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Sample records for human inter-individual variability

  1. Inter-Individual Variability in Human Response to Low-Dose Ionizing Radiation, Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Rocke, David [Univ. of California, Davis, CA (United States)

    2016-08-01

    In order to investigate inter-individual variability in response to low-dose ionizing radiation, we are working with three models, 1) in-vivo irradiated human skin, for which we have a realistic model, but with few subjects, all from a previous project, 2) ex-vivo irradiated human skin, for which we also have a realistic model, though with the limitations involved in keeping skin pieces alive in media, and 3) MatTek EpiDermFT skin plugs, which provides a more realistic model than cell lines, which is more controllable than human samples.

  2. Inter-Individual Variability in Human Response to Low-Dose Ionizing Radiation, Final Report

    International Nuclear Information System (INIS)

    Rocke, David

    2016-01-01

    In order to investigate inter-individual variability in response to low-dose ionizing radiation, we are working with three models, 1) in-vivo irradiated human skin, for which we have a realistic model, but with few subjects, all from a previous project, 2) ex-vivo irradiated human skin, for which we also have a realistic model, though with the limitations involved in keeping skin pieces alive in media, and 3) MatTek EpiDermFT skin plugs, which provides a more realistic model than cell lines, which is more controllable than human samples.

  3. Chromosomal radiosensitivity: a study of the chromosomal G2 assay in human blood lymphocytes indicating significant inter-individual variability

    International Nuclear Information System (INIS)

    Smart, V.; Curwen, G.B.; Whitehouse, C.A.; Edwards, A.; Tawn, E.J.

    2003-01-01

    The G 2 chromosomal radiosensitivity assay is a technically demanding assay. To ensure that it is reproducible in our laboratory, we have examined the effects of storage and culture conditions by applying the assay to a group of healthy controls and determined the extent of intra- and inter-individual variations. Nineteen different individuals provided one or more blood samples resulting in a total of 57 successful tests. Multiple cultures from a single blood sample showed no statistically significant difference in the number of chromatid type aberrations between cultures. A 24 h delay prior to culturing the lymphocytes did not significantly affect the induced G 2 score. Intra-individual variation was not statistically significant in seven out of nine individuals. Inter-individual variation was highly statistically significant (P<0.001), indicating that there is a real difference between individuals in the response to radiation using this assay

  4. Quantitative Comparison of Effects of Dofetilide, Sotalol, Quinidine, and Verapamil between Human Ex vivo Trabeculae and In silico Ventricular Models Incorporating Inter-Individual Action Potential Variability

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    Oliver J. Britton

    2017-08-01

    Full Text Available Background:In silico modeling could soon become a mainstream method of pro-arrhythmic risk assessment in drug development. However, a lack of human-specific data and appropriate modeling techniques has previously prevented quantitative comparison of drug effects between in silico models and recordings from human cardiac preparations. Here, we directly compare changes in repolarization biomarkers caused by dofetilide, dl-sotalol, quinidine, and verapamil, between in silico populations of human ventricular cell models and ex vivo human ventricular trabeculae.Methods and Results:Ex vivo recordings from human ventricular trabeculae in control conditions were used to develop populations of in silico human ventricular cell models that integrated intra- and inter-individual variability in action potential (AP biomarker values. Models were based on the O'Hara-Rudy ventricular cardiomyocyte model, but integrated experimental AP variability through variation in underlying ionic conductances. Changes to AP duration, triangulation and early after-depolarization occurrence from application of the four drugs at multiple concentrations and pacing frequencies were compared between simulations and experiments. To assess the impact of variability in IC50 measurements, and the effects of including state-dependent drug binding dynamics, each drug simulation was repeated with two different IC50 datasets, and with both the original O'Hara-Rudy hERG model and a recently published state-dependent model of hERG and hERG block. For the selective hERG blockers dofetilide and sotalol, simulation predictions of AP prolongation and repolarization abnormality occurrence showed overall good agreement with experiments. However, for multichannel blockers quinidine and verapamil, simulations were not in agreement with experiments across all IC50 datasets and IKr block models tested. Quinidine simulations resulted in overprolonged APs and high incidence of repolarization

  5. Impact of Flavonols on Cardiometabolic Biomarkers: A Meta-Analysis of Randomized Controlled Human Trials to Explore the Role of Inter-Individual Variability

    Science.gov (United States)

    Menezes, Regina; Rodriguez-Mateos, Ana; Kaltsatou, Antonia; González-Sarrías, Antonio; Greyling, Arno; Giannaki, Christoforos; Andres-Lacueva, Cristina; Milenkovic, Dragan; Gibney, Eileen R.; Dumont, Julie; Schär, Manuel; Garcia-Aloy, Mar; Palma-Duran, Susana Alejandra; Ruskovska, Tatjana; Maksimova, Viktorija; Combet, Emilie; Pinto, Paula

    2017-01-01

    Several epidemiological studies have linked flavonols with decreased risk of cardiovascular disease (CVD). However, some heterogeneity in the individual physiological responses to the consumption of these compounds has been identified. This meta-analysis aimed to study the effect of flavonol supplementation on biomarkers of CVD risk such as, blood lipids, blood pressure and plasma glucose, as well as factors affecting their inter-individual variability. Data from 18 human randomized controlled trials were pooled and the effect was estimated using fixed or random effects meta-analysis model and reported as difference in means (DM). Variability in the response of blood lipids to supplementation with flavonols was assessed by stratifying various population subgroups: age, sex, country, and health status. Results showed significant reductions in total cholesterol (DM = −0.10 mmol/L; 95% CI: −0.20, −0.01), LDL cholesterol (DM = −0.14 mmol/L; 95% CI: −0.21, 0.07), and triacylglycerol (DM = −0.10 mmol/L; 95% CI: −0.18, 0.03), and a significant increase in HDL cholesterol (DM = 0.05 mmol/L; 95% CI: 0.02, 0.07). A significant reduction was also observed in fasting plasma glucose (DM = −0.18 mmol/L; 95% CI: −0.29, −0.08), and in blood pressure (SBP: DM = −4.84 mmHg; 95% CI: −5.64, −4.04; DBP: DM = −3.32 mmHg; 95% CI: −4.09, −2.55). Subgroup analysis showed a more pronounced effect of flavonol intake in participants from Asian countries and in participants with diagnosed disease or dyslipidemia, compared to healthy and normal baseline values. In conclusion, flavonol consumption improved biomarkers of CVD risk, however, country of origin and health status may influence the effect of flavonol intake on blood lipid levels. PMID:28208791

  6. Inter-individual Differences in Heart Rate Variability Are Associated with Inter-individual Differences in Empathy and Alexithymia

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    Alexander Lischke

    2018-02-01

    Full Text Available In the present study, we investigated whether inter-individual differences in vagally mediated heart rate variability (vmHRV would be associated with inter-individual differences in empathy and alexithymia. To this end, we determined resting state HF-HRV in 90 individuals that also completed questionnaires assessing inter-individual differences in empathy and alexithymia. Our categorical and dimensional analyses revealed that inter-individual differences in HF-HRV were differently associated with inter-individual differences in empathy and alexithymia. We found that individuals with high HF-HRV reported more empathy and less alexithymia than individuals with low HF-HRV. Moreover, we even found that an increase in HF-HRV was associated with an increase in empathy and a decrease in alexithymia across all participants. Taken together, these findings indicate that individuals with high HF-HRV are more empathetic and less alexithymic than individuals with low HF-HRV. These differences in empathy and alexithymia may explain why individuals with high HF-HRV are more successful in sharing and understanding the mental and emotional states of others than individuals with low HF-HRV.

  7. Identification of early target genes of aflatoxin B1 in human hepatocytes, inter-individual variability and comparison with other genotoxic compounds

    International Nuclear Information System (INIS)

    Josse, Rozenn; Dumont, Julie; Fautrel, Alain; Robin, Marie-Anne; Guillouzo, André

    2012-01-01

    Gene expression profiling has recently emerged as a promising approach to identify early target genes and discriminate genotoxic carcinogens from non-genotoxic carcinogens and non-carcinogens. However, early gene changes induced by genotoxic compounds in human liver remain largely unknown. Primary human hepatocytes and differentiated HepaRG cells were exposed to aflatoxin B1 (AFB1) that induces DNA damage following enzyme-mediated bioactivation. Gene expression profile changes induced by a 24 h exposure of these hepatocyte models to 0.05 and 0.25 μM AFB1 were analyzed by using oligonucleotide pangenomic microarrays. The main altered signaling pathway was the p53 pathway and related functions such as cell cycle, apoptosis and DNA repair. Direct involvement of the p53 protein in response to AFB1 was verified by using siRNA directed against p53. Among the 83 well-annotated genes commonly modulated in two pools of three human hepatocyte populations and HepaRG cells, several genes were identified as altered by AFB1 for the first time. In addition, a subset of 10 AFB1-altered genes, selected upon basis of their function or tumor suppressor role, was tested in four human hepatocyte populations and in response to other chemicals. Although they exhibited large variable inter-donor fold-changes, several of these genes, particularly FHIT, BCAS3 and SMYD3, were found to be altered by various direct and other indirect genotoxic compounds and unaffected by non-genotoxic compounds. Overall, this comprehensive analysis of early gene expression changes induced by AFB1 in human hepatocytes identified a gene subset that included several genes representing potential biomarkers of genotoxic compounds. -- Highlights: ► Gene expression profile changes induced by aflatoxin B1 in human hepatocytes. ► AFB1 modulates various genes including tumor suppressor genes and proto-oncogenes. ► Important inter-individual variations in the response to AFB1. ► Some genes also altered by other

  8. Inter-Individual Variability in Acute Toxicity of R-Pulegone and R-Menthofuran in Human Liver Slices and Their Influence on miRNA Expression Changes in Comparison to Acetaminophen

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    Tomáš Zárybnický

    2018-06-01

    Full Text Available Monoterpenes R-pulegone (PUL and R-menthofuran (MF, abundant in the Lamiaceae family, are frequently used in herb and food products. Although their hepatotoxicity was shown in rodent species, information about their effects in human liver has been limited. The aim of our study was to test the effects of PUL, MF and acetaminophen (APAP, as a reference compound on cell viability and microRNA (miRNA expression in human precision-cut liver slices. Slices from five patients were used to follow up on the inter-individual variability. PUL was toxic in all liver samples (the half-maximal effective concentration was 4.0 µg/mg of tissue, while MF and surprisingly APAP only in two and three liver samples, respectively. PUL also changed miRNA expression more significantly than MF and APAP. The most pronounced effect was a marked decrease of miR-155-5p expression caused by PUL even in non-toxic concentrations in all five liver samples. Our results showed that PUL is much more toxic than MF and APAP in human liver and that miR-155-5p could be a good marker of PUL early hepatotoxicity. Marked inter-individual variabilities in all our results demonstrate the high probability of significant differences in the hepatotoxicity of tested compounds among people.

  9. Longitudinal intra- and inter-individual variability in young swimmers' performance and determinant competition factors

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    Jorge Estrela Morais

    2014-09-01

    Full Text Available The main purpose of this study was to follow-up the intra- and inter-individual variability of young swimmers' performance and determinant factors over two competitive seasons. Thirty young swimmers (14 boys: 12.33±0.65 years-old; 16 girls: 11.15±0.55 years-old were followed-up throughout two consecutive seasons (seven evaluation moments. Performance (100m freestyle, anthropometric, kinematic, hydrodynamic and efficiency features were evaluated. A gender and skill-level effect was observed. Boys improved in a higher amount (% comparing to girls. Overall, swimmers in skill-level 2 (both genders presented a higher intra-individual variability. Performance and anthropometrics showed a significant inter-individual variability in most moments, but hydrodynamics, kinematics and efficiency did not. Within each skill-level hydrodynamics, kinematics and efficiency were the variables that showed a high inter-individual variability. As a gender and skill-level effect was noticed in an age-group of young swimmers, coaches and practitioners should put the focus in specific and customized training plans for each skill-level of swimmers.

  10. Inter-individual cognitive variability in children with Asperger’s syndrome

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    Maria Luz Gonzalez-Gadea

    2014-07-01

    Full Text Available Multiple studies have tried to establish the distinctive profile of individuals with Asperger’s syndrome (AS. However, recent reports suggest that adults with AS feature heterogeneous cognitive profiles. The present study explores inter-individual variability in children with AS through group comparison and multiple case series analysis. All participants completed an extended battery including measures of fluid and crystallized intelligence, executive functions, theory of mind, and classical neuropsychological tests. Significant group differences were found in theory of mind and other domains related to global information processing. However, the AS group showed high inter-individual variability (both sub- and supra-normal performance on most cognitive tasks. Furthermore, high fluid intelligence correlated with less general cognitive impairment, high cognitive flexibility, and speed motor processing. In light of these findings, we propose that children with AS are characterized by a distinct, uneven pattern of cognitive strengths and weaknesses.

  11. Inter-individual variability in the production of flavan-3-ol colonic metabolites: preliminary elucidation of urinary metabotypes.

    Science.gov (United States)

    Mena, Pedro; Ludwig, Iziar A; Tomatis, Virginia B; Acharjee, Animesh; Calani, Luca; Rosi, Alice; Brighenti, Furio; Ray, Sumantra; Griffin, Julian L; Bluck, Les J; Del Rio, Daniele

    2018-04-03

    There is much information on the bioavailability of (poly)phenolic compounds following acute intake of various foods. However, there are only limited data on the effects of repeated and combined exposure to specific (poly)phenol food sources and the inter-individual variability in their bioavailability. This study evaluated the combined urinary excretion of (poly)phenols from green tea and coffee following daily consumption by healthy subjects in free-living conditions. The inter-individual variability in the production of phenolic metabolites was also investigated. Eleven participants consumed both tablets of green tea and green coffee bean extracts daily for 8 weeks and 24-h urine was collected on five different occasions. The urinary profile of phenolic metabolites and a set of multivariate statistical tests were used to investigate the putative existence of characteristic metabotypes in the production of flavan-3-ol microbial metabolites. (Poly)phenolic compounds in the green tea and green coffee bean extracts were absorbed and excreted after simultaneous consumption, with green tea resulting in more inter-individual variability in urinary excretion of phenolic metabolites. Three metabotypes in the production of flavan-3-ol microbial metabolites were tentatively defined, characterized by the excretion of different amounts of trihydroxyphenyl-γ-valerolactones, dihydroxyphenyl-γ-valerolactones, and hydroxyphenylpropionic acids. The selective production of microbiota-derived metabolites from flavan-3-ols and the putative existence of characteristic metabotypes in their production represent an important development in the study of the bioavailability of plant bioactives. These observations will contribute to better understand the health effects and individual differences associated with consumption of flavan-3-ols, arguably the main class of flavonoids in the human diet.

  12. How plantar exteroceptive efficiency modulates postural and oculomotor control: inter-individual variability

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    Arnaud eFoisy

    2016-05-01

    Full Text Available In a previous experiment, we showed that among young and healthy subjects, thin plantar inserts improve postural control and modify vergence amplitudes. In this experiment, however, significant inter-individual variability was observed. We hypothesize that its origin could be attributed to a different reliance upon feet cutaneous afferents. In order to test this hypothesis, we re-analyzed the data relative to 31 young (age 25,7±3,8 and healthy subjects who participated in the first experiment after having classified them into two groups depending on their Plantar Quotient (PQ = Surface area of CoP foam / Surface area of CoP firm ground x100. Foam decreases the information arising from the feet, normally resulting in a PQ>100. Hence, the PQ provides information on the weight of plantar cutaneous afferents used in postural control. Twelve people were Plantar-Independent Subjects, as indicated by a PQ<100. These individuals did not behave like the Normal Plantar Quotient Subjects: they were almost insensitive to the plantar stimulations in terms of postural control and totally insensitive in terms of oculomotor control. We conclude that the inter-individual variability observed in our first experiment is explained by the subjects’ degree of plantar reliance. We propose that plantar independence is a dysfunctional situation revealing an inefficiency in plantar cutaneous afferents. The latter could be due to a latent somatosensory dysfunction generating a noise which prevents the CNS from correctly processing and using feet somatosensory afferents both for balance and vergence control: Plantar Irritating Stimulus. Considering the non-noxious nature and prevalence of this phenomenon, these results can be of great interest to researchers and clinicians who attempt to trigger postural or oculomotor responses through mechanical stimulation of the foot sole.

  13. Inter-individual variations of human mercury exposure biomarkers: a cross-sectional assessment

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    Einarsson Östen

    2005-10-01

    Full Text Available Abstract Background Biomarkers for mercury (Hg exposure have frequently been used to assess exposure and risk in various groups of the general population. We have evaluated the most frequently used biomarkers and the physiology on which they are based, to explore the inter-individual variations and their suitability for exposure assessment. Methods Concentrations of total Hg (THg, inorganic Hg (IHg and organic Hg (OHg, assumed to be methylmercury; MeHg were determined in whole blood, red blood cells, plasma, hair and urine from Swedish men and women. An automated multiple injection cold vapour atomic fluorescence spectrophotometry analytical system for Hg analysis was developed, which provided high sensitivity, accuracy, and precision. The distribution of the various mercury forms in the different biological media was explored. Results About 90% of the mercury found in the red blood cells was in the form of MeHg with small inter-individual variations, and part of the IHg found in the red blood cells could be attributed to demethylated MeHg. THg in plasma was associated with both IHg and MeHg, with large inter-individual variations in the distribution between red blood cells and plasma. THg in hair reflects MeHg exposure at all exposure levels, and not IHg exposure. The small fraction of IHg in hair is most probably emanating from demethylated MeHg. The inter-individual variation in the blood to hair ratio was very large. The variability seemed to decrease with increasing OHg in blood, most probably due to more frequent fish consumption and thereby blood concentrations approaching steady state. THg in urine reflected IHg exposure, also at very low IHg exposure levels. Conclusion The use of THg concentration in whole blood as a proxy for MeHg exposure will give rise to an overestimation of the MeHg exposure depending on the degree of IHg exposure, why speciation of mercury forms is needed. THg in RBC and hair are suitable proxies for MeHg exposure

  14. Longitudinal intra and inter-individual variability in young swimmers performance and determinant factors

    OpenAIRE

    Morais, Jorge; Costa, Mário; Moreira, Marc; Forte, Pedro; Silva, António; Marinho, Daniel; Barbosa, Tiago

    2014-01-01

    The aim of study was to follow-up the intra-individual and inter-individual stability of talented swimmers’ performance and its anthropometrics, kinematics, hydrodynamics and efficiency during two competitive seasons. Thirty talented swimmers (14 boys: 12.33 ± 0.65 years; and 16 girls: 11.15 ± 0.55 years) were followed-up. Performance (100-m freestyle), anthropometrics (body mass, height, arm span, chest perimeter, trunk transverse surface area, hand and foot surface area), kinematics (stroke...

  15. Inter-individual variability of stone marten behavioral responses to a highway.

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    Fernando Ascensão

    Full Text Available Efforts to reduce the negative impacts of roads on wildlife may be hindered if individuals within the population vary widely in their responses to roads and mitigation strategies ignore this variability. This knowledge is particularly important for medium-sized carnivores as they are vulnerable to road mortality, while also known to use available road passages (e.g., drainage culverts for safely crossing highways. Our goal in this study was to assess whether this apparently contradictory pattern of high road-kill numbers associated with a regular use of road passages is attributable to the variation in behavioral responses toward the highway between individuals. We investigated the responses of seven radio-tracked stone martens (Martes foina to a highway by measuring their utilization distribution, response turning angles and highway crossing patterns. We compared the observed responses to simulated movement parameterized by the observed space use and movement characteristics of each individual, but naïve to the presence of the highway. Our results suggested that martens demonstrate a diversity of responses to the highway, including attraction, indifference, or avoidance. Martens also varied in their highway crossing patterns, with some crossing repeatedly at the same location (often coincident with highway passages. We suspect that the response variability derives from the individual's familiarity of the landscape, including their awareness of highway passage locations. Because of these variable yet potentially attributable responses, we support the use of exclusionary fencing to guide transient (e.g., dispersers individuals to existing passages to reduce the road-kill risk.

  16. Mechanistic Physiologically Based Pharmacokinetic (PBPK) Model of the Heart Accounting for Inter-Individual Variability: Development and Performance Verification.

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    Tylutki, Zofia; Mendyk, Aleksander; Polak, Sebastian

    2018-04-01

    Modern model-based approaches to cardiac safety and efficacy assessment require accurate drug concentration-effect relationship establishment. Thus, knowledge of the active concentration of drugs in heart tissue is desirable along with inter-subject variability influence estimation. To that end, we developed a mechanistic physiologically based pharmacokinetic model of the heart. The models were described with literature-derived parameters and written in R, v.3.4.0. Five parameters were estimated. The model was fitted to amitriptyline and nortriptyline concentrations after an intravenous infusion of amitriptyline. The cardiac model consisted of 5 compartments representing the pericardial fluid, heart extracellular water, and epicardial intracellular, midmyocardial intracellular, and endocardial intracellular fluids. Drug cardiac metabolism, passive diffusion, active efflux, and uptake were included in the model as mechanisms involved in the drug disposition within the heart. The model accounted for inter-individual variability. The estimates of optimized parameters were within physiological ranges. The model performance was verified by simulating 5 clinical studies of amitriptyline intravenous infusion, and the simulated pharmacokinetic profiles agreed with clinical data. The results support the model feasibility. The proposed structure can be tested with the goal of improving the patient-specific model-based cardiac safety assessment and offers a framework for predicting cardiac concentrations of various xenobiotics. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  17. Inter-individual relationships in proboscis monkeys: a preliminary comparison with other non-human primates.

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    Matsuda, Ikki; Tuuga, Augustine; Bernard, Henry; Furuichi, Takeshi

    2012-01-01

    This is the first report on inter-individual relationships within a one-male group of proboscis monkeys (Nasalis larvatus) based on detailed identification of individuals. From May 2005 to 2006, focal and ad libitum data of agonistic and grooming behaviour were collected in a forest along the Menanggul River, Sabah, Malaysia. During the study period, we collected over 1,968 h of focal data on the adult male and 1,539 h of focal data on the six females. Their social interactions, including agonistic and grooming behaviour, appeared to follow typical patterns reported for other colobines: the incidence of social interaction within groups is low. Of 39 agonistic events, 26 were displacement from sleeping places along the river, 6 were the α male threatening other monkeys to mediate quarrels between females and between females and juveniles, and 7 were displacement from feeding places. Although the agonistic behaviour matrix based on the 33 intra-group agonistic events (excluding events between adults and juveniles and between adults and infants) was indicative of non-significant linearity, there were some specific dominated individuals within the group of proboscis monkeys. Nonetheless, grooming behaviour among adult females within a group were not affected by the dominance hierarchy. This study also conducted initial comparisons of grooming patterns among proboscis monkeys and other primate species. On the basis of comparison of their grooming networks, similar grooming patterns among both-sex-disperse and male-philopatric/female-disperse species were detected. Because adult females in these species migrate to groups repeatedly, it may be difficult to establish the firm grooming exchange relationship for particular individuals within groups, unlike in female-philopatric/male-disperse species. However, grooming distribution patterns within groups among primate species were difficult to explain solely on the basis of their dispersal patterns. Newly immigrated females

  18. Inter-individual and inter-cell type variation in residual DNA damage after in vivo irradiation of human skin

    International Nuclear Information System (INIS)

    Chua, Melvin Lee Kiang; Somaiah, Navita; Bourne, Sara; Daley, Frances; A'Hern, Roger; Nuta, Otilia; Davies, Sue; Herskind, Carsten; Pearson, Ann; Warrington, Jim; Helyer, Sarah; Owen, Roger; Yarnold, John; Rothkamm, Kai

    2011-01-01

    Purpose: The aim of this study was to compare inter-individual and inter-cell type variation in DNA double-strand break (DSB) repair following in vivo irradiation of human skin. Materials and methods: Duplicate 4 mm core biopsies of irradiated and unirradiated skin were collected from 35 patients 24 h after 4 Gy exposure using 6 MeV electrons. Residual DSB were quantified by scoring 53BP1 foci in dermal fibroblasts, endothelial cells, superficial keratinocytes and basal epidermal cells. Results: Coefficients of inter-individual variation for levels of residual foci 24 h after in vivo irradiation of skin were 39.9% in dermal fibroblasts, 44.3% in endothelial cells, 32.9% in superficial keratinocytes and 46.4% in basal epidermal cells (p < 0.001, ANOVA). In contrast, the coefficient of inter-cell type variation for residual foci levels was only 11.3% in human skin between the different epidermal and dermal cells (p = 0.034, ANOVA). Foci levels between the different skin cell types were correlated (Pearson's R = 0.855-0.955, p < 0.001). Conclusions: Patient-specific factors appear to be more important than cell type-specific factors in determining residual foci levels following in vivo irradiation of human skin.

  19. Inter-individual variability in cortical excitability and motor network connectivity following multiple blocks of rTMS.

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    Nettekoven, Charlotte; Volz, Lukas J; Leimbach, Martha; Pool, Eva-Maria; Rehme, Anne K; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

    2015-09-01

    The responsiveness to non-invasive neuromodulation protocols shows high inter-individual variability, the reasons of which remain poorly understood. We here tested whether the response to intermittent theta-burst stimulation (iTBS) - an effective repetitive transcranial magnetic stimulation (rTMS) protocol for increasing cortical excitability - depends on network properties of the cortical motor system. We furthermore investigated whether the responsiveness to iTBS is dose-dependent. To this end, we used a sham-stimulation controlled, single-blinded within-subject design testing for the relationship between iTBS aftereffects and (i) motor-evoked potentials (MEPs) as well as (ii) resting-state functional connectivity (rsFC) in 16 healthy subjects. In each session, three blocks of iTBS were applied, separated by 15min. We found that non-responders (subjects not showing an MEP increase of ≥10% after one iTBS block) featured stronger rsFC between the stimulated primary motor cortex (M1) and premotor areas before stimulation compared to responders. However, only the group of responders showed increases in rsFC and MEPs, while most non-responders remained close to baseline levels after all three blocks of iTBS. Importantly, there was still a large amount of variability in both groups. Our data suggest that responsiveness to iTBS at the local level (i.e., M1 excitability) depends upon the pre-interventional network connectivity of the stimulated region. Of note, increasing iTBS dose did not turn non-responders into responders. The finding that higher levels of pre-interventional connectivity precluded a response to iTBS could reflect a ceiling effect underlying non-responsiveness to iTBS at the systems level. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Genomic instability after targeted irradiation of human lymphocytes: Evidence for inter-individual differences under bystander conditions

    International Nuclear Information System (INIS)

    Kadhim, Munira A.; Lee, Ryonfa; Moore, Stephen R.; Macdonald, Denise A.; Chapman, Kim L.; Patel, Gaurang; Prise, Kevin M.

    2010-01-01

    Environmental 222 radon exposure is a human health concern, and many studies demonstrate that very low doses of high LET α-particle irradiation initiate deleterious genetic consequences in both irradiated and non-irradiated bystander cells. One consequence, radiation-induced genomic instability (RIGI), is a hallmark of tumorigenesis and is often assessed by measuring delayed chromosomal aberrations. We utilised a technique that facilitates transient immobilization of primary lymphocytes for targeted microbeam irradiation and have reported that environmentally relevant doses, e.g. a single 3 He 2+ particle traversal to a single cell, are sufficient to induce RIGI. Herein we sought to determine differences in radiation response in lymphocytes isolated from five healthy male donors. Primary lymphocytes were irradiated with a single particle per cell nucleus. We found evidence for inter-individual variation in radiation response (RIGI, measured as delayed chromosome aberrations). Although this was not highly significant, it was possibly masked by high levels of intra-individual variation. While there are many studies showing a link between genetic predisposition and RIGI, there are few studies linking genetic background with bystander effects in normal human lymphocytes. In an attempt to investigate inter-individual variation in the induction of bystander effects, primary lymphocytes were irradiated with a single particle under conditions where fractions of the population were traversed. We showed a marked genotype-dependent bystander response in one donor after exposure to 15% of the population. The findings may also be regarded as a radiation-induced genotype-dependent bystander effect triggering an instability phenotype.

  1. Genomic instability after targeted irradiation of human lymphocytes: Evidence for inter-individual differences under bystander conditions

    Energy Technology Data Exchange (ETDEWEB)

    Kadhim, Munira A., E-mail: mkadhim@brookes.ac.uk [School of Life Sciences, Oxford Brookes University, Oxford OX3 0BP (United Kingdom); Lee, Ryonfa [Biophysics, GSI Helmholtzzentrum fuer Schwerionenforschung GmbH, Planckstrasse 1, D-64291 Darmstadt (Germany); Moore, Stephen R.; Macdonald, Denise A. [Radiation and Genome Stability Unit, Medical Research Council, Harwell, Oxfordshire OX11 0RD (United Kingdom); Chapman, Kim L. [School of Life Sciences, Oxford Brookes University, Oxford OX3 0BP (United Kingdom); Patel, Gaurang; Prise, Kevin M. [Centre for Cancer Research and Cell Biology, Queen' s University Belfast, Belfast BT9 7BL (United Kingdom)

    2010-06-01

    Environmental {sup 222}radon exposure is a human health concern, and many studies demonstrate that very low doses of high LET {alpha}-particle irradiation initiate deleterious genetic consequences in both irradiated and non-irradiated bystander cells. One consequence, radiation-induced genomic instability (RIGI), is a hallmark of tumorigenesis and is often assessed by measuring delayed chromosomal aberrations. We utilised a technique that facilitates transient immobilization of primary lymphocytes for targeted microbeam irradiation and have reported that environmentally relevant doses, e.g. a single {sup 3}He{sup 2+} particle traversal to a single cell, are sufficient to induce RIGI. Herein we sought to determine differences in radiation response in lymphocytes isolated from five healthy male donors. Primary lymphocytes were irradiated with a single particle per cell nucleus. We found evidence for inter-individual variation in radiation response (RIGI, measured as delayed chromosome aberrations). Although this was not highly significant, it was possibly masked by high levels of intra-individual variation. While there are many studies showing a link between genetic predisposition and RIGI, there are few studies linking genetic background with bystander effects in normal human lymphocytes. In an attempt to investigate inter-individual variation in the induction of bystander effects, primary lymphocytes were irradiated with a single particle under conditions where fractions of the population were traversed. We showed a marked genotype-dependent bystander response in one donor after exposure to 15% of the population. The findings may also be regarded as a radiation-induced genotype-dependent bystander effect triggering an instability phenotype.

  2. Development from childhood to adulthood increases morphological and functional inter-individual variability in the right superior temporal cortex.

    Science.gov (United States)

    Bonte, Milene; Frost, Martin A; Rutten, Sanne; Ley, Anke; Formisano, Elia; Goebel, Rainer

    2013-12-01

    We study the developmental trajectory of morphology and function of the superior temporal cortex (STC) in children (8-9 years), adolescents (14-15 years) and young adults. We analyze cortical surface landmarks and functional MRI (fMRI) responses to voices, other natural categories and tones and examine how hemispheric asymmetry and inter-subject variability change across age. Our results show stable morphological asymmetries across age groups, including a larger left planum temporale and a deeper right superior temporal sulcus. fMRI analyses show that a rightward lateralization for voice-selective responses is present in all groups but decreases with age. Furthermore, STC responses to voices change from being less selective and more spatially diffuse in children to highly selective and focal in adults. Interestingly, the analysis of morphological landmarks reveals that inter-subject variability increases during development in the right--but not in the left--STC. Similarly, inter-subject variability of cortically-realigned functional responses to voices, other categories and tones increases with age in the right STC. Our findings reveal asymmetric developmental changes in brain regions crucial for auditory and voice perception. The age-related increase of inter-subject variability in right STC suggests that anatomy and function of this region are shaped by unique individual developmental experiences. © 2013.

  3. Intra- and inter-individual variability of Aspergillus fumigatus reactive T-cell frequencies in healthy volunteers in dependency of mould exposure in residential and working environment.

    Science.gov (United States)

    Wurster, Sebastian; Weis, Philipp; Page, Lukas; Helm, Johanna; Lazariotou, Maria; Einsele, Hermann; Ullmann, Andrew J

    2017-10-01

    Invasive aspergillosis remains a deadly disease in immunocompromised patients, whereas the combination of an exaggerated immune response and continuous exposure lead to various hyperinflammatory diseases. This pilot study aimed to gain an overview of the intra- and inter-individual variability in Aspergillus fumigatus reactive T-helper cells in healthy adults and the correlation with environmental mould exposure. In this flow cytometric study, the frequencies of CD154 + A. fumigatus reactive T cells were evaluated in 70 healthy volunteers. All subjects completed a standardised questionnaire addressing their mould exposure. Subjects with intensive mould exposure in their professional or residential surrounding demonstrated considerably higher mean frequencies of A. fumigatus reactive T-helper and T-memory cells. Comparative evaluation of multiple measurements over time demonstrated relatively conserved reactive T-cell frequencies in the absence of major changes to the exposure profile, whereas those frequently exposed in professional environment or with changes to their risk score demonstrated a marked dependency of antigen reactive T-cell frequencies on recent mould exposure. This pilot study was the first to provide data on the intra-individual variability in A. fumigatus reactive T-cell frequencies and its linkage to mould encounter. Fungus reactive T cells are to be considered a valued tool for the assessment of environmental mould exposure. © 2017 Blackwell Verlag GmbH.

  4. Association between DNA methylation in the miR-328 5'-flanking region and inter-individual differences in miR-328 and BCRP expression in human placenta.

    Directory of Open Access Journals (Sweden)

    Jumpei Saito

    Full Text Available MicroRNA (miRNA are non-coding small RNA that regulate gene expression. MiR-328 is reported to influence breast cancer resistance protein (BCRP expression in cancer cells. As a large inter-individual difference in BCRP levels is observed in various human tissues, the contribution of miR-328 to these differences is of interest. We hypothesized that DNA methylation in the miR-328 promoter region is responsible for the difference in miR-328 levels, leading to inter-individual variability in BCRP levels in human placenta. The association between placental miR-328 and BCRP levels was analyzed, and then DNA methylation in the miR-328 5'-flanking region and regulatory mechanisms causing inter-individual differences in miR-328 and BCRP levels were examined. MiR-328 expression was significantly correlated with BCRP mRNA (Rs = -0.560, P < 0.01 and protein (Rs = -0.730, P < 0.01 levels. It was also up-regulated by the demethylating agent 5-aza-2'-deoxycytidine in BCRP-expressing cells. Luciferase assays with differentially methylated reporter constructs indicated that methylation in the miR-328 5'-flanking region including a predicted CpG island remarkably decreased transcriptional activity compared to that in unmethylated constructs. We selected CCAAT/enhancer binding protein α (C/EBPα, located within the predicted CpG island, by in silico analysis. To elucidate the role of C/EBPα in miR-328 expression, a chromatin immunoprecipitation assay, promoter deletion analysis, and electrophoretic mobility shift assay (EMSA were performed. C/EBPα-binding site-truncated constructs showed significantly decreased promoter activity, and EMSA indicated that the C/EBPα-binding sites were located in the CpG island. Finally, the methylation patterns of several CpG dinucleotides proximal to two C/EBPα-binding sites in the miR-328 5'-flanking region were correlated negatively with miR-328 levels, and positively with BCRP levels in human placental samples. These

  5. Arabinoxylo-Oligosaccharides and Inulin Impact Inter-Individual Variation on Microbial Metabolism and Composition, Which Immunomodulates Human Cells.

