.; Pyka, G.; Nesvig, C.; Greenleaf, J. E.

1984-01-01

The effects of nonosmotic and nonvolumetric factors on vasopressin secretion in dehydrated humans has been investigated experimentally, before and after drinking. The subjects of the experiment were five adult men and three adult women weighing 69-77 kg. In order to determine the influence of nonosmotic and nonvolumetric factors on vasopressin secretion, measurements were obtained of the following blood hematological indices: serum Na(+) content; serum K(+) content; osmolality; and hemoglobin. Measurements of hematocrit, plasma arginine vasopressin (AVP), aldosterone, and renin activity were also obtained. It is found that dehydration increased mean serum Na(+) content, osmolality,and AVP. No significant changes were observed in renin activity, hemoglobin, hematocrit, or plasma volume, while plasma aldosterone increased from 11.1 ng/dl after dehydration to 15.6 ng/dl between 30 and 60 min after drinking. A rapid fall of AVP content following rehydration occurred in the absence of changes in the primary regulators of AVP osmolality and plasma volume, with no change in blood pressure. On the basis of the experimental results, it is suggested that oropharyngeal factors may be the mechanism, for the observed decrease in AVP following rehydration.

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.

[Influence of light and electromagnetic radiation of Sun on circadian rhythms of the total antioxidant capacity of human saliva in the North].

PubMed

Borisenkov, M F; Perminova, E V; Kosova, A L

2008-01-01

The literature and results of own researches concerning the influence of climatic conditions of the North on human organism are analyzed in the paper. Experimental and clinical data are in accordance with a hypothesis of "circadian destruction" covering the mechanism of negative influence of factors of the North on human health. The model to describe the possible mechanism of action of electromagnetic radiations on circadian system of an organism is offered.

Human factors research problems in electronic voice warning system design

NASA Technical Reports Server (NTRS)

Simpson, C. A.; Williams, D. H.

1975-01-01

The speech messages issued by voice warning systems must be carefully designed in accordance with general principles of human decision making processes, human speech comprehension, and the conditions in which the warnings can occur. The operator's effectiveness must not be degraded by messages that are either inappropriate or difficult to comprehend. Important experimental variables include message content, linguistic redundancy, signal/noise ratio, interference with concurrent tasks, and listener expectations generated by the pragmatic or real world context in which the messages are presented.

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

Effects on five species of shorebirds of experimental closure of a beach in New Jersey: implications for severe storms and sea-level rise.

PubMed

Burger, Joanna; Niles, Larry

2014-01-01

For management, it is important to understand the factors that affect foraging efficiency of birds during migration, especially in the face of severe storms and sea-level rise. An experiment was conducted whereby a beach used extensively by migrant shorebirds and people was open and experimentally closed to human activity to examine factors affecting feeding when there was no disturbance, with the beach opened or closed to human activity, and following disturbances. When the beach was closed, the factors affecting the percent of shorebirds foraging varied by species, but involved the number of conspecifics or other shorebirds, location along the beach, and number of raptors. Overall, 30% of flocks were disturbed as a function of type of disturbance, location along the beach, and whether the beach was open or closed. These data suggest that individuals, vehicles, and raptors influence the ability of shorebirds to forage undisturbed, indicating the importance of having some sections of important stopover beaches where shorebirds can feed and roost undisturbed by human activity. A corollary is that other parts of the beach can be freely used by people; environmental health can encompass both protected areas for shorebirds and open areas for fishing and recreation. Severe storms and sea-level rise will limit beach space for both human and avian activities, and understanding mitigation for both is essential to wise adaptive management.

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

Human factors phase IV : risk analysis tool for new train control technology.

DOT National Transportation Integrated Search

2005-01-31

This report covers the theoretical development of the safety state model for railroad operations. Using data from a train control technology experiment, experimental application of the model is demonstrated. A stochastic model of system behavior is d...

Human factors phase IV : risk analysis tool for new train control technology

DOT National Transportation Integrated Search

2005-01-01

This report covers the theoretical development of the safety state model for railroad operations. Using data from a train control technology experiment, experimental application of the model is demonstrated. A stochastic model of system behavior is d...

The Antimicrobial Peptide Human Beta-Defensin-3 Is Induced by Platelet-Released Growth Factors in Primary Keratinocytes

PubMed Central

Lammel, Justus; Tohidnezhad, Mersedeh; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Cremer, Jochen; Jahr, Holger; Rademacher, Franziska; Gläser, Regine; Harder, Jürgen

2017-01-01

Platelet-released growth factors (PRGF) and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF®)) contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3) is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting activities suggests that hBD-3 may play a crucial role in wound healing. Therefore, we analyzed the influence of PRGF on hBD-3 expression in human primary keratinocytes in vitro. In addition, we investigated the influence of Vivostat PRF on hBD-3 expression in artificially generated human skin wounds in vivo. PRGF treatment of primary keratinocytes induced a significant, concentration- and time-dependent increase in hBD-3 gene expression which was partially mediated by the epidermal growth factor receptor (EGFR). In line with these cell culture data, in vivo experiments revealed an enhanced hBD-3 expression in experimentally produced human wounds after the treatment with Vivostat PRF. Thus, the induction of hBD-3 may contribute to the beneficial effects of thrombocyte concentrate lysates in the treatment of chronic or infected wounds. PMID:28811680

Milk-derived or recombinant transforming growth factor-beta has effects on immunological outcomes: a review of evidence from animal experimental studies.

PubMed

Oddy, W H; McMahon, R J

2011-06-01

Identified factors from milk have been shown to improve health outcomes. One specific factor, transforming growth factor-Beta (TGF)-β, has been identified previously as having the potential to impact on immunological outcomes in the newborn offspring. The primary objective of this review was to examine the published studies that have considered TGF-β in association with immunological outcomes of experimental models. We hypothesized that oral administration of TGF-β (through human milk, cow's milk, infant formula) or recombinant TGF-β delivered via gavage, may down-regulate immune activation in newborn offspring. Animal experimental studies were identified through MEDLINE, CAB Abstracts, Biological Abstracts and Scopus. Selection criteria included well-described animal populations, sample and study design, source of TGF-β, age and immunological outcomes measured and effect size. The findings were summarized temporally in tabular format, giving an overall measure of effect based on the literature available since 1994. Animal experimental studies (n=13) were included in the review to determine an association between maternal TGF-β and immunological outcomes. Overall 92% of these studies (12/13) showed a positive association with TGF-β1 or TGF-β2, demonstrating protection against immunologically related outcomes in early life in an animal model. TGF-β is important in developing and maintaining appropriate immune responses in the offspring. TGF-β delivered orally to neonatal animals provides protection against adverse immunological outcomes, corroborating and supporting findings from human studies. Animal studies provide important clues to the pathogenesis and therapeutics of immune activation and allergy in early childhood. TGF-βs are important growth factors involved in maintaining homeostasis in the intestine, regulating inflammation and allergy development and promoting oral tolerance in infants. Thus, taken as a whole, these and our other findings suggest that this cytokine in milk may influence the development of immunological outcomes in offspring. © 2011 Blackwell Publishing Ltd.

Region-specific protein misfolding cyclic amplification reproduces brain tropism of prion strains.

PubMed

Privat, Nicolas; Levavasseur, Etienne; Yildirim, Serfildan; Hannaoui, Samia; Brandel, Jean-Philippe; Laplanche, Jean-Louis; Béringue, Vincent; Seilhean, Danielle; Haïk, Stéphane

2017-10-06

Human prion diseases such as Creutzfeldt-Jakob disease are transmissible brain proteinopathies, characterized by the accumulation of a misfolded isoform of the host cellular prion protein (PrP) in the brain. According to the prion model, prions are defined as proteinaceous infectious particles composed solely of this abnormal isoform of PrP (PrP Sc ). Even in the absence of genetic material, various prion strains can be propagated in experimental models. They can be distinguished by the pattern of disease they produce and especially by the localization of PrP Sc deposits within the brain and the spongiform lesions they induce. The mechanisms involved in this strain-specific targeting of distinct brain regions still are a fundamental, unresolved question in prion research. To address this question, we exploited a prion conversion in vitro assay, protein misfolding cyclic amplification (PMCA), by using experimental scrapie and human prion strains as seeds and specific brain regions from mice and humans as substrates. We show here that region-specific PMCA in part reproduces the specific brain targeting observed in experimental, acquired, and sporadic Creutzfeldt-Jakob diseases. Furthermore, we provide evidence that, in addition to cellular prion protein, other region- and species-specific molecular factors influence the strain-dependent prion conversion process. This important step toward understanding prion strain propagation in the human brain may impact research on the molecular factors involved in protein misfolding and the development of ultrasensitive methods for diagnosing prion disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Wound-healing potential of human umbilical cord blood-derived mesenchymal stromal cells in vitro--a pilot study.

PubMed

You, Hi-Jin; Namgoong, Sik; Han, Seung-Kyu; Jeong, Seong-Ho; Dhong, Eun-Sang; Kim, Woo-Kyung

2015-11-01

Our previous studies demonstrated that human bone marrow-derived mesenchymal stromal cells have great potential for wound healing. However, it is difficult to clinically utilize cultured stem cells. Recently, human umbilical cord blood-derived mesenchymal stromal cells (hUCB-MSCs) have been commercialized for cartilage repair as a first cell therapy product that uses allogeneic stem cells. Should hUCB-MSCs have a superior effect on wound healing as compared with fibroblasts, which are the main cell source in current cell therapy products for wound healing, they may possibly replace fibroblasts. The purpose of this in vitro study was to compare the wound-healing activity of hUCB-MSCs with that of fibroblasts. This study was particularly designed to compare the effect of hUCB-MSCs on diabetic wound healing with those of allogeneic and autologous fibroblasts. Healthy (n = 5) and diabetic (n = 5) fibroblasts were used as the representatives of allogeneic and autologous fibroblasts for diabetic patients in the control group. Human UCB-MSCs (n = 5) were used in the experimental group. Cell proliferation, collagen synthesis and growth factor (basic fibroblast growth factor, vascular endothelial growth factor and transforming growth factor-β) production were compared among the three cell groups. Human UCB-MSCs produced significantly higher amounts of vascular endothelial growth factor and basic fibroblast growth factor when compared with both fibroblast groups. Human UCB-MSCs were superior to diabetic fibroblasts but not to healthy fibroblasts in collagen synthesis. There were no significant differences in cell proliferation and transforming growth factor-β production. Human UCB-MSCs may have greater capacity for diabetic wound healing than allogeneic or autologous fibroblasts, especially in angiogenesis. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

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.

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.

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

Probabilistic modeling of discourse-aware sentence processing.

PubMed

Dubey, Amit; Keller, Frank; Sturt, Patrick

2013-07-01

Probabilistic models of sentence comprehension are increasingly relevant to questions concerning human language processing. However, such models are often limited to syntactic factors. This restriction is unrealistic in light of experimental results suggesting interactions between syntax and other forms of linguistic information in human sentence processing. To address this limitation, this article introduces two sentence processing models that augment a syntactic component with information about discourse co-reference. The novel combination of probabilistic syntactic components with co-reference classifiers permits them to more closely mimic human behavior than existing models. The first model uses a deep model of linguistics, based in part on probabilistic logic, allowing it to make qualitative predictions on experimental data; the second model uses shallow processing to make quantitative predictions on a broad-coverage reading-time corpus. Copyright © 2013 Cognitive Science Society, Inc.

Bio-environmental factors associated with myopia: An updated review.

PubMed

Galvis, V; Tello, A; Camacho, P A; Parra, M M; Merayo-Lloves, J

2017-07-01

Experimental studies in animals, as well as observational and intervention studies in humans, seem to support the premise that the development of juvenile myopia is promoted by a combination of the effect of genetic and environmental factors, with a complex interaction between them. The very rapid increase in myopia rates in some parts of the world, such as Southeast Asia, supports a significant environmental effect. Several lines of evidence suggest that humans might respond to various external factors, such as increased activity in near vision, increased educational pressure, decreased exposure to sunlight outdoors, dietary changes (including increased intake of carbohydrates), as well as low light levels indoors. All these factors could be associated with a higher prevalence of myopia. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

PPARγ Agonists Improve Survival and Neurocognitive Outcomes in Experimental Cerebral Malaria and Induce Neuroprotective Pathways in Human Malaria

PubMed Central

Serghides, Lena; Friedel, Miriam; Cui, Cheryl; Ho, Keith T.; Mount, Howard T. J.; Sled, John G.; Kain, Kevin C.

2014-01-01

Cerebral malaria (CM) is associated with a high mortality rate, and long-term neurocognitive impairment in approximately one third of survivors. Adjunctive therapies that modify the pathophysiological processes involved in CM may improve outcome over anti-malarial therapy alone. PPARγ agonists have been reported to have immunomodulatory effects in a variety of disease models. Here we report that adjunctive therapy with PPARγ agonists improved survival and long-term neurocognitive outcomes in the Plasmodium berghei ANKA experimental model of CM. Compared to anti-malarial therapy alone, PPARγ adjunctive therapy administered to mice at the onset of CM signs, was associated with reduced endothelial activation, and enhanced expression of the anti-oxidant enzymes SOD-1 and catalase and the neurotrophic factors brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brains of infected mice. Two months following infection, mice that were treated with anti-malarials alone demonstrated cognitive dysfunction, while mice that received PPARγ adjunctive therapy were completely protected from neurocognitive impairment and from PbA-infection induced brain atrophy. In humans with P. falciparum malaria, PPARγ therapy was associated with reduced endothelial activation and with induction of neuroprotective pathways, such as BDNF. These findings provide insight into mechanisms conferring improved survival and preventing neurocognitive injury in CM, and support the evaluation of PPARγ agonists in human CM. PMID:24603727

[Experimental bases of the use of pharmacologic agents aimed at higher heat resistance of humans as means of individual protection].

PubMed

Makarov, V I; Tiurenkov, I N; Klauchek, S V; Nalivaĭko, I O; Antipova, A Iu

1997-01-01

A group of volunteers was exposed to action of heating microclimate (ambient temperature 30 +/- 1 degrees C, relative humidity 35 +/- 5%) and other critical occupation factors (physical loading, personal protective equipment). They received simultaneously one of the medicines: placebo, bemethyl (0.5 g), phenibut (0.25 g), obsidan (0.08 g), or phenibut (0.25 g) combined with obsidan (0.08 g). Combined phenibut (0.25 g) with obsidan (0.08 g) were proved to be the most effective method to increase stability of the human body against studying critical occupational factors.

Environmental factors and puberty timing: Expert panel research needs

EPA Science Inventory

An expert panel reviewed the literature on endocrine disrupting chemicals (EDCs), body size and puberty. The panel concluded that available experimental animal and human data support a possible role of EDCs and body size in relation to alterations in pubertal onset and progressio...

Passenger train emergency systems : single-level commuter rail car egress experiments

DOT National Transportation Integrated Search

2015-04-01

Under FRA sponsorship, a series of three experimental egress trials was conducted in 2005 and 2006 to obtain human factors data relating to the amount of time necessary for individuals to exit from a passenger rail car. This final report describes th...

Surprise braking trials, time-to-collision judgments, and "first look" maneuvers under realistic rear-end crash scenarios

DOT National Transportation Integrated Search

2005-08-01

This project continues to build upon the foundation provided by the human factors experimentation conducted in the previous Crash Avoidance Metrics Partnership (CAMP) Forward Collision Warning (FCW) system efforts. As in the previous CAMP FCW researc...

Novel Burkholderia mallei Virulence Factors Linked to Specific Host-Pathogen Protein Interactions

DTIC Science & Technology

2013-06-23

Wallqvist‡ Burkholderia mallei is an infectious intracellular pathogen whose virulence and resistance to antibiotics makes it a potential bioterrorism agent ...experimental Burkholderia data to ini- tially select a small number of proteins as putative viru- lence factors. We then used yeast two-hybrid assays...causative agent of glan- ders, a disease primarily affecting horses but transmittable to humans; and Burkholderia pseudomallei, which is responsible for

Animal Models in Cardiovascular Research: Hypertension and Atherosclerosis

PubMed Central

Ng, Chun-Yi; Jaarin, Kamsiah

2015-01-01

Hypertension and atherosclerosis are among the most common causes of mortality in both developed and developing countries. Experimental animal models of hypertension and atherosclerosis have become a valuable tool for providing information on etiology, pathophysiology, and complications of the disease and on the efficacy and mechanism of action of various drugs and compounds used in treatment. An animal model has been developed to study hypertension and atherosclerosis for several reasons. Compared to human models, an animal model is easily manageable, as compounding effects of dietary and environmental factors can be controlled. Blood vessels and cardiac tissue samples can be taken for detailed experimental and biomolecular examination. Choice of animal model is often determined by the research aim, as well as financial and technical factors. A thorough understanding of the animal models used and complete analysis must be validated so that the data can be extrapolated to humans. In conclusion, animal models for hypertension and atherosclerosis are invaluable in improving our understanding of cardiovascular disease and developing new pharmacological therapies. PMID:26064920

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.

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.

Vertical ridge augmentation using an equine bone and collagen block infused with recombinant human platelet-derived growth factor-BB: a randomized single-masked histologic study in non-human primates.

PubMed

Nevins, Myron; Al Hezaimi, Khalid; Schupbach, Peter; Karimbux, Nadeem; Kim, David M

2012-07-01

This study tests the effectiveness of hydroxyapatite and collagen bone blocks of equine origin (eHAC), infused with recombinant human platelet-derived growth factor-BB (rhPDGF-BB), to augment localized posterior mandibular defects in non-human primates (Papio hamadryas). Bilateral critical-sized defects simulating severe atrophy were created at the time of the posterior teeth extraction. Test and control blocks (without growth factor) were randomly grafted into the respective sites in each non-human primate. All sites exhibited vertical ridge augmentation, with physiologic hard- and soft-tissue integration of the blocks when clinical and histologic examinations were done at 4 months after the vertical ridge augmentation procedure. There was a clear, although non-significant, tendency to increased regeneration in the test sites. As in the first two preclinical studies in this series using canines, experimental eHAC blocks infused with rhPDGF-BB proved to be a predictable and technically viable method to predictably regenerate bone and soft tissue in critical-sized defects. This investigation supplies additional evidence that eHAC blocks infused with rhPDGF-BB growth factor is a predictable and technically feasible option for vertical augmentation of severely resorbed ridges.

Potentiation by Tumor Necrosis Factor of Mitoxantrone Cytotoxicity to Human Ovarian Cancer Cell Lines

PubMed Central

Parodi, Silvio; Billi, Giovanna; Oliva, Cristina; Venturing, Marco; Noviello, Elvira; Conte, PierFranco

1992-01-01

The cytotoxic activity of human recombinant tumor necrosis factor (rHuTNF) (from 0.01 to 10000 U/ml) was assayed on six human ovarian cancer cell lines and one human cervical carcinoma cell line using a crystal violet assay. rHuTNF was cytotoxic to four cell lines (A2780, A2774, SW626, PAD, while 3 cell lines (IGROV1, SKOV3, Mel80) were marginally sensitive to its activity. However, under the same experimental conditions rHuTNF markedly enhanced the cytotoxicity of mitoxantrone, a chemotherapeutic drug targeted at DNA topoisomerase II, in six cell lines. The potentiation of mitoxantrone cytotoxicity was not caused by increased drug accumulation after rHuTNF treatment. No significant increase in cytotoxicity to Me180 cell line was seen when rHuTNF was added to mitoxantrone. PMID:1517145

Three-dimensional organotypic culture: experimental models of mammalian biology and disease.

PubMed

Shamir, Eliah R; Ewald, Andrew J

2014-10-01

Mammalian organs are challenging to study as they are fairly inaccessible to experimental manipulation and optical observation. Recent advances in three-dimensional (3D) culture techniques, coupled with the ability to independently manipulate genetic and microenvironmental factors, have enabled the real-time study of mammalian tissues. These systems have been used to visualize the cellular basis of epithelial morphogenesis, to test the roles of specific genes in regulating cell behaviours within epithelial tissues and to elucidate the contribution of microenvironmental factors to normal and disease processes. Collectively, these novel models can be used to answer fundamental biological questions and generate replacement human tissues, and they enable testing of novel therapeutic approaches, often using patient-derived cells.

The evolved psychological mechanisms of fertility motivation: hunting for causation in a sea of correlation

PubMed Central

McAllister, Lisa S.; Pepper, Gillian V.; Virgo, Sandra

2016-01-01

Cultural, ecological, familial and physiological factors consistently influence fertility behaviours, however, the proximate psychological mechanisms underlying fertility decisions in humans are poorly understood. Understanding the psychological mechanisms underlying human fertility may illuminate the final processes by which some of these known predictors have their influence. To date, research into the psychological mechanisms underlying fertility has been fragmented. Aspects of reproductive psychology have been examined by researchers in a range of fields, but the findings have not been systematically integrated in one review. We provide such a review, examining current theories and research on psychological mechanisms of fertility. We examine the methods and populations used in the research, as well as the disciplines and theoretical perspectives from which the work has come. Much of the work that has been done to date is methodologically limited to examining correlations between ecological, social and economic factors and fertility. We propose, and support with examples, the use of experimental methods to differentiate causal factors from correlates. We also discuss weaknesses in the experimental research, including limited work with non-WEIRD (western, educated, industrialized, rich and democratic) populations. PMID:27022078

Inflammasomes make the case for littermate-controlled experimental design in studying host-microbiota interactions.

PubMed

Mamantopoulos, Michail; Ronchi, Francesca; McCoy, Kathy D; Wullaert, Andy

2018-04-19

Several human diseases are thought to evolve due to a combination of host genetic mutations and environmental factors that include alterations in intestinal microbiota composition termed dysbiosis. Although in some cases, host genetics may shape the gut microbiota and enable it to provoke disease, experimentally disentangling cause and consequence in such host-microbe interactions requires strict control over non-genetic confounding factors. Mouse genetic studies previously proposed Nlrp6/ASC inflammasomes as innate immunity regulators of the intestinal ecosystem. In contrast, using littermate-controlled experimental setups, we recently showed that Nlrp6/ASC inflammasomes do not alter the gut microbiota composition. Our analyses indicated that maternal inheritance and long-term separate housing are non-genetic confounders that preclude the use of non-littermate mice when analyzing host genetic effects on intestinal ecology. Here, we summarize and discuss our gut microbiota analyses in inflammasome-deficient mice for illustrating the importance of littermate experimental design in studying host-microbiota interactions.

An integrated approach to rotorcraft human factors research

NASA Technical Reports Server (NTRS)

Hart, Sandra G.; Hartzell, E. James; Voorhees, James W.; Bucher, Nancy M.; Shively, R. Jay

1988-01-01

As the potential of civil and military helicopters has increased, more complex and demanding missions in increasingly hostile environments have been required. Users, designers, and manufacturers have an urgent need for information about human behavior and function to create systems that take advantage of human capabilities, without overloading them. Because there is a large gap between what is known about human behavior and the information needed to predict pilot workload and performance in the complex missions projected for pilots of advanced helicopters, Army and NASA scientists are actively engaged in Human Factors Research at Ames. The research ranges from laboratory experiments to computational modeling, simulation evaluation, and inflight testing. Information obtained in highly controlled but simpler environments generates predictions which can be tested in more realistic situations. These results are used, in turn, to refine theoretical models, provide the focus for subsequent research, and ensure operational relevance, while maintaining predictive advantages. The advantages and disadvantages of each type of research are described along with examples of experimental results.

Does granulocyte colony-stimulating factor ameliorate the proinflammatory response in human meningococcal septic shock?

PubMed

Rojahn, Astrid; Brusletto, Berit; Øvstebø, Reidun; Haug, Kari B F; Kierulf, Peter; Brandtzaeg, Petter

2008-09-01

To test the hypothesis that granulocyte colony-stimulating factor acts cooperatively with interleukin-10 in down-regulating monocyte function in severe meningococcal septic shock. 1) We quantified the plasma levels of granulocyte colony-stimulating factor, interleukin-10, Neisseria meningitidis lipopolysaccharide and the number of N. meningitidis DNA copies in 28 patients with systemic meningococcal disease. 2) We studied the inhibitory effect of recombinant human granulocyte colony-stimulating factor on normal human monocytes stimulated with purified meningococcal lipopolysaccaride. 3) We monitored the inhibitory effects of endogenously produced granulocyte colony-stimulating factor and interleukin-10 in meningococcal shock plasmas on monocytes. Comparative, experimental study. University Hospital and laboratory. Twenty-eight patients with systemic meningococcal disease, 13 with persistent shock, 7 died, and 15 without shock. The median levels of granulocyte colony-stimulating factor in shock and nonshock patients were 1.7 x 10(6) and 8.1 x 10(2) pg/mL; interleukin-10, 2.1 x 10(4) and 4 x 10(1) pg/mL; number of N. meningitidis DNA copies, 2.9 x 10(7) and <10(3)/mL; and lipopolysaccharide, 105 and <0.04 endotoxin units/mL, respectively. The plasma levels of granulocyte colony-stimulating factor were reduced by 50% within 4 to 6 hrs after initiation of antibiotic treatment. In model experiments with lipopolysaccharide-stimulated human monocytes, recombinant human granulocyte colony-stimulating factor and interleukin-10 reduced the release of tumor necrosis factor-alpha by mean 30% and 92%, respectively. When plasmas from three shock patients were depleted of native granulocyte colony-stimulating factor or interleukin-10 by immunoprecipitation, no increase in tumor necrosis factor-alpha release occurred after removal of granulocyte colony-stimulating factor, whereas removal of interleukin-10 increased the tumor necrosis factor-alpha release eight-fold. Although granulocyte colony-stimulating factor in plasma increases by five orders of magnitude in patients with meningococcal shock, the anti-inflammatory effect on patients' monocytes is uncertain.

Interpretation of human pointing by African elephants: generalisation and rationality.

PubMed

Smet, Anna F; Byrne, Richard W

2014-11-01

Factors influencing the abilities of different animals to use cooperative social cues from humans are still unclear, in spite of long-standing interest in the topic. One of the few species that have been found successful at using human pointing is the African elephant (Loxodonta africana); despite few opportunities for learning about pointing, elephants follow a pointing gesture in an object-choice task, even when the pointing signal and experimenter's body position are in conflict, and when the gesture itself is visually subtle. Here, we show that the success of captive African elephants at using human pointing is not restricted to situations where the pointing signal is sustained until the time of choice: elephants followed human pointing even when the pointing gesture was withdrawn before they had responded to it. Furthermore, elephants rapidly generalised their response to a type of social cue they were unlikely to have seen before: pointing with the foot. However, unlike young children, they showed no sign of evaluating the 'rationality' of this novel pointing gesture according to its visual context: that is, whether the experimenter's hands were occupied or not.

Human Factors in Field Experimentation Design and Analysis of Analytical Suppression Model

DTIC Science & Technology

1978-09-01

men in uf"an-dachine- Systems " supports the development of new doctrines, design of weapon systems as well as training programs for trQops. One...Experimentation Design -Master’s thesis: and Analysis.of an Analytical Suppression.Spebr17 Model PR@~w 3.RPR 7. AUTHOR(@) COT RIETeo 31AN? wijMu~aw...influences to suppression. Techniques are examined for including. the suppre.ssive effects of weapon systems in Lanchester-type combat m~odels, whir~h may be

Human error and human factors engineering in health care.

PubMed

Welch, D L

1997-01-01

Human error is inevitable. It happens in health care systems as it does in all other complex systems, and no measure of attention, training, dedication, or punishment is going to stop it. The discipline of human factors engineering (HFE) has been dealing with the causes and effects of human error since the 1940's. Originally applied to the design of increasingly complex military aircraft cockpits, HFE has since been effectively applied to the problem of human error in such diverse systems as nuclear power plants, NASA spacecraft, the process control industry, and computer software. Today the health care industry is becoming aware of the costs of human error and is turning to HFE for answers. Just as early experimental psychologists went beyond the label of "pilot error" to explain how the design of cockpits led to air crashes, today's HFE specialists are assisting the health care industry in identifying the causes of significant human errors in medicine and developing ways to eliminate or ameliorate them. This series of articles will explore the nature of human error and how HFE can be applied to reduce the likelihood of errors and mitigate their effects.

77 FR 54402 - Dichlorvos (DDVP); Order Denying NRDC's Objections on Remand

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-05

... may be calculated separately for different age-based population groups (e.g., non-nursing infants) or... in conjunction with experimental toxicity data in assessing risk to humans from exposure to chemical substances. (Ref. 4). These numerical factors are designed to provide an additional margin of safety so that...

Differential effect of isotype on efficacy of anti-tumor necrosis factor alpha chimeric antibodies in experimental septic shock

PubMed Central

1994-01-01

Immune complexes containing human gamma (g)1 or murine g2a antibodies generate secondary effector mechanisms via Fc receptor binding or complement activation, whereas those containing human g4 or murine g1 antibodies generally do not. Therefore, isotype selection of therapeutic antibodies may have important clinical consequences. In a rabbit model of human tumor necrosis factor (rhuTNF)-induced pyrexia, a murine/human chimeric g4 anti-human TNF-alpha monoclonal antibody (mAb) (cCB0011) showed a dose-dependent inhibition of pyrexia, whereas a g1 isotype variant of the same mAb gave a marked pyrexia that was seen at all doses indicative of an immune complex-mediated response. To investigate whether isotype difference could influence mAb efficacy in pathological disease states, hamster/murine chimeric g1 and g2a anti- murine TNF-alpha mAbs (TN3g1, TN3g2a) were studied in experimental shock in mice and rats. In lipopolysaccharide-induced shock in mice, treatment with TN3g1 mAb at 30 and 3 mg/kg resulted in 90% survival by 72 h (p < or = 0.004), and prolonged survival to 45 h (p < or = 0.05), respectively, compared with 100% mortality by 27 h in controls. In contrast, a g2a isotype variant of the same mAb (30 mg/kg) resulted in only 10% survival by 72 h (p < or = 0.05). In a neutropenic sepsis model in rats there was greater survival in animals receiving the g1 isotype of TN3 compared with g2a isotype variant (70 vs. 27%; p < or = 0.005) with 100% mortality in the controls. These differences were not due to the pharmacokinetic profiles of the mAbs. In models of experimental shock antibody isotype can affect outcome with inactive isotypes (human g4 and murine g1) being more efficacious than active isotypes (human g1 and murine g2a). PMID:8113678

Targeting Host Factors to Treat West Nile and Dengue Viral Infections

PubMed Central

Krishnan, Manoj N.; Garcia-Blanco, Mariano A.

2014-01-01

West Nile (WNV) and Dengue (DENV) viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines) or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans. PMID:24517970

Targeting host factors to treat West Nile and dengue viral infections.

PubMed

Krishnan, Manoj N; Garcia-Blanco, Mariano A

2014-02-10

West Nile (WNV) and Dengue (DENV) viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines) or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans.

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.

Development and validation of LC-MS/MS method for the quantification of oxcarbazepine in human plasma using an experimental design.

PubMed

Srinubabu, Gedela; Ratnam, Bandaru Veera Venkata; Rao, Allam Appa; Rao, Medicherla Narasimha

2008-01-01

A rapid tandem mass spectrometric (MS-MS) method for the quantification of Oxcarbazepine (OXB) in human plasma using imipramine as an internal standard (IS) has been developed and validated. Chromatographic separation was achieved isocratically on a C18 reversed-phase column within 3.0 min, using a mobile phase of acetonitrile-10 mM ammonium formate (90 : 10 v/v) at a flow rate of 0.3 ml/min. Quantitation was achieved using multiple reaction monitoring (MRM) scan at MRM transitions m/z 253>208 and m/z 281>86 for OXB and the IS respectively. Calibration curves were linear over the concentration range of 0.2-16 mug/ml (r>0.999) with a limit of quantification of 0.2 mug/ml. Analytical recoveries of OXB from spiked human plasma were in the range of 74.9 to 76.3%. Plackett-Burman design was applied for screening of chromatographic and mass spectrometric factors; factorial design was applied for optimization of essential factors for the robustness study. A linear model was postulated and a 2(3) full factorial design was employed to estimate the model coefficients for intermediate precision. More specifically, experimental design helps the researcher to verify if changes in factor values produce a statistically significant variation of the observed response. The strategy is most effective if statistical design is used in most or all stages of the screening and optimizing process for future method validation of pharmacokinetic and bioequivalence studies.

Expression of β-nerve growth factor and homeobox A10 in experimental cryptorchidism treated with exogenous nerve growth factor.

PubMed

Xian, Hua; Xian, Yun; Liu, Lili; Wang, Yongjun; He, Jianghong; Huang, Jianfei

2015-04-01

With the exception of standard inguinal orchidopexy, treatment of cryptorchidism with human chorionic gonadotropin has been performed for several years; however, its side effects have limited its application. The β‑nerve growth factor (NGF) and homeobox A10 (HoxA10) genes are closely associated with the development of the testes. To the best of our knowledge, whether exogenous NGF alters the endogenous levels of NGF and HoxA10 in cryptorchidism in rats remains to be elucidated. The aim of the present study was to evaluate the gene and protein expression of NGF and HoxA10 in experimental cryptorchidism following treatment with exogenous NGF. A unilateral mechanical cryptorchidism model in Sprague-Dawley rats was established and different concentrations of exogenous NGF were administered to observe the effects of NGF on cryptorchidism. Changes in the gene and protein expression levels of NGF and HoxA10 in the cryptorchid tissues of each group were identified using one step reverse transcription-quantitative polymerase chain reaction, in situ hybridization with digoxigenin‑labeled‑β‑NGF RNA probes, immunofluorescence and immunohistochemistry, respectively. The expression levels of NGF and HoxA10 were markedly higher in the group treated with a high dose of exogenous NGF compared with the group treated with a low dose of exogenous NGF and the group treated with human chorionic gonadotropin. These results confirmed the potential therapeutic effect of exogenous NGF in human cryptorchidism.

Trust in automation: integrating empirical evidence on factors that influence trust.

PubMed

Hoff, Kevin Anthony; Bashir, Masooda

2015-05-01

We systematically review recent empirical research on factors that influence trust in automation to present a three-layered trust model that synthesizes existing knowledge. Much of the existing research on factors that guide human-automation interaction is centered around trust, a variable that often determines the willingness of human operators to rely on automation. Studies have utilized a variety of different automated systems in diverse experimental paradigms to identify factors that impact operators' trust. We performed a systematic review of empirical research on trust in automation from January 2002 to June 2013. Papers were deemed eligible only if they reported the results of a human-subjects experiment in which humans interacted with an automated system in order to achieve a goal. Additionally, a relationship between trust (or a trust-related behavior) and another variable had to be measured. All together, 101 total papers, containing 127 eligible studies, were included in the review. Our analysis revealed three layers of variability in human-automation trust (dispositional trust, situational trust, and learned trust), which we organize into a model. We propose design recommendations for creating trustworthy automation and identify environmental conditions that can affect the strength of the relationship between trust and reliance. Future research directions are also discussed for each layer of trust. Our three-layered trust model provides a new lens for conceptualizing the variability of trust in automation. Its structure can be applied to help guide future research and develop training interventions and design procedures that encourage appropriate trust. © 2014, Human Factors and Ergonomics Society.

Capturing the Value: Earth Applications of Space Human Factors Research

NASA Technical Reports Server (NTRS)

Connors, Mary M.; Shafto, Michael G. (Technical Monitor)

1995-01-01

This paper details how the Space Human Factors/Life Sciences program at Ames Research Center (ARC) has provided, and continues to provide, a variety of Earth-based benefits. These benefits will be considered under five categories: aeronautics, space-like environments, general applications, human/automation interaction, and methodology. The human factors work at ARC includes a range of activities whose products serve the aerospace community. Some areas of research focus specifically on aeronautical requirements; others are driven by space needs. However, the symbiosis between these two domains allows a sharing of resources, and the insights and experimental results gathered in one domain can often be applied in the other. Aeronautics is an industry whose survival is generally viewed as critical to American competitiveness, and where benefits can result in a very high payoff. The ability to apply space-initiated research to aeronautical requirements represents one example of bringing space benefits down to Earth. The second-order value of space human factors research goes well beyond the aerospace community. Spaceflight shares with a number of other activities certain environmental characteristics that drive human factors engineering design and procedural specification. Spaceflight is an isolated activity, conducted under severely confined conditions, with a high level of risk, and where provisions are restricted and opportunities for outside help are limited. A number of Earth-based activities including submarines and other naval vessels, oil rigs, remote weather stations, and scientific and polar expeditions, share many of these characteristics. These activities serve as testbeds for space-related research and, in turn, space-related research provides beneficial insight to the conduct of these activities.

Three-dimensional organotypic culture: experimental models of mammalian biology and disease

PubMed Central

Shamir, Eliah R.; Ewald, Andrew J.

2015-01-01

Mammalian organs are challenging to study as they are fairly inaccessible to experimental manipulation and optical observation. Recent advances in three-dimensional (3D) culture techniques, coupled with the ability to independently manipulate genetic and microenvironmental factors, have enabled the real-time study of mammalian tissues. These systems have been used to visualize the cellular basis of epithelial morphogenesis, to test the roles of specific genes in regulating cell behaviours within epithelial tissues and to elucidate the contribution of microenvironmental factors to normal and disease processes. Collectively, these novel models can be used to answer fundamental biological questions and generate replacement human tissues, and they enable testing of novel therapeutic approaches, often using patient-derived cells. PMID:25237826

Integrated voice and visual systems research topics

NASA Technical Reports Server (NTRS)

Williams, Douglas H.; Simpson, Carol A.

1986-01-01

A series of studies was performed to investigate factors of helicopter speech and visual system design and measure the effects of these factors on human performance, both for pilots and non-pilots. The findings and conclusions of these studies were applied by the U.S. Army to the design of the Army's next generation threat warning system for helicopters and to the linguistic functional requirements for a joint Army/NASA flightworthy, experimental speech generation and recognition system.

Biomedical and Human Factors Requirements for a Manned Earth Orbiting Station

NASA Technical Reports Server (NTRS)

Helvey, W.; Martell, C.; Peters, J.; Rosenthal, G.; Benjamin, F.; Albright, G.

1964-01-01

The primary objective of this study is to determine which biomedical and human factors measurements must be made aboard a space station to assure adequate evaluation of the astronaut's health and performance during prolonged space flights. The study has employed, where possible, a medical and engineering systems analysis to define the pertinent life sciences and space station design parameters and their influence on a measurement program. The major areas requiring evaluation in meeting the study objectives include a definition of the space environment, man's response to the environment, selection of measurement and data management techniques, experimental program, space station design requirements, and a trade-off analysis with final recommendations. The space environment factors that are believed to have a significant effect on man were evaluated. This includes those factors characteristic of the space environment (e. g. weightlessness, radiation) as well as those created within the space station (e. g. toxic contaminants, capsule atmosphere). After establishing the general features of the environment, an appraisal was made of the anticipated response of the astronaut to each of these factors. For thoroughness, the major organ systems and functions of the body were delineated, and a determination was made of their anticipated response to each of the environmental categories. A judgment was then made on the medical significance or importance of each response, which enabled a determination of which physiological and psychological effects should be monitored. Concurrently, an extensive list of measurement techniques and methods of data management was evaluated for applicability to the space station program. The various space station configurations and design parameters were defined in terms of the biomedical and human factors requirements to provide the measurements program. Research design of experimental programs for various station configurations, mission durations, and crew sizes were prepared, and, finally, a trade-off analysis of the critical variables in the station planning was completed with recommendations to enhance the confidence in the measurement program.

The risk of transmitting prion disease by blood or plasma products.

PubMed

Knight, Richard

2010-12-01

Various experimental studies have shown infectivity in blood in relation to bovine spongiform encephalitis (BSE) and variant Creutzfeldt-Jakob disease (vCJD). Human to human transmission vCJD infection has been reported via transfusion of non-leukocyte-reduced red cells and, probably, via factor VIII concentrates. A number of precautionary measures are in place but uncertainties remain, especially concerning the number of BSE-infected people in the population. Additional measures such as prion filtration need consideration. Copyright © 2010 Elsevier Ltd. All rights reserved.

Factor XI and Contact Activation as Targets for Antithrombotic Therapy

PubMed Central

Gailani, David; Bane, Charles E.; Gruber, Andras

2015-01-01

Summary The most commonly used anticoagulants produce therapeutic antithrombotic effects either by inhibiting thrombin or factor Xa, or by lowering the plasma levels of the precursors of these key enzymes, prothrombin and factor X. These drugs do not distinguish between thrombin generation contributing to thrombosis from thrombin generation required for hemostasis. Thus, anticoagulants increase bleeding risk, and many patients who would benefit from therapy go untreated because of comorbidities that place them at unacceptable risk for hemorrhage. Studies in animals demonstrate that components of the plasma contact activation system contribute to experimentally-induced thrombosis, despite playing little or no role in hemostasis. Attention has focused on factor XII, the zymogen of a protease (factor XIIa) that initiates contact activation when blood is exposed to foreign surfaces; and factor XI, the zymogen of the protease factor XIa, which links contact activation to the thrombin generation mechanism. In the case of factor XI, epidemiologic data indicate this protein contributes to stroke and venous thromboembolism, and perhaps myocardial infarction, in humans. A phase 2 trial showing that reduction of factor XI may be more effective than low-molecular-weight heparin at preventing venous thrombosis during knee replacement surgery provides proof of concept for the premise that an antithrombotic effect can be uncoupled from an anticoagulant effect in humans by targeting components of contact activation. Here we review data on the role of factor XI and factor XII in thrombosis, and results of pre-clinical and human trials for therapies targeting these proteins. PMID:25976012

General equation for the differential pathlength factor of the frontal human head depending on wavelength and age.

PubMed

Scholkmann, Felix; Wolf, Martin

2013-10-01

Continuous-wave near-infrared spectroscopy and near-infrared imaging enable the measurement of relative concentration changes in oxy- and deoxyhemoglobin and thus hemodynamics and oxygenation. The accuracy of determined changes depends mainly on the modeling of the light transport through the probed tissue. Due to the highly scattering nature of tissue, the light path is longer than the source-detector separation (d). This is incorporated in modeling by multiplying d by a differential pathlength factor (DPF) which depends on several factors such as wavelength, age of the subject, and type of tissue. In the present work, we derive a general DPF equation for the frontal human head, incorporating dependency on wavelength and age, based on published data. We validated the equation using different data sets of experimentally determined DPFs from six independent studies.

Cytokines, chemokines, and colony-stimulating factors in human milk: the 1997 update.

PubMed

Garofalo, R P; Goldman, A S

1998-01-01

Epidemiologic studies conducted over the past 30 years to investigate the protective functions of human milk strongly support the notion that breast-feeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult due to its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. Nevertheless, a host of bioactive substances including hormones, growth factors, and immunological factors such as cytokines have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of the immune system. Several different cytokines and chemokines have been discovered in human milk over the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system.

Cell mechanics and human disease states

NASA Astrophysics Data System (ADS)

Suresh, Subra

2006-03-01

This presentation will provide summary of our very recent studies exploring the effects of biochemical factors, influenced by foreign organisms or in vivo processes, on intracellular structural reorganization, single-cell mechanical response and motility of a population of cells in the context of two human diseases: malaria induced by Plasmodium falciparum merozoites that invade red blood cells, and gastrointestinal cancer metastasis involving epithelial cells. In both cases, particular attention will be devoted to systematic changes induced in specific molecular species in response to controlled alterations in disease state. The role of critical proteins in influencing the mechanical response of human red bloods during the intra-erythrocytic development of P. falciparum merozoites has also been assessed quantitatively using specific protein knock-out experiments by recourse to gene inactivation methods. Single-cell mechanical response characterization entails such tools as optical tweezers and mechanical plate stretchers whereas cell motility assays and cell-population biorheology characterization involves microfluidic channels. The experimental studies are accompanied by three-dimensional computational simulations at the continuum and mesoscopic scales of cell deformation. An outcome of such combined experimental and computational biophysical studies is the realization of how chemical factors influence single-cell mechanical response, cytoadherence, the biorheology of a large population of cells through microchannels representative of in vivo conditions, and the onset and progression of disease states.

Transplantation of cryopreserved human umbilical cord blood mononuclear cells does not induce sustained recovery after experimental stroke in spontaneously hypertensive rats

PubMed Central

Weise, Gesa; Lorenz, Marlene; Pösel, Claudia; Maria Riegelsberger, Ute; Störbeck, Veronika; Kamprad, Manja; Kranz, Alexander; Wagner, Daniel-Christoph; Boltze, Johannes

2014-01-01

Previous studies have highlighted the enormous potential of cell-based therapies for stroke not only to prevent ischemic brain damage, but also to amplify endogenous repair processes. Considering its widespread availability and low immunogenicity human umbilical cord blood (HUCB) is a particularly attractive stem cell source. Our goal was to investigate the neurorestorative potential of cryopreserved HUCB mononuclear cells (MNC) after permanent middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats (SHR). Human umbilical cord blood MNC or vehicle solution was administered intravenously 24 hours after MCAO. Experimental groups were as follows: (1) quantitative polymerase chain reaction (PCR) of host-derived growth factors up to 48 hours after stroke; (2) immunohistochemical analysis of astroglial scarring; (3) magnetic resonance imaging (MRI) and weekly behavioral tests for 2 months after stroke. Long-term functional outcome and lesion development on MRI were not beneficially influenced by HUCB MNC therapy. Furthermore, HUCB MNC treatment did not change local growth factor levels and glial scarring extent. In summary, we could not demonstrate neurorestorative properties of HUCB MNC after stroke in SHR. Our results advise caution regarding a prompt translation of cord blood therapy into clinical stroke trials as long as deepened knowledge about its precise modes of action is missing. PMID:24169850

Phenylalanine transfer across the isolated perfused human placenta: an experimental and modeling investigation

PubMed Central

Lofthouse, E. M.; Perazzolo, S.; Brooks, S.; Crocker, I. P.; Glazier, J. D.; Johnstone, E. D.; Panitchob, N.; Sibley, C. P.; Widdows, K. L.; Sengers, B. G.

2015-01-01

Membrane transporters are considered essential for placental amino acid transfer, but the contribution of other factors, such as blood flow and metabolism, is poorly defined. In this study we combine experimental and modeling approaches to understand the determinants of [14C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [14C]phenylalanine across the isolated perfused human placenta was determined at different maternal and fetal flow rates. Maternal flow rate was set at 10, 14, and 18 ml/min for 1 h each. At each maternal flow rate, fetal flow rates were set at 3, 6, and 9 ml/min for 20 min each. Appearance of [14C]phenylalanine was measured in the maternal and fetal venous exudates. Computational modeling of phenylalanine transfer was undertaken to allow comparison of the experimental data with predicted phenylalanine uptake and transfer under different initial assumptions. Placental uptake (mol/min) of [14C]phenylalanine increased with maternal, but not fetal, flow. Delivery (mol/min) of [14C]phenylalanine to the fetal circulation was not associated with fetal or maternal flow. The absence of a relationship between placental phenylalanine uptake and net flux of phenylalanine to the fetal circulation suggests that factors other than flow or transporter-mediated uptake are important determinants of phenylalanine transfer. These observations could be explained by tight regulation of free amino acid levels within the placenta or properties of the facilitated transporters mediating phenylalanine transport. We suggest that amino acid metabolism, primarily incorporation into protein, is controlling free amino acid levels and, thus, placental transfer. PMID:26676251

Lipopolysaccharide and hypoxia significantly alters interleukin-8 and macrophage chemoattractant protein-1 production by human fibroblasts but not fibrosis related factors.

PubMed

Eleftheriadis, T; Liakopoulos, V; Lawson, B; Antoniadi, G; Stefanidis, I; Galaktidou, G

2011-07-01

Besides extracellular matrix production, fibroblasts are able to produce various cytokines. Their ubiquitous position makes fibroblasts appropriate cells for sensing various noxious stimuli and for attracting immune cells in the affected area. In the present study the effect of lipopolysaccharide (LPS) and cobalt chloride (CoCl(2)) on the above fibroblasts functions were evaluated in primary human skin fibroblasts cultures. Collagen, matrix metalloproteinase-1, tissue inhibitor of metalloproteinases-1, transforming growth factor-β1, interleukin-8 (IL-8) and macrophage chemoattractant protein-1 (MCP-1) were measured in fibroblasts culture supernatants. Fibroblasts proliferation and viability were assessed as well. Hypoxia inducible factor-1α and the phosphorylated p65 portion of NF-κB were assessed in fibroblasts protein extracts. LPS and CoCl(2) had a minor effect on fibrosis related factors in human primary fibroblasts, possibly due to the absence of interplay with other cell types in the used experimental system. On the contrary both LPS and CoCl(2) increased significantly IL-8. LPS also increased considerably MCP-1, but CoCl(2) decreased it. Thus LPS and CoCl(2) induce a sentinel, nevertheless not identical, phenotype in primary human fibroblasts. The last disparity could result in different body response to infectious or hypoxic noxious stimuli.

Persistence of fecal shedding of Salmonella Enteritidis by experimentally infected laying hens housed in conventional or enriched cages

USDA-ARS?s Scientific Manuscript database

: Because Salmonella Enteritidis can be deposited inside eggs laid by infected hens, the prevalence of this pathogen in commercial egg-producing flocks is an important risk factor for human illness. Opportunities for the introduction, transmission, and persistence of salmonellae in poultry are poten...

Horizontal transmission of Salmonella Enteritidis in experimentally infected laying hens housed in conventional or enriched cages

USDA-ARS?s Scientific Manuscript database

The majority of human illnesses caused by Salmonella Enteritidis are attributed to contaminated eggs, and the prevalence of this pathogen in commercial laying flocks has been identified as a leading epidemiologic risk factor. Flock housing and management systems can affect opportunities for the intr...

Persistence of fecal shedding of Salmonella Enteritidis by experimentally infected laying hens housed in conventional or enriched cages.

USDA-ARS?s Scientific Manuscript database

Because Salmonella Enteritidis can be deposited inside eggs laid by infected hens, the prevalence of this pathogen in commercial egg-producing flocks is an important risk factor for human illness. Opportunities for the introduction, transmission, and persistence of salmonellae in poultry are potenti...

Detection of VEGF-A(xxx)b isoforms in human tissues.

PubMed

Bates, David O; Mavrou, Athina; Qiu, Yan; Carter, James G; Hamdollah-Zadeh, Maryam; Barratt, Shaney; Gammons, Melissa V; Millar, Ann B; Salmon, Andrew H J; Oltean, Sebastian; Harper, Steven J

2013-01-01

Vascular Endothelial Growth Factor-A (VEGF-A) can be generated as multiple isoforms by alternative splicing. Two families of isoforms have been described in humans, pro-angiogenic isoforms typified by VEGF-A165a, and anti-angiogenic isoforms typified by VEGF-A165b. The practical determination of expression levels of alternative isoforms of the same gene may be complicated by experimental protocols that favour one isoform over another, and the use of specific positive and negative controls is essential for the interpretation of findings on expression of the isoforms. Here we address some of the difficulties in experimental design when investigating alternative splicing of VEGF isoforms, and discuss the use of appropriate control paradigms. We demonstrate why use of specific control experiments can prevent assumptions that VEGF-A165b is not present, when in fact it is. We reiterate, and confirm previously published experimental design protocols that demonstrate the importance of using positive controls. These include using known target sequences to show that the experimental conditions are suitable for PCR amplification of VEGF-A165b mRNA for both q-PCR and RT-PCR and to ensure that mispriming does not occur. We also provide evidence that demonstrates that detection of VEGF-A165b protein in mice needs to be tightly controlled to prevent detection of mouse IgG by a secondary antibody. We also show that human VEGF165b protein can be immunoprecipitated from cultured human cells and that immunoprecipitating VEGF-A results in protein that is detected by VEGF-A165b antibody. These findings support the conclusion that more information on the biology of VEGF-A165b isoforms is required, and confirm the importance of the experimental design in such investigations, including the use of specific positive and negative controls.

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.

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.

The Interaction Between Human Papillomavirus and Other Viruses

PubMed Central

Guidry, J. T.; Scott, R. S.

2016-01-01

The etiological role of human papillomavirus (HPV) in anogenital tract and head and neck cancers is well established. However, only a low percentage of HPV-positive women develop cancer, indicating that HPV is necessary but not sufficient in carcinogenesis. Several biological and environmental cofactors have been implicated in the development of HPV-associated carcinoma that include immune status, hormonal changes, parity, dietary habits, tobacco usage, and co-infection with other sexually transmissible agents. Such cofactors likely contribute to HPV persistent infection through diverse mechanisms related to immune control, efficiency of HPV infection, and influences on tumor initiation and progression. Conversely, HPV co-infection with other factors may also harbor anti-tumor effects. Here, we review epidemiological and experimental studies investigating human immunodeficiency virus (HIV), herpes simplex virus (HSV) 1 and 2, human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), BK virus (BKV) JC virus (JCV), and adeno-associated virus (AAV) as viral cofactors in or therapeutic factors against the development of genital and oral HPV-associated carcinomas. PMID:27826043

From HSV infection to erythema multiforme through autoimmune crossreactivity.

PubMed

Lucchese, Alberta

2018-06-01

Scientific and clinical data indicate that human herpes simplex virus 1 (HSV1) and, at a lesser extent, human herpes simplex virus 2 (HSV2) are factor(s) implicated in the development of erythema multiforme (EM). With a focus on oral EM, the present structured review of proteomic and epitope databases searched for the molecular basis that might link HSV1 and HSV2 infections to EM. It was found that a high number of peptides are shared between the two HSVs and human proteins related to the oral mucosa. Moreover, a great number of the shared peptides are also present in epitopes that have been experimentally validated as immunopositive in the human host. The results suggest the involvement of HSV infections in the induction of oral EM via a mechanism of autoimmune cross-reactivity and, in particular, highlight a potential major role for 180kDa bullous pemphigoid antigen and HSV1 infection in the genesis of crossreactions potentially conducive to EM. Copyright © 2018 Elsevier B.V. All rights reserved.

Zinc is an Antioxidant and Anti-Inflammatory Agent: Its Role in Human Health

PubMed Central

Prasad, Ananda S.