    Science.gov (United States)

    Van den Abbeele, Pieter; Taminiau, Bernard; Pinheiro, Iris; Duysburgh, Cindy; Jacobs, Heidi; Pijls, Loek; Marzorati, Massimo

    2018-02-07

    Fecal batch fermentations coupled to cocultures of epithelial cells and macrophages were used to compare how arabinoxylo-oligosaccharides (AXOS) and inulin modulate gut microbial activity and composition of three different human donors and subsequently the epithelial permeability and immune response. Both inulin and AXOS decreased the pH during incubation (-1.5 pH units), leading to increased productions of acetate, propionate, and butyrate. Differences in terms of metabolites production could be linked to specific microbial alterations at genus level upon inulin/AXOS supplementation (i.e., Bifidobacterium, Bacteroides, Prevotella and unclassified Erysipelotrichaceae), as shown by 16S-targeted Illumina sequencing. Both products stimulated gut barrier and immune function with increases in TEER, NF-KB, IL-10, and IL-6. Ingredients with different structures selectively modulate the microbiota of a specific donor leading to differential changes at metabolic level. The extent of this effect is donor specific and is linked to a final specific modulation of the host's immune system.

  6. More than just noise: Inter-individual differences in fear acquisition, extinction and return of fear in humans - Biological, experiential, temperamental factors, and methodological pitfalls.

    Science.gov (United States)

    Lonsdorf, Tina B; Merz, Christian J

    2017-09-01

    Why do only some individuals develop pathological anxiety following adverse events? Fear acquisition, extinction and return of fear paradigms serve as experimental learning models for the development, treatment and relapse of anxiety. Individual differences in experimental performance were however mostly regarded as 'noise' by researchers interested in basic associative learning principles. Our work for the first time presents a comprehensive literature overview and methodological discussion on inter-individual differences in fear acquisition, extinction and return of fear. We tell a story from noise that steadily develops into a meaningful tune and converges to a model of mechanisms contributing to individual risk/resilience with respect to fear and anxiety-related behavior. Furthermore, in light of the present 'replicability crisis' we identify methodological pitfalls and provide suggestions for study design and analyses tailored to individual difference research in fear conditioning. Ultimately, synergistic transdisciplinary and collaborative efforts hold promise to not only improve our mechanistic understanding but can also be expected to contribute to the development of specifically tailored ('individualized') intervention and targeted prevention programs in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. High Inter-Individual Diversity of Point Mutations, Insertions, and Deletions in Human Influenza Virus Nucleoprotein-Specific Memory B Cells.

    Directory of Open Access Journals (Sweden)

    Sven Reiche

    Full Text Available The diversity of virus-specific antibodies and of B cells among different individuals is unknown. Using single-cell cloning of antibody genes, we generated recombinant human monoclonal antibodies from influenza nucleoprotein-specific memory B cells in four adult humans with and without preceding influenza vaccination. We examined the diversity of the antibody repertoires and found that NP-specific B cells used numerous immunoglobulin genes. The heavy chains (HCs originated from 26 and the kappa light chains (LCs from 19 different germ line genes. Matching HC and LC chains gave rise to 43 genetically distinct antibodies that bound influenza NP. The median lengths of the CDR3 of the HC, kappa and lambda LC were 14, 9 and 11 amino acids, respectively. We identified changes at 13.6% of the amino acid positions in the V gene of the antibody heavy chain, at 8.4% in the kappa and at 10.6 % in the lambda V gene. We identified somatic insertions or deletions in 8.1% of the variable genes. We also found several small groups of clonal relatives that were highly diversified. Our findings demonstrate broadly diverse memory B cell repertoires for the influenza nucleoprotein. We found extensive variation within individuals with a high number of point mutations, insertions, and deletions, and extensive clonal diversification. Thus, structurally conserved proteins can elicit broadly diverse and highly mutated B-cell responses.

  8. Weight-correction of carbon dioxide diffusion coefficient (DCO2 ) reduces its inter-individual variability and improves its correlation with blood carbon dioxide levels in neonates receiving high-frequency oscillatory ventilation.

    Science.gov (United States)

    Belteki, Gusztav; Lin, Benjamin; Morley, Colin J

    2017-10-01

    Carbon-dioxide elimination during high-frequency oscillatory ventilation (HFOV) is thought to be proportional to the carbon dioxide diffusion coefficient (DCO 2 ) which is calculated as frequency x (tidal volume) 2 . DCO 2 can be used to as an indicator of CO 2 elimination but values obtained in different patients cannot be directly compared. To analyze the relationship between DCO 2 , the weight-corrected DCO 2 (DCO 2 corr) and blood gas PCO 2 values obtained from infants receiving HFOV. DCO 2 data were obtained from 14 infants at 1/s sampling rate and the mean DCO 2 was determined over 10 min periods preceding the time of the blood gas. DCO 2 corr was calculated by dividing the DCO 2 by the square of the body weight in kg. Weight-correction significantly reduced the inter-individual variability of DCO 2 . When data from all the babies were combined, standard DCO 2 showed no correlation with PCO 2 but DCO 2 corr showed a weak but statistically significant inverse correlation. The correlation was better when the endotracheal leak was correlation between the HFOV tidal volume (VThf) and the PCO 2 . In any baby, DCO 2 corr >50 mL 2 /sec/kg 2 or VThf > 2.5 mL/kg was rarely needed to avoid hypercapnia. Weight-correction of DCO 2 values improved its comparability between patients. Weight-corrected DCO 2 correlated better with PCO 2 than uncorrected DCO 2 but the correlation was weak. © 2017 Wiley Periodicals, Inc.

  9. The variability problem of normal human walking

    DEFF Research Database (Denmark)

    Simonsen, Erik B; Alkjær, Tine

    2012-01-01

    Previous investigations have suggested considerable inter-individual variability in the time course pattern of net joint moments during normal human walking, although the limited sample sizes precluded statistical analyses. The purpose of the present study was to obtain joint moment patterns from...... a group of normal subjects and to test whether or not the expected differences would prove to be statistically significant. Fifteen healthy male subjects were recorded on video while they walked across two force platforms. Ten kinematic and kinetic parameters were selected and input to a statistical...... cluster analysis to determine whether or not the 15 subjects could be divided into different 'families' (clusters) of walking strategy. The net joint moments showed a variability corroborating earlier reports. The cluster analysis showed that the 15 subjects could be grouped into two clusters of 5 and 10...

  10. Sources of variability in human communicative skills

    Directory of Open Access Journals (Sweden)

    Inge eVolman

    2012-11-01

    Full Text Available When established communication systems cannot be used, people rapidly create novel systems to modify the mental state of another agent according to their intentions. However, there are dramatic inter-individual differences in the implementation of this human competence for communicative innovation. Here we characterize psychological sources of inter-individual variability in the ability to build a shared communication system from scratch. We consider two potential sources of variability in communicative skills. Cognitive traits of two individuals could independently influence their joint ability to establish a communication system. Another possibility is that the overlap between those individual traits influences the communicative performance of a dyad. We assess these possibilities by quantifying the relationship between cognitive traits and behavior of communicating dyads. Cognitive traits were assessed with psychometric scores quantifying cooperative attitudes and fluid intelligence. Competence for implementing successful communicative innovations was assessed by using a non-verbal communicative task. Individual capacities influence communicative success when communicative innovations are generated. Dyadic similarities and individual traits modulate the type of communicative strategy chosen. The ability to establish novel communicative actions was influenced by a combination of the communicator’s ability to understand intentions and the addressee’s ability to recognize patterns. Communicative pairs with comparable systemizing abilities or behavioral inhibition were more likely to explore the search space of possible communicative strategies by systematically adding new communicative behaviors to those already available. No individual psychometric measure seemed predominantly responsible for communicative success. These findings support the notion that the human ability for fast communicative innovations represents a special type of

  11. Sources of variability in human communicative skills

    NARCIS (Netherlands)

    Volman, Inge; Noordzij, Matthijs Leendert; Toni, Ivan

    2012-01-01

    When established communication systems cannot be used, people rapidly create novel systems to modify the mental state of another agent according to their intentions. However, there are dramatic inter-individual differences in the implementation of this human competence for communicative innovation.

  12. Inter-individual variation of selenium in maternal plasma, cord plasma and placenta

    International Nuclear Information System (INIS)

    Lee, Anne M.; Huel, Guy; Godin, Jean; Hellier, Georgette; Sahuquillo, Josiane; Moreau, Thierry; Blot, Phillipe

    1994-01-01

    Selenium (Se) in high doses has been known to cause injury to the fetus and newborn. The major difficulty in assessing the effects of selenium on human reproduction stems from the need for a suitable means of estimating maternal and fetal exposure. The present investigation, therefore, examines the respective reliability of maternal plasma, cord plasma and placenta as epidemiological indicators as well as inter-individual variation of this trace element. An unselected population of 128 pregnancies was studied. Obstetrical characteristics were noted. Selenium concentrations were determined for maternal plasma, cord plasma, and placental tissue by fluorometric analysis. Maternal plasma selenium concentrations (Se-Bm) were significantly greater than fetal concentrations (Se-Bc). Placental selenium (Se-Pl) levels were four times that of fetal levels. Variability of Se-Bc is best explained by placental concentrations. Maternal weight and ethnic origin are significantly correlated with Se-Bc. Female newborn have higher selenium levels than male newborn. The present study demonstrates the significance of the placenta as an indicator of fetal selenium exposure

  13. Inter-individual differences in audio-motor learning of piano melodies and white matter fiber tract architecture

    NARCIS (Netherlands)

    Engel, Annerose; Hijmans, Brenda S.; Cerliani, Leonardo; Bangert, Marc; Nanetti, Luca; Keller, Peter E.; Keysers, Christian

    Humans vary substantially in their ability to learn new motor skills. Here, we examined inter-individual differences in learning to play the piano, with the goal of identifying relations to structural properties of white matter fiber tracts relevant to audio-motor learning. Non-musicians (n = 18)

  14. Inter-Individual Differences in Neurobehavioural Impairment following Sleep Restriction Are Associated with Circadian Rhythm Phase

    Science.gov (United States)

    Sletten, Tracey L.; Segal, Ahuva Y.; Flynn-Evans, Erin E.; Lockley, Steven W.; Rajaratnam, Shantha M. W.

    2015-01-01

    Although sleep restriction is associated with decrements in daytime alertness and neurobehavioural performance, there are considerable inter-individual differences in the degree of impairment. This study examined the effects of short-term sleep restriction on neurobehavioural performance and sleepiness, and the associations between individual differences in impairments and circadian rhythm phase. Healthy adults (n = 43; 22 M) aged 22.5 ± 3.1 (mean ± SD) years maintained a regular 8:16 h sleep:wake routine for at least three weeks prior to laboratory admission. Sleep opportunity was restricted to 5 hours time-in-bed at home the night before admission and 3 hours time-in-bed in the laboratory, aligned by wake time. Hourly saliva samples were collected from 5.5 h before until 5 h after the pre-laboratory scheduled bedtime to assess dim light melatonin onset (DLMO) as a marker of circadian phase. Participants completed a 10-min auditory Psychomotor Vigilance Task (PVT), the Karolinska Sleepiness Scale (KSS) and had slow eye movements (SEM) measured by electrooculography two hours after waking. We observed substantial inter-individual variability in neurobehavioural performance, particularly in the number of PVT lapses. Increased PVT lapses (r = -0.468, p circadian phase. When the difference between DLMO and sleep onset was less than 2 hours, individuals were significantly more likely to have at least three attentional lapses the following morning. This study demonstrates that the phase of an individual’s circadian system is an important variable in predicting the degree of neurobehavioural performance impairment in the hours after waking following sleep restriction, and confirms that other factors influencing performance decrements require further investigation. PMID:26043207

  15. Inter-Individual Differences in Neurobehavioural Impairment following Sleep Restriction Are Associated with Circadian Rhythm Phase.

    Directory of Open Access Journals (Sweden)

    Tracey L Sletten

    Full Text Available Although sleep restriction is associated with decrements in daytime alertness and neurobehavioural performance, there are considerable inter-individual differences in the degree of impairment. This study examined the effects of short-term sleep restriction on neurobehavioural performance and sleepiness, and the associations between individual differences in impairments and circadian rhythm phase. Healthy adults (n = 43; 22 M aged 22.5 ± 3.1 (mean ± SD years maintained a regular 8:16 h sleep:wake routine for at least three weeks prior to laboratory admission. Sleep opportunity was restricted to 5 hours time-in-bed at home the night before admission and 3 hours time-in-bed in the laboratory, aligned by wake time. Hourly saliva samples were collected from 5.5 h before until 5 h after the pre-laboratory scheduled bedtime to assess dim light melatonin onset (DLMO as a marker of circadian phase. Participants completed a 10-min auditory Psychomotor Vigilance Task (PVT, the Karolinska Sleepiness Scale (KSS and had slow eye movements (SEM measured by electrooculography two hours after waking. We observed substantial inter-individual variability in neurobehavioural performance, particularly in the number of PVT lapses. Increased PVT lapses (r = -0.468, p < 0.01, greater sleepiness (r = 0.510, p < 0.0001, and more slow eye movements (r = 0.375, p = 0.022 were significantly associated with later DLMO, consistent with participants waking at an earlier circadian phase. When the difference between DLMO and sleep onset was less than 2 hours, individuals were significantly more likely to have at least three attentional lapses the following morning. This study demonstrates that the phase of an individual's circadian system is an important variable in predicting the degree of neurobehavioural performance impairment in the hours after waking following sleep restriction, and confirms that other factors influencing performance decrements require further

  16. 2 D gel based analysis of biological variability of the human plasma proteome

    DEFF Research Database (Denmark)

    Rentsch, Maria Louise; Jessen, Flemming

    individuals and within an individual changes will also happen over time (e.g. after meal intake). Thus, the aim of the present study was to examine the inter-individual variability of plasma protein levels in humans after meal intake. Five subjects consumed three single meals in a randomised order separated...... by one-week interval. Blood samples were drawn before the meal intake and five times during 24 hours for proteome analysis. Plasma was fractionated by use of IgY-12 spin column depleting the 12 highly abundant proteins and further processed for two-dimensional gel electrophoresis. The plasma proteome...

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

    Science.gov (United States)

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

  18. Variability in human body size

    Science.gov (United States)

    Annis, J. F.

    1978-01-01

    The range of variability found among homogeneous groups is described and illustrated. Those trends that show significantly marked differences between sexes and among a number of racial/ethnic groups are also presented. Causes of human-body size variability discussed include genetic endowment, aging, nutrition, protective garments, and occupation. The information is presented to aid design engineers of space flight hardware and equipment.

  19. Genes: Interactions with Language on Three Levels—Inter-Individual Variation, Historical Correlations and Genetic Biasing

    Science.gov (United States)

    Dediu, Dan

    The complex inter-relationships between genetics and linguistics encompass all four scales highlighted by the contributions to this book and, together with cultural transmission, the genetics of language holds the promise to offer a unitary understanding of this fascinating phenomenon. There are inter-individual differences in genetic makeup which contribute to the obvious fact that we are not identical in the way we understand and use language and, by studying them, we will be able to both better treat and enhance ourselves. There are correlations between the genetic configuration of human groups and their languages, reflecting the historical processes shaping them, and there also seem to exist genes which can influence some characteristics of language, biasing it towards or against certain states by altering the way language is transmitted across generations. Besides the joys of pure knowledge, the understanding of these three aspects of genetics relevant to language will potentially trigger advances in medicine, linguistics, psychology or the understanding of our own past and, last but not least, a profound change in the way we regard one of the emblems of being human: our capacity for language.

  20. Time-on-task decrement in vigilance is modulated by inter-individual vulnerability to homeostatic sleep pressure manipulation

    Directory of Open Access Journals (Sweden)

    Micheline eMaire

    2014-03-01

    Full Text Available Under sleep loss, vigilance is reduced and attentional failures emerge progressively. It becomes difficult to maintain stable performance over time, leading to growing performance variability (i.e. state instability in an individual and among subjects. Task duration plays a major role in the maintenance of stable vigilance levels, such that the longer the task, the more likely state instability will be observed. Vulnerability to sleep-loss-dependent performance decrements is highly individual and is also modulated by a polymorphism in the human clock gene PERIOD3 (PER3. By combining two different protocols, we manipulated sleep-wake history by once extending wakefulness for 40 h (high sleep pressure condition and once by imposing a short sleep-wake cycle by alternating 160 min of wakefulness and 80 min naps (low sleep pressure condition in a within-subject design. We observed that homozygous carriers of the long repeat allele of PER3 (PER35/5 experienced a greater time-on-task dependent performance decrement (i.e., a steeper increase in the number of lapses in the Psychomotor Vigilance Task compared to the carriers of the short repeat allele (PER34/4. These genotype-dependent effects disappeared under low sleep pressure conditions, and neither motivation, nor perceived effort accounted for these differences. Our data thus suggest that greater sleep-loss related attentional vulnerability based on the PER3 polymorphism is mirrored by a greater state instability under extended wakefulness in the short compared to the long allele carriers. Our results undermine the importance of time-on-task related aspects when investigating inter-individual differences in sleep loss-induced behavioural vulnerability.

  1. Stay tuned: Inter-individual neural synchronization during mutual gaze and joint attention

    Directory of Open Access Journals (Sweden)

    Daisuke N Saito

    2010-11-01

    Full Text Available Eye contact provides a communicative link between humans, prompting joint attention. As spontaneous brain activity may have an important role in coordination of neuronal processing within the brain, their inter-subject synchronization may occur during eye contact. To test this, we conducted simultaneous functional MRI in pairs of adults. Eye contact was maintained at baseline while the subjects engaged in real-time gaze exchange in a joint attention task. Averted gaze activated the bilateral occipital pole extending to the right posterior superior temporal sulcus, the dorso-medial prefrontal cortex, and bilateral inferior frontal gyrus. Following a partner’s gaze towards an object activated the left intraparietal sulcus. After all task-related effects were modeled out, inter-individual correlation analysis of residual time-courses was performed. Paired subjects showed more prominent correlations than non-paired subjects in the right inferior frontal gyrus, suggesting that this region is involved in sharing intention during eye contact that provides the context for joint attention.

  2. Inter-individual differences in sleep response to shift work in novice police officers - A prospective study.

    Science.gov (United States)

    Lammers-van der Holst, Heidi M; Van Dongen, Hans P A; Drosopoulos, Spyridon; Kerkhof, Gerard A

    2016-01-01

    The aim of this longitudinal study on novice police officers was to investigate inter-individual differences in sleep response to shift work, and to identify potential baseline predictors thereof. A total of 42 subjects were assessed at baseline, prior to commencing shift work. They were re-assessed during three follow-up sessions within the first 2 years of shift work exposure after approximately 4, 12, and 20 months of rotating shift work. Wrist actigraphy and sleep logs were used to investigate nocturnal sleep at baseline and daytime sleep after night shifts during the follow-up sessions. Actigraphically estimated total sleep time and subjective sleep quality were analyzed as outcome variables, using mixed-effects analysis of variance. Systematic inter-individual differences were observed in the overall response of these outcome variables to shift work. In this sample, flexibility of sleeping habits and gender were found to be predictors of daytime total sleep time in the first 2 years of shift work exposure. Flexibility of sleeping habits and subjective quality of nighttime sleep prior to shift work were found to be predictors of subjective quality of daytime sleep. These results suggest that it may be possible to detect and even predict sleep deficiencies in response to shift work early on, which could be a basis for the development of individualized interventions to improve shift work tolerance.

  3. Functional analysis of inter-individual transcriptome differential expression in pig longissimus muscle

    NARCIS (Netherlands)

    Zhao, S.; Hulsegge, B.; Harders, F.L.; Bossers, R.; Keuning, E.; Hoekman, A.J.W.; Hoving-Bolink, A.H.; Pas, te M.F.W.

    2013-01-01

    Selection of pigs for increased meat production or improved meat quality changes muscle mass and muscle composition. This will be related to transcriptome expression profile changes in muscle tissue, generating inter-individual differences. This study investigated the differentially expressed genes

  4. Inter-individual variability in optimal current direction for transcranial magnetic stimulation of the motor cortex

    DEFF Research Database (Denmark)

    Balslev, Daniela; Braet, Wouter; McAllister, Craig

    2007-01-01

    , stimulation in the majority of participants was most effective when the first current pulse flowed towards postero-lateral in the brain. However, in four participants, the optimal coil orientation deviated from this pattern. A principal component analysis using all eight orientations suggests that in our...

  5. Intergrating in Vitro and In Silico Approaches to Assess Inter-individual Toxicokinetic Variability

    Science.gov (United States)

    This educational talk provided an introduction to what is currently known to contribute to differences in how various populations and life stages metabolize chemicals to which they are exposed. These differences will impact how different populations may be affected following chem...

  6. Fear or greed? Oxytocin regulates inter-individual conflict by enhancing fear in men.

    Science.gov (United States)

    Zheng, Huimin; Kendrick, Keith M; Yu, Rongjun

    2016-09-01

    People may choose non-cooperation in social dilemmas either out of fear (if others choose to defect) or out of greed (when others choose to cooperate). Previous studies have shown that exogenous oxytocin motivates a "tend and defend" pattern in inter-group conflict in which oxytocin stimulates in-group cooperation and out-group defense. Using a double-blind placebo-controlled design combined with a modified Prisoner's dilemma game (PDG), we examined the effect of oxytocin on social motivations in inter-individual conflict in men. Results showed that compared with the placebo group, oxytocin-exposed participants were less cooperative in general. Specifically, oxytocin amplified the effect of fear on defection but did not influence the effect of greed. Another non-social control study confirmed participants' decisions were sensitive to social factors. Our findings suggest that even when social group conflict is removed, oxytocin promotes distrust of strangers in "me and you" inter-individual conflict by elevating social fear in men. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Inter individual variations of the fish skin microbiota: host genetics basis of mutualism?

    Directory of Open Access Journals (Sweden)

    Sébastien Boutin

    Full Text Available The commensal microbiota of fish skin is suspected to provide a protection against opportunist infections. The skin of fish harbors a complex and diverse microbiota that closely interacts with the surrounding water microbial communities. Up to now there is no clear evidence as to whether the host regulates the recruitment of environmental bacteria to build a specific skin microbiota. To address this question, we detected Quantitative Trait Loci (QTL associated with the abundance of specific skin microbiota bacterial strains in brook charr (Salvelinus fontinalis, combining 16S RNA tagged-amplicon 454 pyrosequencing with genetic linkage analysis. Skin microbiota analysis revealed high inter-individual variation among 86 F2 fish progeny based upon the relative abundance of bacterial operational taxonomic units (OTUs. Out of those OTUs, the pathogenic strain Flavobacterium psychrophilum and the non-pathogenic strain Methylobacterium rhodesianum explained the majority of inter-individual distances. Furthermore, a strong negative correlation was found between Flavobacterium and Methylobacterium, suggesting a mutually competitive relationship. Finally, after considering a total of 266 markers, genetic linkage analysis highlighted three major QTL associated with the abundance of Lysobacter, Rheinheimera and Methylobacterium. All these three genera are known for their beneficial antibacterial activity. Overall, our results provide evidence that host genotype may regulate the abundance of specific genera among their surface microbiota. They also indicate that Lysobacter, Rheinheimera and Methylobacterium are potentially important genera in providing protection against pathogens.

  8. Inter individual variations of the fish skin microbiota: host genetics basis of mutualism?

    Science.gov (United States)

    Boutin, Sébastien; Sauvage, Christopher; Bernatchez, Louis; Audet, Céline; Derome, Nicolas

    2014-01-01

    The commensal microbiota of fish skin is suspected to provide a protection against opportunist infections. The skin of fish harbors a complex and diverse microbiota that closely interacts with the surrounding water microbial communities. Up to now there is no clear evidence as to whether the host regulates the recruitment of environmental bacteria to build a specific skin microbiota. To address this question, we detected Quantitative Trait Loci (QTL) associated with the abundance of specific skin microbiota bacterial strains in brook charr (Salvelinus fontinalis), combining 16S RNA tagged-amplicon 454 pyrosequencing with genetic linkage analysis. Skin microbiota analysis revealed high inter-individual variation among 86 F2 fish progeny based upon the relative abundance of bacterial operational taxonomic units (OTUs). Out of those OTUs, the pathogenic strain Flavobacterium psychrophilum and the non-pathogenic strain Methylobacterium rhodesianum explained the majority of inter-individual distances. Furthermore, a strong negative correlation was found between Flavobacterium and Methylobacterium, suggesting a mutually competitive relationship. Finally, after considering a total of 266 markers, genetic linkage analysis highlighted three major QTL associated with the abundance of Lysobacter, Rheinheimera and Methylobacterium. All these three genera are known for their beneficial antibacterial activity. Overall, our results provide evidence that host genotype may regulate the abundance of specific genera among their surface microbiota. They also indicate that Lysobacter, Rheinheimera and Methylobacterium are potentially important genera in providing protection against pathogens.

  9. Event-related potential indices of inter-individual and age differences in visual attention capacity

    DEFF Research Database (Denmark)

    Wiegand, Iris; Töllner, Thomas; Dyrholm, Mads

    The ‘Theory of Visual Attention’ quantifies an individual’s capacity of attentional resources in parameters visual processing speed C and vSTM storage capacity K. By combining TVA-based assessment with neurophysiology, we showed that distinct ERP components index inter-individual differences......-related changes in attentional capacities, these ERP markers of individual differences in processing speed and storage capacity were validated in an older group. Furthermore, additional components were related to performance exclusively in older inidividuals: Anterior N1 amplitudes were reduced for slower older...... that reorganization of attentional brain networks, including age-specific decline and compensation mechanisms, determines older individuals’ attention capacity. Furthermore, we show that the distinctiveness of the two functions, as defined in TVA, is preserved (or even increased) in older age....

  10. Inter-individual susceptibility to environmental toxicants-A current assessment

    International Nuclear Information System (INIS)

    Nebert, Daniel W.

    2005-01-01

    Virtually all diseases have an environmental component. The two most important factors affecting your unique risk of an environmental disease (toxicity or cancer) are (a) your exposure to the environmental agent and (b) your genes. Epidemiologists have found ways to calculate inter-individual risk-if the exposure to environmental agents is sufficiently high and can be documented (e.g., years of cigarette smoking, taking prescribed drugs, drinking alcohol, or exposure to radon or other radioactive material, etc.). If the dose of environmental agents is lower and more ambiguous (e.g., exposure to chemicals on the job, herbicides sprayed on a golf course, outdoor or indoor air pollution, endocrine disruptors in cans of food, living near a toxic waste dump site, etc.), however, calculations of inter-individual risk become much more difficult. Highly accurate DNA tests for genetic susceptibility to toxicity and cancer have been sought in order to identify individuals at increased risk; this type of research represents the leading edge of phenotype-genotype association studies and is the major goal of most public health and preventive medicine programs. The task, however, has turned out to be far more challenging than anticipated. The major stumbling block has been the difficulty in determining an unequivocal phenotype or an unequivocal genotype. We were quite optimistic 5-10 years ago that this would be easy, but now we are beginning to appreciate how difficult it is to determine an unequivocal phenotype or genotype with certainty. For many reasons set forth in this overview, it appears that DNA testing alone, to predict and prevent environmental disease on an individual basis, may be virtually impossible with current knowledge and technologies and will require novel insights before major practical applications will evolve

  11. Glomerular epithelial foot processes in normal man and rats. Distribution of true width and its intra- and inter-individual variation.

    Science.gov (United States)

    Gundersen, H J; Seefeldt, T; Osterby, R

    1980-01-01

    The width of individual glomerular epithelial foot processes appears very different on electron micrographs. A method for obtainining distributions of the true width of foot processes from that of their apparent width on electron micrographs has been developed based on geometric probability theory pertaining to a specific geometric model. Analyses of foot process width in humans and rats show a remarkable interindividual invariance implying rigid control and therefore great biological significance of foot process width or a derivative thereof. The very low inter-individual variation of the true width, shown in the present paper, makes it possible to demonstrate slight changes in rather small groups of patients or experimental animals.

  12. Inter-individual variation in nucleotide excision repair pathway is modulated by non-synonymous polymorphisms in ERCC4 and MBD4 genes

    Energy Technology Data Exchange (ETDEWEB)

    Allione, Alessandra, E-mail: alessandra.allione@hugef-torino.org [Human Genetics Foundation (HuGeF), Via Nizza 52, 10126 Turin (Italy); Guarrera, Simonetta; Russo, Alessia [Human Genetics Foundation (HuGeF), Via Nizza 52, 10126 Turin (Italy); Ricceri, Fulvio [Human Genetics Foundation (HuGeF), Via Nizza 52, 10126 Turin (Italy); Department of Medical Sciences, University of Turin, Via Santena 19, 10126 Turin (Italy); Purohit, Rituraj [Human Genetics Foundation (HuGeF), Via Nizza 52, 10126 Turin (Italy); Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu (India); Pagnani, Andrea; Rosa, Fabio; Polidoro, Silvia; Voglino, Floriana [Human Genetics Foundation (HuGeF), Via Nizza 52, 10126 Turin (Italy); Matullo, Giuseppe [Human Genetics Foundation (HuGeF), Via Nizza 52, 10126 Turin (Italy); Department of Medical Sciences, University of Turin, Via Santena 19, 10126 Turin (Italy)

    2013-11-15

    Highlights: • We reported a large inter-individual variability of NER capacity. • ERCC4 rs1800124 and MBD4 rs10342 nsSNP variants were associated with DNA repair capacity. • DNA–protein interaction analyses showed alteration of binding for ERCC4 and MBD4 variants. • A new possible cross-talk between NER and BER pathways has been reported. - Abstract: Inter-individual differences in DNA repair capacity (DRC) may lead to genome instability and, consequently, modulate individual cancer risk. Among the different DNA repair pathways, nucleotide excision repair (NER) is one of the most versatile, as it can eliminate a wide range of helix-distorting DNA lesions caused by ultraviolet light irradiation and chemical mutagens. We performed a genotype–phenotype correlation study in 122 healthy subjects in order to assess if any associations exist between phenotypic profiles of NER and DNA repair gene single nucleotide polymorphisms (SNPs). Individuals were genotyped for 768 SNPs with a custom Illumina Golden Gate Assay, and peripheral blood mononuclear cells (PBMCs) of the same subjects were tested for a NER comet assay to measure DRC after challenging cells by benzo(a)pyrene diolepoxide (BPDE). We observed a large inter-individual variability of NER capacity, with women showing a statistically significant lower DRC (mean ± SD: 6.68 ± 4.76; p = 0.004) than men (mean ± SD: 8.89 ± 5.20). Moreover, DRC was significantly lower in individuals carrying a variant allele for the ERCC4 rs1800124 non-synonymous SNP (nsSNP) (p = 0.006) and significantly higher in subjects with the variant allele of MBD4 rs2005618 SNP (p = 0.008), in linkage disequilibrium (r{sup 2} = 0.908) with rs10342 nsSNP. Traditional in silico docking approaches on protein–DNA and protein–protein interaction showed that Gly875 variant in ERCC4 (rs1800124) decreases the DNA–protein interaction and that Ser273 and Thr273 variants in MBD4 (rs10342) indicate complete loss of protein

  13. Inter-individual differences in decision-making, flexible and goal-directed behaviors: novel insights within the prefronto-striatal networks.

    Science.gov (United States)

    Fitoussi, Aurélie; Renault, Prisca; Le Moine, Catherine; Coutureau, Etienne; Cador, Martine; Dellu-Hagedorn, Françoise

    2018-03-01

    Inflexible behavior is a hallmark of several decision-making-related disorders such as ADHD and addiction. As in humans, a subset of healthy rats makes poor decisions and prefers immediate larger rewards despite suffering large losses in a rat gambling task (RGT). They also display a combination of traits reminiscent of addiction, notably inflexible behavior and perseverative responses. The goal of the present work was twofold: (1) to elucidate if behavioral inflexibility of poor decision-makers could be related to a lower quality of goal-directed behavior (action-outcome associations); (2) to uncover the neural basis of inter-individual differences in goal-directed behavior. We specifically assessed inter-individual differences in decision-making in the RGT, flexibility in the RGT-reversed version and goal-directed behavior in a contingency degradation test, i.e., response adaptation when dissociating reward delivery from the animal's action. The contributions of the medial prefrontal cortex and the dorsal striatum to action-outcome associations were assessed using Zif268 immunodetection. Inflexible behavior was related to a lower sensitivity to contingency degradation in all poor decision-makers and only in a few good decision-makers. This poorer sensitivity was associated with a lower immunoreactivity in prelimbic and infralimbic cortices and a higher one in the dorsomedial and dorsolateral striatum. These findings suggest that an imbalanced prefronto-striatal activity could underlie inaccurate goal representation in changing environments and may promote maladaptive habit formation among poor decision-makers. These data strengthen our previous work identifying biomarkers of vulnerability to develop psychiatric disorders and demonstrate the relevance of inter-individual differences to model maladaptive behaviors.

  14. Otolith signals contribute to inter-individual differences in the perception of gravity-centered space.

    Science.gov (United States)

    Cian, C; Barraud, P A; Paillard, A C; Hidot, S; Denise, P; Ventre-Dominey, J

    2014-03-01

    The aim of the present study was to investigate (1) the relative contribution of the egocentric reference as well as body orientation perception to visual horizon percept during tilt or during increased gravito-inertial acceleration (GiA, hypergravity environment) conditions and (2) the role of vestibular signals in the inter-individual differences observed in these perceptual modalities. Perceptual estimates analysis showed that backward tilt induced (1) an elevation of the visual horizon, (2) an elevation of the egocentric estimation (visual straight ahead) and (3) an overestimation of body tilt. The increase in the magnitude of GiA induced (1) a lowering of the apparent horizon, (2) a lowering of the straight ahead and (3) a perception of backward tilt. Overall, visual horizon percept can be expressed as the combination of body orientation perception and egocentric estimation. When assessing otolith reactivity using off-vertical axis rotation (OVAR), only visual egocentric estimation was significantly correlated with horizontal OVAR performance. On the one hand, we found a correlation between a low modulation amplitude of the otolith responses and straight ahead accuracy when the head axis was tilted relative to gravity. On the other hand, the bias of otolith responses was significantly correlated with straight ahead accuracy when subjects were submitted to an increase in the GiA. Thus, straight ahead sense would be dependent to some extent to otolith function. These results are discussed in terms of the contribution of otolith inputs in the overall multimodal integration subtending spatial constancy.

  15. Flexibility of Physiological Traits Underlying Inter-Individual Growth Differences in Intertidal and Subtidal Mussels Mytilusgalloprovincialis.

    Directory of Open Access Journals (Sweden)

    María José Fernández-Reiriz

    Full Text Available Mussel seed (Mytilusgalloprovincialis gathered from the intertidal and subtidal environments of a Galician embayment (NW, Spain were maintained in the laboratory during five months to select fast (F and slow (S growing mussels. The physiological basis underlying inter-individual growth variations were compared for F and S mussels from both origins. Fast growing seemed to be a consequence of greater energy intake (20% higher clearance and ingestion rate and higher food absorption rate coupled with low metabolic costs. The enhanced energy absorption (around 65% higher resulted in 3 times higher Scope for Growth in F mussels (20.5±4.9 J h(-1 than S individuals (7.3±1.1 J h(-1. The higher clearance rate of F mussels appears to be linked with larger gill filtration surface compared to S mussels. Intertidal mussels showed higher food acquisition and absorption per mg of organic weight (i.e. mass-specific standardization than subtidal mussels under the optimal feeding conditions of the laboratory. However, the enhanced feeding and digestive rates were not enough to compensate for the initial differences in tissue weight between mussels of similar shell length collected from the intertidal and subtidal environments. At the end of the experiment, subtidal individuals had higher gill efficiency, which probably lead to higher total feeding and absorption rates relative to intertidal individuals.

  16. Quantitative label-free proteomics for discovery of biomarkers in cerebrospinal fluid: assessment of technical and inter-individual variation.

    Directory of Open Access Journals (Sweden)

    Richard J Perrin

    Full Text Available Biomarkers are required for pre-symptomatic diagnosis, treatment, and monitoring of neurodegenerative diseases such as Alzheimer's disease. Cerebrospinal fluid (CSF is a favored source because its proteome reflects the composition of the brain. Ideal biomarkers have low technical and inter-individual variability (subject variance among control subjects to minimize overlaps between clinical groups. This study evaluates a process of multi-affinity fractionation (MAF and quantitative label-free liquid chromatography tandem mass spectrometry (LC-MS/MS for CSF biomarker discovery by (1 identifying reparable sources of technical variability, (2 assessing subject variance and residual technical variability for numerous CSF proteins, and (3 testing its ability to segregate samples on the basis of desired biomarker characteristics.Fourteen aliquots of pooled CSF and two aliquots from six cognitively normal individuals were randomized, enriched for low-abundance proteins by MAF, digested endoproteolytically, randomized again, and analyzed by nano-LC-MS. Nano-LC-MS data were time and m/z aligned across samples for relative peptide quantification. Among 11,433 aligned charge groups, 1360 relatively abundant ones were annotated by MS2, yielding 823 unique peptides. Analyses, including Pearson correlations of annotated LC-MS ion chromatograms, performed for all pairwise sample comparisons, identified several sources of technical variability: i incomplete MAF and keratins; ii globally- or segmentally-decreased ion current in isolated LC-MS analyses; and iii oxidized methionine-containing peptides. Exclusion of these sources yielded 609 peptides representing 81 proteins. Most of these proteins showed very low coefficients of variation (CV<5% whether they were quantified from the mean of all or only the 2 most-abundant peptides. Unsupervised clustering, using only 24 proteins selected for high subject variance, yielded perfect segregation of pooled and

  17. Sexual dimorphism and inter-individual variation in the rove beetle, Creophilus maxillosus L. (Col: Staphylinidae

    Directory of Open Access Journals (Sweden)

    Mohammad Shahbaz

    2017-12-01

    Full Text Available Sexual selection is expected to drive phenotypic differences between conspecific male and females, a widespread phenomenon known as sexual dimorphism. At the same time, individuals may exhibit some degree of intra-sexual variation. We examined the sexual dimorphism and inter-individual variation in different body parts of Creophilus maxillosus L. (Col: Staphylinidae, a cosmopolitan rove beetle commonly found on carrion. Male C. maxillosus had significantly wider head and pronotum, longer mandibles, and more distant eyes than females. The head width was positively correlated to mandible length, which may reflect stronger adductor muscles and higher bite force in larger individuals. The allometry of traits can be examined by plotting the logarithms of that specific trait against the logarithm of body size and determining the slope (b of the regression line. Isometry occurs when b=1, i.e. the ratio of given traits to body size remains constant across individuals. Negative allometry occurs when b1, so that larger individuals have disproportionately larger traits. A positive allometry was found in head width (b=1.32, mandible length (b=2.28, and ocular distance (b=1.49 of males. Our results show that, particularly head size, mandible length and ocular distance are probably under sexual selection in males, while traits such as eye size are isometric to body size. The potential role of these traits in male-male combat as well as female attractiveness has been frequently documented in different insect taxa. The striking similarities in patterns of sexual dimorphism among independently evolved insects indicate that common evolutionary force(s are probably at work.

  18. Analysis of Inter-Individual Bacterial Variation in Gut of Cicada Meimuna mongolica (Hemiptera: Cicadidae).

    Science.gov (United States)

    Zhou, Wenting; Nan, Xiaoning; Zheng, Zhou; Wei, Cong; He, Hong

    2015-01-01

    Intestinal bacterial community plays a crucial role in the nutrition, development, survival, and reproduction of insects. When compared with other insects with piercing-sucking mouthparts, the habitats of cicada nymphs and adults are totally different. However, little is known about the differences in the gut bacterial communities in the nymphs and adults within any cicada species. The diversity of bacteria in the gut of nymphs and adults of both genders of Meimuna mongolica (Distant) was studied using the denaturing gradient gel electrophoresis (DGGE) method. Few inter-individual variations among gut microbiota were observed, suggesting that M. mongolica typically harbors a limited and consistent suite of bacterial species. Bacteria in the genera Pseudomonas and Enterobacter were the predominant components of the gut microflora of M. mongolica at all life stages. Bacteria of Pantoea, Streptococcus, and Uruburuella were also widespread in the cicada samples but at relatively lower concentrations. The relative stability and similarity of the PCR-DGGE patterns indicate that all individuals of this cicada species harbor a characteristic bacterial community which is independent from developmental stages and genders. Related endosymbionts that could be harbored in bacteromes of cicadas were not detected in any gut samples, which could be related to the cicada species and the distribution of these endosymbionts in the cicada cavity, or due to some of the possible limitations of PCR-DGGE community profiling. It is worthwhile to further address if related cicada endosymbiont clades distribute in the alimentary canals and other internal organs through diagnostic PCR using group-specific primer sets. © The Author 2015. Published by Oxford University Press on behalf of the Entomological Society of America.

  19. Inter-individual differences in how presentation modality affects verbal learning performance in children aged 5 to 16

    NARCIS (Netherlands)

    Meijs, Celeste; Hurks, Petra P M; Wassenberg, Renske; Feron, Frans J M; Jolles, Jelle

    2016-01-01

    This study examines inter-individual differences in how presentation modality affects verbal learning performance. Children aged 5 to 16 performed a verbal learning test within one of three presentation modalities: pictorial, auditory, or textual. The results indicated that a beneficial effect of

  20. Seasonal Trends and Inter-Individual Heterogeneity: A multi-species record of Mg, Sr, Ba, & Mn in Planktic Foraminifera from the Modern Cariaco Basin

    Science.gov (United States)

    Davis, C. V.; Thunell, R.; Astor, Y. M.

    2017-12-01

    The trace element to calcium ratios (TE/Ca) of planktic foraminifera shells are a valuable tool for paleoceanographic reconstructions, and represent a combination of environmental, ecological and biological signals. We present here a three-year record (2010-2013) of TE/Ca (Mg, Sr, Ba, Mn) from four species of foraminifera (Orbulina universa, Globigerina ruber, Globigerinella siphonifera, and Globorotalia menardii) collected by plankton tow in the modern Cariaco basin. Each tow is paired with in situ measurements of water column properties, allowing a direct comparison between shell geochemistry and calcification environment. A combination of Laser Ablation and solution ICP-MS analyses are used to document seasonality, primarily due to the alternating influence of wind-driven coastal upwelling and riverine inputs, in shell TE/Ca. Individual shell data further allows for the quantification of trace element heterogeneity among individual shells within single tows. All TE/Ca ratios vary temporally and show inter-individual variability within single tows. The spread in TE/Ca differs between element and species, with Mg/Ca ratios being the most variable. Despite this, Mg/Ca still tracks temperature changes in G. ruber, O. universa, and G. menardii, with G. ruber most closely reproducing sea surface temperature. Some species show chamber-to-chamber differences in trace element ratios, with G. ruber Mg/Ca and Ba/Ca decreasing in younger chambers (but not other elements) and Mg/Ca, Mn/Ca and Ba/Ca decreasing in younger chambers in G. siphonifera. We find the original Mn/Ca to be variable both temporally and between species, with G. menardii in some samples having extremely high ratios (100 μmol/mol). Assessing seasonal trends and environmental drivers of TE/Ca variability and quantifying the extent of inter-individual heterogeneity in these species will inform the use of their shells as geochemical proxies.

  1. Measurement invariance within and between individuals: a distinct problem in testing the equivalence of intra- and inter-individual model structures.

    Science.gov (United States)

    Adolf, Janne; Schuurman, Noémi K; Borkenau, Peter; Borsboom, Denny; Dolan, Conor V

    2014-01-01

    We address the question of equivalence between modeling results obtained on intra-individual and inter-individual levels of psychometric analysis. Our focus is on the concept of measurement invariance and the role it may play in this context. We discuss this in general against the background of the latent variable paradigm, complemented by an operational demonstration in terms of a linear state-space model, i.e., a time series model with latent variables. Implemented in a multiple-occasion and multiple-subject setting, the model simultaneously accounts for intra-individual and inter-individual differences. We consider the conditions-in terms of invariance constraints-under which modeling results are generalizable (a) over time within subjects, (b) over subjects within occasions, and (c) over time and subjects simultaneously thus implying an equivalence-relationship between both dimensions. Since we distinguish the measurement model from the structural model governing relations between the latent variables of interest, we decompose the invariance constraints into those that involve structural parameters and those that involve measurement parameters and relate to measurement invariance. Within the resulting taxonomy of models, we show that, under the condition of measurement invariance over time and subjects, there exists a form of structural equivalence between levels of analysis that is distinct from full structural equivalence, i.e., ergodicity. We demonstrate how measurement invariance between and within subjects can be tested in the context of high-frequency repeated measures in personality research. Finally, we relate problems of measurement variance to problems of non-ergodicity as currently discussed and approached in the literature.

  2. Finite element analysis to investigate variability of MR elastography in the human thigh.

    Science.gov (United States)

    Hollis, L; Barnhill, E; Perrins, M; Kennedy, P; Conlisk, N; Brown, C; Hoskins, P R; Pankaj, P; Roberts, N

    2017-11-01

    To develop finite element analysis (FEA) of magnetic resonance elastography (MRE) in the human thigh and investigate inter-individual variability of measurement of muscle mechanical properties. Segmentation was performed on MRI datasets of the human thigh from 5 individuals and FEA models consisting of 12 muscles and surrounding tissue created. The same material properties were applied to each tissue type and a previously developed transient FEA method of simulating MRE using Abaqus was performed at 4 frequencies. Synthetic noise was applied to the simulated data at various levels before inversion was performed using the Elastography Software Pipeline. Maps of material properties were created and visually assessed to determine key features. The coefficient of variation (CoV) was used to assess the variability of measurements in each individual muscle and in the groups of muscles across the subjects. Mean measurements for the set of muscles were ranked in size order and compared with the expected ranking. At noise levels of 2% the CoV in measurements of |G * | ranged from 5.3 to 21.9% and from 7.1 to 36.1% for measurements of ϕ in the individual muscles. A positive correlation (R 2 value 0.80) was attained when the expected and measured |G * | ranking were compared, whilst a negative correlation (R 2 value 0.43) was found for ϕ. Created elastograms demonstrated good definition of muscle structure and were robust to noise. Variability of measurements across the 5 subjects was dramatically lower for |G * | than it was for ϕ. This large variability in ϕ measurements was attributed to artefacts. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. A standardized approach to study human variability in isometric thermogenesis during low-intensity physical activity

    Directory of Open Access Journals (Sweden)

    Delphine eSarafian

    2013-07-01

    Full Text Available Limitations of current methods: The assessment of human variability in various compartments of daily energy expenditure (EE under standardized conditions is well defined at rest (as basal metabolic rate and thermic effect of feeding, and currently under validation for assessing the energy cost of low-intensity dynamic work. However, because physical activities of daily life consist of a combination of both dynamic and isometric work, there is also a need to develop standardized tests for assessing human variability in the energy cost of low-intensity isometric work.Experimental objectives: Development of an approach to study human variability in isometric thermogenesis by incorporating a protocol of intermittent leg press exercise of varying low-intensity isometric loads with measurements of EE by indirect calorimetry. Results: EE was measured in the seated position with the subject at rest or while intermittently pressing both legs against a press-platform at 5 low-intensity isometric loads (+5, +10, + 15, +20 and +25 kg force, each consisting of a succession of 8 cycles of press (30 s and rest (30 s. EE, integrated over each 8-min period of the intermittent leg press exercise, was found to increase linearly across the 5 isometric loads with a correlation coefficient (r > 0.9 for each individual. The slope of this EE-Load relationship, which provides the energy cost of this standardized isometric exercise expressed per kg force applied intermittently (30 s in every min, was found to show good repeatability when assessed in subjects who repeated the same experimental protocol on 3 separate days: its low intra-individual coefficient of variation (CV of ~ 10% contrasted with its much higher inter-individual CV of 35%; the latter being mass-independent but partly explained by height. Conclusion: This standardized approach to study isometric thermogenesis opens up a new avenue for research in EE phenotyping and metabolic predisposition to obesity

  4. Intra- and Inter-Individual Differences in Adolescent Depressive Mood: the Role of Relationships with Parents and Friends

    OpenAIRE

    Zhang, S. (Shiyu); Baams, L. (Laura); van de Bongardt, D. (Daphne); Dubas, J.S. (Judith Semon)

    2017-01-01

    textabstractUtilizing four waves of data from 1126 secondary school Dutch adolescents (Mage = 13.95 at the first wave; 53% boys), the current study examined the interplay between parent-adolescent and friend-adolescent relationship quality (satisfaction and conflict) in relation to adolescents’ depressive mood. Using multilevel analyses, the interacting effects of parent/friend relationship quality on depressive mood were tested at both the intra- and inter-individual level. Analyses at the i...

  5. Intra- and Inter-Individual Differences in Adolescent Depressive Mood: the Role of Relationships with Parents and Friends.

    Science.gov (United States)

    Zhang, Shiyu; Baams, Laura; van de Bongardt, Daphne; Dubas, Judith Semon

    2018-05-01

    Utilizing four waves of data from 1126 secondary school Dutch adolescents (Mage = 13.95 at the first wave; 53% boys), the current study examined the interplay between parent-adolescent and friend-adolescent relationship quality (satisfaction and conflict) in relation to adolescents' depressive mood. Using multilevel analyses, the interacting effects of parent/friend relationship quality on depressive mood were tested at both the intra- and inter-individual level. Analyses at the intra-individual level investigated whether individual depressive mood fluctuated along with changes in their social relationships regardless of one's general level of depressive mood; and analyses at the inter-individual level examined whether the average differences in depressive mood between adolescents were associated with different qualities of social relationships. We interpreted the patterns of interactions between parent and friend relationships using four theoretical models: the reinforcement, toxic friends, compensation, and additive model. The results demonstrate the covariation of parent- and friend- relationship quality with adolescents' depressive mood, and highlight that parent and peer effects are not independent from each other-affirming the compensation and additive models at the intra-individual and the reinforcement and additive models at the inter-individual level. The findings highlight the robustness of the protective effects of parent and peer support and the deleterious effects of conflictual relationships for adolescent mental health. The results have implications for both the theoretical and practical design of (preventive) interventions aimed at decreasing adolescents' depressive mood.

  6. Sequence determinants of human microsatellite variability

    Directory of Open Access Journals (Sweden)

    Jakobsson Mattias

    2009-12-01

    Full Text Available Abstract Background Microsatellite loci are frequently used in genomic studies of DNA sequence repeats and in population studies of genetic variability. To investigate the effect of sequence properties of microsatellites on their level of variability we have analyzed genotypes at 627 microsatellite loci in 1,048 worldwide individuals from the HGDP-CEPH cell line panel together with the DNA sequences of these microsatellites in the human RefSeq database. Results Calibrating PCR fragment lengths in individual genotypes by using the RefSeq sequence enabled us to infer repeat number in the HGDP-CEPH dataset and to calculate the mean number of repeats (as opposed to the mean PCR fragment length, under the assumption that differences in PCR fragment length reflect differences in the numbers of repeats in the embedded repeat sequences. We find the mean and maximum numbers of repeats across individuals to be positively correlated with heterozygosity. The size and composition of the repeat unit of a microsatellite are also important factors in predicting heterozygosity, with tetra-nucleotide repeat units high in G/C content leading to higher heterozygosity. Finally, we find that microsatellites containing more separate sets of repeated motifs generally have higher heterozygosity. Conclusions These results suggest that sequence properties of microsatellites have a significant impact in determining the features of human microsatellite variability.

  7. Inter-individual Variability in CAF: A Case Study of Two Individuals and Two Pairs’ Written Productions

    Directory of Open Access Journals (Sweden)

    Mahboobeh Saadat

    2017-06-01

    Full Text Available The present study tracked the development of general measures of complexity, accuracy and fluency (CAF, and specific measures of accuracy and complexity in the writings of two EFL learners writing individually, and those of two pairs of EFL learners writing in pairs within the framework of dynamic systems theory. The individuals and the pairs were similarly asked to do 7 tasks during a semester. The learners’ developmental pathways as well as the differences between individuals and pairs in terms of general and specific measures of CAF across the 7 tasks were depicted through graphs. Results indicated that the performance of learners in each of the measures was non-linear during the semester. Moreover, concerning general measures of CAF, learners writing individually outperformed in terms of fluency and complexity features. However, no clear distinction emerged in terms of general accuracy measures of their writings. Furthermore, development of general and specific accuracy measures in the writings was consistent. However, although it was found that the learners writing individually outperformed in terms of general measure of complexity, this developmental pattern was not evident in their performance in terms of specific complexity measures.

  8. Inter-individual differences in trait negative affect moderate cortisol's effects on memory formation: preliminary findings from two studies.

    Science.gov (United States)

    Abercrombie, Heather C; Wirth, Michelle M; Hoks, Roxanne M

    2012-05-01

    Acute emotional arousal moderates the effects of cortisol on memory. However, it is currently unknown how stable inter-individual differences (i.e., traits) moderate cortisol's effects on memory. In two studies using within-subjects designs - 31 healthy males in Study 1 and 42 healthy subjects (22 female) in Study 2 - we measured trait negative affect (NA) and presented emotional and neutral pictures. In Study 1, we manipulated endogenous cortisol levels using a speech stressor following encoding. In Study 2, using a randomized placebo-controlled design, we pharmacologically manipulated cortisol levels prior to encoding (0.1mg/kg hydrocortisone vs. saline infused over 30min). Free recall for pictures was subsequently assessed. Trait NA repeatedly moderated the relationship between cortisol and memory formation. Findings suggested the speculative conclusion that the direction of effects may vary by sex. In males, cortisol was related to memory facilitation in subjects with lower Trait NA. Conversely, females with higher Trait NA showed greater cortisol-related increases in memory. Trait NA may be a stable inter-individual difference predicting neurocognitive effects of cortisol during stressors. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Intra- and inter-individual variation in flight direction in a migratory butterfly co-vary with individual mobility.

    Science.gov (United States)

    Larranaga, Nicolas; Baguette, Michel; Calvez, Olivier; Trochet, Audrey; Ducatez, Simon; Legrand, Delphine

    2013-08-15

    Flight direction is a major component of an animal's migratory success. However, few studies have focused on variation in flight direction both between and within individuals, which is likely to be correlated with other traits implied in migration processes. We report patterns of intra- and inter-individual variation in flight direction in the large white butterfly Pieris brassicae. The presence of inter-individual variation in flight direction for individuals tested in the same conditions suggests that this trait is inherited in P. brassicae and we propose that a rapid loss of migratory skills may exist in the absence of selection for migration. The magnitude of intra-individual variation was negatively correlated to two surrogates of the potential for migration: mobility and wing length. Highly mobile and longed-winged individuals within the same family were found to fly in similar directions, whereas less mobile and short-winged individuals displayed divergent flight direction compared with the average direction of their kin. There was also a negative correlation between the variance to the mean flight direction of a family and its average mobility, but no correlation with wing length. We discuss these issues in terms of the evolution of traits potentially implied in both migration and dispersal in P. brassicae.

  10. Accounting for human variability and sensitivity in setting standards for electromagnetic fields.

    Science.gov (United States)

    Bailey, William H; Erdreich, Linda S

    2007-06-01

    Biological sensitivity and variability are key issues for risk assessment and standard setting. Variability encompasses general inter-individual variations in population responses, while sensitivity relates to unusual or extreme responses based on genetic, congenital, medical, or environmental conditions. For risk assessment and standard setting, these factors affect estimates of thresholds for effects and dose-response relationships and inform efforts to protect the more sensitive members of the population, not just the typical or average person. While issues of variability and sensitivity can be addressed by experimental and clinical studies of electromagnetic fields, investigators have paid little attention to these important issues. This paper provides examples that illustrate how default assumptions regarding variability can be incorporated into estimates of 60-Hz magnetic field exposures with no risk of cardiac stimulation and how population thresholds and variability of peripheral nerve stimulation responses at 60-Hz can be estimated from studies of pulsed gradient magnetic fields in magnetic resonance imaging studies. In the setting of standards for radiofrequency exposures, the International Commission for Non-Ionizing Radiation Protection uses inter-individual differences in thermal sensitivity as one of the considerations in the development of "safety factors." However, neither the range of sensitivity nor the sufficiency or excess of the 10-fold and the additional 5-fold safety factors have been assessed quantitatively. Data on the range of responses between median and sensitive individuals regarding heat stress and cognitive function should be evaluated to inform a reassessment of these safety factors and to identify data gaps.

  11. Translating inter-individual genetic variation to biological function in complex phenotypes

    DEFF Research Database (Denmark)

    Yadav, Rachita

    , Chapter 1 provides an introduction to various methodologies utilised in this thesis work. Subsequently, chapters 2, 3 and 4 in the second section, address finding causal variations in childhood asthma. Chapter 2 focuses on a genome wide association study (GWAS) performed on asthma exacerbation case cohort....... This study reports a new susceptibility locus within the gene CDHR3 for exacerbation phenotype of childhood asthma. Chapter 3 of the thesis presents a pilot study, which aims at designing a candidate gene panel for childhood asthma to identify the causal variants from known asthma genes. Chapter 4 describes...... in adipose depots, which is a major tissue implicated in obesity. Chapter 5 sheds light on different mechanisms that result in the replacement of metabolism efficient brown fat with the storage-type white fat in large mammals (including human) especially within the first few months following birth...

  12. Linking inter-individual differences in the conflict adaptation effect to spontaneous brain activity.

    Science.gov (United States)

    Wang, Ting; Chen, Zhencai; Zhao, Guang; Hitchman, Glenn; Liu, Congcong; Zhao, Xiaoyue; Liu, Yijun; Chen, Antao

    2014-04-15

    Conflict adaptation has been widely researched in normal and clinical populations. There are large individual differences in conflict adaptation, and it has been linked to the schizotypal trait. However, no study to date has examined how individual differences in spontaneous brain activity are related to behavioral conflict adaptation (performance). Resting-state functional magnetic resonance imaging (RS-fMRI) is a promising tool to investigate this issue. The present study evaluated the regional homogeneity (ReHo) of RS-fMRI signals in order to explore the neural basis of individual differences in conflict adaptation across two independent samples comprising a total of 67 normal subjects. A partial correlation analysis was carried out to examine the relationship between ReHo and behavioral conflict adaptation, while controlling for reaction time, standard deviation and flanker interference effects. This analysis was conducted on 39 subjects' data (sample 1); the results showed significant positive correlations in the left dorsolateral prefrontal cortex (DLPFC) and left ventrolateral prefrontal cortex. We then conducted a test-validation procedure on the remaining 28 subjects' data (sample 2) to examine the reliability of the results. Regions of interest were defined based on the correlation results. Regression analysis showed that variability in ReHo values in the DLPFC accounted for 48% of the individual differences in the conflict adaptation effect in sample 2. The present findings provide further support for the importance of the DLPFC in the conflict adaptation process. More importantly, we demonstrated that ReHo of RS-fMRI signals in the DLPFC can predict behavioral performance in conflict adaptation, which provides potential biomarkers for the early detection of cognitive control deterioration. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Tree phyllosphere bacterial communities: exploring the magnitude of intra- and inter-individual variation among host species

    Directory of Open Access Journals (Sweden)

    Isabelle Laforest-Lapointe

    2016-08-01

    Full Text Available Background The diversity and composition of the microbial community of tree leaves (the phyllosphere varies among trees and host species and along spatial, temporal, and environmental gradients. Phyllosphere community variation within the canopy of an individual tree exists but the importance of this variation relative to among-tree and among-species variation is poorly understood. Sampling techniques employed for phyllosphere studies include picking leaves from one canopy location to mixing randomly selected leaves from throughout the canopy. In this context, our goal was to characterize the relative importance of intra-individual variation in phyllosphere communities across multiple species, and compare this variation to inter-individual and interspecific variation of phyllosphere epiphytic bacterial communities in a natural temperate forest in Quebec, Canada. Methods We targeted five dominant temperate forest tree species including angiosperms and gymnosperms: Acer saccharum, Acer rubrum, Betula papyrifera, Abies balsamea and Picea glauca. For one randomly selected tree of each species, we sampled microbial communities at six distinct canopy locations: bottom-canopy (1–2 m height, the four cardinal points of mid-canopy (2–4 m height, and the top-canopy (4–6 m height. We also collected bottom-canopy leaves from five additional trees from each species. Results Based on an analysis of bacterial community structure measured via Illumina sequencing of the bacterial 16S gene, we demonstrate that 65% of the intra-individual variation in leaf bacterial community structure could be attributed to the effect of inter-individual and inter-specific differences while the effect of canopy location was not significant. In comparison, host species identity explains 47% of inter-individual and inter-specific variation in leaf bacterial community structure followed by individual identity (32% and canopy location (6%. Discussion Our results suggest that

  14. Consistent inter-individual differences in common marmosets (Callithrix jacchus) in Boldness-Shyness, Stress-Activity, and Exploration-Avoidance.

    Science.gov (United States)

    Šlipogor, Vedrana; Gunhold-de Oliveira, Tina; Tadić, Zoran; Massen, Jorg J M; Bugnyar, Thomas

    2016-09-01

    The study of animal personality, defined as consistent inter-individual differences in correlated behavioral traits stable throughout time and/or contexts, has recently become one of the fastest growing areas in animal biology, with study species ranging from insects to non-human primates. The latter have, however, only occasionally been tested with standardized experiments. Instead their personality has usually been assessed using questionnaires. Therefore, this study aimed to test 21 common marmosets (Callithrix jacchus) living in three family groups, in five different experiments, and their corresponding controls. We found that behavioral differences between our animals were not only consistent over time, but also across different contexts. Moreover, the consistent behaviors formed a construct of four major non-social personality components: Boldness-Shyness in Foraging, Boldness-Shyness in Predation, Stress-Activity, and Exploration-Avoidance. We found no sex or age differences in these components, but our results did reveal differences in Exploration-Avoidance between the three family groups. As social environment can have a large influence on behavior of individuals, our results may suggest group-level similarity in personality (i.e., "group personality") in common marmosets, a species living in highly cohesive social groups. Am. J. Primatol. 78:961-973, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. La estructura social de la industria biotecnológica en Francia: un estudio de las relaciones inter-organizacionales a nivel inter-individual.

    Directory of Open Access Journals (Sweden)

    Piña-Stranger, Alvaro

    2010-06-01

    Full Text Available Various authors have shown the importance of collaborative relationships for inter-organizational performance, the mode of governance or the trajectory of biotechnology companies. Most of these works analyze the exclusive contractual agreements between companies and their main relationships among individuals. We show that this purely economic approach presents a major limitation: the nature of contractual relationships does not explore in detail how players cooperate. We propose to extend the study of these inter-organizational social relations, seen through the resource exchange in inter-individual. An empirical study on the leaders of the biotechnology industry in the area of human health in France has allowed us to map their relationships and resources they exchange them. Our results confirm the existence of a system of exchange dense and multiple. It presents a hierarchical distribution of various types of resources, where the centre is different from the periphery relations denser, more numerous and more reciprocal. However, comparative analysis of different networks reveals that the relationships of the board are highly centralized, while those of friendship following a more even distribution. We suggest that this phenomenon is part of a compensation mechanism to less central actors to maintain inter-organizational relationships. Finally, two standards of the cooperation process, revealed by the relational behaviour of actors, have been discovered. We suggest that they reflect in part the difficult process of adjustment that must cross a science project out of the realm of academic research and develop in a private structure: the biotech company.

  16. Using GAMM to examine inter-individual heterogeneity in thermal performance curves for Natrix natrix indicates bet hedging strategy by mothers.

    Science.gov (United States)

    Vickers, Mathew J; Aubret, Fabien; Coulon, Aurélie

    2017-01-01

    The thermal performance curve (TPC) illustrates the dependence on body- and therefore environmental- temperature of many fitness-related aspects of ectotherm ecology and biology including foraging, growth, predator avoidance, and reproduction. The typical thermal performance curve model is linear in its parameters despite the well-known, strong, non-linearity of the response of performance to temperature. In addition, it is usual to consider a single model based on few individuals as descriptive of a species-level response to temperature. To overcome these issues, we used generalized additive mixed modeling (GAMM) to estimate thermal performance curves for 73 individual hatchling Natrix natrix grass snakes from seven clutches, taking advantage of the structure of GAMM to demonstrate that almost 16% of the deviance in thermal performance curves is attributed to inter-individual variation, while only 1.3% is attributable to variation amongst clutches. GAMM allows precise estimation of curve characteristics, which we used to test hypotheses on tradeoffs thought to constrain the thermal performance curve: hotter is better, the specialist-generalist trade off, and resource allocation/acquisition. We observed a negative relationship between maximum performance and performance breadth, indicating a specialist-generalist tradeoff, and a positive relationship between thermal optimum and maximum performance, suggesting "hotter is better". There was a significant difference among matrilines in the relationship between Area Under the Curve and maximum performance - relationship that is an indicator of evenness in acquisition or allocation of resources. As we used unfed hatchlings, the observed matriline effect indicates divergent breeding strategies among mothers, with some mothers provisioning eggs unequally resulting in some offspring being better than others, while other mothers provisioned the eggs more evenly, resulting in even performance throughout the clutch. This

  17. Variables influencing the frictional behaviour of in vivo human skin

    NARCIS (Netherlands)

    Veijgen, N.K.; Masen, Marc Arthur; van der Heide, Emile

    2013-01-01

    In the past decades, skin friction research has focused on determining which variables are important to affect the frictional behaviour of in vivo human skin. Until now, there is still limited knowledge on these variables. This study has used a large dataset to identify the effect of variables on

  18. Variables influencing the frictional behaviour of in vivo human skin

    NARCIS (Netherlands)

    Veijgen, N.K.; Masen, M.A.; Heide, E. van der

    2013-01-01

    In the past decades, skin friction research has focused on determining which variables are important to affect the frictional behaviour of in vivo human skin. Until now, there is still limited knowledge on these variables.This study has used a large dataset to identify the effect of variables on the

  19. Extinction-Induced Variability in Human Behavior

    Science.gov (United States)

    Kinloch, Jennifer M.; Foster, T. Mary; McEwan, James S. A.

    2009-01-01

    Participants earned points by pressing a computer space bar (Experiment 1) or forming rectangles on the screen with the mouse (Experiment 2) under differential-reinforcement-of-low-rate schedules, followed by extinction. Variability in interresponse time (the contingent dimension) increased during extinction, as for Morgan and Lee (1996);…

  20. Antigenic and genetic variability of human metapneumoviruses

    NARCIS (Netherlands)

    S. Herfst (Sander); L. Sprong; P.A. Cane; E. Forleo-Neto; A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron); R.L. de Swart (Rik); B.G. van den Hoogen (Bernadette)

    2004-01-01

    textabstractHuman metapneumovirus (HMPV) is a member of the subfamily Pneumovirinae within the family Paramyxo- viridae. Other members of this subfamily, respiratory syncytial virus and avian pneumovirus, can be divided into subgroups on the basis of genetic or antigenic differences or both. For

  1. Variability in human metabolism of arsenic

    International Nuclear Information System (INIS)

    Loffredo, C.A.; Aposhian, H.V.; Cebrian, M.E.; Yamauchi, Hiroshi; Silbergeld, E.K.

    2003-01-01

    Estimating the nature and extent of human cancer risks due to arsenic (As) in drinking water is currently of great concern, since millions of persons worldwide are exposed to arsenic, primarily through natural enrichment of drinking water drawn from deep wells. Humans metabolize and eliminate As through oxidative methylation and subsequent urinary excretion. While there is debate as to the role of methylation in activation/detoxification, variations in arsenic metabolism may affect individual risks of toxicity and carcinogenesis. Using data from three populations, from Mexico, China, and Chile, we have analyzed the distribution in urine of total arsenic and arsenic species (inorganic arsenic (InAs), monomethyl arsenic (MMA), and dimethyl arsenic (DMA). Data were analyzed in terms of the concentration of each species and by evaluating MMA:DMA and (MMA+DMA):InAs ratios. In all persons most urinary As was present as DMA. Male:female differences were discernible in both high- and low-exposure groups from all three populations, but the gender differences varied by populations. The data also indicated bimodal distributions in the ratios of DMA to InAs and to MMA. While the gene or genes responsible for arsenic methylation are still unknown, the results of our studies among the ethnic groups in this study are consistent with the presence of functional genetic polymorphisms in arsenic methylation leading to measurable differences in toxicity. This analysis highlights the need for continuing research on the health effects of As in humans using molecular epidemiologic methods

  2. Inter-individual variation among young children growing up in a bidialectal community : the acquisition of dialect and standard Dutch vocabulary.