2014-01-01

Zinc supplementation trials in the elderly showed that the incidence of infections was decreased by approximately 66% in the zinc group. Zinc supplementation also decreased oxidative stress biomarkers and decreased inflammatory cytokines in the elderly. In our studies in the experimental model of zinc deficiency in humans, we showed that zinc deficiency per se increased the generation of IL-1β and its mRNA in human mononuclear cells following LPS stimulation. Zinc supplementation upregulated A20, a zinc transcription factor, which inhibited the activation of NF-κB, resulting in decreased generation of inflammatory cytokines. Oxidative stress and chronic inflammation are important contributing factors for several chronic diseases attributed to aging, such as atherosclerosis and related cardiac disorders, cancer, neurodegeneration, immunologic disorders and the aging process itself. Zinc is very effective in decreasing reactive oxygen species (ROS). In this review, the mechanism of zinc actions on oxidative stress and generation of inflammatory cytokines and its impact on health in humans will be presented. PMID:25988117

α-Fetoprotein as a modulator of the pro-inflammatory response of human keratinocytes

PubMed Central

Potapovich, AI; Pastore, S; Kostyuk, VA; Lulli, D; Mariani, V; De Luca, C; Dudich, EI; Korkina, LG

2009-01-01

Background and purpose: The immunomodulatory effects of α-fetoprotein (AFP) on lymphocytes and macrophages have been described in vitro and in vivo. Recombinant forms of human AFP have been proposed as potential therapeutic entities for the treatment of autoimmune diseases. We examined the effects of embryonic and recombinant human AFP on the spontaneous, UVA- and cytokine-induced pro-inflammatory responses of human keratinocytes. Experimental approach: Cultures of primary and immortalized human keratinocytes (HaCaT) and human blood T lymphocytes were used. The effects of AFP on cytokine expression were studied by bioplexed elisa and quantitative reverse transcriptase polymerase chain reaction assay. Kinase and nuclear factor kappa B (NFκB) phosphorylation were quantified by intracellular elisa. Nuclear activator protein 1 and NFκB DNA binding activity was measured by specific assays. Nitric oxide and H2O2 production and redox status were assessed by fluorescent probe and biochemical methods. Key results: All forms of AFP enhanced baseline expression of cytokines, chemokines and growth factors. AFP dose-dependently increased tumour necrosis factor alpha-stimulated granulocyte macrophage colony stimulating factor and interleukin 8 expression and decreased tumour necrosis factor alpha-induced monocyte chemotactic protein 1 and IP-10 (interferon gamma-produced protein of 10 kDa) expression. AFP induced a marked activator protein 1 activation in human keratinocytes. AFP also increased H2O2 and modulated nitrite/nitrate levels in non-stimulated keratinocytes whereas it did not affect these parameters or cytokine release from UVA-stimulated cells. Phosphorylation of extracellular signal-regulated kinase (ERK1/2) and Akt1 but not NFκB was activated by AFP alone or by its combination with UVA. Conclusions and implications: Exogenous AFP induces activation of human keratinocytes, with de novo expression of a number of pro-inflammatory mediators and modulation of their pro-inflammatory response to cytokines or UVA. AFP may modulate inflammatory events in human skin. PMID:19785658

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

A toolbox of immunoprecipitation-grade monoclonal antibodies to human transcription factors.

PubMed

Venkataraman, Anand; Yang, Kun; Irizarry, Jose; Mackiewicz, Mark; Mita, Paolo; Kuang, Zheng; Xue, Lin; Ghosh, Devlina; Liu, Shuang; Ramos, Pedro; Hu, Shaohui; Bayron Kain, Diane; Keegan, Sarah; Saul, Richard; Colantonio, Simona; Zhang, Hongyan; Behn, Florencia Pauli; Song, Guang; Albino, Edisa; Asencio, Lillyann; Ramos, Leonardo; Lugo, Luvir; Morell, Gloriner; Rivera, Javier; Ruiz, Kimberly; Almodovar, Ruth; Nazario, Luis; Murphy, Keven; Vargas, Ivan; Rivera-Pacheco, Zully Ann; Rosa, Christian; Vargas, Moises; McDade, Jessica; Clark, Brian S; Yoo, Sooyeon; Khambadkone, Seva G; de Melo, Jimmy; Stevanovic, Milanka; Jiang, Lizhi; Li, Yana; Yap, Wendy Y; Jones, Brittany; Tandon, Atul; Campbell, Elliot; Montelione, Gaetano T; Anderson, Stephen; Myers, Richard M; Boeke, Jef D; Fenyö, David; Whiteley, Gordon; Bader, Joel S; Pino, Ignacio; Eichinger, Daniel J; Zhu, Heng; Blackshaw, Seth

2018-03-19

A key component of efforts to address the reproducibility crisis in biomedical research is the development of rigorously validated and renewable protein-affinity reagents. As part of the US National Institutes of Health (NIH) Protein Capture Reagents Program (PCRP), we have generated a collection of 1,406 highly validated immunoprecipitation- and/or immunoblotting-grade mouse monoclonal antibodies (mAbs) to 737 human transcription factors, using an integrated production and validation pipeline. We used HuProt human protein microarrays as a primary validation tool to identify mAbs with high specificity for their cognate targets. We further validated PCRP mAbs by means of multiple experimental applications, including immunoprecipitation, immunoblotting, chromatin immunoprecipitation followed by sequencing (ChIP-seq), and immunohistochemistry. We also conducted a meta-analysis that identified critical variables that contribute to the generation of high-quality mAbs. All validation data, protocols, and links to PCRP mAb suppliers are available at http://proteincapture.org.

Fungal-derived semiochemical 1-octen-3-ol disrupts dopamine packaging and causes neurodegeneration

PubMed Central

Inamdar, Arati A.; Hossain, Muhammad M.; Bernstein, Alison I.; Miller, Gary W.; Richardson, Jason R.; Bennett, Joan Wennstrom

2013-01-01

Parkinson disease (PD) is the most common movement disorder and, although the exact causes are unknown, recent epidemiological and experimental studies indicate that several environmental agents may be significant risk factors. To date, these suspected environmental risk factors have been man-made chemicals. In this report, we demonstrate via genetic, biochemical, and immunological studies that the common volatile fungal semiochemical 1-octen-3-ol reduces dopamine levels and causes dopamine neuron degeneration in Drosophila melanogaster. Overexpression of the vesicular monoamine transporter (VMAT) rescued the dopamine toxicity and neurodegeneration, whereas mutations decreasing VMAT and tyrosine hydroxylase exacerbated toxicity. Furthermore, 1-octen-3-ol also inhibited uptake of dopamine in human cell lines expressing the human plasma membrane dopamine transporter (DAT) and human VMAT ortholog, VMAT2. These data demonstrate that 1-octen-3-ol exerts toxicity via disruption of dopamine homeostasis and may represent a naturally occurring environmental agent involved in parkinsonism. PMID:24218591

[Placental transfer of drugs].

PubMed

Evain-Brion, Danièle; Berveiller, Paul; Gil, Sophie

2014-01-01

With more than 830,000 live births in France, a great number of pregnant women are concerned by a treatment during pregnancy and many questions revolve around appreciating medication-related risks during pregnancy. The human placenta is the interface between mother and fetus and remains difficult to study for ethical reasons. Placental transfer of drugs from mother to fetus is dependent on their physicochemical properties, maternal and fetal factors and placental factors. The human placental perfusion model is the only experimental model to study human placental transfer of drugs in organized placental tissue. In vitro models utilizing cell cultures are mostly limited to the investigation of cellular toxicity along pregnancy or specific transfer mechanisms, such as their interaction with transporters. Taking advantage of the complementarity of these models, it will be possible to develop a rational use of drugs during this period. © 2014 Société Française de Pharmacologie et de Thérapeutique.

Kruppel-Like Factor 15 Is Critical for the Development of Left Ventricular Hypertrophy.

PubMed

Patel, Sheila K; Ramchand, Jay; Crocitti, Vincenzo; Burrell, Louise M

2018-04-27

Left ventricular hypertrophy (LVH) is an independent risk factor for adverse cardiovascular events and is often present in patients with hypertension. Treatment to reduce blood pressure and regress LVH is key to improving health outcomes, but currently available drugs have only modest cardioprotective effects. Improved understanding of the molecular mechanisms involved in the development of LVH may lead to new therapeutic targets in the future. There is now compelling evidence that the transcription factor Kruppel-like factor 15 (KLF15) is an important negative regulator of cardiac hypertrophy in both experimental models and in man. Studies have reported that loss or suppression of KLF15 contributes to LVH, through lack of inhibition of pro-hypertrophic transcription factors and stimulation of trophic and fibrotic signaling pathways. This review provides a summary of the experimental and human studies that have investigated the role of KLF15 in the development of cardiac hypertrophy. It also discusses our recent paper that described the contribution of genetic variants in KLF15 to the development of LVH and heart failure in high-risk patients.

Positional cloning in mice and its use for molecular dissection of inflammatory arthritis.

PubMed

Abe, Koichiro; Yu, Philipp

2009-02-01

One of the upcoming next quests in the field of genetics might be molecular dissection of the genetic and environmental components of human complex diseases. In humans, however, there are certain experimental limitations for identification of a single component of the complex interactions by genetic analyses. Experimental animals offer simplified models for genetic and environmental interactions in human complex diseases. In particular, mice are the best mammalian models because of a long history and ample experience for genetic analyses. Forward genetics, which includes genetic screen and subsequent positional cloning of the causative genes, is a powerful strategy to dissect a complex phenomenon without preliminarily molecular knowledge of the process. In this review, first, we describe a general scheme of positional cloning in mice. Next, recent accomplishments on the patho-mechanisms of inflammatory arthritis by forward genetics approaches are introduced; Positional cloning effort for skg, Ali5, Ali18, cmo, and lupo mutants are provided as examples for the application to human complex diseases. As seen in the examples, the identification of genetic factors by positional cloning in the mouse have potential in solving molecular complexity of gene-environment interactions in human complex diseases.

The reaction of the cardio-vascular and sympathico-adrenal systems to intellectual activity with emotional stress. [human operator performance

NASA Technical Reports Server (NTRS)

Tomashevskaya, L. I.

1975-01-01

The effect of emotiogenic factors on an operator's intellectual activity were studied for differing working regimes on an experimental control panel that provided for light, sonic, and electrocutaneous stimuli. The latter stimulus was activated automatically if the subject gave an incorrect response. It was shown that the working capacity of the operator under stress depends to a great extent on the effect of the emotiogenic factors on the individual functioning characteristics of the cardiovascular and sympathetic-adrenal systems. Moral, intellectual, willpower, emotional, and other personality traits are decisive factors of operator function.

Manipulation of host factors optimizes the pathogenesis of western equine encephalitis virus infections in mice for antiviral drug development.

PubMed

Blakely, Pennelope K; Delekta, Phillip C; Miller, David J; Irani, David N

2015-02-01

While alphaviruses spread naturally via mosquito vectors, some can also be transmitted as aerosols making them potential bioterrorism agents. One such pathogen, western equine encephalitis virus (WEEV), causes fatal human encephalitis via multiple routes of infection and thus presumably via multiple mechanisms. Although WEEV also produces acute encephalitis in non-human primates, a small animal model that recapitulates features of human disease would be useful for both pathogenesis studies and to evaluate candidate antiviral therapies. We have optimized conditions to infect mice with a low passage isolate of WEEV, thereby allowing detailed investigation of virus tropism, replication, neuroinvasion, and neurovirulence. We find that host factors strongly influence disease outcome, and in particular, that age, gender, and genetic background all have significant effects on disease susceptibility independent of virus tropism or replication within the central nervous system. Our data show that experimental variables can be adjusted in mice to recapitulate disease features known to occur in both non-human primates and humans, thus aiding further study of WEEV pathogenesis and providing a realistic therapeutic window for antiviral drug delivery.

Manipulation of host factors optimizes the pathogenesis of western equine encephalitis virus infections in mice for antiviral drug development

PubMed Central

Blakely, Pennelope K.; Delekta, Phillip C.; Miller, David J.; Irani, David N.

2014-01-01

While alphaviruses spread naturally via mosquito vectors, some can also be transmitted as aerosols making them potential bioterrorism agents. One such pathogen, western equine encephalitis virus (WEEV), causes fatal human encephalitis via multiple routes of infection and thus presumably via multiple mechanisms. Although WEEV also produces acute encephalitis in non-human primates, a small animal model that recapitulates features of human disease would be useful for both pathogenesis studies and to evaluate candidate antiviral therapies. We have optimized conditions to infect mice with a low passage isolate of WEEV, thereby allowing detailed investigation of virus tropism, replication, neuroinvasion, and neurovirulence. We find that host factors strongly influence disease outcome, and in particular that age, gender and genetic background all have significant effects on disease susceptibility independent of virus tropism or replication within the central nervous system. Our data show that experimental variables can be adjusted in mice to recapitulate disease features known to occur in both non-human primates and humans, thus aiding further study of WEEV pathogenesis and providing a realistic therapeutic window for antiviral drug delivery. PMID:25361697

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.

Anesthesia in Experimental Stroke Research

PubMed Central

Hoffmann, Ulrike; Sheng, Huaxin; Ayata, Cenk; Warner, David S.

2016-01-01

Anesthetics have enabled major advances in development of experimental models of human stroke. Yet their profound pharmacologic effects on neural function can confound the interpretation of experimental stroke research. Anesthetics have drug and dose-specific effects on cerebral blood flow and metabolism, neurovascular coupling, autoregulation, ischemic depolarizations, excitotoxicity, inflammation, neural networks, and numerous molecular pathways relevant for stroke outcome. Both pre- and post-conditioning properties have been described. Anesthetics also modulate systemic arterial blood pressure, lung ventilation, and thermoregulation, all of which may interact with the ischemic insult as well as the therapeutic interventions. These confounds present a dilemma. Here, we provide an overview of the anesthetic mechanisms of action and molecular and physiologic effects on factors relevant to stroke outcomes that can guide the choice and optimization of the anesthetic regimen in experimental stroke. PMID:27534542

From whole body to cellular models of hepatic triglyceride metabolism: man has got to know his limitations

PubMed Central

Green, Charlotte J.; Pramfalk, Camilla; Morten, Karl J.

2014-01-01

The liver is a main metabolic organ in the human body and carries out a vital role in lipid metabolism. Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, encompassing a spectrum of conditions from simple fatty liver (hepatic steatosis) through to cirrhosis. Although obesity is a known risk factor for hepatic steatosis, it remains unclear what factor(s) is/are responsible for the primary event leading to retention of intrahepatocellular fat. Studying hepatic processes and the etiology and progression of disease in vivo in humans is challenging, not least as NAFLD may take years to develop. We present here a review of experimental models and approaches that have been used to assess liver triglyceride metabolism and discuss their usefulness in helping to understand the aetiology and development of NAFLD. PMID:25352434

The developing oligodendrocyte: key cellular target in brain injury in the premature infant

PubMed Central

Volpe, Joseph J.; Kinney, Hannah C.; Jensen, Frances, E.; Rosenberg, Paul A.

2011-01-01

Brain injury in the premature infant, a problem of enormous importance, is associated with a high risk of neurodevelopmental disability. The major type of injury involves cerebral white matter and the principal cellular target is the developing oligodendrocyte. The specific phase of the oligodendroglial lineage affected has been defined from study of both human brain and experimental models. This premyelinating cell (pre-OL) is vulnerable because of a series of maturation-dependent events. The pathogenesis of pre-OL injury relates to operation of two upstream mechanisms, hypoxia-ischemia and systemic infection/inflammation, both of which are common occurrences in premature infants. The focus of this review and of our research over the past 15-20 years has been the cellular and molecular bases for the maturation-dependent vulnerability of the pre-OL to the action of the two upstream mechanisms. Three downstream mechanisms have been identified, i.e., microglial activation, excitotoxicity and free radical attack. The work in both experimental models and human brain has identified a remarkable confluence of maturation-dependent factors that render the pre-OL so exquisitely vulnerable to these downstream mechanisms. Most importantly, elucidation of these factors has led to delineation of a series of potential therapeutic interventions, which in experimental models show marked protective properties. The critical next step, i.e., clinical trials in the living infant, is now on the horizon. PMID:21382469

Dynamic Socialized Gaussian Process Models for Human Behavior Prediction in a Health Social Network

PubMed Central

Shen, Yelong; Phan, NhatHai; Xiao, Xiao; Jin, Ruoming; Sun, Junfeng; Piniewski, Brigitte; Kil, David; Dou, Dejing

2016-01-01

Modeling and predicting human behaviors, such as the level and intensity of physical activity, is a key to preventing the cascade of obesity and helping spread healthy behaviors in a social network. In our conference paper, we have developed a social influence model, named Socialized Gaussian Process (SGP), for socialized human behavior modeling. Instead of explicitly modeling social influence as individuals' behaviors influenced by their friends' previous behaviors, SGP models the dynamic social correlation as the result of social influence. The SGP model naturally incorporates personal behavior factor and social correlation factor (i.e., the homophily principle: Friends tend to perform similar behaviors) into a unified model. And it models the social influence factor (i.e., an individual's behavior can be affected by his/her friends) implicitly in dynamic social correlation schemes. The detailed experimental evaluation has shown the SGP model achieves better prediction accuracy compared with most of baseline methods. However, a Socialized Random Forest model may perform better at the beginning compared with the SGP model. One of the main reasons is the dynamic social correlation function is purely based on the users' sequential behaviors without considering other physical activity-related features. To address this issue, we further propose a novel “multi-feature SGP model” (mfSGP) which improves the SGP model by using multiple physical activity-related features in the dynamic social correlation learning. Extensive experimental results illustrate that the mfSGP model clearly outperforms all other models in terms of prediction accuracy and running time. PMID:27746515

Frequency and persistence of fecal shedding of Salmonella Enteritidis by experimentally infected laying hens housed in enriched colony cages at different stocking densities

USDA-ARS?s Scientific Manuscript database

Human infections with Salmonella Enteritidis are often attributed to the consumption of contaminated eggs, so the prevalence of this pathogen in egg-laying poultry is an important public health risk factor. Numerous and complex environmental influences on Salmonella persistence and transmission are ...

Human Factors in Industrial and Consumer Products and Services

DTIC Science & Technology

2006-03-24

modeling; simulation and intelligent agents; Transportation ; Space and aviation; Telecommunication and web applications; Consumer products; and Customer...the user feedback throughout the product development. Self-explaining and forgiving roads to improve safety Karel Brookhuis, Dick de Waard...in a simulated ambulance dispatcher’s task Ben Mulder, Anje Kruizinga & Dick de Waard University of Groningen, Experimental and Work Psychology

The Food Service Worker and the Travis Air Force Base Experimental Food System: Worker Opinion and Job Satisfaction

DTIC Science & Technology

1975-04-01

Surveys and interviews were administered to both civilian and military food service workers at Travis Air Force Base, both before and after dining system changes, to assess job satisfaction, opinions about additional training, and opinions about environmental and equipment features relevant to potential human factors problems.

DEBLICOM: Deaf-Blind Communication and Control Systems. Interim Progress Report, August 1974-August 1975.

ERIC Educational Resources Information Center

Kafafian, Haig

Presented is a report on the work of Cybernetics Research Institute (CRI) investigators on the development of deaf-blind communication and control systems (DEBLICOM). Described in Part One is one embodiment of DEBLICOM designed and built by CRI engineers. Reported in Part Two are experimental procedures and human factors considerations of…

Methods for Improving Information from "Undesigned" Human Factors Experiments. Technical Report No. p75-287.

ERIC Educational Resources Information Center

Simon, Charles W.

An "undesigned" experiment is one in which the predictor variables are correlated, either due to a failure to complete a design or because the investigator was unable to select or control relevant experimental conditions. The traditional method of analyzing this class of experiment--multiple regression analysis based on a least squares…

Cognitive Style Factors and Learning from Micro-Computer Based and Programmed Instructional Materials: A Preliminary Analysis.

ERIC Educational Resources Information Center

Canelos, James; And Others

This study examined the effects of two cognitive styles--field dependents-independents and reflectivity-impulsivity--on learning from microcomputer-based instruction. In the first of three experimental designs, a programmed instruction text on the human heart was used which contained both visual and verbal information in an instructional display,…

Detection and survival of Toxoplasma gondii in milk and cheese from experimentally infected goats

USDA-ARS?s Scientific Manuscript database

The consumption of unpasteurized goat cheese and milk has been suggested as a risk factor for toxoplasmosis in humans. In the present study, detection and survival of Toxoplasma gondii in milk and cheese was studied. Eight goats were inoculated orally with 300-10000 oocysts of T. gondii strain TgGoa...

Frequency and persistence of fecal shedding of Salmonella Enteritidis by experimentally infected laying hens housed in enriched colony cages at different stocking densities

USDA-ARS?s Scientific Manuscript database

Human Salmonella Enteritidis infections are often linked with consuming contaminated eggs, so the prevalence of this pathogen in egg-laying poultry is an important risk factor for public health. Salmonella persistence and transmission in commercial egg producing flocks are influenced by the complex ...

The neonatal marmoset monkey ovary is very primitive exhibiting many oogonia

PubMed Central

Fereydouni, B; Drummer, C; Aeckerle, N; Schlatt, S; Behr, R

2014-01-01

Oogonia are characterized by diploidy and mitotic proliferation. Human and mouse oogonia express several factors such as OCT4, which are characteristic of pluripotent cells. In human, almost all oogonia enter meiosis between weeks 9 and 22 of prenatal development or undergo mitotic arrest and subsequent elimination from the ovary. As a consequence, neonatal human ovaries generally lack oogonia. The same was found in neonatal ovaries of the rhesus monkey, a representative of the old world monkeys (Catarrhini). By contrast, proliferating oogonia were found in adult prosimians (now called Strepsirrhini), which is a group of ‘lower’ primates. The common marmoset monkey (Callithrix jacchus) belongs to the new world monkeys (Platyrrhini) and is increasingly used in reproductive biology and stem cell research. However, ovarian development in the marmoset monkey has not been widely investigated. Herein, we show that the neonatal marmoset ovary has an extremely immature histological appearance compared with the human ovary. It contains numerous oogonia expressing the pluripotency factors OCT4A, SALL4, and LIN28A (LIN28). The pluripotency factor-positive germ cells also express the proliferation marker MKI67 (Ki-67), which has previously been shown in the human ovary to be restricted to premeiotic germ cells. Together, the data demonstrate the primitiveness of the neonatal marmoset ovary compared with human. This study may introduce the marmoset monkey as a non-human primate model to experimentally study the aspects of primate primitive gonad development, follicle assembly, and germ cell biology in vivo. PMID:24840529

Fear of humans and its relationships with productivity in laying hens at commercial farms.

PubMed

Barnett, J L; Hemsworth, P H; Newman, E A

1992-09-01

1. The relationship between the behavioural responses of laying hens to humans and productivity was determined at 16 commercial sheds from 14 farms. 2. A number of behaviour variables were moderately to highly correlated with production variables; for example, the proportion of birds that moved away from an approaching experimenter in an unfamiliar environment ('shute test') was negatively correlated with peak hen day production, (PKHDP). 3. Behavioural responses to humans accounted for between 23 and 63% of the variation in a number of production variables, including PKHDP and the duration of a high level of production. 4. Inclusion of farm factor variables increased the amount of variation accounted for by the behaviour variables. For example, adding the variable 'time/day spent in the shed by stockpeople' to the behaviour variables 'the proportion of birds that moved away from an approaching human' in the shute test and 'the number of times birds in cages adopted an erect posture' in response to an approaching human increased the variation accounted for in PKHDP from 53 to 61%. 5. The results suggest that fear of humans may be a factor that limits the productivity of commercial laying hens.

Improved inhalation technology for setting safe exposure levels for workplace chemicals

NASA Technical Reports Server (NTRS)

Stuart, Bruce O.

1993-01-01

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

Access to resources shapes maternal decision making: evidence from a factorial vignette experiment.

PubMed

Kushnick, Geoff

2013-01-01

The central assumption of behavioral ecology is that natural selection has shaped individuals with the capacity to make decisions that balance the fitness costs and benefits of behavior. A number of factors shape the fitness costs and benefits of maternal care, but we lack a clear understanding how they, taken together, play a role in the decision-making process. In animal studies, the use of experimental methods has allowed for the tight control of these factors. Standard experimentation is inappropriate in human behavioral ecology, but vignette experiments may solve the problem. I used a confounded factorial vignette experiment to gather 640 third-party judgments about the maternal care decisions of hypothetical women and their children from 40 female karo Batak respondents in rural Indonesia. This allowed me to test hypotheses derived from parental investment theory about the relative importance of five binary factors in shaping maternal care decisions with regard to two distinct scenarios. As predicted, access to resources--measured as the ability of a woman to provide food for her children--led to increased care. A handful of other factors conformed to prediction, but they were inconsistent across scenarios. The results suggest that mothers may use simple heuristics, rather than a full accounting for costs and benefits, to make decisions about maternal care. Vignettes have become a standard tool for studying decision making, but have made only modest inroads to evolutionarily informed studies of human behavior.

Experimental Psychopathology Paradigms for Alcohol Use Disorders: Applications for Translational Research

PubMed Central

Bujarski, Spencer; Ray, Lara A.

2016-01-01

In spite of high prevalence and disease burden, scientific consensus on the etiology and treatment of Alcohol Use Disorder (AUD) has yet to be reached. The development and utilization of experimental psychopathology paradigms in the human laboratory represents a cornerstone of AUD research. In this review, we describe and critically evaluate the major experimental psychopathology paradigms developed for AUD, with an emphasis on their implications, strengths, weaknesses, and methodological considerations. Specifically we review alcohol administration, self-administration, cue-reactivity, and stress-reactivity paradigms. We also provide an introduction to the application of experimental psychopathology methods to translational research including genetics, neuroimaging, pharmacological and behavioral treatment development, and translational science. Through refining and manipulating key phenotypes of interest, these experimental paradigms have the potential to elucidate AUD etiological factors, improve the efficiency of treatment developments, and refine treatment targets thus advancing precision medicine. PMID:27266992

Experimental psychopathology paradigms for alcohol use disorders: Applications for translational research.

PubMed

Bujarski, Spencer; Ray, Lara A

2016-11-01

In spite of high prevalence and disease burden, scientific consensus on the etiology and treatment of Alcohol Use Disorder (AUD) has yet to be reached. The development and utilization of experimental psychopathology paradigms in the human laboratory represents a cornerstone of AUD research. In this review, we describe and critically evaluate the major experimental psychopathology paradigms developed for AUD, with an emphasis on their implications, strengths, weaknesses, and methodological considerations. Specifically we review alcohol administration, self-administration, cue-reactivity, and stress-reactivity paradigms. We also provide an introduction to the application of experimental psychopathology methods to translational research including genetics, neuroimaging, pharmacological and behavioral treatment development, and translational science. Through refining and manipulating key phenotypes of interest, these experimental paradigms have the potential to elucidate AUD etiological factors, improve the efficiency of treatment developments, and refine treatment targets thus advancing precision medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Future of Mechatronics and Human

NASA Astrophysics Data System (ADS)

Harashima, Fumio; Suzuki, Satoshi

This paper mentions circumstance of mechatronics that sustain our human society, and introduces HAM(Human Adaptive Mechatronics)-project as one of research projects to create new human-machine system. The key point of HAM is skill, and analysis of skill and establishment of assist method to enhance total performance of human-machine system are main research concerns. As study of skill is an elucidation of human itself, analyses of human higher function are significant. In this paper, after surveying researches of human brain functions, an experimental analysis of human characteristic in machine operation is shown as one example of our research activities. We used hovercraft simulator as verification system including observation, voluntary motion control and machine operation that are needed to general machine operation. Process and factors to become skilled were investigated by identification of human control characteristics with measurement of the operator's line-of sight. It was confirmed that early switching of sub-controllers / reference signals in human and enhancement of space perception are significant.

Validating a behavioral economic approach to assess food demand: effects of body mass index, dietary restraint, and impulsivity.

PubMed

Reslan, Summar; Saules, Karen K; Greenwald, Mark K

2012-10-01

Behavioral economic theory is a useful framework for analyzing factors influencing choice, but the majority of human behavioral economic research has focused on drug choice. The behavioral economic choice paradigm may also be valuable for understanding food-maintained behavior. Our primary objective was two-fold: (1) Validate a human laboratory model of food-appetitive behavior, and (2) Assess the contribution of individual level factors that may differentially impact food choice behavior. Two studies were conducted. In Study 1, female subjects (N=17) participated in two consecutive food choice experimental sessions, whereas in Study 2, female subjects (N=21) participated in one concurrent food choice experimental session. During consecutive choice sessions (Study 1), demand for the more palatable food (i.e., high-sugar/high-fat) was more inelastic than the less palatable (i.e., low-sugar/low-fat) option. During concurrent choice sessions, demand for the more palatable food (i.e., high-sugar/high-fat) was more inelastic for restrained vs. unrestrained eaters, and for those who were overweight vs. normal weight. Demand for both palatable and less palatable choices was more elastic for high-impulsive vs. low-impulsive subjects. These findings suggest that the behavioral economic framework can be used successfully to develop a human laboratory model of food-appetitive behavior. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Environmental factors and male fertility].

PubMed

Köhn, F-M; Schuppe, H C

2016-07-01

The identification of potential environmental hazards may have clinical relevance for diagnosis of male infertility. Knowledge about these factors will improve prevention of fertility disorders. Apart from drugs or factors related to lifestyle such as alcohol and tobacco smoke, various environmental and occupational agents, both chemical and physical, may impair male reproductive functions. With regard to the complex regulation of the male reproductive system, the available information concerning single exogenous factors and their mechanisms of action in humans is limited. This is also due to the fact that extrapolation of results obtained from experimental animal studies remains difficult. Nevertheless, the assessment of relevant exposures to reproductive toxicants should be carefully evaluated during diagnostic procedures of andrological patients.

Nonexercise activity thermogenesis (NEAT): environment and biology.

PubMed

Levine, James A

2004-05-01

Nonexercise activity thermogenesis (NEAT) is the energy expended for everything that is not sleeping, eating, or sports-like exercise. It includes the energy expended walking to work, typing, performing yard work, undertaking agricultural tasks, and fidgeting. NEAT can be measured by one of two approaches. The first is to measure or estimate total NEAT. Here, total daily energy expenditure is measured, and from it "basal metabolic rate-plus-thermic effect of food" is subtracted. The second is the factoral approach, whereby the components of NEAT are quantified, and total NEAT is calculated by summing these components. The amount of NEAT that humans perform represents the product of the amount and types of physical activities and the thermogenic cost of each activity. The factors that impact a human's NEAT are readily divisible into environmental factors, such as occupation or dwelling within a "concrete jungle," and biological factors such as weight, gender, and body composition. The combined impact of these factors explains the substantial variance in human NEAT. The variability in NEAT might be viewed as random, but human and animal data contradict this. It appears that changes in NEAT subtly accompany experimentally induced changes in energy balance and are important in the physiology of weight change. Inadequate modulation of NEAT plus a sedentary lifestyle may thus be important in obesity. It then becomes intriguing to dissect mechanistic studies that delineate how NEAT is regulated into neural, peripheral, and humoral factors. A scheme is described in this review in which NEAT corresponds to a carefully regulated "tank" of physical activity that is crucial for weight control.

The identification of factors contributing to self-reported anomalies in civil aviation.

PubMed

Andrzejczak, Chris; Karwowski, Waldemar; Thompson, William

2014-01-01

The main objective of this study was to analyze anomalies voluntarily reported by pilots in civil aviation sector and identify factors leading to such anomalies. Experimental data were obtained from the NASA aviation safety reporting system (ASRS) database. These data contained a range of text records spanning 30 years of civilian aviation, both commercial (airline operations) and general aviation (private aircraft). Narrative data as well as categorical data were used. The associations between incident contributing factors and self-reported anomalies were investigated using data mining and correspondence analysis. The results revealed that a broadly defined human factors category and weather conditions were the main contributors to self-reported civil aviation anomalies. New associations between identified factors and reported anomaly conditions were also reported.

Toward a digital camera to rival the human eye

NASA Astrophysics Data System (ADS)

Skorka, Orit; Joseph, Dileepan

2011-07-01

All things considered, electronic imaging systems do not rival the human visual system despite notable progress over 40 years since the invention of the CCD. This work presents a method that allows design engineers to evaluate the performance gap between a digital camera and the human eye. The method identifies limiting factors of the electronic systems by benchmarking against the human system. It considers power consumption, visual field, spatial resolution, temporal resolution, and properties related to signal and noise power. A figure of merit is defined as the performance gap of the weakest parameter. Experimental work done with observers and cadavers is reviewed to assess the parameters of the human eye, and assessment techniques are also covered for digital cameras. The method is applied to 24 modern image sensors of various types, where an ideal lens is assumed to complete a digital camera. Results indicate that dynamic range and dark limit are the most limiting factors. The substantial functional gap, from 1.6 to 4.5 orders of magnitude, between the human eye and digital cameras may arise from architectural differences between the human retina, arranged in a multiple-layer structure, and image sensors, mostly fabricated in planar technologies. Functionality of image sensors may be significantly improved by exploiting technologies that allow vertical stacking of active tiers.

An Experimental Test of Factors Attracting Deer Mice into Buildings.

PubMed

Kuenzi, Amy J; Douglass, Richard

2009-09-01

Deer mice (Peromyscus maniculatus) are the principal reservoir host of Sin Nombre virus (SNV). Deer mice use a wide variety of habitats including peridomestic settings in and around human dwellings, their presence in and around homes has been implicated as a risk factor for acquiring Hantavirus Pulmonary Syndrome. Deer mice are believed to enter buildings in order to gain access to a variety of resources including food, bedding material, and better thermal microclimates. However, no one has experimentally tested which factors influence mice use of buildings. We conducted experiments using small simulated buildings to determine the effects of two factors, i.e., food and bedding material, on mouse activity in these buildings. We also examined if these effects varied with time of year. We found that deer mice entered our buildings regardless of the presence or absence of food or bedding. However, the amount of activity in buildings was affected by what they contained. We found significantly higher indices of activity in buildings containing food compared to both empty buildings (control) and buildings containing bedding material. Time of year did not affect activity in buildings.

Biomedical and Human Factors Requirements for a Manned Earth-Orbiting Station

NASA Technical Reports Server (NTRS)

Reynolds, J. B.

1963-01-01

The study reported here has presented a measurement data pool for the determination of biomedical and behavioral effects of long-term exposure to weightlessness. This includes measures, techniques, equipment, and requirements in terms of weight, power, volume, time, crew activities, subsystem interfaces and experimental programs and designs, and confidence ratings for their effectiveness for determining weightlessness effects.

Evaluating a Computational Model of Social Causality and Responsibility

DTIC Science & Technology

2006-01-01

Evaluating a Computational Model of Social Causality and Responsibility Wenji Mao University of Southern California Institute for Creative...empirically evaluate a computa- tional model of social causality and responsibility against human social judgments. Results from our experimental...developed a general computational model of social cau- sality and responsibility [10, 11] that formalizes the factors people use in reasoning about

Gender, sex hormones and pulmonary hypertension

PubMed Central

Austin, Eric D.; Lahm, Tim; West, James; Tofovic, Stevan P.; Johansen, Anne Katrine; MacLean, Margaret R.; Alzoubi, Abdallah; Oka, Masahiko

2013-01-01

Most subtypes of pulmonary arterial hypertension (PAH) are characterized by a greater susceptibility to disease among females, although females with PAH appear to live longer after diagnosis. While this “estrogen paradoxȍ of enhanced female survival despite increased female susceptibility remains a mystery, recent progress has begun to shed light upon the interplay of sex hormones, the pathogenesis of pulmonary hypertension, and the right ventricular response to stress. For example, emerging data in humans and experimental models suggest that estrogens or differential sex hormone metabolism may modify disease risk among susceptible subjects, and that estrogens may interact with additional local factors such as serotonin to enhance the potentially damaging chronic effects of estrogens on the pulmonary vasculature. Regardless, it remains unclear why not all estrogenic compounds behave equally, nor why estrogens appear to be protective in certain settings but detrimental in others. The contribution of androgens and other compounds, such as dehydroepiandrosterone, to pathogenesis and possibly treatment must be considered as well. In this review, we will discuss the recent understandings on how estrogens, estrogen metabolism, dehydroepiandrosterone, and additional susceptibility factors may all contribute to the pathogenesis or potentially to the treatment of pulmonary hypertension, by evaluating current human, cell-based, and experimental model data. PMID:24015330

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

CDDO-Me protects normal lung and breast epithelial cells but not cancer cells from radiation.

PubMed

El-Ashmawy, Mariam; Delgado, Oliver; Cardentey, Agnelio; Wright, Woodring E; Shay, Jerry W

2014-01-01

Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs). In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF) = 1.3), and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs) with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients.

CDDO-Me Protects Normal Lung and Breast Epithelial Cells but Not Cancer Cells from Radiation

PubMed Central

El-Ashmawy, Mariam; Delgado, Oliver; Cardentey, Agnelio; Wright, Woodring E.; Shay, Jerry W.

2014-01-01

Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs). In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF) = 1.3), and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs) with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients. PMID:25536195

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

Mental workload prediction based on attentional resource allocation and information processing.

PubMed

Xiao, Xu; Wanyan, Xiaoru; Zhuang, Damin

2015-01-01

Mental workload is an important component in complex human-machine systems. The limited applicability of empirical workload measures produces the need for workload modeling and prediction methods. In the present study, a mental workload prediction model is built on the basis of attentional resource allocation and information processing to ensure pilots' accuracy and speed in understanding large amounts of flight information on the cockpit display interface. Validation with an empirical study of an abnormal attitude recovery task showed that this model's prediction of mental workload highly correlated with experimental results. This mental workload prediction model provides a new tool for optimizing human factors interface design and reducing human errors.

Viral Organization of Human Proteins

PubMed Central

Wuchty, Stefan; Siwo, Geoffrey; Ferdig, Michael T.

2010-01-01

Although maps of intracellular interactions are increasingly well characterized, little is known about large-scale maps of host-pathogen protein interactions. The investigation of host-pathogen interactions can reveal features of pathogenesis and provide a foundation for the development of drugs and disease prevention strategies. A compilation of experimentally verified interactions between HIV-1 and human proteins and a set of HIV-dependency factors (HDF) allowed insights into the topology and intricate interplay between viral and host proteins on a large scale. We found that targeted and HDF proteins appear predominantly in rich-clubs, groups of human proteins that are strongly intertwined among each other. These assemblies of proteins may serve as an infection gateway, allowing the virus to take control of the human host by reaching protein pathways and diversified cellular functions in a pronounced and focused way. Particular transcription factors and protein kinases facilitate indirect interactions between HDFs and viral proteins. Discerning the entanglement of directly targeted and indirectly interacting proteins may uncover molecular and functional sites that can provide novel perspectives on the progression of HIV infection and highlight new avenues to fight this virus. PMID:20827298

Programming by early nutrition: an experimental approach.

PubMed

Lucas, A

1998-02-01

That events during critical or sensitive periods of development may "program" long-term or life-time structure or function of the organism is well recognized. Evidence for programming by nutrition is established in animals, in whom brief pre- or postnatal nutritional manipulations may program adult size, metabolism, blood lipids, diabetes, blood pressure, obesity, atherosclerosis, learning, behavior and life span. Human epidemiological data link potential markers of early nutrition (size at birth or in infancy) to cardiovascular disease and its risk factors in adulthood. However, these retrospective data cannot prove nutritional cause or underpin health policies. After 16 y, however, of ethical, randomized intervention studies of early nutrition in humans with long-term follow-up to test experimentally the nutritional programming hypothesis, we find that humans, like other species, have sensitive windows for nutrition in terms of later outcomes; for instance, perinatal diet influences neurodevelopment and bone mineralization into mid-childhood. Possible biological mechanisms for storing throughout life the "memory" of early nutritional experience and its expression in adulthood include adaptive changes in gene expression, preferential clonal selection of adapted cells in programmed tissues and programmed differential proliferation of tissue cell types. Animal and human evidence supporting nutritional programming has major potential biological and medical significance.

Risk Factors for Antimicrobial Resistance in Escherichia coli in Pigs Receiving Oral Antimicrobial Treatment: A Systematic Review.

PubMed

Burow, Elke; Käsbohrer, Annemarie

2017-03-01

The aim of this literature review was to identify risk factors in addition to antimicrobial treatment for antimicrobial resistance (AMR) occurrence in commensal Escherichia coli in pigs. A variety of studies were searched in 2014 and 2015. Studies identified as potentially relevant were assessed against eligibility criteria such as observation or experiment (no review), presentation of risk factors in addition to (single dosage) antimicrobial use, risk factors for but not resulting from AMR, and the same antimicrobial used and tested. Thirteen articles (nine on observational, four on experimental studies) were finally selected as relevant. It was reported that space allowance, production size/stage, cleanliness, entry of animals and humans into herds, dosage/frequency/route of administration, time span between treatment and sampling date, herd size, distance to another farm, coldness, and season had an impact on AMR occurrence. Associations were shown by one to four studies per factor and differed in magnitude, direction, and level of significance. The risk of bias was unclear in nearly half of the information of observational studies and in most of the information from experimental studies. Further research on the effects of specific management practices is needed to develop well-founded management advice.

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.

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

Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies.

PubMed

Soler, Miguel A; de Marco, Ario; Fortuna, Sara

2016-10-10

Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular recognition. Their small size represents a precious advantage for rational mutagenesis based on modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate mutations by developing a simulation protocol based on all-atom molecular dynamics and whole-molecule docking. The method was tested on two sets of nanobodies characterized experimentally for their biophysical features. One set contained point mutations introduced to humanize a wild type sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae and human hallmarks. The method resulted in accurate scoring approaches to predict experimental yields and enabled to identify the structural modifications induced by mutations. This work is a promising tool for the in silico development of single-domain antibodies and opens the opportunity to customize single functional domains of larger macromolecules.

Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies

NASA Astrophysics Data System (ADS)

Soler, Miguel A.; De Marco, Ario; Fortuna, Sara

2016-10-01

Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular recognition. Their small size represents a precious advantage for rational mutagenesis based on modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate mutations by developing a simulation protocol based on all-atom molecular dynamics and whole-molecule docking. The method was tested on two sets of nanobodies characterized experimentally for their biophysical features. One set contained point mutations introduced to humanize a wild type sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae and human hallmarks. The method resulted in accurate scoring approaches to predict experimental yields and enabled to identify the structural modifications induced by mutations. This work is a promising tool for the in silico development of single-domain antibodies and opens the opportunity to customize single functional domains of larger macromolecules.

The flaws and human harms of animal experimentation.

PubMed

Akhtar, Aysha

2015-10-01

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

Population-Based in Vitro Hazard and Concentration–Response Assessment of Chemicals: The 1000 Genomes High-Throughput Screening Study

PubMed Central

Abdo, Nour; Xia, Menghang; Brown, Chad C.; Kosyk, Oksana; Huang, Ruili; Sakamuru, Srilatha; Zhou, Yi-Hui; Jack, John R.; Gallins, Paul; Xia, Kai; Li, Yun; Chiu, Weihsueh A.; Motsinger-Reif, Alison A.; Austin, Christopher P.; Tice, Raymond R.

2015-01-01

Background: Understanding of human variation in toxicity to environmental chemicals remains limited, so human health risk assessments still largely rely on a generic 10-fold factor (10½ each for toxicokinetics and toxicodynamics) to account for sensitive individuals or subpopulations. Objectives: We tested a hypothesis that population-wide in vitro cytotoxicity screening can rapidly inform both the magnitude of and molecular causes for interindividual toxicodynamic variability. Methods: We used 1,086 lymphoblastoid cell lines from the 1000 Genomes Project, representing nine populations from five continents, to assess variation in cytotoxic response to 179 chemicals. Analysis included assessments of population variation and heritability, and genome-wide association mapping, with attention to phenotypic relevance to human exposures. Results: For about half the tested compounds, cytotoxic response in the 1% most “sensitive” individual occurred at concentrations within a factor of 10½ (i.e., approximately 3) of that in the median individual; however, for some compounds, this factor was > 10. Genetic mapping suggested important roles for variation in membrane and transmembrane genes, with a number of chemicals showing association with SNP rs13120371 in the solute carrier SLC7A11, previously implicated in chemoresistance. Conclusions: This experimental approach fills critical gaps unaddressed by recent large-scale toxicity testing programs, providing quantitative, experimentally based estimates of human toxicodynamic variability, and also testable hypotheses about mechanisms contributing to interindividual variation. Citation: Abdo N, Xia M, Brown CC, Kosyk O, Huang R, Sakamuru S, Zhou YH, Jack JR, Gallins P, Xia K, Li Y, Chiu WA, Motsinger-Reif AA, Austin CP, Tice RR, Rusyn I, Wright FA. 2015. Population-based in vitro hazard and concentration–response assessment of chemicals: the 1000 Genomes high-throughput screening study. Environ Health Perspect 123:458–466; http://dx.doi.org/10.1289/ehp.1408775 PMID:25622337

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.

Plants as models for the study of human pathogenesis.

PubMed

Guttman, David S

2004-05-01

There are many common disease mechanisms used by bacterial pathogens of plants and humans. They use common means of attachment, secretion and genetic regulation. They share many virulence factors, such as extracellular polysaccharides and some type III secreted effectors. Plant and human innate immune systems also share many similarities. Many of these shared bacterial virulence mechanisms are homologous, but even more appear to have independently converged on a common function. This combination of homologous and analogous systems reveals conserved and critical steps in the disease process. Given these similarities, and the many experimental advantages of plant biology, including ease of replication, stringent genetic and reproductive control, and high throughput with low cost, it is proposed that plants would make excellent models for the study of human pathogenesis.

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.

Ising game: Nonequilibrium steady states of resource-allocation systems

NASA Astrophysics Data System (ADS)

Xin, C.; Yang, G.; Huang, J. P.

2017-04-01

Resource-allocation systems are ubiquitous in the human society. But how external fields affect the state of such systems remains poorly explored due to the lack of a suitable model. Because the behavior of spins pursuing energy minimization required by physical laws is similar to that of humans chasing payoff maximization studied in game theory, here we combine the Ising model with the market-directed resource-allocation game, yielding an Ising game. Based on the Ising game, we show theoretical, simulative and experimental evidences for a formula, which offers a clear expression of nonequilibrium steady states (NESSs). Interestingly, the formula also reveals a convertible relationship between the external field (exogenous factor) and resource ratio (endogenous factor), and a class of saturation as the external field exceeds certain limits. This work suggests that the Ising game could be a suitable model for studying external-field effects on resource-allocation systems, and it could provide guidance both for seeking more relations between NESSs and equilibrium states and for regulating human systems by choosing NESSs appropriately.

[Experimental whooping cough of nonhuman primate].

PubMed

Kubrava, D T; Medkova, A Iu; Siniashina, L N; Shevtsova, Z V; Matua, A Z; Kondzharia, I G; Barkaia, V S; Elistratova, Zh V; Karataev, G I; Mikvabia, Z Ia; Gintsburg, A L

2013-01-01

Despite considerable success in study of Bordetella pertussis virulence factors, pathogenesis of whooping cough, duration of B. pertussis bacteria persistence, types and mechanisms of immune response are still keep underinvestigated. It can be explained by the absence ofadequate experimental animal model for pertussis study. Our study estimates clinical and laboratory parameters of whooping cough in non-human primates of the Old World in the process of intranasan infection by virulent B. pertussis bacteria. Also the duration of B. pertussis bacteria persistence in animals was investigated. 14 animal units of 4 species of non-human primates of the Old World were used for intranasal infection. The examination of infect animals included: visual exploration of nasopharynx, thermometry, clinical and biochemical blood analyses, identification ofB. pertussis, using microbiologic and molecular genetic analyses, estimation of innate and adoptive immune factors. The development of infectious process was accompanied by generation of B. pertussis bacteria, catarrhal inflammation of nasopharyngeal mucosa, leucocytosis, hypoglycemia specific for pertussis, and activation of innate and adaptive immunity for all primates regardless of specie were seen. While repeated experimental infection in primates single bacterial colonies were registered during only first week after challenge. It occurs like the absence of inflammation of nasopharyngeal mucosa and the lack of laboratory marks of whooping cough, recorded after first challenge. The evident booster effect of humoral immunity was observed. As a model for investigation of B. pertussis bacteria persistence and immune response against whooping cough we suggest the usage of rhesus macaque as more available to experiments.

Hormone and Cytokine Responses to Repeated Endotoxin Exposures-No Evidence of Endotoxin Tolerance After 5 Weeks in Humans.

PubMed

Rittig, Nikolaj; Thomsen, Henrik H; Bach, Ermina; Jørgensen, Jens Otto L; Møller, Niels

2015-07-01

Endotoxin administrations are used in experimental models of inflammatory disease. Short-term endotoxin tolerance in response to repeated endotoxin exposure is well known, but the duration of endotoxin tolerance in humans remains unknown. The main purpose of this study was to test whether endotoxin tolerance is present in vivo when separating endotoxin exposures with more than 5 weeks, a time span often used between individual investigations in clinical experimental studies. Seventeen healthy young men were exposed twice to Escherichia coli endotoxin. The inflammatory response was calculated as area under the curve between the first and second endotoxin exposures for heart rate, mean arterial blood pressure, temperature, cortisol, tumor necrosis factor α, and interleukin (IL)-1β, IL-6, and IL-10. The median interval between exposures was 90 days (range, 37-244). The ratio between the inflammatory responses during the second and the first endotoxin exposures was 0.89 ± 0.09 (P = 0.28) for tumor necrosis factor α, 0.96 ± 0.07 (P = 0.53) for IL-1β, 0.97 ± 0.11 (P = 0.78) for IL-6, 1.30 ± 0.18 (P = 0.12) for IL-10, and 0.92 ± 0.04 (P = 0.10) for cortisol. Our data do not show evidence of in vivo tolerance to repeated endotoxin exposure when administrations are separated with at least 5 weeks. This observation is important in the planning and interpretation of future experimental endotoxin studies.

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...

Immunohistochemical profile of VEGF, TGF-β and PGE₂ in human pterygium and normal conjunctiva: experimental study and review of the literature.

PubMed

Bianchi, E; Scarinci, F; Grande, C; Plateroti, R; Plateroti, P; Plateroti, A M; Fumagalli, L; Capozzi, P; Feher, J; Artico, M

2012-01-01

Human pterygium is made up of chronic proliferative fibro-vascular tissue growing on the ocular surface. This disease exhibits both degenerative and hyperplastic properties. Some fibroangiogenic factors have recently been shown to play a potential role in fibrovascular diseases via the angiogenesis process. The aim of this study is to evaluate VEGF, TGF-β and PGE₂ expression in the epithelial, endothelial and stromal cells of human pterygium and normal conjunctiva in order to determine whether these factors participate in the development of pterygium. Ten specimens from patients with pterygium and two normal conjunctivas (cadavers) were analyzed by immunohistochemistry using specific antibodies against these growth factors. The technique used was ABC/HRP (Avidin complexed with biotinylated peroxidase). Immunoreactivity of VEGF was significantly increased in the epithelium, vascular endothelium and stromal cells in primary pterygium as compared with normal conjunctiva. A moderate expression of TGF-β in the pterygium was observed in the epithelial and stromal layers. On the contrary, immunolabeling of this growth factor in the human normal conjunctiva was weak. PGE₂ was strongly expressed in the epithelium of patients with pterygium, as in control conjunctival tissues, and the immunolabeling was moderate in the stroma from the same patients. Our results suggest that these growth factors may contribute to the progression of primary pterygium by increasing angiogenesis, thus leading to the formation of new blood vessels from the pre-existing vasculature. We conclude that VEGF, TGF-β and PGE₂ may be potential therapeutic targets in the treatment of this disease although proof of this evidence requires further studies.

Scaling effects in a non-linear electromagnetic energy harvester for wearable sensors

NASA Astrophysics Data System (ADS)

Geisler, M.; Boisseau, S.; Perez, M.; Ait-Ali, I.; Perraud, S.

2016-11-01

In the field of inertial energy harvesters targeting human mechanical energy, the ergonomics of the solutions impose to find the best compromise between dimensions reduction and electrical performance. In this paper, we study the properties of a non-linear electromagnetic generator at different scales, by performing simulations based on an experimentally validated model and real human acceleration recordings. The results display that the output power of the structure is roughly proportional to its scaling factor raised to the power of five, which indicates that this system is more relevant at lengths over a few centimetres.

Conceptions of learning factors in postgraduate health sciences master students: a comparative study with non-health science students and between genders.

PubMed

Campos, Fernando; Sola, Miguel; Santisteban-Espejo, Antonio; Ruyffelaert, Ariane; Campos-Sánchez, Antonio; Garzón, Ingrid; Carriel, Víctor; de Dios Luna-Del-Castillo, Juan; Martin-Piedra, Miguel Ángel; Alaminos, Miguel

2018-06-07

The students' conceptions of learning in postgraduate health science master studies are poorly understood. The aim of this study was to compare the factors influencing conceptions of learning in health sciences and non-health sciences students enrolled in postgraduate master programs in order to obtain information that may be useful for students and for future postgraduate programs. A modified version of the Learning Inventory Conception Questionnaire (COLI) was used to compare students' conception learning factors in 131 students at the beginning of their postgraduate studies in health sciences, experimental sciences, arts and humanities and social sciences. The present study demonstrates that a set of factors may influence conception of learning of health sciences postgraduate students, with learning as gaining information, remembering, using, and understanding information, awareness of duty and social commitment being the most relevant. For these students, learning as a personal change, a process not bound by time or place or even as acquisition of professional competences, are less relevant. According to our results, this profile is not affected by gender differences. Our results show that the overall conceptions of learning differ among students of health sciences and non-health sciences (experimental sciences, arts and humanities and social sciences) master postgraduate programs. These finding are potentially useful to foster the learning process of HS students, because if they are metacognitively aware of their own conception or learning, they will be much better equipped to self-regulate their learning behavior in a postgraduate master program in health sciences.

Human periodontal ligament stem cells secretome from multiple sclerosis patients suppresses NALP3 inflammasome activation in experimental autoimmune encephalomyelitis

PubMed Central

Soundara Rajan, Thangavelu; Giacoppo, Sabrina; Diomede, Francesca; Bramanti, Placido; Trubiani, Oriana; Mazzon, Emanuela

2017-01-01

Research in recent years has largely explored the immunomodulatory effects of mesenchymal stem cells (MSCs) and their secretory products, called “secretome,” in the treatment of neuroinflammatory diseases. Here, we examined whether such immunosuppressive effects might be elicited due to inflammasome inactivation. To this end, we treated experimental autoimmune encephalomyelitis (EAE) mice model of multiple sclerosis (MS) with the conditioned medium or purified exosomes/microvesicles (EMVs) obtained from relapsing-remitting-MS patients human periodontal ligament stem cells (hPDLSCs) and investigated the regulation of NALP3 inflammasome. We noticed enhanced expression of NALP3, Cleaved Caspase 1, interleukin (IL)-1β, and IL-18 in EAE mouse spinal cord. Conversely, hPDLSCs-conditioned medium and EMVs significantly blocked NALP3 inflammasome activation and provided protection from EAE. Reduction in NALP3, Cleaved Caspase 1, IL-1β, and IL-18 level was noticed in conditioned medium and EMVs-treated EAE mice. Pro-inflammatory Toll-like receptor (TLR)-4 and nuclear factor (NF)-κB were elevated in EAE, while hPDLSCs-conditioned medium and EMVs treatment reduced their expression and increased IκB-α expression. Characterization of hPDLSCs-conditioned medium showed substantial level of anti-inflammatory IL-10, transforming growth factor (TGF)-β, and stromal cell–derived factor 1α (SDF-1α). We propose that the immunosuppressive role of hPDLSCs-derived conditioned medium and EMVs in EAE mice may partly attribute to the presence of soluble immunomodulatory factors, NALP3 inflammasome inactivation, and NF-κB reduction. PMID:28764573

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

The pulmonary vasculature--lessons from Tibetans and from rare diseases of oxygen sensing.