    NARCIS (Netherlands)

    Francot, Ryanne; van den Heuij, Kirsten; Blom, Elma; Heeringa, W.J.; Cornips, L.M.E.A.; Buchstaller, Isabella; Siebenhaar, Beat

    2017-01-01

    This study focuses on the relationship between dialect use and the acquisition of standard Dutch vocabulary by young children in the Dutch province of Limburg. The results of a newly-developed dialect expressive vocabulary task show extensive inter-individual variation that does not support a

  3. Preanalytical Variables Affecting the Integrity of Human Biospecimens in Biobanking

    DEFF Research Database (Denmark)

    Ellervik, Christina; Vaught, Jim

    2015-01-01

    BACKGROUND: Most errors in a clinical chemistry laboratory are due to preanalytical errors. Preanalytical variability of biospecimens can have significant effects on downstream analyses, and controlling such variables is therefore fundamental for the future use of biospecimens in personalized...... medicine for diagnostic or prognostic purposes. CONTENT: The focus of this review is to examine the preanalytical variables that affect human biospecimen integrity in biobanking, with a special focus on blood, saliva, and urine. Cost efficiency is discussed in relation to these issues. SUMMARY: The quality...

  4. Analysis of the in vivo confocal Raman spectral variability in human skin

    Science.gov (United States)

    Mogilevych, Borys; dos Santos, Laurita; Rangel, Joao L.; Grancianinov, Karen J. S.; Sousa, Mariane P.; Martin, Airton A.

    2015-06-01

    Biochemical composition of the skin changes in each layer and, therefore, the skin spectral profile vary with the depth. In this work, in vivo Confocal Raman spectroscopy studies were performed at different skin regions and depth profile (from the surface down to 10 μm) of the stratum corneum, to verify the variability and reproducibility of the intra- and interindividual Raman data. The Raman spectra were collected from seven healthy female study participants using a confocal Raman system from Rivers Diagnostic, with 785 nm excitation line and a CCD detector. Measurements were performed in the volar forearm region, at three different points at different depth, with the step of 2 μm. For each depth point, three spectra were acquired. Data analysis included the descriptive statistics (mean, standard deviation and residual) and Pearson's correlation coefficient calculation. Our results show that inter-individual variability is higher than intraindividual variability, and variability inside the SC is higher than on the skin surface. In all these cases we obtained r values, higher than 0.94, which correspond to high correlation between Raman spectra. It reinforces the possibility of the data reproducibility and direct comparison of in vivo results obtained with different study participants of the same age group and phototype.

  5. A meta analysis of the variability in firm performance attributable to human resource variables

    Directory of Open Access Journals (Sweden)

    Lloyd Kapondoro

    2015-01-01

    Full Text Available The contribution of Human Resource Management (HRM practices to organisation-wide performance is a critical aspect of the Human Resource (HR value proposition. The purpose of the study was to describe the strength of HRM practices and systems in influencing overall organisational performance. While research has concluded that there is a significant positive relationship between HRM practices or systems and an organisation’s market performance, the strength of this relationship has relatively not received much analysis in order to explain the degree to which HRM practices explain variance in firm performance. The study undertook a meta-analysis of published researches in international journals. The study established that HRM variables accounted for an average of 31% of the variability in firm performance. Cohen’s f2 calculated for this study as a meta effect size calculation yielded an average of 0.681, implying that HRM variables account for 68% of variability in firm performance. A one sample Kolmogorov-Smirnov test showed that the distribution of R2 is not normal. A major managerial implication of this study is that effective HRM practices have a significant business case. The study provides, quantitatively, the average variability in firm success that HRM accounts for.

  6. Human activity and climate variability project: annual report 2001

    International Nuclear Information System (INIS)

    Harle, K.J.; Heijnis, H.; Henderson-Sellers, A.; Sharmeen, S.; Zahorowski, W.

    2002-01-01

    Knowledge of the state of the Australian environment, including natural climate variability, prior to colonial settlement is vital if we are to define and understand the impact of over two hundred years of post-industrial human activity on our landscape. ANSTO, in conjunction with university partners, is leading a major research effort to provide natural archives of human activity and climate variability over the last 500 years in Australia, utilising a variety of techniques, including lead-210 and radiocarbon dating and analyses of proxy indicators (such as microfossils) as well as direct evidence (such as trace elements) of human activity and climate variability. The other major project objectives were to contribute to the understanding of the impact of human induced and natural aerosols in the East Asian region on climate through analysis and sourcing of fine particles and characterisation of air samples using radon concentrations and to contribute to the improvement of land surface parameterisation schemes and investigate the potential to use stable isotopes to improve global climate models and thus improve our understanding of future climate

  7. Human Responses to Climate Variability: The Case of South Africa

    Science.gov (United States)

    Oppenheimer, M.; Licker, R.; Mastrorillo, M.; Bohra-Mishra, P.; Estes, L. D.; Cai, R.

    2014-12-01

    Climate variability has been associated with a range of societal and individual outcomes including migration, violent conflict, changes in labor productivity, and health impacts. Some of these may be direct responses to changes in mean temperature or precipitation or extreme events, such as displacement of human populations by tropical cyclones. Others may be mediated by a variety of biological, social, or ecological factors such as migration in response to long-term changes in crops yields. Research is beginning to elucidate and distinguish the many channels through which climate variability may influence human behavior (ranging from the individual to the collective, societal level) in order to better understand how to improve resilience in the face of current variability as well as future climate change. Using a variety of data sets from South Africa, we show how climate variability has influenced internal (within country) migration in recent history. We focus on South Africa as it is a country with high levels of internal migration and dramatic temperature and precipitation changes projected for the 21st century. High poverty rates and significant levels of rain-fed, smallholder agriculture leave large portions of South Africa's population base vulnerable to future climate change. In this study, we utilize two complementary statistical models - one micro-level model, driven by individual and household level survey data, and one macro-level model, driven by national census statistics. In both models, we consider the effect of climate on migration both directly (with gridded climate reanalysis data) and indirectly (with agricultural production statistics). With our historical analyses of climate variability, we gain insights into how the migration decisions of South Africans may be influenced by future climate change. We also offer perspective on the utility of micro and macro level approaches in the study of climate change and human migration.

  8. Variables associated with human papillomavirus (HPV) vaccine acceptance by men.

    Science.gov (United States)

    Ferris, Daron G; Waller, Jennifer L; Miller, Jeremiah; Patel, Pratik; Price, George A; Jackson, Lanier; Wilson, Courtesia

    2009-01-01

    To determine correlates of human papillomavirus (HPV) vaccine acceptance for men. A convenience sample of men aged 18 to 45 years read a one-page information sheet about HPV and the HPV vaccine, then completed a 29-item questionnaire. chi(2) tests were used to determine whether differences in demographic, sexual, and vaccine-related variables existed between levels of wanting the HPV vaccine. Positive correlates of HPV vaccine acceptance included higher education (P acceptance of the HPV vaccine by men.

  9. The macro-structural variability of the human neocortex.

    Science.gov (United States)

    Kruggel, Frithjof

    2018-05-15

    The human neocortex shows a considerable individual structural variability. While primary gyri and sulci are found in all normally developed brains and bear clear-cut gross structural descriptions, secondary structures are highly variable and not present in all brains. The blend of common and individual structures poses challenges when comparing structural and functional results from quantitative neuroimaging studies across individuals, and sets limits on the precision of location information much above the spatial resolution of current neuroimaging methods. This work aimed at quantifying structural variability on the neocortex, and at assessing the spatial relationship between regions common to all brains and their individual structural variants. Based on structural MRI data provided as the "900 Subjects Release" of the Human Connectome Project, a data-driven analytic approach was employed here from which the definition of seven cortical "communities" emerged. Apparently, these communities comprise common regions of structural features, while the individual variability is confined within a community. Similarities between the community structure and the state of the brain development at gestation week 32 lead suggest that communities are segregated early. Subdividing the neocortex into communities is suggested as anatomically more meaningful than the traditional lobar structure. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Inter-individual and intragenomic variations in the ITS region of Clonorchis sinensis (Trematoda: Opisthorchiidae) from Russia and Vietnam.

    Science.gov (United States)

    Tatonova, Yulia V; Chelomina, Galina N; Nguyen, Hung Manh

    2017-11-01

    Here we examined the intraspecific genetic variability of Clonorchis sinensis from Russia and Vietnam using nuclear DNA sequences (the 5.8S gene and two internal transcribed spacers of the ribosomal cluster). Despite the low level of variability in the ITS1 region, this marker has revealed some features of C. sinensis across multiple geographic regions. The genetic diversity levels for the Russian and Vietnamese populations were similar (0.1 and 0.09%, respectively) but were significantly lower than the C. sinensis from China (0.31%). About half of the sequences of the Chinese (53%) and Korean (47%) populations and about a tenth of the Vietnamese (12%) and Russian (8%) sequences included a 5bp insertion. No sequences with nucleotide substitutions both upstream and downstream of the 5bp insertion were found within the whole data set. The population of northern China had both sequence variants (with substitutions either upstream or downstream of the insertion), while only one of these variants was presented at the other localities. The Vietnamese population had a higher frequency of intragenomic polymorphism than the Russian population (69% vs. 46% and 23% vs. 3% at the 114bp and 339bp positions, respectively). These data are discussed in connection with parasite origin and adaptation, and also its invasive capacity and drug-resistance. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Psychobiological Factors Affecting Cortisol Variability in Human-Dog Dyads.

    Directory of Open Access Journals (Sweden)

    Iris Schöberl

    Full Text Available Stress responses within dyads are modulated by interactions such as mutual emotional support and conflict. We investigated dyadic psychobiological factors influencing intra-individual cortisol variability in response to different challenging situations by testing 132 owners and their dogs in a laboratory setting. Salivary cortisol was measured and questionnaires were used to assess owner and dog personality as well as owners' social attitudes towards the dog and towards other humans. We calculated the individual coefficient of variance of cortisol (iCV = sd/mean*100 over the different test situations as a parameter representing individual variability of cortisol concentration. We hypothesized that high cortisol variability indicates efficient and adaptive coping and a balanced individual and dyadic social performance. Female owners of male dogs had lower iCV than all other owner gender-dog sex combinations (F = 14.194, p<0.001, whereas owner Agreeableness (NEO-FFI scaled positively with owner iCV (F = 4.981, p = 0.028. Dogs of owners high in Neuroticism (NEO-FFI and of owners who were insecure-ambivalently attached to their dogs (FERT, had low iCV (F = 4.290, p = 0.041 and F = 5.948, p = 0.016, as had dogs of owners with human-directed separation anxiety (RSQ or dogs of owners with a strong desire of independence (RSQ (F = 7.661, p = 0.007 and F = 9.192, p = 0.003. We suggest that both owner and dog social characteristics influence dyadic cortisol variability, with the human partner being more influential than the dog. Our results support systemic approaches (i.e. considering the social context in science and in counselling.

  12. General anesthesia suppresses normal heart rate variability in humans

    Science.gov (United States)

    Matchett, Gerald; Wood, Philip

    2014-06-01

    The human heart normally exhibits robust beat-to-beat heart rate variability (HRV). The loss of this variability is associated with pathology, including disease states such as congestive heart failure (CHF). The effect of general anesthesia on intrinsic HRV is unknown. In this prospective, observational study we enrolled 100 human subjects having elective major surgical procedures under general anesthesia. We recorded continuous heart rate data via continuous electrocardiogram before, during, and after anesthesia, and we assessed HRV of the R-R intervals. We assessed HRV using several common metrics including Detrended Fluctuation Analysis (DFA), Multifractal Analysis, and Multiscale Entropy Analysis. Each of these analyses was done in each of the four clinical phases for each study subject over the course of 24 h: Before anesthesia, during anesthesia, early recovery, and late recovery. On average, we observed a loss of variability on the aforementioned metrics that appeared to correspond to the state of general anesthesia. Following the conclusion of anesthesia, most study subjects appeared to regain their normal HRV, although this did not occur immediately. The resumption of normal HRV was especially delayed on DFA. Qualitatively, the reduction in HRV under anesthesia appears similar to the reduction in HRV observed in CHF. These observations will need to be validated in future studies, and the broader clinical implications of these observations, if any, are unknown.

  13. Genetic Variants Contribute to Gene Expression Variability in Humans

    Science.gov (United States)

    Hulse, Amanda M.; Cai, James J.

    2013-01-01

    Expression quantitative trait loci (eQTL) studies have established convincing relationships between genetic variants and gene expression. Most of these studies focused on the mean of gene expression level, but not the variance of gene expression level (i.e., gene expression variability). In the present study, we systematically explore genome-wide association between genetic variants and gene expression variability in humans. We adapt the double generalized linear model (dglm) to simultaneously fit the means and the variances of gene expression among the three possible genotypes of a biallelic SNP. The genomic loci showing significant association between the variances of gene expression and the genotypes are termed expression variability QTL (evQTL). Using a data set of gene expression in lymphoblastoid cell lines (LCLs) derived from 210 HapMap individuals, we identify cis-acting evQTL involving 218 distinct genes, among which 8 genes, ADCY1, CTNNA2, DAAM2, FERMT2, IL6, PLOD2, SNX7, and TNFRSF11B, are cross-validated using an extra expression data set of the same LCLs. We also identify ∼300 trans-acting evQTL between >13,000 common SNPs and 500 randomly selected representative genes. We employ two distinct scenarios, emphasizing single-SNP and multiple-SNP effects on expression variability, to explain the formation of evQTL. We argue that detecting evQTL may represent a novel method for effectively screening for genetic interactions, especially when the multiple-SNP influence on expression variability is implied. The implication of our results for revealing genetic mechanisms of gene expression variability is discussed. PMID:23150607

  14. Transcranial Direct Current Stimulation of the Leg Motor Cortex Enhances Coordinated Motor Output During Walking With a Large Inter-Individual Variability

    NARCIS (Netherlands)

    van Asseldonk, Edwin H.F.; Boonstra, Tjitske

    2016-01-01

    Background Transcranial direct current stimulation (tDCS) can augment force generation and control in single leg joints in healthy subjects and stroke survivors. However, it is unknown whether these effects also result in improved force production and coordination during walking and whether

  15. Tissue-specific and minor inter-individual variation in imprinting of IGF2R is a common feature of Bos taurus Concepti and not correlated with fetal weight.

    Directory of Open Access Journals (Sweden)

    Daniela Bebbere

    Full Text Available The insulin-like growth factor 2 receptor (IGF2R is essential for prenatal growth regulation and shows gene dosage effects on fetal weight that can be affected by in-vitro embryo culture. Imprinted maternal expression of murine Igf2r is well documented for all fetal tissues excluding brain, but polymorphic imprinting and biallelic expression were reported for IGF2R in human. These differences have been attributed to evolutionary changes correlated with specific reproductive strategies. However, data from species suitable for testing this hypothesis are lacking. The domestic cow (Bos taurus carries a single conceptus with a similar gestation length as human. We identified 12 heterozygous concepti informative for imprinting studies among 68 Bos taurus fetuses at Day 80 of gestation (28% term and found predominantly maternal IGF2R expression in all fetal tissues but brain, which escapes imprinting. Inter-individual variation in allelic expression bias, i.e. expression of the repressed paternal allele relative to the maternal allele, ranged from 4.6-8.9% in heart, 4.3-10.2% in kidney, 6.1-11.2% in liver, 4.6-15.8% in lung and 3.2-12.2% in skeletal muscle. Allelic bias for mesodermal tissues (heart, skeletal muscle differed significantly (P<0.05 from endodermal tissues (liver, lung. The placenta showed partial imprinting with allelic bias of 22.9-34.7% and differed significantly (P<0.001 from all other tissues. Four informative fetuses were generated by in-vitro fertilization (IVF with embryo culture and two individuals displayed fetal overgrowth. However, there was no evidence for changes in imprinting or DNA methylation after IVF, or correlations between allelic bias and fetal weight. In conclusion, imprinting of Bos taurus IGF2R is similar to mouse except in placenta, which could indicate an effect of reproductive strategy. Common minor inter-individual variation in allelic bias and absence of imprinting abnormalities in IVF fetuses suggest

  16. Protein profiling reveals inter-individual protein homogeneity of arachnoid cyst fluid and high qualitative similarity to cerebrospinal fluid

    Directory of Open Access Journals (Sweden)

    Berle Magnus

    2011-05-01

    Full Text Available Abstract Background The mechanisms behind formation and filling of intracranial arachnoid cysts (AC are poorly understood. The aim of this study was to evaluate AC fluid by proteomics to gain further knowledge about ACs. Two goals were set: 1 Comparison of AC fluid from individual patients to determine whether or not temporal AC is a homogenous condition; and 2 Evaluate the protein content of a pool of AC fluid from several patients and qualitatively compare this with published protein lists of cerebrospinal fluid (CSF and plasma. Methods AC fluid from 15 patients with temporal AC was included in this study. In the AC protein comparison experiment, AC fluid from 14 patients was digested, analyzed by LC-MS/MS using a semi-quantitative label-free approach and the data were compared by principal component analysis (PCA to gain knowledge of protein homogeneity of AC. In the AC proteome evaluation experiment, AC fluid from 11 patients was pooled, digested, and fractionated by SCX chromatography prior to analysis by LC-MS/MS. Proteins identified were compared to published databases of proteins identified from CSF and plasma. AC fluid proteins not found in these two databases were experimentally searched for in lumbar CSF taken from neurologically-normal patients, by a targeted protein identification approach called MIDAS (Multiple Reaction Monitoring (MRM initiated detection and sequence analysis. Results We did not identify systematic trends or grouping of data in the AC protein comparison experiment, implying low variability between individual proteomic profiles of AC. In the AC proteome evaluation experiment, we identified 199 proteins. When compared to previously published lists of proteins identified from CSF and plasma, 15 of the AC proteins had not been reported in either of these datasets. By a targeted protein identification approach, we identified 11 of these 15 proteins in pooled CSF from neurologically-normal patients, demonstrating that

  17. Country-Specific Effects of Climate Variability on Human Migration

    Science.gov (United States)

    Gray, Clark; Wise, Erika

    2016-01-01

    Involuntary human migration is among the social outcomes of greatest concern in the current era of global climate change. Responding to this concern, a growing number of studies have investigated the consequences of short to medium-term climate variability for human migration using demographic and econometric approaches. These studies have provided important insights, but at the same time have been significantly limited by lack of expertise in the use of climate data, access to cross-national data on migration, and attention to model specification. To address these limitations, we link data on internal and international migration over a 6-year period from 9,812 origin households in Kenya, Uganda, Nigeria, Burkina Faso and Senegal to high-resolution gridded climate data from both station and satellite sources. Analyses of these data using several plausible specifications reveal that climate variability has country-specific effects on migration: Migration tends to increase with temperature anomalies in Uganda, tends to decrease with temperature anomalies in Kenya and Burkina Faso, and shows no consistent relationship with temperature in Nigeria and Senegal. Consistent with previous studies, precipitation shows weak and inconsistent relationships with migration across countries. These results challenge generalizing narratives that foresee a consistent migratory response to climate change across the globe. PMID:27092012

  18. Country-Specific Effects of Climate Variability on Human Migration.

    Science.gov (United States)

    Gray, Clark; Wise, Erika

    2016-04-01

    Involuntary human migration is among the social outcomes of greatest concern in the current era of global climate change. Responding to this concern, a growing number of studies have investigated the consequences of short to medium-term climate variability for human migration using demographic and econometric approaches. These studies have provided important insights, but at the same time have been significantly limited by lack of expertise in the use of climate data, access to cross-national data on migration, and attention to model specification. To address these limitations, we link data on internal and international migration over a 6-year period from 9,812 origin households in Kenya, Uganda, Nigeria, Burkina Faso and Senegal to high-resolution gridded climate data from both station and satellite sources. Analyses of these data using several plausible specifications reveal that climate variability has country-specific effects on migration: Migration tends to increase with temperature anomalies in Uganda, tends to decrease with temperature anomalies in Kenya and Burkina Faso, and shows no consistent relationship with temperature in Nigeria and Senegal. Consistent with previous studies, precipitation shows weak and inconsistent relationships with migration across countries. These results challenge generalizing narratives that foresee a consistent migratory response to climate change across the globe.

  19. Intra- and inter-individual variations of blood and urinary water-soluble vitamins in Japanese young adults consuming a semi-purified diet for 7 days.

    Science.gov (United States)

    Shibata, Katsumi; Fukuwatari, Tsutomu; Watanabe, Toshiaki; Nishimuta, Mamoru

    2009-12-01

    We have previously reported the levels of water-soluble vitamins in the blood and urine of Japanese young adults. In the present paper, to assess the variations in these water-soluble vitamin markers during the above experiment, we comprehensively determined the intra- and inter-individual variations of blood and urinary water-soluble vitamins to exactly the same amount of water-soluble vitamin intakes in the same experiment. The blood samples before breakfast and the 24-h urine samples were periodically collected from Japanese college male (n=10) and female (n=10) students consuming a semi-purified diet with water-soluble vitamins based on Japanese Dietary Reference Intakes for 7 d, and the intra- and inter-individual variations of blood and urinary water-soluble vitamins or their metabolites in blood and urine samples after adaptation were calculated. Although urinary excretion of vitamin B(12) and vitamin C showed high intra-individual variations in both males and females, other urinary vitamins and all blood vitamins showed less than 20% of within-subject coefficients of variance in either male or female. Those showing more than 20% of between-subject coefficients of variances in both male and female were blood vitamin B(6), vitamin B(12) and folate levels, and urinary vitamin B(1), vitamin B(2), vitamin B(12), nicotinamide metabolites, pantothenic acid, biotin and vitamin C. These results showed that oral administration of constant of water-soluble vitamins generally decreased intra-individual variation, while individual differences in urinary vitamin excretion were observed.

  20. MicroRNA expression variability in human cervical tissues.

    Directory of Open Access Journals (Sweden)

    Patrícia M Pereira

    Full Text Available MicroRNAs (miRNAs are short (approximately 22 nt non-coding regulatory RNAs that control gene expression at the post-transcriptional level. Deregulation of miRNA expression has been discovered in a wide variety of tumours and it is now clear that they contribute to cancer development and progression. Cervical cancer is one of the most common cancers in women worldwide and there is a strong need for a non-invasive, fast and efficient method to diagnose the disease. We investigated miRNA expression profiles in cervical cancer using a microarray platform containing probes for mature miRNAs. We have evaluated miRNA expression profiles of a heterogeneous set of cervical tissues from 25 different patients. This set included 19 normal cervical tissues, 4 squamous cell carcinoma, 5 high-grade squamous intraepithelial lesion (HSIL and 9 low-grade squamous intraepithelial lesion (LSIL samples. We observed high variability in miRNA expression especially among normal cervical samples, which prevented us from obtaining a unique miRNA expression signature for this tumour type. However, deregulated miRNAs were identified in malignant and pre-malignant cervical tissues after tackling the high expression variability observed. We were also able to identify putative target genes of relevant candidate miRNAs. Our results show that miRNA expression shows natural variability among human samples, which complicates miRNA data profiling analysis. However, such expression noise can be filtered and does not prevent the identification of deregulated miRNAs that play a role in the malignant transformation of cervical squamous cells. Deregulated miRNAs highlight new candidate gene targets allowing for a better understanding of the molecular mechanism underlying the development of this tumour type.

  1. Human phoneme recognition depending on speech-intrinsic variability.

    Science.gov (United States)

    Meyer, Bernd T; Jürgens, Tim; Wesker, Thorsten; Brand, Thomas; Kollmeier, Birger

    2010-11-01

    The influence of different sources of speech-intrinsic variation (speaking rate, effort, style and dialect or accent) on human speech perception was investigated. In listening experiments with 16 listeners, confusions of consonant-vowel-consonant (CVC) and vowel-consonant-vowel (VCV) sounds in speech-weighted noise were analyzed. Experiments were based on the OLLO logatome speech database, which was designed for a man-machine comparison. It contains utterances spoken by 50 speakers from five dialect/accent regions and covers several intrinsic variations. By comparing results depending on intrinsic and extrinsic variations (i.e., different levels of masking noise), the degradation induced by variabilities can be expressed in terms of the SNR. The spectral level distance between the respective speech segment and the long-term spectrum of the masking noise was found to be a good predictor for recognition rates, while phoneme confusions were influenced by the distance to spectrally close phonemes. An analysis based on transmitted information of articulatory features showed that voicing and manner of articulation are comparatively robust cues in the presence of intrinsic variations, whereas the coding of place is more degraded. The database and detailed results have been made available for comparisons between human speech recognition (HSR) and automatic speech recognizers (ASR).

  2. Water baths for farmed mink: intra-individual consistency and inter-individual variation in swimming behaviour, and effects on stereotyped behaviour

    Directory of Open Access Journals (Sweden)

    J. MONONEN

    2008-12-01

    Full Text Available Swimming behaviour and effects of water baths on stereotyped behaviour in farmed mink (Mustela vison were studied in three experiments. The singly-housed mink had access from their home cages to extra cages with 20.5 litre water baths. Two short-term experiments aimed to investigate how quickly adult and juvenile mink start using and how consistently they use water baths over 10 days, and whether the extent of the use correlates between dams and their females kits. A four-month experiment was designed to compare the development of stereotyped behaviour in juvenile mink housed with and without swimming opportunity. The behavioural analyses were based on several 24-hour video recordings carried out in all three experiments. There were obvious inter-individual differences and intra-individual consistency in swimming frequency and time. Farmed mink’s motivation to swim can be assessed in short-term experiments, and measurement of water losses from the swimming baths and use of instantaneous sampling with 10 min sampling intervals provide quite reliable measures of the amount of swimming. The bath use of the juveniles correlated with that of their dams, indicating that an individual mink’s eagerness to swim may have a genetic component. The lower amount of stereotyped behaviour in mink housed with water baths indicates that long-term access to baths may alleviate frustration in singly-housed juvenile farmed mink.;

  3. Clinical Characteristics and Genetic Variability of Human Rhinovirus in Mexico

    Directory of Open Access Journals (Sweden)

    Hilda Montero

    2012-01-01

    Full Text Available Human rhinovirus (HRV is a leading cause of acute respiratory infection (ARI in young children and infants worldwide and has a high impact on morbidity and mortality in this population. Initially, HRV was classified into two species: HRV-A and HRV-B. Recently, a species called HRV-C and possibly another species, HRV-D, were identified. In Mexico, there is little information about the role of HRV as a cause of ARI, and the presence and importance of species such as HRV-C are not known. The aim of this study was to determine the clinical characteristics and genetic variability of HRV in Mexican children. Genetic characterization was carried out by phylogenetic analysis of the 5′-nontranslated region (5′-NTR of the HRV genome. The results show that the newly identified HRV-C is circulating in Mexican children more frequently than HRV-B but not as frequently as HRV-A, which was the most frequent species. Most of the cases of the three species of HRV were in children under 2 years of age, and all species were associated with very mild and moderate ARI.

  4. Evaluating variability and uncertainty in radiological impact assessment using SYMBIOSE

    International Nuclear Information System (INIS)

    Simon-Cornu, M.; Beaugelin-Seiller, K.; Boyer, P.; Calmon, P.; Garcia-Sanchez, L.; Mourlon, C.; Nicoulaud, V.; Sy, M.; Gonze, M.A.

    2015-01-01

    SYMBIOSE is a modelling platform that accounts for variability and uncertainty in radiological impact assessments, when simulating the environmental fate of radionuclides and assessing doses to human populations. The default database of SYMBIOSE is partly based on parameter values that are summarized within International Atomic Energy Agency (IAEA) documents. To characterize uncertainty on the transfer parameters, 331 Probability Distribution Functions (PDFs) were defined from the summary statistics provided within the IAEA documents (i.e. sample size, minimal and maximum values, arithmetic and geometric means, standard and geometric standard deviations) and are made available as spreadsheet files. The methods used to derive the PDFs without complete data sets, but merely the summary statistics, are presented. Then, a simple case-study illustrates the use of the database in a second-order Monte Carlo calculation, separating parametric uncertainty and inter-individual variability. - Highlights: • Parametric uncertainty in radioecology was derived from IAEA documents. • 331 Probability Distribution Functions were defined for transfer parameters. • Parametric uncertainty and inter-individual variability were propagated

  5. Human activity and climate variability project - annual report 2002

    International Nuclear Information System (INIS)

    Chambers, S.; Harle, K.J.; Sharmeen, S.; Zahorowski, W.; Cohen, D.; Heijnis, H.; Henderson-Sellers, A

    2002-01-01

    Work is well underway on identifying the spatial and temporal extent, direction and range of trace element transport across Tasmania through analysis of lake sediments; A follow up investigation of sedimentation and pollution in the Nattai River catchment following the devastating 2001 bushfires in the region has been completed; The project has been extended to include investigations of evidence of human impacts in the highly sensitive and ecologically important Great Lakes of coastal NSW. This has involved the expansion of our collaboration to include Geoscience Australia; Contributions have been made to the IGBP HITE project. Further contributions will be made as the evidence gathered is drawn together and interpreted; Over the coming year, focus will be placed on completion of the investigation of the extent of aerial transport of trace elements across Tasmania over the last 200 years as well as evidence for human activity and impacts on the Great Lakes region of NSW. Further investigation of potential climate signals from sites in northern Australia will also be made. The first 12 months of data for all ACE-Asia radon and fine particle sites is now available with preliminary analyses performed; The seasonal variability of background radon concentration at each of the radon monitoring sites has been characterised for the available data; Major components related to industrial pollution and soil sources in China have been identified and quantified; Regional and seasonal variations and trends in aerosol constituents have been measured and compared across more than 2.8Mk 2 of sampling area; The Hok Tsui and Kosan detectors were visited for general maintenance and recalibration; A grant application to the APN has been submitted in support of regional inventory analyses based on radon time series; Progress on the processing and interpretation of radon data was presented at the Cape Grim Science Meeting (6-7 February 2002) and the 7th Biennial SPERA Conference on

  6. Human activity and climate variability project - annual report 2002

    Energy Technology Data Exchange (ETDEWEB)

    Chambers, S; Harle, K J; Sharmeen, S; Zahorowski, W; Cohen, D; Heijnis, H; Henderson-Sellers, A [Australian Nuclear Science and Technology Organisation, Menai, NSW (Australia)

    2002-07-01

    Work is well underway on identifying the spatial and temporal extent, direction and range of trace element transport across Tasmania through analysis of lake sediments; A follow up investigation of sedimentation and pollution in the Nattai River catchment following the devastating 2001 bushfires in the region has been completed; The project has been extended to include investigations of evidence of human impacts in the highly sensitive and ecologically important Great Lakes of coastal NSW. This has involved the expansion of our collaboration to include Geoscience Australia; Contributions have been made to the IGBP HITE project. Further contributions will be made as the evidence gathered is drawn together and interpreted; Over the coming year, focus will be placed on completion of the investigation of the extent of aerial transport of trace elements across Tasmania over the last 200 years as well as evidence for human activity and impacts on the Great Lakes region of NSW. Further investigation of potential climate signals from sites in northern Australia will also be made. The first 12 months of data for all ACE-Asia radon and fine particle sites is now available with preliminary analyses performed; The seasonal variability of background radon concentration at each of the radon monitoring sites has been characterised for the available data; Major components related to industrial pollution and soil sources in China have been identified and quantified; Regional and seasonal variations and trends in aerosol constituents have been measured and compared across more than 2.8Mk{sup 2} of sampling area; The Hok Tsui and Kosan detectors were visited for general maintenance and recalibration; A grant application to the APN has been submitted in support of regional inventory analyses based on radon time series; Progress on the processing and interpretation of radon data was presented at the Cape Grim Science Meeting (6-7 February 2002) and the 7th Biennial SPERA Conference on

  7. Fermentation to short-chain fatty acids and lactate in human faecal batch cultures. Intra- and inter-individual variations versus variations caused by changes in fermented saccharides

    DEFF Research Database (Denmark)

    Mortensen, P B; Hove, H; Clausen, M R

    1991-01-01

    in homogenates pooled from three individuals increased short-chain fatty acid production linearly. Amounts and ratios of short-chain fatty acids formed were highly dependent on the type of substrate fermented. Fermentable saccharides increased ammonia assimilation, in contrast to the metabolic inert cellulose...

  8. Habitual dietary fibre intake influences gut microbiota response to an inulin-type fructan prebiotic:a randomised, double-blind, placebo-controlled, cross-over, human intervention study

    OpenAIRE

    Healey, Genelle; Murphy, Rinki; Butts, Chrissie; Brough, Louise; Whelan, Kevin; Coad, Jane

    2018-01-01

    Dysbiotic gut microbiota have been implicated in human disease. Diet-based therapeutic strategies have been used to manipulate the gut microbiota towards a more favourable profile. However, it has been demonstrated that large inter-individual variability exists in gut microbiota response to a dietary intervention. The primary objective of this study was to investigate whether habitually low dietary fibre (LDF) v. high dietary fibre (HDF) intakes influence gut microbiota response to an inulin-...

  9. Statistical validity of using ratio variables in human kinetics research.

    Science.gov (United States)

    Liu, Yuanlong; Schutz, Robert W

    2003-09-01

    The purposes of this study were to investigate the validity of the simple ratio and three alternative deflation models and examine how the variation of the numerator and denominator variables affects the reliability of a ratio variable. A simple ratio and three alternative deflation models were fitted to four empirical data sets, and common criteria were applied to determine the best model for deflation. Intraclass correlation was used to examine the component effect on the reliability of a ratio variable. The results indicate that the validity, of a deflation model depends on the statistical characteristics of the particular component variables used, and an optimal deflation model for all ratio variables may not exist. Therefore, it is recommended that different models be fitted to each empirical data set to determine the best deflation model. It was found that the reliability of a simple ratio is affected by the coefficients of variation and the within- and between-trial correlations between the numerator and denominator variables. It was recommended that researchers should compute the reliability of the derived ratio scores and not assume that strong reliabilities in the numerator and denominator measures automatically lead to high reliability in the ratio measures.