PubMed

Frise, Matthew C; Robbins, Peter A

2015-11-01

What is the topic of this review? This review is principally concerned with results from studies of the pulmonary vasculature in humans, particularly in relation to hypoxia and rare diseases that affect oxygen sensing. What advances does it highlight? This review highlights the degree to which the hypoxia-inducible factor (HIF) transcription system influences human pulmonary vascular responses to hypoxia. Upregulation of the HIF pathway augments hypoxic pulmonary vasoconstriction, while alterations to the pathway found in Tibetans are associated with suppression of the progressive increase in pulmonary artery pressure with sustained hypoxia. It also highlights the potential importance of iron, which modulates the HIF pathway, in modifying the pulmonary vascular response to hypoxia. The human pulmonary circulation loses its natural distensibility during sustained hypoxia, leading to pulmonary arterial hypertension and a much higher workload for the right ventricle. The hypoxia-inducible factor (HIF) pathway is implicated in this pulmonary vascular response to continued hypoxia by animal studies, and additionally, by rare human diseases where the pathway is upregulated. However, there are no known human genetic diseases downregulating HIF. Tibetans, though, demonstrate blunted pulmonary vascular responses to sustained hypoxia. This seems to be accounted for by an altered HIF pathway as a consequence of natural selection over a period of many thousands of years lived at high altitude. In addition to genetic differences, iron is another important modulator of HIF pathway function. Experimental work in humans demonstrates that manipulation of iron stores can influence the behaviour of the pulmonary circulation during hypoxia, in ways analogous to that seen in Tibetans and patients with rare diseases that affect oxygen sensing. The importance of physiological differences in iron bioavailability in modulating hypoxic pulmonary vasoconstriction in health and disease is yet to be established. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Seven Experiment Designs Addressing Problems of Safety and Capacity on Two-Lane Rural Highways : Volume 3. Experimental Design to Evaluate MUTCD and Other Traffic Controls for Highway Construction and Maintenance Operations on Two-Lane Highways

DOT National Transportation Integrated Search

1996-11-01

The purpose of Task A was to conduct a literature review of human factors-applicable articles associated with Advanced Traveler Information Systems (ATIS) and ATIS-related commercial vehicle operations (CVO) systems. Specifically, Task A was to asses...

Annotated Bibliography on Human Factors in Software Development

DTIC Science & Technology

1979-06-01

Information Sciences, 1976, 5, 123-143. Shneiderman. B., Mayer, R., McKay, D., & Heller, P. Experimental investi- gations of the utility of flowcharts ...REPRESENTATIONS OF PROGRAMS, PRODUCTION SCHEDULIWG, AUTOMATIC FLOWCHARTING , -MAPFSR,- AND CERTIFICATION TECHNIQUES. EXAMPLES OF HOW THSSE AIOS AND METHODS CAN...PROCiSS ARE PRESENTED, AND THE ANALYSIS Of THREE SPECIFIC MODELS IS REVIEWED. (0)SP, 5R. . 65 FLOWCHARTING CHAPIN, N. FLOWCHARTING WITH THE ANSI

HAMLET -Human Model MATROSHKA for Radiation Exposure Determination of Astronauts -Current status and results

NASA Astrophysics Data System (ADS)

Reitz, Guenther; Berger, Thomas; Bilski, Pawel; Burmeister, Soenke; Labrenz, Johannes; Hager, Luke; Palfalvi, Jozsef K.; Hajek, Michael; Puchalska, Monika; Sihver, Lembit

The exploration of space as seen in specific projects from the European Space Agency (ESA) acts as groundwork for human long duration space missions. One of the main constraints for long duration human missions is radiation. The radiation load on astronauts and cosmonauts in space (as for the ISS) is a factor of 100 higher than the natural radiation on Earth and will further increase should humans travel to Mars. In preparation for long duration space missions it is important to evaluate the impact of space radiation in order to secure the safety of the astronauts and minimize their radiation risks. To determine the radiation risk on humans one has to measure the radiation doses to radiosensitive organs within the human body. One way to approach this is the ESA facility MATROSHKA (MTR), under the scientific and project lead of DLR. It is dedicated to determining the radiation load on astronauts within and outside the International Space Station (ISS), and was launched in January 2004. MTR is currently preparing for its fourth experimental phase inside the Japanese Experimental Module (JEM) in summer 2010. MTR, which mimics a human head and torso, is an anthropomorphic phantom containing over 6000 radiation detectors to determine the depth dose and organ dose distribution in the body. It is the largest international research initiative ever performed in the field of space dosimetry and combines the expertise of leading research institutions around the world, thereby generating a huge pool of data of potentially immense value for research. Aiming at optimal scientific exploitation, the FP7 project HAMLET aims to process and compile the data acquired individually by the participating laboratories of the MATROSHKA experiment. Based on experimental input from the MATROSHKA experiment phases as well as on radiation transport calculations, a three-dimensional model for the distribution of radiation dose in an astronaut's body will be built up. The scientific achievements contribute essentially to radiation risk estimations for future interplanetary space exploration by humans, putting them on a solid experimental and theoretical basis. The talk will give an overview of the current status of the MATROSHKA data evaluation and results and comparisons of the first three MTR experimental phases (MTR-1, 2A and 2B). The HAMLET project is funded by the European Commission under the EUs Seventh Frame-work Programme (FP7) under Project Nr: 218817 and coordinated by the German Aerospace Center (DLR) http://www-fp7-hamlet.eu

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...

[Soy isoflavones and human health: breast cancer and puberty timing].

PubMed

Valladares, Luis; Garrido, Argelia; Sierralta, Walter

2012-04-01

Accumulated exposure to high levels of estrogen is associated with an increased incidence of breast cancer. Thus, factors such as early puberty, late menopause and hormone replacement therapy are considered to be risk factors, whereas early childbirth, breastfeeding and puberty at a later age are known to consistently decrease the lifetime breast cancer risk. Epidemiological studies suggest that consumption of isoflavones correlates with a lower incidence of breast cancer. Data from human intervention studies show that the effects of isoflavones on early breast cancer markers differ between pre- and post-menopausal women. The reports from experimental animals (rats and mice) on mammary tumors are variable. These results taken together with heterogeneous outcomes of human interventions, have led to a controversy surrounding the intake of isoflavones to reduce breast cancer risk. This review summarizes recent studies and analyzes factors that could explain the variability of results. In mammary tissue, from the cellular endocrine viewpoint, we analyze the effect of isoflavones on the estrogen receptor and their capacity to act as agonists or antagonists. On the issue of puberty timing, we analyze the mechanisms by which girls, but not boys, with higher prepuberal isoflavone intakes appear to enter puberty at a later age.

A new paradigm for transcription factor TFIIB functionality

PubMed Central

Gelev, Vladimir; Zabolotny, Janice M.; Lange, Martin; Hiromura, Makoto; Yoo, Sang Wook; Orlando, Joseph S.; Kushnir, Anna; Horikoshi, Nobuo; Paquet, Eric; Bachvarov, Dimcho; Schaffer, Priscilla A.; Usheva, Anny

2014-01-01

Experimental and bioinformatic studies of transcription initiation by RNA polymerase II (RNAP2) have revealed a mechanism of RNAP2 transcription initiation less uniform across gene promoters than initially thought. However, the general transcription factor TFIIB is presumed to be universally required for RNAP2 transcription initiation. Based on bioinformatic analysis of data and effects of TFIIB knockdown in primary and transformed cell lines on cellular functionality and global gene expression, we report that TFIIB is dispensable for transcription of many human promoters, but is essential for herpes simplex virus-1 (HSV-1) gene transcription and replication. We report a novel cell cycle TFIIB regulation and localization of the acetylated TFIIB variant on the transcriptionally silent mitotic chromatids. Taken together, these results establish a new paradigm for TFIIB functionality in human gene expression, which when downregulated has potent anti-viral effects. PMID:24441171

32-channel 3 Tesla receive-only phased-array head coil with soccer-ball element geometry.

PubMed

Wiggins, G C; Triantafyllou, C; Potthast, A; Reykowski, A; Nittka, M; Wald, L L

2006-07-01

A 32-channel 3T receive-only phased-array head coil was developed for human brain imaging. The helmet-shaped array was designed to closely fit the head with individual overlapping circular elements arranged in patterns of hexagonal and pentagonal symmetry similar to that of a soccer ball. The signal-to-noise ratio (SNR) and noise amplification (g-factor) in accelerated imaging applications were quantitatively evaluated in phantom and human images and compared with commercially available head coils. The 32-channel coil showed SNR gains of up to 3.5-fold in the cortex and 1.4-fold in the corpus callosum compared to a (larger) commercial eight-channel head coil. The experimentally measured g-factor performance of the helmet array showed significant improvement compared to the eight-channel array (peak g-factor 59% and 26% of the eight-channel values for four- and fivefold acceleration). The performance of the arrays is demonstrated in high-resolution and highly accelerated brain images. Copyright (c) 2006 Wiley-Liss, Inc.

Use of Human Modeling Simulation Software in the Task Analysis of the Environmental Control and Life Support System Component Installation Procedures

NASA Technical Reports Server (NTRS)

Estes, Samantha; Parker, Nelson C. (Technical Monitor)

2001-01-01

Virtual reality and simulation applications are becoming widespread in human task analysis. These programs have many benefits for the Human Factors Engineering field. Not only do creating and using virtual environments for human engineering analyses save money and time, this approach also promotes user experimentation and provides increased quality of analyses. This paper explains the human engineering task analysis performed on the Environmental Control and Life Support System (ECLSS) space station rack and its Distillation Assembly (DA) subsystem using EAI's human modeling simulation software, Jack. When installed on the International Space Station (ISS), ECLSS will provide the life and environment support needed to adequately sustain crew life. The DA is an Orbital Replaceable Unit (ORU) that provides means of wastewater (primarily urine from flight crew and experimental animals) reclamation. Jack was used to create a model of the weightless environment of the ISS Node 3, where the ECLSS is housed. Computer aided drawings of the ECLSS rack and DA system were also brought into the environment. Anthropometric models of a 95th percentile male and 5th percentile female were used to examine the human interfaces encountered during various ECLSS and DA tasks. The results of the task analyses were used in suggesting modifications to hardware and crew task procedures to improve accessibility, conserve crew time, and add convenience for the crew. This paper will address some of those suggested modifications and the method of presenting final analyses for requirements verification.

Surfactant protein A is expressed in the central nervous system of rats with experimental autoimmune encephalomyelitis, and suppresses inflammation in human astrocytes and microglia

PubMed Central

Yang, Xue; Yan, Jun; Feng, Juan

2017-01-01

The collectin surfactant protein-A (SP-A), a potent host defense molecule, is well recognized for its role in the maintenance of pulmonary homeostasis and the modulation of inflammatory responses. While previous studies have detected SP-A in numerous extrapulmonary tissues, there is still a lack of information regarding its expression in central nervous system (CNS) and potential effects in neuroinflammatory diseases, such as multiple sclerosis (MS). The present study used experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS, to investigate the expression of SP-A in the CNS at different stages of disease progression. In addition, in vitro experiments with lipopolysaccharide (LPS)-stimulated human astrocytes and microglia were performed to investigate the potential role of SP-A in the modulation of CNS inflammatory responses. The results of the present study demonstrated widespread distribution of SP-A in the rat CNS, and also identified specific expression patterns of SP-A at different stages of EAE. In vitro, the current study revealed that treatment of human astrocytes and microglia with LPS promoted SP-A expression in a dose-dependent manner. Furthermore, exogenous SP-A protein significantly decreased Toll-like receptor 4 and nuclear factor-κB expression, and reduced interleukin-1β and tumor necrosis factor-α levels. The results of the current study indicate a potential role for SP-A in the modulation of CNS inflammatory responses. PMID:28393255

Disentangling prenatal and inherited influences in humans with an experimental design.

PubMed

Rice, Frances; Harold, Gordon T; Boivin, Jacky; Hay, Dale F; van den Bree, Marianne; Thapar, Anita

2009-02-17

Exposure to adversity in utero at a sensitive period of development can bring about physiological, structural, and metabolic changes in the fetus that affect later development and behavior. However, the link between prenatal environment and offspring outcomes could also arise and confound because of the relation between maternal and offspring genomes. As human studies cannot randomly assign offspring to prenatal conditions, it is difficult to test whether in utero events have true causal effects on offspring outcomes. We used an unusual approach to overcome this difficulty whereby pregnant mothers are either biologically unrelated or related to their child as a result of in vitro fertilization (IVF). In this sample, prenatal smoking reduces offspring birth weight in both unrelated and related offspring, consistent with effects arising through prenatal mechanisms independent of the relation between the maternal and offspring genomes. In contrast, the association between prenatal smoking and offspring antisocial behavior depended on inherited factors because association was only present in related mothers and offspring. The results demonstrate that this unusual prenatal cross-fostering design is feasible and informative for disentangling inherited and prenatal effects on human health and behavior. Disentangling these different effects is invaluable for pinpointing markers of prenatal adversity that have a causal effect on offspring outcomes. The origins of behavior and many common complex disorders may begin in early life, therefore this experimental design could pave the way for identifying prenatal factors that affect behavior in future generations.

Neuroprotective effects of placenta-derived mesenchymal stromal cells in a rat model of experimental autoimmune encephalomyelitis.

PubMed

Selim, Assmaa O; Selim, Sally A; Shalaby, Sally M; Mosaad, Hala; Saber, Taisir

2016-09-01

Current therapies for multiple sclerosis (MS) are largely palliative, not curative. Mesenchymal stromal cells (MSCs) harbor regenerative and immunosuppressive functions, indicating a potential therapy for MS. A preparation of MSCs derived from full-term human placenta (PDMSCs) is a new approach in the treatment of patients with MS. This study aimed to rule out the possible therapy by PDMSCs in experimental autoimmune encephalomyelitis (EAE), a rat model of MS. Thirty-five female Wistar rats were classified into the following groups: I, control; II, EAE untreated; III and IV, EAE treated with phosphate-buffered saline (PBS) at 9 and 16 days post-immunization (dpi), respectively; V and VI, EAE treated with PDMSCs at 9 and 16 dpi, respectively. Intravenous administration of PDMSCs at 9 or 16 dpi significantly ameliorated the disease course, decreasing brain inflammation and degenerating neurons. A reduction of axonal damage as well as an increase of oligodendrocyte precursors were recorded. Moreover, there was an engraftment of the PDMSCs into the brain tissue. Human brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin 3 (NTF3) were significantly expressed in brains of rats treated by PDMSCs. Human PDMSCs have demonstrated striking therapeutic effects when delivered at the onset or at the peak of the disease. PDMSCs have direct neurotrophic support after their engraftment within the lesion through expression of the neurotrophins. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Using a Low Cost Flight Simulation Environment for Interdisciplinary Education

NASA Technical Reports Server (NTRS)

Khan, M. Javed; Rossi, Marcia; ALi, Syed F.

2004-01-01

A multi-disciplinary and inter-disciplinary education is increasingly being emphasized for engineering undergraduates. However, often the focus is on interaction between engineering disciplines. This paper discusses the experience at Tuskegee University in providing interdisciplinary research experiences for undergraduate students in both Aerospace Engineering and Psychology through the utilization of a low cost flight simulation environment. The environment, which is pc-based, runs a low-cost of-the-shelf software and is configured for multiple out-of-the-window views and a synthetic heads down display with joystick, rudder and throttle controls. While the environment is being utilized to investigate and evaluate various strategies for training novice pilots, students were involved to provide them with experience in conducting such interdisciplinary research. On the global inter-disciplinary level these experiences included developing experimental designs and research protocols, consideration of human participant ethical issues, and planning and executing the research studies. During the planning phase students were apprised of the limitations of the software in its basic form and the enhancements desired to investigate human factors issues. A number of enhancements to the flight environment were then undertaken, from creating Excel macros for determining the performance of the 'pilots', to interacting with the software to provide various audio/video cues based on the experimental protocol. These enhancements involved understanding the flight model and performance, stability & control issues. Throughout this process, discussions of data analysis included a focus from a human factors perspective as well as an engineering point of view.

Towards understanding addiction factors of mobile devices: An eye tracking study on effect of screen size.

PubMed

Wibirama, Sunu; Nugroho, Hanung A

2017-07-01

Mobile devices addiction has been an important research topic in cognitive science, mental health, and human-machine interaction. Previous works observed mobile device addiction by logging mobile devices activity. Although immersion has been linked as a significant predictor of video game addiction, investigation on addiction factors of mobile device with behavioral measurement has never been done before. In this research, we demonstrated the usage of eye tracking to observe effect of screen size on experience of immersion. We compared subjective judgment with eye movements analysis. Non-parametric analysis on immersion score shows that screen size affects experience of immersion (p<;0.05). Furthermore, our experimental results suggest that fixational eye movements may be used as an indicator for future investigation of mobile devices addiction. Our experimental results are also useful to develop a guideline as well as intervention strategy to deal with smartphone addiction.

Gut Microbiota in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis: Current Applications and Future Perspectives

PubMed Central

Lang, Yue

2018-01-01

The gut environment and gut microbiome dysbiosis have been demonstrated to significantly influence a range of disorders in humans, including obesity, diabetes, rheumatoid arthritis, and multiple sclerosis (MS). MS is an autoimmune disease affecting the central nervous system (CNS). The etiology of MS is not clear, and it should involve both genetic and extrinsic factors. The extrinsic factors responsible for predisposition to MS remain elusive. Recent studies on MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have found that gastrointestinal microbiota may play an important role in the pathogenesis of MS/EAE. Thus, gut microbiome adjustment may be a future direction of treatment in MS. In this review, we discuss the characteristics of the gut microbiota, the connection between the brain and the gut, and the changes in gut microbiota in MS/EAE, and we explore the possibility of applying microbiota therapies in patients with MS. PMID:29805314

Optimizing Associative Experimental Design for Protein Crystallization Screening

PubMed Central

Dinç, Imren; Pusey, Marc L.; Aygün, Ramazan S.

2016-01-01

The goal of protein crystallization screening is the determination of the main factors of importance to crystallizing the protein under investigation. One of the major issues about determining these factors is that screening is often expanded to many hundreds or thousands of conditions to maximize combinatorial chemical space coverage for maximizing the chances of a successful (crystalline) outcome. In this paper, we propose an experimental design method called “Associative Experimental Design (AED)” and an optimization method includes eliminating prohibited combinations and prioritizing reagents based on AED analysis of results from protein crystallization experiments. AED generates candidate cocktails based on these initial screening results. These results are analyzed to determine those screening factors in chemical space that are most likely to lead to higher scoring outcomes, crystals. We have tested AED on three proteins derived from the hyperthermophile Thermococcus thioreducens, and we applied an optimization method to these proteins. Our AED method generated novel cocktails (count provided in parentheses) leading to crystals for three proteins as follows: Nucleoside diphosphate kinase (4), HAD superfamily hydrolase (2), Nucleoside kinase (1). After getting promising results, we have tested our optimization method on four different proteins. The AED method with optimization yielded 4, 3, and 20 crystalline conditions for holo Human Transferrin, archaeal exosome protein, and Nucleoside diphosphate kinase, respectively. PMID:26955046

Design and development of a novel strain gauge automatic pasting device for mini split Hopkinson pressure bar

NASA Astrophysics Data System (ADS)

Huang, Wenkai; Huan, Shi; He, Junfeng; Jiang, Jichang

2018-03-01

In a split Hopkinson pressure bar (SHPB) experiment, the pasting quality of strain gauges will directly affect the accuracy of the measurement results. The traditional method of pasting the strain gauges is done manually by the experimenter. In the process of pasting, it is easy to shift or twist the strain gauge, and the experimental results are greatly affected by human factors. In this paper, a novel type automatic pasting device for strain gauges is designed and developed, which can be used to accurately and rapidly paste the strain gauges. The paste quality is reliable, and it can guarantee the consistency of SHPB experimental measurement. We found that a clamping force of 74 N achieved a success rate of 97%, whilst ensuring good adhesion.

Cytokines in human milk.

PubMed

Garofalo, Roberto

2010-02-01

Epidemiologic studies conducted in the past 30 years to investigate the protective functions of human milk strongly support the notion that breastfeeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult because of its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. However, a host of bioactive substances, including hormones, growth factors, and immunological factors such as cytokines, have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of immune system. Several different cytokines and chemokines have been discovered in human milk in the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system. Copyright 2010. Published by Mosby, Inc.

Differences in problem-solving between canid populations: Do domestication and lifetime experience affect persistence?

PubMed

Brubaker, Lauren; Dasgupta, Sandipan; Bhattacharjee, Debottam; Bhadra, Anindita; Udell, Monique A R

2017-07-01

Past research has suggested that a variety of factors, phylogenetic and ontogenetic, play a role in how canines behave during problem-solving tasks and the degree to which the presence of a human influences their problem-solving behaviour. While comparisons between socialized wolves and domestic dogs have commonly been used to tease apart these predictive factors, in many cases a single dog population, often pets, have been used for these comparisons. Less is understood about how different populations of dogs may behave when compared with wolves, or with each other, during an independent problem-solving task. This experiment compared the independent persistence of four populations of canines (two groups of pet domestic dogs, a group of free-ranging domestic dogs, and human-socialized wolves) on an independent problem-solving task in the presence of an on looking human. Results showed that wolves persisted the most at the task while free-ranging dogs persisted the least. Free-ranging dogs gazed at the human experimenter for the longest durations during the task. While further research is needed to understand why these differences exist, this study demonstrates that dogs, even those living outside human homes as scavengers, show comparatively low levels of persistence when confronted with a solvable task in the presence of a human as well as significantly greater duration of human-directed gaze when compared with wolves.

Epigenesis of behavioural lateralization in humans and other animals

PubMed Central

Schaafsma, S.M.; Riedstra, B.J.; Pfannkuche, K.A.; Bouma, A.; Groothuis, T.G.G.

2008-01-01

Despite several decades of research, the epigenesis of behavioural and brain lateralization is still elusive, although its knowledge is important in understanding developmental plasticity, function and evolution of lateralization, and its relationship with developmental disorders. Over the last decades, it has become clear that behavioural lateralization is not restricted to humans, but a fundamental principle in the organization of behaviour in vertebrates. This has opened the possibility of extending descriptive studies on human lateralization with descriptive and experimental studies on other vertebrate species. In this review, we therefore explore the evidence for the role of genes and environment on behavioural lateralization in humans and other animals. First, we discuss the predominant genetic models for human handedness, and conclude that their explanatory power alone is not sufficient, leaving, together with ambiguous results from adoption studies and selection experiments in animals, ample opportunity for a role of environmental factors. Next, we discuss the potential influence of such factors, including perinatal asymmetrical perception induced by asymmetrical head position or parental care, and social modulation, both in humans and other vertebrates, presenting some evidence from our own work on the domestic chick. We conclude that both perinatal asymmetrical perception and later social modulation are likely candidates in influencing the degree or strength of lateralization in both humans and other vertebrates. However, in most cases unequivocal evidence for this is lacking and we will point out further avenues for research. PMID:19064352

[Factors behind action, emotion, and decision making].

PubMed

Watanabe, Katsumi

2009-12-01

Human actions, emotions, and decision making are products of complex interactions between explicit and implicit processes at various levels of spatial and temporal scales. Although it may not be possible to obtain to experimental data for all the complexity of human behavioral and emotional processes in our everyday life, recent studies have investigated the effects of social contexts on actions, emotions, and decision making; these studies include those in the fields of experimental psychology, cognitive science, and neuroscience. In this paper, we review several empirical studies that exemplify how our actions, social emotions, and decision making are influenced by the presence of implicit external, rather than internal factors, particularly by presence of other individuals. The following are the main principles identified. (1) Unconscious behavioral contagion: Individuals tend to mimic others' actions. This tendency occurs unconsciously even when the observed and the to-be-executed movements are unrelated at various levels and aspects of behaviors (e. g., behavioral tempo and speed). (2) Neural substrates of social emotions: Various social emotions, including admiration, compassion, envy, and schadenfreude, are represented in neuronal networks that are similar to those of basic emotional processes. (3) Evasive nature of human decision making: Individuals tend to overrate their own subjective impression of and emotional reaction in forecasting affective reaction to events in the future, even though the predictive power of information from peer group is much larger in this regard. Individuals are seldom aware of the dissociation between their intended choice and excuted actions and are willing to give elaborate explanations for the choices they, in fact, did not make. Using these empirical examples, I will illustrate the considerable influences of implicit, unconscious processes on human actions, emotions, and decision making.

Generation of human cortical neurons from a new immortal fetal neural stem cell line.

PubMed

Cacci, E; Villa, A; Parmar, M; Cavallaro, M; Mandahl, N; Lindvall, O; Martinez-Serrano, A; Kokaia, Z

2007-02-01

Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markers like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were dramatically reduced, and the hc-NSCs differentiated into glia and neurons (mostly glutamatergic and GABAergic, as well as tyrosine hydroxylase-positive, presumably dopaminergic neurons). RT-PCR analysis showed that the hc-NSCs retained expression of Pax6, Emx2 and Neurogenin2, which are genes associated with regionalization and cell commitment in cortical precursors during brain development. Our data indicate that this hc-NSC line could be useful for exploring the potential of human NSCs to replace dead or damaged cortical cells in animal models of acute and chronic neurodegenerative diseases. Taking advantage of its clonality and homogeneity, this cell line will also be a valuable experimental tool to study the regulatory role of intrinsic and extrinsic factors in human NSC biology.

Lifestyle impacts on the aging associated expression of biomarkers of DNA damage and telomere dysfunction in human blood

PubMed Central

Song, Zhangfa; von Figura, Guido; Liu, Yan; Kraus, Johann M.; Torrice, Chad; Dillon, Patric; Rudolph-Watabe, Masami; Ju, Zhenyu; Kestler, Hans A.; Sanoff, Hanna; Rudolph, K. Lenhard

2010-01-01

Summary Cellular aging is characterised by telomere shortening, which can lead to uncapping of chromosome ends (telomere dysfunction) and that activation of DNA damage responses. There is some evidence the DNA damage accumulates during human aging and that lifestyle factors contribute to the accumulation of DNA damage. Recent studies have identified a set of serum markers that are induced by telomere dysfunction and DNA damage and these markers showed an increased expression in blood during human aging. Here, we investigated the influence of lifestyle factors (such as exercise, smoking, body mass) on the aging associated expression of serum markers of DNA damage (CRAMP, EF-1α, Stathmin, n-acetyl-glucosaminidase, and chitinase) in comparison to other described markers of cellular aging (p16INK4a upregulation and telomere shortening) in human peripheral blood. The study shows that lifestyle factors have an age-independent impact on the expression level of biomarkers of DNA damage. Smoking and increased body mass indices were associated with elevated levels of biomarkers of DNA damage independent of the age of the individuals. In contrast, exercise was associated with an age-independent reduction in the expression of biomarkers of DNA damage in human blood. The expression of biomarkers of DNA damage correlated positively with p16INK4a expression and negatively with telomere length in peripheral blood T-lymphocytes. Together, these data provide experimental evidence that both aging and lifestyle impact on the accumulation of DNA damage during human aging. PMID:20560902

Long-term effects of prenatal x-ray of human females. II. Growth and development.

PubMed

Meyer, M B; Tonascia, J

1981-09-01

Experimental studies and studies of survivors of in-utero exposure to atomic bomb blasts have shown significant stunting of growth and mental retardation following these exposures. Central nervous system damage following very low doses of x-ray at around the time of birth has also been observed in experimental animals. This long term follow-up studies of 1458 human females exposed in utero to diagnostic x-rays and of 1458 matched unexposed controls studied in Baltimore, Maryland, included measurements of height, weight and school achievement. Women who had been exposed to x-rays in utero were significantly shorter in their mid-twenties than were their matched, unexposed controls, even after adjustment for other social and economic factors. However, additional follow-up revealed that mothers of exposed women were also shorter than the control mothers. Short stature appeared to be a selective factor for x-ray during pregnancy (mostly pelvimetry, 1947-1952). Mothers' and daughters' heights were similarly correctly among exposed and control mother-daughter pairs, suggesting that the height differences between exposed daughters and their controls were due to these selective factor rather than to any direct effect of radiation on growth. Exposed women reported poorer school achievement than control women. However, except for a higher proportion of exposed women leaving school because of pregnancy, these measurements were no longer significantly different when rates were simultaneously adjusted for socioeconomic differences between exposed and control women.

Short-Lived Human Umbilical Cord-Blood-Derived Neural Stem Cells Influence the Endogenous Secretome and Increase the Number of Endogenous Neural Progenitors in a Rat Model of Lacunar Stroke.

PubMed

Jablonska, Anna; Drela, Katarzyna; Wojcik-Stanaszek, Luiza; Janowski, Miroslaw; Zalewska, Teresa; Lukomska, Barbara

2016-11-01

Stroke is the leading cause of severe disability, and lacunar stroke is related to cognitive decline and hemiparesis. There is no effective treatment for the majority of patients with stroke. Thus, stem cell-based regenerative medicine has drawn a growing body of attention due to the capabilities for trophic factor expression and neurogenesis enhancement. Moreover, it was shown in an experimental autoimmune encephalomyelitis (EAE) model that even short-lived stem cells can be therapeutic, and we have previously observed that phenomenon indirectly. Here, in a rat model of lacunar stroke, we investigated the molecular mechanisms underlying the positive therapeutic effects of short-lived human umbilical cord-blood-derived neural stem cells (HUCB-NSCs) through the distinct measurement of exogenous human and endogenous rat trophic factors. We have also evaluated neurogenesis and metalloproteinase activity as cellular components of therapeutic activity. As expected, we observed an increased proliferation and migration of progenitors, as well as metalloproteinase activity up to 14 days post transplantation. These changes were most prominent at the 7-day time point when we observed 30 % increases in the number of bromodeoxyuridine (BrdU)-positive cells in HUCB-NSC transplanted animals. The expression of human trophic factors was present until 7 days post transplantation, which correlated well with the survival of the human graft. For these 7 days, the level of messenger RNA (mRNA) in the analyzed trophic factors was from 300-fold for CNTF to 10,000-fold for IGF, much higher compared to constitutive expression in HUCB-NSCs in vitro. What is interesting is that there was no increase in the expression of rat trophic factors during the human graft survival, compared to that in non-transplanted animals. However, there was a prolongation of a period of increased trophic expression until 14 days post transplantation, while, in non-transplanted animals, there was a significant drop in rat trophic expression at that time point. We conclude that the positive therapeutic effect of short-lived stem cells may be related to the net increase in the amount of trophic factors (rat + human) until graft death and to the prolonged increase in rat trophic factor expression subsequently.

Hypermedia Applications for Army Installation Master Planning

DTIC Science & Technology

1993-01-01

expertise were evaluated, and this firm was selected because it had previously developed a prototype system for St. Louis. MO, municipal planners, and wai...display of information are supported by the experimental performance and memory evaluations on the relative value of pictures and text in conveying...lnfornmation: Performance and Memory Evaluations," Proceedings of the Human Factors Society 30th Annual Meeting (1986). pp 1269-1272. 12 m m4 Access

Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization.

PubMed

Lee, Jung Eun; Kim, Koung Li; Kim, Danbi; Yeo, Yeongju; Han, Hyounkoo; Kim, Myung Goo; Kim, Sun Hwa; Kim, Hyuncheol; Jeong, Ji Hoon; Suh, Wonhee

2017-01-01

Pathological angiogenesis is one of the major symptoms of severe ocular diseases, including corneal neovascularization. The blockade of vascular endothelial growth factor (VEGF) action has been recognized as an efficient strategy for treating corneal neovascularization. In this study, we aimed to investigate whether nanoparticle-based delivery of apatinib, a novel and selective inhibitor of VEGF receptor 2, inhibits VEGF-mediated angiogenesis and suppresses experimental corneal neovascularization. Water-insoluble apatinib was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro angiogenesis assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles potently inhibited VEGF-induced tube formation, scratch wounding migration, and proliferation of human endothelial cells. In a rat model of alkali burn injury-induced corneal neovascularization, a subconjunctival injection of Apa-HSA-PEG nanoparticles induced a significant decrease in neovascularization compared to that observed with an injection of free apatinib solution or phosphate-buffered saline. An in vivo distribution study using HSA-PEG nanoparticles loaded with fluorescent hydrophobic model drugs revealed the presence of a substantial number of nanoparticles in the corneal stroma within 24 h after injection. These in vitro and in vivo results demonstrate that apatinib-loaded nanoparticles may be promising for the prevention and treatment of corneal neovascularization-related ocular disorders.

Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization

PubMed Central

Lee, Jung Eun; Kim, Koung Li; Kim, Danbi; Yeo, Yeongju; Han, Hyounkoo; Kim, Myung Goo; Kim, Sun Hwa; Kim, Hyuncheol; Jeong, Ji Hoon; Suh, Wonhee

2017-01-01

Pathological angiogenesis is one of the major symptoms of severe ocular diseases, including corneal neovascularization. The blockade of vascular endothelial growth factor (VEGF) action has been recognized as an efficient strategy for treating corneal neovascularization. In this study, we aimed to investigate whether nanoparticle-based delivery of apatinib, a novel and selective inhibitor of VEGF receptor 2, inhibits VEGF-mediated angiogenesis and suppresses experimental corneal neovascularization. Water-insoluble apatinib was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro angiogenesis assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles potently inhibited VEGF-induced tube formation, scratch wounding migration, and proliferation of human endothelial cells. In a rat model of alkali burn injury-induced corneal neovascularization, a subconjunctival injection of Apa-HSA-PEG nanoparticles induced a significant decrease in neovascularization compared to that observed with an injection of free apatinib solution or phosphate-buffered saline. An in vivo distribution study using HSA-PEG nanoparticles loaded with fluorescent hydrophobic model drugs revealed the presence of a substantial number of nanoparticles in the corneal stroma within 24 h after injection. These in vitro and in vivo results demonstrate that apatinib-loaded nanoparticles may be promising for the prevention and treatment of corneal neovascularization-related ocular disorders. PMID:28740387

Chimeric Vaccine Stimulation of Human Dendritic Cell Indoleamine 2, 3-Dioxygenase Occurs via the Non-Canonical NF-κB Pathway

PubMed Central

Kim, Nan-Sun; Mbongue, Jacques C.; Nicholas, Dequina A.; Esebanmen, Grace E.; Unternaehrer, Juli J.; Firek, Anthony F.; Langridge, William H. R.

2016-01-01

A chimeric protein vaccine composed of the cholera toxin B subunit fused to proinsulin (CTB-INS) was shown to suppress type 1 diabetes onset in NOD mice and upregulate biosynthesis of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1) in human dendritic cells (DCs). Here we demonstrate siRNA inhibition of the NF-κB-inducing kinase (NIK) suppresses vaccine-induced IDO1 biosynthesis as well as IKKα phosphorylation. Chromatin immunoprecipitation (ChIP) analysis of CTB-INS inoculated DCs showed that RelB bound to NF-κB consensus sequences in the IDO1 promoter, suggesting vaccine stimulation of the non-canonical NF-κB pathway activates IDO1 expression in vivo. The addition of Tumor Necrosis Factor Associated Factors (TRAF) TRAF 2, 3 and TRAF6 blocking peptides to vaccine inoculated DCs was shown to inhibit IDO1 biosynthesis. This experimental outcome suggests vaccine activation of the TNFR super-family receptor pathway leads to upregulation of IDO1 biosynthesis in CTB-INS inoculated dendritic cells. Together, our experimental data suggest the CTB-INS vaccine uses a TNFR-dependent signaling pathway of the non-canonical NF-κB signaling pathway resulting in suppression of dendritic cell mediated type 1 diabetes autoimmunity. PMID:26881431

Beam and tissue factors affecting Cherenkov image intensity for quantitative entrance and exit dosimetry on human tissue

PubMed Central

Zhang, Rongxiao; Glaser, Adam K.; Andreozzi, Jacqueline; Jiang, Shudong; Jarvis, Lesley A.; Gladstone, David J.; Pogue, Brian W.

2017-01-01

This study’s goal was to determine how Cherenkov radiation emission observed in radiotherapy is affected by predictable factors expected in patient imaging. Factors such as tissue optical properties, radiation beam properties, thickness of tissues, entrance/exit geometry, curved surface effects, curvature and imaging angles were investigated through Monte Carlo simulations. The largest physical cause of variation of the correlation factor between of Cherenkov emission and dose was the entrance/exit geometry (~50%). The largest human tissue effect was from different optical properties (~45%). Beyond these, clinical beam energy varies the correlation factor significantly (~20% for x-ray beams), followed by curved surfaces (~15% for x-ray beams and ~8% for electron beams), and finally, the effect of field size (~5% for x-ray beams). Other investigated factors which caused variations less than 5% were tissue thicknesses and source to surface distance. The effect of non-Lambertian emission was negligible for imaging angles smaller than 60 degrees. The spectrum of Cherenkov emission tends to blue-shift along the curved surface. A simple normalization approach based on the reflectance image was experimentally validated by imaging a range of tissue phantoms, as a first order correction for different tissue optical properties. PMID:27507213

Clinical application of neurotrophic factors: the potential for primary auditory neuron protection

PubMed Central

Gillespie, Lisa N.; Shepherd, Robert K.

2007-01-01

Sensorineural hearing loss, as a result of damage to or destruction of the sensory epithelia within the cochlea, is a common cause of deafness. The subsequent degeneration of the neural elements within the inner ear may impinge upon the efficacy of the cochlear implant. Experimental studies have demonstrated that neurotrophic factors can prevent this degeneration in animal models of deafness, and can even provide functional benefits. Neurotrophic factor therapy may, therefore, provide similar protective effects in humans, resulting in improved speech perception outcomes among cochlear implant patients. There are, however, numerous issues pertaining to delivery techniques and treatment regimes which need to be addressed prior to any clinical application. This review considers these issues in view of the potential therapeutic application of neurotrophic factors within the auditory system. PMID:16262651

DSN human factors project

NASA Technical Reports Server (NTRS)

Chafin, R. L.; Martin, T. H.

1980-01-01

The project plan was to hold focus groups to identify the factors influencing the ease of use characteristics of software and to bond the problem. A questionnaire survey was conducted to evaluate those factors which were more appropriately measured with that method. The performance oriented factors were analyzed and relationships hypothesized. The hypotheses were put to test in the experimental phase of the project. In summary, the initial analysis indicates that there is an initial performance effect favoring computer controlled dialogue but the advantage fades fast as operators become experienced. The user documentation style is seen to have a significant effect on performance. The menu and prompt command formats are preferred by inexperienced operators. The short form mnemonic is least favored. There is no clear best command format but the short form mnemonic is clearly the worst.

Experimental identification and analytical modelling of human walking forces: Literature review

NASA Astrophysics Data System (ADS)

Racic, V.; Pavic, A.; Brownjohn, J. M. W.

2009-09-01

Dynamic forces induced by humans walking change simultaneously in time and space, being random in nature and varying considerably not only between different people but also for a single individual who cannot repeat two identical steps. Since these important aspects of walking forces have not been adequately researched in the past, the corresponding lack of knowledge has reflected badly on the quality of their mathematical models used in vibration assessments of pedestrian structures such as footbridges, staircases and floors. To develop better force models which can be used with more confidence in the structural design, an adequate experimental and analytical approach must be taken to account for their complexity. This paper is the most comprehensive review published to date, of 270 references dealing with different experimental and analytical characterizations of human walking loading. The source of dynamic human-induced forces is in fact in the body motion. To date, human motion has attracted a lot of interest in many scientific branches, particularly in medical and sports science, bioengineering, robotics, and space flight programs. Other fields include biologists of various kinds, physiologists, anthropologists, computer scientists (graphics and animation), human factors and ergonomists, etc. It resulted in technologically advanced tools that can help understanding the human movement in more detail. Therefore, in addition to traditional direct force measurements utilizing a force plate and an instrumented treadmill, this review also introduces methods for indirect measurement of time-varying records of walking forces via combination of visual motion tracking (imaging) data and known body mass distribution. The review is therefore an interdisciplinary article that bridges the gaps between biomechanics of human gait and civil engineering dynamics. Finally, the key reason for undertaking this review is the fact that human-structure dynamic interaction and pedestrian synchronization when walking on more or less perceptibly moving structures are increasingly giving serious cause for concern in vibration serviceability design. There is a considerable uncertainty about how excessive structural vibrations modify walking and hence affect pedestrian-induced forces, significantly in many cases. Modelling of this delicate mechanism is one of the challenges that the international civil structural engineering community face nowadays and this review thus provides a step toward understanding better the problem.

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.

Remote monitoring of the progression of primary pneumonic plague in Brown Norway rats in high-capacity, high-containment housing

PubMed Central

Coate, Eric A.; Kocsis, Andrew G.; Peters, Kristen N.; Anderson, Paul E.; Ellersieck, Mark R.; Fine, Deborah M.; Anderson, Deborah M.

2014-01-01

Development of new vaccines, diagnostics and therapeutics for biodefense or other relatively rare infectious diseases is hindered by the lack of naturally occurring human disease on which to conduct clinical trials of efficacy. To overcome this experimental gap, the U.S. Food and Drug Administration established the Animal Rule, in which efficacy testing in two well-characterized animal models that closely resemble human disease may be accepted in lieu of large scale clinical trials for diseases with limited natural human incidence. In this report, we evaluated the Brown Norway rat as a model for pneumonic plague and describe the natural history of clinical disease following inhalation exposure to Yersinia pestis. In high-capacity, high-containment housing, we monitored temperature, activity, heart rate and rhythm by capturing electronic impulses transmitted from abdominal telemeter implants. Using this system, we show that reduced activity and development of fever are sensitive indications of disease progression. Furthermore, we identified heart arrhythmias as contributing factors to the rapid progression to lethality following the fever response. Together these data validate the Brown Norway rat as an experimental model for human pneumonic plague and provide new insight that may ultimately lead to novel approaches in post-exposure treatment of this devastating infection. PMID:24719212

Ridge augmentation using recombinant human fibroblast growth factor-2 with biodegradable gelatin sponges incorporating β-tricalcium phosphate: a preclinical study in dogs.

PubMed

Hoshi, S; Akizuki, T; Matsuura, T; Ikawa, T; Kinoshita, A; Oda, S; Tabata, Y; Matsui, M; Izumi, Y

2016-02-01

Fibroblast growth factor-2 (FGF-2) regulates the proliferation and differentiation of osteogenic cells, resulting in the promotion of bone formation. Biodegradable gelatin sponges incorporating β-tricalcium phosphate (β-TCP) have been reported as a scaffold, which has the ability to control growth factor release, offering sufficient mechanical strength and efficient migration of mesenchymal cells. In this study, we evaluated the effects of the combined use of recombinant human FGF-2 (rhFGF-2) and gelatin/β-TCP sponge on ridge augmentation in dogs. Six male beagle dogs were used in this study. Twelve wk after tooth extraction, bilateral 10 × 5 mm (width × depth) saddle-type defects were created 3 mm apart from the mesial side of the maxillary canine. At the experimental sites, the defects were filled with gelatin/β-TCP sponge infiltrated with 0.3% rhFGF-2, whereas gelatin/β-TCP sponge infiltrated with saline was applied to the control sites. Eight wk after surgery, qualitative and quantitative analyses were performed. There were no signs of clinical inflammation at 8 wk after surgery. Histometric measurements revealed that new bone height at the experimental sites (2.98 ± 0.65 mm) was significantly greater than that at the control sites (1.56 ± 0.66 mm; p = 0.004). The total tissue height was greater at the experimental sites (6.62 ± 0.66 mm) than that at the control sites (5.95 ± 0.74 mm), although there was no statistical significant difference (p = 0.051). Cast model measurements revealed that the residual defect height at the experimental sites (2.31 ± 0.50 mm) was significantly smaller than that at the control sites (3.51 ± 0.78 mm; p = 0.012). The combined use of rhFGF-2 and gelatin/β-TCP sponge promotes ridge augmentation in canine saddle-type bone defects. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Task complexity, posture, age, sex: which is the main factor influencing manual laterality in captive Cercocebus torquatus torquatus?

PubMed

Laurence, Agathe; Wallez, Catherine; Blois-Heulin, Catherine

2011-09-01

Behavioural asymmetries reflect brain asymmetry in nonhuman primates (NHP) as in humans. By investigating manual laterality, researchers can study the evolution of brain hemisphere specialisation. Three dominant theories aim to establish an evolutionary scenario. The most recent theory relates different levels of manual laterality to task complexity. Our investigation aimed to evaluate the importance of two extrinsic factors (posture and the need for manual coordination) and two intrinsic factors (age and sex) on the expression of manual laterality by red-capped mangabeys. We observed 19 captive-born mangabeys, in spontaneous situations and under experimental conditions (seven experimental tasks varying in complexity). No directionality was observed in hand preference at the group level whatever the task. But our data revealed an effect of task complexity: more subjects were lateralised than not lateralised for the bipedal task and for the three most complex tasks. Finally, we evidenced an age and a sex effect. We compare our results with data for several other primate species and discuss them in the light of different manual laterality theories.

Obesity and infection: reciprocal causality.

PubMed

Hainer, V; Zamrazilová, H; Kunešová, M; Bendlová, B; Aldhoon-Hainerová, I

2015-01-01

Associations between different infectious agents and obesity have been reported in humans for over thirty years. In many cases, as in nosocomial infections, this relationship reflects the greater susceptibility of obese individuals to infection due to impaired immunity. In such cases, the infection is not related to obesity as a causal factor but represents a complication of obesity. In contrast, several infections have been suggested as potential causal factors in human obesity. However, evidence of a causal linkage to human obesity has only been provided for adenovirus 36 (Adv36). This virus activates lipogenic and proinflammatory pathways in adipose tissue, improves insulin sensitivity, lipid profile and hepatic steatosis. The E4orf1 gene of Adv36 exerts insulin senzitizing effects, but is devoid of its pro-inflammatory modalities. The development of a vaccine to prevent Adv36-induced obesity or the use of E4orf1 as a ligand for novel antidiabetic drugs could open new horizons in the prophylaxis and treatment of obesity and diabetes. More experimental and clinical studies are needed to elucidate the mutual relations between infection and obesity, identify additional infectious agents causing human obesity, as well as define the conditions that predispose obese individuals to specific infections.

Stretchable, Transparent, Ultrasensitive, and Patchable Strain Sensor for Human-Machine Interfaces Comprising a Nanohybrid of Carbon Nanotubes and Conductive Elastomers.

PubMed

Roh, Eun; Hwang, Byeong-Ung; Kim, Doil; Kim, Bo-Yeong; Lee, Nae-Eung

2015-06-23

Interactivity between humans and smart systems, including wearable, body-attachable, or implantable platforms, can be enhanced by realization of multifunctional human-machine interfaces, where a variety of sensors collect information about the surrounding environment, intentions, or physiological conditions of the human to which they are attached. Here, we describe a stretchable, transparent, ultrasensitive, and patchable strain sensor that is made of a novel sandwich-like stacked piezoresisitive nanohybrid film of single-wall carbon nanotubes (SWCNTs) and a conductive elastomeric composite of polyurethane (PU)-poly(3,4-ethylenedioxythiophene) polystyrenesulfonate ( PSS). This sensor, which can detect small strains on human skin, was created using environmentally benign water-based solution processing. We attributed the tunability of strain sensitivity (i.e., gauge factor), stability, and optical transparency to enhanced formation of percolating networks between conductive SWCNTs and PEDOT phases at interfaces in the stacked PU-PEDOT:PSS/SWCNT/PU-PEDOT:PSS structure. The mechanical stability, high stretchability of up to 100%, optical transparency of 62%, and gauge factor of 62 suggested that when attached to the skin of the face, this sensor would be able to detect small strains induced by emotional expressions such as laughing and crying, as well as eye movement, and we confirmed this experimentally.

Sheep Feed and Scrapie, France

PubMed Central

Philippe, Sandrine; Ducrot, Christian; Roy, Pascal; Remontet, Laurent; Jarrige, Nathalie

2005-01-01

Scrapie is a small ruminant, transmissible spongiform encephalopathy (TSE). Although in the past scrapie has not been considered a zoonosis, the emergence of bovine spongiform encephalopathy, transmissible to humans and experimentally to sheep, indicates that risk exists for small ruminant TSEs in humans. To identify the risk factors for introducing scrapie into sheep flocks, a case-control study was conducted in France from 1999 to 2000. Ninety-four case and 350 control flocks were matched by location and main breed. Three main hypotheses were tested: direct contact between flocks, indirect environmental contact, and foodborne risk. Statistical analysis was performed by using adjusted generalized linear models with the complementary log-log link function, considering flock size as an offset. A notable effect of using proprietary concentrates and milk replacers was observed. The risk was heterogeneous among feed factories. Contacts between flocks were not shown to be a risk factor. PMID:16102318

Extravehicular activity welding experiment

NASA Technical Reports Server (NTRS)

Watson, J. Kevin

1989-01-01

The In-Space Technology Experiments Program (INSTEP) provides an opportunity to explore the many critical questions which can only be answered by experimentation in space. The objective of the Extravehicular Activity Welding Experiment definition project was to define the requirements for a spaceflight experiment to evaluate the feasibility of performing manual welding tasks during EVA. Consideration was given to experiment design, work station design, welding hardware design, payload integration requirements, and human factors (including safety). The results of this effort are presented. Included are the specific objectives of the flight test, details of the tasks which will generate the required data, and a description of the equipment which will be needed to support the tasks. Work station requirements are addressed as are human factors, STS integration procedures and, most importantly, safety considerations. A preliminary estimate of the cost and the schedule for completion of the experiment through flight and postflight analysis are given.

A hypothetical model of host-pathogen interaction of Streptococcus suis in the gastro-intestinal tract

PubMed Central

Ferrando, Maria Laura; Schultsz, Constance

2016-01-01

ABSTRACT Streptococcus suis (SS) is a zoonotic pathogen that can cause systemic infection in pigs and humans. The ingestion of contaminated pig meat is a well-established risk factor for zoonotic S. suis disease. In our studies, we provide experimental evidence that S. suis is capable to translocate across the host gastro-intestinal tract (GIT) using in vivo and in vitro models. Hence, S. suis should be considered an emerging foodborne pathogen. In this addendum, we give an overview of the complex interactions between S. suis and host-intestinal mucosa which depends on the host origin, the serotype and genotype of S. suis, as well as the presence and expression of virulence factors involved in host-pathogen interaction. Finally, we propose a hypothetical model of S. suis interaction with the host-GIT taking in account differences in conditions between the porcine and human host. PMID:26900998

Neurocysticercosis: regional status, epidemiology, impact and control measures in the Americas.

PubMed

Flisser, Ana; Sarti, Elsa; Lightowlers, Marshall; Schantz, Peter

2003-06-01

The analysis of epidemiological data concerning human cysticercosis point to important advances in understanding the magnitude and distribution of this parasitic disease in Latin America, as well as the relationship of the elements that conform the life cycle of Taenia solium. The data indicate that the main risk factor for acquiring human neurocysticercosis and swine cysticercosis is the presence of the tapeworm carrier in the household. Therefore, several intervention measures for the control of cysticercosis have been evaluated: mass treatment in order to cure tapeworm carriers, health education towards understanding the risk factors, pig control by restraining them, experimental vaccination of pigs and treatment of swine cysticercosis. In this paper, we review the information obtained in these areas. We hope it will be useful in other endemic countries that wish to elaborate an action plan for the control and ultimate eradication of T. solium.

Encapsulated Hsp70 decreases endotoxin-induced production of ROS and TNFα in human phagocytes.

PubMed

Yurinskaya, M M; Kochetkova, O Yu; Shabarchina, L I; Antonova, O Yu; Suslikov, A V; Evgen'ev, M B; Vinokurov, M G

2017-01-01

Human heat shock protein Hsp70 was experimentally inserted into polyelectrolyte microcapsules. Encapsulated recombinant Hsp70 was studied in terms of its effects on neutrophil apoptosis, the production of reactive oxygen species, and the secretion of tumor necrosis factor alpha by promonocytic THP-1 cells. It was found that encapsulated Hsp70 effectively inhibits neutrophil apoptosis, unlike free exogenous protein used in solution. In THP-1 cells, encapsulated and free Hsp70 reduced LPS-induced tumor necrosis factor alpha production with a similar efficiency. Encapsulated Hsp70 reduces LPS-induced reactive oxygen species production by neutrophils in the course of its release from the microcapsules but not as much as free Hsp70. Thus, the polyelectrolyte microcapsules can be used as containers for the effective delivery of Hsp70 to neutrophils and monocytes to significantly improve the functioning of the innate immune system.

Chemerin as an independent predictor of cardiovascular event risk

PubMed Central

İnci, Sinan; Aksan, Gökhan; Doğan, Pınar

2016-01-01

Currently, coronary artery disease (CAD) is considered a major ailment in humans with widespread prevalence. CAD also accounts for high mortality rates around the world that involves several known risk factors. Chemerin is a novel adipokinine that is associated with inflammation and adipogenesis. Furthermore, experimental and clinical data indicate that localized as well as circulating chemerin expression and activation are elevated in numerous metabolic and inflammatory diseases including psoriasis, obesity, type 2 diabetes, metabolic syndrome and cardiovascular disease. Chemerin is accepted as being a strong marker because the serum chemerin levels are increased in a CAD condition. However, the chimeric characteristics of chemerin have not been fully investigated. Although chemerin is known to be responsible for CAD development among other factors, authors still investigate it at the marker level. This review focuses on chemerin expression, processing, biological function and relevance to human diseases, and on the role of chemerin in the maintenance of a cardiovascular disease. PMID:27092231

Experimentally induced innovations lead to persistent culture via conformity in wild birds

PubMed Central

Aplin, L.M.; Farine, D.R.; Morand-Ferron, J.; Cockburn, A.; Thornton, A.; Sheldon, B.C.