  10. Variability of human hepatic UDP-glucuronosyltransferase activity

    NARCIS (Netherlands)

    Little, JM; Lester, R; Kuipers, F; Vonk, R; Mackenzie, PI; Drake, RR; Frame, L; Radominska-Pandya, A

    1999-01-01

    The availability of a unique series of liver samples from human subjects, both control patients (9) and those with liver disease (6; biliary atresia (2), retransplant, chronic tyrosinemia type I, tyrosinemia, Wilson's disease) allowed us to characterize human hepatic UDP-glucuronosyltransferases

  11. Variable high pressure processing sensitivities for GII human noroviruses

    Science.gov (United States)

    Human norovirus (HuNoV) is the leading cause of foodborne diseases worldwide. High pressure processing (HPP) is one of the most promising non-thermal technologies for decontamination of viral pathogens in foods. However, the survival of HuNoVs by HPP is poorly understood because these viruses cann...

  12. Determination of some variables of human dentin for dosimetric purposes

    International Nuclear Information System (INIS)

    Peres, C.

    1990-01-01

    The initial objective of this work is to determine the atomic composition of human dentin, using various techniques of measurements such as X-Ray fluorescence, atomic absorption, spectrophotometry, volumetric analysis, chemistry, colorimetry and thermogravimetry. With the values of the effective atomic number Z bar dependent of the quality of the ionizing radiation, one can find the kind of material that can be used for a phantom equivalent to dentin. (author)

  13. Post-contractile BOLD contrast in skeletal muscle at 7 T reveals inter-individual heterogeneity in the physiological responses to muscle contraction.

    Science.gov (United States)

    Towse, Theodore F; Elder, Christopher P; Bush, Emily C; Klockenkemper, Samuel W; Bullock, Jared T; Dortch, Richard D; Damon, Bruce M

    2016-12-01

    Muscle blood oxygenation-level dependent (BOLD) contrast is greater in magnitude and potentially more influenced by extravascular BOLD mechanisms at 7 T than it is at lower field strengths. Muscle BOLD imaging of muscle contractions at 7 T could, therefore, provide greater or different contrast than at 3 T. The purpose of this study was to evaluate the feasibility of using BOLD imaging at 7 T to assess the physiological responses to in vivo muscle contractions. Thirteen subjects (four females) performed a series of isometric contractions of the calf muscles while being scanned in a Philips Achieva 7 T human imager. Following 2 s maximal isometric plantarflexion contractions, BOLD signal transients ranging from 0.3 to 7.0% of the pre-contraction signal intensity were observed in the soleus muscle. We observed considerable inter-subject variability in both the magnitude and time course of the muscle BOLD signal. A subset of subjects (n = 7) repeated the contraction protocol at two different repetition times (T R : 1000 and 2500 ms) to determine the potential of T 1 -related inflow effects on the magnitude of the post-contractile BOLD response. Consistent with previous reports, there was no difference in the magnitude of the responses for the two T R values (3.8 ± 0.9 versus 4.0 ± 0.6% for T R  = 1000 and 2500 ms, respectively; mean ± standard error). These results demonstrate that studies of the muscle BOLD responses to contractions are feasible at 7 T. Compared with studies at lower field strengths, post-contractile 7 T muscle BOLD contrast may afford greater insight into microvascular function and dysfunction. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes

    KAUST Repository

    Tawe, Leabaneng

    2018-03-14

    Identification of inter-individual variability for drug metabolism through cytochrome P450 2B6 (CYP2B6) enzyme is important for understanding the differences in clinical responses to malaria and HIV. This study evaluates the distribution of CYP2B6 alleles, haplotypes and inferred metabolic phenotypes among subjects with different ethnicity in Botswana. A total of 570 subjects were analyzed for CYP2B6 polymorphisms at position 516 G > T (rs3745274), 785 A > G (rs2279343) and 983 T > C (rs28399499). Samples were collected in three districts of Botswana where the population belongs to Bantu (Serowe/Palapye and Chobe) and San-related (Ghanzi) ethnicity. The three districts showed different haplotype composition according to the ethnic background but similar metabolic inferred phenotypes, with 59.12%, 34.56%, 2.10% and 4.21% of the subjects having, respectively, an extensive, intermediate, slow and rapid metabolic profile. The results hint at the possibility of a convergent adaptation of detoxifying metabolic phenotypes despite a different haplotype structure due to the different genetic background. The main implication is that, while there is substantial homogeneity of metabolic inferred phenotypes among the country, the response to drugs metabolized via CYP2B6 could be individually associated to an increased risk of treatment failure and toxicity. These are important facts since Botswana is facing malaria elimination and a very high HIV prevalence.

  15. Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype diversity and convergent phenotypes

    KAUST Repository

    Tawe, Leabaneng; Motshoge, Thato; Ramatlho, Pleasure; Mutukwa, Naledi; Muthoga, Charles Waithaka; Dongho, Ghyslaine Bruna Djeunang; Martinelli, Axel; Peloewetse, Elias; Russo, Gianluca; Quaye, Isaac Kweku; Paganotti, Giacomo Maria

    2018-01-01

    Identification of inter-individual variability for drug metabolism through cytochrome P450 2B6 (CYP2B6) enzyme is important for understanding the differences in clinical responses to malaria and HIV. This study evaluates the distribution of CYP2B6 alleles, haplotypes and inferred metabolic phenotypes among subjects with different ethnicity in Botswana. A total of 570 subjects were analyzed for CYP2B6 polymorphisms at position 516 G > T (rs3745274), 785 A > G (rs2279343) and 983 T > C (rs28399499). Samples were collected in three districts of Botswana where the population belongs to Bantu (Serowe/Palapye and Chobe) and San-related (Ghanzi) ethnicity. The three districts showed different haplotype composition according to the ethnic background but similar metabolic inferred phenotypes, with 59.12%, 34.56%, 2.10% and 4.21% of the subjects having, respectively, an extensive, intermediate, slow and rapid metabolic profile. The results hint at the possibility of a convergent adaptation of detoxifying metabolic phenotypes despite a different haplotype structure due to the different genetic background. The main implication is that, while there is substantial homogeneity of metabolic inferred phenotypes among the country, the response to drugs metabolized via CYP2B6 could be individually associated to an increased risk of treatment failure and toxicity. These are important facts since Botswana is facing malaria elimination and a very high HIV prevalence.

  16. Gene expression variability in human hepatic drug metabolizing enzymes and transporters.

    Directory of Open Access Journals (Sweden)

    Lun Yang

    Full Text Available Interindividual variability in the expression of drug-metabolizing enzymes and transporters (DMETs in human liver may contribute to interindividual differences in drug efficacy and adverse reactions. Published studies that analyzed variability in the expression of DMET genes were limited by sample sizes and the number of genes profiled. We systematically analyzed the expression of 374 DMETs from a microarray data set consisting of gene expression profiles derived from 427 human liver samples. The standard deviation of interindividual expression for DMET genes was much higher than that for non-DMET genes. The 20 DMET genes with the largest variability in the expression provided examples of the interindividual variation. Gene expression data were also analyzed using network analysis methods, which delineates the similarities of biological functionalities and regulation mechanisms for these highly variable DMET genes. Expression variability of human hepatic DMET genes may affect drug-gene interactions and disease susceptibility, with concomitant clinical implications.

  17. Modeling the variability of shapes of a human placenta.

    Science.gov (United States)

    Yampolsky, M; Salafia, C M; Shlakhter, O; Haas, D; Eucker, B; Thorp, J

    2008-09-01

    Placentas are generally round/oval in shape, but "irregular" shapes are common. In the Collaborative Perinatal Project data, irregular shapes were associated with lower birth weight for placental weight, suggesting variably shaped placentas have altered function. (I) Using a 3D one-parameter model of placental vascular growth based on Diffusion Limited Aggregation (an accepted model for generating highly branched fractals), models were run with a branching density growth parameter either fixed or perturbed at either 5-7% or 50% of model growth. (II) In a data set with detailed measures of 1207 placental perimeters, radial standard deviations of placental shapes were calculated from the umbilical cord insertion, and from the centroid of the shape (a biologically arbitrary point). These two were compared to the difference between the observed scaling exponent and the Kleiber scaling exponent (0.75), considered optimal for vascular fractal transport systems. Spearman's rank correlation considered pcentroid) was associated with differences from the Kleiber exponent (p=0.006). A dynamical DLA model recapitulates multilobate and "star" placental shapes via changing fractal branching density. We suggest that (1) irregular placental outlines reflect deformation of the underlying placental fractal vascular network, (2) such irregularities in placental outline indicate sub-optimal branching structure of the vascular tree, and (3) this accounts for the lower birth weight observed in non-round/oval placentas in the Collaborative Perinatal Project.

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

    DEFF Research Database (Denmark)

    Volianitis, S.; Secher, Niels H.

    2009-01-01

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

  19. Inter-subject variability in human atrial action potential in sinus rhythm versus chronic atrial fibrillation.

    Directory of Open Access Journals (Sweden)

    Carlos Sánchez

    Full Text Available Human atrial electrophysiology exhibits high inter-subject variability in both sinus rhythm (SR and chronic atrial fibrillation (cAF patients. Variability is however rarely investigated in experimental and theoretical electrophysiological studies, thus hampering the understanding of its underlying causes but also its implications in explaining differences in the response to disease and treatment. In our study, we aim at investigating the ability of populations of human atrial cell models to capture the inter-subject variability in action potential (AP recorded in 363 patients both under SR and cAF conditions.Human AP recordings in atrial trabeculae (n = 469 from SR and cAF patients were used to calibrate populations of computational SR and cAF atrial AP models. Three populations of over 2000 sampled models were generated, based on three different human atrial AP models. Experimental calibration selected populations of AP models yielding AP with morphology and duration in range with experimental recordings. Populations using the three original models can mimic variability in experimental AP in both SR and cAF, with median conductance values in SR for most ionic currents deviating less than 30% from their original peak values. All cAF populations show similar variations in G(K1, G(Kur and G(to, consistent with AF-related remodeling as reported in experiments. In all SR and cAF model populations, inter-subject variability in I(K1 and I(NaK underlies variability in APD90, variability in I(Kur, I(CaL and I(NaK modulates variability in APD50 and combined variability in Ito and I(Kur determines variability in APD20. The large variability in human atrial AP triangulation is mostly determined by I(K1 and either I(NaK or I(NaCa depending on the model.Experimentally-calibrated human atrial AP models populations mimic AP variability in SR and cAF patient recordings, and identify potential ionic determinants of inter-subject variability in human atrial AP

  20. Human Performance Technology (HPT): An Examination of Definitions through Dependent and Independent Variables.

    Science.gov (United States)

    Irlbeck, Sonja A.

    2002-01-01

    Provides a chronological perspective of human performance technology (HPT) definitions and an evaluation of them in terms of independent and dependent variables. Discusses human competence and performance technology and compares the definitions with the goals that have been articulated for HPT. (Author/LRW)

  1. Fuzzy variable impedance control based on stiffness identification for human-robot cooperation

    Science.gov (United States)

    Mao, Dachao; Yang, Wenlong; Du, Zhijiang

    2017-06-01

    This paper presents a dynamic fuzzy variable impedance control algorithm for human-robot cooperation. In order to estimate the intention of human for co-manipulation, a fuzzy inference system is set up to adjust the impedance parameter. Aiming at regulating the output fuzzy universe based on the human arm’s stiffness, an online stiffness identification method is developed. A drag interaction task is conducted on a 5-DOF robot with variable impedance control. Experimental results demonstrate that the proposed algorithm is superior.

  2. Identification of variables and their influence on the human resources planning in the territorial level

    Energy Technology Data Exchange (ETDEWEB)

    Martínez Vivar, R.; Sánchez Rodríguez, A.; Pérez Campdesuñer, R.; García Vidal, G.

    2016-07-01

    The purpose of this paper lies in the use of experimental way through empirical tools for identification of the set of variables and their interrelationships and influences on the human resources planning at the territorial level. The methodology used to verify the existence of the variables that affect the planning of human resources at the territorial level consists of two phases: a qualitative study of the variables that influence the planning of human resources, where the explicit variables are measured and / or implied raised in the literature analyzing the main contributions and limitations expressed by each of the authors consulted. Then it proceeds to confirmatory phase (quantitative) to prove the existence of the dimensions of the planning of human resources in the territorial level through the use of multivariate statistics through the combination of expert analysis and techniques of factorial grouping. Identification is achieved by using empirical methods, variables that affect human resources planning at the territorial level, as well as their grouping essential dimensions, while the description of a theoretical model that integrates the dimensions is made essential and relationships that affect human resource planning at the regional level, which is characterized by the existence of systemic and prospective nature. The literature shows two streams that address a wide range of approaches to human resources planning. The first is oriented from the business object and the second part of the management in highlighting a limited territorial level to address this latest theoretical development, an element that has contributed to the fragmented treatment of human resources planning and management in general at this level. The originality of this paper is part of the creation and adaptation, on a scientific basis of a theoretical model developed from the conceptual contribution of this process at the territorial level where the key variables that affect this

  3. Variable responses of human and non-human primate gut microbiomes to a Western diet.

    Science.gov (United States)

    Amato, Katherine R; Yeoman, Carl J; Cerda, Gabriela; Schmitt, Christopher A; Cramer, Jennifer Danzy; Miller, Margret E Berg; Gomez, Andres; Turner, Trudy R; Wilson, Brenda A; Stumpf, Rebecca M; Nelson, Karen E; White, Bryan A; Knight, Rob; Leigh, Steven R

    2015-11-16

    The human gut microbiota interacts closely with human diet and physiology. To better understand the mechanisms behind this relationship, gut microbiome research relies on complementing human studies with manipulations of animal models, including non-human primates. However, due to unique aspects of human diet and physiology, it is likely that host-gut microbe interactions operate differently in humans and non-human primates. Here, we show that the human microbiome reacts differently to a high-protein, high-fat Western diet than that of a model primate, the African green monkey, or vervet (Chlorocebus aethiops sabaeus). Specifically, humans exhibit increased relative abundance of Firmicutes and reduced relative abundance of Prevotella on a Western diet while vervets show the opposite pattern. Predictive metagenomics demonstrate an increased relative abundance of genes associated with carbohydrate metabolism in the microbiome of only humans consuming a Western diet. These results suggest that the human gut microbiota has unique properties that are a result of changes in human diet and physiology across evolution or that may have contributed to the evolution of human physiology. Therefore, the role of animal models for understanding the relationship between the human gut microbiota and host metabolism must be re-focused.

  4. Evidence for a time-invariant phase variable in human ankle control.

    Directory of Open Access Journals (Sweden)

    Robert D Gregg

    Full Text Available Human locomotion is a rhythmic task in which patterns of muscle activity are modulated by state-dependent feedback to accommodate perturbations. Two popular theories have been proposed for the underlying embodiment of phase in the human pattern generator: a time-dependent internal representation or a time-invariant feedback representation (i.e., reflex mechanisms. In either case the neuromuscular system must update or represent the phase of locomotor patterns based on the system state, which can include measurements of hundreds of variables. However, a much simpler representation of phase has emerged in recent designs for legged robots, which control joint patterns as functions of a single monotonic mechanical variable, termed a phase variable. We propose that human joint patterns may similarly depend on a physical phase variable, specifically the heel-to-toe movement of the Center of Pressure under the foot. We found that when the ankle is unexpectedly rotated to a position it would have encountered later in the step, the Center of Pressure also shifts forward to the corresponding later position, and the remaining portion of the gait pattern ensues. This phase shift suggests that the progression of the stance ankle is controlled by a biomechanical phase variable, motivating future investigations of phase variables in human locomotor control.

  5. Contribution of geodiversity, climate and spatial variables for biodiversity across a gradient of human influence

    Science.gov (United States)

    Tukiainen, Helena; Alahuhta, Janne; Ala-Hulkko, Terhi; Field, Richard; Lampinen, Raino; Hjort, Jan

    2016-04-01

    Implementation of geodiversity may provide new perspectives for nature conservation. The relation between geodiversity and biodiversity has been established in recent studies but remains underexplored in environments with high human pressure. In this study, we explored the effect of geodiversity (i.e. geological, hydrological and geomorphological diversity), climate and spatial variables on biodiversity (vascular plant species richness) in environments with different human impact. The study area ranged trough the boreal vegetation zone in Finland and included altogether 1401 1-km2 grid cells from urban, rural and natural environments. The contribution of environmental variable groups for species diversity in different environments was statistically analyzed with variation partitioning method. According to the results, the contribution of geodiversity decreased and the contribution of climate and spatial variables increased as the land use became more human-induced. Hence, the connection between geodiversity and species richness was most pronounced in natural state environments.

  6. A highly variable segment of human subterminal 16p reveals a history of population growth for modern humans outside Africa

    Science.gov (United States)

    Alonso, Santos; Armour, John A. L.

    2001-01-01

    We have sequenced a highly polymorphic subterminal noncoding region from human chromosome 16p13.3, flanking the 5′ end of the hypervariable minisatellite MS205, in 100 chromosomes sampled from different African and Euroasiatic populations. Coalescence analysis indicates that the time to the most recent common ancestor (approximately 1 million years) predates the appearance of anatomically modern human forms. The root of the network describing this variability lies in Africa. African populations show a greater level of diversity and deeper branches. Most Euroasiatic variability seems to have been generated after a recent out-of-Africa range expansion. A history of population growth is the most likely scenario for the Euroasiatic populations. This pattern of nuclear variability can be reconciled with inferences based on mitochondrial DNA. PMID:11158547

  7. Pathogen prevalence predicts human cross-cultural variability in individualism/collectivism

    OpenAIRE

    Fincher, Corey L; Thornhill, Randy; Murray, Damian R; Schaller, Mark

    2008-01-01

    Pathogenic diseases impose selection pressures on the social behaviour of host populations. In humans (Homo sapiens), many psychological phenomena appear to serve an antipathogen defence function. One broad implication is the existence of cross-cultural differences in human cognition and behaviour contingent upon the relative presence of pathogens in the local ecology. We focus specifically on one fundamental cultural variable: differences in individualistic versus collectivist values. We sug...

  8. Mechanism of blood pressure and R-R variability: insights from ganglion blockade in humans

    Science.gov (United States)

    Zhang, Rong; Iwasaki, Kenichi; Zuckerman, Julie H.; Behbehani, Khosrow; Crandall, Craig G.; Levine, Benjamin D.; Blomqvist, C. G. (Principal Investigator)

    2002-01-01

    Spontaneous blood pressure (BP) and R-R variability are used frequently as 'windows' into cardiovascular control mechanisms. However, the origin of these rhythmic fluctuations is not completely understood. In this study, with ganglion blockade, we evaluated the role of autonomic neural activity versus other 'non-neural' factors in the origin of BP and R-R variability in humans. Beat-to-beat BP, R-R interval and respiratory excursions were recorded in ten healthy subjects (aged 30 +/- 6 years) before and after ganglion blockade with trimethaphan. The spectral power of these variables was calculated in the very low (0.0078-0.05 Hz), low (0.05-0.15 Hz) and high (0.15-0.35 Hz) frequency ranges. The relationship between systolic BP and R-R variability was examined by cross-spectral analysis. After blockade, R-R variability was virtually abolished at all frequencies; however, respiration and high frequency BP variability remained unchanged. Very low and low frequency BP variability was reduced substantially by 84 and 69 %, respectively, but still persisted. Transfer function gain between systolic BP and R-R interval variability decreased by 92 and 88 % at low and high frequencies, respectively, while the phase changed from negative to positive values at the high frequencies. These data suggest that under supine resting conditions with spontaneous breathing: (1) R-R variability at all measured frequencies is predominantly controlled by autonomic neural activity; (2) BP variability at high frequencies (> 0.15 Hz) is mediated largely, if not exclusively, by mechanical effects of respiration on intrathoracic pressure and/or cardiac filling; (3) BP variability at very low and low frequencies (rhythmicity; and (4) the dynamic relationship between BP and R-R variability as quantified by transfer function analysis is determined predominantly by autonomic neural activity rather than other, non-neural factors.

  9. Predicting aboveground forest biomass with topographic variables in human-impacted tropical dry forest landscapes

    NARCIS (Netherlands)

    Salinas-Melgoza, Miguel A.; Skutsch, Margaret; Lovett, Jon C.

    2018-01-01

    Topographic variables such as slope and elevation partially explain spatial variations in aboveground biomass (AGB) within landscapes. Human activities that impact vegetation, such as cattle grazing and shifting cultivation, often follow topographic features and also play a key role in determining

  10. A mathematical description of nerve fiber bundle trajectories and their variability in the human retina

    NARCIS (Netherlands)

    Jansonius, N. M.; Nevalainen, J.; Selig, B.; Zangwill, L. M.; Sample, P. A.; Budde, W. M.; Jonas, J. B.; Lagreze, W. A.; Airaksinen, P. J.; Vonthein, R.; Levin, L. A.; Paetzold, J.; Schiefer, U.

    2009-01-01

    We developed a mathematical model wherein retinal nerve fiber trajectories can be described and the corresponding inter-subject variability analyzed. The model was based on traced nerve fiber bundle trajectories extracted from 55 fundus photographs of 55 human subjects. The model resembled the

  11. Nonlinear Synchronization for Automatic Learning of 3D Pose Variability in Human Motion Sequences

    Directory of Open Access Journals (Sweden)

    Mozerov M

    2010-01-01

    Full Text Available A dense matching algorithm that solves the problem of synchronizing prerecorded human motion sequences, which show different speeds and accelerations, is proposed. The approach is based on minimization of MRF energy and solves the problem by using Dynamic Programming. Additionally, an optimal sequence is automatically selected from the input dataset to be a time-scale pattern for all other sequences. The paper utilizes an action specific model which automatically learns the variability of 3D human postures observed in a set of training sequences. The model is trained using the public CMU motion capture dataset for the walking action, and a mean walking performance is automatically learnt. Additionally, statistics about the observed variability of the postures and motion direction are also computed at each time step. The synchronized motion sequences are used to learn a model of human motion for action recognition and full-body tracking purposes.

  12. Variable ATP yields and uncoupling of oxygen consumption in human brain

    DEFF Research Database (Denmark)

    Gjedde, Albert; Aanerud, Joel; Peterson, Ericka

    2011-01-01

    normalized the metabolic rate to the population average of that region. Coefficients of variation ranged from 10 to 15% in the different regions of the human brain and the normalized regional metabolic rates ranged from 70% to 140% of the population average for each region, equal to a two-fold variation......The distribution of brain oxidative metabolism values among healthy humans is astoundingly wide for a measure that reflects normal brain function and is known to change very little with most changes of brain function. It is possible that the part of the oxygen consumption rate that is coupled...... to ATP turnover is the same in all healthy human brains, with different degrees of uncoupling explaining the variability of total oxygen consumption among people. To test the hypothesis that about 75% of the average total oxygen consumption of human brains is common to all individuals, we determined...

  13. Genetic variability in the human cannabinoid receptor 1 is associated with resting state EEG theta power in humans.

    Science.gov (United States)

    Heitland, I; Kenemans, J L; Böcker, K B E; Baas, J M P

    2014-11-01

    It has long been postulated that exogenous cannabinoids have a profound effect on human cognitive functioning. These cannabinoid effects are thought to depend, at least in parts, on alterations of phase-locking of local field potential neuronal firing. The latter can be measured as activity in the theta frequency band (4-7Hz) by electroencephalogram. Theta oscillations are supposed to serve as a mechanism in neural representations of behaviorally relevant information. However, it remains unknown whether variability in endogenous cannabinoid activity is involved in theta rhythms and therefore, may serve as an individual differences index of human cognitive functioning. To clarify this issue, we recorded resting state EEG activity in 164 healthy human subjects and extracted EEG power across frequency bands (δ, θ, α, and β). To assess variability in the endocannabinoid system, two genetic polymorphisms (rs1049353, rs2180619) within the cannabinoid receptor 1 (CB1) were determined in all participants. As expected, we observed significant effects of rs1049353 on EEG power in the theta band at frontal, central and parietal electrode regions. Crucially, these effects were specific for the theta band, with no effects on activity in the other frequency bands. Rs2180619 showed no significant associations with theta power after Bonferroni correction. Taken together, we provide novel evidence in humans showing that genetic variability in the cannabinoid receptor 1 is associated with resting state EEG power in the theta frequency band. This extends prior findings of exogenous cannabinoid effects on theta power to the endogenous cannabinoid system. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Bioavailability and pharmacokinetic profile of grape pomace phenolic compounds in humans.

    Science.gov (United States)

    Castello, Fabio; Costabile, Giuseppina; Bresciani, Letizia; Tassotti, Michele; Naviglio, Daniele; Luongo, Delia; Ciciola, Paola; Vitale, Marilena; Vetrani, Claudia; Galaverna, Gianni; Brighenti, Furio; Giacco, Rosalba; Del Rio, Daniele; Mena, Pedro

    2018-05-15

    Grape pomace, the major byproduct of the wine and juice industry, is a relevant source of bioactive phenolic compounds. However, polyphenol bioavailability in humans is not well understood, and the inter-individual variability in the production of phenolic metabolites has not been comprehensively assessed to date. The pharmacokinetic and excretive profiles of phenolic metabolites after the acute administration of a drink made from red grape pomace was here investigated in ten volunteers. A total of 35 and 28 phenolic metabolites were quantified in urine and plasma, respectively. The main circulating metabolites included phenyl-γ-valerolactones, hydroxybenzoic acids, simple phenols, hydroxyphenylpropionic acids, hydroxycinnamates, and (epi)catechin phase II conjugates. A high inter-individual variability was shown both in urine and plasma samples, and different patterns of circulating metabolites were unravelled by applying unsupervised multivariate analysis. Besides the huge variability in the production of microbial metabolites of colonic origin, an important variability was observed due to phase II conjugates. These results are of interest to further understand the potential health benefits of phenolic metabolites on individual basis. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Understanding The Individual Impacts Of Human Interventions And Climate Change On Hydrologic Variables In India

    Science.gov (United States)

    Sharma, T.; Chhabra, S., Jr.; Karmakar, S.; Ghosh, S.

    2015-12-01

    We have quantified the historical climate change and Land Use Land Cover (LULC) change impacts on the hydrologic variables of Indian subcontinent by using Variable Infiltration Capacity (VIC) mesoscale model at 0.5° spatial resolution and daily temporal resolution. The results indicate that the climate change in India has predominating effects on the basic water balance components such as water yield, evapotranspiration and soil moisture. This analysis is with the assumption of naturalised hydrologic cycle, i.e., the impacts of human interventions like construction of controlled (primarily dams, diversions and reservoirs) and water withdrawals structures are not taken into account. The assumption is unrealistic since there are numerous anthropogenic disturbances which result in large changes on vegetation composition and distribution patterns. These activities can directly or indirectly influence the dynamics of water cycle; subsequently affecting the hydrologic processes like plant transpiration, infiltration, evaporation, runoff and sublimation. Here, we have quantified the human interventions by using the reservoir and irrigation module of VIC model which incorporates the irrigation schemes, reservoir characteristics and water withdrawals. The impact of human interventions on hydrologic variables in many grids are found more predominant than climate change and might be detrimental to water resources at regional level. This spatial pattern of impacts will facilitate water manager and planners to design and station hydrologic structures for a sustainable water resources management.

  16. Pathogen prevalence predicts human cross-cultural variability in individualism/collectivism.

    Science.gov (United States)

    Fincher, Corey L; Thornhill, Randy; Murray, Damian R; Schaller, Mark

    2008-06-07

    Pathogenic diseases impose selection pressures on the social behaviour of host populations. In humans (Homo sapiens), many psychological phenomena appear to serve an antipathogen defence function. One broad implication is the existence of cross-cultural differences in human cognition and behaviour contingent upon the relative presence of pathogens in the local ecology. We focus specifically on one fundamental cultural variable: differences in individualistic versus collectivist values. We suggest that specific behavioural manifestations of collectivism (e.g. ethnocentrism, conformity) can inhibit the transmission of pathogens; and so we hypothesize that collectivism (compared with individualism) will more often characterize cultures in regions that have historically had higher prevalence of pathogens. Drawing on epidemiological data and the findings of worldwide cross-national surveys of individualism/collectivism, our results support this hypothesis: the regional prevalence of pathogens has a strong positive correlation with cultural indicators of collectivism and a strong negative correlation with individualism. The correlations remain significant even when controlling for potential confounding variables. These results help to explain the origin of a paradigmatic cross-cultural difference, and reveal previously undocumented consequences of pathogenic diseases on the variable nature of human societies.

  17. An agent-based model of cellular dynamics and circadian variability in human endotoxemia.

    Directory of Open Access Journals (Sweden)

    Tung T Nguyen

    Full Text Available As cellular variability and circadian rhythmicity play critical roles in immune and inflammatory responses, we present in this study an agent-based model of human endotoxemia to examine the interplay between circadian controls, cellular variability and stochastic dynamics of inflammatory cytokines. The model is qualitatively validated by its ability to reproduce circadian dynamics of inflammatory mediators and critical inflammatory responses after endotoxin administration in vivo. Novel computational concepts are proposed to characterize the cellular variability and synchronization of inflammatory cytokines in a population of heterogeneous leukocytes. Our results suggest that there is a decrease in cell-to-cell variability of inflammatory cytokines while their synchronization is increased after endotoxin challenge. Model parameters that are responsible for IκB production stimulated by NFκB activation and for the production of anti-inflammatory cytokines have large impacts on system behaviors. Additionally, examining time-dependent systemic responses revealed that the system is least vulnerable to endotoxin in the early morning and most vulnerable around midnight. Although much remains to be explored, proposed computational concepts and the model we have pioneered will provide important insights for future investigations and extensions, especially for single-cell studies to discover how cellular variability contributes to clinical implications.

  18. An exploration of diffusion tensor eigenvector variability within human calf muscles.

    Science.gov (United States)

    Rockel, Conrad; Noseworthy, Michael D

    2016-01-01

    To explore the effect of diffusion tensor imaging (DTI) acquisition parameters on principal and minor eigenvector stability within human lower leg skeletal muscles. Lower leg muscles were evaluated in seven healthy subjects at 3T using an 8-channel transmit/receive coil. Diffusion-encoding was performed with nine signal averages (NSA) using 6, 15, and 25 directions (NDD). Individual DTI volumes were combined into aggregate volumes of 3, 2, and 1 NSA according to number of directions. Tensor eigenvalues (λ1 , λ2 , λ3 ), eigenvectors (ε1 , ε2 , ε3 ), and DTI metrics (fractional anisotropy [FA] and mean diffusivity [MD]) were calculated for each combination of NSA and NDD. Spatial maps of signal-to-noise ratio (SNR), λ3 :λ2 ratio, and zenith angle were also calculated for region of interest (ROI) analysis of vector orientation consistency. ε1 variability was only moderately related to ε2 variability (r = 0.4045). Variation of ε1 was affected by NDD, not NSA (P < 0.0002), while variation of ε2 was affected by NSA, not NDD (P < 0.0003). In terms of tensor shape, vector variability was weakly related to FA (ε1 :r = -0.1854, ε2 : ns), but had a stronger relation to the λ3 :λ2 ratio (ε1 :r = -0.5221, ε2 :r = -0.1771). Vector variability was also weakly related to SNR (ε1 :r = -0.2873, ε2 :r = -0.3483). Zenith angle was found to be strongly associated with variability of ε1 (r = 0.8048) but only weakly with that of ε2 (r = 0.2135). The second eigenvector (ε2 ) displayed higher directional variability relative to ε1 , and was only marginally affected by experimental conditions that impacted ε1 variability. © 2015 Wiley Periodicals, Inc.

  19. Modelling Inter-relationships among water, governance, human development variables in developing countries with Bayesian networks.

    Science.gov (United States)

    Dondeynaz, C.; Lopez-Puga, J.; Carmona-Moreno, C.

    2012-04-01

    Improving Water and Sanitation Services (WSS), being a complex and interdisciplinary issue, passes through collaboration and coordination of different sectors (environment, health, economic activities, governance, and international cooperation). This inter-dependency has been recognised with the adoption of the "Integrated Water Resources Management" principles that push for the integration of these various dimensions involved in WSS delivery to ensure an efficient and sustainable management. The understanding of these interrelations appears as crucial for decision makers in the water sector in particular in developing countries where WSS still represent an important leverage for livelihood improvement. In this framework, the Joint Research Centre of the European Commission has developed a coherent database (WatSan4Dev database) containing 29 indicators from environmental, socio-economic, governance and financial aid flows data focusing on developing countries (Celine et al, 2011 under publication). The aim of this work is to model the WatSan4Dev dataset using probabilistic models to identify the key variables influencing or being influenced by the water supply and sanitation access levels. Bayesian Network Models are suitable to map the conditional dependencies between variables and also allows ordering variables by level of influence on the dependent variable. Separated models have been built for water supply and for sanitation because of different behaviour. The models are validated if complying with statistical criteria but either with scientific knowledge and literature. A two steps approach has been adopted to build the structure of the model; Bayesian network is first built for each thematic cluster of variables (e.g governance, agricultural pressure, or human development) keeping a detailed level for interpretation later one. A global model is then built based on significant indicators of each cluster being previously modelled. The structure of the

  20. Human Capital Variables and Economic Growth in Nigeria: An Interactive Effect

    Directory of Open Access Journals (Sweden)

    Adenike Mosunmola Osoba

    2017-05-01

    Full Text Available Various studies have focused on the relationship between human capital and economic growth all over the world. However, there is still a missing gap on the joint influence of human capital investment components on economic growth particularly in Nigeria. This study therefore examines the interactive effects of the relationship between human capital investment components and economic growth in Nigeria for the period of 1986 – 2014. The study employed secondary annual data on education expenditure, health expenditure, real gross domestic product and gross capital formation obtained from the Central Bank Statistical bulletin, 2014. The data were analyzed using Fully Modified Ordinary Least Squares (FMOLS technique. The results of the study showed that there was positive and significant relationship between the interactive effects of human capital components and growth in Nigeria. The study concluded that the interactive effect of the human capital variables was also in conformity with the theoretical proposition that increase in human capital will enhance growth as stipulated in the modified Solow growth model by Mankiw, Romer & Weil (1992.

  1. An analytical approach to separate climate and human contributions to basin streamflow variability

    Science.gov (United States)

    Li, Changbin; Wang, Liuming; Wanrui, Wang; Qi, Jiaguo; Linshan, Yang; Zhang, Yuan; Lei, Wu; Cui, Xia; Wang, Peng

    2018-04-01

    Climate variability and anthropogenic regulations are two interwoven factors in the ecohydrologic system across large basins. Understanding the roles that these two factors play under various hydrologic conditions is of great significance for basin hydrology and sustainable water utilization. In this study, we present an analytical approach based on coupling water balance method and Budyko hypothesis to derive effectiveness coefficients (ECs) of climate change, as a way to disentangle contributions of it and human activities to the variability of river discharges under different hydro-transitional situations. The climate dominated streamflow change (ΔQc) by EC approach was compared with those deduced by the elasticity method and sensitivity index. The results suggest that the EC approach is valid and applicable for hydrologic study at large basin scale. Analyses of various scenarios revealed that contributions of climate change and human activities to river discharge variation differed among the regions of the study area. Over the past several decades, climate change dominated hydro-transitions from dry to wet, while human activities played key roles in the reduction of streamflow during wet to dry periods. Remarkable decline of discharge in upstream was mainly due to human interventions, although climate contributed more to runoff increasing during dry periods in the semi-arid downstream. Induced effectiveness on streamflow changes indicated a contribution ratio of 49% for climate and 51% for human activities at the basin scale from 1956 to 2015. The mathematic derivation based simple approach, together with the case example of temporal segmentation and spatial zoning, could help people understand variation of river discharge with more details at a large basin scale under the background of climate change and human regulations.

  2. A general auditory bias for handling speaker variability in speech? Evidence in humans and songbirds

    Directory of Open Access Journals (Sweden)

    Buddhamas eKriengwatana

    2015-08-01

    Full Text Available Different speakers produce the same speech sound differently, yet listeners are still able to reliably identify the speech sound. How listeners can adjust their perception to compensate for speaker differences in speech, and whether these compensatory processes are unique only to humans, is still not fully understood. In this study we compare the ability of humans and zebra finches to categorize vowels despite speaker variation in speech in order to test the hypothesis that accommodating speaker and gender differences in isolated vowels can be achieved without prior experience with speaker-related variability. Using a behavioural Go/No-go task and identical stimuli, we compared Australian English adults’ (naïve to Dutch and zebra finches’ (naïve to human speech ability to categorize /ɪ/ and /ɛ/ vowels of an novel Dutch speaker after learning to discriminate those vowels from only one other speaker. Experiment 1 and 2 presented vowels of two speakers interspersed or blocked, respectively. Results demonstrate that categorization of vowels is possible without prior exposure to speaker-related variability in speech for zebra finches, and in non-native vowel categories for humans. Therefore, this study is the first to provide evidence for what might be a species-shared auditory bias that may supersede speaker-related information during vowel categorization. It additionally provides behavioural evidence contradicting a prior hypothesis that accommodation of speaker differences is achieved via the use of formant ratios. Therefore, investigations of alternative accounts of vowel normalization that incorporate the possibility of an auditory bias for disregarding inter-speaker variability are warranted.

  3. Variability of tissue mineral density can determine physiological creep of human vertebral cancellous bone.

    Science.gov (United States)

    Kim, Do-Gyoon; Shertok, Daniel; Ching Tee, Boon; Yeni, Yener N

    2011-06-03

    Creep is a time-dependent viscoelastic deformation observed under a constant prolonged load. It has been indicated that progressive vertebral deformation due to creep may increase the risk of vertebral fracture in the long-term. The objective of this study was to examine the relationships of creep with trabecular architecture and tissue mineral density (TMD) parameters in human vertebral cancellous bone at a physiological static strain level. Architecture and TMD parameters of cancellous bone were analyzed using microcomputerized tomography (micro-CT) in specimens cored out of human vertebrae. Then, creep and residual strains of the specimens were measured after a two-hour physiological compressive constant static loading and unloading cycle. Creep developed (3877 ± 2158 με) resulting in substantial levels of non-recoverable post-creep residual strain (1797 ± 1391 με). A strong positive linear correlation was found between creep and residual strain (r = 0.94, p creep rate. The TMD variability (GL(COV)) was the strongest correlate of creep rate (r = 0.79, p < 0.001). This result suggests that TMD variability may be a useful parameter for estimating the long-term deformation of a whole vertebral body. The results further suggest that the changes in TMD variability resulting from bone remodeling are of importance and may provide an insight into the understanding of the mechanisms underlying progressive failure of vertebral bodies and development of a clinical fracture. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Cytokine response to selected MTB antigens in Ghanaian TB patients, before and at 2 weeks of anti-TB therapy is characterized by high expression of IFN-γ and Granzyme B and inter- individual variation.

    Science.gov (United States)

    Mensah, Gloria Ivy; Addo, Kennedy Kwasi; Tetteh, John Amissah; Sowah, Sandra; Loescher, Thomas; Geldmacher, Christof; Jackson-Sillah, Dolly

    2014-09-10

    There has been a long held belief that patients with drug-susceptible TB are non-infectious after two weeks of therapy. Recent microbiological and epidemiological evidence has challenged this dogma, however, the nature of the Mtb-specific cellular immune response during this period has not been adequately investigated. This knowledge could be exploited in the development of immunological biomarkers of early treatment response. Cellular response to four Mtb infection phase-dependent antigens, ESAT-6/CFP-10 fusion protein and three DosR encoded proteins (Rv1733c, Rv2029c, Rv2628) were evaluated in a Ghanaian TB cohort (n=20) before and after 2 weeks of anti TB therapy. After 6-days in vitro stimulation, Peripheral blood mononuclear cell (PBMC) culture supernatant was harvested and the concentration of IFN-γ, Granzyme B, IL-10, IL-17, sIL2Rα and TNF-α were determined in a 6-plex Luminex assay. Frequencies of IFN-γ + CD4 and CD8 T cells were also determined in an intracellular cytokine assay. All antigens induced higher levels of IFN-γ, followed by Granzyme B, TNF-α and IL-17 and low levels of IL-10 and sIL-2R-α in PBMC before treatment and after 2 weeks of treatment. Median cytokine levels of IFN-γ, Granzyme B, IL-17 and sIL-2R-α increased during week two, but it was significant for only Rv1733-specific production of Granzyme B (P = 0. 013). The median frequency of antigen specific IFN-γ + CD4 T cells increased at week two; however, only the increase in the ESAT-6/CFP-10-specific response was significant (P = 0. 0008). In contrast, the median frequency of ESAT-6/CFP-10- specific IFN-γ + CD8 T cell responses declined during week two (P = 0. 0024). Additionally, wide inter-individual variation with three distinct patterns were observed; increase in all cytokine levels, decrease in all cytokine levels and fluctuating cytokine levels after 2 weeks of treatment. The second week of effective chemotherapy was characterized by a general increase in cytokine

  5. Quasi-supervised scoring of human sleep in polysomnograms using augmented input variables.

    Science.gov (United States)

    Yaghouby, Farid; Sunderam, Sridhar

    2015-04-01

    The limitations of manual sleep scoring make computerized methods highly desirable. Scoring errors can arise from human rater uncertainty or inter-rater variability. Sleep scoring algorithms either come as supervised classifiers that need scored samples of each state to be trained, or as unsupervised classifiers that use heuristics or structural clues in unscored data to define states. We propose a quasi-supervised classifier that models observations in an unsupervised manner but mimics a human rater wherever training scores are available. EEG, EMG, and EOG features were extracted in 30s epochs from human-scored polysomnograms recorded from 42 healthy human subjects (18-79 years) and archived in an anonymized, publicly accessible database. Hypnograms were modified so that: 1. Some states are scored but not others; 2. Samples of all states are scored but not for transitional epochs; and 3. Two raters with 67% agreement are simulated. A framework for quasi-supervised classification was devised in which unsupervised statistical models-specifically Gaussian mixtures and hidden Markov models--are estimated from unlabeled training data, but the training samples are augmented with variables whose values depend on available scores. Classifiers were fitted to signal features incorporating partial scores, and used to predict scores for complete recordings. Performance was assessed using Cohen's Κ statistic. The quasi-supervised classifier performed significantly better than an unsupervised model and sometimes as well as a completely supervised model despite receiving only partial scores. The quasi-supervised algorithm addresses the need for classifiers that mimic scoring patterns of human raters while compensating for their limitations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Variable postpartum responsiveness among humans and other primates with "cooperative breeding": A comparative and evolutionary perspective.

    Science.gov (United States)

    Hrdy, Sarah B

    2016-01-01

    This article is part of a Special Issue "Parental Care".Until recently, evolutionists reconstructing mother-infant bonding among human ancestors relied on nonhuman primate models characterized by exclusively maternal care, overlooking the highly variable responsiveness exhibited by mothers in species with obligate reliance on allomaternal care and provisioning. It is now increasingly recognized that apes as large-brained, slow maturing, and nutritionally dependent for so long as early humans were, could not have evolved unless "alloparents" (group members other than genetic parents), in addition to parents, had helped mothers to care for and provision offspring, a rearing system known as "cooperative breeding." Here I review situation-dependent maternal responses ranging from highly possessive to permissive, temporarily distancing, rejecting, or infanticidal, documented for a small subset of cooperatively breeding primates. As in many mammals, primate maternal responsiveness is influenced by physical condition, endocrinological priming, prior experience and local environments (especially related to security). But mothers among primates who evolved as cooperative breeders also appear unusually sensitive to cues of social support. In addition to more "sapient" or rational decision-making, humankind's deep history of cooperative breeding must be considered when trying to understand the extremely variable responsiveness of human mothers. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Human θ burst stimulation enhances subsequent motor learning and increases performance variability.

    Science.gov (United States)

    Teo, James T H; Swayne, Orlando B C; Cheeran, Binith; Greenwood, Richard J; Rothwell, John C

    2011-07-01

    Intermittent theta burst stimulation (iTBS) transiently increases motor cortex excitability in healthy humans by a process thought to involve synaptic long-term potentiation (LTP), and this is enhanced by nicotine. Acquisition of a ballistic motor task is likewise accompanied by increased excitability and presumed intracortical LTP. Here, we test how iTBS and nicotine influences subsequent motor learning. Ten healthy subjects participated in a double-blinded placebo-controlled trial testing the effects of iTBS and nicotine. iTBS alone increased the rate of learning but this increase was blocked by nicotine. We then investigated factors other than synaptic strengthening that may play a role. Behavioral analysis and modeling suggested that iTBS increased performance variability, which correlated with learning outcome. A control experiment confirmed the increase in motor output variability by showing that iTBS increased the dispersion of involuntary transcranial magnetic stimulation-evoked thumb movements. We suggest that in addition to the effect on synaptic plasticity, iTBS may have facilitated performance by increasing motor output variability; nicotine negated this effect on variability perhaps via increasing the signal-to-noise ratio in cerebral cortex.

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

    Science.gov (United States)

    McNally, Kevin; Loizou, George D

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kevin eMcNally

    2015-10-01

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

  10. Modeling impacts of human footprint and soil variability on the potential distribution of invasive plant species in different biomes

    Science.gov (United States)

    Wan, Ji-Zhong; Wang, Chun-Jing; Yu, Fei-Hai

    2017-11-01

    Human footprint and soil variability may be important in shaping the spread of invasive plant species (IPS). However, until now, there is little knowledge on how human footprint and soil variability affect the potential distribution of IPS in different biomes. We used Maxent modeling to project the potential distribution of 29 IPS with wide distributions and long introduction histories in China based on various combinations of climatic correlates, soil characteristics and human footprint. Then, we evaluated the relative importance of each type of environmental variables (climate, soil and human footprint) as well as the difference in range and similarity of the potential distribution of IPS between different biomes. Human footprint and soil variables contributed to the prediction of the potential distribution of IPS, and different types of biomes had varying responses and degrees of impacts from the tested variables. Human footprint and soil variability had the highest tendency to increase the potential distribution of IPS in Montane Grasslands and Shrublands. We propose to integrate the assessment in impacts of human footprint and soil variability on the potential distribution of IPS in different biomes into the prevention and control of plant invasion.

  11. Identifying populations sensitive to environmental chemicals by simulating toxicokinetic variability.

    Science.gov (United States)

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

    2017-09-01

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

  12. Effects of supine, prone, and lateral positions on cardiovascular and renal variables in humans

    DEFF Research Database (Denmark)

    Pump, Bettina; Talleruphuus, Ulrik; Christensen, Niels Juel

    2002-01-01

    The hypothesis was tested that changing the direction of the transverse gravitational stress in horizontal humans modulates cardiovascular and renal variables. On different study days, 14 healthy males were placed for 6 h in either the horizontal supine or prone position following 3 h of being...... supine. Eight of the subjects were in addition investigated in the horizontal left lateral position. Compared with supine, the prone position slightly increased free water clearance (349 +/- 38 vs. 447 +/- 39 ml/6 h, P = 0.05) and urine output (1,387 +/- 55 vs. 1,533 +/- 52 ml/6 h, P = 0...

  13. An Inclusive Design Method for Addressing Human Variability and Work Performance Issues

    Directory of Open Access Journals (Sweden)

    Amjad Hussain

    2013-07-01

    Full Text Available Humans play vital roles in manufacturing systems, but work performance is strongly influenced by factors such as experience, age, level of skill, physical and cognitive abilities and attitude towards work. Current manufacturing system design processes need to consider these human variability issues and their impact on work performance. An ‘inclusive design’ approach is proposed to consider the increasing diversity of the global workforce in terms of age, gender, cultural background, skill and experience. The decline in physical capabilities of older workers creates a mismatch between job demands and working capabilities which can be seen in manufacturing assembly that typically requires high physical demands for repetitive and accurate motions. The inclusive design approach leads to a reduction of this mismatch that results in a more productive, safe and healthy working environment giving benefits to the organization and individuals in terms of workforce satisfaction, reduced turnover, higher productivity and improved product quality.

  14. Imprecision in estimates of dose from ingested 137Cs due to variability in human biological characteristics

    International Nuclear Information System (INIS)

    Schwarz, G.; Dunning, D.E. Jr.

    1982-01-01

    An attempt has been made to quantify the variability in human biological parameters determining dose to man from ingestion of a unit activity of soluble 137 Cs and the resulting imprecision in the predicted total-body dose commitment. The analysis is based on an extensive review of the literature along with the application of statistical methods to determine parameter variability, correlations between parameters, and predictive imprecision. The variability in the principal biological parameters (biological half-time and total-body mass) involved can be described by a geometric standard deviation of 1.2-1.5 for adults and 1.6-1.9 for children/ adolescents of age 0.1-18 yr. The estimated predictive imprecision (using a Monte Carlo technique) in the total-body dose commitment from ingested 137 Cs can be described by a geometric standard deviation on the order of 1.3-1.4, meaning that the 99th percentile of the predicted distribution of dose is within approximately 2.1 times the mean value. The mean dose estimate is 0.009 Sv/MBq (34 mrem/μ Ci) for children/adolescents and 0.01 Sv/MBq (38 mrem/μ Ci) for adults. Little evidence of age dependence in the total-body dose from ingested 137 Cs is observed. (author)

  15. Genetic variability and cadmium metabolism and toxicity

    OpenAIRE

    Rentschler, Gerda

    2014-01-01

    Abstract: Cadmium (Cd) is ubiquitous in the environment. Human exposure in non-smokers occurs mainly via intake of healthy food like vegetables, cereals, and shellfish. Adverse health effects on kidney and bone at low-level environmental Cd exposure are well-documented in adults. There is considerable inter-individual variation in both metabolism (toxicokinetics) and toxicity (toxicodynamics) of Cd. This may be due to genetic factors. The aim of this thesis was to identify genetic fact...

  16. Contouring variability of human- and deformable-generated contours in radiotherapy for prostate cancer

    International Nuclear Information System (INIS)

    Gardner, Stephen J; Wen, Ning; Kim, Jinkoo; Liu, Chang; Pradhan, Deepak; Aref, Ibrahim; Cattaneo, Richard II; Vance, Sean; Movsas, Benjamin; Chetty, Indrin J; Elshaikh, Mohamed A

    2015-01-01

    This study was designed to evaluate contouring variability of human-and deformable-generated contours on planning CT (PCT) and CBCT for ten patients with low-or intermediate-risk prostate cancer. For each patient in this study, five radiation oncologists contoured the prostate, bladder, and rectum, on one PCT dataset and five CBCT datasets. Consensus contours were generated using the STAPLE method in the CERR software package. Observer contours were compared to consensus contour, and contour metrics (Dice coefficient, Hausdorff distance, Contour Distance, Center-of-Mass [COM] Deviation) were calculated. In addition, the first day CBCT was registered to subsequent CBCT fractions (CBCTn: CBCT2–CBCT5) via B-spline Deformable Image Registration (DIR). Contours were transferred from CBCT1 to CBCTn via the deformation field, and contour metrics were calculated through comparison with consensus contours generated from human contour set. The average contour metrics for prostate contours on PCT and CBCT were as follows: Dice coefficient—0.892 (PCT), 0.872 (CBCT-Human), 0.824 (CBCT-Deformed); Hausdorff distance—4.75 mm (PCT), 5.22 mm (CBCT-Human), 5.94 mm (CBCT-Deformed); Contour Distance (overall contour)—1.41 mm (PCT), 1.66 mm (CBCT-Human), 2.30 mm (CBCT-Deformed); COM Deviation—2.01 mm (PCT), 2.78 mm (CBCT-Human), 3.45 mm (CBCT-Deformed). For human contours on PCT and CBCT, the difference in average Dice coefficient between PCT and CBCT (approx. 2%) and Hausdorff distance (approx. 0.5 mm) was small compared to the variation between observers for each patient (standard deviation in Dice coefficient of 5% and Hausdorff distance of 2.0 mm). However, additional contouring variation was found for the deformable-generated contours (approximately 5.0% decrease in Dice coefficient and 0.7 mm increase in Hausdorff distance relative to human-generated contours on CBCT). Though deformable contours provide a reasonable starting point for contouring

  17. Statistical Learning and Adaptive Decision-Making Underlie Human Response Time Variability in Inhibitory Control

    Directory of Open Access Journals (Sweden)

    Ning eMa

    2015-08-01

    Full Text Available Response time (RT is an oft-reported behavioral measure in psychological and neurocognitive experiments, but the high level of observed trial-to-trial variability in this measure has often limited its usefulness. Here, we combine computational modeling and psychophysics to examine the hypothesis that fluctuations in this noisy measure reflect dynamic computations in human statistical learning and corresponding cognitive adjustments. We present data from the stop-signal task, in which subjects respond to a go stimulus on each trial, unless instructed not to by a subsequent, infrequently presented stop signal. We model across-trial learning of stop signal frequency, P(stop, and stop-signal onset time, SSD (stop-signal delay, with a Bayesian hidden Markov model, and within-trial decision-making with an optimal stochastic control model. The combined model predicts that RT should increase with both expected P(stop and SSD. The human behavioral data (n=20 bear out this prediction, showing P(stop and SSD both to be significant, independent predictors of RT, with P(stop being a more prominent predictor in 75% of the subjects, and SSD being more prominent in the remaining 25%. The results demonstrate that humans indeed readily internalize environmental statistics and adjust their cognitive/behavioral strategy accordingly, and that subtle patterns in RT variability can serve as a valuable tool for validating models of statistical learning and decision-making. More broadly, the modeling tools presented in this work can be generalized to a large body of behavioral paradigms, in order to extract insights about cognitive and neural processing from apparently quite noisy behavioral measures. We also discuss how this behaviorally validated model can then be used to conduct model-based analysis of neural data, in order to help identify specific brain areas for representing and encoding key computational quantities in learning and decision-making.

  18. Human platelet lysate supplementation of mesenchymal stromal cell delivery: issues of xenogenicity and species variability.

    Science.gov (United States)

    Allen, Ashley B; Butts, Emily B; Copland, Ian B; Stevens, Hazel Y; Guldberg, Robert E

    2017-10-01

    Immunogenicity of fetal bovine serum (FBS) poses a problem for its use in the propagation of autologous mesenchymal stromal cells (MSCs) for cell therapy. Human platelet lysate (hPL), an enriched growth factor solution containing mitogenic and angiogenic cues, has potential utility in replacing FBS for human MSC (hMSC) delivery strategies. Despite its potentiation of hMSC number in vitro, little is known concerning its capacity to supplement implanted hMSC-seeded constructs and promote tissue regeneration in vivo. In this study, we tested the effects of incorporating hPL in cell-seeded constructs implanted subcutaneously into immunocompromised rats, investigated in vitro interactions between hPL and rat MSCs (rMSCs) and determined interspecies variability in the PL product [hPL vs rat PL (rPL)] and its effect on cultured MSCs (hPL/hMSCs vs rPL/rMSCs). The overarching aim was to determine the utility of hPL to foster MSC survival in preclinical rodent models. Exposure to hPL-supplemented media resulted in rMSC death, by a process attributable to heat-labile proteins, but not membrane attack complex formation. In the in vitro syngeneic model, the rodent product proved fundamentally distinct from the human product, with rPL having substantially lower growth factor content than hPL. Moreover, contrary to the positive effects of hPL on hMSC expansion, rPL did not reduce rMSC doubling time for the serum concentrations examined. When tested in vivo, hPL did not improve cell survival within hydrogel constructs through 2 weeks postimplantation. In summary, this study highlights the many facets of xenogenicity and interspecies variability that must be considered in the preclinical evaluation of hPL. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Statistical learning and adaptive decision-making underlie human response time variability in inhibitory control.

    Science.gov (United States)

    Ma, Ning; Yu, Angela J

    2015-01-01

    Response time (RT) is an oft-reported behavioral measure in psychological and neurocognitive experiments, but the high level of observed trial-to-trial variability in this measure has often limited its usefulness. Here, we combine computational modeling and psychophysics to examine the hypothesis that fluctuations in this noisy measure reflect dynamic computations in human statistical learning and corresponding cognitive adjustments. We present data from the stop-signal task (SST), in which subjects respond to a go stimulus on each trial, unless instructed not to by a subsequent, infrequently presented stop signal. We model across-trial learning of stop signal frequency, P(stop), and stop-signal onset time, SSD (stop-signal delay), with a Bayesian hidden Markov model, and within-trial decision-making with an optimal stochastic control model. The combined model predicts that RT should increase with both expected P(stop) and SSD. The human behavioral data (n = 20) bear out this prediction, showing P(stop) and SSD both to be significant, independent predictors of RT, with P(stop) being a more prominent predictor in 75% of the subjects, and SSD being more prominent in the remaining 25%. The results demonstrate that humans indeed readily internalize environmental statistics and adjust their cognitive/behavioral strategy accordingly, and that subtle patterns in RT variability can serve as a valuable tool for validating models of statistical learning and decision-making. More broadly, the modeling tools presented in this work can be generalized to a large body of behavioral paradigms, in order to extract insights about cognitive and neural processing from apparently quite noisy behavioral measures. We also discuss how this behaviorally validated model can then be used to conduct model-based analysis of neural data, in order to help identify specific brain areas for representing and encoding key computational quantities in learning and decision-making.

  20. Early variability in the conceptualisation of "sustainable development and human factors".

    Science.gov (United States)

    Thatcher, Andrew

    2012-01-01

    The sub-discipline of "sustainable development and human factors" is relatively new, first being used in 2006 with a Technical Committee of the IEA being established only in 2009 and a similar special interest group on "green ergonomics" at the Institute of Ergonomics and Human Factors being established in 2010. In general though, the definitions and practice of "sustainable development" is highly contentious and ambiguous across a range of disciplines. This paper examines the diversity of definitions and approaches to sustainable development and human factors in the early papers in this sub-discipline. An examination of 45 chapters and papers (from 2008 to 2011) reveals a surprising consistency in the definitions used for sustainable development but also a large proportion of the papers where no definitions are given at all. The majority of papers were, however, biased towards an economic capital and social capital emphasis, which is to be expected of work traditionally in the ergonomics paradigm. Further, most papers were theoretical in nature demonstrating a great opportunity for empirical work. The variability in definitions is discussed in relation to the future challenges facing the growth of this emergent sub-discipline and opportunities for further theoretical and empirical work.

  1. THE SEAFARERS’ HUMAN CAPITAL VARIABLES AND THE CREW PROFILE DYNAMIC ADJUSTMENT

    Directory of Open Access Journals (Sweden)

    Catalin POPA

    2016-06-01

    Full Text Available The human capital is one of the most relevant functional dimensions of the maritime transportation business, considering the seaborne particularities in the crossing countries, cultures and heterogeneous environment as onboard the maritime vessels. The nowadays great competitiveness in this area of transportation services has encouraged many companies to pursue new ways to maintain a competitive advantage, valuing its human capital. Thus, in spite of the propensity for standardisation in field of human resources profile, the seafaring crews’ management is still facing lots of issues in operational tasks’ fulfilment onboard to maritime ships, due to individual misalignment within the collective framework of the on-board teams. As is presented in the article, the individual profile of a seafarer has to be precisely defined to be efficiently integrated in the crew, but not only in professional matters, but also into a comprehensive manner, in order to support a proper adjustment of the individual seafarer behaviour to the group profile requirement, onboard to maritime vessels. STCW provisions are very welcomed in establishing common standards for professional variable of the seafarers’ individual profile, but is still missing to approach the organizational dimensions, apart to the leadership skills or risk behaviour. As shown in the article below, for a recruitment agent and further, for the ship Master is important to find the suitable employee, not only in terms of professional knowledge, skills and abilities, but also in cultural or psycho-sociological individual dimensions, as to adjust the individual to the group profile, accordingly and effectively.

  2. Enhancing the effectiveness of human-robot teaming with a closed-loop system.

    Science.gov (United States)

    Teo, Grace; Reinerman-Jones, Lauren; Matthews, Gerald; Szalma, James; Jentsch, Florian; Hancock, Peter

    2018-02-01

    With technological developments in robotics and their increasing deployment, human-robot teams are set to be a mainstay in the future. To develop robots that possess teaming capabilities, such as being able to communicate implicitly, the present study implemented a closed-loop system. This system enabled the robot to provide adaptive aid without the need for explicit commands from the human teammate, through the use of multiple physiological workload measures. Such measures of workload vary in sensitivity and there is large inter-individual variability in physiological responses to imposed taskload. Workload models enacted via closed-loop system should accommodate such individual variability. The present research investigated the effects of the adaptive robot aid vs. imposed aid on performance and workload. Results showed that adaptive robot aid driven by an individualized workload model for physiological response resulted in greater improvements in performance compared to aid that was simply imposed by the system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Analysing inter-relationships among water, governance, human development variables in developing countries

    Science.gov (United States)

    Dondeynaz, C.; Carmona Moreno, C.; Céspedes Lorente, J. J.

    2012-10-01

    The "Integrated Water Resources Management" principle was formally laid down at the International Conference on Water and Sustainable development in Dublin 1992. One of the main results of this conference is that improving Water and Sanitation Services (WSS), being a complex and interdisciplinary issue, passes through collaboration and coordination of different sectors (environment, health, economic activities, governance, and international cooperation). These sectors influence or are influenced by the access to WSS. The understanding of these interrelations appears as crucial for decision makers in the water sector. In this framework, the Joint Research Centre (JRC) of the European Commission (EC) has developed a new database (WatSan4Dev database) containing 42 indicators (called variables in this paper) from environmental, socio-economic, governance and financial aid flows data in developing countries. This paper describes the development of the WatSan4Dev dataset, the statistical processes needed to improve the data quality, and finally, the analysis to verify the database coherence is presented. Based on 25 relevant variables, the relationships between variables are described and organised into five factors (HDP - Human Development against Poverty, AP - Human Activity Pressure on water resources, WR - Water Resources, ODA - Official Development Aid, CEC - Country Environmental Concern). Linear regression methods are used to identify key variables having influence on water supply and sanitation. First analysis indicates that the informal urbanisation development is an important factor negatively influencing the percentage of the population having access to WSS. Health, and in particular children's health, benefits from the improvement of WSS. Irrigation is also enhancing Water Supply service thanks to multi-purpose infrastructure. Five country profiles are also created to deeper understand and synthetize the amount of information gathered. This new

  4. Analysing inter-relationships among water, governance, human development variables in developing countries

    Directory of Open Access Journals (Sweden)

    C. Dondeynaz

    2012-10-01

    Full Text Available The "Integrated Water Resources Management" principle was formally laid down at the International Conference on Water and Sustainable development in Dublin 1992. One of the main results of this conference is that improving Water and Sanitation Services (WSS, being a complex and interdisciplinary issue, passes through collaboration and coordination of different sectors (environment, health, economic activities, governance, and international cooperation. These sectors influence or are influenced by the access to WSS. The understanding of these interrelations appears as crucial for decision makers in the water sector. In this framework, the Joint Research Centre (JRC of the European Commission (EC has developed a new database (WatSan4Dev database containing 42 indicators (called variables in this paper from environmental, socio-economic, governance and financial aid flows data in developing countries. This paper describes the development of the WatSan4Dev dataset, the statistical processes needed to improve the data quality, and finally, the analysis to verify the database coherence is presented. Based on 25 relevant variables, the relationships between variables are described and organised into five factors (HDP – Human Development against Poverty, AP – Human Activity Pressure on water resources, WR – Water Resources, ODA – Official Development Aid, CEC – Country Environmental Concern. Linear regression methods are used to identify key variables having influence on water supply and sanitation. First analysis indicates that the informal urbanisation development is an important factor negatively influencing the percentage of the population having access to WSS. Health, and in particular children's health, benefits from the improvement of WSS. Irrigation is also enhancing Water Supply service thanks to multi-purpose infrastructure. Five country profiles are also created to deeper understand and synthetize the amount of information gathered

  5. Variability in anatomical features of human clavicle: Its forensic anthropological and clinical significance

    Directory of Open Access Journals (Sweden)

    Jagmahender Singh Sehrawat

    2016-06-01

    Full Text Available Bones can reflect the basic framework of human body and may provide valuable information about the biological identity of the deceased. They, often, survive the morphological alterations, taphonomic destructions, decay/mutilation and decomposition insults. In-depth knowledge of variations in clavicular shape, size and its dimensions is very important from both clinical (fixation of clavicular fractures using external or inter-medullary devices, designing orthopedic fixation devices as well as forensic anthropological perspectives. Human clavicle is the most frequently fractured bone of human skeleton, possessing high degree of variability in its anatomical, biomechanical and morphological features. Extended period of skeletal growth (up to third decade in clavicle imparts it an additional advantage for forensic identification purposes. In present study, five categories of clavicular features like lengths, diameters, angles, indices and robustness were examined to explore the suitability of collarbone for forensic and clinical purposes. For this purpose, 263 pairs of adult clavicles (195 Males and 68 Females were collected from autopsied cadavers and were studied for 13 anatomical features. Gender and occupational affiliations of cadavers were found to have significant influences on anatomical dimensions of their clavicles. Product index, weight and circumference of collarbone were found the best univariate variables, discriminating sex of more than 80% individuals. The best multivariate Function-I (DF: -17.315 + 0.054 CL-L+0.196 CC-R+0.184 DM-L could identify sex and occupation of 89.4% (89.2% Male and 89.7% Female and 65.4% individuals, respectively. All clavicular variables were found bilaterally asymmetric; left clavicles being significantly longer in length, lighter in weight, smooth in texture and less curved than the right side bones. Among non-metric traits, sub-clavian groove, nutrient foramina and ‘type’ of clavicle exhibited

  6. Searching for the variables that control human rule-governed "insensitivity".

    Science.gov (United States)

    Fox, Adam E; Kyonka, Elizabeth G E

    2017-09-01

    Verbal rules or instructions often exert obvious and meaningful control over human behavior. Sometimes instructions benefit the individual by enabling faster acquisition of a skill or by obviating an aversive consequence. However, research has also suggested a clear disadvantage: "insensitivity" to changing underlying contingencies. The two experiments described here investigated the variables that control initial rule-following behavior and rule-following insensitivity. When the initial rule was inaccurate, behavior was consistent with the rule for approximately half of participants and all participants' behavior was mostly insensitive to changing contingencies. When the initial rule was accurate, behavior of all participants was consistent with it and behavior for nearly all participants was insensitive to changes in underlying contingencies. These findings have implications for how best to establish and maintain rule-following behavior in applied settings when deviant behavior would be more reinforcing to the individual. © 2017 Society for the Experimental Analysis of Behavior.

  7. Androgen responsiveness to competition in humans: the role of cognitive variables

    Directory of Open Access Journals (Sweden)

    Oliveira GA

    2014-02-01

    Full Text Available Gonçalo A Oliveira,1 Rui F Oliveira1,2 1Unidade de Investigação em Eco-Etologia, ISPA – Instituto Universitário, Lisbon, Portugal; 2Champalimaud Neuroscience Program, Instituto Gulbenkian de Ciência, Oeiras, Portugal Abstract: Although androgens are commonly seen as male sex hormones, it has been established over the years that in both sexes, androgens also respond to social challenges. To explain the socially driven changes in androgens, two theoretical models have been proposed: the biosocial model and the challenge hypothesis. These models are typically seen as partly overlapping; however, they generate different predictions that are clarified here. In humans, sports competition and nonmetabolic competitive tasks have been used in the laboratory setting, as a proxy for agonistic interactions in animals. The results reviewed here show that the testosterone (T response to competition in humans is highly variable – the studies present postcompetition T levels and changes in T that depend on the contest outcome and that cannot be predicted by the current theoretical models. These conflicting results bring to the foreground the importance of considering cognitive factors that could moderate the androgen response to competition. Among these variables, we elect cognitive appraisal and its components as a key candidate modulating factor. It is known that T also modulates the cognitive processes that are relevant to performance in competition. In this article, we reviewed the evidence arising from studies investigating the effect of administering exogenous T and compare those results with the findings from studies that measured endogenous T levels. Finally, we summarized the importance of also considering the interaction between androgens and other hormones, such as cortisol, when investigating the social modulation of T, as proposed by the dual-hormone hypothesis. Keywords: testosterone, challenge hypothesis, biosocial model, cognitive

  8. Climate Variability and Human Migration in the Netherlands, 1865–1937

    Science.gov (United States)

    Jennings, Julia A.; Gray, Clark L.