2014-01-01

In human societies, cultural norms arise when behaviours are transmitted with high-fidelity social learning through social networks1. However a paucity of experimental studies has meant that there is no comparable understanding of the process by which socially transmitted behaviours may spread and persist in animal populations2,3. Here, we introduce alternative novel foraging techniques into replicated wild sub-populations of great tits (Parus major), and employ automated tracking to map the diffusion, establishment and long-term persistence of seeded behaviours. We further use social network analysis to examine social factors influencing diffusion dynamics. From just two trained birds in each sub-population, information spread rapidly through social network ties to reach an average of 75% of individuals, with 508 knowledgeable individuals performing 58,975 solutions. Sub-populations were heavily biased towards the technique originally introduced, resulting in established local arbitrary traditions that were stable over two generations, despite high population turnover. Finally, we demonstrate a strong effect of social conformity, with individuals disproportionately adopting the most frequent local variant when first learning, but then also continuing to favour social over personal information by matching their technique to the majority variant. Cultural conformity is thought to be a key factor in the evolution of complex culture in humans4-7. In providing the first experimental demonstration of conformity in a wild non-primate, and of cultural norms in foraging techniques in any wild animal, our results suggest a much wider evolutionary occurrence of such apparently complex cultural behaviour. PMID:25470065

Effect of Lactobacillus plantarum 299v on cardiovascular disease risk factors in smokers.

PubMed

Naruszewicz, Marek; Johansson, Marie-Louise; Zapolska-Downar, Danuta; Bukowska, Hanna

2002-12-01

The short-chain fatty acids formed in the human colon by the bacterial fermentation of fiber may have an antiinflammatory effect, may reduce insulin production, and may improve lipid metabolism. We previously showed in hypercholesterolemic patients that supplementation with the probiotic bacteria Lactobacillus plantarum 299v significantly lowers concentrations of LDL cholesterol and fibrinogen. We determined the influence of a functional food product containing L. plantarum 299v on lipid profiles, inflammatory markers, and monocyte function in heavy smokers. Thirty-six healthy volunteers (18 women and 18 men) aged 35-45 y participated in a controlled, randomized, double-blind trial. The experimental group drank 400 mL/d of a rose-hip drink containing L. plantarum 299v (5 x 10(7) colony-forming units/mL); the control group consumed the same volume of product without bacteria. The experiment lasted 6 wk and entailed no changes in lifestyle. Significant decreases in systolic blood pressure (P < 0.000), leptin (P < 0.000), and fibrinogen (P < 0.001) were recorded in the experimental group. No such changes were observed in the control group. Decreases in F(2)-isoprostanes (37%) and interleukin 6 (42%) were also noted in the experimental group in comparison with baseline. Monocytes isolated from subjects treated with L. plantarum showed significantly reduced adhesion (P < 0.001) to native and stimulated human umbilical vein endothelial cells. L. plantarum administration leads to a reduction in cardiovascular disease risk factors and could be useful as a protective agent in the primary prevention of atherosclerosis in smokers.

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.

[Host-microbiota crosstalk and cardiovascular diseases].

PubMed

Amar, Jacques

2018-06-13

When analyzing the microbiota-host crosstalk, we have to consider three participants in this dialogue: the gut microbiota, the intestinal barrier and bacterial translocation. Experimental data demonstrate that host microbiota crosstalk plays a causal on the regulation of blood pressure, glucose metabolism and the development of atherosclerosis. Host microbiota crosstalk is associated in humans with main cardiovascular risk factors notably hypertension and type 2 diabetes. Host microbiota crosstalk is associated in humans with the onset of cardiovascular diseases. The Mediterranean diet has proven as proven to be an effective strategy in improving cardiovascular prognosis and in changing gut microbiota. Copyright © 2018. Published by Elsevier Masson SAS.

[Sex differentiation of central nervous system--brain of man and woman].

PubMed

Arai, Yasumasa

2004-02-01

Sex differentiation of human brain is mostly dependent on the prenatal exposure to androgen(testosterone). Congenital aromatase deficiency does not disturb male brain development in men. This is quite different from experimental evidence from rodents whose brains need intraneuronal aromatization from androgen to estrogen to induce sex differentiation. There is evidence for male-female differences in brain structures. Some of them(INHA-3) appear to be related with sexual orientation. The other(BNST) might participate in forming gender-identity. In addition, sexually dimorphic features are recognized in some cognitive activities. The possible involvement of genetic factors in human brain sex differentiation is also discussed.

Human Lineage-Specific Transcriptional Regulation through GA-Binding Protein Transcription Factor Alpha (GABPa)

PubMed Central

Perdomo-Sabogal, Alvaro; Nowick, Katja; Piccini, Ilaria; Sudbrak, Ralf; Lehrach, Hans; Yaspo, Marie-Laure; Warnatz, Hans-Jörg; Querfurth, Robert

2016-01-01

A substantial fraction of phenotypic differences between closely related species are likely caused by differences in gene regulation. While this has already been postulated over 30 years ago, only few examples of evolutionary changes in gene regulation have been verified. Here, we identified and investigated binding sites of the transcription factor GA-binding protein alpha (GABPa) aiming to discover cis-regulatory adaptations on the human lineage. By performing chromatin immunoprecipitation-sequencing experiments in a human cell line, we found 11,619 putative GABPa binding sites. Through sequence comparisons of the human GABPa binding regions with orthologous sequences from 34 mammals, we identified substitutions that have resulted in 224 putative human-specific GABPa binding sites. To experimentally assess the transcriptional impact of those substitutions, we selected four promoters for promoter-reporter gene assays using human and African green monkey cells. We compared the activities of wild-type promoters to mutated forms, where we have introduced one or more substitutions to mimic the ancestral state devoid of the GABPa consensus binding sequence. Similarly, we introduced the human-specific substitutions into chimpanzee and macaque promoter backgrounds. Our results demonstrate that the identified substitutions are functional, both in human and nonhuman promoters. In addition, we performed GABPa knock-down experiments and found 1,215 genes as strong candidates for primary targets. Further analyses of our data sets link GABPa to cognitive disorders, diabetes, KRAB zinc finger (KRAB-ZNF), and human-specific genes. Thus, we propose that differences in GABPa binding sites played important roles in the evolution of human-specific phenotypes. PMID:26814189

Comparative transcriptional analysis of three human ligaments with distinct biomechanical properties

PubMed Central

Lorda-Diez, Carlos I; Canga-Villegas, Ana; Cerezal, Luis; Plaza, Santiago; Hurlé, Juan M; García-Porrero, Juan A; Montero, Juan A

2013-01-01

One major aim of regenerative medicine targeting the musculoskeletal system is to provide complementary and/or alternative therapeutic approaches to current surgical therapies, often involving the removal and prosthetic substitution of damaged tissues such as ligaments. For these approaches to be successful, detailed information regarding the cellular and molecular composition of different musculoskeletal tissues is required. Ligaments have often been considered homogeneous tissues with common biomechanical properties. However, advances in tissue engineering research have highlighted the functional relevance of the organisational and compositional differences between ligament types, especially in those with higher risks of injury. The aim of this study was to provide information concerning the relative expression levels of a subset of key genes (including extracellular matrix components, transcription factors and growth factors) that confer functional identity to ligaments. We compared the transcriptomes of three representative human ligaments subjected to different biomechanical demands: the anterior cruciate ligament (ACL); the ligamentum teres of the hip (LT); and the iliofemoral ligament (IL). We revealed significant differences in the expression of type I collagen, elastin, fibromodulin, biglycan, transforming growth factor β1, transforming growth interacting factor 1, hypoxia-inducible factor 1-alpha and transforming growth factor β-induced gene between the IL and the other two ligaments. Thus, considerable molecular heterogeneity can exist between anatomically distinct ligaments with differing biomechanical demands. However, the LT and ACL were found to show remarkable molecular homology, suggesting common functional properties. This finding provides experimental support for the proposed role of the LT as a hip joint stabiliser in humans. PMID:24128114

The role of cortistatin in the human immune system.

PubMed

van Hagen, P Martin; Dalm, Virgil A; Staal, Frank; Hofland, Leo J

2008-05-14

Cortistatin (CST) is a recently described neuropeptide that shares high homology with somatostatin (somatotropin release-inhibiting factor, SRIF) and binds with high affinity to all somatostatin (sst) receptor subtypes. CST is currently known to have a widespread distribution in many human organs including the immune system. The activities specific to CST may be partially attributable to its binding to the growth hormone secretagogue (GHS)-receptor (GHS-R) and the orphan G-protein-coupled receptor MrgX2. Human immune cells produce CST, whereas macrophage lineage and activated endothelium express sst2, and human lymphocytes express sst3. The human thymus expresses sst1, 2, 3, MrgX2 and almost all immune cells express GHS-R. Moreover, at this very moment promising research with CST in experimental animal models is being performed. On the basis of these promising results, studies aiming to further evaluate the possibilities of CST as a therapeutic agent in human immune-mediated inflammatory diseases are warranted.

Umbilical Cord Blood Platelet Lysate as Serum Substitute in Expansion of Human Mesenchymal Stem Cells.

PubMed

Shirzad, Negin; Bordbar, Sima; Goodarzi, Alireza; Mohammad, Monire; Khosravani, Pardis; Sayahpour, Froughazam; Baghaban Eslaminejad, Mohamadreza; Ebrahimi, Marzieh

2017-10-01

The diverse clinical applications for human mesenchymal stem cells (hMSCs) in cellular therapy and regenerative medicine warrant increased focus on developing adequate culture supplements devoid of animal-derived products. In the present study, we have investigated the feasibility of umbilical cord blood-platelet lysate (UCB-PL) as a standard substitute for fetal bovine serum (FBS) and human peripheral blood-PL (PB-PL). In this experimental study, platelet concentrates (PC) from UCB and human PB donors were frozen, melted, and sterilized to obtain PL. Quality control included platelet cell counts, sterility testing (viral and microbial), total protein concentrations, growth factor levels, and PL stability. The effects of UCB-PL and PB-PL on hMSCs proliferation and differentiation into osteocytes, chondrocytes, and adipocytes were studied and the results compared with FBS. UCB-PL contained high levels of protein content, platelet-derived growth factor- AB (PDGF-AB), and transforming growth factor (TGF) compared to PB-PL. All growth factors were stable for at least nine months post-storage at -70˚C. hMSCs proliferation enhanced following treatment with UCB-PL. With all three supplements, hMSCs could differentiate into all three lineages. PB-PL and UCB-PL both were potent in hMSCs proliferation. However, PB promoted osteoblastic differentiation and UCB-PL induced chondrogenic differentiation. Because of availability, ease of use and feasible standardization of UCB-PL, we have suggested that UCB-PL be used as an alternative to FBS and PB-PL for the cultivation and expansion of hMSCs in cellular therapy. Copyright© by Royan Institute. All rights reserved.

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.

Chronic cigarette smoking alters erythrocyte membrane lipid composition and properties in male human volunteers.

PubMed

Padmavathi, Pannuru; Reddy, Vaddi Damodara; Kavitha, Godugu; Paramahamsa, Maturu; Varadacharyulu, Nallanchakravarthula

2010-11-01

Cigarette smoking is a major lifestyle factor influencing the health of human beings. The present study investigates smoking induced alterations on the erythrocyte membrane lipid composition, fluidity and the role of nitric oxide. Thirty experimental and control subjects (age 35+/-8) were selected for the study. Experimental subjects smoke 12+/-2 cigarettes per day for 7-10 years. In smokers elevated nitrite/nitrate levels in plasma and red cell lysates were observed. Smokers showed increased hemolysis, erythrocyte membrane lipid peroxidation, protein carbonyls, C/P ratio (cholesterol and phospholipid ratio), anisotropic (gamma) value with decreased Na(+)/K(+)-ATPase activity and sulfhydryl groups. Alterations in smokers erythrocyte membrane individual phospholipids were also evident from the study. Red cell lysate nitric oxide positively correlated with C/P ratio (r=0.565) and fluorescent anisotropic (gamma) value (r=0.386) in smokers. Smoking induced generation of reactive oxygen/nitrogen species might have altered erythrocyte membrane physico-chemical properties. Copyright 2010 Elsevier Inc. All rights reserved.

Unified Approach to the Biomechanics of Dental Implantology

NASA Technical Reports Server (NTRS)

Grenoble, D. E.; Knoell, A. C.

1973-01-01

The human need for safe and effective dental implants is well-recognized. Although many implant designs have been tested and are in use today, a large number have resulted in clinical failure. These failures appear to be due to biomechanical effects, as well as biocompatibility and surgical factors. A unified approach is proposed using multidisciplinary systems technology, for the study of the biomechanical interactions between dental implants and host tissues. The approach progresses from biomechanical modeling and analysis, supported by experimental investigations, through implant design development, clinical verification, and education of the dental practitioner. The result of the biomechanical modeling, analysis, and experimental phases would be the development of scientific design criteria for implants. Implant designs meeting these criteria would be generated, fabricated, and tested in animals. After design acceptance, these implants would be tested in humans, using efficient and safe surgical and restorative procedures. Finally, educational media and instructional courses would be developed for training dental practitioners in the use of the resulting implants.

A spotlight on liquefaction: evidence from clinical settings and experimental models in tuberculosis.

PubMed

Cardona, Pere-Joan

2011-01-01

Liquefaction is one of the most intriguing aspects of human tuberculosis. It is a major cause of the transition from the infection to active disease (tuberculosis, TB) as well as the transmission of M. tuberculosis to other persons. This paper reviews the natural history of liquefaction in humans from a pathological and radiological point of view and discusses how the experimental models available can be used to address the topic of liquefaction and cavity formation. Different concepts that have been related to liquefaction, from the influence of immune response to mechanical factors, are reviewed. Synchronic necrosis or apoptosis of infected macrophages in a close area, together with an ineffective fibrosis, appears to be clue in this process, in which macrophages, the immune response, and bacillary load interact usually in a particular scenario: the upper lobes of the lung. The summary would be that even if being a stochastic effect, liquefaction would result if the organization of the intragranulomatous necrosis (by means of fibrosis) would be disturbed.

A Spotlight on Liquefaction: Evidence from Clinical Settings and Experimental Models in Tuberculosis

PubMed Central

Cardona, Pere-Joan

2011-01-01

Liquefaction is one of the most intriguing aspects of human tuberculosis. It is a major cause of the transition from the infection to active disease (tuberculosis, TB) as well as the transmission of M. tuberculosis to other persons. This paper reviews the natural history of liquefaction in humans from a pathological and radiological point of view and discusses how the experimental models available can be used to address the topic of liquefaction and cavity formation. Different concepts that have been related to liquefaction, from the influence of immune response to mechanical factors, are reviewed. Synchronic necrosis or apoptosis of infected macrophages in a close area, together with an ineffective fibrosis, appears to be clue in this process, in which macrophages, the immune response, and bacillary load interact usually in a particular scenario: the upper lobes of the lung. The summary would be that even if being a stochastic effect, liquefaction would result if the organization of the intragranulomatous necrosis (by means of fibrosis) would be disturbed. PMID:21437230

Design and evaluation of a trilateral shared-control architecture for teleoperated training robots.

PubMed

Shamaei, Kamran; Kim, Lawrence H; Okamura, Allison M

2015-08-01

Multilateral teleoperated robots can be used to train humans to perform complex tasks that require collaborative interaction and expert supervision, such as laparoscopic surgical procedures. In this paper, we explain the design and performance evaluation of a shared-control architecture that can be used in trilateral teleoperated training robots. The architecture includes dominance and observation factors inspired by the determinants of motor learning in humans, including observational practice, focus of attention, feedback and augmented feedback, and self-controlled practice. Toward the validation of such an architecture, we (1) verify the stability of a trilateral system by applying Llewellyn's criterion on a two-port equivalent architecture, and (2) demonstrate that system transparency remains generally invariant across relevant observation factors and movement frequencies. In a preliminary experimental study, a dyad of two human users (one novice, one expert) collaborated on the control of a robot to follow a trajectory. The experiment showed that the framework can be used to modulate the efforts of the users and adjust the source and level of haptic feedback to the novice user.

A Rat Body Phantom for Radiation Analysis

NASA Technical Reports Server (NTRS)

Qualls, Garry D.; Clowdsley, Martha S.; Slaba, Tony C.; Walker, Steven A.

2010-01-01

To reduce the uncertainties associated with estimating the biological effects of ionizing radiation in tissue, researchers rely on laboratory experiments in which mono-energetic, single specie beams are applied to cell cultures, insects, and small animals. To estimate the radiation effects on astronauts in deep space or low Earth orbit, who are exposed to mixed field broad spectrum radiation, these experimental results are extrapolated and combined with other data to produce radiation quality factors, radiation weighting factors, and other risk related quantities for humans. One way to reduce the uncertainty associated with such extrapolations is to utilize analysis tools that are applicable to both laboratory and space environments. The use of physical and computational body phantoms to predict radiation exposure and its effects is well established and a wide range of human and non-human phantoms are in use today. In this paper, a computational rat phantom is presented, as well as a description of the process through which that phantom has been coupled to existing radiation analysis tools. Sample results are presented for two space radiation environments.

Neural Tube Defects

PubMed Central

Greene, Nicholas D.E.; Copp, Andrew J.

2015-01-01

Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development when the neural tube fails to close completely. Human NTDs are multifactorial, with contributions from both genetic and environmental factors. The genetic basis is not yet well understood, but several nongenetic risk factors have been identified as have possibilities for prevention by maternal folic acid supplementation. Mechanisms underlying neural tube closure and NTDs may be informed by experimental models, which have revealed numerous genes whose abnormal function causes NTDs and have provided details of critical cellular and morphological events whose regulation is essential for closure. Such models also provide an opportunity to investigate potential risk factors and to develop novel preventive therapies. PMID:25032496

Dispelling urban myths about default uncertainty factors in chemical risk assessment – sufficient protection against mixture effects?

PubMed Central

2013-01-01

Assessing the detrimental health effects of chemicals requires the extrapolation of experimental data in animals to human populations. This is achieved by applying a default uncertainty factor of 100 to doses not found to be associated with observable effects in laboratory animals. It is commonly assumed that the toxicokinetic and toxicodynamic sub-components of this default uncertainty factor represent worst-case scenarios and that the multiplication of those components yields conservative estimates of safe levels for humans. It is sometimes claimed that this conservatism also offers adequate protection from mixture effects. By analysing the evolution of uncertainty factors from a historical perspective, we expose that the default factor and its sub-components are intended to represent adequate rather than worst-case scenarios. The intention of using assessment factors for mixture effects was abandoned thirty years ago. It is also often ignored that the conservatism (or otherwise) of uncertainty factors can only be considered in relation to a defined level of protection. A protection equivalent to an effect magnitude of 0.001-0.0001% over background incidence is generally considered acceptable. However, it is impossible to say whether this level of protection is in fact realised with the tolerable doses that are derived by employing uncertainty factors. Accordingly, it is difficult to assess whether uncertainty factors overestimate or underestimate the sensitivity differences in human populations. It is also often not appreciated that the outcome of probabilistic approaches to the multiplication of sub-factors is dependent on the choice of probability distributions. Therefore, the idea that default uncertainty factors are overly conservative worst-case scenarios which can account both for the lack of statistical power in animal experiments and protect against potential mixture effects is ill-founded. We contend that precautionary regulation should provide an incentive to generate better data and recommend adopting a pragmatic, but scientifically better founded approach to mixture risk assessment. PMID:23816180

Dispelling urban myths about default uncertainty factors in chemical risk assessment--sufficient protection against mixture effects?

PubMed

Martin, Olwenn V; Martin, Scholze; Kortenkamp, Andreas

2013-07-01

Assessing the detrimental health effects of chemicals requires the extrapolation of experimental data in animals to human populations. This is achieved by applying a default uncertainty factor of 100 to doses not found to be associated with observable effects in laboratory animals. It is commonly assumed that the toxicokinetic and toxicodynamic sub-components of this default uncertainty factor represent worst-case scenarios and that the multiplication of those components yields conservative estimates of safe levels for humans. It is sometimes claimed that this conservatism also offers adequate protection from mixture effects. By analysing the evolution of uncertainty factors from a historical perspective, we expose that the default factor and its sub-components are intended to represent adequate rather than worst-case scenarios. The intention of using assessment factors for mixture effects was abandoned thirty years ago. It is also often ignored that the conservatism (or otherwise) of uncertainty factors can only be considered in relation to a defined level of protection. A protection equivalent to an effect magnitude of 0.001-0.0001% over background incidence is generally considered acceptable. However, it is impossible to say whether this level of protection is in fact realised with the tolerable doses that are derived by employing uncertainty factors. Accordingly, it is difficult to assess whether uncertainty factors overestimate or underestimate the sensitivity differences in human populations. It is also often not appreciated that the outcome of probabilistic approaches to the multiplication of sub-factors is dependent on the choice of probability distributions. Therefore, the idea that default uncertainty factors are overly conservative worst-case scenarios which can account both for the lack of statistical power in animal experiments and protect against potential mixture effects is ill-founded. We contend that precautionary regulation should provide an incentive to generate better data and recommend adopting a pragmatic, but scientifically better founded approach to mixture risk assessment.

Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model

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

Perna, J.J.; Mannix, M.L.; Rooney, J.F.

1987-09-01

Infection with herpes simplex virus often results in a latent infection of local sensory ganglia and a disease characterized by periodic viral reactivation and mucocutaneous lesions. The factors that trigger reactivation in humans are still poorly defined. In our study, five patients with documented histories of recurrent herpes simplex virus infection on the buttocks or sacrum were exposed to three times their minimal erythema dose of ultraviolet light. Site-specific cutaneous herpes simplex virus infection occurred at 4.4 +/- 0.4 days after exposure to ultraviolet light in 8 of 13 attempts at reactivation. We conclude that ultraviolet light can reactivate herpesmore » simplex virus under experimentally defined conditions. This model in humans should prove useful in evaluating the pathophysiology and prevention of viral reactivation.« less

Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model.

PubMed

Perna, J J; Mannix, M L; Rooney, J F; Notkins, A L; Straus, S E

1987-09-01

Infection with herpes simplex virus often results in a latent infection of local sensory ganglia and a disease characterized by periodic viral reactivation and mucocutaneous lesions. The factors that trigger reactivation in humans are still poorly defined. In our study, five patients with documented histories of recurrent herpes simplex virus infection on the buttocks or sacrum were exposed to three times their minimal erythema dose of ultraviolet light. Site-specific cutaneous herpes simplex virus infection occurred at 4.4 +/- 0.4 days after exposure to ultraviolet light in 8 of 13 attempts at reactivation. We conclude that ultraviolet light can reactivate herpes simplex virus under experimentally defined conditions. This model in humans should prove useful in evaluating the pathophysiology and prevention of viral reactivation.

Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway

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

Zhang, Liang, E-mail: countryspring@sina.com; Ji, Yunxia, E-mail: 413499057@qq.com; Kang, Zechun, E-mail: davidjiangwl@163.com

An abnormal high mobility group box 1 (HMGB1) activation and a decrease in receptor for advanced glycation end-product (RAGE) play a key role in the pathogenesis of pulmonary fibrosis. Protocatechuic aldehyde (PA) is a naturally occurring compound, which is extracted from the degradation of phenolic acids. However, whether PA has anti-fibrotic functions is unknown. In this study, the effects of PA on the transforming growth factor-β1 (TGF-β1)-mediated epithelial–mesenchymal transition (EMT) in A549 cells, on the apoptosis of human type I alveolar epithelial cells (AT I), on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on bleomycin (BLM)-induced pulmonarymore » fibrosis in vivo were investigated. PA treatment resulted in a reduction of EMT in A549 cells with a decrease in vimentin and HMGB, an increase of E-cadherin and RAGE, a reduction of HLF-1 proliferation with a decrease of fibroblast growth factor 2 (FGF-2) and platelet-derived growth factor (PDGF). Apoptosis of AT I was attenuated with an increase of RAGE. PA ameliorated BLM-induced pulmonary fibrosis in rats with a reduction of histopathological scores and collagen deposition, and a lower FGF-2, PDGF, α-smooth muscle actin (α-SMA) and HMGB1 expression, whereas higher RAGE was found in BLM-instilled lungs. Through the decrease of HGMB1 and the regulation of RAGE, PA reversed the EMT, inhibited HLF-1 proliferation as well as reduced apoptosis in AT I, and prevented pulmonary fibrosis in vivo. Collectively, our results demonstrate that PA prevents experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway. - Highlights: • PA prevents EMT, reduces the apoptosis of AT1 in vitro. • PA decreases proliferation of HLF-1, reduces PDGF and FGF expression in vitro. • PA prevents experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.« less

First Person Experience of Body Transfer in Virtual Reality

PubMed Central

Slater, Mel; Spanlang, Bernhard; Sanchez-Vives, Maria V.; Blanke, Olaf

2010-01-01

Background Altering the normal association between touch and its visual correlate can result in the illusory perception of a fake limb as part of our own body. Thus, when touch is seen to be applied to a rubber hand while felt synchronously on the corresponding hidden real hand, an illusion of ownership of the rubber hand usually occurs. The illusion has also been demonstrated using visuomotor correlation between the movements of the hidden real hand and the seen fake hand. This type of paradigm has been used with respect to the whole body generating out-of-the-body and body substitution illusions. However, such studies have only ever manipulated a single factor and although they used a form of virtual reality have not exploited the power of immersive virtual reality (IVR) to produce radical transformations in body ownership. Principal Findings Here we show that a first person perspective of a life-sized virtual human female body that appears to substitute the male subjects' own bodies was sufficient to generate a body transfer illusion. This was demonstrated subjectively by questionnaire and physiologically through heart-rate deceleration in response to a threat to the virtual body. This finding is in contrast to earlier experimental studies that assume visuotactile synchrony to be the critical contributory factor in ownership illusions. Our finding was possible because IVR allowed us to use a novel experimental design for this type of problem with three independent binary factors: (i) perspective position (first or third), (ii) synchronous or asynchronous mirror reflections and (iii) synchrony or asynchrony between felt and seen touch. Conclusions The results support the notion that bottom-up perceptual mechanisms can temporarily override top down knowledge resulting in a radical illusion of transfer of body ownership. The research also illustrates immersive virtual reality as a powerful tool in the study of body representation and experience, since it supports experimental manipulations that would otherwise be infeasible, with the technology being mature enough to represent human bodies and their motion. PMID:20485681

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.

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

PubMed

Bigham-Sadegh, Amin; Oryan, Ahmad

2015-06-01

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

Video Games: A Human Factors Guide to Visual Display Design and Instructional System Design

DTIC Science & Technology

1984-04-01

Electronic video games have many of the same technological and psychological characteristics that are found in military computer-based systems. For...both of which employ video games as experimental stimuli, are presented here. The first research program seeks to identify and exploit the...characteristics of video games in the design of game-based training devices. The second program is designed to explore the effects of electronic video display

Retrospective studies of operating problems in air transport

NASA Technical Reports Server (NTRS)

Billings, C. E.; Lauber, J. K.; Cooper, G. E.; Ruffell-Smith, H. P.

1976-01-01

An epidemiological model for the study of human errors in aviation is presented. In this approach, retrospective data are used as the basis for formulation of hypotheses as to system factors which may have contributed to such errors. Prospective experimental studies of aviation operations are also required in order to prove or disprove the hypotheses, and to evaluate the effectiveness of intervention techniques designed to solve operational problems in the aviation system.

The Relative Efficacy of Intuitive and Analytical Cognition: A Second Direct Comparison

DTIC Science & Technology

1984-06-01

Review, 90(4), 293-315. Wallsten, T. S., & Budescu, D. V. (1981). Addivity and nonaddivity in judging MMPI profiles. Journal of Experimental Psychology...San Diego, CA 92152 "CDR Thomas Berghage Vaval Health Research Center San Diego, CA 92152 7 Department of the Navy Department of the Navy Mr. Paul...Research Lab Pensacola, FL 32508 Dr. S. Schiflett Human Factors Section Commanding Officer Systems Engineering Test Naval Health Research Center

Hepatocyte growth factor secreted by ovarian cancer cells stimulates peritoneal implantation via the mesothelial-mesenchymal transition of the peritoneum.

PubMed

Nakamura, Michihiko; Ono, Yoshihiro J; Kanemura, Masanori; Tanaka, Tomohito; Hayashi, Masami; Terai, Yoshito; Ohmichi, Masahide

2015-11-01

A current working model for the metastatic process of ovarian carcinoma suggests that cancer cells are shed from the ovarian tumor into the peritoneal cavity and attach to the layer of mesothelial cells that line the inner surface of the peritoneum, and several studies suggest that hepatocyte growth factor (HGF) plays an important role in the dissemination of ovarian cancer. Our objectives were to evaluate the HGF expression of ovarian cancer using clinical data and assess the effect of HGF secreted from human ovarian cancer cells to human mesothelial cells. HGF expression was immunohistochemically evaluated in 165 epithelial ovarian cancer patients arranged as tissue microarrays. HGF expression in four ovarian cancer cell lines was evaluated by using semi-quantitative polymerase chain reaction, Western blotting and enzyme-linked immunosorbent assay. The effect of ovarian cancer cell derived HGF to the human mesothelial cells was assessed by using morphologic analysis, Western blotting and cell invasion assay. The effect of HGF on ovarian cancer metastasis was assessed by using in vivo experimental model. The clinical data showed a significantly high correlation between the HGF expression and the cancer stage. The in vivo and in vitro experimental models revealed that HGF secreted by ovarian cancer cells induces the mesothelial-to-mesenchymal transition and stimulates the invasion of mesothelial cells. Furthermore, manipulating the HGF activity affected the degree of dissemination and ascite formation. We demonstrated that HGF secreted by ovarian cancer cells plays an important role in cancer peritoneal implantation. Copyright © 2015 Elsevier Inc. All rights reserved.

RegNetwork: an integrated database of transcriptional and post-transcriptional regulatory networks in human and mouse

PubMed Central

Liu, Zhi-Ping; Wu, Canglin; Miao, Hongyu; Wu, Hulin

2015-01-01

Transcriptional and post-transcriptional regulation of gene expression is of fundamental importance to numerous biological processes. Nowadays, an increasing amount of gene regulatory relationships have been documented in various databases and literature. However, to more efficiently exploit such knowledge for biomedical research and applications, it is necessary to construct a genome-wide regulatory network database to integrate the information on gene regulatory relationships that are widely scattered in many different places. Therefore, in this work, we build a knowledge-based database, named ‘RegNetwork’, of gene regulatory networks for human and mouse by collecting and integrating the documented regulatory interactions among transcription factors (TFs), microRNAs (miRNAs) and target genes from 25 selected databases. Moreover, we also inferred and incorporated potential regulatory relationships based on transcription factor binding site (TFBS) motifs into RegNetwork. As a result, RegNetwork contains a comprehensive set of experimentally observed or predicted transcriptional and post-transcriptional regulatory relationships, and the database framework is flexibly designed for potential extensions to include gene regulatory networks for other organisms in the future. Based on RegNetwork, we characterized the statistical and topological properties of genome-wide regulatory networks for human and mouse, we also extracted and interpreted simple yet important network motifs that involve the interplays between TF-miRNA and their targets. In summary, RegNetwork provides an integrated resource on the prior information for gene regulatory relationships, and it enables us to further investigate context-specific transcriptional and post-transcriptional regulatory interactions based on domain-specific experimental data. Database URL: http://www.regnetworkweb.org PMID:26424082

Reversal of experimental Laron Syndrome by xenotransplantation of microencapsulated porcine Sertoli cells.

PubMed

Luca, Giovanni; Calvitti, Mario; Mancuso, Francesca; Falabella, Giulia; Arato, Iva; Bellucci, Catia; List, Edward O; Bellezza, Enrico; Angeli, Giovanni; Lilli, Cinzia; Bodo, Maria; Becchetti, Ennio; Kopchick, John J; Cameron, Don F; Baroni, Tiziano; Calafiore, Riccardo

2013-01-10

Recombinant human IGF-1 currently represents the only available treatment option for the Laron Syndrome, a rare human disorder caused by defects in the gene encoding growth hormone receptor, resulting in irreversibly retarded growth. Unfortunately, this treatment therapy, poorly impacts longitudinal growth (13% in females and 19% in males), while burdening the patients with severe side effects, including hypoglycemia, in association with the unfair chore of taking multiple daily injections that cause local intense pain. In this study, we have demonstrated that a single intraperitoneal graft of microencapsulated pig Sertoli cells, producing pig insulin-like growth factor-1, successfully promoted significant proportional growth in the Laron mouse, a unique animal model of the human Laron Syndrome. These findings indicate a novel, simply, safe and successful method for the cell therapy-based cure of the Laron Syndrome, potentially applicable to humans. Copyright © 2012 Elsevier B.V. All rights reserved.

The Second Conference on Lunar Bases and Space Activities of the 21st Century, volume 2

NASA Technical Reports Server (NTRS)

Mendell, Wendell W. (Editor); Alred, John W. (Editor); Bell, Larry S. (Editor); Cintala, Mark J. (Editor); Crabb, Thomas M. (Editor); Durrett, Robert H. (Editor); Finney, Ben R. (Editor); Franklin, H. Andrew (Editor); French, James R. (Editor); Greenberg, Joel S. (Editor)

1992-01-01

These 92 papers comprise a peer-reviewed selection of presentations by authors from NASA, the Lunar and Planetary Institute (LPI), industry, and academia at the Second Conference on Lunar Bases and Space Activities of the 21st Century. These papers go into more technical depth than did those published from the first NASA-sponsored symposium on the topic, held in 1984. Session topics included the following: (1) design and operation of transportation systems to, in orbit around, and on the Moon; (2) lunar base site selection; (3) design, architecture, construction, and operation of lunar bases and human habitats; (4) lunar-based scientific research and experimentation in astronomy, exobiology, and lunar geology; (5) recovery and use of lunar resources; (6) environmental and human factors of and life support technology for human presence on the Moon; and (7) program management of human exploration of the Moon and space.

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

PubMed

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

2009-04-01

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

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.

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.

Generation of human cortical neurons from a new immortal fetal neural stem cell line

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

Cacci, E.; Villa, A.; Parmar, M.

2007-02-01

Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markersmore » like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were dramatically reduced, and the hc-NSCs differentiated into glia and neurons (mostly glutamatergic and GABAergic, as well as tyrosine hydroxylase-positive, presumably dopaminergic neurons). RT-PCR analysis showed that the hc-NSCs retained expression of Pax6, Emx2 and Neurogenin2, which are genes associated with regionalization and cell commitment in cortical precursors during brain development. Our data indicate that this hc-NSC line could be useful for exploring the potential of human NSCs to replace dead or damaged cortical cells in animal models of acute and chronic neurodegenerative diseases. Taking advantage of its clonality and homogeneity, this cell line will also be a valuable experimental tool to study the regulatory role of intrinsic and extrinsic factors in human NSC biology.« less

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

McLaughlin, J.K.

A review of the epidemiology of renal cell cancer is presented. Risk factors for renal cell cancer such as cigarette smoking, obesity, diet, and use of analgesics and prescription diuretics are examined. Although uncommon, occupational risk factors are also reviewed. Studies examining gasoline exposure and renal cell cancer are evaluated, including investigations recently presented at a meeting on this topic. Overall, most studies find no link between gasoline exposure and renal cell cancer; moreover, the experimental evidence that initiated the health concern is no longer considered relevant to humans. Positive associations, however, reported in two recent studies prevent a firmmore » conclusion of no risk for this exposure. 48 refs.« less

Renal cell cancer and exposure to gasoline: a review.

PubMed Central

McLaughlin, J K

1993-01-01

A review of the epidemiology of renal cell cancer is presented. Risk factors for renal cell cancer such as cigarette smoking, obesity, diet, and use of analgesics and prescription diuretics are examined. Although uncommon, occupational risk factors are also reviewed. Studies examining gasoline exposure and renal cell cancer are evaluated, including investigations recently presented at a meeting on this topic. Overall, most studies find no link between gasoline exposure and renal cell cancer; moreover, the experimental evidence that initiated the health concern is no longer considered relevant to humans. Positive associations, however, reported in two recent studies prevent a firm conclusion of no risk for this exposure. PMID:8020434

Acute and chronic psychological stress as risk factors for cardiovascular disease: Insights gained from epidemiological, clinical and experimental studies.

PubMed

Lagraauw, H Maxime; Kuiper, Johan; Bot, Ilze

2015-11-01

Cardiovascular disease (CVD) remains a leading cause of death worldwide and identification and therapeutic modulation of all its risk factors is necessary to ensure a lower burden on the patient and on society. The physiological response to acute and chronic stress exposure has long been recognized as a potent modulator of immune, endocrine and metabolic pathways, however its direct implications for cardiovascular disease development, progression and as a therapeutic target are not completely understood. More and more attention is given to the bidirectional interaction between psychological and physical health in relation to cardiovascular disease. With atherosclerosis being a chronic disease starting already at an early age the contribution of adverse early life events in affecting adult health risk behavior, health status and disease development is receiving increased attention. In addition, experimental research into the biological pathways involved in stress-induced cardiovascular complications show important roles for metabolic and immunologic maladaptation, resulting in increased disease development and progression. Here we provide a concise overview of human and experimental animal data linking chronic and acute stress to CVD risk and increased progression of the underlying disease atherosclerosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Balance of antiangiogenic and angiogenic factors in the context of the etiology of preeclampsia.

PubMed

Seki, Hiroyuki

2014-10-01

The "two-stage disorder" theory that is assumed for the etiology of preeclampsia hypothesizes that antiangiogenic and angiogenic factors and/or placental debris play an important role in this disorder. The physiological actions of placental debris occur via the balance between antiangiogenic and angiogenic factors. Accordingly, this balance between antiangiogenic and angiogenic factors should be investigated to elucidate the various pathological features of preeclampsia. Their accurate evaluation is needed to investigate not only antiangiogenic factors (such as sFlt-1 and sEng) and angiogenic factors (such as vascular endothelial growth factor, placental growth factor and transforming growth factor-β) but also the expression level of their receptors such as Flt-1 and Eng. However, it is ethically and technically difficult to investigate the above-mentioned factors at antepartum in human patients. The examination of the ratios of sFlt-1/vascular endothelial growth factor receptor ligands and sEng/transforming vascular endothelial growth factor-β and the use of experimental animal models may help in elucidating various unresolved issues in preeclampsia. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Can exercise affect the course of inflammatory bowel disease? Experimental and clinical evidence.

PubMed

Bilski, Jan; Mazur-Bialy, Agnieszka; Brzozowski, Bartosz; Magierowski, Marcin; Zahradnik-Bilska, Janina; Wójcik, Dagmara; Magierowska, Katarzyna; Kwiecien, Slawomir; Mach, Tomasz; Brzozowski, Tomasz

2016-08-01

The inflammatory bowel disease (IBD) consisting of Crohn's disease (CD) and ulcerative colitis (UC) are defined as idiopathic, chronic and relapsing intestinal disorders occurring in genetically predisposed individuals exposed to environmental risk factors such as diet and microbiome changes. Since conventional drug therapy is expensive and not fully efficient, there is a need for alternative remedies that can improve the outcome in patients suffering from IBD. Whether exercise, which has been proposed as adjunct therapy in IBD, can be beneficial in patients with IBD remains an intriguing question. In this review, we provide an overview of the effects of exercise on human IBD and experimental colitis in animal models that mimic human disease, although the information on exercise in human IBD are sparse and poorly understood. Moderate exercise can exert a beneficial ameliorating effect on IBD and improve the healing of experimental animal colitis due to the activity of protective myokines such as irisin released from working skeletal muscles. CD patients with higher levels of exercise were significantly less likely to develop active disease at six months. Moreover, voluntary exercise has been shown to exert a positive effect on IBD patients' mood, weight maintenance and osteoporosis. On the other hand, depending on its intensity and duration, exercise can evoke transient mild systemic inflammation and enhances pro-inflammatory cytokine release, thereby exacerbating the gastrointestinal symptoms. We discuss recent advances in the mechanism of voluntary and strenuous exercise affecting the outcome of IBD in patients and experimental animal models. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

The Epidermal Growth Factor Receptor Promotes Glomerular Injury and Renal Failure in Rapidly Progressive Crescentic Glomerulonephritis; the Identification of Possible Therapy

PubMed Central

Bollée, Guillaume; Flamant, Martin; Schordan, Sandra; Fligny, Cécile; Rumpel, Elisabeth; Milon, Marine; Schordan, Eric; Sabaa, Nathalie; Vandermeersch, Sophie; Galaup, Ariane; Rodenas, Anita; Casal, Ibrahim; Sunnarborg, Susan W; Salant, David J; Kopp, Jeffrey B.; Threadgill, David W; Quaggin, Susan E; Dussaule, Jean-Claude; Germain, Stéphane; Mesnard, Laurent; Endlich, Karlhans; Boucheix, Claude; Belenfant, Xavier; Callard, Patrice; Endlich, Nicole; Tharaux, Pierre-Louis

2011-01-01

Rapidly progressive glomerulonephritis (RPGN) is a clinical a morphological expression of severe glomerular injury. Glomerular injury manifests as a proliferative histological pattern (“crescents”) with accumulation of T cells and macrophages, and proliferation of intrinsic glomerular cells. We show de novo induction of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in intrinsic glomerular epithelial cells (podocytes) from both mice and humans with RPGN. HB-EGF induction increases phosphorylation of the EGFR/ErbB1 receptor in mice with RPGN. In HB-EGF-deficient mice, EGFR activation in glomeruli is absent and the course of RPGN is improved. Autocrine HB-EGF induces a phenotypic switch in podocytes in vitro. Conditional deletion of the Egfr gene from podocytes of mice alleviates the severity of RPGN. Pharmacological blockade of EGFR also improves the course of RPGN, even when started 4 days after the induction of experimental RPGN. This suggests that targeting the HB-EGF/EGFR pathway could also be beneficial for treatment of human RPGN. PMID:21946538

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...

Analysis of extrinsic and intrinsic factors affecting event related desynchronization production.

PubMed

Takata, Yohei; Kondo, Toshiyuki; Saeki, Midori; Izawa, Jun; Takeda, Kotaro; Otaka, Yohei; It, Koji

2012-01-01

Recently there has been an increase in the number of stroke patients with motor paralysis. Appropriate re-afferent sensory feedback synchronized with a voluntary motor intention would be effective for promoting neural plasticity in the stroke rehabilitation. Therefore, BCI technology is considered to be a promising approach in the neuro-rehabilitation. To estimate human motor intention, an event-related desynchronization (ERD), a feature of electroencephalogram (EEG) evoked by motor execution or motor imagery is usually used. However, there exists various factors that affect ERD production, and its neural mechanism is still an open question. As a preliminary stage, we evaluate mutual effects of intrinsic (voluntary motor imagery) and extrinsic (visual and somatosensory stimuli) factors on the ERD production. Experimental results indicate that these three factors are not always additively interacting with each other and affecting the ERD production.

In vitro inactivation of complement by a serum factor present in Junin-virus infected guinea-pigs.

PubMed Central

Rimoldi, M T; de Bracco, M M

1980-01-01

A serum factor(s) of guinea-pigs infected with Junin virus, the etiological agent of Argentine haemorrhagic fever, is endowed with a potent anticomplementary activity. It is resistant to heat (56 degrees, 30 min) and elutes from a Sephadex G-200 column between albumin and haemoglobin. It is ineffective in the presence of EDTA or EGTA and does not sediment at 82,000 g. It has no direct effect on C4 unless functional Cl is present. However, it induces Cl activation that consumes C4 haemolytic activity in normal human and guinea-pig sera. The evidence presented in this report demonstrates that the complement activation observed in experimental Argentine haemorrhagic fever is at least in part due to a direct effect of this serum factor on the classical complement pathway. PMID:6247264

Estimation of fast and slow wave properties in cancellous bone using Prony's method and curve fitting.

PubMed

Wear, Keith A

2013-04-01

The presence of two longitudinal waves in poroelastic media is predicted by Biot's theory and has been confirmed experimentally in through-transmission measurements in cancellous bone. Estimation of attenuation coefficients and velocities of the two waves is challenging when the two waves overlap in time. The modified least squares Prony's (MLSP) method in conjuction with curve-fitting (MLSP + CF) is tested using simulations based on published values for fast and slow wave attenuation coefficients and velocities in cancellous bone from several studies in bovine femur, human femur, and human calcaneus. The search algorithm is accelerated by exploiting correlations among search parameters. The performance of the algorithm is evaluated as a function of signal-to-noise ratio (SNR). For a typical experimental SNR (40 dB), the root-mean-square errors (RMSEs) for one example (human femur) with fast and slow waves separated by approximately half of a pulse duration were 1 m/s (slow wave velocity), 4 m/s (fast wave velocity), 0.4 dB/cm MHz (slow wave attenuation slope), and 1.7 dB/cm MHz (fast wave attenuation slope). The MLSP + CF method is fast (requiring less than 2 s at SNR = 40 dB on a consumer-grade notebook computer) and is flexible with respect to the functional form of the parametric model for the transmission coefficient. The MLSP + CF method provides sufficient accuracy and precision for many applications such that experimental error is a greater limiting factor than estimation error.

The Effect of Secretory Factors of Adipose-Derived Stem Cells on Human Keratinocytes

PubMed Central

Moon, Kyoung Mi; Park, Ye-Hyoung; Lee, Jae Seol; Chae, Yong-Byung; Kim, Moon-Moo; Kim, Dong-Soo; Kim, Byung-Woo; Nam, Soo-Wan; Lee, Jong-Hwan

2012-01-01

The beneficial effects of adipose-derived stem cell conditioned medium (ADSC-CM) on skin regeneration have been reported. Although the mechanism of how ADSC-CM promotes skin regeneration is unclear, ADSC-CM contained various growth factors and it is an excellent raw material for skin treatment. ADSC-CM produced in a hypoxia condition of ADSC—in other words, Advanced Adipose-Derived Stem cell Protein Extract (AAPE)—has great merits for skin regeneration. In this study, human primary keratinocytes (HKs), which play fundamental roles in skin tissue, was used to examine how AAPE affects HK. HK proliferation was significantly higher in the experimental group (1.22 μg/mL) than in the control group. DNA gene chip demonstrated that AAPE in keratinocytes (p < 0.05) notably affected expression of 290 identified transcripts, which were associated with cell proliferation, cycle and migration. More keratinocyte wound healing and migration was shown in the experimental group (1.22 μg/mL). AAPE treatment significantly stimulated stress fiber formation, which was linked to the RhoA-ROCK pathway. We identified 48 protein spots in 2-D gel analysis and selected proteins were divided into 64% collagen components and 30% non-collagen components as shown by the MALDI-TOF analysis. Antibody array results contained growth factor/cytokine such as HGF, FGF-1, G-CSF, GM-CSF, IL-6, VEGF, and TGF-β3 differing from that shown by 2-D analysis. Conclusion: AAPE activates HK proliferation and migration. These results highlight the potential of the topical application of AAPE in the treatment of skin regeneration. PMID:22312315

An experimental investigation of referential looking in free-ranging Barbary macaques (Macaca sylvanus).

PubMed

Roberts, Sam G B; McComb, Karen; Ruffman, Ted

2008-02-01

The authors examined looking behavior between 15 Barbary macaque (Macaca sylvanus) infants and their mothers in the presence of a rubber snake (experimental period) and in the absence of the snake (control period). Two of the 15 infants looked referentially at their mother in the experimental period. Including both referential and nonreferential looks, the six older infants (aged 5 to 12 months) displayed a higher frequency of looks to mother than nine younger infants (aged 3 to 4.5 months) in the experimental period, but not in the control period. Older infants looked more to the mother in the experimental condition, whereas the younger infants looked more to the mother in the control condition, or looked equally in the two conditions. These results suggest that age is an important factor in determining looking behavior to mother in situations of uncertainty. Compared to hand-reared chimpanzees or human infants tested in standard social referencing paradigms, the infant macaques displayed a low rate of referential looking. Possible explanations for this are discussed. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

Novel and sensitive reversed-phase high-pressure liquid chromatography method with electrochemical detection for the simultaneous and fast determination of eight biogenic amines and metabolites in human brain tissue.

PubMed

Van Dam, Debby; Vermeiren, Yannick; Aerts, Tony; De Deyn, Peter Paul

2014-08-01

A fast and simple RP-HPLC method with electrochemical detection (ECD) and ion pair chromatography was developed, optimized and validated in order to simultaneously determine eight different biogenic amines and metabolites in post-mortem human brain tissue in a single-run analytical approach. The compounds of interest are the indolamine serotonin (5-hydroxytryptamine, 5-HT), the catecholamines dopamine (DA) and (nor)epinephrine ((N)E), as well as their respective metabolites, i.e. 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), 5-hydroxy-3-indoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG). A two-level fractional factorial experimental design was applied to study the effect of five experimental factors (i.e. the ion-pair counter concentration, the level of organic modifier, the pH of the mobile phase, the temperature of the column, and the voltage setting of the detector) on the chromatographic behaviour. The cross effect between the five quantitative factors and the capacity and separation factors of the analytes were then analysed using a Standard Least Squares model. The optimized method was fully validated according to the requirements of SFSTP (Société Française des Sciences et Techniques Pharmaceutiques). Our human brain tissue sample preparation procedure is straightforward and relatively short, which allows samples to be loaded onto the HPLC system within approximately 4h. Additionally, a high sample throughput was achieved after optimization due to a total runtime of maximally 40min per sample. The conditions and settings of the HPLC system were found to be accurate with high intra and inter-assay repeatability, recovery and accuracy rates. The robust analytical method results in very low detection limits and good separation for all of the eight biogenic amines and metabolites in this complex mixture of biological analytes. Copyright © 2014 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2016-09-01

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

Heparin binding epidermal growth factor in renal ischaemia/reperfusion injury.

PubMed

Mulder, Gemma M; Nijboer, Willemijn N; Seelen, Marc A; Sandovici, Maria; Bos, Eelke M; Melenhorst, Wynand B W H; Trzpis, Monika; Kloosterhuis, Niels J; Visser, Lydia; Henning, Rob H; Leuvenink, Henri G D; Ploeg, Rutger J; Sunnarborg, Susan W; van Goor, Harry

2010-06-01

The epidermal growth factor (EGF) receptor and its ligands are crucially involved in the renal response to ischaemia. We studied the heparin binding-epidermal growth factor (HB-EGF), a major ligand for the EGF receptor, in experimental and human ischaemia/reperfusion injury (IRI). HB-EGF mRNA and protein expression was studied in rat kidneys and cultured human tubular (HK-2) cells that were subjected to IRI and in human donor kidneys during transplantation. The effect of EGF receptor inhibition was investigated in vivo and in vitro. Furthermore, urinary HB-EGF protein excretion was studied after renal transplantation. Finally, HB-EGF KO and WT mice were subjected to IRI to study the role of HB-EGF in renal injury. HB-EGF mRNA was significantly up-regulated in the early phase of IRI in rats, cells, and human donor biopsies. Treatment with PKI-166 reduces macrophage accumulation and interstitial alpha-SMA in the early phase of IRI in rats. In vitro, PKI-166 causes a marked reduction in HB-EGF-induced cellular proliferation. Urinary HB-EGF is increased after transplantation compared with control urines from healthy subjects. HB-EGF KO mice subjected to IRI revealed significantly less morphological damage after IRI, compared with WT mice. We conclude that IRI results in early induction of HB-EGF mRNA and protein in vivo and in vitro. Absence of HB-EGF and inhibition of the EGF receptor in the early phase of IRI has protective effects, suggesting a modulating role for HB-EGF.

Paracrine Engineering of Human Explant-Derived Cardiac Stem Cells to Over-Express Stromal-Cell Derived Factor 1α Enhances Myocardial Repair.

PubMed

Tilokee, Everad L; Latham, Nicholas; Jackson, Robyn; Mayfield, Audrey E; Ye, Bin; Mount, Seth; Lam, Buu-Khanh; Suuronen, Erik J; Ruel, Marc; Stewart, Duncan J; Davis, Darryl R

2016-07-01

First generation cardiac stem cell products provide indirect cardiac repair but variably produce key cardioprotective cytokines, such as stromal-cell derived factor 1α, which opens the prospect of maximizing up-front paracrine-mediated repair. The mesenchymal subpopulation within explant derived human cardiac stem cells underwent lentiviral mediated gene transfer of stromal-cell derived factor 1α. Unlike previous unsuccessful attempts to increase efficacy by boosting the paracrine signature of cardiac stem cells, cytokine profiling revealed that stromal-cell derived factor 1α over-expression prevented lv-mediated "loss of cytokines" through autocrine stimulation of CXCR4+ cardiac stem cells. Stromal-cell derived factor 1α enhanced angiogenesis and stem cell recruitment while priming cardiac stem cells to readily adopt a cardiac identity. As compared to injection with unmodified cardiac stem cells, transplant of stromal-cell derived factor 1α enhanced cells into immunodeficient mice improved myocardial function and angiogenesis while reducing scarring. Increases in myocardial stromal-cell derived factor 1α content paralleled reductions in myocyte apoptosis but did not influence long-term engraftment or the fate of transplanted cells. Transplantation of stromal-cell derived factor 1α transduced cardiac stem cells increased the generation of new myocytes, recruitment of bone marrow cells, new myocyte/vessel formation and the salvage of reversibly damaged myocardium to enhance cardiac repair after experimental infarction. Stem Cells 2016;34:1826-1835. © 2016 AlphaMed Press.

Excision of a viral reprogramming cassette by delivery of synthetic Cre mRNA

PubMed Central

Loh, Yuin-Han; Yang, Jimmy Chen; De Los Angeles, Alejandro; Guo, Chunguang; Cherry, Anne; Rossi, Derrick J.; Park, In-Hyun; Daley, George Q.

2012-01-01

The generation of patient-specific induced pluripotent stem (iPS) cells provides an invaluable resource for cell therapy, in vitro modeling of human disease, and drug screening. To date, most human iPS cells have been generated with integrating retro- and lenti-viruses and are limited in their potential utility because residual transgene expression may alter their differentiation potential or induce malignant transformation. Alternatively, transgene-free methods using adenovirus and protein transduction are limited by low efficiency. This report describes a protocol for the generation of transgene-free human induced pluripotent stem cells using retroviral transfection of a single vector, which includes the coding sequences of human OCT4, SOX2, KLF4, and cMYC linked with picornaviral 2A plasmids. Moreover, after reprogramming has been achieved, this cassette can be removed using mRNA transfection of Cre recombinase. The method described herein to excise reprogramming factors with ease and efficiency facilitates the experimental generation and use of transgene-free human iPS cells. PMID:22605648

The N2-P3 complex of the evoked potential and human performance

NASA Technical Reports Server (NTRS)

Odonnell, Brian F.; Cohen, Ronald A.

1988-01-01

The N2-P3 complex and other endogenous components of human evoked potential provide a set of tools for the investigation of human perceptual and cognitive processes. These multidimensional measures of central nervous system bioelectrical activity respond to a variety of environmental and internal factors which have been experimentally characterized. Their application to the analysis of human performance in naturalistic task environments is just beginning. Converging evidence suggests that the N2-P3 complex reflects processes of stimulus evaluation, perceptual resource allocation, and decision making that proceed in parallel, rather than in series, with response generation. Utilization of these EP components may provide insights into the central nervous system mechanisms modulating task performance unavailable from behavioral measures alone. The sensitivity of the N2-P3 complex to neuropathology, psychopathology, and pharmacological manipulation suggests that these components might provide sensitive markers for the effects of environmental stressors on the human central nervous system.

Assessing the scientific research productivity of a leading toxicology journal: A case study of Human & Experimental Toxicology from 2003 to 2012.

PubMed

Zyoud, Sa'ed H; Al-Jabi, Samah W; Sweileh, Waleed M; Awang, Rahmat

2014-01-01

Bibliometric studies are increasingly being used for research assessments. Bibliometric indicators involve the application of statistical methods to scientific publications to obtain the bibliographics for each journal. The main objective of this study was to conduct a bibliometric evaluation of Human & Experimental Toxicology retrieved from the Scopus database. This study obtained data from Scopus published from 1 January 2003 till 31 December 2012. The keywords entered in Scopus to accomplish the objective of this study were 'Human', 'Experimental' and 'Toxicology' as 'Source Title'. Research productivity was evaluated based on a methodology developed and used in other bibliometric studies by analysing (a) total and trends in Human & Experimental Toxicology contributions in research between 2003 and 2012; (b) Human & Experimental Toxicology authorship patterns and productivity; (c) collaboration patterns; and (d) the citations received by the publications. There were 1229 research articles published in Human & Experimental Toxicology. Of the articles included, 947 (77.1%) were original articles and 104 (8.5%) were review articles. The Hirsch-index of the retrieved documents was 35. The largest number of publications in Human & Experimental Toxicology was from the United States (19.6%), followed by India (12.8%) and Turkey (10.9%). The total number of citations was 9119, with a median (interquartile range) of 3 (1-9) in 6797 documents. The highest median (interquartile range) number of citations was 8 (2.7-12.7) for France, followed by 7.5 (2-22.5) for Iran and 6 (3-13.5) for the United Kingdom. The country most often citing articles that were published in Human & Experimental Toxicology was the United States, which made citations in 1508 documents, followed by India with citations in 792 documents. The documents in Human & Experimental Toxicology focus principally on original data, with very few review articles. Review articles tend to have higher citation rates than original articles, and hence, the editors and authors of Human & Experimental Toxicology might usefully promote the submission of reviews in the future to improve the impact of the journal.

Social dysfunction after pediatric traumatic brain injury: a translational perspective

PubMed Central

Ryan, Nicholas P.; Catroppa, Cathy; Godfrey, Celia; Noble-Haeusslein, Linda J.; Shultz, Sandy R.; O'Brien, Terence J.; Anderson, Vicki; Semple, Bridgette D.

2016-01-01

Social dysfunction is common after traumatic brain injury (TBI), contributing to reduced quality of life for survivors. Factors which influence the emergence, development or persistence of social deficits after injury remain poorly understood, particularly in the context of ongoing brain maturation during childhood. Aberrant social interactions have recently been modeled in adult and juvenile rodents after experimental TBI, providing an opportunity to gain new insights into the underlying neurobiology of these behaviors. Here, we review our current understanding of social dysfunction in both humans and rodent models of TBI, with a focus on brain injuries acquired during early development. Modulators of social outcomes are discussed, including injury-related and environmental risk and resilience factors. Disruption of social brain network connectivity and aberrant neuroendocrine function are identified as potential mechanisms of social impairments after pediatric TBI. Throughout, we highlight the overlap and disparities between outcome measures and findings from clinical and experimental approaches, and explore the translational potential of future research to prevent or ameliorate social dysfunction after childhood TBI. PMID:26949224

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

Comparative study of MSX-2, DLX-5, and DLX-7 gene expression during early human tooth development.

PubMed

Davideau, J L; Demri, P; Hotton, D; Gu, T T; MacDougall, M; Sharpe, P; Forest, N; Berdal, A

1999-12-01

Msx and Dlx family transcription factors are key elements of craniofacial development and act in specific combinations with growth factors to control the position and shape of various skeletal structures in mice. In humans, the mutations of MSX and DLX genes are associated with specific syndromes, such as tooth agenesis, craniosynostosis, and tricho-dento-osseous syndrome. To establish some relationships between those reported human syndromes, previous experimental data in mice, and the expression patterns of MSX and DLX homeogenes in the human dentition, we investigated MSX-2, DLX-5, and DLX-7 expression patterns and compared them in orofacial tissues of 7.5- to 9-wk-old human embryos by using in situ hybridization. Our data showed that MSX-2 was strongly expressed in the progenitor cells of human orofacial skeletal structures, including mandible and maxilla bones, Meckel's cartilage, and tooth germs, as shown for DLX-5. DLX-7 expression was restricted to the vestibular lamina and, later on, to the vestibular part of dental epithelium. The comparison of MSX-2, DLX-5, and DLX-7 expression patterns during the early stages of development of different human tooth types showed the existence of spatially ordered sequences of homeogene expression along the vestibular/lingual axis of dental epithelium. The expression of MSX-2 in enamel knot, as well as the coincident expression of MSX-2, DLX-5, and DLX-7 in a restricted vestibular area of dental epithelium, suggests the existence of various organizing centers involved in the control of human tooth morphogenesis.

Predicting Human Clearance of OATP substrates using Cynomolgus monkey: In vitro-in vivo scaling of hepatic uptake clearance.

PubMed

de Bruyn, Tom; Ufuk, Ayse; Cantrill, Carina; Kosa, Rachel E; Bi, Yi-An; Niosi, Mark; Modi, Sweta; Rodrigues, A David; Tremaine, Larry M; Varma, Manthena Vs; Galetin, Aleksandra; Houston, J Brian

2018-05-02

This work explores the utility of the cynomolgus monkey as a preclinical model to predict hepatic uptake clearance mediated by organic anion transporting polypeptide (OATP) transporters. Nine OATP substrates (rosuvastatin, pravastatin, repaglinide, fexofenadine, cerivastatin, telmisartan, pitavastatin, bosentan and valsartan) were investigated in plated cynomolgus monkey and human hepatocytes. Total uptake clearance and passive diffusion were measured in vitro from initial rates in the absence and presence of the OATP inhibitor rifamycin SV, respectively. Total uptake clearance values in plated hepatocytes ranged over three orders of magnitude in both species with a similar rank order and good agreement in the relative contribution of active transport to total uptake between cynomolgus monkey and human. In vivo hepatic clearance for these nine drugs was determined in cynomolgus monkey after intravenous dosing. Hepatic clearances showed a similar range to human parameters and good predictions from respective hepatocyte parameters (with 2.7 and 3.8-fold bias on average, respectively). The use of cross species empirical scaling factors (based on either dataset average or individual drug scaling factor from cynomolgus monkey data) improved prediction (less bias, better concordance) of human hepatic clearance from human hepatocyte data alone. In vitro intracellular binding in hepatocytes also correlated well between species. It is concluded that the minimal species differences observed for the current dataset between cynomolgus monkey and human hepatocyte uptake, both in vitro and in vivo, support future use of this preclinical model to delineate drug hepatic uptake and enable prediction of human in vivo intrinsic hepatic clearance. The American Society for Pharmacology and Experimental Therapeutics.

Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways

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

Kabilan, S.; Suffield, S. R.; Recknagle, K. P.

Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived respectively from computed tomography (CT) and µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation–exhalation breathingmore » conditions using average species-specific minute volumes. Two different exposure scenarios were modeled in the rabbit based upon experimental inhalation studies. For comparison, human simulations were conducted at the highest exposure concentration used during the rabbit experimental exposures. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the nasal sinus compared to the human at the same air concentration of anthrax spores. In contrast, higher spore deposition was predicted in the lower conducting airways of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology for deposition.« less

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.

Experimental system, and its evaluation for the control of surgically inducted infections

NASA Technical Reports Server (NTRS)

Tevebaugh, M. D.; Nelson, J. P.

1972-01-01

The effect is reported to design, fabricate, test and evaluate a prototype experimental system for the control of surgically induced infections. The purpose is to provide the cleanest possible environment within a hospital surgery room and eliminate contamination sources that could cause infections during surgery. The system design is described. The system provides for a portable laminar flow clean room, a full bubble helmet system with associated communications and ventilation subsystems for operating room personnel, and surgical gowns that minimize the migration of bacteria. The development test results consisting of portability, laminar flowrate, air flow pattern, electrostatic buildup, noise level, ventilation, human factors, electrical and material compatibility tests are summarized. The conclusions are that the experimental system is effective in reducing the airborne and wound contamination although the helmets and gowns may not be a significant part of this reduction. Definitive conclusions with regard to the infection rate cannot be made at this time.

CamOptimus: a tool for exploiting complex adaptive evolution to optimize experiments and processes in biotechnology.

PubMed

Cankorur-Cetinkaya, Ayca; Dias, Joao M L; Kludas, Jana; Slater, Nigel K H; Rousu, Juho; Oliver, Stephen G; Dikicioglu, Duygu

2017-06-01

Multiple interacting factors affect the performance of engineered biological systems in synthetic biology projects. The complexity of these biological systems means that experimental design should often be treated as a multiparametric optimization problem. However, the available methodologies are either impractical, due to a combinatorial explosion in the number of experiments to be performed, or are inaccessible to most experimentalists due to the lack of publicly available, user-friendly software. Although evolutionary algorithms may be employed as alternative approaches to optimize experimental design, the lack of simple-to-use software again restricts their use to specialist practitioners. In addition, the lack of subsidiary approaches to further investigate critical factors and their interactions prevents the full analysis and exploitation of the biotechnological system. We have addressed these problems and, here, provide a simple-to-use and freely available graphical user interface to empower a broad range of experimental biologists to employ complex evolutionary algorithms to optimize their experimental designs. Our approach exploits a Genetic Algorithm to discover the subspace containing the optimal combination of parameters, and Symbolic Regression to construct a model to evaluate the sensitivity of the experiment to each parameter under investigation. We demonstrate the utility of this method using an example in which the culture conditions for the microbial production of a bioactive human protein are optimized. CamOptimus is available through: (https://doi.org/10.17863/CAM.10257).

Biological life-support systems

NASA Technical Reports Server (NTRS)

Shepelev, Y. Y.

1975-01-01

The establishment of human living environments by biologic methods, utilizing the appropriate functions of autotrophic and heterotrophic organisms is examined. Natural biologic systems discussed in terms of modeling biologic life support systems (BLSS), the structure of biologic life support systems, and the development of individual functional links in biologic life support systems are among the factors considered. Experimental modeling of BLSS in order to determine functional characteristics, mechanisms by which stability is maintained, and principles underlying control and regulation is also discussed.

Method for evaluating human exposure to 60 HZ electric fields

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

Deno, D.W.; Silva, M.

1984-07-01

This paper describes a method that has been successfully used to evaluate human exposure to 60 Hz electric fields. An exposure measuring system that uses an electric field sensor vest and data collection instrumentation is presented. Exposure concepts and activity factors are discussed and experimental data collected with the exposure system are provided. This method can be used to measure exposure to a wide range of electric field with intensities from less than 1 V/m to more than 10 kV/m. Results may be translated to characterize various exposure criteria (time histogram of unperturbed field, surface fields, internal current density, totalmore » body current, etc).« less

Guidance of visual attention by semantic information in real-world scenes

PubMed Central

Wu, Chia-Chien; Wick, Farahnaz Ahmed; Pomplun, Marc

2014-01-01

Recent research on attentional guidance in real-world scenes has focused on object recognition within the context of a scene. This approach has been valuable for determining some factors that drive the allocation of visual attention and determine visual selection. This article provides a review of experimental work on how different components of context, especially semantic information, affect attentional deployment. We review work from the areas of object recognition, scene perception, and visual search, highlighting recent studies examining semantic structure in real-world scenes. A better understanding on how humans parse scene representations will not only improve current models of visual attention but also advance next-generation computer vision systems and human-computer interfaces. PMID:24567724

Assessing the Role of the 'Unity Assumption' on Multisensory Integration: A Review.

PubMed

Chen, Yi-Chuan; Spence, Charles

2017-01-01

There has been longstanding interest from both experimental psychologists and cognitive neuroscientists in the potential modulatory role of various top-down factors on multisensory integration/perception in humans. One such top-down influence, often referred to in the literature as the 'unity assumption,' is thought to occur in those situations in which an observer considers that various of the unisensory stimuli that they have been presented with belong to one and the same object or event (Welch and Warren, 1980). Here, we review the possible factors that may lead to the emergence of the unity assumption. We then critically evaluate the evidence concerning the consequences of the unity assumption from studies of the spatial and temporal ventriloquism effects, from the McGurk effect, and from the Colavita visual dominance paradigm. The research that has been published to date using these tasks provides support for the claim that the unity assumption influences multisensory perception under at least a subset of experimental conditions. We then consider whether the notion has been superseded in recent years by the introduction of priors in Bayesian causal inference models of human multisensory perception. We suggest that the prior of common cause (that is, the prior concerning whether multisensory signals originate from the same source or not) offers the most useful way to quantify the unity assumption as a continuous cognitive variable.

Estimation of the kinetic energy dissipation in fall-arrest system and manikin during fall impact.

PubMed

Wu, John Z; Powers, John R; Harris, James R; Pan, Christopher S

2011-04-01

Fall-arrest systems (FASs) have been widely applied to provide a safe stop during fall incidents for occupational activities. The mechanical interaction and kinetic energy exchange between the human body and the fall-arrest system during fall impact is one of the most important factors in FAS ergonomic design. In the current study, we developed a systematic approach to evaluate the energy dissipated in the energy absorbing lanyard (EAL) and in the harness/manikin during fall impact. The kinematics of the manikin and EAL during the impact were derived using the arrest-force time histories that were measured experimentally. We applied the proposed method to analyse the experimental data of drop tests at heights of 1.83 and 3.35 m. Our preliminary results indicate that approximately 84-92% of the kinetic energy is dissipated in the EAL system and the remainder is dissipated in the harness/manikin during fall impact. The proposed approach would be useful for the ergonomic design and performance evaluation of an FAS. STATEMENT OF RELEVANCE: Mechanical interaction, especially kinetic energy exchange, between the human body and the fall-arrest system during fall impact is one of the most important factors in the ergonomic design of a fall-arrest system. In the current study, we propose an approach to quantify the kinetic energy dissipated in the energy absorbing lanyard and in the harness/body system during fall impact.

Signal-to-noise ratio and MR tissue parameters in human brain imaging at 3, 7, and 9.4 tesla using current receive coil arrays.

PubMed

Pohmann, Rolf; Speck, Oliver; Scheffler, Klaus

2016-02-01

Relaxation times, transmit homogeneity, signal-to-noise ratio (SNR) and parallel imaging g-factor were determined in the human brain at 3T, 7T, and 9.4T, using standard, tight-fitting coil arrays. The same human subjects were scanned at all three field strengths, using identical sequence parameters and similar 31- or 32-channel receive coil arrays. The SNR of three-dimensional (3D) gradient echo images was determined using a multiple replica approach and corrected with measured flip angle and T2 (*) distributions and the T1 of white matter to obtain the intrinsic SNR. The g-factor maps were derived from 3D gradient echo images with several GRAPPA accelerations. As expected, T1 values increased, T2 (*) decreased and the B1 -homogeneity deteriorated with increasing field. The SNR showed a distinctly supralinear increase with field strength by a factor of 3.10 ± 0.20 from 3T to 7T, and 1.76 ± 0.13 from 7T to 9.4T over the entire cerebrum. The g-factors did not show the expected decrease, indicating a dominating role of coil design. In standard experimental conditions, SNR increased supralinearly with field strength (SNR ∼ B0 (1.65) ). To take full advantage of this gain, the deteriorating B1 -homogeneity and the decreasing T2 (*) have to be overcome. © 2015 Wiley Periodicals, Inc.

Auditory Contagious Yawning in Humans: An Investigation into Affiliation and Status Effects

PubMed Central

Massen, Jorg J. M.; Church, Allyson M.; Gallup, Andrew C.

2015-01-01

While comparative research on contagious yawning has grown substantially in the past few years, both the interpersonal factors influencing this response and the sensory modalities involved in its activation in humans remain relatively unknown. Extending upon previous studies showing various in-group and status effects in non-human great apes, we performed an initial study to investigate how the political affiliation (Democrat vs. Republican) and status (high vs. low) of target stimuli influences auditory contagious yawning, as well as the urge to yawn, in humans. Self-report responses and a subset of video recordings were analyzed from 118 undergraduate students in the US following exposure to either breathing (control) or yawning (experimental) vocalizations paired with images of former US Presidents (high status) and their respective Cabinet Secretaries of Commerce (low status). The overall results validate the use of auditory stimuli to prompt yawn contagion, with greater response in the experimental than the control condition. There was also a negative effect of political status on self-reported yawning and the self-reported urge to yawn irrespective of the condition. In contrast, we found no evidence for a political affiliation bias in this response. These preliminary findings are discussed in terms of the existing comparative evidence, though we highlight limitations in the current investigation and we provide suggestions for future research in this area. PMID:26617557

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.

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.

Using experimental design to define boundary manikins.

PubMed

Bertilsson, Erik; Högberg, Dan; Hanson, Lars

2012-01-01

When evaluating human-machine interaction it is central to consider anthropometric diversity to ensure intended accommodation levels. A well-known method is the use of boundary cases where manikins with extreme but likely measurement combinations are derived by mathematical treatment of anthropometric data. The supposition by that method is that the use of these manikins will facilitate accommodation of the expected part of the total, less extreme, population. In literature sources there are differences in how many and in what way these manikins should be defined. A similar field to the boundary case method is the use of experimental design in where relationships between affecting factors of a process is studied by a systematic approach. This paper examines the possibilities to adopt methodology used in experimental design to define a group of manikins. Different experimental designs were adopted to be used together with a confidence region and its axes. The result from the study shows that it is possible to adapt the methodology of experimental design when creating groups of manikins. The size of these groups of manikins depends heavily on the number of key measurements but also on the type of chosen experimental design.

Development and Application of a Clinical Microsystem Simulation Methodology for Human Factors-Based Research of Alarm Fatigue.

PubMed

Kobayashi, Leo; Gosbee, John W; Merck, Derek L

2017-07-01

(1) To develop a clinical microsystem simulation methodology for alarm fatigue research with a human factors engineering (HFE) assessment framework and (2) to explore its application to the comparative examination of different approaches to patient monitoring and provider notification. Problems with the design, implementation, and real-world use of patient monitoring systems result in alarm fatigue. A multidisciplinary team is developing an open-source tool kit to promote bedside informatics research and mitigate alarm fatigue. Simulation, HFE, and computer science experts created a novel simulation methodology to study alarm fatigue. Featuring multiple interconnected simulated patient scenarios with scripted timeline, "distractor" patient care tasks, and triggered true and false alarms, the methodology incorporated objective metrics to assess provider and system performance. Developed materials were implemented during institutional review board-approved study sessions that assessed and compared an experimental multiparametric alerting system with a standard monitor telemetry system for subject response, use characteristics, and end-user feedback. A four-patient simulation setup featuring objective metrics for participant task-related performance and response to alarms was developed along with accompanying structured HFE assessment (questionnaire and interview) for monitor systems use testing. Two pilot and four study sessions with individual nurse subjects elicited true alarm and false alarm responses (including diversion from assigned tasks) as well as nonresponses to true alarms. In-simulation observation and subject questionnaires were used to test the experimental system's approach to suppressing false alarms and alerting providers. A novel investigative methodology applied simulation and HFE techniques to replicate and study alarm fatigue in controlled settings for systems assessment and experimental research purposes.

A virtual experimenter to increase standardization for the investigation of placebo effects.

PubMed

Horing, Bjoern; Newsome, Nathan D; Enck, Paul; Babu, Sabarish V; Muth, Eric R

2016-07-18

Placebo effects are mediated by expectancy, which is highly influenced by psychosocial factors of a treatment context. These factors are difficult to standardize. Furthermore, dedicated placebo research often necessitates single-blind deceptive designs where biases are easily introduced. We propose a study protocol employing a virtual experimenter - a computer program designed to deliver treatment and instructions - for the purpose of standardization and reduction of biases when investigating placebo effects. To evaluate the virtual experimenter's efficacy in inducing placebo effects via expectancy manipulation, we suggest a partially blinded, deceptive design with a baseline/retest pain protocol (hand immersions in hot water bath). Between immersions, participants will receive an (actually inert) medication. Instructions pertaining to the medication will be delivered by one of three metaphors: The virtual experimenter, a human experimenter, and an audio/text presentation (predictor "Metaphor"). The second predictor includes falsely informing participants that the medication is an effective pain killer, or correctly informing them that it is, in fact, inert (predictor "Instruction"). Analysis will be performed with hierarchical linear modelling, with a sample size of N = 50. Results from two pilot studies are presented that indicate the viability of the pain protocol (N = 33), and of the virtual experimenter software and placebo manipulation (N = 48). It will be challenging to establish full comparability between all metaphors used for instruction delivery, and to account for participant differences in acceptance of their virtual interaction partner. Once established, the presence of placebo effects would suggest that the virtual experimenter exhibits sufficient cues to be perceived as a social agent. He could consequently provide a convenient platform to investigate effects of experimenter behavior, or other experimenter characteristics, e.g., sex, age, race/ethnicity or professional status. More general applications are possible, for example in psychological research such as bias research, or virtual reality research. Potential applications also exist for standardizing clinical research by documenting and communicating instructions used in clinical trials.

[A preliminary study for the effect of nano hydroxyapatite on human adipose-derived mesenchymal stem cells mixture 3D bio-printing].

PubMed

Song, Y; Wang, X F; Wang, Y G; Dong, F; Lv, P J

2016-10-18

To study the effect of nano hydroxyapatite on human adipose-derived mesenchymal stem cells(hASCs) mixture 3D bio-printing for cells' proliferation and osteogenesis. P5 hASCs were used as seed cells, 10 g/L nano hydroxyapatite was added into the cell-sodium alginate-gelatin mixture (concentration: 20 g/L sodium alginate, 80 g/L gelatin; cell density: 1×10 6 /mL), then the mixture was printed by 3D bio-printer as the experimental group. And the cell-sodium alginate-gelatin mixture without nano hydroxyapatite was printed as the control group. Respectively, both the experimental and control groups were detected by microscope, CCK-8, Western blot and PCR at certain time pointsafter being printed, whose cells' proliferation and osteogenic differentiation were analyzed. The microscopic observation and CCK-8 results showed that the cells of the experimental group and the control group both had a good proliferation 24 h and 7 d after being printed. The Western blot results showed that 14 d after printing, the expression of Runt-related transcription factor 2 (RUNX2) had no statistical difference between the experimental group and control group. The PCR results showed that 14 d after printing, the expression of osteogenesis-related genes (RUNX2, osterix, and osteocalcin) was significantly higher in the experimental group than in the control group. Nano hydroxyapatite can increase osteogenic differentiation of the hASCs mixture after bio-printing, in which the cells still have a good proliferation.

Pre-birth origins of allergy and asthma.

PubMed

Gatford, K L; Wooldridge, A L; Kind, K L; Bischof, R; Clifton, V L

2017-09-01

Allergy is a chronic disease that can develop as early as infancy, suggesting that early life factors are important in its aetiology. Variable associations between size at birth, a crude marker of the fetal environment, and allergy have been reported in humans and require comprehensive review. Associations between birth weight and allergy are however confounded in humans, and we and others have therefore begun exploring the effects of early life events on allergy in experimental models. In particular, we are using ovine models to investigate whether and how a restricted environment before birth protects against allergy, whether methyl donor availability contributes to allergic protection in IUGR, and why maternal asthma during pregnancy is associated with increased risks of allergic disease in children. We found that experimental intrauterine growth restriction (IUGR) in sheep reduced cutaneous responses to antigens in progeny, despite normal or elevated IgE responses. Furthermore, maternal methyl donor supplementation in late pregnancy partially reversed effects of experimental IUGR, consistent with the proposal that epigenetic pathways underlie some but not all effects of IUGR on allergic susceptibility. Ovine experimental allergic asthma with exacerbations reduces relative fetal size in late gestation, with some changes in immune populations in fetal thymus suggestive of increased activation. Maternal allergic asthma in mice also predisposes progeny to allergy development. In conclusion, these findings in experimental models provide direct evidence that a perturbed environment before birth alters immune system development and postnatal function, and provide opportunities to investigate underlying mechanisms and develop and evaluate interventions. Copyright © 2017 Elsevier B.V. All rights reserved.

Using portable particle sizing instrumentation to rapidly measure the penetration of fine and ultrafine particles in unoccupied residences.

PubMed

Zhao, H; Stephens, B

2017-01-01

Much of human exposure to particulate matter of outdoor origin occurs inside buildings, particularly in residences. The particle penetration factor through leaks in a building's exterior enclosure assembly is a key parameter that governs the infiltration of outdoor particles. However, experimental data for size-resolved particle penetration factors in real buildings, as well as penetration factors for fine particles less than 2.5 μm (PM 2.5 ) and ultrafine particles less than 100 nm (UFPs), remain limited, in part because of previous limitations in instrumentation and experimental methods. Here, we report on the development and application of a modified test method that utilizes portable particle sizing instrumentation to measure size-resolved infiltration factors and envelope penetration factors for 0.01-2.5 μm particles, which are then used to estimate penetration factors for integral measures of UFPs and PM 2.5 . Eleven replicate measurements were made in an unoccupied apartment unit in Chicago, IL to evaluate the accuracy and repeatability of the test procedure and solution methods. Mean estimates of size-resolved penetration factors ranged from 0.41 ± 0.14 to 0.73 ± 0.05 across the range of measured particle sizes, while mean estimates of penetration factors for integral measures of UFPs and PM 2.5 were 0.67 ± 0.05 and 0.73 ± 0.05, respectively. Average relative uncertainties for all particle sizes/classes were less than 20%. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Angiogenin Expression during Early Human Placental Development; Association with Blood Vessel Formation

PubMed Central

Pavlov, Nadine; Guibourdenche, Jean; Degrelle, Séverine A.; Evain-Brion, Danièle

2014-01-01

The placenta is a transient organ essential for fetal development. During human placental development, chorionic villi grow in coordination with a large capillary network resulting from both vasculogenesis and angiogenesis. Angiogenin is one of the most potent inducers of neovascularisation in experimental models in vivo. We and others have previously mapped angiogenin expression in the human term placenta. Here, we explored angiogenin involvement in early human placental development. We studied, angiogenin expression by in situ hybridisation and/or by RT-PCR in tissues and primary cultured trophoblastic cells and angiogenin cellular distribution by coimmunolabelling with cell markers: CD31 (PECAM-1), vascular endothelial cadherin (VE-cadherin), vascular endothelial growth factor receptor-2 (VEGF-R2), Tie-2, von Willebrand factor, CD34, erythropoeitin receptor (Epo-R), alpha-smooth muscle actin, CD45, cytokeratin 7, and Ki-67. Extravillous and villous cytotrophoblasts, isolated and differentiated in vitro, expressed and secreted angiogenin. Angiogenin was detected in villous trophoblastic layers, and structured and nascent fetal vessels. In decidua, it was expressed by glandular epithelial cells, vascular cells and macrophages. The observed pattern of angiogenin expression is compatible with a role in blood vessel formation and in cross-talk between trophoblasts and endothelial cells. In view of angiogenin properties, we suggest that angiogenin may participate in placental vasculogenesis and organogenesis. PMID:25093183

Using knowledge from human research to improve understanding of contest theory and contest dynamics

PubMed Central

Denson, Thomas F.

2017-01-01

Our understanding of animal contests and the factors that affect contest dynamics and decisions stems from a long and prosperous collaboration between empiricists and theoreticians. Over the last two decades, however, theoretical predictions regarding the factors that affect individual decisions before, during and after a contest are becoming increasingly difficult to test empirically. Extremely large sample sizes are necessary to experimentally test the nuanced theoretical assumptions surrounding how information is used by animals during a contest, how context changes the information used, and how individuals change behaviour as a result of both the information available and the context in which the information is acquired. In this review, we discuss how the investigation of contests in humans through the collaboration of biologists and psychologists may advance contest theory and dynamics in general. We argue that a long and productive history exploring human behaviour and psychology combined with technological advancements provide a unique opportunity to manipulate human perception during contests and collect unbiased data, allowing more targeted examinations of particular aspects of contest theory (e.g. winner/loser effects, information use as a function of age). We hope that our perspective provides the impetus for many future collaborations between biologists and psychologists. PMID:29237857

Toward a Neurology of Loneliness

PubMed Central

Cacioppo, Stephanie; Capitanio, John P.; Cacioppo, John T.

2016-01-01

Social isolation has been recognized as a major risk factor for morbidity and mortality in humans for more than a quarter century. The brain is the key organ of social connections and processes, however, and the same objective social relationship can be experienced as caring and protective or as exploitive and isolating. We review evidence that the perception of social isolation (i.e., loneliness) impacts brain and behavior and is a risk factor for broad-based morbidity and mortality. However, the causal role of loneliness on neural mechanisms and mortality is difficult to test conclusively in humans. Mechanistic animal studies provide a lens through which to evaluate the neurological effects of a member of a social species living chronically on the social perimeter. Experimental studies show that social isolation produces significant changes in brain structures and processes in adult social animals. These effects are not uniform across the brain or across species but instead are most evident in brain regions that reflect differences in the functional demands of solitary versus social living for a particular species. The human and animal literatures have developed independently, however, and significant gaps also exist. The current review underscores the importance of integrating human and animal research to delineate the mechanisms through which social relationships impact the brain, health, and well-being. PMID:25222636

Development, Testing, and Validation of a Model-Based Tool to Predict Operator Responses in Unexpected Workload Transitions

NASA Technical Reports Server (NTRS)

Sebok, Angelia; Wickens, Christopher; Sargent, Robert

2015-01-01

One human factors challenge is predicting operator performance in novel situations. Approaches such as drawing on relevant previous experience, and developing computational models to predict operator performance in complex situations, offer potential methods to address this challenge. A few concerns with modeling operator performance are that models need to realistic, and they need to be tested empirically and validated. In addition, many existing human performance modeling tools are complex and require that an analyst gain significant experience to be able to develop models for meaningful data collection. This paper describes an effort to address these challenges by developing an easy to use model-based tool, using models that were developed from a review of existing human performance literature and targeted experimental studies, and performing an empirical validation of key model predictions.

Phase transitions in oleic acid and in human breast tissue as studied by Raman spectroscopy and Raman imaging.

PubMed

Brozek-Pluska, Beata; Jablonska-Gajewicz, Joanna; Kordek, Radzislaw; Abramczyk, Halina

2011-05-12

We present the results of differential scanning calorimetry (DSC) and Raman studies in the temperature range of 293-77 K on vibrational properties of the oleic acid and the human breast tissue as a function of temperature. We have found that vibrational properties are very sensitive indicators to specify phases and phase transitions at the molecular level. We have found that water content confined in the cancerous tissue is markedly different from that in the noncancerous tissue. The OH stretching vibrations of water are useful as potential Raman biomarkers to distinguish between the cancerous and the noncancerous human breast tissues. Our results provide experimental evidence on the role of lipid profile and cell hydration as factors of particular significance in differentiation of the noncancerous and cancerous breast tissues.

The Use of Empirical Data Sources in HRA

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

Bruce Hallbert; David Gertman; Julie Marble

This paper presents a review of available information related to human performance to support Human Reliability Analysis (HRA) performed for nuclear power plants (NPPs). A number of data sources are identified as potentially useful. These include NPP licensee event reports (LERs), augmented inspection team (AIT) reports, operator requalification data, results from the literature in experimental psychology, and the Aviation Safety Reporting System (ASRSs). The paper discusses how utilizing such information improves our capability to model and quantify human performance. In particular the paper discusses how information related to performance shaping factors (PSFs) can be extracted from empirical data to determinemore » their size effect, their relative effects, as well as their interactions. The paper concludes that appropriate use of existing sources can help addressing some of the important issues we are currently facing in HRA.« less

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

On high b diffusion imaging in the human brain: ruminations and experimental insights.

PubMed

Mulkern, Robert V; Haker, Steven J; Maier, Stephan E

2009-10-01

Interest in the manner in which brain tissue signal decays with b factor in diffusion imaging schemes has grown in recent years following the observation that the decay curves depart from purely monoexponential decay behavior. Regardless of the model or fitting function proposed for characterizing sufficiently sampled decay curves (vide infra), the departure from monoexponentiality spells increased tissue characterization potential. The degree to which this potential can be harnessed to improve specificity, sensitivity and spatial localization of diseases in brain, and other tissues, largely remains to be explored. Furthermore, the degree to which currently popular diffusion tensor imaging methods, including visually impressive white matter fiber "tractography" results, have almost completely ignored the nonmonoexponential nature of the basic signal decay with b factor is worthy of communal introspection. Here we limit our attention to a review of the basic experimental features associated with brain water signal diffusion decay curves as measured over extended b-factor ranges, the simple few parameter fitting functions that have been proposed to characterize these decays and the more involved models, e.g.,"ruminations," which have been proposed to account for the nonmonoexponentiality to date.

On high b diffusion imaging in the human brain: ruminations and experimental insights✩

PubMed Central

Mulkern, Robert V.; Haker, Steven J.; Maier, Stephan E.

2010-01-01

Interest in the manner in which brain tissue signal decays with b factor in diffusion imaging schemes has grown in recent years following the observation that the decay curves depart from purely monoexponential decay behavior. Regardless of the model or fitting function proposed for characterizing sufficiently sampled decay curves (vide infra), the departure from monoexponentiality spells increased tissue characterization potential. The degree to which this potential can be harnessed to improve specificity, sensitivity and spatial localization of diseases in brain, and other tissues, largely remains to be explored. Furthermore, the degree to which currently popular diffusion tensor imaging methods, including visually impressive white matter fiber “tractography” results, have almost completely ignored the nonmonoexponential nature of the basic signal decay with b factor is worthy of communal introspection. Here we limit our attention to a review of the basic experimental features associated with brain water signal diffusion decay curves as measured over extended b-factor ranges, the simple few parameter fitting functions that have been proposed to characterize these decays and the more involved models, e.g.,“ruminations,” which have been proposed to account for the nonmonoexponentiality to date. PMID:19520535

Strawberry Phytochemicals Inhibit Azoxymethane/Dextran Sodium Sulfate-Induced Colorectal Carcinogenesis in Crj: CD-1 Mice

PubMed Central

Shi, Ni; Clinton, Steven K.; Liu, Zhihua; Wang, Yongquan; Riedl, Kenneth M.; Schwartz, Steven J.; Zhang, Xiaoli; Pan, Zui; Chen, Tong

2015-01-01

Human and experimental colon carcinogenesis are enhanced by a pro-inflammatory microenvironment. Pharmacologically driven chemopreventive agents and dietary variables are hypothesized to have future roles in the prevention of colon cancer by targeting these processes. The current study was designed to determine the ability of dietary lyophilized strawberries to inhibit inflammation-promoted colon carcinogenesis in a preclinical animal model. Mice were given a single i.p. injection of azoxymethane (10 mg kg−1 body weight). One week after injection, mice were administered 2% (w/v) dextran sodium sulfate in drinking water for seven days and then an experimental diet containing chemically characterized lyophilized strawberries for the duration of the bioassay. Mice fed control diet, or experimental diet containing 2.5%, 5.0% or 10.0% strawberries displayed tumor incidence of 100%, 64%, 75% and 44%, respectively (p < 0.05). The mechanistic studies demonstrate that strawberries reduced expression of proinflammatory mediators, suppressed nitrosative stress and decreased phosphorylation of phosphatidylinositol 3-kinase, Akt, extracellular signal-regulated kinase and nuclear factor kappa B. In conclusion, strawberries target proinflammatory mediators and oncogenic signaling for the preventive efficacies against colon carcinogenesis in mice. This works supports future development of fully characterized and precisely controlled functional foods for testing in human clinical trials for this disease. PMID:25763529

Bioconcentration of gaseous organic chemicals in plant leaves: Comparison of experimental data with model predictions

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

Polder, M.D.; Hulzebos, E.M.; Jager, D.T.

1998-01-01

This literature study is performed to support the implementation of two models in a risk assessment system for the evaluation of chemicals and their risk for human health and the environment. One of the exposure pathways for humans and cattle is the uptake of chemicals by plants. In this risk assessment system the transfer of gaseous organic substances from air to plants modeled by Riederer is included. A similar model with a more refined approach, including dilution by growth, is proposed by Trapp and Matthies, which was implemented in the European version of this risk assessment system (EUSES). In thismore » study both models are evaluated by comparison with experimental data on leaf/air partition coefficients found in the literature. For herbaceous plants both models give good estimations for the leaf/air partition coefficient up to 10{sup 7}, with deviations for most substances within a factor of five. For the azalea and spruce group the fit between experimental BCF values and the calculated model values is less adequate. For substances for which Riederer estimates a leaf/air partition coefficient above 10{sup 7}, the approach of Trapp and Matthies seems more adequate; however, few data were available.« less

Integration of biological data by kernels on graph nodes allows prediction of new genes involved in mitotic chromosome condensation

PubMed Central

Hériché, Jean-Karim; Lees, Jon G.; Morilla, Ian; Walter, Thomas; Petrova, Boryana; Roberti, M. Julia; Hossain, M. Julius; Adler, Priit; Fernández, José M.; Krallinger, Martin; Haering, Christian H.; Vilo, Jaak; Valencia, Alfonso; Ranea, Juan A.; Orengo, Christine; Ellenberg, Jan

2014-01-01

The advent of genome-wide RNA interference (RNAi)–based screens puts us in the position to identify genes for all functions human cells carry out. However, for many functions, assay complexity and cost make genome-scale knockdown experiments impossible. Methods to predict genes required for cell functions are therefore needed to focus RNAi screens from the whole genome on the most likely candidates. Although different bioinformatics tools for gene function prediction exist, they lack experimental validation and are therefore rarely used by experimentalists. To address this, we developed an effective computational gene selection strategy that represents public data about genes as graphs and then analyzes these graphs using kernels on graph nodes to predict functional relationships. To demonstrate its performance, we predicted human genes required for a poorly understood cellular function—mitotic chromosome condensation—and experimentally validated the top 100 candidates with a focused RNAi screen by automated microscopy. Quantitative analysis of the images demonstrated that the candidates were indeed strongly enriched in condensation genes, including the discovery of several new factors. By combining bioinformatics prediction with experimental validation, our study shows that kernels on graph nodes are powerful tools to integrate public biological data and predict genes involved in cellular functions of interest. PMID:24943848

Suppression of chronic experimental autoimmune neuritis by nasally administered recombinant rat interleukin-6

PubMed Central

DERETZI, G; PELIDOU, S-H; ZOU, L-P; QUIDING, C; MIX, E; LEVI, M; WAHREN, B; ZHU, J

1999-01-01

Experimental autoimmune neuritis (EAN) is a CD4+ T-cell-mediated demyelinating disease of the peripheral nervous system (PNS) and serves as experimental model for human immune-demyelinating neurophathies, especially the Guillain–Barré syndrome. In this study, we examined the effect of recombinant rat interleukin-6 (rrIL-6) on chronic EAN in Lewis rats induced by immunization with P2 peptide 57-81 and Freund’s complete adjuvant (FCA). Nasal administration of rat rIL-6 (1 μg/rat/day) beginning in the initial phase of EAN as a therapeutic agent, decreased the severity and the duration of clinical EAN. Low-grade inflammation and suppression of regional demyelination within the sciatic nerves were seen in rrIL-6-treated rats. Hyporesponsiveness of lymph node T cells, down-regulation of serum tumour necrosis factor-α (TNF-α) and increased levels of P2-specific immunoglobulin G1 (IgG1) antibodies document that nasal administration of rrIL-6 was effective systemically. However, because of the non-specific nature of the treatment and multiple effects of IL-6, more experience and great caution are needed, before nasal administration of IL-6 can be considered as a treatment of human autoimmune demyelinating neurophathies. PMID:10447716

Automatized set-up procedure for transcranial magnetic stimulation protocols.

PubMed

Harquel, S; Diard, J; Raffin, E; Passera, B; Dall'Igna, G; Marendaz, C; David, O; Chauvin, A

2017-06-01

Transcranial Magnetic Stimulation (TMS) established itself as a powerful technique for probing and treating the human brain. Major technological evolutions, such as neuronavigation and robotized systems, have continuously increased the spatial reliability and reproducibility of TMS, by minimizing the influence of human and experimental factors. However, there is still a lack of efficient set-up procedure, which prevents the automation of TMS protocols. For example, the set-up procedure for defining the stimulation intensity specific to each subject is classically done manually by experienced practitioners, by assessing the motor cortical excitability level over the motor hotspot (HS) of a targeted muscle. This is time-consuming and introduces experimental variability. Therefore, we developed a probabilistic Bayesian model (AutoHS) that automatically identifies the HS position. Using virtual and real experiments, we compared the efficacy of the manual and automated procedures. AutoHS appeared to be more reproducible, faster, and at least as reliable as classical manual procedures. By combining AutoHS with robotized TMS and automated motor threshold estimation methods, our approach constitutes the first fully automated set-up procedure for TMS protocols. The use of this procedure decreases inter-experimenter variability while facilitating the handling of TMS protocols used for research and clinical routine. Copyright © 2017 Elsevier Inc. All rights reserved.

Nondestructive Testing of Overhead Transmission LINES—NUMERICAL and Experimental Investigation

NASA Astrophysics Data System (ADS)

Kulkarni, S.; Hurlebaus, S.

2009-03-01

Overhead transmission lines are periodically inspected using both on-ground and helicopter-aided visual inspection. Factors including sun glare, cloud cover, close proximity to power lines and the rapidly changing visual circumstances make airborne inspection of power lines a particularly hazardous task. In this study, a finite element model is developed that can be used to create the theoretical dispersion curves of an overhead transmission line. The numerical results are then verified with experimental test using a non-contact and broadband laser detection technique. The methodology developed in this study can be further extended to a continuous monitoring system and be applied to other cable monitoring applications, such as bridge cable monitoring, which would otherwise put human inspectors at risk.

Effects of different growth factors and carriers on bone regeneration: a systematic review.

PubMed

Khojasteh, Arash; Behnia, Hossein; Naghdi, Navid; Esmaeelinejad, Mohammad; Alikhassy, Zahra; Stevens, Mark

2013-12-01

The application and subsequent investigations in the use of varied osteogenic growth factors in bone regeneration procedures have grown dramatically over the past several years. Owing to this rapid gain in popularity and documentation, a review was undertaken to evaluate the in vivo effects of growth factors on bone regeneration. Using related key words, electronic databases (Medline, Embase, and Cochrane) were searched for articles published from 1999 to April 2010 to find growth factor application in bone regeneration in human or animal models. A total of 63 articles were matched with the inclusion criteria of this study. Bone morphogenetic protein 2 (BMP-2) was the most studied growth factor. Carriers for the delivery, experimental sites, and methods of evaluation were different, and therefore articles did not come to a general agreement. Within the limitations of this review, BMP-2 may be an appropriate growth factor for osteogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2016-07-01

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

Modeling RNA polymerase interaction in mitochondria of chordates

PubMed Central

2012-01-01

Background In previous work, we introduced a concept, a mathematical model and its computer realization that describe the interaction between bacterial and phage type RNA polymerases, protein factors, DNA and RNA secondary structures during transcription, including transcription initiation and termination. The model accurately reproduces changes of gene transcription level observed in polymerase sigma-subunit knockout and heat shock experiments in plant plastids. The corresponding computer program and a user guide are available at http://lab6.iitp.ru/en/rivals. Here we apply the model to the analysis of transcription and (partially) translation processes in the mitochondria of frog, rat and human. Notably, mitochondria possess only phage-type polymerases. We consider the entire mitochondrial genome so that our model allows RNA polymerases to complete more than one circle on the DNA strand. Results Our model of RNA polymerase interaction during transcription initiation and elongation accurately reproduces experimental data obtained for plastids. Moreover, it also reproduces evidence on bulk RNA concentrations and RNA half-lives in the mitochondria of frog, human with or without the MELAS mutation, and rat with normal (euthyroid) or hyposecretion of thyroid hormone (hypothyroid). The transcription characteristics predicted by the model include: (i) the fraction of polymerases terminating at a protein-dependent terminator in both directions (the terminator polarization), (ii) the binding intensities of the regulatory protein factor (mTERF) with the termination site and, (iii) the transcription initiation intensities (initiation frequencies) of all promoters in all five conditions (frog, healthy human, human with MELAS syndrome, healthy rat, and hypothyroid rat with aberrant mtDNA methylation). Using the model, absolute levels of all gene transcription can be inferred from an arbitrary array of the three transcription characteristics, whereas, for selected genes only relative RNA concentrations have been experimentally determined. Conversely, these characteristics and absolute transcription levels can be obtained using relative RNA concentrations and RNA half-lives known from various experimental studies. In this case, the “inverse problem” is solved with multi-objective optimization. Conclusions In this study, we demonstrate that our model accurately reproduces all relevant experimental data available for plant plastids, as well as the mitochondria of chordates. Using experimental data, the model is applied to estimate binding intensities of phage-type RNA polymerases to their promoters as well as predicting terminator characteristics, including polarization. In addition, one can predict characteristics of phage-type RNA polymerases and the transcription process that are difficult to measure directly, e.g., the association between the promoter’s nucleotide composition and the intensity of polymerase binding. To illustrate the application of our model in functional predictions, we propose a possible mechanism for MELAS syndrome development in human involving a decrease of Phe-tRNA, Val-tRNA and rRNA concentrations in the cell. In addition, we describe how changes in methylation patterns of the mTERF binding site and three promoters in hypothyroid rat correlate with changes in intensities of the mTERF binding and transcription initiations. Finally, we introduce an auxiliary model to describe the interaction between polysomal mRNA and ribonucleases. PMID:22873568

Specification of functional cranial placode derivatives from human pluripotent stem cells.

PubMed

Dincer, Zehra; Piao, Jinghua; Niu, Lei; Ganat, Yosif; Kriks, Sonja; Zimmer, Bastian; Shi, Song-Hai; Tabar, Viviane; Studer, Lorenz

2013-12-12

Cranial placodes are embryonic structures essential for sensory and endocrine organ development. Human placode development has remained largely inaccessible despite the serious medical conditions caused by the dysfunction of placode-derived tissues. Here, we demonstrate the efficient derivation of cranial placodes from human pluripotent stem cells. Timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Concomitant inhibition of fibroblast growth factor signaling disrupts placode derivation and induces surface ectoderm. Further fate specification at the preplacode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers, and anterior pituitary hormone-producing cells that upon transplantation produce human growth hormone and adrenocorticotropic hormone in vivo. Our results establish a powerful experimental platform to study human cranial placode development and set the stage for the development of human cell-based therapies in sensory and endocrine disease. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Mouse Models for Investigating the Developmental Bases of Human Birth Defects

PubMed Central

MOON, ANNE M.

2006-01-01

Clinicians and basic scientists share an interest in discovering how genetic or environmental factors interact to perturb normal development and cause birth defects and human disease. Given the complexity of such interactions, it is not surprising that 4% of human infants are born with a congenital malformation, and cardiovascular defects occur in nearly 1%. Our research is based on the fundamental hypothesis that an understanding of normal and abnormal development will permit us to generate effective strategies for both prevention and treatment of human birth defects. Animal models are invaluable in these efforts because they allow one to interrogate the genetic, molecular and cellular events that distinguish normal from abnormal development. Several features of the mouse make it a particularly powerful experimental model: it is a mammalian system with similar embryology, anatomy and physiology to humans; genes, proteins and regulatory programs are largely conserved between human and mouse; and finally, gene targeting in murine embryonic stem cells has made the mouse genome amenable to sophisticated genetic manipulation currently unavailable in any other model organism. PMID:16641221

Direct and indirect reputation formation in nonhuman great apes (Pan paniscus, Pan troglodytes, Gorilla gorilla, Pongo pygmaeus) and human children (Homo sapiens).

PubMed

Herrmann, Esther; Keupp, Stefanie; Hare, Brian; Vaish, Amrisha; Tomasello, Michael

2013-02-01

Humans make decisions about when and with whom to cooperate based on their reputations. People either learn about others by direct interaction or by observing third-party interactions or gossip. An important question is whether other animal species, especially our closest living relatives, the nonhuman great apes, also form reputations of others. In Study 1, chimpanzees, bonobos, orangutans, and 2.5-year-old human children experienced a nice experimenter who tried to give food/toys to the subject and a mean experimenter who interrupted the food/toy giving. In studies 2 and 3, nonhuman great apes and human children could only passively observe a similar interaction, in which a nice experimenter and a mean experimenter interacted with a third party. Orangutans and 2.5-year-old human children preferred to approach the nice experimenter rather than the mean one after having directly experienced their respective behaviors. Orangutans, chimpanzees, and 2.5-year-old human children also took into account experimenter actions toward third parties in forming reputations. These studies show that the human ability to form direct and indirect reputation judgment is already present in young children and shared with at least some of the other great apes. PsycINFO Database Record (c) 2013 APA, all rights reserved

Health risks associated with inhaled nasal toxicants.

PubMed

Feron, V J; Arts, J H; Kuper, C F; Slootweg, P J; Woutersen, R A

2001-05-01

Health risks of inhaled nasal toxicants were reviewed with emphasis on chemically induced nasal lesions in humans, sensory irritation, olfactory and trigeminal nerve toxicity, nasal immunopathology and carcinogenesis, nasal responses to chemical mixtures, in vitro models, and nasal dosimetry- and metabolism-based extrapolation of nasal data in animals to humans. Conspicuous findings in humans are the effects of outdoor air pollution on the nasal mucosa, and tobacco smoking as a risk factor for sinonasal squamous cell carcinoma. Objective methods in humans to discriminate between sensory irritation and olfactory stimulation and between adaptation and habituation have been introduced successfully, providing more relevant information than sensory irritation studies in animals. Against the background of chemoperception as a dominant window of the brain on the outside world, nasal neurotoxicology is rapidly developing, focusing on olfactory and trigeminal nerve toxicity. Better insight in the processes underlying neurogenic inflammation may increase our knowledge of the causes of the various chemical sensitivity syndromes. Nasal immunotoxicology is extremely complex, which is mainly due to the pivotal role of nasal lymphoid tissue in the defense of the middle ear, eye, and oral cavity against antigenic substances, and the important function of the nasal passages in brain drainage in rats. The crucial role of tissue damage and reactive epithelial hyperproliferation in nasal carcinogenesis has become overwhelmingly clear as demonstrated by the recently developed biologically based model for predicting formaldehyde nasal cancer risk in humans. The evidence of carcinogenicity of inhaled complex mixtures in experimental animals is very limited, while there is ample evidence that occupational exposure to mixtures such as wood, leather, or textile dust or chromium- and nickel-containing materials is associated with increased risk of nasal cancer. It is remarkable that these mixtures are aerosols, suggesting that their "particulate nature" may be a major factor in their potential to induce nasal cancer. Studies in rats have been conducted with defined mixtures of nasal irritants such as aldehydes, using a model for competitive agonism to predict the outcome of such mixed exposures. When exposure levels in a mixture of nasal cytotoxicants were equal to or below the "No-Observed-Adverse-Effect-Levels" (NOAELs) of the individual chemicals, neither additivity nor potentiation was found, indicating that the NOAEL of the "most risky chemical" in the mixture would also be the NOAEL of the mixture. In vitro models are increasingly being used to study mechanisms of nasal toxicity. However, considering the complexity of the nasal cavity and the many factors that contribute to nasal toxicity, it is unlikely that in vitro experiments ever will be substitutes for in vivo inhalation studies. It is widely recognized that a strategic approach should be available for the interpretation of nasal effects in experimental animals with regard to potential human health risk. Mapping of nasal lesions combined with airflow-driven dosimetry and knowledge about local metabolism is a solid basis for extrapolation of animal data to humans. However, more research is needed to better understand factors that determine the susceptibility of human and animal tissues to nasal toxicants, in particular nasal carcinogens.

Linking brains and brawn: exercise and the evolution of human neurobiology.

PubMed

Raichlen, David A; Polk, John D

2013-01-07

The hunting and gathering lifestyle adopted by human ancestors around 2 Ma required a large increase in aerobic activity. High levels of physical activity altered the shape of the human body, enabling access to new food resources (e.g. animal protein) in a changing environment. Recent experimental work provides strong evidence that both acute bouts of exercise and long-term exercise training increase the size of brain components and improve cognitive performance in humans and other taxa. However, to date, researchers have not explored the possibility that the increases in aerobic capacity and physical activity that occurred during human evolution directly influenced the human brain. Here, we hypothesize that proximate mechanisms linking physical activity and neurobiology in living species may help to explain changes in brain size and cognitive function during human evolution. We review evidence that selection acting on endurance increased baseline neurotrophin and growth factor signalling (compounds responsible for both brain growth and for metabolic regulation during exercise) in some mammals, which in turn led to increased overall brain growth and development. This hypothesis suggests that a significant portion of human neurobiology evolved due to selection acting on features unrelated to cognitive performance.

Gambling for Gatorade: risk-sensitive decision making for fluid rewards in humans

PubMed Central

Platt, Michael L.

2009-01-01

Determining how both humans and animals make decisions in risky situations is a central problem in economics, experimental psychology, behavioral economics, and neurobiology. Typically, humans are risk seeking for gains and risk averse for losses, while animals may display a variety of preferences under risk depending on, amongst other factors, internal state. Such differences in behavior may reflect major cognitive and cultural differences or they may reflect differences in the way risk sensitivity is probed in humans and animals. Notably, in most studies humans make one or a few choices amongst hypothetical or real monetary options, while animals make dozens of repeated choices amongst options offering primary rewards like food or drink. To address this issue, we probed risk-sensitive decision making in human participants using a paradigm modeled on animal studies, in which rewards were either small squirts of Gatorade or small amounts of real money. Possible outcomes and their probabilities were not made explicit in either case. We found that individual patterns of decision making were strikingly similar for both juice and for money, both in overall risk preferences and in trial-to-trial effects of reward outcome on choice. Comparison with decisions made by monkeys for juice in a similar task revealed highly similar gambling styles. These results unite known patterns of risk-sensitive decision making in human and nonhuman primates and suggest that factors such as the way a decision is framed or internal state may underlie observed variation in risk preferences between and within species. PMID:18719953

Aluminium and the human breast.