    2014-01-01

    Human migration is frequently cited as a potential social outcome of climate change and variability, and these effects are often assumed to be stronger in the past when economies were less developed and markets more localized. Yet, few studies have used historical data to test the relationship between climate and migration directly. In addition, the results of recent studies that link demographic and climate data are not consistent with conventional narratives of displacement responses. Using longitudinal individual-level demographic data from the Historical Sample of the Netherlands (HSN) and climate data that cover the same period, we examine the effects of climate variability on migration using event history models. Only internal moves in the later period and for certain social groups are associated with negative climate conditions, and the strength and direction of the observed effects change over time. International moves decrease with extreme rainfall, suggesting that the complex relationships between climate and migration that have been observed for contemporary populations extend into the nineteenth century. PMID:25937689

  9. Dynamic Network Communication in the Human Functional Connectome Predicts Perceptual Variability in Visual Illusion.

    Science.gov (United States)

    Wang, Zhiwei; Zeljic, Kristina; Jiang, Qinying; Gu, Yong; Wang, Wei; Wang, Zheng

    2018-01-01

    Ubiquitous variability between individuals in visual perception is difficult to standardize and has thus essentially been ignored. Here we construct a quantitative psychophysical measure of illusory rotary motion based on the Pinna-Brelstaff figure (PBF) in 73 healthy volunteers and investigate the neural circuit mechanisms underlying perceptual variation using functional magnetic resonance imaging (fMRI). We acquired fMRI data from a subset of 42 subjects during spontaneous and 3 stimulus conditions: expanding PBF, expanding modified-PBF (illusion-free) and expanding modified-PBF with physical rotation. Brain-wide graph analysis of stimulus-evoked functional connectivity patterns yielded a functionally segregated architecture containing 3 discrete hierarchical networks, commonly shared between rest and stimulation conditions. Strikingly, communication efficiency and strength between 2 networks predominantly located in visual areas robustly predicted individual perceptual differences solely in the illusory stimulus condition. These unprecedented findings demonstrate that stimulus-dependent, not spontaneous, dynamic functional integration between distributed brain networks contributes to perceptual variability in humans. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. UL146 variability among clinical isolates of Human Cytomegalovirus from Japan

    Directory of Open Access Journals (Sweden)

    Francisco Aguayo

    2010-01-01

    Full Text Available Human Cytomegalovirus (HCMV is a herpesvirus associated with serious diseases in immunocompromised subjects. The region between ORF UL133 and UL151 from HCMV, named ULb' is frequently deleted in attenuated AD169 and in highly passaged laboratory strains. However, this region is conserved in low-passaged and more virulent HCMV, like the Toledo strain. The UL146 gene, which is located in the ULb' region, encodes a CXC-chemokine analogue. The diversity of UL146 gene was evaluated among fifty-six clinical isolates of HCMV from Japan. Results show that UL146 gene was successfully amplified by the polymerase chain reaction (PCR in only 17/56 strains (30%, while the success rate for UL145/UL147 gene was 18/56 strains (32%. After DNA sequencing, the 35 amplified strains were classified into 8 groups. When compared, variability of UL146 ranged from 25.1% to 52.9% at the DNA level and from 34.5% to 67% at the amino acid level. Seven groups had the interleukin-8 (IL-8 motif ERL (Glu-Leu-Arg CXC and one group had only the CXC motif, suggesting the absence of the IL-8 function of UL146. In conclusion, we found that UL146 gene of HCMV is hyper-variable in clinical strains from Japan suggesting the possibility of a different function in each sequence group.

  11. Exploring the impact of climate variability during the Last Glacial Maximum on the pattern of human occupation of Iberia.

    Science.gov (United States)

    Burke, Ariane; Levavasseur, Guillaume; James, Patrick M A; Guiducci, Dario; Izquierdo, Manuel Arturo; Bourgeon, Lauriane; Kageyama, Masa; Ramstein, Gilles; Vrac, Mathieu

    2014-08-01

    The Last Glacial Maximum (LGM) was a global climate event, which had significant repercussions for the spatial distribution and demographic history of prehistoric populations. In Eurasia, the LGM coincides with a potential bottleneck for modern humans and may mark the divergence date for Asian and European populations (Keinan et al., 2007). In this research, the impact of climate variability on human populations in the Iberian Peninsula during the Last Glacial Maximum (LGM) is examined with the aid of downscaled high-resolution (16 × 16 km) numerical climate experiments. Human sensitivity to short time-scale (inter-annual) climate variability during this key time period, which follows the initial modern human colonisation of Eurasia and the extinction of the Neanderthals, is tested using the spatial distribution of archaeological sites. Results indicate that anatomically modern human populations responded to small-scale spatial patterning in climate variability, specifically inter-annual variability in precipitation levels as measured by the standard precipitation index. Climate variability at less than millennial scale, therefore, is shown to be an important component of ecological risk, one that played a role in regulating the spatial behaviour of prehistoric human populations and consequently affected their social networks. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Human and bovine viruses in the Milwaukee River Watershed: hydrologically relevant representation and relations with environmental variables

    Science.gov (United States)

    Corsi, Steven R.; Borchardt, M. A.; Spencer, S. K.; Hughes, Peter E.; Baldwin, Austin K.

    2014-01-01

    To examine the occurrence, hydrologic variability, and seasonal variability of human and bovine viruses in surface water, three stream locations were monitored in the Milwaukee River watershed in Wisconsin, USA, from February 2007 through June 2008. Monitoring sites included an urban subwatershed, a rural subwatershed, and the Milwaukee River at the mouth. To collect samples that characterize variability throughout changing hydrologic periods, a process control system was developed for unattended, large-volume (56–2800 L) filtration over extended durations. This system provided flow-weighted mean concentrations during runoff and extended (24-h) low-flow periods. Human viruses and bovine viruses were detected by real-time qPCR in 49% and 41% of samples (n = 63), respectively. All human viruses analyzed were detected at least once including adenovirus (40% of samples), GI norovirus (10%), enterovirus (8%), rotavirus (6%), GII norovirus (1.6%) and hepatitis A virus (1.6%). Three of seven bovine viruses analyzed were detected including bovine polyomavirus (32%), bovine rotavirus (19%), and bovine viral diarrhea virus type 1 (5%). Human viruses were present in 63% of runoff samples resulting from precipitation and snowmelt, and 20% of low-flow samples. Maximum human virus concentrations exceeded 300 genomic copies/L. Bovine viruses were present in 46% of runoff samples resulting from precipitation and snowmelt and 14% of low-flow samples. The maximum bovine virus concentration was 11 genomic copies/L. Statistical modeling indicated that stream flow, precipitation, and season explained the variability of human viruses in the watershed, and hydrologic condition (runoff event or low-flow) and season explained the variability of the sum of human and bovine viruses; however, no model was identified that could explain the variability of bovine viruses alone. Understanding the factors that affect virus fate and transport in rivers will aid watershed management for minimizing

  13. Expression profiling of interindividual variability following xenobiotic exposures in primary human hepatocyte cultures

    International Nuclear Information System (INIS)

    Goyak, Katy M.O.; Johnson, Mary C.; Strom, Stephen C.; Omiecinski, Curtis J.

    2008-01-01

    To examine the magnitude of human variability across the entire transcriptome after chemical challenge, we profiled gene expression responses to three different prototypic chemical inducers in primary human hepatocyte cultures from ten independent donors. Correlation between basal expression in any two hepatocyte donors ranged from r 2 values of 0.967 to 0.857, and chemical treatment tended to negatively impact correlation between donors. Including anticipated target genes, 10,812, 8373, and 7847 genes were changed in at least one donor by Aroclor 1254 (A1254), di(2-ethylhexyl) phthalate (DEHP), and phenobarbital (PB), respectively. A subset of these gene targets (n = 41) were altered with a high level of reproducibility in at least 9 donors, gene responses that correlated well with literature-reported mechanism of action. Filtering responses to the level of gene subsets clarified the biological impact associated with the respective chemical effectors, in lieu of substantial interindividual variation among donor responses. In these respects, the use of hierarchical clustering methods successfully grouped seven of the ten donors into chemical-specific rather than donor-specific clusters. However, at the whole-genome level, the magnitude of conserved gene expression changes among donors was surprisingly small, with fewer than 50% of the gene responses altered by a single chemical conserved in more than one donor. The use of higher level descriptors, such as those defined by the PANTHER classification system, may enable more consistent categorization of gene expression changes across individuals, as increased reproducibility was identified using this method

  14. On the Climate Variability and Energy Demands for Indoor Human Comfort Levels in Tropical Urban Environment

    Science.gov (United States)

    Pokhrel, R.; Ortiz, L. E.; González, J. E.; Ramírez-Beltran, N. D.

    2017-12-01

    The main objective of this study is to identify how climate variability influences human comfort levels in tropical urban environments. San Juan Metropolitan Area (SJMA) of the island of Puerto Rico was chosen as a reference point. A new human discomfort index (HDI) based on environmental enthalpy is defined. This index is expanded to determine the energy required to maintain indoor human comfort levels and was compared to Total Electricity consumption for the Island of Puerto Rico. Regression analysis shows that both Temperature and HDI are good indictor to predict total electrical energy consumption. Results showed that over the past 35 years the average enthalpy have increased and have mostly been above thresholds for human comfort for SJMA. The weather stations data further shows a clear indication of urbanization biases ramping up the index considered. From the trend analysis local scale (weather station) data shows a decreasing rate of maximum cooling at -11.41 kW-h/years, and minimum is increasing at 10.64 kW-h/years. To compare human comfort levels under extreme heat wave events conditions, an event of 2014 in the San Juan area was identified. The analysis for this extreme heat event is complemented by data from the National Center for environmental Prediction (NCEP) at 250km spatial resolution, North American Re-Analysis (NARR) at 32 km spatial resolution, by simulations of the Weather Forecasting System (WRF) at a resolution of 2 km, and by weather station data for San Juan. WRF simulation's results showed an improvement for both temperature and relative humidity from the input NCEP data. It also shows that difference in Energy per Capita (EPC) in urban area during a heat wave event can increase to 16% over a non-urban area. Sensitivity analysis was done by modifying the urban land cover to the most common rural references of evergreen broadleaf forest and cropland to investigate the Urban Heat Island (UHI) effect on HDI. UHI is seen to be maximum during

  15. Elasticity in ecosystem services: exploring the variable relationship between ecosystems and human well-being

    Directory of Open Access Journals (Sweden)

    Tim M. Daw

    2016-06-01

    Full Text Available Although ecosystem services are increasingly recognized as benefits people obtain from nature, we still have a poor understanding of how they actually enhance multidimensional human well-being, and how well-being is affected by ecosystem change. We develop a concept of "ecosystem service elasticity" (ES elasticity that describes the sensitivity of human well-being to changes in ecosystems. ES Elasticity is a result of complex social and ecological dynamics and is context dependent, individually variable, and likely to demonstrate nonlinear dynamics such as thresholds and hysteresis. We present a conceptual framework that unpacks the chain of causality from ecosystem stocks through flows, goods, value, and shares to contribute to the well-being of different people. This framework builds on previous conceptualizations, but places multidimensional well-being of different people as the final element. This ultimately disaggregated approach emphasizes how different people access benefits and how benefits match their needs or aspirations. Applying this framework to case studies of individual coastal ecosystem services in East Africa illustrates a wide range of social and ecological factors that can affect ES elasticity. For example, food web and habitat dynamics affect the sensitivity of different fisheries ecosystem services to ecological change. Meanwhile high cultural significance, or lack of alternatives enhance ES elasticity, while social mechanisms that prevent access can reduce elasticity. Mapping out how chains are interlinked illustrates how different types of value and the well-being of different people are linked to each other and to common ecological stocks. We suggest that examining chains for individual ecosystem services can suggest potential interventions aimed at poverty alleviation and sustainable ecosystems while mapping out of interlinkages between chains can help to identify possible ecosystem service trade-offs and winners and

  16. Environmental spread of microbes impacts the development of metabolic phenotypes in mice transplanted with microbial communities from humans

    DEFF Research Database (Denmark)

    Zhang, Li; Bahl, Martin Iain; Roager, Henrik Munch

    2017-01-01

    Microbiota transplantation to germ-free animals is a powerful method to study involvement of gut microbes in the aetiology of metabolic syndrome. Owing to large interpersonal variability in gut microbiota, studies with broad coverage of donors are needed to elucidate the establishment of human......, thereby allowing us to explore the extent of microbial spread between cages in a well-controlled environment. Despite high group-wise similarity between obese and control human microbiotas, transplanted mice in the four isolators developed distinct gut bacterial composition and activity, body mass gain......, and insulin resistance. Spread of microbes between cages within isolators interacted with establishment of the transplanted microbiotas in mice, and contributed to the transmission of metabolic phenotypes. Our findings highlight the impact of donor variability and reveal that inter-individual spread...

  17. Relating Linear and Volumetric Variables Through Body Scanning to Improve Human Interfaces in Space

    Science.gov (United States)

    Margerum, Sarah E.; Ferrer, Mike A.; Young, Karen S.; Rajulu, Sudhakar

    2010-01-01

    Designing space suits and vehicles for the diverse human population present unique challenges for the methods of traditional anthropometry. Space suits are bulky and allow the operator to shift position within the suit and inhibit the ability to identify body landmarks. Limited suit sizing options also cause variability in fit and performance between similarly sized individuals. Space vehicles are restrictive in volume in both the fit and the ability to collect data. NASA's Anthropometric and Biomechanics Facility (ABF) has utilized 3D scanning to shift from traditional linear anthropometry to explore and examine volumetric capabilities to provide anthropometric solutions for design. Overall, the key goals are to improve the human-system performance and develop new processes to aid in the design and evaluation of space systems. Four case studies are presented that illustrate the shift from purely linear analyses to an augmented volumetric toolset to predict and analyze the human within the space suit and vehicle. The first case study involves the calculation of maximal head volume to estimate total free volume in the helmet for proper air exchange. Traditional linear measurements resulted in an inaccurate representation of the head shape, yet limited data exists for the determination of a large head volume. Steps were first taken to identify and classify a maximum head volume and the resulting comparisons to the estimate are presented in this paper. This study illustrates the gap between linear components of anthropometry and the need for overall volume metrics in order to provide solutions. A second case study examines the overlay of the space suit scans and components onto scanned individuals to quantify fit and clearance to aid in sizing the suit to the individual. Restrictions in space suit size availability present unique challenges to optimally fit the individual within a limited sizing range while maintaining performance. Quantification of the clearance and

  18. Impacts of climate variability and future climate change on harmful algal blooms and human health

    Science.gov (United States)

    Moore, Stephanie K; Trainer, Vera L; Mantua, Nathan J; Parker, Micaela S; Laws, Edward A; Backer, Lorraine C; Fleming, Lora E

    2008-01-01

    Anthropogenically-derived increases in atmospheric greenhouse gas concentrations have been implicated in recent climate change, and are projected to substantially impact the climate on a global scale in the future. For marine and freshwater systems, increasing concentrations of greenhouse gases are expected to increase surface temperatures, lower pH, and cause changes to vertical mixing, upwelling, precipitation, and evaporation patterns. The potential consequences of these changes for harmful algal blooms (HABs) have received relatively little attention and are not well understood. Given the apparent increase in HABs around the world and the potential for greater problems as a result of climate change and ocean acidification, substantial research is needed to evaluate the direct and indirect associations between HABs, climate change, ocean acidification, and human health. This research will require a multidisciplinary approach utilizing expertise in climatology, oceanography, biology, epidemiology, and other disciplines. We review the interactions between selected patterns of large-scale climate variability and climate change, oceanic conditions, and harmful algae. PMID:19025675

  19. Neuronal Substrates Underlying Performance Variability in Well-Trained Skillful Motor Task in Humans.

    Science.gov (United States)

    Mizuguchi, Nobuaki; Uehara, Shintaro; Hirose, Satoshi; Yamamoto, Shinji; Naito, Eiichi

    2016-01-01

    Motor performance fluctuates trial by trial even in a well-trained motor skill. Here we show neural substrates underlying such behavioral fluctuation in humans. We first scanned brain activity with functional magnetic resonance imaging while healthy participants repeatedly performed a 10 s skillful sequential finger-tapping task. Before starting the experiment, the participants had completed intensive training. We evaluated task performance per trial (number of correct sequences in 10 s) and depicted brain regions where the activity changes in association with the fluctuation of the task performance across trials. We found that the activity in a broader range of frontoparietocerebellar network, including the bilateral dorsolateral prefrontal cortex (DLPFC), anterior cingulate and anterior insular cortices, and left cerebellar hemisphere, was negatively correlated with the task performance. We further showed in another transcranial direct current stimulation (tDCS) experiment that task performance deteriorated, when we applied anodal tDCS to the right DLPFC. These results indicate that fluctuation of brain activity in the nonmotor frontoparietocerebellar network may underlie trial-by-trial performance variability even in a well-trained motor skill, and its neuromodulation with tDCS may affect the task performance.

  20. Climate Variability and the Occurrence of Human Puumala Hantavirus Infections in Europe: A Systematic Review.

    Science.gov (United States)

    Roda Gracia, J; Schumann, B; Seidler, A

    2015-09-01

    Hantaviruses are distributed worldwide and are transmitted by rodents. In Europe, the infection usually manifests as a mild form of haemorrhagic fever with renal syndrome (HFRS) known as nephropathia epidemica (NE), which is triggered by the virus species Puumala. Its host is the bank vole (Myodes glareolus). In the context of climate change, interest in the role of climatic factors for the disease has increased. A systematic review was conducted to investigate the association between climate variability and the occurrence of human Puumala hantavirus infections in Europe. We performed a literature search in the databases MEDLINE, EMBASE and Web of Science. Studies that investigated Puumala virus infection and climatic factors in any European country with a minimum collection period of 2 years were included. The selection of abstracts and the evaluation of included studies were performed by two independent reviewers. A total of 434 titles were identified in the databases, of which nine studies fulfilled the inclusion criteria. The majority of studies were conducted in central Europe (Belgium, France and Germany), while only two came from the north (Sweden) and one from the south (Bosnia). Strong evidence was found for a positive association between temperature and NE incidence in central Europe, while the evidence for northern Europe so far appears insufficient. Results regarding precipitation were contradictory. Overall, the complex relationships between climate and hantavirus infections need further exploration to identify specific health risks and initiate appropriate intervention measures in the context of climate change. © 2014 Blackwell Verlag GmbH.

  1. Impacts of climate variability and future climate change on harmful algal blooms and human health.

    Science.gov (United States)

    Moore, Stephanie K; Trainer, Vera L; Mantua, Nathan J; Parker, Micaela S; Laws, Edward A; Backer, Lorraine C; Fleming, Lora E

    2008-11-07

    Anthropogenically-derived increases in atmospheric greenhouse gas concentrations have been implicated in recent climate change, and are projected to substantially impact the climate on a global scale in the future. For marine and freshwater systems, increasing concentrations of greenhouse gases are expected to increase surface temperatures, lower pH, and cause changes to vertical mixing, upwelling, precipitation, and evaporation patterns. The potential consequences of these changes for harmful algal blooms (HABs) have received relatively little attention and are not well understood. Given the apparent increase in HABs around the world and the potential for greater problems as a result of climate change and ocean acidification, substantial research is needed to evaluate the direct and indirect associations between HABs, climate change, ocean acidification, and human health. This research will require a multidisciplinary approach utilizing expertise in climatology, oceanography, biology, epidemiology, and other disciplines. We review the interactions between selected patterns of large-scale climate variability and climate change, oceanic conditions, and harmful algae.

  2. Human and bovine viruses in the Milwaukee River watershed: Hydrologically relevant representation and relations with environmental variables

    Energy Technology Data Exchange (ETDEWEB)

    Corsi, S.R., E-mail: srcorsi@usgs.gov [U.S. Geological Survey, Wisconsin Water Science Center, Middleton, WI 53562 (United States); Borchardt, M.A.; Spencer, S.K. [U.S. Department of Agriculture, Agricultural Research Service, 2615 Yellowstone Dr., Marshfield, WI 54449 (United States); Hughes, P.E.; Baldwin, A.K. [U.S. Geological Survey, Wisconsin Water Science Center, Middleton, WI 53562 (United States)

    2014-08-15

    To examine the occurrence, hydrologic variability, and seasonal variability of human and bovine viruses in surface water, three stream locations were monitored in the Milwaukee River watershed in Wisconsin, USA, from February 2007 through June 2008. Monitoring sites included an urban subwatershed, a rural subwatershed, and the Milwaukee River at the mouth. To collect samples that characterize variability throughout changing hydrologic periods, a process control system was developed for unattended, large-volume (56–2800 L) filtration over extended durations. This system provided flow-weighted mean concentrations during runoff and extended (24-h) low-flow periods. Human viruses and bovine viruses were detected by real-time qPCR in 49% and 41% of samples (n = 63), respectively. All human viruses analyzed were detected at least once including adenovirus (40% of samples), GI norovirus (10%), enterovirus (8%), rotavirus (6%), GII norovirus (1.6%) and hepatitis A virus (1.6%). Three of seven bovine viruses analyzed were detected including bovine polyomavirus (32%), bovine rotavirus (19%), and bovine viral diarrhea virus type 1 (5%). Human viruses were present in 63% of runoff samples resulting from precipitation and snowmelt, and 20% of low-flow samples. Maximum human virus concentrations exceeded 300 genomic copies/L. Bovine viruses were present in 46% of runoff samples resulting from precipitation and snowmelt and 14% of low-flow samples. The maximum bovine virus concentration was 11 genomic copies/L. Statistical modeling indicated that stream flow, precipitation, and season explained the variability of human viruses in the watershed, and hydrologic condition (runoff event or low-flow) and season explained the variability of the sum of human and bovine viruses; however, no model was identified that could explain the variability of bovine viruses alone. Understanding the factors that affect virus fate and transport in rivers will aid watershed management for minimizing

  3. Human and bovine viruses in the Milwaukee River watershed: Hydrologically relevant representation and relations with environmental variables

    International Nuclear Information System (INIS)

    Corsi, S.R.; Borchardt, M.A.; Spencer, S.K.; Hughes, P.E.; Baldwin, A.K.

    2014-01-01

    To examine the occurrence, hydrologic variability, and seasonal variability of human and bovine viruses in surface water, three stream locations were monitored in the Milwaukee River watershed in Wisconsin, USA, from February 2007 through June 2008. Monitoring sites included an urban subwatershed, a rural subwatershed, and the Milwaukee River at the mouth. To collect samples that characterize variability throughout changing hydrologic periods, a process control system was developed for unattended, large-volume (56–2800 L) filtration over extended durations. This system provided flow-weighted mean concentrations during runoff and extended (24-h) low-flow periods. Human viruses and bovine viruses were detected by real-time qPCR in 49% and 41% of samples (n = 63), respectively. All human viruses analyzed were detected at least once including adenovirus (40% of samples), GI norovirus (10%), enterovirus (8%), rotavirus (6%), GII norovirus (1.6%) and hepatitis A virus (1.6%). Three of seven bovine viruses analyzed were detected including bovine polyomavirus (32%), bovine rotavirus (19%), and bovine viral diarrhea virus type 1 (5%). Human viruses were present in 63% of runoff samples resulting from precipitation and snowmelt, and 20% of low-flow samples. Maximum human virus concentrations exceeded 300 genomic copies/L. Bovine viruses were present in 46% of runoff samples resulting from precipitation and snowmelt and 14% of low-flow samples. The maximum bovine virus concentration was 11 genomic copies/L. Statistical modeling indicated that stream flow, precipitation, and season explained the variability of human viruses in the watershed, and hydrologic condition (runoff event or low-flow) and season explained the variability of the sum of human and bovine viruses; however, no model was identified that could explain the variability of bovine viruses alone. Understanding the factors that affect virus fate and transport in rivers will aid watershed management for minimizing

  4. Distinguishing the impacts of human activities and climate variability on runoff and sediment load change based on paired periods with similar weather conditions

    NARCIS (Netherlands)

    Wang, Fei; Hessel, Rudi; Mu, Xingmin; Maroulis, Jerry; Zhao, Guangju; Geissen, Violette; Ritsema, Coen

    2015-01-01

    Runoff and sediment loads from river basin are largely affected by the interplay of climate variability and human activities within the basin. However, distinguishing the impacts of climate variability and human activities would vastly improve our knowledge of water resources, climate variability

  5. Long-term variability and impact on human health of biologically active UV radiation in Moscow

    Science.gov (United States)

    Zhdanova, Ekaterina; Chubarova, Natalia

    2014-05-01

    the developed classification for Moscow. Booth, C.R. and S. Madronich, 1994: Radiation amplification factors: improved formulation accounts for large increases in ultraviolet radiation associated with Antarctic ozone depletion. In: Ultraviolet Radiation in Antarctica: Measurements and Biological Research [Weiler, C.S. and P.A. Penhale (eds.)]. AGU Antarctic Research Series, 62, Washington, DC, USA, 39-42. Chubarova N.Y., 2008: UV variability in Moscow according to long-term UV measurements and reconstruction model. Atmos.Chem.Phys., 8, 3025-3031 Oriowo, M. et al., 2001:, Action spectrum for in vitro UV-induced cataract using whole lenses. Invest.Ophthalmol.&Vis.Sci, 42, 2596-2602. CIE, 1993: Reference Action Spectra for Ultraviolet Induced Erythema and Pigmentation of Different Human skin Types. CIE Research Note, CIE Technical Collection., N.3 CIE, 2006: Action spectrum for the production of previtamin D3 in human skin, Technical report 174, International commission on illumination

  6. Characterizing synaptic protein development in human visual cortex enables alignment of synaptic age with rat visual cortex

    Directory of Open Access Journals (Sweden)

    Joshua G.A Pinto

    2015-02-01

    Full Text Available Although many potential neuroplasticity based therapies have been developed in the lab, few have translated into established clinical treatments for human neurologic or neuropsychiatric diseases. Animal models, especially of the visual system, have shaped our understanding of neuroplasticity by characterizing the mechanisms that promote neural changes and defining timing of the sensitive period. The lack of knowledge about development of synaptic plasticity mechanisms in human cortex, and about alignment of synaptic age between animals and humans, has limited translation of neuroplasticity therapies. In this study, we quantified expression of a set of highly conserved pre- and post-synaptic proteins (Synapsin, Synaptophysin, PSD-95, Gephyrin and found that synaptic development in human primary visual cortex continues into late childhood. Indeed, this is many years longer than suggested by neuroanatomical studies and points to a prolonged sensitive period for plasticity in human sensory cortex. In addition, during childhood we found waves of inter-individual variability that are different for the 4 proteins and include a stage during early development (<1 year when only Gephyrin has high inter-individual variability. We also found that pre- and post-synaptic protein balances develop quickly, suggesting that maturation of certain synaptic functions happens within the first year or two of life. A multidimensional analysis (principle component analysis showed that most of the variance was captured by the sum of the 4 synaptic proteins. We used that sum to compare development of human and rat visual cortex and identified a simple linear equation that provides robust alignment of synaptic age between humans and rats. Alignment of synaptic ages is important for age-appropriate targeting and effective translation of neuroplasticity therapies from the lab to the clinic.

  7. Heart rate variability is associated with psychosocial stress in distinct social domains.

    Science.gov (United States)

    Lischke, Alexander; Jacksteit, Robert; Mau-Moeller, Anett; Pahnke, Rike; Hamm, Alfons O; Weippert, Matthias

    2018-03-01

    Psychosocial stress is associated with substantial morbidity and mortality. Accordingly, there is a growing interest in biomarkers that indicate whether individuals show adaptive (i.e., stress-buffering and health-promoting) or maladaptive (i.e., stress-escalating and health-impairing) stress reactions in social contexts. As heart rate variability (HRV) has been suggested to be a biomarker of adaptive behavior during social encounters, it may be possible that inter-individual differences in HRV are associated with inter-individual differences regarding stress in distinct social domains. To test this hypothesis, resting state HRV and psychosocial stress was assessed in 83 healthy community-dwelling individuals (age: 18-35years). HRV was derived from heart rate recordings during spontaneous and instructed breathing to assess the robustness of possible associations between inter-individual differences in HRV and inter-individual differences in psychosocial stress. Psychosocial stress was determined with a self-report questionnaire assessing stress in distinct social domains. A series of categorical and dimensional analyses revealed an association between inter-individual differences in HRV and inter-individual differences in psychosocial stress: Individuals with high HRV reported less stress in social life, but not in family life, work life or everyday life, than individuals with low HRV. On basis of these findings, it may be assumed that individuals with high HRV experience less psychosocial stress than individuals with low HRV. Although such an assumption needs to be corroborated by further findings, it seems to be consistent with previous findings showing that individuals with high HRV suffer less from stress and stress-related disorders than individuals with low HRV. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. European climate variability and human susceptibility over the past 2500 years

    Science.gov (United States)

    Buentgen, U.

    2010-09-01

    Climate variations including droughts in the western US and African Sahel, landfalls of Atlantic hurricanes, and shifts in the Asian monsoon have affected human societies throughout history mainly by modulating water supply and agricultural productivity, health risk and civil conflict. Yet, discriminations of environmental impacts from political, economical and technological drivers of societal shifts are may be hampered by the indirect effects of climate on society, but certainly by the paucity of high-resolution palaeoclimatic evidence. Here we present a tree-ring network of 7284 precipitation sensitive oak series from lower elevations in France and Germany, and a compilation of 1546 temperature responsive conifers from higher elevations in the Austrian Alps, both covering the past 2500 years. Temporal distribution of historical felling dates of construction timber refers to changes in settlement activity that mirror different stages of economic wealth. Variations in Central European summer precipitation and temperature are contrasted with societal benchmarks. Prolonged periods of generally wet and warm summers, favourable for cultural prosperity, appeared during the Roman epoch between ~200 BC and 200 AD and from ~700-1000 AD, with the latter facilitating the rapid economic, cultural and political growth of medieval Europe. Unprecedented climate variability from ~200-500 AD coincides with the demise of the Western Roman Empire and the subsequent Barbarian Migrations. This period was characterized by continental-scale political turmoil, cultural stagnation and socio-economic instability including settlement abandonment, population migration, and societal collapse. Driest and coldest summers of the Late Holocene concurred in the 6th century, during which regional consolidation began. The recent political, cultural and fiscal reluctance to adapt to and mitigate projected climate change reflects the common belief of societal insusceptibility to environmental

  9. Analysis of Intra- and Intersubject Variability in Oral Drug Absorption in Human Bioequivalence Studies of 113 Generic Products.

    Science.gov (United States)

    Sugihara, Masahisa; Takeuchi, Susumu; Sugita, Masaru; Higaki, Kazutaka; Kataoka, Makoto; Yamashita, Shinji

    2015-12-07

    In this study, the data of 113 human bioequivalence (BE) studies of immediate release (IR) formulations of 74 active pharmaceutical ingredients (APIs) conducted at Sawai Pharmaceutical Co., Ltd., was analyzed to understand the factors affecting intra- and intersubject variabilities in oral drug absorption. The ANOVA CV (%) calculated from area under the time-concentration curve (AUC) in each BE study was used as an index of intrasubject variability (Vintra), and the relative standard deviation (%) in AUC was used as that of intersubject variability (Vinter). Although no significant correlation was observed between Vintra and Vinter of all drugs, Vintra of class 3 drugs was found to increase in association with a decrease in drug permeability (P(eff)). Since the absorption of class 3 drugs was rate-limited by the permeability, it was suggested that, for such drugs, the low P(eff) might be a risk factor to cause a large intrasubject variability. To consider the impact of poor water solubility on the variability in BE study, a parameter of P(eff)/Do (Do; dose number) was defined to discriminate the solubility-limited and dissolution-rate-limited absorption of class 2 drugs. It was found that the class 2 drugs with a solubility-limited absorption (P(eff)/Do high intrasubject variability. Furthermore, as a reason for high intra- or intersubject variability in AUC for class 1 drugs, effects of drug metabolizing enzymes were investigated. It was demonstrated that intrasubject variability was high for drugs metabolized by CYP3A4 while intersubject variability was high for drugs metabolized by CYP2D6. For CYP3A4 substrate drugs, the Km value showed the significant relation with Vintra, indicating that the affinity to the enzyme can be a parameter to predict the risk of high intrasubject variability. In conclusion, by analyzing the in house data of human BE study, low permeability, solubility-limited absorption, and high affinity to CYP3A4 are identified as risk factors for

  10. The sequence of cortical activity inferred by response latency variability in the human ventral pathway of face processing.

    Science.gov (United States)

    Lin, Jo-Fu Lotus; Silva-Pereyra, Juan; Chou, Chih-Che; Lin, Fa-Hsuan

    2018-04-11

    Variability in neuronal response latency has been typically considered caused by random noise. Previous studies of single cells and large neuronal populations have shown that the temporal variability tends to increase along the visual pathway. Inspired by these previous studies, we hypothesized that functional areas at later stages in the visual pathway of face processing would have larger variability in the response latency. To test this hypothesis, we used magnetoencephalographic data collected when subjects were presented with images of human faces. Faces are known to elicit a sequence of activity from the primary visual cortex to the fusiform gyrus. Our results revealed that the fusiform gyrus showed larger variability in the response latency compared to the calcarine fissure. Dynamic and spectral analyses of the latency variability indicated that the response latency in the fusiform gyrus was more variable than in the calcarine fissure between 70 ms and 200 ms after the stimulus onset and between 4 Hz and 40 Hz, respectively. The sequential processing of face information from the calcarine sulcus to the fusiform sulcus was more reliably detected based on sizes of the response variability than instants of the maximal response peaks. With two areas in the ventral visual pathway, we show that the variability in response latency across brain areas can be used to infer the sequence of cortical activity.

  11. Physical-mathematical model for cybernetic description of the human organs with trace element concentrations as input variables

    International Nuclear Information System (INIS)

    Mihai, Maria; Popescu, I.V.

    2003-01-01

    In this paper we report a physical-mathematical model for studying the organs and humans fluids by cybernetic principle. The input variables represent the trace elements which are determined by atomic and nuclear methods of elemental analysis. We have determined the health limits between which the organs might function. (authors)

  12. Dose uncertainties for large solar particle events: Input spectra variability and human geometry approximations

    International Nuclear Information System (INIS)

    Townsend, Lawrence W.; Zapp, E. Neal

    1999-01-01

    The true uncertainties in estimates of body organ absorbed dose and dose equivalent, from exposures of interplanetary astronauts to large solar particle events (SPEs), are essentially unknown. Variations in models used to parameterize SPE proton spectra for input into space radiation transport and shielding computer codes can result in uncertainty about the reliability of dose predictions for these events. Also, different radiation transport codes and their input databases can yield significant differences in dose predictions, even for the same input spectra. Different results may also be obtained for the same input spectra and transport codes if different spacecraft and body self-shielding distributions are assumed. Heretofore there have been no systematic investigations of the variations in dose and dose equivalent resulting from these assumptions and models. In this work we present a study of the variability in predictions of organ dose and dose equivalent arising from the use of different parameters to represent the same incident SPE proton data and from the use of equivalent sphere approximations to represent human body geometry. The study uses the BRYNTRN space radiation transport code to calculate dose and dose equivalent for the skin, ocular lens and bone marrow using the October 1989 SPE as a model event. Comparisons of organ dose and dose equivalent, obtained with a realistic human geometry model and with the oft-used equivalent sphere approximation, are also made. It is demonstrated that variations of 30-40% in organ dose and dose equivalent are obtained for slight variations in spectral fitting parameters obtained when various data points are included or excluded from the fitting procedure. It is further demonstrated that extrapolating spectra from low energy (≤30 MeV) proton fluence measurements, rather than using fluence data extending out to 100 MeV results in dose and dose equivalent predictions that are underestimated by factors as large as 2

  13. Agricultural, socioeconomic and environmental variables as risks for human verotoxigenic Escherichia coli (VTEC) infection in Finland.