PubMed

Darbre, P D

2016-06-01

The human population is exposed to aluminium (Al) from diet, antacids and vaccine adjuvants, but frequent application of Al-based salts to the underarm as antiperspirant adds a high additional exposure directly to the local area of the human breast. Coincidentally the upper outer quadrant of the breast is where there is also a disproportionately high incidence of breast cysts and breast cancer. Al has been measured in human breast tissues/fluids at higher levels than in blood, and experimental evidence suggests that at physiologically relevant concentrations, Al can adversely impact on human breast epithelial cell biology. Gross cystic breast disease is the most common benign disorder of the breast and evidence is presented that Al may be a causative factor in formation of breast cysts. Evidence is also reviewed that Al can enable the development of multiple hallmarks associated with cancer in breast cells, in particular that it can cause genomic instability and inappropriate proliferation in human breast epithelial cells, and can increase migration and invasion of human breast cancer cells. In addition, Al is a metalloestrogen and oestrogen is a risk factor for breast cancer known to influence multiple hallmarks. The microenvironment is established as another determinant of breast cancer development and Al has been shown to cause adverse alterations to the breast microenvironment. If current usage patterns of Al-based antiperspirant salts contribute to causation of breast cysts and breast cancer, then reduction in exposure would offer a strategy for prevention, and regulatory review is now justified. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The monkey puzzle: a systematic review of studies of stress, social hierarchies, and heart disease in monkeys.

PubMed

Petticrew, Mark; Davey Smith, George

2012-01-01

It is often suggested that psychosocial factors, such as stress, or one's social position, may play an important role in producing social gradients in human disease. Evidence in favour of this model of health inequalities has relied, in part, on studies of the health effects of the natural social hierarchies found among non-human primates. This study aimed to assess the strength of this evidence. A systematic review was carried out to identify all studies of psychosocial factors and coronary artery disease (CAD) in non-human primates. We searched databases (MEDLINE, PsycInfo, EMBASE, and Primatelit from inception to November 2010) to identify experimental and observational studies of the impact of social reorganisation, social instability, and disruption of dominance hierarchies on primate CAD outcomes. We also handsearched bibliographies and examined the citations to those studies in public health articles. Fourteen studies were found which presented evidence on CAD and social status and/or psychosocial stress. These suggested that the association between social status and disease may be sex-specific: in female monkeys dominant status may be protective, with subordinate females having a greater extent of atherosclerosis. In male monkeys the reverse may be the case. Overall, non-human primate studies present only limited evidence for an association between social status and CAD, Despite this, there is selective citation of individual non-human primate studies in reviews and commentaries relating to human disease aetiology. Such generalisation of data from monkey studies to human societies does not appear warranted.

The Monkey Puzzle: A Systematic Review of Studies of Stress, Social Hierarchies, and Heart Disease in Monkeys

PubMed Central

Petticrew, Mark; Davey Smith, George

2012-01-01

Background It is often suggested that psychosocial factors, such as stress, or one's social position, may play an important role in producing social gradients in human disease. Evidence in favour of this model of health inequalities has relied, in part, on studies of the health effects of the natural social hierarchies found among non-human primates. This study aimed to assess the strength of this evidence. Methodology/Principal Findings A systematic review was carried out to identify all studies of psychosocial factors and coronary artery disease (CAD) in non-human primates. We searched databases (MEDLINE, PsycInfo, EMBASE, and Primatelit from inception to November 2010) to identify experimental and observational studies of the impact of social reorganisation, social instability, and disruption of dominance hierarchies on primate CAD outcomes. We also handsearched bibliographies and examined the citations to those studies in public health articles. Fourteen studies were found which presented evidence on CAD and social status and/or psychosocial stress. These suggested that the association between social status and disease may be sex-specific: in female monkeys dominant status may be protective, with subordinate females having a greater extent of atherosclerosis. In male monkeys the reverse may be the case. Conclusions/Significance Overall, non-human primate studies present only limited evidence for an association between social status and CAD, Despite this, there is selective citation of individual non-human primate studies in reviews and commentaries relating to human disease aetiology. Such generalisation of data from monkey studies to human societies does not appear warranted. PMID:22470414

A preliminary study to find a possible association between occlusal wear and maximum bite force in humans.

PubMed

Jain, Veena; Mathur, Vijay Prakash; Kumar, Abhishek

2013-01-01

The objective of the study was to investigate whether moderate-to-severe attrition is associated with maximum bite force in the first molar region. Maximum bite force in the first molar region was measured for a total of 60 subjects having moderate-to-severe attrition of occlusal surface (experimental group) using a specially-designed piezoelectric sensor based bite force measuring device. An equal number of age, gender, height and weight matched controls (control group) were also subjected to bite force measurement for comparison. The maximum bite force was found to be significantly lower (p < 0.05) in the experimental group [480.32 (153.40)] as compared to the controls [640.63 (148.90)]. While analyzing the possible etiology for occlusal wear mainly two reasons were elicited, i.e. history of parafunctional habits like use of known abrasive tooth powder (sub-group A) and Bruxism (sub-group B). However, there were many subjects in which no known definite etiological factors be attributed to occlusal wear (sub-group C). On analysing further with respect to the possibly correlated etiological factors with maximum bite force, no significant difference was found within the experimental sub-group. However, all three experimental sub-groups had significantly lower maximum bite force as compared to age, gender and BMI matched controls. A significantly lower maximum bite force was found to be associated with moderate-to-severe attrition as compared to subjects without attrition. However, no specific relation could be found between bite force and possible etiological factors like history of parafunctional habits, history of use of known abrasive tooth powder, etc.

Cryopreservation induces macrophage colony stimulating factor from human periodontal ligament cells in vitro.

PubMed

Rhim, E-M; Ahn, S-J; Kim, J-Y; Chang, Y-R; Kim, K-H; Lee, H-W; Jung, S-H; Kim, E-C; Park, S-H

2013-10-01

Cryopreservation is used to protect vital periodontal ligaments during the transplantation of teeth. We investigated which gene products implicated in root resorption are upregulated in human periodontal ligament cells by cryopreservation, and whether cryopreservation affects the expression of macrophage-colony stimulating factor (M-CSF) in human periodontal ligament cells. We used customized microarrays to compare gene expression in human periodontal ligament cells cultured from teeth immediately after extraction and from cryopreserved teeth. Based on the result of these assays, we examined M-CSF expression in periodontal ligament cells from the immediately extracted tooth and cryopreserved teeth by real-time PCR, enzyme-linked immunosorbent assay (ELISA), Western blot analysis, and immunofluorescence. We also investigated whether human bone marrow cells differentiate into tartrate-resistant acid phosphatase (TRAP) positive osteoclasts when stimulated with RANKL (Receptor Activator for Nuclear Factor κ B Ligand) together with any secreted M-CSF present in the supernatants of the periodontal ligament cells cultured from the various groups of teeth. M-CSF was twofold higher in the periodontal ligament cells from the rapid freezing teeth than in those from the immediately extracted group (p < 0.05). Cryopreservation increased M-CSF expression in the periodontal ligament cells when analyzed by real time PCR, ELISA, Western blotting, and immunofluorescence (p < 0.05). TRAP positive osteoclasts were formed in response to RANKL and the secreted M-CSF present in the supernatants of all the experimental groups except negative control. These results demonstrate that cryopreservation promotes the production of M-CSF, which plays an important role in root resorption by periodontal ligament cells. Copyright © 2013 Elsevier Inc. All rights reserved.

Mesenchymal Stem Cells Derived from Human Gingiva Are Capable of Immunomodulatory Functions and Ameliorate Inflammation-Related Tissue Destruction in Experimental Colitis1

PubMed Central

Zhang, Qunzhou; Shi, Shihong; Liu, Yi; Uyanne, Jettie; Shi, Yufang; Shi, Songtao; Le, Anh D.

2010-01-01

Aside from the well-established self-renewal and multipotent differentiation properties, mesenchymal stem cells exhibit both immunomodulatory and anti-inflammatory roles in several experimental autoimmune and inflammatory diseases. In this study, we isolated a new population of stem cells from human gingiva, a tissue source easily accessible from the oral cavity, namely, gingiva-derived mesenchymal stem cells (GMSCs), which exhibited clonogenicity, self-renewal, and multipotent differentiation capacities. Most importantly, GMSCs were capable of immunomodulatory functions, specifically suppressed peripheral blood lymphocyte proliferation, induced expression of a wide panel of immunosuppressive factors including IL-10, IDO, inducible NO synthase (iNOS), and cyclooxygenase 2 (COX-2) in response to the inflammatory cytokine, IFN-γ. Cell-based therapy using systemic infusion of GMSCs in experimental colitis significantly ameliorated both clinical and histopathological severity of the colonic inflammation, restored the injured gastrointestinal mucosal tissues, reversed diarrhea and weight loss, and suppressed the overall disease activity in mice. The therapeutic effect of GMSCs was mediated, in part, by the suppression of inflammatory infiltrates and inflammatory cytokines/mediators and the increased infiltration of regulatory T cells and the expression of anti-inflammatory cytokine IL-10 at the colonic sites. Taken together, GMSCs can function as an immunomodulatory and anti-inflammatory component of the immune system in vivo and is a promising cell source for cell-based treatment in experimental inflammatory diseases. PMID:19923445

Oestrogen exposure and breast cancer risk

PubMed Central

Travis, Ruth C; Key, Timothy J

2003-01-01

Epidemiological and experimental evidence implicates oestrogens in the aetiology of breast cancer. Most established risk factors for breast cancer in humans probably act through hormone-related pathways, and increased concentrations of circulating oestrogens have been found to be strongly associated with increased risk for breast cancer in postmenopausal women. This article explores the evidence for the hypothesis that oestrogen exposure is a major determinant of risk for breast cancer. We review recent data on oestrogens and breast cancer risk, consider oestrogen-related risk factors and examine possible mechanisms that might account for the effects of oestrogen. Finally, we discuss how these advances might influence strategies for reducing the incidence of breast cancer. PMID:12927032

Genesis of Prolactinomas: Studies Using Estrogen-Treated Animals

PubMed Central

Sarkar, Dipak K.

2010-01-01

Prolactin-secreting adenomas (prolactinomas) are the most prevalent form of pituitary tumors in humans. Our knowledge of the formation of these tumors is limited. Experimental work in animal has uncovered that estradiol exposure leads to prolactinoma formation via orchestrated events involving dopamine D2 receptors, transforming growth factor-β (TGF-β) isoforms and their receptors, as well as factors secondary to TGF-β action. Additionally, these studies determined that TGF-β and b-FGF interact to facilitate the communication between lactotropes and folliculo-stellate cells that is necessary for the mitogenic action of estradiol. The downstream signaling that governs lactotropic cell proliferation involves activation of the MAP kinase p44/42-dependent pathway. PMID:16809921

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.

Uterus transplantation: From animal models through the first heart beating pregnancy to the first human live birth

PubMed Central

Ozkan, Omer; Dogan, Nasuh Utku; Ozkan, Ozlenen; Mendilcioglu, Inanc; Dogan, Selen; Aydinuraz, Batu; Simsek, Mehmet

2016-01-01

Absolute uterine factor infertility affects 3–5% of the general population, and unfortunately this condition is untreatable. There are some available options, including surrogacy or adoption, but neither of these suits each and every woman who desires to have her own genetic child. With recent advances in surgery and transplant immunology, uterus transplantation may be a source of hope for these women with uterine infertility. In the last decade, a number of animal species including rats, mice, rabbits, pigs, sheep, and primates have been used as experimental models, and pregnancies were achieved in some of these. Human data consist of 11 subjects yielding positive pregnancy results with no live births in the second trial from Turkey and, more fortunately, live births from the latest trial from Sweden. In the light of all these studies, uterus transplantation has been proven to be a viable option for women with uterine factor infertility. PMID:27638900

Apoptosis of mouse hippocampal cells induced by Taenia crassiceps metacestode factor.

PubMed

Zepeda, N; Solano, S; Copitin, N; Chávez, J L; Fernández, A M; García, F; Tato, P; Molinari, J L

2017-03-01

Seizures, headache, depression and neurological deficits are the signs and symptoms most frequently reported in human neurocysticercosis. However, the cause of the associated learning and memory deficits is unknown. Here, we used Taenia crassiceps infection in mice as a model of human cysticercosis. The effects of T. crassiceps metacestode infection or T. crassiceps metacestode factor (MF) treatment on mouse hippocampal cells were studied; control mice were included. At 45 days after infection or treatment of the mice with MF, all mice were anaesthetized and perfused transcardially with saline followed by phosphate-buffered 10% formalin. Then the brains were carefully removed. Coronal sections stained using several techniques were analysed. Extensive and significant apoptosis was found in the experimental animals, mainly in the dentate gyrus, CA1, CA2, CA3 and neighbouring regions, in comparison with the apparently intact cells from control mice (P < 0.01). These results suggest that neurological deficits, especially the learning and memory deficits, may be generated by extensive apoptosis of hippocampal cells.

Trichomonas vaginalis: pathogenicity and potential role in human reproductive failure.

PubMed

Mielczarek, Ewelina; Blaszkowska, Joanna

2016-08-01

Trichomonas vaginalis, which colonizes the genitourinary tract of men and women, is a sexually transmitted parasite causing symptomatic or asymptomatic trichomoniasis. The host-parasite relationship is very complex, and clinical symptoms cannot likely be attributed to a single pathogenic effect. Among the many factors responsible for interactions between T. vaginalis and host tissues, contact-dependent and contact-independent mechanisms are important in pathogenicity, as is the immune response. This review focuses on the potential virulence properties of T. vaginalis and its role in female and male infertility. It highlights the association between T. vaginalis infection and serious adverse health consequences experienced by women, including infertility, preterm birth and low-birth-weight infants. Long-term clinical observations and results of in vitro experimental studies indicate that in men, trichomoniasis has been also associated with infertility through inflammatory damage to the genitourinary tract or interference with sperm function. These results contribute significantly to improving our knowledge of the role of parasitic virulence factors in the development of infection and its role in human infertility.

Analysis of Factors Influencing Measurement Accuracy of Al Alloy Tensile Test Results

NASA Astrophysics Data System (ADS)

Podgornik, Bojan; Žužek, Borut; Sedlaček, Marko; Kevorkijan, Varužan; Hostej, Boris

2016-02-01

In order to properly use materials in design, a complete understanding of and information on their mechanical properties, such as yield and ultimate tensile strength must be obtained. Furthermore, as the design of automotive parts is constantly pushed toward higher limits, excessive measuring uncertainty can lead to unexpected premature failure of the component, thus requiring reliable determination of material properties with low uncertainty. The aim of the present work was to evaluate the effect of different metrology factors, including the number of tested samples, specimens machining and surface quality, specimens input diameter, type of testing and human error on the tensile test results and measurement uncertainty when performed on 2xxx series Al alloy. Results show that the most significant contribution to measurement uncertainty comes from the number of samples tested, which can even exceed 1 %. Furthermore, moving from experimental laboratory conditions to very intense industrial environment further amplifies measurement uncertainty, where even if using automated systems human error cannot be neglected.

Keeping adolescent orphans in school to prevent human immunodeficiency virus infection: evidence from a randomized controlled trial in Kenya.

PubMed

Cho, Hyunsan; Hallfors, Denise D; Mbai, Isabella I; Itindi, Janet; Milimo, Benson W; Halpern, Carolyn T; Iritani, Bonita J

2011-05-01

We report the findings from a pilot study in western Kenya, using an experimental design to test whether comprehensive support used to keep adolescent orphans in school can reduce risk factors associated with infection with human immunodeficiency virus. Adolescent orphans aged 12-14 years (N = 105) in Nyanza Province were randomized to condition, after stratifying by household, gender, and baseline survey report of sexual behavior. The intervention comprised school fees, uniforms, and a "community visitor" who monitored school attendance and helped to resolve problems that would lead to absence or dropout. Data were analyzed using generalized estimating equations over two time points, controlling for gender and age. Compared with the control group, intervention students were less likely to drop out of school, commence sexual intercourse, or report attitudes supporting early sex. School support also increased prosocial bonding and gender equity attitudes. After 1 year of exposure to the intervention, we found evidence suggesting that comprehensive school support can prevent school dropout, delay sexual debut, and reduce risk factors associated with infection with human immunodeficiency virus. Further research, with much larger samples, is needed to better understand factors that mediate the association between educational support and delayed sexual debut, and how gender might moderate these relationships. Copyright © 2011 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Apparent diffusion coefficient of the normal human brain for various experimental conditions

NASA Astrophysics Data System (ADS)

Moraru, Luminita; Dimitrievici, Lucian

2017-01-01

Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) is being increasingly used to assess both brain tissues and cerebrospinal fluid integrity. In this paper we study inter-site reproducibility of the apparent diffusion coefficient values for the main cerebral tissues such as gray matter, white matter and into cerebrospinal fluid and for three different stacks of slices that were spaced at L = 79.8, 84.9 and 90 mm. We assessed the impact of the attenuation factor and diffusion gradient on the results reproducibility.

Mechanisms of Osteoarthritic Pain. Studies in Humans and Experimental Models

PubMed Central

Eitner, Annett; Hofmann, Gunther O.; Schaible, Hans-Georg

2017-01-01

Pain due to osteoarthritis (OA) is one of the most frequent causes of chronic pain. However, the mechanisms of OA pain are poorly understood. This review addresses the mechanisms which are thought to be involved in OA pain, derived from studies on pain mechanisms in humans and in experimental models of OA. Three areas will be considered, namely local processes in the joint associated with OA pain, neuronal mechanisms involved in OA pain, and general factors which influence OA pain. Except the cartilage all structures of the joints are innervated by nociceptors. Although the hallmark of OA is the degradation of the cartilage, OA joints show multiple structural alterations of cartilage, bone and synovial tissue. In particular synovitis and bone marrow lesions have been proposed to determine OA pain whereas the contribution of the other pathologies to pain generation has been studied less. Concerning the peripheral neuronal mechanisms of OA pain, peripheral nociceptive sensitization was shown, and neuropathic mechanisms may be involved at some stages. Structural changes of joint innervation such as local loss and/or sprouting of nerve fibers were shown. In addition, central sensitization, reduction of descending inhibition, descending excitation and cortical atrophies were observed in OA. The combination of different neuronal mechanisms may define the particular pain phenotype in an OA patient. Among mediators involved in OA pain, nerve growth factor (NGF) is in the focus because antibodies against NGF significantly reduce OA pain. Several studies show that neutralization of interleukin-1β and TNF may reduce OA pain. Many patients with OA exhibit comorbidities such as obesity, low grade systemic inflammation and diabetes mellitus. These comorbidities can significantly influence the course of OA, and pain research just began to study the significance of such factors in pain generation. In addition, psychologic and socioeconomic factors may aggravate OA pain, and in some cases genetic factors influencing OA pain were found. Considering the local factors in the joint, the neuronal processes and the comorbidities, a better definition of OA pain phenotypes may become possible. Studies are under way in order to improve OA and OA pain monitoring. PMID:29163027

Detecting regulatory gene-environment interactions with unmeasured environmental factors.

PubMed

Fusi, Nicoló; Lippert, Christoph; Borgwardt, Karsten; Lawrence, Neil D; Stegle, Oliver

2013-06-01

Genomic studies have revealed a substantial heritable component of the transcriptional state of the cell. To fully understand the genetic regulation of gene expression variability, it is important to study the effect of genotype in the context of external factors such as alternative environmental conditions. In model systems, explicit environmental perturbations have been considered for this purpose, allowing to directly test for environment-specific genetic effects. However, such experiments are limited to species that can be profiled in controlled environments, hampering their use in important systems such as human. Moreover, even in seemingly tightly regulated experimental conditions, subtle environmental perturbations cannot be ruled out, and hence unknown environmental influences are frequent. Here, we propose a model-based approach to simultaneously infer unmeasured environmental factors from gene expression profiles and use them in genetic analyses, identifying environment-specific associations between polymorphic loci and individual gene expression traits. In extensive simulation studies, we show that our method is able to accurately reconstruct environmental factors and their interactions with genotype in a variety of settings. We further illustrate the use of our model in a real-world dataset in which one environmental factor has been explicitly experimentally controlled. Our method is able to accurately reconstruct the true underlying environmental factor even if it is not given as an input, allowing to detect genuine genotype-environment interactions. In addition to the known environmental factor, we find unmeasured factors involved in novel genotype-environment interactions. Our results suggest that interactions with both known and unknown environmental factors significantly contribute to gene expression variability. and implementation: Software available at http://pmbio.github.io/envGPLVM/. Supplementary data are available at Bioinformatics online.

Dementia Research: Populations, Progress, Problems, and Predictions.

PubMed

Hunter, Sally; Smailagic, Nadja; Brayne, Carol

2018-05-16

Alzheimer's disease (AD) is a clinicopathologically defined syndrome leading to cognitive impairment. Following the recent failures of amyloid-based randomized controlled trials to change the course of AD, there are growing calls for a re-evaluation of basic AD research. Epidemiology offers one approach to integrating the available evidence. Here we examine relationships between evidence from population-based, clinicopathological studies of brain aging and a range of hypotheses from all areas of AD research. We identify various problems, including a lack of systematic approach to measurement of clinical and neuropathological factors associated with dementia in experimental and clinical settings, poor understanding of the strengths and weaknesses of different observational and experimental designs, a lack of clarity in relation to disease definitions from the clinical, neuropathological, and molecular perspectives, inadequate characterization of brain aging in the human population, difficulties in translation between laboratory-based and population-based evidence bases, and a lack of communication between different sections of the dementia research community. Population studies highlight complexity and predict that therapeutic approaches based on single disease features will not be successful. Better characterization of brain aging in the human population is urgently required to select biomarkers and therapeutic targets that are meaningful to human disease. The generation of detailed and reliable evidence must be addressed before progress toward therapeutic interventions can be made.

Methodology challenges in studying human gut microbiota - effects of collection, storage, DNA extraction and next generation sequencing technologies.

PubMed

Panek, Marina; Čipčić Paljetak, Hana; Barešić, Anja; Perić, Mihaela; Matijašić, Mario; Lojkić, Ivana; Vranešić Bender, Darija; Krznarić, Željko; Verbanac, Donatella

2018-03-23

The information on microbiota composition in the human gastrointestinal tract predominantly originates from the analyses of human faeces by application of next generation sequencing (NGS). However, the detected composition of the faecal bacterial community can be affected by various factors including experimental design and procedures. This study evaluated the performance of different protocols for collection and storage of faecal samples (native and OMNIgene.GUT system) and bacterial DNA extraction (MP Biomedicals, QIAGEN and MO BIO kits), using two NGS platforms for 16S rRNA gene sequencing (Ilumina MiSeq and Ion Torrent PGM). OMNIgene.GUT proved as a reliable and convenient system for collection and storage of faecal samples although favouring Sutterella genus. MP provided superior DNA yield and quality, MO BIO depleted Gram positive organisms while using QIAGEN with OMNIgene.GUT resulted in greatest variability compared to other two kits. MiSeq and IT platforms in their supplier recommended setups provided comparable reproducibility of donor faecal microbiota. The differences included higher diversity observed with MiSeq and increased capacity of MiSeq to detect Akkermansia muciniphila, [Odoribacteraceae], Erysipelotrichaceae and Ruminococcaceae (primarily Faecalibacterium prausnitzii). The results of our study could assist the investigators using NGS technologies to make informed decisions on appropriate tools for their experimental pipelines.

Innovativeness as an emergent property: a new alignment of comparative and experimental research on animal innovation

PubMed Central

Griffin, Andrea S.

2016-01-01

Innovation and creativity are key defining features of human societies. As we face the global challenges of the twenty-first century, they are also facets upon which we must become increasingly reliant. But what makes Homo sapiens so innovative and where does our high innovation propensity come from? Comparative research on innovativeness in non-human animals allows us to peer back through evolutionary time and investigate the ecological factors that drove the evolution of innovativeness, whereas experimental research identifies and manipulates underpinning creative processes. In commenting on the present theme issue, I highlight the controversies that have typified this research field and show how a paradigmatic shift in our thinking about innovativeness will contribute to resolving these tensions. In the past decade, innovativeness has been considered by many as a trait, a direct product of cognition, and a direct target of selection. The evidence I review here suggests that innovativeness will be hereon viewed as one component, or even an emergent property of a larger array of traits, which have evolved to deal with environmental variation. I illustrate how research should capitalize on taxonomic diversity to unravel the full range of psychological processes that underpin innovativeness in non-human animals. PMID:26926287

Analysis of malondialdehyde in human plasma samples through derivatization with 2,4-dinitrophenylhydrazine by ultrasound-assisted dispersive liquid-liquid microextraction-GC-FID approach.

PubMed

Malaei, Reyhane; Ramezani, Amir M; Absalan, Ghodratollah

2018-05-04

A sensitive and reliable ultrasound-assisted dispersive liquid-liquid microextraction (UA-DLLME) procedure was developed and validated for extraction and analysis of malondialdehyde (MDA) as an important lipids-peroxidation biomarker in human plasma. In this methodology, to achieve an applicable extraction procedure, the whole optimization processes were performed in human plasma. To convert MDA into readily extractable species, it was derivatized to hydrazone structure-base by 2,4-dinitrophenylhydrazine (DNPH) at 40 °C within 60 min. Influences of experimental variables on the extraction process including type and volume of extraction and disperser solvents, amount of derivatization agent, temperature, pH, ionic strength, sonication and centrifugation times were evaluated. Under the optimal experimental conditions, the enhancement factor and extraction recovery were 79.8 and 95.8%, respectively. The analytical signal linearly (R 2  = 0.9988) responded over a concentration range of 5.00-4000 ng mL -1 with a limit of detection of 0.75 ng mL -1 (S/N = 3) in the plasma sample. To validate the developed procedure, the recommend guidelines of Food and Drug Administration for bioanalytical analysis have been employed. Copyright © 2018. Published by Elsevier B.V.

Humanized theta-defensins (retrocyclins) enhance macrophage performance and protect mice from experimental anthrax infections.

PubMed

Welkos, S; Cote, C K; Hahn, U; Shastak, O; Jedermann, J; Bozue, J; Jung, G; Ruchala, P; Pratikhya, P; Tang, T; Lehrer, R I; Beyer, W

2011-09-01

Retrocyclins are humanized versions of the -defensin peptides expressed by the leukocytes of several nonhuman primates. Previous studies, performed in serum-free media, determined that retrocyclins 1 (RC1) and RC2 could prevent successful germination of Bacillus anthracis spores, kill vegetative B. anthracis cells, and inactivate anthrax lethal factor. We now report that retrocyclins are extensively bound by components of native mouse, human, and fetal calf sera, that heat-inactivated sera show greatly enhanced retrocyclin binding, and that native and (especially) heat-inactivated sera greatly reduce the direct activities of retrocyclins against spores and vegetative cells of B. anthracis. Nevertheless, we also found that retrocyclins protected mice challenged in vivo by subcutaneous, intraperitoneal, or intranasal instillation of B. anthracis spores. Retrocyclin 1 bound extensively to B. anthracis spores and enhanced their phagocytosis and killing by murine RAW264.7 cells. Based on the assumption that spore-bound RC1 enters phagosomes by "piggyback phagocytosis," model calculations showed that the intraphagosomal concentration of RC1 would greatly exceed its extracellular concentration. Murine alveolar macrophages took up fluorescently labeled retrocyclin, suggesting that macrophages may also acquire extracellular RC1 directly. Overall, these data demonstrate that retrocyclins are effective in vivo against experimental murine anthrax infections and suggest that enhanced macrophage function contributes to this property.

Genome-Wide and Experimental Resolution of Relative Translation Elongation Speed at Individual Gene Level in Human Cells

PubMed Central

Gu, Wei; Cui, Yizhi; Zhong, Jiayong; Jin, Jingjie; He, Qing-Yu; Wang, Tong; Zhang, Gong

2016-01-01

In the process of translation, ribosomes first assemble on mRNAs (translation initiation) and then translate along the mRNA (elongation) to synthesize proteins. Elongation pausing is deemed highly relevant to co-translational folding of nascent peptides and the functionality of protein products, which positioned the evaluation of elongation speed as one of the central questions in the field of translational control. By integrating three types of RNA-seq methods, we experimentally and computationally resolved elongation speed, with our proposed elongation velocity index (EVI), a relative measure at individual gene level and under physiological condition in human cells. We successfully distinguished slow-translating genes from the background translatome. We demonstrated that low-EVI genes encoded more stable proteins. We further identified cell-specific slow-translating codons, which might serve as a causal factor of elongation deceleration. As an example for the biological relevance, we showed that the relatively slow-translating genes tended to be associated with the maintenance of malignant phenotypes per pathway analyses. In conclusion, EVI opens a new view to understand why human cells tend to avoid simultaneously speeding up translation initiation and decelerating elongation, and the possible cancer relevance of translating low-EVI genes to gain better protein quality. PMID:26926465

Evaluation of food chain transfer of the antibiotic oxytetracycline and human risk assessment.

PubMed

Boonsaner, Maliwan; Hawker, Darryl W

2013-10-01

There has been recent concern regarding the possibility of antibiotics entering the aquatic food chain and impacting human consumers. This work reports experimental results of the bioconcentration of the antibiotic oxytetracycline (OTC) by the Asian watermeal plant (Wolffia globosa Hartog & Plas) and bioaccumulation of OTC in watermeal and water by the seven-striped carp (Probarbus jullieni). They show, for the first time, the extent to which OTC is able to transfer from water to plant to fish and enter the food chain. The mean bioconcentration factor (dry weight basis) with watermeal was 1.28 × 10(3) L kg(-1). Separate experiments were undertaken to characterize accumulation of OTC by carp from water and watermeal. These showed the latter pathway to be dominant under the conditions employed. The bioconcentration and biomagnification factors for these processes were 1.75 L kg(-1) and 2 × 10(-4) kg g(-1) respectively. Using an aqueous concentration range of 0.34-3.0 μg L(-1), hazard quotients for human consumption of contaminated fish of 1.3 × 10(-2) to 1.15 × 10(-1) were derived. Copyright © 2013 Elsevier Ltd. All rights reserved.

A concise review of testosterone and bone health

PubMed Central

Mohamad, Nur-Vaizura; Soelaiman, Ima-Nirwana; Chin, Kok-Yong

2016-01-01

Osteoporosis is a condition causing significant morbidity and mortality in the elderly population worldwide. Age-related testosterone deficiency is the most important factor of bone loss in elderly men. Androgen can influence bone health by binding to androgen receptors directly or to estrogen receptors (ERs) indirectly via aromatization to estrogen. This review summarized the direct and indirect effects of androgens on bone derived from in vitro, in vivo, and human studies. Cellular studies showed that androgen stimulated the proliferation of preosteoblasts and differentiation of osteoblasts. The converted estrogen suppressed osteoclast formation and resorption activity by blocking the receptor activator of nuclear factor k-B ligand pathway. In animal studies, activation of androgen and ERα, but not ERβ, was shown to be important in acquisition and maintenance of bone mass. Human epidemiological studies demonstrated a significant relationship between estrogen and testosterone in bone mineral density and fracture risk, but the relative significance between the two remained debatable. Human experimental studies showed that estrogen was needed in suppressing bone resorption, but both androgen and estrogen were indispensable for bone formation. As a conclusion, maintaining optimal level of androgen is essential in preventing osteoporosis and its complications in elderly men. PMID:27703340

Enhancing proliferation and optimizing the culture condition for human bone marrow stromal cells using hypoxia and fibroblast growth factor-2.

PubMed

Lee, Jung-Seok; Kim, Seul Ki; Jung, Byung-Joo; Choi, Seong-Bok; Choi, Eun-Young; Kim, Chang-Sung

2018-04-01

This study aimed to determine the cellular characteristics and behaviors of human bone marrow stromal cells (hBMSCs) expanded in media in a hypoxic or normoxic condition and with or without fibroblast growth factor-2 (FGF-2) treatment. hBMSCs isolated from the vertebral body and expanded in these four groups were evaluated for cellular proliferation/migration, colony-forming units, cell-surface characterization, in vitro differentiation, in vivo transplantation, and gene expression. Culturing hBMSCs using a particular environmental factor (hypoxia) and with the addition of FGF-2 increased the cellular proliferation rate while enhancing the regenerative potential, modulated the multipotency-related processes (enhanced chondrogenesis-related processes/osteogenesis, but reduced adipogenesis), and increased cellular migration and collagen formation. The gene expression levels in the experimental samples showed activation of the hypoxia-inducible factor-1 pathway and glycolysis in the hypoxic condition, with this not being affected by the addition of FGF-2. The concurrent application of hypoxia and FGF-2 could provide a favorable condition for culturing hBMSCs to be used in clinical applications associated with bone tissue engineering, due to the enhancement of cellular proliferation and regenerative potential. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

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...

Using Animal Models to Determine the Role of Gustatory Neural Input in the Control of Ingestive Behavior and the Maintenance of Body Weight

PubMed Central

Ciullo, Dana L.

2015-01-01

Introduction Decades of research have suggested that nutritional intake contributes to the development of human disease, mainly by influencing the development of obesity and obesity-related conditions. A relatively large body of research indicates that functional variation in human taste perception can influence nutritional intake as well as body mass accumulation. However, there are a considerable number of studies that suggest that no link between these variables actually exists. These discrepancies in the literature likely result from the confounding influence of a variety of other, uncontrolled, factors that can influence ingestive behavior. Strategy In this review, the use of controlled animal experimentation to alleviate at least some of these issues related to the lack of control of experimental variables is discussed. Specific examples of the use of some of these techniques are examined. Discussion and conclusions The review will close with some specific suggestions aimed at strengthening the link between gustatory neural input and its putative influence on ingestive behaviors and the maintenance of body weight. PMID:26557212

Highly Disordered Proteins in Prostate Cancer.

PubMed

Uversky, Vladimir N; Na, Insung; Landau, Kevin S; Schenck, Ryan O

2017-01-01

Prostate cancer is one of the major threats to the man's health. There are several mechanisms of the prostate cancer development characterized by the involvement of various androgen-related and androgen-unrelated factors in prostate cancer pathogenesis and in the metastatic carcinogenesis of prostate. In all these processes, proteins play various important roles, and the KEGG database has information on 88 human proteins experimentally shown to be involved in prostate cancer. It is known that many proteins associated with different human maladies are intrinsically disordered (i.e., they do not have stable secondary and/or tertiary structure in their unbound states). The goal of this review is to consider several highly disordered proteins known to be associated with the prostate cancer pathogenesis in order to better understand the roles of disordered proteins in this disease. We also hope that consideration of the pathology-related proteins from the perspective of intrinsic disorder can potentially lead to future experimental studies of these proteins to find novel pathways associated with prostate cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Measuring the effects of heat wave episodes on the human body's thermal balance

NASA Astrophysics Data System (ADS)

Katavoutas, George; Theoharatos, George; Flocas, Helena A.; Asimakopoulos, Dimosthenis N.

2009-03-01

During the peak of an extensive heat wave episode on 23-25 July 2007, simultaneous thermophysiological measurements were made in two non-acclimated healthy adults of different sex in a suburban area of Greater Athens, Greece. Based on experimental measurements of mean skin temperature and metabolic heat production, heat fluxes to and from the human body were calculated, and the biometeorological index heat load (HL) produced was determined according to the heat balance equation. Comparing experimental values with those derived from theoretical estimates revealed a great heat stress for both individuals, especially the male, while theoretical values underestimated heat stress. The study also revealed that thermophysiological factors, such as mean skin temperature and metabolic heat production, play an important role in determining heat fluxes patterns in the heat balance equation. The theoretical values of mean skin temperature as derived from an empirical equation may not be appropriate to describe the changes that take place in a non-acclimated individual. Furthermore, the changes in metabolic heat production were significant even for standard activity.

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

Loading rate effect on mechanical properties of cervical spine ligaments.

PubMed

Trajkovski, Ana; Omerovic, Senad; Krasna, Simon; Prebil, Ivan

2014-01-01

Mechanical properties of cervical spine ligaments are of great importance for an accurate finite element model when analyzing the injury mechanism. However, there is still little experimental data in literature regarding fresh human cervical spine ligaments under physiological conditions. The focus of the present study is placed on three cervical spine ligaments that stabilize the spine and protect the spinal cord: the anterior longitudinal ligament, the posterior longitudinal ligament and the ligamentum flavum. The ligaments were tested within 24-48 hours after death, under two different loading rates. An increase trend in failure load, failure stress, stiffness and modulus was observed, but proved not to be significant for all ligament types. The loading rate had the highest impact on failure forces for all three ligaments (a 39.1% average increase was found). The observed increase trend, compared to the existing increase trends reported in literature, indicates the importance of carefully applying the existing experimental data, especially when creating scaling factors. A better understanding of the loading rate effect on ligaments properties would enable better case-specific human modelling.

A key role for Pre-B cell colony-enhancing factor in experimental hepatitis.

PubMed

Moschen, Alexander R; Gerner, Romana; Schroll, Andrea; Fritz, Teresa; Kaser, Arthur; Tilg, Herbert

2011-08-01

Pre-B cell colony-enhancing factor (PBEF), also known as nicotinamide phosphoribosyltransferase or visfatin, plays an important role in metabolic, inflammatory, and malignant diseases. Recent evidence suggests that blocking its enzymatic activity using a specific small-molecule inhibitor (FK866) might be beneficial in acute experimental inflammation. We investigated the role of PBEF in human liver disease and experimental hepatitis. PBEF serum levels and hepatic expression were determined in patients with chronic liver diseases. These studies were followed by in vivo experiments using concanavalin A (ConA) and D-galactosamine/lipopolysaccharide (LPS) models of experimental hepatitis. PBEF was either overexpressed by hydrodynamic perfusion or inhibited by FK866. In vivo findings were corroborated studying inflammatory responses of lentivirally PBEF-silenced or control FL83B mouse hepatocytes. Here, we demonstrate that PBEF serum levels were increased in patients with chronic liver diseases irrespective of disease stage and etiology. In particular, we observed enhanced PBEF expression in hepatocytes. Liver-targeted overexpression of PBEF rendered mice more susceptible to ConA- and D-galactosamine/LPS-induced hepatitis compared with control animals. In contrast, inhibition of PBEF using FK866 protected mice from ConA-induced liver damage and apoptosis. Administration of FK866 resulted in depletion of liver nicotinamide adenine dinucleotide+ levels and reduced proinflammatory cytokine expression. Additionally, FK866 protected mice in the D-galactosamine/LPS model of acute hepatitis. In vitro, PBEF-silenced mouse hepatocytes showed decreased responses after stimulation with LPS, lipoteichoic acid, and tumor necrosis factor α. In primary murine Kupffer cells, FK866 suppressed LPS-induced interleukin (IL)-6 production, whereas incubation with recombinant PBEF resulted in increased IL-6 release. Our data suggest that PBEF is of key importance in experimental hepatitis. Its specific inhibition might be considered a novel treatment option for inflammatory liver diseases. Copyright © 2011 American Association for the Study of Liver Diseases.

Ethical review of human experimentation in the consumer products industry.

PubMed

Steadman, J H

1998-04-01

Ethical review of human experimentation in the consumer products industry is important and provides instructive parallels and contrasts with clinical medical research. The procedures used in Unilever NV/plc are described. A central body sets standards for and monitors compliance with ethical review of human studies throughout Unilever. Guidance has been produced on many topics including issues applying generally to human experimentation and more specifically to the consumer products sector. Deficiencies and inconsistencies in the procedures for ethical review and the care of subjects during the conduct of studies have been identified and corrected. Appropriate uniform standards have been achieved across all Unilever operations. All human experimentation in the industry needs adequate ethical review. Although the methods used by individual companies may differ, procedures must ensure uniform high standards across a global industry.

Inhibition of Protease-Activated Receptor (PAR1) Reduces Activation of the Endothelium, Coagulation, Fibrinolysis and Inflammation during Human Endotoxemia.

PubMed

Schoergenhofer, Christian; Schwameis, Michael; Gelbenegger, Georg; Buchtele, Nina; Thaler, Barbara; Mussbacher, Marion; Schabbauer, Gernot; Wojta, Johann; Jilma-Stohlawetz, Petra; Jilma, Bernd

2018-06-04

The protease-activated receptor-1 (PAR-1) is critically involved in the co-activation of coagulation and inflammatory responses. Vorapaxar is a reversible, orally active, low molecular weight, competitive antagonist of PAR-1.We investigated the effects of PAR-1 inhibition by vorapaxar on the inflammatory response, the activation of coagulation, fibrinolysis and endothelium during experimental endotoxemia. In this randomized, double blind, crossover trial, 16 healthy volunteers received a bolus infusion of 2 ng/kg lipopolysaccharide (LPS) ± placebo/vorapaxar with a washout period of 8 weeks. Vorapaxar dosing was guided by thrombin receptor-activating peptide-6-induced whole blood aggregometry. Participants received 10 mg vorapaxar or placebo as an initial dose and, depending on the aggregometry, potentially an additional 10 mg. Goal was > 80% inhibition of aggregation compared with baseline. Vorapaxar significantly reduced the LPS-induced increase in pro-thrombin fragments F1 + 2 by a median of 27% (quartiles: 11-49%), thrombin-anti-thrombin concentrations by 22% (-3 to 46%) and plasmin-anti-plasmin levels by 38% (23-53%). PAR-1 inhibition dampened peak concentrations of tumour necrosis factor -α, interleukin-6 and consequently C-reactive protein by 66% (-11-71%), 50% (15-79%) and 23% (16-38%), respectively. Vorapaxar decreased maximum von Willebrand factor levels by 29% (26-51%) and soluble E-selectin concentrations by 30% (25-38%) after LPS infusion. PAR-1 inhibition did not affect thrombomodulin, soluble P-selectin and platelet factor-4 concentrations.PAR-1 inhibition significantly reduced the activation of coagulation, fibrinolysis, the inflammatory response and endothelial activation during experimental human endotoxemia. Schattauer GmbH Stuttgart.

Fibroblasts Influence Survival and Therapeutic Response in a 3D Co-Culture Model

PubMed Central

Majety, Meher; Pradel, Leon P.; Gies, Manuela; Ries, Carola H.

2015-01-01

In recent years, evidence has indicated that the tumor microenvironment (TME) plays a significant role in tumor progression. Fibroblasts represent an abundant cell population in the TME and produce several growth factors and cytokines. Fibroblasts generate a suitable niche for tumor cell survival and metastasis under the influence of interactions between fibroblasts and tumor cells. Investigating these interactions requires suitable experimental systems to understand the cross-talk involved. Most in vitro experimental systems use 2D cell culture and trans-well assays to study these interactions even though these paradigms poorly represent the tumor, in which direct cell-cell contacts in 3D spaces naturally occur. Investigating these interactions in vivo is of limited value due to problems regarding the challenges caused by the species-specificity of many molecules. Thus, it is essential to use in vitro models in which human fibroblasts are co-cultured with tumor cells to understand their interactions. Here, we developed a 3D co-culture model that enables direct cell-cell contacts between pancreatic, breast and or lung tumor cells and human fibroblasts/ or tumor-associated fibroblasts (TAFs). We found that co-culturing with fibroblasts/TAFs increases the proliferation in of several types of cancer cells. We also observed that co-culture induces differential expression of soluble factors in a cancer type-specific manner. Treatment with blocking antibodies against selected factors or their receptors resulted in the inhibition of cancer cell proliferation in the co-cultures. Using our co-culture model, we further revealed that TAFs can influence the response to therapeutic agents in vitro. We suggest that this model can be reliably used as a tool to investigate the interactions between a tumor and the TME. PMID:26053043

The role of diet and nutrition in the etiology and prevention of oral diseases.

PubMed

Moynihan, Paula J

2005-09-01

Diet plays an important role in preventing oral diseases including dental caries, dental erosion, developmental defects, oral mucosal diseases and, to a lesser extent, periodontal disease. This paper is intended to provide an overview of the evidence for an association between diet, nutrition and oral diseases and to clarify areas of uncertainty. Undernutrition increases the severity of oral mucosal and periodontal diseases and is a contributing factor to life-threatening noma. Undernutrition is associated with developmental defects of the enamel which increase susceptibility to dental caries. Dental erosion is perceived to be increasing. Evidence suggests that soft drinks, a major source of acids in the diet in developed countries, are a significant causative factor. Convincing evidence from experimental, animal, human observational and human intervention studies shows that sugars are the main dietary factor associated with dental caries. Despite the indisputable role of fluoride in the prevention of caries, it has not eliminated dental caries and many communities are not exposed to optimal quantities of fluoride. Controlling the intake of sugars therefore remains important for caries prevention. Research has consistently shown that when the intake of free sugars is < 15 kg/person/year, the level of dental caries is low. Despite experimental and animal studies suggesting that some starch-containing foods and fruits are cariogenic, this is not supported by epidemiological data, which show that high intakes of starchy staple foods, fruits and vegetables are associated with low levels of dental caries. Following global recommendations that encourage a diet high in starchy staple foods, fruit and vegetables and low in free sugars and fat will protect both oral and general health.

The role of diet and nutrition in the etiology and prevention of oral diseases.

PubMed Central

Moynihan, Paula J.

2005-01-01

Diet plays an important role in preventing oral diseases including dental caries, dental erosion, developmental defects, oral mucosal diseases and, to a lesser extent, periodontal disease. This paper is intended to provide an overview of the evidence for an association between diet, nutrition and oral diseases and to clarify areas of uncertainty. Undernutrition increases the severity of oral mucosal and periodontal diseases and is a contributing factor to life-threatening noma. Undernutrition is associated with developmental defects of the enamel which increase susceptibility to dental caries. Dental erosion is perceived to be increasing. Evidence suggests that soft drinks, a major source of acids in the diet in developed countries, are a significant causative factor. Convincing evidence from experimental, animal, human observational and human intervention studies shows that sugars are the main dietary factor associated with dental caries. Despite the indisputable role of fluoride in the prevention of caries, it has not eliminated dental caries and many communities are not exposed to optimal quantities of fluoride. Controlling the intake of sugars therefore remains important for caries prevention. Research has consistently shown that when the intake of free sugars is < 15 kg/person/year, the level of dental caries is low. Despite experimental and animal studies suggesting that some starch-containing foods and fruits are cariogenic, this is not supported by epidemiological data, which show that high intakes of starchy staple foods, fruits and vegetables are associated with low levels of dental caries. Following global recommendations that encourage a diet high in starchy staple foods, fruit and vegetables and low in free sugars and fat will protect both oral and general health. PMID:16211161

Nrf2 protects against airway disorders

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

Cho, Hye-Youn, E-mail: cho2@niehs.nih.go; Kleeberger, Steven R.

Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that regulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. In the unstressed condition, Kelch-like ECH-associated protein 1 (Keap1) suppresses cellular Nrf2 in cytoplasm and drives its proteasomal degradation. Nrf2 can be activated by diverse stimuli including oxidants, pro-oxidants, antioxidants, and chemopreventive agents. Nrf2 induces cellular rescue pathways against oxidative injury, abnormal inflammatory and immune responses, apoptosis, and carcinogenesis. Application of Nrf2 germ-line mutant mice has identified an extensive range of protective roles for Nrf2 in experimental models of human disorders in the liver,more » gastrointestinal tract, airway, kidney, brain, circulation, and immune or nerve system. In the lung, lack of Nrf2 exacerbated toxicity caused by multiple oxidative insults including supplemental respiratory therapy (e.g., hyperoxia, mechanical ventilation), cigarette smoke, allergen, virus, bacterial endotoxin and other inflammatory agents (e.g., carrageenin), environmental pollution (e.g., particles), and a fibrotic agent bleomycin. Microarray analyses and bioinformatic studies elucidated functional AREs and Nrf2-directed genes that are critical components of signaling mechanisms in pulmonary protection by Nrf2. Association of loss of function with promoter polymorphisms in NRF2 or somatic and epigenetic mutations in KEAP1 and NRF2 has been found in cohorts of patients with acute lung injury/acute respiratory distress syndrome or lung cancer, which further supports the role for NRF2 in these lung diseases. In the current review, we address the role of Nrf2 in airways based on emerging evidence from experimental oxidative disease models and human studies.« less

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.

Assessing the scientific research productivity of a leading toxicology journal: A case study of Human & Experimental Toxicology from 2003 to 2012

PubMed Central

Al-Jabi, Samah W; Sweileh, Waleed M; Awang, Rahmat

2014-01-01

Background: Bibliometric studies are increasingly being used for research assessments. Bibliometric indicators involve the application of statistical methods to scientific publications to obtain the bibliographics for each journal. The main objective of this study was to conduct a bibliometric evaluation of Human & Experimental Toxicology retrieved from the Scopus database. Methods: This study obtained data from Scopus published from 1 January 2003 till 31 December 2012. The keywords entered in Scopus to accomplish the objective of this study were ‘Human’, ‘Experimental’ and ‘Toxicology’ as ‘Source Title’. Research productivity was evaluated based on a methodology developed and used in other bibliometric studies by analysing (a) total and trends in Human & Experimental Toxicology contributions in research between 2003 and 2012; (b) Human & Experimental Toxicology authorship patterns and productivity; (c) collaboration patterns; and (d) the citations received by the publications. Results: There were 1229 research articles published in Human & Experimental Toxicology. Of the articles included, 947 (77.1%) were original articles and 104 (8.5%) were review articles. The Hirsch-index of the retrieved documents was 35. The largest number of publications in Human & Experimental Toxicology was from the United States (19.6%), followed by India (12.8%) and Turkey (10.9%). The total number of citations was 9119, with a median (interquartile range) of 3 (1–9) in 6797 documents. The highest median (interquartile range) number of citations was 8 (2.7–12.7) for France, followed by 7.5 (2–22.5) for Iran and 6 (3–13.5) for the United Kingdom. The country most often citing articles that were published in Human & Experimental Toxicology was the United States, which made citations in 1508 documents, followed by India with citations in 792 documents. Conclusion: The documents in Human & Experimental Toxicology focus principally on original data, with very few review articles. Review articles tend to have higher citation rates than original articles, and hence, the editors and authors of Human & Experimental Toxicology might usefully promote the submission of reviews in the future to improve the impact of the journal. PMID:26770709

Evaluating droplet digital PCR for the quantification of human genomic DNA: converting copies per nanoliter to nanograms nuclear DNA per microliter.

PubMed

Duewer, David L; Kline, Margaret C; Romsos, Erica L; Toman, Blaza

2018-05-01

The highly multiplexed polymerase chain reaction (PCR) assays used for forensic human identification perform best when used with an accurately determined quantity of input DNA. To help ensure the reliable performance of these assays, we are developing a certified reference material (CRM) for calibrating human genomic DNA working standards. To enable sharing information over time and place, CRMs must provide accurate and stable values that are metrologically traceable to a common reference. We have shown that droplet digital PCR (ddPCR) limiting dilution end-point measurements of the concentration of DNA copies per volume of sample can be traceably linked to the International System of Units (SI). Unlike values assigned using conventional relationships between ultraviolet absorbance and DNA mass concentration, entity-based ddPCR measurements are expected to be stable over time. However, the forensic community expects DNA quantity to be stated in terms of mass concentration rather than entity concentration. The transformation can be accomplished given SI-traceable values and uncertainties for the number of nucleotide bases per human haploid genome equivalent (HHGE) and the average molar mass of a nucleotide monomer in the DNA polymer. This report presents the considerations required to establish the metrological traceability of ddPCR-based mass concentration estimates of human nuclear DNA. Graphical abstract The roots of metrological traceability for human nuclear DNA mass concentration results. Values for the factors in blue must be established experimentally. Values for the factors in red have been established from authoritative source materials. HHGE stands for "haploid human genome equivalent"; there are two HHGE per diploid human genome.

Stress exposure in early post-natal life reduces telomere length: an experimental demonstration in a long-lived seabird

PubMed Central

Herborn, Katherine A.; Heidinger, Britt J.; Boner, Winnie; Noguera, Jose C.; Adam, Aileen; Daunt, Francis; Monaghan, Pat

2014-01-01

Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequently subjected to several confounding factors; also, being based on leucocyte populations, where cell composition is variable and some telomere restoration can occur, the extent to which these effects extend beyond the immune system has been questioned. In this study, we experimentally manipulated stress exposure early in post-natal life in nestling European shags (Phalacrocorax aristotelis) in the wild and examined the effect on telomere length in erythrocytes. Our results show that greater stress exposure during early post-natal life increases telomere loss at this life-history stage, and that such an effect is not confined to immune cells. The delayed effects of increased telomere attrition in early life could therefore give rise to a ‘time bomb’ that reduces longevity in the absence of any obvious phenotypic consequences early in life. PMID:24648221

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.

Host adaptation of a bacterial toxin from the human pathogen Salmonella Typhi

PubMed Central

Deng, Lingquan; Song, Jeongmin; Gao, Xiang; Wang, Jiawei; Yu, Hai; Chen, Xi; Varki, Nissi; Naito-Matsui, Yuko; Galán, Jorge E.; Varki, Ajit

2014-01-01

Salmonella Typhi is an exclusive human pathogen that causes typhoid fever. Typhoid toxin is a S. Typhi virulence factor that can reproduce most of the typhoid fever symptoms in experimental animals. Toxicity depends on toxin binding to terminally sialylated glycans on surface glycoproteins. Human glycans are unusual because of the lack of CMAH, which in other mammals converts N-acetylneuraminic acid (Neu5Ac) to N-glycolylneuraminic acid (Neu5Gc). Here we report that typhoid toxin binds to and is toxic towards cells expressing glycans terminated in Neu5Ac (expressed by humans) over glycans terminated in Neu5Gc (expressed by other mammals). Mice constitutively expressing CMAH thus displaying Neu5Gc in all tissues are resistant to typhoid toxin. The atomic structure of typhoid toxin bound to Neu5Ac reveals the structural bases for its binding specificity. These findings provide insight into the molecular bases for Salmonella Typhi’s host specificity and may help the development of therapies for typhoid fever. PMID:25480294

THE SYMPATHETIC NERVOUS SYSTEM ALTERATIONS IN HUMAN HYPERTENSION

PubMed Central

Grassi, Guido; Mark, Allyn; Esler, Murray

2015-01-01

A number of articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as “promoters” and “amplifiers” of human hypertension. We expand on the role of the sympathetic nervous system in two increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves. PMID:25767284

Mycotoxins as human carcinogens-the IARC Monographs classification.

PubMed

Ostry, Vladimir; Malir, Frantisek; Toman, Jakub; Grosse, Yann

2017-02-01

Humans are constantly exposed to mycotoxins (e.g. aflatoxins, ochratoxins), mainly via food intake of plant and animal origin. The health risks stemming from mycotoxins may result from their toxicity, in particular their carcinogenicity. In order to prevent these risks, the International Agency for Research on Cancer (IARC) in Lyon (France)-through its IARC Monographs programme-has performed the carcinogenic hazard assessment of some mycotoxins in humans, on the basis of epidemiological data, studies of cancer in experimental animals and mechanistic studies. The present article summarizes the carcinogenic hazard assessments of those mycotoxins, especially aflatoxins (aflatoxin B 1 , B 2 , G 1 , G 2 and M 1 ), fumonisins (fumonisin B 1 and B 2 ) and ochratoxin A (OTA). New information regarding the genotoxicity of OTA (formation of OTA-DNA adducts), the role of OTA in oxidative stress and the identification of epigenetic factors involved in OTA carcinogenesis-should they indeed provide strong evidence that OTA carcinogenicity is mediated by a mechanism that also operates in humans-could lead to the reclassification of OTA.

Pandemic HIV-1 Vpu overcomes intrinsic herd immunity mediated by tetherin.

PubMed

Iwami, Shingo; Sato, Kei; Morita, Satoru; Inaba, Hisashi; Kobayashi, Tomoko; Takeuchi, Junko S; Kimura, Yuichi; Misawa, Naoko; Ren, Fengrong; Iwasa, Yoh; Aihara, Kazuyuki; Koyanagi, Yoshio

2015-07-17

Among the four groups of HIV-1 (M, N, O, and P), HIV-1M alone is pandemic and has rapidly expanded across the world. However, why HIV-1M has caused a devastating pandemic while the other groups remain contained is unclear. Interestingly, only HIV-1M Vpu, a viral protein, can robustly counteract human tetherin, which tethers budding virions. Therefore, we hypothesize that this property of HIV-1M Vpu facilitates human-to-human viral transmission. Adopting a multilayered experimental-mathematical approach, we demonstrate that HIV-1M Vpu confers a 2.38-fold increase in the prevalence of HIV-1 transmission. When Vpu activity is lost, protected human populations emerge (i.e., intrinsic herd immunity develops) through the anti-viral effect of tetherin. We also reveal that all Vpus of transmitted/founder HIV-1M viruses maintain anti-tetherin activity. These findings indicate that tetherin plays the role of a host restriction factor, providing 'intrinsic herd immunity', whereas Vpu has evolved in HIV-1M as a tetherin antagonist.

The Road to Certainty and Back.

PubMed

Westheimer, Gerald

2016-10-14

The author relates his intellectual journey from eye-testing clinician to experimental vision scientist. Starting with the quest for underpinning in physics and physiology of vague clinical propositions and of psychology's acceptance of thresholds as "fuzzy-edged," and a long career pursuing a reductionist agenda in empirical vision science, his journey led to the realization that the full understanding of human vision cannot proceed without factoring in an observer's awareness, with its attendant uncertainty and open-endedness. He finds support in the loss of completeness, finality, and certainty revealed in fundamental twentieth-century formulations of mathematics and physics. Just as biology prospered with the introduction of the emergent, nonreductionist concepts of evolution, vision science has to become comfortable accepting data and receiving guidance from human observers' conscious visual experience.

Behavioral and cerebellar transmission deficits in mice lacking the autism-linked gene islet brain-2.

PubMed

Giza, Joanna; Urbanski, Michael J; Prestori, Francesca; Bandyopadhyay, Bhaswati; Yam, Annie; Friedrich, Victor; Kelley, Kevin; D'Angelo, Egidio; Goldfarb, Mitchell

2010-11-03

Deletion of the human SHANK3 gene near the terminus of chromosome 22q is associated with Phelan-McDermid syndrome and autism spectrum disorders. Nearly all such deletions also span the tightly linked IB2 gene. We show here that IB2 protein is broadly expressed in the brain and is highly enriched within postsynaptic densities. Experimental disruption of the IB2 gene in mice reduces AMPA and enhances NMDA receptor-mediated glutamatergic transmission in cerebellum, changes the morphology of Purkinje cell dendritic arbors, and induces motor and cognitive deficits suggesting an autism phenotype. These findings support a role for human IB2 mutation as a contributing genetic factor in Chr22qter-associated cognitive disorders.

Neurotrophins, their receptors and KI-67 in human GH-secreting pituitary adenomas: an immunohistochemical analysis.

PubMed

Artico, M; Bianchi, E; Magliulo, G; De Vincentiis, M; De Santis, E; Orlandi, A; Santoro, A; Pastore, F S; Giangaspero, F; Caruso, R; Re, M; Fumagalli, L

2012-01-01

Pituitary adenomas are a diverse group of tumors arising from the pituitary gland. Typically, they are small, slow-growing, hormonally inactive lesions that come to light as incidental findings on radiologic or postmortem examinations, although some small, slow-growing lesions with excessive hormonal activity may manifest with a clinical syndrome. The family of neurotrophins plays a key role in the development and maintenance of the pituitary endocrine cell function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. The objective of our experimental study is to investigate the localization of the neurotrophins, their relative receptors and to detect the expression level of Ki-67 to determine whether all these factors participate in the transformation and development of human pituitary adenomas. A very strong expression of Neurotrophin-3 (NT-3) and its receptor TrKC was observed in the extracellular matrix (ECM) and vessel endothelium, together with a clear/marked presence of Brain-derived neurotrophic factor (BDNF), and its receptor TrKB, thus confirming their direct involvement in the progression of pituitary adenomas. On the contrary, NGF (Nerve growth factor) and its receptor TrKA and p75NTR were weakly expressed in the epithelial gland cells and the ECM.

Phosphate toxicity: new insights into an old problem

PubMed Central

RAZZAQUE, M. Shawkat

2011-01-01

Phosphorus is an essential nutrient required for critical biological reactions that maintain the normal homoeostatic control of the cell. This element is an important component of different cellular structures, including nucleic acids and cell membranes. Adequate phosphorus balance is vital for maintaining basic cellular functions, ranging from energy metabolism to cell signalling. In addition, many intracellular pathways utilize phosphate ions for important cellular reactions; therefore, homoeostatic control of phosphate is one of the most delicate biological regulations. Impaired phosphorus balance can affect the functionality of almost every human system, including musculoskeletal and cardiovascular systems, ultimately leading to an increase in morbidity and mortality of the affected patients. Human and experimental studies have found that delicate balance among circulating factors, like vitamin D, PTH (parathyroid hormone) and FGF23 (fibroblast growth factor 23), are essential for regulation of physiological phosphate balance. Dysregulation of these factors, either alone or in combination, can induce phosphorus imbalance. Recent studies have shown that suppression of the FGF23–klotho system can lead to hyperphosphataemia with extensive tissue damage caused by phosphate toxicity. The cause and consequences of phosphate toxicity will be briefly summarized in the present review. PMID:20958267

Phosphate toxicity: new insights into an old problem.

PubMed

Razzaque, M Shawkat

2011-02-01

Phosphorus is an essential nutrient required for critical biological reactions that maintain the normal homoeostatic control of the cell. This element is an important component of different cellular structures, including nucleic acids and cell membranes. Adequate phosphorus balance is vital for maintaining basic cellular functions, ranging from energy metabolism to cell signalling. In addition, many intracellular pathways utilize phosphate ions for important cellular reactions; therefore, homoeostatic control of phosphate is one of the most delicate biological regulations. Impaired phosphorus balance can affect the functionality of almost every human system, including musculoskeletal and cardiovascular systems, ultimately leading to an increase in morbidity and mortality of the affected patients. Human and experimental studies have found that delicate balance among circulating factors, like vitamin D, PTH (parathyroid hormone) and FGF23 (fibroblast growth factor 23), are essential for regulation of physiological phosphate balance. Dysregulation of these factors, either alone or in combination, can induce phosphorus imbalance. Recent studies have shown that suppression of the FGF23-klotho system can lead to hyperphosphataemia with extensive tissue damage caused by phosphate toxicity. The cause and consequences of phosphate toxicity will be briefly summarized in the present review.

In vivo over-expression of KGF mimic human middle ear cholesteatoma.

PubMed

Yamamoto-Fukuda, Tomomi; Akiyama, Naotaro; Shibata, Yasuaki; Takahashi, Haruo; Ikeda, Tohru; Koji, Takehiko

2015-10-01

We reported previously that keratinocyte growth factor (KGF), a mesenchymal cell-derived paracrine growth factor, plays an important role in middle ear cholesteatoma formation, which is characterized by marked proliferation of epithelial cells. Here, we investigated whether KGF, the main factor that induces cholesteatoma, overexpression in vivo results in the formation of cholesteatoma. Flag-hKGF cDNA driven by CMV14 promoter was transfected through electroporation into the external auditory canal (EAC) of rats once (short-term model) or five times on every fourth day (long-term model). Ears transfected with empty vector were used as controls. Successful transfection of plasmids into epithelial and stromal cells was confirmed by Flag immunohistochemistry. In the short-term model, the intensity of KGF protein was the strongest in hKGF transfected ear at day 4. KGF expression induced epithelial cell proliferation, reaching a peak level at day 4 and then decreased later, while in the long-term model, KGF expression in the EAC led to middle ear cholesteatoma formation. In conclusion, we described here a new experimental model of human middle ear cholesteatoma, and demonstrated that KGF and KGF receptor paracrine action play an essential role in middle ear cholesteatoma formation in an in vivo model.

Impact factors on development of cirrhosis and subsequent hepatocellular carcinoma.

PubMed

Holmes-McNary, M

2001-07-01

Hepatocellular carcinoma (HCC), on the rise in many countries, is of multifactorial etiology. Its etiological associations differ between populations at high and low risk. Africans and Chinese have the highest incidence of HCC, but other affected groups include African Americans, Japanese, and Native Americans. Chronic infections by hepatitis B and hepatitis C viruses are major risk factors worldwide, although mechanisms through which the infections cause liver cancer are yet to be explained. Other documented risk factors have been postulated and include dietary exposure, cigarette smoking, alcohol consumption, diabetes, oral infection, and oral contraceptive use. In addition, many naturally occurring and synthetic chemicals to which humans are exposed via accidental contamination of food or water are shown to induce liver cancer in experimental animals. Consequently, assessment of possible human liver cancer risk associated with such exposures is complex. Early diagnosis and transplantation are the best treatments presently, although transplantation is not widely available due to donor shortage. Every effort should be directed toward the prevention of HCC, through the treatment and prevention of hepatitis and oral infections, prevention of chronic hepatitis progressing to cirrhosis, and prevention of the cirrhotic liver from developing HCC through chemopreventive modalities. However, at present, very few such studies exist.

Visualization of light propagation in visible Chinese human head for functional near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Li, Ting; Gong, Hui; Luo, Qingming

2011-04-01

Using the visible Chinese human data set, which faithfully represents human anatomy, we visualize the light propagation in the head in detail based on Monte Carlo simulation. The simulation is verified to agree with published experimental results in terms of a differential path-length factor. The spatial sensitivity profile turns out to seem like a fat tropical fish with strong distortion along the folding cerebral surface. The sensitive brain region covers the gray matter and extends to the superficial white matter, leading to a large penetration depth (>3 cm). Finally, the optimal source-detector separation is suggested to be narrowed down to 3-3.5 cm, while the sensitivity of the detected signal to brain activation reaches the peak of 8%. These results indicate that the cerebral cortex folding geometry actually has substantial effects on light propagation, which should be necessarily considered for applications of functional near-infrared spectroscopy.

Clinical Application of Induced Pluripotent Stem Cells in Cardiovascular Medicine.

PubMed

Chi, Hong-jie; Gao, Song; Yang, Xin-chun; Cai, Jun; Zhao, Wen-shu; Sun, Hao; Geng, Yong-Jian

2015-01-01

Induced pluripotent stem cells (iPSCs) are generated by reprogramming human somatic cells through the overexpression of four transcription factors: Oct4, Sox2, Klf4 and c-Myc. iPSCs are capable of indefinite self-renewal, and they can differentiate into almost any type of cell in the body. These cells therefore offer a highly valuable therapeutic strategy for tissue repair and regeneration. Recent experimental and preclinical research has revealed their potential for cardiovascular disease diagnosis, drug screening and cellular replacement therapy. Nevertheless, significant challenges remain in terms of the development and clinical application of human iPSCs. Here, we review current progress in research related to patient-specific iPSCs for ex vivo modeling of cardiovascular disorders and drug screening, and explore the potential of human iPSCs for use in the field of cardiovascular regenerative medicine. © 2015 S. Karger AG, Basel.

Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation.

PubMed

Sampaziotis, Fotios; de Brito, Miguel Cardoso; Madrigal, Pedro; Bertero, Alessandro; Saeb-Parsy, Kourosh; Soares, Filipa A C; Schrumpf, Elisabeth; Melum, Espen; Karlsen, Tom H; Bradley, J Andrew; Gelson, William Th; Davies, Susan; Baker, Alastair; Kaser, Arthur; Alexander, Graeme J; Hannan, Nicholas R F; Vallier, Ludovic

2015-08-01

The study of biliary disease has been constrained by a lack of primary human cholangiocytes. Here we present an efficient, serum-free protocol for directed differentiation of human induced pluripotent stem cells into cholangiocyte-like cells (CLCs). CLCs show functional characteristics of cholangiocytes, including bile acids transfer, alkaline phosphatase activity, γ-glutamyl-transpeptidase activity and physiological responses to secretin, somatostatin and vascular endothelial growth factor. We use CLCs to model in vitro key features of Alagille syndrome, polycystic liver disease and cystic fibrosis (CF)-associated cholangiopathy. Furthermore, we use CLCs generated from healthy individuals and patients with polycystic liver disease to reproduce the effects of the drugs verapamil and octreotide, and we show that the experimental CF drug VX809 rescues the disease phenotype of CF cholangiopathy in vitro. Our differentiation protocol will facilitate the study of biological mechanisms controlling biliary development, as well as disease modeling and drug screening.

Neuro-fuzzy model for estimating race and gender from geometric distances of human face across pose

NASA Astrophysics Data System (ADS)

Nanaa, K.; Rahman, M. N. A.; Rizon, M.; Mohamad, F. S.; Mamat, M.

2018-03-01

Classifying human face based on race and gender is a vital process in face recognition. It contributes to an index database and eases 3D synthesis of the human face. Identifying race and gender based on intrinsic factor is problematic, which is more fitting to utilizing nonlinear model for estimating process. In this paper, we aim to estimate race and gender in varied head pose. For this purpose, we collect dataset from PICS and CAS-PEAL databases, detect the landmarks and rotate them to the frontal pose. After geometric distances are calculated, all of distance values will be normalized. Implementation is carried out by using Neural Network Model and Fuzzy Logic Model. These models are combined by using Adaptive Neuro-Fuzzy Model. The experimental results showed that the optimization of address fuzzy membership. Model gives a better assessment rate and found that estimating race contributing to a more accurate gender assessment.

The Role of Oxidative Stress and Inflammation in Cardiovascular Aging

PubMed Central

Wu, Junzhen; Xia, Shijin; Kalionis, Bill; Sun, Tao

2014-01-01

Age is an independent risk factor of cardiovascular disease, even in the absence of other traditional factors. Emerging evidence in experimental animal and human models has emphasized a central role for two main mechanisms of age-related cardiovascular disease: oxidative stress and inflammation. Excess reactive oxygen species (ROS) and superoxide generated by oxidative stress and low-grade inflammation accompanying aging recapitulate age-related cardiovascular dysfunction, that is, left ventricular hypertrophy, fibrosis, and diastolic dysfunction in the heart as well as endothelial dysfunction, reduced vascular elasticity, and increased vascular stiffness. We describe the signaling involved in these two main mechanisms that include the factors NF-κB, JunD, p66Shc, and Nrf2. Potential therapeutic strategies to improve the cardiovascular function with aging are discussed, with a focus on calorie restriction, SIRT1, and resveratrol. PMID:25143940

Alternative source of stem cells derived from human periodontal ligament: a new treatment for experimental autoimmune encephalomyelitis.

PubMed

Trubiani, Oriana; Giacoppo, Sabrina; Ballerini, Patrizia; Diomede, Francesca; Piattelli, Adriano; Bramanti, Placido; Mazzon, Emanuela

2016-01-04

Multiple sclerosis is a demyelinating disease mostly of autoimmune origin that affects and damages the central nervous system, leading to a disabling condition. The aim of the present study was to investigate whether administration of mesenchymal stem cells from human periodontal ligament (hPDLSCs) could ameliorate multiple sclerosis progression by exerting neuroprotective effects in an experimental model of autoimmune encephalomyelitis (EAE). EAE was induced by immunization with myelin oligodendroglial glycoprotein peptide (MOG)35-55 in C57BL/6 mice. After immunization, mice were observed every 48 hours for signs of EAE and weight loss. At the onset of disease, approximately 14 days after immunization, EAE mice were subjected to a single intravenous injection of hPDLSCs (10(6) cells/150 μl) into the tail vein. At the point of animal sacrifice on day 56 after EAE induction, spinal cord and brain tissues were collected in order to perform histological evaluation, immunohistochemistry and western blotting analysis. Achieved results reveal that treatment with hPDLSCs may exert neuroprotective effects against EAE, diminishing both clinical signs and histological score typical of the disease (lymphocytic infiltration and demyelination) probably through the production of neurotrophic factors (results focused on brain-derived neurotrophic factor and nerve growth factor expression). Furthermore, administration of hPDLSCs modulates expression of inflammatory key markers (tumor necrosis factor-α, interleukin (IL)-1β, IL-10, glial fibrillary acidic protein, Nrf2 and Foxp3), the release of CD4 and CD8α T cells, and the triggering of apoptotic death pathway (data shown for cleaved caspase 3, p53 and p21). In light of the achieved results, transplantation of hPDLSCs may represent a putative novel and helpful tool for multiple sclerosis treatment. These cells could have considerable implication for future therapies for multiple sclerosis and this study may represent the starting point for further investigations.

Maternal Stress Combined with Terbutaline Leads to Comorbid Autistic-Like Behavior and Epilepsy in a Rat Model.

PubMed

Bercum, Florencia M; Rodgers, Krista M; Benison, Alex M; Smith, Zachariah Z; Taylor, Jeremy; Kornreich, Elise; Grabenstatter, Heidi L; Dudek, F Edward; Barth, Daniel S

2015-12-02

Human autism is comorbid with epilepsy, yet, little is known about the causes or risk factors leading to this combined neurological syndrome. Although genetic predisposition can play a substantial role, our objective was to investigate whether maternal environmental factors alone could be sufficient. We examined the independent and combined effects of maternal stress and terbutaline (used to arrest preterm labor), autism risk factors in humans, on measures of both autistic-like behavior and epilepsy in Sprague-Dawley rats. Pregnant dams were exposed to mild stress (foot shocks at 1 week intervals) throughout pregnancy. Pups were injected with terbutaline on postnatal days 2-5. Either maternal stress or terbutaline resulted in autistic-like behaviors in offspring (stereotyped/repetitive behaviors and deficits in social interaction or communication), but neither resulted in epilepsy. However, their combination resulted in severe behavioral symptoms, as well as spontaneous recurrent convulsive seizures in 45% and epileptiform spikes in 100%, of the rats. Hippocampal gliosis (GFAP reactivity) was correlated with both abnormal behavior and spontaneous seizures. We conclude that prenatal insults alone can cause comorbid autism and epilepsy but it requires a combination of teratogens to achieve this; testing single teratogens independently and not examining combinatorial effects may fail to reveal key risk factors in humans. Moreover, astrogliosis may be common to both teratogens. This new animal model of combined autism and epilepsy permits the experimental investigation of both the cellular mechanisms and potential intervention strategies for this debilitating comorbid syndrome. Copyright © 2015 the authors 0270-6474/15/3515894-09$15.00/0.

Aviation Human-in-the-Loop Simulation Studies: Experimental Planning, Design, and Data Management

DTIC Science & Technology

2014-01-01

Aviation Human-in-the-Loop Simulation Studies: Experimental Planning, Design , and Data Management Kevin W. Williams1 Bonny Christopher2 Gena...Simulation Studies: Experimental Planning, Design , and Data Management January 2014 6. Performing Organization Code 7. Author(s) 8. Performing...describe the process by which we designed our human-in-the-loop (HITL) simulation study and the methodology used to collect and analyze the results

CamOptimus: a tool for exploiting complex adaptive evolution to optimize experiments and processes in biotechnology

PubMed Central

Cankorur-Cetinkaya, Ayca; Dias, Joao M. L.; Kludas, Jana; Slater, Nigel K. H.; Rousu, Juho; Dikicioglu, Duygu

2017-01-01

Multiple interacting factors affect the performance of engineered biological systems in synthetic biology projects. The complexity of these biological systems means that experimental design should often be treated as a multiparametric optimization problem. However, the available methodologies are either impractical, due to a combinatorial explosion in the number of experiments to be performed, or are inaccessible to most experimentalists due to the lack of publicly available, user-friendly software. Although evolutionary algorithms may be employed as alternative approaches to optimize experimental design, the lack of simple-to-use software again restricts their use to specialist practitioners. In addition, the lack of subsidiary approaches to further investigate critical factors and their interactions prevents the full analysis and exploitation of the biotechnological system. We have addressed these problems and, here, provide a simple‐to‐use and freely available graphical user interface to empower a broad range of experimental biologists to employ complex evolutionary algorithms to optimize their experimental designs. Our approach exploits a Genetic Algorithm to discover the subspace containing the optimal combination of parameters, and Symbolic Regression to construct a model to evaluate the sensitivity of the experiment to each parameter under investigation. We demonstrate the utility of this method using an example in which the culture conditions for the microbial production of a bioactive human protein are optimized. CamOptimus is available through: (https://doi.org/10.17863/CAM.10257). PMID:28635591

High levels of the extracellular matrix proteoglycan decorin are associated with inhibition of testicular function

PubMed Central

Adam, Marion; Urbanski, Henryk F.; Garyfallou, Vasilios T.; Welsch, Ulrich; Köhn, Frank M.; Schwarzer, J. Ullrich; Strauss, Leena; Poutanen, Matti; Mayerhofer, Artur

2011-01-01

Decorin (DCN), a component of the extracellular matrix of the peritubular wall and the interstitial areas of the human testis, can interact with growth factor (GF) signaling, thereby blocking downstream actions of GFs. In the present study the expression and regulation of DCN using both human testes and two experimental animal models, namely the rhesus monkey and mouse, were examined. DCN protein was present in peritubular and interstitial areas of adult human and monkey testes, while it was almost undetectable in adult wild-type mice. Interestingly, the levels and sites of testicular DCN expression in the monkeys were inversely correlated with testicular maturation markers. A strong DCN expression associated with the abundant connective tissue of the interstitial areas in the postnatal through prepubertal phases was observed. In adult and old monkeys the DCN pattern was similar to the one in normal human testes, presenting strong expression at the peritubular region. In the testes of both infertile men and in a mouse model of inflammation associated infertility (aromatase-overexpressing transgenic mice), the fibrotic changes and increased numbers of Tumor necrosis factor (TNF)-α-producing immune cells were shown to be associated with increased production of DCN. Furthermore, studies with human testicular peritubular cells isolated from fibrotic testis indicated that TNF-α significantly increased DCN production. The data, thus, show that an increased DCN level is associated with impaired testicular function, supporting our hypothesis that DCN interferes with paracrine signaling of the testis in health and disease. PMID:22413766

Effect of combination of thalidomide and sulfasalazine in experimentally induced inflammatory bowel disease in rats.

PubMed

Prakash, O; Medhi, B; Saikia, U N; Pandhi, P

2011-09-01

Thalidomide provided significant protection against tri nitro benzene sulfonic acid induced colitis. Combination therapy also reduced colonic inflammation and all the biochemical parameters (myeloperoxidase assay, malondialdehyde assay and tumor necrosis factor-alpha, estimation) were significant as compared to control as well as thalidomide alone treated group. Combination therapy showed additive effect of thalidomide which restored lipid peroxidation as well as reduced myeloperoxidase and TNF-a towards the normal levels. Morphological and histological scores were significantly reduced in combination groups. In experimental model of colitis, oral administration of thalidomide (150 mg/kg) alone as well as its combination with sulfasalazine (360 mg/kg) significantly reduced the colonic inflammation. The results indicate the additive effect of thalidomide with sulfasalazine in rat colitis model which requires further confirmation in human studies.

In silico simulations of experimental protocols for cardiac modeling.

PubMed

Carro, Jesus; Rodriguez, Jose Felix; Pueyo, Esther

2014-01-01

A mathematical model of the AP involves the sum of different transmembrane ionic currents and the balance of intracellular ionic concentrations. To each ionic current corresponds an equation involving several effects. There are a number of model parameters that must be identified using specific experimental protocols in which the effects are considered as independent. However, when the model complexity grows, the interaction between effects becomes increasingly important. Therefore, model parameters identified considering the different effects as independent might be misleading. In this work, a novel methodology consisting in performing in silico simulations of the experimental protocol and then comparing experimental and simulated outcomes is proposed for parameter model identification and validation. The potential of the methodology is demonstrated by validating voltage-dependent L-type calcium current (ICaL) inactivation in recently proposed human ventricular AP models with different formulations. Our results show large differences between ICaL inactivation as calculated from the model equation and ICaL inactivation from the in silico simulations due to the interaction between effects and/or to the experimental protocol. Our results suggest that, when proposing any new model formulation, consistency between such formulation and the corresponding experimental data that is aimed at being reproduced needs to be first verified considering all involved factors.

The Impact of Environmental Design on Doffing Personal Protective Equipment in a Healthcare Environment: A Formative Human Factors Trial.

PubMed

Herlihey, Tracey A; Gelmi, Stefano; Cafazzo, Joseph A; Hall, Trevor N T

2017-06-01

OBJECTIVE To explore the impact of environmental design on doffing personal protective equipment in a simulated healthcare environment. METHODS A mixed-methods approach was used that included human-factors usability testing and qualitative questionnaire responses. A patient room and connecting anteroom were constructed for testing purposes. This experimental doffing area was designed to overcome the environmental failures identified in a previous study and was not constructed based on any generalizable hospital standard. RESULTS In total, 72 healthcare workers from Ontario, Canada, took part in the study and tested the simulated doffing area. The following environmental design changes were tested and were deemed effective: increasing prominence of color-coded zones; securing disinfectant wipes and hand sanitizer; outlining disposal bins locations; providing mirrors to detect possible contamination; providing hand rails to assist with doffing; and restricting the space to doff. Further experimentation and iterative design are required with regard to several important features: positioning the disposal bins for safety, decreasing the risk of contamination and user accessibility; optimal positioning of mirrors for safety; communication within the team; and positioning the secondary team member for optimal awareness. Additional design suggestions also emerged during this study, and they require future investigation. CONCLUSIONS This study highlights the importance of the environment on doffing personal protective equipment in a healthcare setting. Iterative testing and modification of the design of the environment (doffing area) are important to enhancing healthcare worker safety. Infect Control Hosp Epidemiol 2017;38:712-717.

Determinants of shortened, disrupted, and mistimed sleep and associated metabolic health consequences in healthy humans.

PubMed

Cedernaes, Jonathan; Schiöth, Helgi B; Benedict, Christian

2015-04-01

Recent increases in the prevalence of obesity and type 2 diabetes mellitus (T2DM) in modern societies have been paralleled by reductions in the time their denizens spend asleep. Epidemiological studies have shown that disturbed sleep-comprising short, low-quality, and mistimed sleep-increases the risk of metabolic diseases, especially obesity and T2DM. Supporting a causal role of disturbed sleep, experimental animal and human studies have found that sleep loss can impair metabolic control and body weight regulation. Possible mechanisms for the observed changes comprise sleep loss-induced changes in appetite-signaling hormones (e.g., higher levels of the hunger-promoting hormone ghrelin) or hedonic brain responses, altered responses of peripheral tissues to metabolic signals, and changes in energy intake and expenditure. Even though the overall consensus is that sleep loss leads to metabolic perturbations promoting the development of obesity and T2DM, experimental evidence supporting the validity of this view has been inconsistent. This Perspective aims at discussing molecular to behavioral factors through which short, low-quality, and mistimed sleep may threaten metabolic public health. In this context, possible factors that may determine the extent to which poor sleep patterns increase the risk of metabolic pathologies within and across generations will be discussed (e.g., timing and genetics). © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Magnetic solid phase extraction of gemfibrozil from human serum and pharmaceutical wastewater samples utilizing a β-cyclodextrin grafted graphene oxide-magnetite nano-hybrid.

PubMed

Abdolmohammad-Zadeh, Hossein; Talleb, Zeynab

2015-03-01

A magnetic solid phase extraction method based on β-cyclodextrin (β-CD) grafted graphene oxide (GO)/magnetite (Fe3O4) nano-hybrid as an innovative adsorbent was developed for the separation and pre-concentration of gemfibrozil prior to its determination by spectrofluorometry. The as-prepared β-CD/GO/Fe3O4 nano-hybrid possesses the magnetism property of Fe3O4 nano-particles that makes it easily manipulated by an external magnetic field. On the other hand, the surface modification of GO by β-CD leads to selective separation of the target analyte from sample matrices. The structure and morphology of the synthesized adsorbent were characterized using powder X-ray diffraction, Fourier transform infrared spectroscopy, and field emission scanning electron microscopy. The experimental factors affecting the extraction/pre-concentration and determination of the analyte were investigated and optimized. Under the optimized experimental conditions, the calibration graph was linear in the range between 10 and 5000 pg mL(-1) with a correlation coefficient of 0.9989. The limit of detection and enrichment factor for gemfibrozil were 3 pg mL(-1) and 100, respectively. The maximum sorption capacity of the adsorbent for gemfibrozil was 49.8 mg g(-1). The method was successfully applied to monitoring gemfibrozil in human serum and pharmaceutical wastewaters samples with recoveries in the range of 96.0-104.0% for the spiked samples. Copyright © 2014 Elsevier B.V. All rights reserved.

Expression profile of undifferentiated cell transcription factor 1 in normal and cancerous human epithelia.

PubMed

Mouallif, Mustapha; Albert, Adelin; Zeddou, Mustapha; Ennaji, My Mustapha; Delvenne, Philippe; Guenin, Samuel

2014-08-01

Undifferentiated cell Transcription Factor 1 (UTF1) is a chromatin-bound protein involved in stem cell differentiation. It was initially reported to be restricted to stem cells or germinal tissues. However, recent work suggests that UTF1 is also expressed in somatic cells and that its expression may increase during carcinogenesis. To further clarify the expression profile of UTF1, we evaluated UTF1 expression levels immunohistochemically in eight normal human epithelia (from breast, prostate, endometrium, bladder, colon, oesophagus, lung and kidney) and their corresponding tumours as well as in several epithelial cell lines. We showed UTF1 staining in normal and tumour epithelial tissues, but with varying intensities according to the tissue location. In vitro analyses also revealed that UTF1 is expressed in somatic epithelial cell lines even in the absence of Oct4A and Sox2, its two main known regulators. The comparison of UTF1 levels in normal and tumoral tissues revealed significant overexpression in endometrial and prostatic adenocarcinomas, whereas lower intensity of the staining was observed in renal and colic tumours, suggesting a potential tissue-specific function of UTF1. Altogether, these results highlight a potential dual role for UTF1, acting either as an oncogene or as a tumour suppressor depending on the tissue. These findings also question its role as a specific marker for stem cells. © 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.

Paracrine Engineering of Human Cardiac Stem Cells With Insulin-Like Growth Factor 1 Enhances Myocardial Repair.

PubMed

Jackson, Robyn; Tilokee, Everad L; Latham, Nicholas; Mount, Seth; Rafatian, Ghazaleh; Strydhorst, Jared; Ye, Bin; Boodhwani, Munir; Chan, Vincent; Ruel, Marc; Ruddy, Terrence D; Suuronen, Erik J; Stewart, Duncan J; Davis, Darryl R

2015-09-11

Insulin-like growth factor 1 (IGF-1) activates prosurvival pathways and improves postischemic cardiac function, but this key cytokine is not robustly expressed by cultured human cardiac stem cells. We explored the influence of an enhanced IGF-1 paracrine signature on explant-derived cardiac stem cell-mediated cardiac repair. Receptor profiling demonstrated that IGF-1 receptor expression was increased in the infarct border zones of experimentally infarcted mice by 1 week after myocardial infarction. Human explant-derived cells underwent somatic gene transfer to overexpress human IGF-1 or the green fluorescent protein reporter alone. After culture in hypoxic reduced-serum media, overexpression of IGF-1 enhanced proliferation and expression of prosurvival transcripts and prosurvival proteins and decreased expression of apoptotic markers in both explant-derived cells and cocultured neonatal rat ventricular cardiomyocytes. Transplant of explant-derived cells genetically engineered to overexpress IGF-1 into immunodeficient mice 1 week after infarction boosted IGF-1 content within infarcted tissue and long-term engraftment of transplanted cells while reducing apoptosis and long-term myocardial scarring. Paracrine engineering of explant-derived cells to overexpress IGF-1 provided a targeted means of improving cardiac stem cell-mediated repair by enhancing the long-term survival of transplanted cells and surrounding myocardium. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Beta-glucan-depleted, glycopeptide-rich extracts from Brewer's and Baker's yeast (Saccharomyces cerevisiae) lower interferon-gamma production by stimulated human blood cells in vitro.

PubMed

Williams, Roderick; Dias, Daniel A; Jayasinghe, Nirupama; Roessner, Ute; Bennett, Louise E

2016-04-15

Regulation of the human immune system requires controlled pro- and anti-inflammatory responses for host defence against infection and disease states. Yeasts (Saccharomyces cerevisiae), as used in brewing and baking, are mostly known for ability to stimulate the human immune-system predominantly reflecting the pro-inflammatory cell wall β-glucans. However, in this study, using food-compatible processing methods, glycopeptide-enriched and β-glucan-depleted products were each prepared from Brewer's and Baker's yeasts, which suppressed production of interferon-γ (IFN-γ) in human whole blood cell assay, signifying that anti-inflammatory factors are also present in yeast. Anti-inflammatory bioactivities of products prepared from Brewer's and Baker's yeast were compared with the commercial yeast product, Epicor®. While unfractionated Epicor was inactive, the C18 resin-binding fractions of Brewer's and Baker's yeast products and Epicor dose-dependently lowered IFN-γ, demonstrating that Epicor also contained both pro-inflammatory (β-glucans) and anti-inflammatory components. Anti-inflammatory activity was attributed to C18 resin-binding species glyco-peptides in Epicor and experimental yeast products. This study demonstrated that pro- and anti-inflammatory factors could be resolved and enriched in yeasts by suitable processing, with potential to improve specific activities. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Three-dimensional computer-aided human factors engineering analysis of a grafting robot.

PubMed

Chiu, Y C; Chen, S; Wu, G J; Lin, Y H

2012-07-01

The objective of this research was to conduct a human factors engineering analysis of a grafting robot design using computer-aided 3D simulation technology. A prototype tubing-type grafting robot for fruits and vegetables was the subject of a series of case studies. To facilitate the incorporation of human models into the operating environment of the grafting robot, I-DEAS graphic software was applied to establish individual models of the grafting robot in line with Jack ergonomic analysis. Six human models (95th percentile, 50th percentile, and 5th percentile by height for both males and females) were employed to simulate the operating conditions and working postures in a real operating environment. The lower back and upper limb stresses of the operators were analyzed using the lower back analysis (LBA) and rapid upper limb assessment (RULA) functions in Jack. The experimental results showed that if a leg space is introduced under the robot, the operator can sit closer to the robot, which reduces the operator's level of lower back and upper limbs stress. The proper environmental layout for Taiwanese operators for minimum levels of lower back and upper limb stress are to set the grafting operation at 23.2 cm away from the operator at a height of 85 cm and with 45 cm between the rootstock and scion units.

In vivo evidence for a functional role of both tumor necrosis factor (TNF) receptors and transmembrane TNF in experimental hepatitis.

PubMed

Küsters, S; Tiegs, G; Alexopoulou, L; Pasparakis, M; Douni, E; Künstle, G; Bluethmann, H; Wendel, A; Pfizenmaier, K; Kollias, G; Grell, M

1997-11-01

The significance of tumor necrosis factor receptor 1 (TNFR1) for TNF function in vivo is well documented, whereas the role of TNFR2 so far remains obscure. In a model of concanavalin A (Con A)-induced, CD4+ T cell-dependent experimental hepatitis in mice, in which TNF is a central mediator of apoptotic and necrotic liver damage, we now provide evidence for an essential in vivo function of TNFR2 in this pathophysiological process. We demonstrate that a cooperation of TNFR1 and TNFR2 is required for hepatotoxicity as mice deficient of either receptor were resistant against Con A. A significant role of TNFR2 for Con A-induced hepatitis is also shown by the enhanced sensitivity of transgenic mice overexpressing the human TNFR2. The ligand for cytotoxic signaling via both TNF receptors is the precursor of soluble TNF, i.e. transmembrane TNF. Indeed, transmembrane TNF is sufficient to mediate hepatic damage, as transgenic mice deficient in wild-type soluble TNF but expressing a mutated nonsecretable form of TNF developed inflammatory liver disease.

Comment on "Topically Applied Connective Tissue Growth Factor/CCN2 Improves Diabetic Preclinical Cutaneous Wound Healing: Potential Role for CTGF in Human Diabetic Foot Ulcer Healing".

PubMed

Li, Hongling; Cao, Cong; Huang, Ai; Man, Yi

2015-01-01

A recent paper in this journal, presented a novel method by topical application of growth factors in stimulating diabetic cutaneous wound healing that caught our attention. We believe that the experimental method in the article is efficient and creative, but it also has some controversies and shortcomings to be discussed. We noted that the authors used "Tegaderm" as a semiocclusive dressing film and stated that it exerted a "splinting effect" on the wound margins and controlled contraction. Indeed, the "Tegaderm" itself can serve as a dressing film to isolate the wound bed with outside environments while the "splinting effect" is mainly achieved by adding silicone splints around the wound. Considering the unique properties of silicone splints and "Tegaderm," our experimental group propose an alternative method named "combined-suturing" technique that is not only suturing the silicone splints but also securing the "Tegaderm" around the wound. The specific reasons and operative procedures are explained in detail in this letter.

Sympathetic nervous system influences on the kidney. Role in hypertension.

PubMed

DiBona, G F

1989-03-01

Efferent renal sympathetic nerve activity (ERSNA) is elevated in human essential hypertension as well as several forms of experimental hypertension in animals. In addition, bilateral complete renal denervation delays the development and/or attenuates the magnitude of the hypertension in several different forms of experimental hypertension in animals. Efferent renal sympathetic nerve activity is known to have dose-dependent effects on renal blood flow and glomerular filtration rate, renal tubular sodium and water reabsorption, and renin secretion rate that are capable of contributing, singly or in combination, to the development, maintenance, and exacerbation of the hypertensive state. Of the many factors known to influence the central nervous system integrative regulation of ERSNA, two environmental factors, dietary sodium intake and environmental stress, are capable of significant interaction. This resultant increase in ERSNA and subsequent renal functional alterations can participate in the hypertensive process. This is especially evident in the presence of an underlying genetic predisposition to the development of hypertension. Thus, interactions between environmental and genetic influences can produce alterations in the sympathetic neural control of renal function that play an important role in hypertension.

Pathophysiological Approaches of Acute Respiratory Distress syndrome: Novel Bases for Study of Lung Injury

PubMed Central

Castillo, R.L; Carrasco Loza, R; Romero-Dapueto, C

2015-01-01

Experimental approaches have been implemented to research the lung damage related-mechanism. These models show in animals pathophysiological events for acute respiratory distress syndrome (ARDS), such as neutrophil activation, reactive oxygen species burst, pulmonary vascular hypertension, exudative edema, and other events associated with organ dysfunction. Moreover, these approaches have not reproduced the clinical features of lung damage. Lung inflammation is a relevant event in the develop of ARDS as component of the host immune response to various stimuli, such as cytokines, antigens and endotoxins. In patients surviving at the local inflammatory states, transition from injury to resolution is an active mechanism regulated by the immuno-inflammatory signaling pathways. Indeed, inflammatory process is regulated by the dynamics of cell populations that migrate to the lung, such as neutrophils and on the other hand, the role of the modulation of transcription factors and reactive oxygen species (ROS) sources, such as nuclear factor kappaB and NADPH oxidase. These experimental animal models reproduce key components of the injury and resolution phases of human ALI/ARDS and provide a methodology to explore mechanisms and potential new therapies. PMID:26312099

Latent Tuberculosis Infection: Myths, Models, and Molecular Mechanisms

PubMed Central

Dutta, Noton K.

2014-01-01

SUMMARY The aim of this review is to present the current state of knowledge on human latent tuberculosis infection (LTBI) based on clinical studies and observations, as well as experimental in vitro and animal models. Several key terms are defined, including “latency,” “persistence,” “dormancy,” and “antibiotic tolerance.” Dogmas prevalent in the field are critically examined based on available clinical and experimental data, including the long-held beliefs that infection is either latent or active, that LTBI represents a small population of nonreplicating, “dormant” bacilli, and that caseous granulomas are the haven for LTBI. The role of host factors, such as CD4+ and CD8+ T cells, T regulatory cells, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ), in controlling TB infection is discussed. We also highlight microbial regulatory and metabolic pathways implicated in bacillary growth restriction and antibiotic tolerance under various physiologically relevant conditions. Finally, we pose several clinically important questions, which remain unanswered and will serve to stimulate future research on LTBI. PMID:25184558

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

Fetal liver-derived mesenchymal stromal cells augment engraftment of transplanted hepatocytes

PubMed Central

Joshi, Meghnad; Patil, Pradeep B.; He, Zhong; Holgersson, Jan; Olausson, Michael; Sumitran-Holgersson, Suchitra

2012-01-01

Background aims One important problem commonly encountered after hepatocyte transplantation is the low numbers of transplanted cells found in the graft. If hepatocyte transplantation is to be a viable therapeutic approach, significant liver parenchyma repopulation is required. Mesenchymal stromal cells (MSC) produce high levels of various growth factors, cytokines and metalloproteinases, and have immunomodulatory effects. We therefore hypothesized that co-transplantation of MSC with human fetal hepatocytes (hFH) could augment in vivo expansion after transplantation. We investigated the ability of human fetal liver MSC (hFLMSC) to augment expansion of phenotypically and functionally well-characterized hFH. Methods Two million hFH (passage 6) were either transplanted alone or together (1:1 ratio) with green fluorescence protein-expressing hFLMSC into the spleen of C57BL/6 nude mice with retrorsine-induced liver injury. Results After 4 weeks, engraftment of cells was detected by fluorescence in situ hybridization using a human-specific DNA probe. Significantly higher numbers of cells expressing human cytokeratin (CK)8, CK18, CK19, Cysteine-rich MNNG HOS Transforming gene (c-Met), alpha-fetoprotein (AFP), human nuclear antigen, mitochondrial antigen, hepatocyte-specific antigen and albumin (ALB) were present in the livers of recipient animals co-transplanted with hFLMSC compared with those without. Furthermore, expression of human hepatocyte nuclear factor (HNF)-4α and HNF-1β, and cytochrome P450 (CYP) 3A7 mRNA was demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR) in these animals. In addition, significantly increased amounts of human ALB were detected. Importantly, hFLMSC did not transdifferentiate into hepatocytes. Conclusions Our study reports the use of a novel strategy for enhanced liver repopulation and thereby advances this experimental procedure closer to clinical liver cell therapy. PMID:22424216

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.

Human and soil exposure during mechanical chlorpyrifos, myclobutanil and copper oxychloride application in a peach orchard in Argentina.

PubMed

Berenstein, Giselle; Nasello, Soledad; Beiguel, Érica; Flores, Pedro; Di Schiena, Johanna; Basack, Silvana; Hughes, Enrique A; Zalts, Anita; Montserrat, Javier M

2017-05-15

The objective of this study was to measure the impact of the mechanized chlorpyrifos, copper oxychloride and myclobutanil application in a small peach orchard, on humans (operators, bystanders and residents) and on the productive soil. The mean Potential Dermal Exposure (PDE) of the workers (tractor drivers) was 30.8mL·h -1 ±16.4mL·h -1 , with no specific pesticide distribution on the laborers body. Although the Margin of Safety (MOS) factor for the application stage were above 1 (safe condition) for myclobutanil and cooper oxycloride it was below 1 for chlorpyrifos. The mix and load stage remained as the riskier operation. Pesticide found on the orchard soil ranged from 5.5% to 14.8% of the total chlorpyrifos, copper oxychloride and myclobutanil applied. Pesticide drift was experimentally measured, finding values in the range of 2.4% to 11.2% of the total pesticide applied. Using experimental drift values, bystander (for one application), resident (for 20 applications) and earthworm (for one application) risk indicators (RIs) were calculated for the chlorpyrifos plus copper oxychloride and for myclobutanil treatments for different distances to the orchard border. Earthworm RI was correlated with experimental Eisenia andrei ecotoxicological assays (enzymatic activities: cholinesterases, carboxylesterases and glutathione S-transferases; behavioral: avoidance and bait-lamina tests) with good correlation. Copyright © 2017 Elsevier B.V. All rights reserved.

Simulation of prompt gamma-ray emission during proton radiotherapy.

PubMed

Verburg, Joost M; Shih, Helen A; Seco, Joao

2012-09-07

The measurement of prompt gamma rays emitted from proton-induced nuclear reactions has been proposed as a method to verify in vivo the range of a clinical proton radiotherapy beam. A good understanding of the prompt gamma-ray emission during proton therapy is key to develop a clinically feasible technique, as it can facilitate accurate simulations and uncertainty analysis of gamma detector designs. Also, the gamma production cross-sections may be incorporated as prior knowledge in the reconstruction of the proton range from the measurements. In this work, we performed simulations of proton-induced nuclear reactions with the main elements of human tissue, carbon-12, oxygen-16 and nitrogen-14, using the nuclear reaction models of the GEANT4 and MCNP6 Monte Carlo codes and the dedicated nuclear reaction codes TALYS and EMPIRE. For each code, we made an effort to optimize the input parameters and model selection. The results of the models were compared to available experimental data of discrete gamma line cross-sections. Overall, the dedicated nuclear reaction codes reproduced the experimental data more consistently, while the Monte Carlo codes showed larger discrepancies for a number of gamma lines. The model differences lead to a variation of the total gamma production near the end of the proton range by a factor of about 2. These results indicate a need for additional theoretical and experimental study of proton-induced gamma emission in human tissue.

Animal experimentation in Japan: regulatory processes and application for microbiological studies.

PubMed

Takahashi-Omoe, H; Omoe, K

2007-07-01

We have conducted animal experimentation as a highly effective technique in biological studies. Also in microbiological studies, we have used experimentation to prevent and treat many infectious diseases in humans and animals. In Japan, the 'Law for the Humane Treatment and Management of Animals', which covers the consideration of the three R principles, refinement, replacement and reduction for an international humane approach to animal experimentation came into effect in June 2006. Looking towards the straightforward operation of the law in animal experimentation, three government ministries established new basic guidelines for experimentation performed in their jurisdictional research and testing facilities. For future microbiological studies involving animals in Japan, we need to perform animal experiments according to the basic guidelines in association with overseas management systems. In this report, we discussed essential actions for the management of animal experimentation in microbiological studies in Japan.

A hybrid computational-experimental approach for automated crystal structure solution

NASA Astrophysics Data System (ADS)

Meredig, Bryce; Wolverton, C.

2013-02-01

Crystal structure solution from diffraction experiments is one of the most fundamental tasks in materials science, chemistry, physics and geology. Unfortunately, numerous factors render this process labour intensive and error prone. Experimental conditions, such as high pressure or structural metastability, often complicate characterization. Furthermore, many materials of great modern interest, such as batteries and hydrogen storage media, contain light elements such as Li and H that only weakly scatter X-rays. Finally, structural refinements generally require significant human input and intuition, as they rely on good initial guesses for the target structure. To address these many challenges, we demonstrate a new hybrid approach, first-principles-assisted structure solution (FPASS), which combines experimental diffraction data, statistical symmetry information and first-principles-based algorithmic optimization to automatically solve crystal structures. We demonstrate the broad utility of FPASS to clarify four important crystal structure debates: the hydrogen storage candidates MgNH and NH3BH3; Li2O2, relevant to Li-air batteries; and high-pressure silane, SiH4.

T Cell Production of GM-CSF Protects the Host during Experimental Tuberculosis.

PubMed

Robinson, Richard T

2017-12-12

Although classically associated with myelopoiesis, granulocyte-macrophage colony-stimulating factor (GM-CSF) is increasingly recognized as being important for tuberculosis (TB) resistance. GM-CSF is expressed by nonhematopoietic and hematopoietic lineages following infection with Mycobacterium tuberculosis and is necessary to restrict M. tuberculosis growth in experimental models. Until the recent study by Rothchild et al. (mBio 8:e01514-17, 2017, https://doi.org/10.1128/mBio.01514-17), it was unknown whether GM-CSF-producing T cells contribute to TB resistance. Rothchild et al. identify which conventional and nonconventional T cell subsets produce GM-CSF during experimental TB, establish their protective nature using a variety of approaches, and provide a mechanistic basis for their ability to restrict M. tuberculosis growth. This commentary discusses the significance of these findings to basic and applied TB research. As translated to human disease, these findings suggest vaccine-mediated expansion of GM-CSF-producing T cells could be an effective prophylactic or therapeutic TB strategy. Copyright © 2017 Robinson.

An experimental study and finite element modeling of head and neck cooling for brain hypothermia.

PubMed

Li, Hui; Chen, Roland K; Tang, Yong; Meurer, William; Shih, Albert J

2018-01-01

Reducing brain temperature by head and neck cooling is likely to be the protective treatment for humans when subjects to sudden cardiac arrest. This study develops the experimental validation model and finite element modeling (FEM) to study the head and neck cooling separately, which can induce therapeutic hypothermia focused on the brain. Anatomically accurate geometries based on CT images of the skull and carotid artery are utilized to find the 3D geometry for FEM to analyze the temperature distributions and 3D-printing to build the physical model for experiment. The results show that FEM predicted and experimentally measured temperatures have good agreement, which can be used to predict the temporal and spatial temperature distributions of the tissue and blood during the head and neck cooling process. Effects of boundary condition, perfusion, blood flow rate, and size of cooling area are studied. For head cooling, the cooling penetration depth is greatly depending on the blood perfusion in the brain. In the normal blood flow condition, the neck internal carotid artery temperature is decreased only by about 0.13°C after 60min of hypothermia. In an ischemic (low blood flow rate) condition, such temperature can be decreased by about 1.0°C. In conclusion, decreasing the blood perfusion and metabolic reduction factor could be more beneficial to cool the core zone. The results also suggest that more SBC researches should be explored, such as the optimization of simulation and experimental models, and to perform the experiment on human subjects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Microphysiological modeling of the reproductive tract: a fertile endeavor.

PubMed

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

2014-09-01

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

Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice.

PubMed

Jaiswal, Smita; Smith, Kenneth; Ramirez, Alejandro; Woda, Marcia; Pazoles, Pamela; Shultz, Leonard D; Greiner, Dale L; Brehm, Michael A; Mathew, Anuja

2015-01-01

The development of small animal models that elicit human immune responses to dengue virus (DENV) is important since prior immunity is a major risk factor for developing severe dengue disease. This study evaluated anti-DENV human antibody (hAb) responses generated from immortalized B cells after DENV-2 infection in NOD-scid IL2rγ(null) mice that were co-transplanted with human fetal thymus and liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the IgM isotype were isolated during acute infection and in convalescence. We found that while a few hAbs recognized the envelope protein produced as a soluble recombinant, a number of hAbs only recognized epitopes on intact virions. The majority of the hAbs isolated during acute infection and in immune mice were serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG mice were significantly decreased after challenge with a clinical strain of dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the characteristics of Abs isolated in humans with natural infection. Humanized BLT-NSG mice provide an attractive preclinical platform to assess the immunogenicity of candidate dengue vaccines. © 2014 by the Society for Experimental Biology and Medicine.

A cellular star atlas: using astrocytes from human pluripotent stem cells for disease studies

PubMed Central

Krencik, Robert; Ullian, Erik M.

2013-01-01

What roles do astrocytes play in human disease?This question remains unanswered for nearly every human neurological disorder. Yet, because of their abundance and complexity astrocytes can impact neurological function in many ways. The differentiation of human pluripotent stem cells (hPSCs) into neuronal and glial subtypes, including astrocytes, is becoming routine, thus their use as tools for modeling neurodevelopment and disease will provide one important approach to answer this question. When designing experiments, careful consideration must be given to choosing paradigms for differentiation, maturation, and functional analysis of these temporally asynchronous cellular populations in culture. In the case of astrocytes, they display heterogeneous characteristics depending upon species of origin, brain region, developmental stage, environmental factors, and disease states, all of which may render experimental results highly variable. In this review, challenges and future directions are discussed for using hPSC-derived astroglial progenitors and mature astrocytes for neurodevelopmental studies with a focus on exploring human astrocyte effects upon neuronal function. As new technologies emerge to measure the functions of astrocytes in vitro and in vivo, there is also a need for a standardized source of human astrocytes that are most relevant to the diseases of interest. PMID:23503583

Induction of interleukin-8 by Naegleria fowleri lysates requires activation of extracellular signal-regulated kinase in human astroglial cells.

PubMed

Kim, Jong-Hyun; Sohn, Hae-Jin; Lee, Sang-Hee; Kwon, Daeho; Shin, Ho-Joon

2012-08-01

Naegleria fowleri is a pathogenic free-living amoeba which causes primary amoebic meningoencephalitis in humans and experimental animals. To investigate the mechanisms of such inflammatory diseases, potential chemokine gene activation in human astroglial cells was investigated following treatment with N. fowleri lysates. We demonstrated that N. fowleri are potent inducers for the expression of interleukin-8 (IL-8) genes in human astroglial cells which was preceded by activation of extracellular signal-regulated kinase (ERK). In addition, N. fowleri lysates induces the DNA binding activity of activator protein-1 (AP-1), an important transcription factor for IL-8 induction. The specific mitogen-activated protein kinase kinase/ERK inhibitor, U0126, blocks N. fowleri-mediated AP-1 activation and subsequent IL-8 induction. N. fowleri-induced IL-8 expression requires activation of ERK in human astroglial cells. These findings indicate that treatment of N. fowleri on human astroglial cells leads to the activation of AP-1 and subsequent expression of IL-8 which are dependent on ERK activation. These results may help understand the N. fowleri-mediated upregulation of chemokine and cytokine expression in the astroglial cells.

[Noise Effects on Mental Health: a review of literature].

PubMed

Makopa Kenda, Israel; Agoub, Mohamed; Ahami, A O T

2014-01-01

Any human activity generates noise. It is considered as a risk factor for people's health. The present review of literature has assessed the impact of noise on mental health; it is summarized into four points: objective, methods, results and conclusion. The main objective of this study is to expose the actual knowledge state of noise effects on mental health after overview and critical analysis of literature to identify the acquired and shortcomings, to reflect on research direction in terms of noise pollution in the future. The literature review was conducted based on: research of keys words in articles published, research of the number of quotations of articles in Journal Citation Reports (JCR), published in web of science, research of impact factor of journals. One hundred articles were selected, after analyzing contents, items were classified into: fundamental studies (25%), experimental studies (50%), and epidemiological studies (25%). The fundamental studies have verified the hypothesis according to which noise generates stress. Researchers have dosed hormones of stress in plasma, urine and saliva in individuals exposed to noise of different decibels. The results found were unanimous: The rates of stress hormones found, were significantly high in three liquids. This means that noise causes stress. For experimental studies, researchers have experienced the role of noise on memory, attention and performance. Human subjects were exposed to different decibels to assess level of disruption to their memory, attention, and performance. The results revealed that noise disturbs memory, distracts attention and decreases performance. Experimental studies are the most abundant and constitute 50% of the current literature review.The epidemiological studies have evaluated the intellectual performance of students in schools located in noisy environments and residents in areas surrounding airports, railways and highways. RESULTS have revealed that students in schools located in noisy environments have presented cognitive impairment. This review of literature on noise effects on mental health lead to the following conclusion. It seems to exist a consensus in fundamental and experimental studies on the detrimental effect of noise but results from epidemiological are not convincing and require further studies.

Contrasting Views on the Role of Mesenchymal Stromal/Stem Cells in Tumour Growth: A Systematic Review of Experimental Design.

PubMed

Oloyo, Ahmed Kolade; Ambele, Melvin Anyasi; Pepper, Michael Sean

2017-11-15

The effect of mesenchymal stromal/stem cells (MSCs) on tumour growth remains controversial. Experimental evidence supports both an inhibitory and a stimulatory effect. We have assessed factors responsible for the contrasting effects of MSCs on tumour growth by doing a meta-analysis of existing literature between 2000 and May 2017. We assessed 183 original research articles comprising 338 experiments. We considered (a) in vivo and in vitro experiments, (b) whether in vivo studies were syngeneic or xenogeneic, and (c) if animals were immune competent or deficient. Furthermore, the sources and types of cancer cells and MSCs were considered together with modes of cancer induction and MSC administration. 56% of all 338 experiments reported that MSCs promote tumour growth. 78% and 79% of all experiments sourced human MSCs and cancer cells, respectively. MSCs were used in their naïve and engineered form in 86% and 14% of experiments, respectively, the latter to produce factors that could alter either their activity or that of the tumour. 53% of all experiments were conducted in vitro with 60% exposing cancer cells to MSCs via coculture. Of all in vivo experiments, 79% were xenogeneic and 63% were conducted in immune-competent animals. Tumour growth was inhibited in 80% of experiments that used umbilical cord-derived MSCs, whereas tumour growth was promoted in 64% and 57% of experiments that used bone marrow- and adipose tissue-derived MSCs, respectively. This contrasting effect of MSCs on tumour growth observed under different experimental conditions may reflect differences in experimental design. This analysis calls for careful consideration of experimental design given the large number of MSC clinical trials currently underway.

Missing focus on Human Factors – organizational and cognitive ergonomics – in the safety management for the petroleum industry

PubMed Central

Johnsen, Stig O; Kilskar, Stine Skaufel; Fossum, Knut Robert

2017-01-01

More attention has recently been given to Human Factors in petroleum accident investigations. The Human Factors areas examined in this article are organizational, cognitive and physical ergonomics. A key question to be explored is as follows: To what degree are the petroleum industry and safety authorities in Norway focusing on these Human Factors areas from the design phase? To investigate this, we conducted an innovative exploratory study of the development of four control centres in Norwegian oil and gas industry in collaboration between users, management and Human Factors experts. We also performed a literature survey and discussion with the professional Human Factors network in Norway. We investigated the Human Factors focus, reasons for not considering Human Factors and consequences of missing Human Factors in safety management. The results revealed an immature focus and organization of Human Factors. Expertise on organizational ergonomics and cognitive ergonomics are missing from companies and safety authorities and are poorly prioritized during the development. The easy observable part of Human Factors (i.e. physical ergonomics) is often in focus. Poor focus on Human Factors in the design process creates demanding conditions for human operators and impact safety and resilience. There is lack of non-technical skills such as communication and decision-making. New technical equipment such as Closed Circuit Television is implemented without appropriate use of Human Factors standards. Human Factors expertise should be involved as early as possible in the responsible organizations. Verification and validation of Human Factors should be improved and performed from the start, by certified Human Factors experts in collaboration with the workforce. The authorities should check-back that the regulatory framework of Human Factors is communicated, understood and followed. PMID:29278242

A neural networks application for the study of the influence of transport conditions on the working performance

NASA Astrophysics Data System (ADS)

Anghel, D.-C.; Ene, A.; Ştirbu, C.; Sicoe, G.

2017-10-01

This paper presents a study about the factors that influence the working performances of workers in the automotive industry. These factors regard mainly the transportations conditions, taking into account the fact that a large number of workers live in places that are far away of the enterprise. The quantitative data obtained from this study will be generalized by using a neural network, software simulated. The neural network is able to estimate the performance of workers even for the combinations of input factors that had been not recorded by the study. The experimental data obtained from the study will be divided in two classes. The first class that contains approximately 80% of data will be used by the Java software for the training of the neural network. The weights resulted from the training process will be saved in a text file. The other class that contains the rest of the 20% of experimental data will be used to validate the neural network. The training and the validation of the networks are performed in a Java software (TrainAndValidate java class). We designed another java class, Test.java that will be used with new input data, for new situations. The experimental data collected from the study. The software that simulated the neural network. The software that estimates the working performance, when new situations are met. This application is useful for human resources department of an enterprise. The output results are not quantitative. They are qualitative (from low performance to high performance, divided in five classes).

Why nature prevails over nurture in the making of the elite athlete.

PubMed

Georgiades, Evelina; Klissouras, Vassilis; Baulch, Jamie; Wang, Guan; Pitsiladis, Yannis

2017-11-14

While the influence of nature (genes) and nurture (environment) on elite sporting performance remains difficult to precisely determine, the dismissal of either as a contributing factor to performance is unwarranted. It is accepted that a complex interaction of a combination of innumerable factors may mold a talented athlete into a champion. The prevailing view today is that understanding elite human performance will require the deciphering of two major sources of individual differences, genes and the environment. It is widely accepted that superior performers are endowed with a high genetic potential actualised through hard and prodigious effort. Heritability studies using the twin model have provided the basis to disentangle genetic and environmental factors that contribute to complex human traits and have paved the way to the detection of specific genes for elite sport performance. Yet, the heritability for most phenotypes essential to elite human performance is above 50% but below 100%, meaning that the environment is also important. Furthermore, individual differences can potentially also be explained not only by the impact of DNA sequence variation on biology and behaviour, but also by the effects of epigenetic changes which affect phenotype by modifying gene expression. Despite this complexity, the overwhelming and accumulating evidence, amounted through experimental research spanning almost two centuries, tips the balance in favour of nature in the "nature" and "nurture" debate. In other words, truly elite-level athletes are built - but only from those born with innate ability.

Production of Experimental Malignant Pleural Effusions Is Dependent on Invasion of the Pleura and Expression of Vascular Endothelial Growth Factor/Vascular Permeability Factor by Human Lung Cancer Cells

PubMed Central

Yano, Seiji; Shinohara, Hisashi; Herbst, Roy S.; Kuniyasu, Hiroki; Bucana, Corazon D.; Ellis, Lee M.; Fidler, Isaiah J.

2000-01-01

We determined the molecular mechanisms that regulate the pathogenesis of malignant pleural effusion (PE) associated with advanced stage of human, non-small-cell lung cancer. Intravenous injection of human PC14 and PC14PE6 (adenocarcinoma) or H226 (squamous cell carcinoma) cells into nude mice yielded numerous lung lesions. PC14 and PC14PE6 lung lesions invaded the pleura and produced PE containing a high level of vascular endothelial growth factor (VEGF)-localized vascular hyperpermeability. Lung lesions produced by H226 cells were confined to the lung parenchyma with no PE. The level of expression of VEGF mRNA and protein by the cell lines directly correlated with extent of PE formation. Transfection of PC14PE6 cells with antisense VEGF165 gene did not inhibit invasion into the pleural space but reduced PE formation. H226 cells transfected with either sense VEGF 165 or sense VEGF 121 genes induced localized vascular hyperpermeability and produced PE only after direct implantation into the thoracic cavity. The production of PE was thus associated with the ability of tumor cells to invade the pleura, a property associated with expression of high levels of urokinase-type plasminogen activator and low levels of TIMP-2. Collectively, the data demonstrate that the production of malignant PE requires tumor cells to invade the pleura and express high levels of VEGF/VPF. PMID:11106562

HRI usability evaluation of interaction modes for a teleoperated agricultural robotic sprayer.

PubMed

Adamides, George; Katsanos, Christos; Parmet, Yisrael; Christou, Georgios; Xenos, Michalis; Hadzilacos, Thanasis; Edan, Yael

2017-07-01

Teleoperation of an agricultural robotic system requires effective and efficient human-robot interaction. This paper investigates the usability of different interaction modes for agricultural robot teleoperation. Specifically, we examined the overall influence of two types of output devices (PC screen, head mounted display), two types of peripheral vision support mechanisms (single view, multiple views), and two types of control input devices (PC keyboard, PS3 gamepad) on observed and perceived usability of a teleoperated agricultural sprayer. A modular user interface for teleoperating an agricultural robot sprayer was constructed and field-tested. Evaluation included eight interaction modes: the different combinations of the 3 factors. Thirty representative participants used each interaction mode to navigate the robot along a vineyard and spray grape clusters based on a 2 × 2 × 2 repeated measures experimental design. Objective metrics of the effectiveness and efficiency of the human-robot collaboration were collected. Participants also completed questionnaires related to their user experience with the system in each interaction mode. Results show that the most important factor for human-robot interface usability is the number and placement of views. The type of robot control input device was also a significant factor in certain dependents, whereas the effect of the screen output type was only significant on the participants' perceived workload index. Specific recommendations for mobile field robot teleoperation to improve HRI awareness for the agricultural spraying task are presented. Copyright © 2017 Elsevier Ltd. All rights reserved.

Study of the effectiveness of propolis extract as a storage medium for avulsed teeth.

PubMed

Casaroto, Ana Regina; Hidalgo, Mirian Marubayashi; Sell, Ana Maria; Franco, Selma Lucy; Cuman, Roberto Kenji Nakamura; Moreschi, Eduardo; Victorino, Fausto Rodrigo; Steffens, Vânia Antunes; Bersani-Amado, Ciomar Aparecida

2010-08-01

The purpose of the present study was to evaluate the efficacy of propolis extract in maintaining the viability of human periodontal ligament (PDL) cells, and to radiographically analyze tooth replantation and the adjacent periodontium in dogs after storage in this extract. Human PDL cells were incubated with the experimental media propolis, milk, saliva, Hank's balanced salt solution (HBSS), and Dulbecco's modified Eagles medium (DMEM, positive controls), and distilled water (negative control). Cell viability was determined 0, 1, 3, 6, 12, and 24 h later by colorimetric MTT assay. Thirty incisors from dogs were divided into two storage time blocks (1 and 3 h) and were maintained in the experimental media. HBSS served as a positive control, and dry teeth (on gauze) as a negative control. The replanted teeth were radiographed once per month for 6 months. The radiographic images were standardized by the shortening/lengthening factor, and were both qualitatively and quantitatively analyzed. The in vitro results showed that the efficacy of propolis in maintaining functional viability of PDL cells was similar to that of milk. Propolis and milk were significantly better than controls from the 6-h time period. The in vivo results showed that teeth maintained in propolis medium exhibited replacement resorption with significant reduction in tooth length, similar to teeth maintained in saliva and dried teeth. This resorption was less intense with the 3-h storage time than the 1-h storage time. Conditions close to normal were found in teeth maintained in milk, similar to the HBSS control. Therefore, although propolis was effective in maintaining the viability of human PDL cells, resorption of the tooth replantation in dogs occurred under these experimental conditions.

Transport of human adenoviruses in porous media

NASA Astrophysics Data System (ADS)

Kokkinos, Petros; Syngouna, Vasiliki I.; Tselepi, Maria A.; Bellou, Maria; Chrysikopoulos, Constantinos V.; Vantarakis, Apostolos

2015-04-01

Groundwater may be contaminated with infective human enteric viruses from various wastewater discharges, sanitary landfills, septic tanks, agricultural practices, and artificial groundwater recharge. Coliphages have been widely used as surrogates of enteric viruses, because they share many fundamental properties and features. Although a large number of studies focusing on various factors (i.e. pore water solution chemistry, fluid velocity, moisture content, temperature, and grain size) that affect biocolloid (bacteria, viruses) transport have been published over the past two decades, little attention has been given toward human adenoviruses (hAdVs). The main objective of this study was to evaluate the effect of pore water velocity on hAdV transport in water saturated laboratory-scale columns packed with glass beads. The effects of pore water velocity on virus transport and retention in porous media was examined at three pore water velocities (0.39, 0.75, and 1.22 cm/min). The results indicated that all estimated average mass recovery values for hAdV were lower than those of coliphages, which were previously reported in the literature by others for experiments conducted under similar experimental conditions. However, no obvious relationship between hAdV mass recovery and water velocity could be established from the experimental results. The collision efficiencies were quantified using the classical colloid filtration theory. Average collision efficiency, α, values decreased with decreasing flow rate, Q, and pore water velocity, U, but no significant effect of U on α was observed. Furthermore, the surface properties of viruses and glass beads were used to construct classical DLVO potential energy profiles. The results revealed that the experimental conditions of this study were unfavorable to deposition and that no aggregation between virus particles is expected to occur. A thorough understanding of the key processes governing virus transport is pivotal for public health protection.

Parkinson disease: a role for autophagy?

PubMed

Yang, Qian; Mao, Zixu

2010-08-01

Autophagy is a term used to describe the process by which lysosomes degrade intracellular components. Known originally as an adaptive response to nutrient deprivation, autophagy has now been recognized to play important roles in several human disorders including neurodegenerative diseases. Experimental results from genetic, cellular, and toxicological studies indicate that many of the etiological factors associated with Parkinson disease (PD) can perturb the autophagic process in various model systems. Thus, the emerging data support the view that dysregulation of autophagy may play a critical role in the pathogenic process of PD.

Aerospace Medicine and Biology: A Continuing Bibliography. Supplement 483

NASA Technical Reports Server (NTRS)

1999-01-01

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

Voice technology and BBN

NASA Technical Reports Server (NTRS)

Wolf, Jared J.

1977-01-01

The following research was discussed: (1) speech signal processing; (2) automatic speech recognition; (3) continuous speech understanding; (4) speaker recognition; (5) speech compression; (6) subjective and objective evaluation of speech communication system; (7) measurement of the intelligibility and quality of speech when degraded by noise or other masking stimuli; (8) speech synthesis; (9) instructional aids for second-language learning and for training of the deaf; and (10) investigation of speech correlates of psychological stress. Experimental psychology, control systems, and human factors engineering, which are often relevant to the proper design and operation of speech systems are described.

Astronaut activity

NASA Technical Reports Server (NTRS)

Loftus, J. P., Jr.; Bond, R. L.; Patton, R. M.

1975-01-01

Human factors pertinent to the design and operation of spacecraft are considered. The geometric characteristics of spacecraft that define the degree and type of confinement imposed on the crew and the character of equipment management and housekeeping necessary for hygiene, comfort and safety are discussed. The controls and displays of various spacecraft are described to indicate the degree to which crew functions become integral to functions of the total spacecraft. The contributions of the crew to system reliability and performance are summarized and the increasing significance of the crew's role in scientific observation and experimentation is noted.

The contributions of human factors on human error in Malaysia aviation maintenance industries

NASA Astrophysics Data System (ADS)

Padil, H.; Said, M. N.; Azizan, A.

2018-05-01

Aviation maintenance is a multitasking activity in which individuals perform varied tasks under constant pressure to meet deadlines as well as challenging work conditions. These situational characteristics combined with human factors can lead to various types of human related errors. The primary objective of this research is to develop a structural relationship model that incorporates human factors, organizational factors, and their impact on human errors in aviation maintenance. Towards that end, a questionnaire was developed which was administered to Malaysian aviation maintenance professionals. Structural Equation Modelling (SEM) approach was used in this study utilizing AMOS software. Results showed that there were a significant relationship of human factors on human errors and were tested in the model. Human factors had a partial effect on organizational factors while organizational factors had a direct and positive impact on human errors. It was also revealed that organizational factors contributed to human errors when coupled with human factors construct. This study has contributed to the advancement of knowledge on human factors effecting safety and has provided guidelines for improving human factors performance relating to aviation maintenance activities and could be used as a reference for improving safety performance in the Malaysian aviation maintenance companies.

Effect of human vascular endothelial growth factor gene transfer on endogenous vascular endothelial growth factor mRNA expression in a rat fibroblast and osteoblast culture model.

PubMed

Li, Ru; Li, Claire H; Nauth, Aaron; McKee, Michael D; Schemitsch, Emil H

2010-09-01

Vascular endothelial growth factor (VEGF) plays an important role in promoting angiogenesis and osteogenesis during fracture repair. Our previous studies have shown that cell-based VEGF gene therapy enhances bone healing of a rabbit tibia segmental bone defect in vivo. The aim of this project was to examine the effect of exogenous human VEGF on the endogenous rat VEGF messenger RNA (mRNA) expression in a cell-based gene transfer model. Rat fibroblasts and osteoblasts were harvested from the dermal tissue and periosteum, respectively, of Fisher 344 rats. The cells were then cultured and transfected with pcDNA-human VEGF using Superfect reagent (Qiagen). Four experimental groups were created: 1) fibroblast-VEGF; 2) osteoblast-VEGF; 3) nontransfected fibroblast controls; and 4) nontransfected osteoblast controls. The cultured cells were harvested at 1, 3, and 7 days after the gene transfection. The total mRNA was extracted (Trizol; Invitrogen); both human VEGF and rat VEGF mRNA were measured by reverse transcriptase-polymerase chain reaction and quantified by VisionWorksLS. The human VEGF165 mRNA was detected by reverse transcriptase-polymerase chain reaction from transfected fibroblasts and osteoblasts at 1, 3, and 7 days after gene transfection. The human VEGF165 levels peaked at Day 1 and then gradually reduced expression in both transfected fibroblasts and osteoblasts. Two endogenous rat VEGF isoforms were detected in this cell culture model: rat VEGF120 and rat VEGF164. We compared the rat VEGF120 and rat VEGF164 expression level of the fibroblasts or osteoblasts that were transfected with human VEGF165, with nontransfected control cells. Both the transfected fibroblasts and osteoblasts showed greater expression of rat VEGF164 than nontransfected controls at Day 1 (peak level) and Day 3, but not at Day 7. The expression of rat VEGF120 was lower in transfected fibroblasts, but higher in transfected osteoblasts, than the relevant control groups at any time point after transfection. In addition, human VEGF gene transfection increased osteoblast cell proliferation after 3 days. These in vitro results suggest that cell-based human VEGF gene therapy is not only effective at causing human VEGF expression, but also enhances endogenous rat VEGF mRNA expression in both fibroblasts and osteoblasts, particularly the rat VEGF164 isoform.

Attention and predictions: control of spatial attention beyond the endogenous-exogenous dichotomy

PubMed Central

Macaluso, Emiliano; Doricchi, Fabrizio

2013-01-01

The mechanisms of attention control have been extensively studied with a variety of methodologies in animals and in humans. Human studies using non-invasive imaging techniques highlighted a remarkable difference between the pattern of responses in dorsal fronto-parietal regions vs. ventral fronto-parietal (vFP) regions, primarily lateralized to the right hemisphere. Initially, this distinction at the neuro-physiological level has been related to the distinction between cognitive processes associated with strategic/endogenous vs. stimulus-driven/exogenous of attention control. Nonetheless, quite soon it has become evident that, in almost any situation, attention control entails a complex combination of factors related to both the current sensory input and endogenous aspects associated with the experimental context. Here, we review several of these aspects first discussing the joint contribution of endogenous and stimulus-driven factors during spatial orienting in complex environments and, then, turning to the role of expectations and predictions in spatial re-orienting. We emphasize that strategic factors play a pivotal role for the activation of the ventral system during stimulus-driven control, and that the dorsal system makes use of stimulus-driven signals for top-down control. We conclude that both the dorsal and the vFP networks integrate endogenous and exogenous signals during spatial attention control and that future investigations should manipulate both these factors concurrently, so as to reveal to full extent of these interactions. PMID:24155707

Manganese concentrations in maternal and umbilical cord blood: related to birth size and environmental factors.

PubMed

Guan, Huai; Wang, Man; Li, Xiaowei; Piao, Fengyuan; Li, Qiujuan; Xu, Lei; Kitamura, Fumihiko; Yokoyama, Kazuhito

2014-02-01

Manganese (Mn) is an essential element and a potential toxicant for developing organism. Deficiency and excess of it were both deleterious to fetal growth in experimental animals. However, literature on relationship between Mn status and birth outcome in humans is sparse. Mn concentrations were measured in mother whole blood (MWB) and umbilical cord blood (UCB) in 125 pairs of mother-infant; birth size was examined and relationship between them was analysed. Potentially environmental factors influencing Mn loads in maternal and fetal organisms were investigated through epidemiological method. Mn level in UCB was significantly higher than that in MWB (mean value: 54.98 vs. 78.75 µg/L), and a significant positive correlation was shown between them. There was a quadratic curvilinear (inverted U-shaped curve) relationship between MWB Mn and birth size, and between UCB Mn and birth size. Both univariate analysis and multiple linear regression analysis showed that exposure to harmful occupational factors during gestation remarkably increased maternal and fetal Mn levels. Living close to major transportation routes (<500 m) also increased the MWB Mn levels. Our results suggested that lower or higher Mn level in maternal and umbilical blood may induce adverse effect on birth size in humans. In addition, increased levels of Mn in MWB or UCB may be associated with exposure to some environmental hazard factors.

The Regulatory Role of Signaling Crosstalk in Hypertrophy of MSCs and Human Articular Chondrocytes.

PubMed

Zhong, Leilei; Huang, Xiaobin; Karperien, Marcel; Post, Janine N

2015-08-14

Hypertrophic differentiation of chondrocytes is a main barrier in application of mesenchymal stem cells (MSCs) for cartilage repair. In addition, hypertrophy occurs occasionally in osteoarthritis (OA). Here we provide a comprehensive review on recent literature describing signal pathways in the hypertrophy of MSCs-derived in vitro differentiated chondrocytes and chondrocytes, with an emphasis on the crosstalk between these pathways. Insight into the exact regulation of hypertrophy by the signaling network is necessary for the efficient application of MSCs for articular cartilage repair and for developing novel strategies for curing OA. We focus on articles describing the role of the main signaling pathways in regulating chondrocyte hypertrophy-like changes. Most studies report hypertrophic differentiation in chondrogenesis of MSCs, in both human OA and experimental OA. Chondrocyte hypertrophy is not under the strict control of a single pathway but appears to be regulated by an intricately regulated network of multiple signaling pathways, such as WNT, Bone morphogenetic protein (BMP)/Transforming growth factor-β (TGFβ), Parathyroid hormone-related peptide (PTHrP), Indian hedgehog (IHH), Fibroblast growth factor (FGF), Insulin like growth factor (IGF) and Hypoxia-inducible factor (HIF). This comprehensive review describes how this intricate signaling network influences tissue-engineering applications of MSCs in articular cartilage (AC) repair, and improves understanding of the disease stages and cellular responses within an OA articular joint.

The Regulatory Role of Signaling Crosstalk in Hypertrophy of MSCs and Human Articular Chondrocytes

PubMed Central

Zhong, Leilei; Huang, Xiaobin; Karperien, Marcel; Post, Janine N.

2015-01-01

Hypertrophic differentiation of chondrocytes is a main barrier in application of mesenchymal stem cells (MSCs) for cartilage repair. In addition, hypertrophy occurs occasionally in osteoarthritis (OA). Here we provide a comprehensive review on recent literature describing signal pathways in the hypertrophy of MSCs-derived in vitro differentiated chondrocytes and chondrocytes, with an emphasis on the crosstalk between these pathways. Insight into the exact regulation of hypertrophy by the signaling network is necessary for the efficient application of MSCs for articular cartilage repair and for developing novel strategies for curing OA. We focus on articles describing the role of the main signaling pathways in regulating chondrocyte hypertrophy-like changes. Most studies report hypertrophic differentiation in chondrogenesis of MSCs, in both human OA and experimental OA. Chondrocyte hypertrophy is not under the strict control of a single pathway but appears to be regulated by an intricately regulated network of multiple signaling pathways, such as WNT, Bone morphogenetic protein (BMP)/Transforming growth factor-β (TGFβ), Parathyroid hormone-related peptide (PTHrP), Indian hedgehog (IHH), Fibroblast growth factor (FGF), Insulin like growth factor (IGF) and Hypoxia-inducible factor (HIF). This comprehensive review describes how this intricate signaling network influences tissue-engineering applications of MSCs in articular cartilage (AC) repair, and improves understanding of the disease stages and cellular responses within an OA articular joint. PMID:26287176

Tea and Cardiovascular Disease

PubMed Central

Deka, Apranta; Vita, Joseph A.

2011-01-01

There is increasing evidence for a protective effect of tea consumption against cardiovascular disease. This review summarizes the available epidemiological data providing evidence for and against such an effect. We also review observational and intervention studies that investigated an effect of tea and tea extracts on cardiovascular risk factors, including blood pressure, serum lipids, diabetes mellitus, and obesity. Finally, we review potential mechanisms of benefit, including anti-inflammatory, anti-oxidant, and anti-proliferative effects, as well as favorable effects on endothelial function. Overall, the observational data suggest a benefit, but results are mixed and likely confounded by lifestyle and background dietary factors. The weight of evidence indicates favorable effects on risk factors and a number of plausible mechanisms have been elucidated in experimental and translational human studies. Despite the growing body evidence, it remains uncertain whether tea consumption should be recommended to the general population or to patients as a strategy to reduce cardiovascular risk. PMID:21477653

Microendophenotypes of psychiatric disorders: phenotypes of psychiatric disorders at the level of molecular dynamics, synapses, neurons, and neural circuits.

PubMed

Kida, S; Kato, T

2015-01-01

Psychiatric disorders are caused not only by genetic factors but also by complicated factors such as environmental ones. Moreover, environmental factors are rarely quantitated as biological and biochemical indicators, making it extremely difficult to understand the pathological conditions of psychiatric disorders as well as their underlying pathogenic mechanisms. Additionally, we have actually no other option but to perform biological studies on postmortem human brains that display features of psychiatric disorders, thereby resulting in a lack of experimental materials to characterize the basic biology of these disorders. From these backgrounds, animal, tissue, or cell models that can be used in basic research are indispensable to understand biologically the pathogenic mechanisms of psychiatric disorders. In this review, we discuss the importance of microendophenotypes of psychiatric disorders, i.e., phenotypes at the level of molecular dynamics, neurons, synapses, and neural circuits, as targets of basic research on these disorders.

Human exposure standards in the frequency range 1 Hz To 100 kHz: the case for adoption of the IEEE standard.

PubMed

Patrick Reilly, J

2014-10-01

Differences between IEEE C95 Standards (C95.6-2002 and C95.1-2005) in the low-frequency (1 Hz-100 kHz) and the ICNIRP-2010 guidelines appear across the frequency spectrum. Factors accounting for lack of convergence include: differences between the IEEE standards and the ICNIRP guidelines with respect to biological induction models, stated objectives, data trail from experimentally derived thresholds through physical and biological principles, selection and justification of safety/reduction factors, use of probability models, compliance standards for the limbs as distinct from the whole body, defined population categories, strategies for central nervous system protection below 20 Hz, and correspondence of environmental electric field limits with contact currents. This paper discusses these factors and makes the case for adoption of the limits in the IEEE standards.

The human factor: behavioral and neural correlates of humanized perception in moral decision making.

PubMed

Majdandžić, Jasminka; Bauer, Herbert; Windischberger, Christian; Moser, Ewald; Engl, Elisabeth; Lamm, Claus

2012-01-01

The extent to which people regard others as full-blown individuals with mental states ("humanization") seems crucial for their prosocial motivation towards them. Previous research has shown that decisions about moral dilemmas in which one person can be sacrificed to save multiple others do not consistently follow utilitarian principles. We hypothesized that this behavior can be explained by the potential victim's perceived humanness and an ensuing increase in vicarious emotions and emotional conflict during decision making. Using fMRI, we assessed neural activity underlying moral decisions that affected fictitious persons that had or had not been experimentally humanized. In implicit priming trials, participants either engaged in mentalizing about these persons (Humanized condition) or not (Neutral condition). In subsequent moral dilemmas, participants had to decide about sacrificing these persons' lives in order to save the lives of numerous others. Humanized persons were sacrificed less often, and the activation pattern during decisions about them indicated increased negative affect, emotional conflict, vicarious emotions, and behavioral control (pgACC/mOFC, anterior insula/IFG, aMCC and precuneus/PCC). Besides, we found enhanced effective connectivity between aMCC and anterior insula, which suggests increased emotion regulation during decisions affecting humanized victims. These findings highlight the importance of others' perceived humanness for prosocial behavior - with aversive affect and other-related concern when imagining harming more "human-like" persons acting against purely utilitarian decisions.

Misleading and reliable markers to differentiate between primate testis-derived multipotent stromal cells and spermatogonia in culture

PubMed Central

Eildermann, K.; Gromoll, J.; Behr, R.

2012-01-01

BACKGROUND Several studies have reported the generation of spermatogonia-derived pluripotent stem cells from human testes. The initial aim of the present study was the derivation of equivalent stem cells from an established and experimentally accessible non-human primate model, the common marmoset monkey (Callithrix jacchus). However, an essential prerequisite in the absence of transgenic reporters in primates and man is the availability of validated endogenous markers for the identification of specific cell types in vitro. METHODS AND RESULTS We cultured marmoset testicular cells in a similar way to that described for human testis-derived pluripotent cells and set out to characterize these cultures under different conditions and in differentiation assays applying established marker panels. Importantly, the cells emerged as testicular multipotent stromal cells (TMSCs) instead of (pluripotent) germ cell-derived cells. TMSCs expressed many markers such as GFR-α, GPR125, THY-1 (CD90), ITGA6, SSEA4 and TRA-1-81, which were considered as spermatogonia specific and were previously used for the enrichment or characterization of spermatogonia. Proliferation of TMSCs was highly dependent on basic fibroblast growth factor, a growth factor routinely present in germ cell culture media. As reliable markers for the distinction between spermatogonia and TMSCs, we established VASA, in combination with the spermatogonia-expressed factors, MAGEA4, PLZF and SALL4. CONCLUSIONS Marmoset monkey TMSCs and spermatogonia exhibit an overlap of markers, which may cause erroneous interpretations of experiments with testis-derived stem cells in vitro. We provide a marker panel for the unequivocal identification of spermatogonia providing a better basis for future studies on primate, including human, testis-derived stem cells. PMID:22442249

Phase I Study of a Poxviral TRICOM-Based Vaccine Directed Against the Transcription Factor Brachyury.

PubMed

Heery, Christopher R; Palena, Claudia; McMahon, Sheri; Donahue, Renee N; Lepone, Lauren M; Grenga, Italia; Dirmeier, Ulrike; Cordes, Lisa; Marté, Jenn; Dahut, William; Singh, Harpreet; Madan, Ravi A; Fernando, Romaine I; Hamilton, Duane H; Schlom, Jeffrey; Gulley, James L

2017-11-15

Purpose: The transcription factor brachyury has been shown in preclinical studies to be a driver of the epithelial-to-mesenchymal transition (EMT) and resistance to therapy of human tumor cells. This study describes the characterization of a Modified Vaccinia Ankara (MVA) vector-based vaccine expressing the transgenes for brachyury and three human costimulatory molecules (B7.1, ICAM-1, and LFA-3, designated TRICOM) and a phase I study with this vaccine. Experimental Design: Human dendritic cells (DC) were infected with MVA-brachyury-TRICOM to define their ability to activate brachyury-specific T cells. A dose-escalation phase I study (NCT02179515) was conducted in advanced cancer patients ( n = 38) to define safety and to identify brachyury-specific T-cell responses. Results: MVA-brachyury-TRICOM-infected human DCs activated CD8 + and CD4 + T cells specific against the self-antigen brachyury in vitro No dose-limiting toxicities were observed due to vaccine in cancer patients at any of the three dose levels. One transient grade 3 adverse event (AE) possibly related to vaccine (diarrhea) resolved without intervention and did not recur with subsequent vaccine. All other AEs related to vaccine were transient and ≤grade 2. Brachyury-specific T-cell responses were observed at all dose levels and in most patients. Conclusions: The MVA-brachyury-TRICOM vaccine directed against a transcription factor known to mediate EMT can be administered safely in patients with advanced cancer and can activate brachyury-specific T cells in vitro and in patients. Further studies of this vaccine in combination therapies are warranted and planned. Clin Cancer Res; 23(22); 6833-45. ©2017 AACR . ©2017 American Association for Cancer Research.

Anthropogenic Halo Disturbances Alter Landscape and Plant Richness: A Ripple Effect

PubMed Central

Liu, Bingliang; Su, Jinbao; Chen, Jianwei; Cui, Guofa; Ma, Jianzhang

2013-01-01

Although anthropogenic landscape fragmentation is often considered as the primary threat to biodiversity, other factors such as immediate human disturbances may also simultaneously threaten species persistence in various ways. In this paper, we introduce a conceptual framework applied to recreation landscapes (RLs), with an aim to provide insight into the composite influences of landscape alteration accompanying immediate human disturbances on plant richness dynamics. These impacts largely occur at patch-edges. They can not only alter patch-edge structure and environment, but also permeate into surrounding natural matrices/patches affecting species persistence–here we term these “Halo disturbance effects” (HDEs). We categorized species into groups based on seed or pollen dispersal mode (animal- vs. wind-dispersed) as they can be associated with species richness dynamics. We evaluated the richness of the two groups and total species in our experimental landscapes by considering the distance from patch-edge, the size of RLs and the intensity of human use over a six-year period. Our results show that animal-dispersed species decreased considerably, whereas wind-dispersed species increased while their richness presented diverse dynamics at different distances from patch-edges. Our findings clearly demonstrate that anthropogenic HDEs produce ripple effects on plant, providing an experimental interpretation for the diverse responses of species to anthropogenic disturbances. This study highlights the importance of incorporating these composite threats into conservation and management strategies. PMID:23424648

An In Vitro Model of Latency and Reactivation of Varicella Zoster Virus in Human Stem Cell-Derived Neurons

PubMed Central

Markus, Amos; Lebenthal-Loinger, Ilana; Yang, In Hong; Kinchington, Paul R.; Goldstein, Ronald S.

2015-01-01

Varicella zoster virus (VZV) latency in sensory and autonomic neurons has remained enigmatic and difficult to study, and experimental reactivation has not yet been achieved. We have previously shown that human embryonic stem cell (hESC)-derived neurons are permissive to a productive and spreading VZV infection. We now demonstrate that hESC-derived neurons can also host a persistent non-productive infection lasting for weeks which can subsequently be reactivated by multiple experimental stimuli. Quiescent infections were established by exposing neurons to low titer cell-free VZV either by using acyclovir or by infection of axons in compartmented microfluidic chambers without acyclovir. VZV DNA and low levels of viral transcription were detectable by qPCR for up to seven weeks. Quiescently-infected human neuronal cultures were induced to undergo renewed viral gene and protein expression by growth factor removal or by inhibition of PI3-Kinase activity. Strikingly, incubation of cultures induced to reactivate at a lower temperature (34°C) resulted in enhanced VZV reactivation, resulting in spreading, productive infections. Comparison of VZV genome transcription in quiescently-infected to productively-infected neurons using RNASeq revealed preferential transcription from specific genome regions, especially the duplicated regions. These experiments establish a powerful new system for modeling the VZV latent state, and reveal a potential role for temperature in VZV reactivation and disease. PMID:26042814

[Anisakidosis a marine parasitic zoonosis: unknown or emerging in Peru?].

PubMed

Cabrera, Rufino; Del Pilar, María; Altamirano, Trillo

2004-01-01

The purpose of this review is to show the experimental studies carried out on the biological cycle, culture, pathogenicity of the anisakidae nematode larvae and to disseminate the information regarding current epidemy and the probable emergence of anisakidosis in Peru, and in addition, to propose measures of prevention and control, as well as the perspective and need for investigation. The studies of experimental pathogenicity in cats, dos, and hamsters are incomplete. Eight cases of acute human anisakidosis have been reported (5 confirmed and 3 unconfirmed). It is probable that it emerges during the "El Niño" Weather Phenomenon; however, during normal conditions it is probably due to the increase of raw fish consumption and other factors. In the coast of Peru, five and four fishes of direct human consumption are parasited by the Anisakis simplex and Anisakis physeteris larva, respectively, and two fishes are parasited by the Pseudoterranova decipiens. The main host for the Anisakis simplex is the dolphin (Delphinus delphia), but the Contracaecum osculatum is hosted by the sea lion: Otaria byronia and Arctocephalus australis, P. decipiens parasita a O. byronia. Eviscerating the fish would be most adequate prevention method to lessen the risk of human infection. There is evidence that anisakidosis is an underestimated zoonosis in Peru, and that it is probably and emerging disease. Therefore, its presence is to be suspected in patients with the prototype clinical syndrome.

Analgesic use in pregnancy and male reproductive development

PubMed Central

Hurtado-Gonzalez, Pablo; Mitchell, Rod T.

2017-01-01

Purpose of review Male reproductive disorders are common and increasing in incidence in many countries. Environmental factors (including pharmaceuticals) have been implicated in the development of these disorders. This review aims to summarise the emerging epidemiological and experimental evidence for a potential role of in-utero exposure to analgesics in the development of male reproductive disorders. Recent findings A number of epidemiological studies have demonstrated an association between in-utero exposure to analgesics and the development of cryptorchidism, although these findings are not consistent across all studies. Where present, these associations primarily relate to exposure during the second trimester of pregnancy. In-vivo and in-vitro experimental studies have demonstrated variable effects of exposure to analgesics on Leydig cell function in the fetal testis of rodents, particularly in terms of testosterone production. These effects frequently involve exposures that are in excess of those to which humans are exposed. Investigation of the effects of analgesics on human fetal testis have also demonstrated effects on Leydig cell function. Variation in species, model system, dosage and timing of exposure is likely to contribute to differences in the findings between studies. Summary There is increasing evidence for analgesic effects on the developing testis that have the potential to impair reproductive function. However, the importance of these findings in relation to human-relevant exposures and the risk of male reproductive disorders remains unclear. PMID:28277341

Work capacity and anticipation in A.A. Ukhtomsky's concept of dominance

NASA Astrophysics Data System (ADS)

Pavlova, L. P.

2015-08-01

This paper presents the results of theoretical and experimental investigations of human activity and anticipation based on A.A. Ukhtomsky's concept of brain dominance - a non-equilibrium system-forming factor in living systems. Facts on the stages of dominance formation are presented in relation to the creative abilities of the human brain and the role of fatigue as a "lever" for increasing systems' work capacity on the basis of "trace exaltation". Individually, specific features of dominantogenesis are compared with variations in behavioural types. On the basis of chronotopic EEG analysis, we delineate cortical dominants that underlie individual specifics of cognitive processes. The relation is shown between anticipation and the "expansion of dominants" - the broadening of "distal perception" in time and space, as framed by A.A. Ukhtomsky.

Considerations in miniaturizing simplified agro-ecosystems for advanced life support

NASA Technical Reports Server (NTRS)

Volk, T.

1996-01-01

Miniaturizing the Earth's biogeochemical cycles to support human life during future space missions is the goal of the NASA research and engineering program in advanced life support. Mission requirements to reduce mass, volume, and power have focused efforts on (1) a maximally simplified agro-ecosystem of humans, food crops, and microbes; and, (2) a design for optimized productivity of food crops with high light levels over long days, with hydroponics, with elevated carbon dioxide and other controlled environmental factors, as well as with genetic selection for desirable crop properties. Mathematical modeling contributes to the goals by establishing trade-offs, by analyzing the growth and development of experimental crops, and by pointing to the possibilities of directed phasic control using modified field crop models to increase the harvest index.

[Endocrine disruptors and obesity: obesogens].

PubMed

García-Mayor, Ricardo V; Larrañaga Vidal, Alejandra; Docet Caamaño, Maria F; Lafuente Giménez, Anunciación

2012-04-01

Incidence and prevalence of owerweight and obesity have greatly increased over the past three decades in almost all countries around the world. This phenomenon is not easily explained by lifestyle changes in populations with very different initial habits. This has led to consider the influence of other factors, the so-called endocrine disruptors, and more specifically obesogens. This study reviewed the available evidence about polluting chemical substances which may potentially be obesogens in humans: DES, genistein, bisphenol A, organotins (TBT, TPT), and phthalates. The first three groups of substances mainly act upon estrogen receptors, while organotins and phthalates activate PPARγ. It was concluded that evidence exists of the obesogenic effect of these chemical substances in tissues and experimental animals, but few data are available in humans. Copyright © 2011 SEEN. Published by Elsevier Espana. All rights reserved.

Considerations in miniaturizing simplified agro-ecosystems for advanced life support.

PubMed

Volk, T

1996-01-01

Miniaturizing the Earth's biogeochemical cycles to support human life during future space missions is the goal of the NASA research and engineering program in advanced life support. Mission requirements to reduce mass, volume, and power have focused efforts on (1) a maximally simplified agro-ecosystem of humans, food crops, and microbes; and, (2) a design for optimized productivity of food crops with high light levels over long days, with hydroponics, with elevated carbon dioxide and other controlled environmental factors, as well as with genetic selection for desirable crop properties. Mathematical modeling contributes to the goals by establishing trade-offs, by analyzing the growth and development of experimental crops, and by pointing to the possibilities of directed phasic control using modified field crop models to increase the harvest index.

Spacecraft crew procedures from paper to computers

NASA Technical Reports Server (NTRS)

Oneal, Michael; Manahan, Meera

1991-01-01

Described here is a research project that uses human factors and computer systems knowledge to explore and help guide the design and creation of an effective Human-Computer Interface (HCI) for spacecraft crew procedures. By having a computer system behind the user interface, it is possible to have increased procedure automation, related system monitoring, and personalized annotation and help facilities. The research project includes the development of computer-based procedure system HCI prototypes and a testbed for experiments that measure the effectiveness of HCI alternatives in order to make design recommendations. The testbed will include a system for procedure authoring, editing, training, and execution. Progress on developing HCI prototypes for a middeck experiment performed on Space Shuttle Mission STS-34 and for upcoming medical experiments are discussed. The status of the experimental testbed is also discussed.

CCL2 and CCL5 Are Novel Therapeutic Targets for Estrogen-Dependent Breast Cancer.

PubMed

Svensson, Susanne; Abrahamsson, Annelie; Rodriguez, Gabriela Vazquez; Olsson, Anna-Karin; Jensen, Lasse; Cao, Yihai; Dabrosin, Charlotta

2015-08-15

Novel therapeutic targets of estrogen receptor (ER)-positive breast cancers are urgently needed because current antiestrogen therapy causes severe adverse effects, nearly 50% of patients are intrinsically resistant, and the majority of recurrences have maintained ER expression. We investigated the role of estrogen-dependent chemokine expression and subsequent cancer growth in human tissues and experimental breast cancer models. For in vivo sampling of human chemokines, microdialysis was used in breast cancers of women or normal human breast tissue before and after tamoxifen therapy. Estrogen exposure and targeted therapies were assessed in immune competent PyMT murine breast cancer, orthotopic human breast cancers in nude mice, cell culture of cancer cells, and freshly isolated human macrophages. Cancer cell dissemination was investigated using zebrafish. ER(+) cancers in women produced high levels of extracellular CCL2 and CCL5 in vivo, which was associated with infiltration of tumor-associated macrophages. In experimental breast cancer, estradiol enhanced macrophage influx and angiogenesis through increased release of CCL2, CCL5, and vascular endothelial growth factor. These effects were inhibited by anti-CCL2 or anti-CCL5 therapy, which resulted in potent inhibition of cancer growth. In addition, estradiol induced a protumorigenic activation of the macrophages. In a zebrafish model, macrophages increased cancer cell dissemination via CCL2 and CCL5 in the presence of estradiol, which was inhibited with anti-CCL2 and anti-CCL5 treatment. Our findings shed new light on the mechanisms underlying the progression of ER(+) breast cancer and indicate the potential of novel therapies targeting CCL2 and CCL5 pathways. ©2015 American Association for Cancer Research.

Concepts in human biological rhythms

PubMed Central

Reinberg, Alain; Ashkenazi, Israel

2003-01-01

Biological rhythms and their temporal organization are adaptive phenomena to periodic changes in environmental factors linked to the earth's rotation on its axis and around the sun. Experimental data from the plant and animal kingdoms have led to many models and concepts related to biological clocks that help describe and understand the mechanisms of these changes. Many of the prevailing concepts apply to all organisms, but most of the experimental data are insufficient to explain the dynamics of human biological clocks. This review presents phenomena thai are mainly characteristic ofand unique to - human chronobiology, and which cannot be fully explained by concepts and models drawn from laboratory experiments. We deal with the functional advantages of the human temporal organization and the problem of desynchronization, with special reference to the period (τ) of the circadian rhythm and its interindividual and intraindividual variability. We describe the differences between right- and left-hand rhythms suggesting the existence of different biological clocks in the right and left cortices, Desynchronization of rhythms is rather frequent (one example is night shift workers). In some individuals, desynchronization causes no clinical symptoms and we propose the concept of “allochronism” to designate a variant of the human temporal organization with no pathological implications. We restrict the term “dyschronism” to changes or alterations in temporal organization associated with a set of symptoms similar to those observed in subjects intolerant to shift work, eg, persisting fatigue and mood and sleep alterations. Many diseases involve chronic deprivation of sleep at night and constitute conditions mimicking thai of night shift workers who are intolerant to desynchronization. We also present a genetic model (the dian-circadian model) to explain interindividual differences in the period of biological rhythms in certain conditions. PMID:22033796

Hardness map of human meta tarsals and phalanges of toes.

PubMed

Manarvi, Irfan

2016-08-01

Predicting location of fracture in human bones has been a keen area of research for the past few decades. A variety of tests for hardness, deformation and strain field measurement have been conducted in the past; but considered insufficient due to various limitations. Researchers therefore have proposed further studies due to inaccuracies in measurement methods, testing machines and experimental errors. Advancement and availability of hardware, measuring instrumentation and testing machines can now provide remedies to these limitations. Human foot is a critical part of body exposed to various forces throughout its life. A number of products are developed for using over it for protection and care. Which many times do not provide sufficient protection and may itself become a source of stress due to non-consideration of the delicacy of bones in the feet. A continuous strain or overloading on feet may occur resulting to discomfort and even fracture. Not knowing how the hardness is spread all over the Meta tarsals and phalanges is one of major contributory factor for unsatisfactory design of foot protection products. This paper provides a complete hardness distribution map developed by experimental testing of all the Meta tarsals and Phalanges of toes for a typical human foot. The bones were taken from two left feet of a 40 and 42 year old male cadaver. These were dehydrated prior to measurements of hardness using Leeb hardness testing method. Hardness was measured around the circumference of a bone as well as along its length. Hardness values can be related to tensile strength of the bones to predict possible values of stress that could be borne by these bones. Results may also be used for design and developing various accessories for human feet health care and comfort.

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

Yuan, Aping; Research Group of Gastrointestinal Diseases, The Second Affiliated Hospital of Zhengzhou University, Henan; Yang, Hang

Diverse T help (Th) cells play a crucial role in the processing and maintaining of chronic inflammation as seen in ulcerative colitis (UC). Th9, a novel subset of Th cells that primarily produces interleukin (IL)-9, has recently been associated with the development of inflammatory diseases. In this study, we evaluated the presentation of Th9 cells in inflamed tissues of human and experimental mouse UC, and examined the therapeutic efficiency of anti Th9 cytokine IL-9 in the experimental mouse UC. Using immunohistochemistry (IHC), we evaluated the presentation of Th9 cells labelled by transcriptional factor PU.1 in both human and dextran sulfatemore » sodium (DSS) induced mouse colitis biopsies. The results showed that increased PU.1 positive Th9 cells were mainly located in the lamina propria in relative with the controls, intraepithelial Th9 cells can also be observed but at low density. Double IHCs revealed that most of PU.1 positive cells were CD3 positive lymphocytes in human UC specimens. Anti-IL-9 antibody injection for 2 weeks reduced the severity of inflammation in DSS induced colitis mice. Our results suggest that The Th9/IL-9 is involved in the pathogenesis of UC. - Highlights: • The density of novel PU.1 positive Th9 cells is significantly increased in both human and mouse colitis tissues. • PU.1 positive Th9 cells are predominately located in the inflamed lamina propria in both human and mouse colitis tissues. • Blocking of Th9 cytokine IL-9 by antibody injection suppresses the severity of inflammation in the bowel in colitis mice. • Novel Th9 cells contribute to the pathogenesis of UC.« less

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.

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.

Intermittent hydrostatic pressure enhances growth factor-induced chondroinduction of human adipose-derived mesenchymal stem cells.

PubMed

Safshekan, Farzaneh; Tafazzoli-Shadpour, Mohammad; Shokrgozar, Mohammad Ali; Haghighipour, Nooshin; Mahdian, Reza; Hemmati, Alireza

2012-12-01

Hydrostatic pressure (HP) plays an essential role in regulating function of chondrocytes and chondrogenic differentiation. The objective of this study was to examine effects of intermittent HP on chondrogenic differentiation of human adipose-derived mesenchymal stem cells (hASCs) in the presence or absence of chemical chondrogenic medium. Cells were isolated from abdominal fat tissue and confirmed for expression of ASC surface proteins and differentiation potential. Passage 3 pellets were treated with chemical (growth factor), mechanical (HP of 5 MPa and 0.5 Hz with duration of 4 h/day for 7 consecutive days), and combined chemical-mechanical stimuli. Using real-time polymerase chain reaction, the expression of Sox9, collagen II, and aggrecan as three major chondrogenic markers were quantified among three experimental groups and compared to those of stem cells and human cartilage tissue. In comparison to the chemical and mechanical groups, the chemical-mechanical group showed the highest expression for all three chondrogenic genes close to that of cartilage tissue. Results show the beneficial role of intermittent HP on chondrogenic differentiation of hASCs, and that this loading regime in combination with chondrogenic medium can be used in cartilage tissue engineering. © 2012, Copyright the Authors. Artificial Organs © 2012, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Phthalocyanine-Peptide Conjugates for Epidermal Growth Factor Receptor Targeting1

PubMed Central

Ongarora, Benson G.; Fontenot, Krystal R.; Hu, Xiaoke; Sehgal, Inder; Satyanarayana-Jois, Seetharama D.; Vicente, M. Graça H.

2012-01-01

Four phthalocyanine (Pc)-peptide conjugates designed to target the epidermal growth factor receptor (EGFR) were synthesized and evaluated in vitro using four cell lines: human carcinoma A431 and HEp2, human colorectal HT-29, and kidney Vero (negative control) cells. Two peptide ligands for EGFR were investigated: EGFR-L1 and -L2, bearing 6 and 13 amino acid residues, respectively. The peptides and Pc-conjugates were shown to bind to EGFR using both theoretical (Autodock) and experimental (SPR) investigations. The Pc-EGFR-L1 conjugates 5a and 5b efficiently targeted EGFR and were internalized, in part due to their cationic charge, whereas the uncharged Pc-EGFR-L2 conjugates 4b and 6a poorly targeted EGFR maybe due to their low aqueous solubility. All conjugates were non-toxic (IC50 > 100 µM) to HT-29 cells, both in the dark and upon light activation (1 J/cm2). Intravenous (iv) administration of conjugate 5b into nude mice bearing A431 and HT-29 human tumor xenografts resulted in a near-IR fluorescence signal at ca. 700 nm, 24 h after administration. Our studies show that Pc-EGFR-L1 conjugates are promising near-IR fluorescent contrast agents for CRC, and potentially other EGFR over-expressing cancers. PMID:22468711

BloodChIP: a database of comparative genome-wide transcription factor binding profiles in human blood cells.

PubMed

Chacon, Diego; Beck, Dominik; Perera, Dilmi; Wong, Jason W H; Pimanda, John E

2014-01-01

The BloodChIP database (http://www.med.unsw.edu.au/CRCWeb.nsf/page/BloodChIP) supports exploration and visualization of combinatorial transcription factor (TF) binding at a particular locus in human CD34-positive and other normal and leukaemic cells or retrieval of target gene sets for user-defined combinations of TFs across one or more cell types. Increasing numbers of genome-wide TF binding profiles are being added to public repositories, and this trend is likely to continue. For the power of these data sets to be fully harnessed by experimental scientists, there is a need for these data to be placed in context and easily accessible for downstream applications. To this end, we have built a user-friendly database that has at its core the genome-wide binding profiles of seven key haematopoietic TFs in human stem/progenitor cells. These binding profiles are compared with binding profiles in normal differentiated and leukaemic cells. We have integrated these TF binding profiles with chromatin marks and expression data in normal and leukaemic cell fractions. All queries can be exported into external sites to construct TF-gene and protein-protein networks and to evaluate the association of genes with cellular processes and tissue expression.

Parts-based stereoscopic image assessment by learning binocular manifold color visual properties

NASA Astrophysics Data System (ADS)

Xu, Haiyong; Yu, Mei; Luo, Ting; Zhang, Yun; Jiang, Gangyi

2016-11-01

Existing stereoscopic image quality assessment (SIQA) methods are mostly based on the luminance information, in which color information is not sufficiently considered. Actually, color is part of the important factors that affect human visual perception, and nonnegative matrix factorization (NMF) and manifold learning are in line with human visual perception. We propose an SIQA method based on learning binocular manifold color visual properties. To be more specific, in the training phase, a feature detector is created based on NMF with manifold regularization by considering color information, which not only allows parts-based manifold representation of an image, but also manifests localized color visual properties. In the quality estimation phase, visually important regions are selected by considering different human visual attention, and feature vectors are extracted by using the feature detector. Then the feature similarity index is calculated and the parts-based manifold color feature energy (PMCFE) for each view is defined based on the color feature vectors. The final quality score is obtained by considering a binocular combination based on PMCFE. The experimental results on LIVE I and LIVE Π 3-D IQA databases demonstrate that the proposed method can achieve much higher consistency with subjective evaluations than the state-of-the-art SIQA methods.