    Science.gov (United States)

    Jalava, Katri; Ollgren, Jukka; Eklund, Marjut; Siitonen, Anja; Kuusi, Markku

    2011-10-18

    Verotoxigenic E. coli (VTEC) is the cause of severe gastrointestinal infection especially among infants. Between 10 and 20 cases are reported annually to the National Infectious Disease Register (NIDR) in Finland. The aim of this study was to identify explanatory variables for VTEC infections reported to the NIDR in Finland between 1997 and 2006. We applied a hurdle model, applicable for a dataset with an excess of zeros. We enrolled 131 domestically acquired primary cases of VTEC between 1997 and 2006 from routine surveillance data. The isolated strains were characterized by virulence type, serogroup, phage type and pulsed-field gel electrophoresis. By applying a two-part Bayesian hurdle model to infectious disease surveillance data, we were able to create a model in which the covariates were associated with the probability for occurrence of the cases in the logistic regression part and the magnitude of covariate changes in the Poisson regression part if cases do occur. The model also included spatial correlations between neighbouring municipalities. The average annual incidence rate was 4.8 cases per million inhabitants based on the cases as reported to the NIDR. Of the 131 cases, 74 VTEC O157 and 58 non-O157 strains were isolated (one person had dual infections). The number of bulls per human population and the proportion of the population with a higher education were associated with an increased occurrence and incidence of human VTEC infections in 70 (17%) of 416 of Finnish municipalities. In addition, the proportion of fresh water per area, the proportion of cultivated land per area and the proportion of low income households with children were associated with increased incidence of VTEC infections. With hurdle models we were able to distinguish between risk factors for the occurrence of the disease and the incidence of the disease for data characterised by an excess of zeros. The density of bulls and the proportion of the population with higher education were

  14. Microchemical and structural regular variability of apatites in 'overbuilt' enamel and dentin of human molar teeth

    International Nuclear Information System (INIS)

    Kuczumow, A.; Nowak, J.; ChaLas, R.

    2011-01-01

    The aim of a recent paper was to recognize the chemical and structural changes in apatites, which form both the enamel and the dentin of the human tooth. The aim was achieved by scrutinizing the linear elemental profiles along the cross-sections of human molar teeth. Essentially, the task was accomplished with the application of the Electron Probe Microanalysis method and with some additional studies by Micro-Raman spectrometry. All the trends in linear profiles were strictly determined. In the enamel zone they were either increasing or decreasing curves of exponential character. The direction of the investigations was to start with the tooth surface and move towards the dentin-enamel junction (DEJ). The results of the elemental studies were more visible when the detected material was divided, in an arbitrary way, into the prevailing 'core' enamel (∼93.5% of the total mass) and the remaining 'overbuilt' enamel. The material in the 'core' enamel was fully stable, with clearly determined chemical and mechanical features. However, the case was totally different in the 'overbuilt enamel', with dynamic changes in the composition. In the 'overbuilt' layer Ca, P, Cl and F profiles present the decaying distribution curves, whereas Mg, Na, K and CO 3 2- present the growing ones. Close to the surface of the tooth the mixture of hydroxy-, chlor- and fluor-apatite is formed, which is much more resistant than the rest of the enamel. On passing towards the DEJ, the apatite is enriched with Na, Mg and CO 3 2- . In this location, three of six phosphate groups were substituted with carbonate groups. Simultaneously, Mg is associated with the hydroxyl groups around the hexad axis. In this way, the mechanisms of exchange reactions were established. The crystallographic structures were proposed for new phases located close to DEJ. In the dentin zone, the variability of elemental profiles looks different, with the most characteristic changes occurring in Mg and Na concentrations. Mg

  15. Human heavy-chain variable region gene family nonrandomly rearranged in familial chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Shen, A.; Humphries, C.; Tucker, P.; Blattner, F.

    1987-01-01

    The authors have identified a family of human immunoglobulin heavy-chain variable-region (V/sub H/) genes, one member of which is rearranged in two affected members of a family in which the father and four of five siblings developed chronic lymphocytic leukemia. Cloning and sequencing of the rearranged V/sub H/ genes from leukemic lymphocytes of three affected siblings showed that two siblings had rearranged V/sub H/ genes (V/sub H/TS1 and V/sub H/WS1) that were 90% homologous. The corresponding germ-line gene, V/sub H/251, was found to part of a small (four gene) V/sub H/ gene family, which they term V/sub H/V. The DNA sequence homology to V/sub H/WS1 (95%) and V/sub H/TS1 (88%) and identical restriction sites on the 5' side of V/sub H/ confirm that rearrangement of V/sub H/251 followed by somatic mutation produced the identical V/sub H/ gene rearrangements in the two siblings. V/sub H/TS1 is not a functional V/sub H/ gene; a functional V/sub H/ rearrangement was found on the other chromosome of this patient. The other two siblings had different V/sub H/ gene rearrangements. All used different diversity genes. Mechanisms proposed for nonrandom selection of a single V/sub H/ gene include developmental regulation of this V/sub H/ gene rearrangement or selection of a subpopulation of B cells in which this V/sub H/ has been rearranged

  16. Relative roles of weather variables and change in human population in malaria: comparison over different states of India.

    Directory of Open Access Journals (Sweden)

    Prashant Goswami

    Full Text Available Pro-active and effective control as well as quantitative assessment of impact of climate change on malaria requires identification of the major drivers of the epidemic. Malaria depends on vector abundance which, in turn, depends on a combination of weather variables. However, there remain several gaps in our understanding and assessment of malaria in a changing climate. Most of the studies have considered weekly or even monthly mean values of weather variables, while the malaria vector is sensitive to daily variations. Secondly, rarely all the relevant meteorological variables have been considered together. An important question is the relative roles of weather variables (vector abundance and change in host (human population, in the change in disease load.We consider the 28 states of India, characterized by diverse climatic zones and changing population as well as complex variability in malaria, as a natural test bed. An annual vector load for each of the 28 states is defined based on the number of vector genesis days computed using daily values of temperature, rainfall and humidity from NCEP daily Reanalysis; a prediction of potential malaria load is defined by taking into consideration changes in the human population and compared with the reported number of malaria cases.For most states, the number of malaria cases is very well correlated with the vector load calculated with the combined conditions of daily values of temperature, rainfall and humidity; no single weather variable has any significant association with the observed disease prevalence.The association between vector-load and daily values of weather variables is robust and holds for different climatic regions (states of India. Thus use of all the three weather variables provides a reliable means of pro-active and efficient vector sanitation and control as well as assessment of impact of climate change on malaria.

  17. Evaluation of the Effects of Variable Helmet Weight on Human Response During Lateral +Gy Impact

    National Research Council Canada - National Science Library

    Perry, Chris

    2003-01-01

    .... A series of tests was conducted by AFRL/HEPA on a horizontal impulse accelerator using human subjects to investigate the effects of helmet inertial properties on human response to short duration...

  18. Effects of human activities and climate variability on water resources in the Saveh plain, Iran.

    Science.gov (United States)

    Mohammadi Ghaleni, M; Ebrahimi, K

    2015-02-01

    Quantity and quality distribution of surface water and groundwater are changing under the impacts of both climate variability and human activities. The main goal of this paper is to evaluate the abovementioned impacts on the water resources in the Saveh plain, central Iran. To achieve this aim, spatial and temporal changes of the surface and groundwater quality and quantity have been analyzed, using hydrometric and meteorological data. The nonparametric Mann-Kendall test was used to identify trends and change points in the annual rainfall and runoff for the period of 1946 to 2011. In order to analyze the impacts of the Saveh Dam on runoff, the dam operation year, 1994, was considered as a change point. Mann-Kendall test results show that rainfall time series was divided into two parts, namely, 1966-1989 and 1990-2007, and averages of annual rainfall in five stations increase from 10 to 21 %. Also, runoff time series was divided into two parts, namely, 1946-1995 and 1996-2007 and averages of annual runoff in four stations decrease from 8 to 83 %. Results show that rainfall changes in Shahabasi, Razin, Jalayer, Emamabad, and Ahmadabad stations increased from 9 to 33 % before and after 1994. Nevertheless, runoff decreased from 24 to 81 %. The results indicate that the greatest lack of runoff between stations is at Shahabasi station and one important reason for the severe lack is operation of the Saveh Dam in 1994. Highest groundwater level decline, about 168.67 cm, occurred in 1994 that is the operation year of the Saveh Dam. Trend analysis of surface water quality show that electrical conductivity increased 957.34 μmho/cm before and after 1994. Also, the Wilcox water quality classification method has been reduced from C3-S1 to C4-S2. Average groundwater electrical conductivity (EC) during 1999-2003 and 2004-2009 increased to 89.6 μmho/cm. Also, the groundwater quality indices for agricultural usages are classified in four classes including, C4-S2 16, C4-S1 46, C3-S

  19. Quantification of collateral flow in humans: a comparison of angiographic, electrocardiographic and hemodynamic variables

    NARCIS (Netherlands)

    van Liebergen, R. A.; Piek, J. J.; Koch, K. T.; de Winter, R. J.; Schotborgh, C. E.; Lie, K. I.

    1999-01-01

    Evaluation of collateral vascular circulation according to hemodynamic variables and its relation to myocardial ischemia. There is limited information regarding the hemodynamic quantification of recruitable collateral vessels. Angiography of the donor coronary artery was performed before and during

  20. Increased heart rate variability but normal resting metabolic rate in hypocretin/orexin-deficient human narcolepsy.

    NARCIS (Netherlands)

    Fronczek, R.; Overeem, S.; Reijntjes, R.; Lammers, G.J.; Dijk, J.G.M.; Pijl, H.

    2008-01-01

    STUDY OBJECTIVES: We investigated autonomic balance and resting metabolic rate to explore their possible involvement in obesity in hypocretin/orexin-deficient narcoleptic subjects. METHODS: Resting metabolic rate (using indirect calorimetry) and variability in heart rate and blood pressure were

  1. Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types

    DEFF Research Database (Denmark)

    Ecker, Simone; Chen, Lu; Pancaldi, Vera

    2017-01-01

    Background: A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability. Results: We apply a novel analytical approach to measure and compare transcriptional and epigenetic v...

  2. Shape of the orbital opening: individual characterization and analysis of variability in modern humans, Gorilla gorilla, and Pan troglodytes.

    Science.gov (United States)

    Schmittbuhl, M; Le Minor, J M; Allenbach, B; Schaaf, A

    1999-05-01

    The description of the human orbital shape is principally qualitative in the classical literature, and characterised by adjectives such as circular, rectangular or quadrangular. In order to provide a precise quantification and interpretation of this shape, a study based on automatic image analysis and Fourier analysis was carried out on 45 human skulls (30 males, 15 females), and for comparison on 61 skulls of Gorilla gorilla (40 males, 21 females), and 34 skulls of Pan troglodytes (20 males, 14 females). Sexual dimorphism in the shape of the orbital opening was not demonstrated. Its dominant morphological features could be characterized by Fourier analysis; elliptical elongation and quadrangularity were dominant morphological features of the shape of the orbital opening in the three species. Elliptical elongation was more marked in humans and Pan, whereas quadrangularity was particularly emphasized in Gorilla. An intraspecific variability of the shape of the orbital opening existed in humans, Gorilla and Pan, and seemed close in the three species. Interspecific partition between humans, Gorilla and Pan was demonstrated despite the variability observed in the three species studied. Interspecific differences between Gorilla and the Pan-humans group were principally explained by the differences in quadrangularity, and by differences in orientation of triangularity and pentagonality. Differences in the shape of the orbital opening between humans and Pan were principally explained by differences in hexagonality, and by differences in orientation of quadrangularity. A closeness of shape between some humans and some individuals in Pan and, to a lesser degree, with some individuals in Gorilla was observed, demonstrating the existence of a morphological continuum of the shape of the orbital opening in hominoids.

  3. Low Residual CBF Variability in Alzheimer's Disease after Correction for CO(2) Effect

    DEFF Research Database (Denmark)

    Rodell, Anders Bertil; Aanerud, Joel; Braendgaard, Hans

    2012-01-01

    We tested the claim that inter-individual CBF variability in Alzheimer's disease (AD) is substantially reduced after correction for arterial carbon dioxide tension (PaCO(2)). Specifically, we tested whether the variability of CBF in brain of patients with AD differed significantly from brain of age...... for the differences of CO(2) tension, the patients with AD lost the inter-individual CBF variability that continued to characterize the HC subjects. The difference (¿K(1)) between the blood-brain clearances (K(1)) of water (the current measure of CBF) and oxygen (the current measure of oxygen clearance) was reduced......-matched healthy control subjects (HC). To eliminate the CO(2)-induced variability, we developed a novel and generally applicable approach to the correction of CBF for changes of PaCO(2) and applied the method to positron emission tomographic (PET) measures of CBF in AD and HC groups of subjects. After correction...

  4. Fault trees and the impact of human variability on probabilistic risk analysis

    International Nuclear Information System (INIS)

    1983-01-01

    It has long been recognized that human reliability is an important factor in probabilistic risk analysis. In the field, this is true in a direct operational sense as well as in the areas of installation and maintenance. The interest in quantification arises from the desire to achieve optimum design in the human factors sense (operability-maintainability) and from the need to include human reliability considerations in probabilistic risk analysis to achieve complete and valid risk evaluation. In order to integrate human reliability into the system analysis, it is necessary to consider two questions. These relate to the way that human functions fit into the existing analytical models and methods as well as the nature of human failure mechanisms, modes and failure (error) rates

  5. Probabilistic tractography recovers a rostrocaudal trajectory of connectivity variability in the human insular cortex

    NARCIS (Netherlands)

    Cerliani, Leonardo; Thomas, Rajat M.; Jbabdi, Saad; Siero, Jeroen C. W.; Nanetti, Luca; Crippa, Alessandro; Gazzola, Valeria; D'Arceuil, Helen; Keysers, Christian

    The insular cortex of macaques has a wide spectrum of anatomical connections whose distribution is related to its heterogeneous cytoarchitecture. Although there is evidence of a similar cytoarchitectural arrangement in humans, the anatomical connectivity of the insula in the human brain has not yet

  6. A universal system for highly efficient cardiac differentiation of human induced pluripotent stem cells that eliminates interline variability.

    Directory of Open Access Journals (Sweden)

    Paul W Burridge

    2011-04-01

    Full Text Available The production of cardiomyocytes from human induced pluripotent stem cells (hiPSC holds great promise for patient-specific cardiotoxicity drug testing, disease modeling, and cardiac regeneration. However, existing protocols for the differentiation of hiPSC to the cardiac lineage are inefficient and highly variable. We describe a highly efficient system for differentiation of human embryonic stem cells (hESC and hiPSC to the cardiac lineage. This system eliminated the variability in cardiac differentiation capacity of a variety of human pluripotent stem cells (hPSC, including hiPSC generated from CD34(+ cord blood using non-viral, non-integrating methods.We systematically and rigorously optimized >45 experimental variables to develop a universal cardiac differentiation system that produced contracting human embryoid bodies (hEB with an improved efficiency of 94.7±2.4% in an accelerated nine days from four hESC and seven hiPSC lines tested, including hiPSC derived from neonatal CD34(+ cord blood and adult fibroblasts using non-integrating episomal plasmids. This cost-effective differentiation method employed forced aggregation hEB formation in a chemically defined medium, along with staged exposure to physiological (5% oxygen, and optimized concentrations of mesodermal morphogens BMP4 and FGF2, polyvinyl alcohol, serum, and insulin. The contracting hEB derived using these methods were composed of high percentages (64-89% of cardiac troponin I(+ cells that displayed ultrastructural properties of functional cardiomyocytes and uniform electrophysiological profiles responsive to cardioactive drugs.This efficient and cost-effective universal system for cardiac differentiation of hiPSC allows a potentially unlimited production of functional cardiomyocytes suitable for application to hPSC-based drug development, cardiac disease modeling, and the future generation of clinically-safe nonviral human cardiac cells for regenerative medicine.

  7. [Variability of the sensitivity of human lymphocytes to the antiproliferative action of alkylating agents].

    Science.gov (United States)

    Veremko, L N; Telegin, L Iu; Pevnitskii, L A

    1983-05-01

    A study was made of variability of the sensitivity of peripheral blood lymphocytes from different donors to an antiproliferative action of cyclophosphamide and thiophosphamide. A similar degree of the sensitivity was revealed to alkylating agents differing in the action mode, with this degree being independent of the "stimulation index" magnitude.

  8. Variability in the Geographic Distribution of Fires in Interior Alaska Considering Cause, Human Proximity, and Level of Suppression

    Science.gov (United States)

    Calef, M. P.; Varvak, A.; McGuire, A. D.; Chapin, T.

    2015-12-01

    The boreal forest of Interior Alaska is characterized by frequent extensive wildfires that have been mapped for the past 70 years. Simple predictions based on this record indicate that area burned will increase as a response to climate warming in Alaska. However, two additional factors have affected the area burned in this time record: the Pacific Decadal Oscillation (PDO) switched from cool and moist to warm and dry in the late 1970s and the Alaska Fire Service instituted a fire suppression policy in the late 1980s. Using Geographic Information Systems (GIS) and statistics, this presentation evaluates the variability in area burned and fire ignitions in Interior Alaska in space and time with particular emphasis on the human influence via ignition and suppression. Our analysis shows that while area burned has been increasing by 2.4% per year, the number of lightning ignitions has decreased by 1.9 ignitions per year. Human ignitions account for 50% of all fire ignitions in Interior Alaska and are clearly influenced by human proximity: human fires mostly occur close to settlements, highways and in intense fire suppression zones (which are in turn close to human settlements and roads); fires close to settlements, highways and in intense fire suppression zones burn much shorter than fires further away from this sphere of human influence; and 60% of all human fire ignitions in Interior Alaska are concentrated in the Fairbanks area and thereby strongly influence regional analyses. Fire suppression has effectively reduced area burned since it was implemented but the PDO change has also had some influence. Finally, we found that human fires start earlier in the year and burn for a shorter duration than lightning fires. This study provides insights into the importance of human behavior as well as regional climate patterns as large-scale controls on fires over time and across the Alaskan boreal forest.

  9. Differential Responding by Rhesus Monkeys (Macaca mulatta and Humans (Homo sapiens to Variable Outcomes in the Assurance Game

    Directory of Open Access Journals (Sweden)

    Audrey E. Parrish

    2014-08-01

    Full Text Available Behavioral flexibility in how one responds to variable partner play can be examined using economic coordination games in which subjects play against a variety of partners and therefore may need to alter their behavior to produce the highest payoff. But how do we study this behavioral flexibility once players have settled on a response? Here, we investigated how responding by rhesus monkeys (Macaca mulatta and humans (Homo sapiens playing a computerized single-player version of a coordination game, the Assurance game, changed as a function of the variable responses (Stag/Hare generated by multiple simulations (SIMs. We were interested in whether individuals could track and differentially respond to changing frequencies of Stag and Hare play by the SIMs, especially with regard to the payoff dominant (Stag-Stag outcome, something that could not be done with real partners as they quickly settled on the Stag response. For both monkeys and humans, there was a linear relationship between proportion of Stag play by the subject and the likelihood of the Stag choice by the SIM such that both species increased their use of Stag as the SIM increased its use of the Stag response. However, humans more closely matched their proportion of Stag responses to that of the SIM, whereas monkeys adopted a different, but equally effective, strategy of exploiting the higher-paying Stag alternative. These results suggest that monkeys and humans demonstrate sensitivity to a dynamic game environment in which they encounter variable contingencies for the same response options, although they may employ different strategies to maximize reward.

  10. Do climate variables and human density affect Achatina fulica (Bowditch) (Gastropoda: Pulmonata) shell length, total weight and condition factor?

    Science.gov (United States)

    Albuquerque, F S; Peso-Aguiar, M C; Assunção-Albuquerque, M J T; Gálvez, L

    2009-08-01

    The length-weight relationship and condition factor have been broadly investigated in snails to obtain the index of physical condition of populations and evaluate habitat quality. Herein, our goal was to describe the best predictors that explain Achatina fulica biometrical parameters and well being in a recently introduced population. From November 2001 to November 2002, monthly snail samples were collected in Lauro de Freitas City, Bahia, Brazil. Shell length and total weight were measured in the laboratory and the potential curve and condition factor were calculated. Five environmental variables were considered: temperature range, mean temperature, humidity, precipitation and human density. Multiple regressions were used to generate models including multiple predictors, via model selection approach, and then ranked with AIC criteria. Partial regressions were used to obtain the separated coefficients of determination of climate and human density models. A total of 1.460 individuals were collected, presenting a shell length range between 4.8 to 102.5 mm (mean: 42.18 mm). The relationship between total length and total weight revealed that Achatina fulica presented a negative allometric growth. Simple regression indicated that humidity has a significant influence on A. fulica total length and weight. Temperature range was the main variable that influenced the condition factor. Multiple regressions showed that climatic and human variables explain a small proportion of the variance in shell length and total weight, but may explain up to 55.7% of the condition factor variance. Consequently, we believe that the well being and biometric parameters of A. fulica can be influenced by climatic and human density factors.

  11. Do climate variables and human density affect Achatina fulica (Bowditch (Gastropoda: Pulmonata shell length, total weight and condition factor?

    Directory of Open Access Journals (Sweden)

    FS. Albuquerque

    Full Text Available The length-weight relationship and condition factor have been broadly investigated in snails to obtain the index of physical condition of populations and evaluate habitat quality. Herein, our goal was to describe the best predictors that explain Achatina fulica biometrical parameters and well being in a recently introduced population. From November 2001 to November 2002, monthly snail samples were collected in Lauro de Freitas City, Bahia, Brazil. Shell length and total weight were measured in the laboratory and the potential curve and condition factor were calculated. Five environmental variables were considered: temperature range, mean temperature, humidity, precipitation and human density. Multiple regressions were used to generate models including multiple predictors, via model selection approach, and then ranked with AIC criteria. Partial regressions were used to obtain the separated coefficients of determination of climate and human density models. A total of 1.460 individuals were collected, presenting a shell length range between 4.8 to 102.5 mm (mean: 42.18 mm. The relationship between total length and total weight revealed that Achatina fulica presented a negative allometric growth. Simple regression indicated that humidity has a significant influence on A. fulica total length and weight. Temperature range was the main variable that influenced the condition factor. Multiple regressions showed that climatic and human variables explain a small proportion of the variance in shell length and total weight, but may explain up to 55.7% of the condition factor variance. Consequently, we believe that the well being and biometric parameters of A. fulica can be influenced by climatic and human density factors.

  12. Variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Hove, Jens D; Freiberg, Jacob

    2002-01-01

    The aim of this study was to assess regional and global variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects and to evaluate potentially responsible factors. Twenty men with a mean age of 64 years, no history of cardiovascular disease, and normal blood pressure...... rest and hyperaemic blood flow during dipyridamole infusion were measured with nitrogen-13 ammonia and positron emission tomography in 16 left ventricular myocardial segments. Intra-individual and inter-individual variability of insulin-stimulated myocardial glucose uptake [relative dispersion...... = (standard deviation/mean)] was 13% and 29% respectively. Although inter-individual variability of glucose uptake and blood flow at rest was of the same magnitude, no correlation was found between these measures. Regional and global insulin-stimulated myocardial glucose uptake correlated linearly with whole...

  13. Quantification and variability in colonic volume with a novel magnetic resonance imaging method

    DEFF Research Database (Denmark)

    Nilsson, M; Sandberg, Thomas Holm; Poulsen, Jakob Lykke

    2015-01-01

    Background: Segmental distribution of colorectal volume is relevant in a number of diseases, but clinical and experimental use demands robust reliability and validity. Using a novel semi-automatic magnetic resonance imaging-based technique, the aims of this study were to describe: (i) inter......-individual and intra-individual variability of segmental colorectal volumes between two observations in healthy subjects and (ii) the change in segmental colorectal volume distribution before and after defecation. Methods: The inter-individual and intra-individual variability of four colorectal volumes (cecum...... (p = 0.02). Conclusions & Inferences: Imaging of segmental colorectal volume, morphology, and fecal accumulation is advantageous to conventional methods in its low variability, high spatial resolution, and its absence of contrast-enhancing agents and irradiation. Hence, the method is suitable...

  14. Construction of an in vivo human spinal cord atlas based on high-resolution MR images at cervical and thoracic levels: preliminary results.

    Science.gov (United States)

    Taso, Manuel; Le Troter, Arnaud; Sdika, Michaël; Ranjeva, Jean-Philippe; Guye, Maxime; Bernard, Monique; Callot, Virginie

    2014-06-01

    Our goal was to build a probabilistic atlas and anatomical template of the human cervical and thoracic spinal cord (SC) that could be used for segmentation algorithm improvement, parametric group studies, and enrichment of biomechanical modelling. High-resolution axial T2*-weighted images were acquired at 3T on 15 healthy volunteers using a multi-echo-gradient-echo sequence (1 slice per vertebral level from C1 to L2). After manual segmentation, linear and affine co-registrations were performed providing either inter-individual morphometric variability maps, or substructure probabilistic maps [CSF, white and grey matter (WM/GM)] and anatomical SC template. The larger inter-individual morphometric variations were observed at the thoraco-lumbar levels and in the posterior GM. Mean SC diameters were in agreement with the literature and higher than post-mortem measurements. A representative SC MR template was generated and values up to 90 and 100% were observed on GM and WM-probability maps. This work provides a probabilistic SC atlas and a template that could offer great potentialities for parametrical MRI analysis (DTI/MTR/fMRI) and group studies, similar to what has already been performed using a brain atlas. It also offers great perspective for biomechanical models usually based on post-mortem or generic data. Further work will consider integration into an automated SC segmentation pipeline.

  15. Differential labeling of dopamine and sigma sites by [3H]nemonapride and [3H]raclopride in postmortem human brains.

    Science.gov (United States)

    Tang, S W; Helmeste, D M; Fang, H; Li, M; Vu, R; Bunney, W; Potkin, S; Jones, E G

    1997-08-08

    The difference between the binding of [3H]nemonapride and [3H]raclopride has been used to quantify dopamine D4 receptors in postmortem schizophrenic brain studies. Recent work, however, has suggested that at least part of the differential between [3H]nemonapride and [3H]raclopride binding may represent sigma rather than D4 receptor sites. We applied the nemonapride-raclopride subtraction method to postmortem, non-schizophrenic human striatum to examine the variation in dopaminergic receptor binding labeled by these ligands. Variation in sigma receptor binding labeled by [3H]nemonapride was studied in frontal cortex, striatum and cerebellum. Specific binding was defined by sulpiride (dopamine receptor ligand), PPAP (sigma receptor ligand) and haloperidol (mixed dopaminergic/sigma agent), respectively. Haloperidol defined a combination of sites, which were approximately the sum of the dopaminergic and sigma components defined by sulpiride and PPAP, respectively. Significant inter-individual variation in the amount of specific binding for dopaminergic and sigma receptor sites was observed. However, no significant nor consistent observation of striatal dopamine D4 receptors or D4-like binding sites was observed in the striatum even though two independent sets of tissues, with different dissections were used. The inconsistencies in some previous postmortem studies appear to be at least partially explained by the inclusion of both sigma and dopaminergic components in [3H]nemonapride binding and the inherent high inter-individual variability of the different components.

  16. Rainfall erosivity and sediment load over the Poyang Lake Basin under variable climate and human activities since the 1960s

    Science.gov (United States)

    Gu, Chaojun; Mu, Xingmin; Gao, Peng; Zhao, Guangju; Sun, Wenyi; Yu, Qiang

    2018-03-01

    Accelerated soil erosion exerts adverse effects on water and soil resources. Rainfall erosivity reflects soil erosion potential driven by rainfall, which is essential for soil erosive risk assessment. This study investigated the spatiotemporal variation of rainfall erosivity and its impacts on sediment load over the largest freshwater lake basin of China (the Poyang Lake Basin, abbreviate to PYLB). The spatiotemporal variations of rainfall erosivity from 1961 to 2014 based on 57 meteorological stations were detected using the Mann-Kendall test, linear regression, and kriging interpolation method. The sequential t test analysis of regime shift (STARS) was employed to identify the abrupt changes of sediment load, and the modified double mass curve was used to assess the impacts of rainfall erosivity variability on sediment load. It was found that there was significant increase (P change-points were identified in both 1985 and 2003. It was found that take annual rainfall erosivity as the explanatory variables of the double mass curves is more reasonable than annual rainfall and erosive rainfall. The estimation via the modified double mass curve demonstrated that compared with the period before change-point (1961-1984), the changes of rainfall erosivity increased 8.0 and 2.1% of sediment load during 1985-2002 and 2003-2014, respectively. Human activities decreased 50.2 and 69.7% of sediment load during the last two periods, which indicated effects of human activities on sediment load change was much larger than that of rainfall erosivity variability in the PYLB.

  17. Use of a variable tracer infusion method to determine glucose turnover in humans

    International Nuclear Information System (INIS)

    Molina, J.M.; Baron, A.D.; Edelman, S.V.; Brechtel, G.; Wallace, P.; Olefsky, J.M.

    1990-01-01

    The single-compartment pool fraction model, when used with the hyperinsulinemic glucose clamp technique to measure rates of glucose turnover, sometimes underestimates true rates of glucose appearance (Ra) resulting in negative values for hepatic glucose output (HGO). We focused our attention on isotope discrimination and model error as possible explanations for this underestimation. We found no difference in [3-3H] glucose specific activity in samples obtained simultaneously from the femoral artery and vein (2,400 +/- 455 vs. 2,454 +/- 522 dpm/mg) in 6 men during a hyperinsulinemic euglycemic clamp study where insulin was infused at 40 mU.m-2.min-1 for 3 h; therefore, isotope discrimination did not occur. We compared the ability of a constant (0.6 microCi/min) vs. variable tracer infusion method (tracer added to the glucose infusate) to measure non-steady-state Ra during hyperinsulinemic clamp studies. Plasma specific activity fell during the constant tracer infusion studies but did not change from base line during the variable tracer infusion studies. By maintaining a constant plasma specific activity the variable tracer infusion method eliminates uncertainty about changes in glucose pool size. This overcame modeling error and more accurately measures non-steady-state Ra (P less than 0.001 by analysis of variance vs. constant infusion method). In conclusion, underestimation of Ra determined isotopically during hyperinsulinemic clamp studies is largely due to modeling error that can be overcome by use of the variable tracer infusion method. This method allows more accurate determination of Ra and HGO under non-steady-state conditions

  18. Human Vulnerability to Climate Variability in the Sahel: Farmers' Adaptation Strategies in Northern Burkina Faso

    Science.gov (United States)

    Barbier, Bruno; Yacouba, Hamma; Karambiri, Harouna; Zoromé, Malick; Somé, Blaise

    2009-05-01

    In this study, the authors investigate farmers’ vulnerability to climate variability and evaluate local adoption of technology and farmers’ perceptions of adaptation strategies to rainfall variability and policies. A survey was conducted in a community in northern Burkina Faso following the crop failure of 2004. In 2006, following a better harvest, another survey was conducted to compare farmers’ actions and reactions during two contrasted rainy seasons. The results confirm that farmers from this community have substantially changed their practices during the last few decades. They have adopted a wide range of techniques that are intended to simultaneously increase crop yield and reduce yield variability. Micro water harvesting (Zaï) techniques have been widely adopted (41%), and a majority of fields have been improved with stone lines (60%). Hay (48%) and sorghum residues are increasingly stored to feed animals during the dry season, making bull and sheep fattening now a common practice. Dry season vegetable production also involves a majority of the population (60%). According to farmers, most of the new techniques have been adopted because of growing land scarcity and new market opportunities, rather than because of climate variability. Population pressure has reached a critical threshold, while land scarcity, declining soil fertility and reduced animal mobility have pushed farmers to intensify agricultural production. These techniques reduce farmers’ dependency on rainfall but are still insufficient to reduce poverty and vulnerability. Thirty-nine percent of the population remains vulnerable after a good rainy season. Despite farmers’ desire to remain in their own communities, migrations are likely to remain a major source of regular income and form of recourse in the event of droughts.

  19. Variability of excretion rates of 210Pb and 210Po of humans at environmental levels

    International Nuclear Information System (INIS)

    Spencer, H.; Holtzman, R.B.; Ilcewicz, F.H.; Kramer, L.

    1977-01-01

    Variability of the excretion rates of the nuclides 210 Pb and 210 Po at natural levels was studied in a group of samples collected from men maintained under the carefully controlled conditions of a metabolic ward. They consumed only the standard diet of the ward in which they had been resident for at least several months prior to this study. The mean urinary rates were about 0.1 to 0.5 pCi/day for both 210 Pb and 210 Po, while fecal rates ranged from 1 to 2.7 pCi/day for the two nuclides. For urinary 210 Pb the coefficients of variation (ratio of standard deviation to mean) for three subjects ranged from 19 to 45 percent for eight continuous 24-hr samples compared to 11 to 13 percent for subsequently collected multiday samples (4 to 9 days each) for each subject. However, the standard errors of the means for the one day collections were about equal to the standard deviations of the pooled samples. Similar variability was noted for the 210 Po data. Six day fecal collections from these time periods exhibited higher variabilities than did the urine, from about 12 percent to 50 percent for each of the nuclides. Multiday collections for 12 subjects showed mean coefficients of variation of about 16 percent for 210 Pb and 13 percent for the 210 Po for urine and 21 and 25 percent, respectively, in fecal collections. Since dietary intake was maintained fairly constant, excreta collections were carefully controlled, and the analytical precision was about 5 percent, these variabilities appear to be due to biological variations and are characteristic of the individuals studied. Some possible causes of these effects are discussed

  20. [Cognitive complaints in people with human immunodeficiency virus in Spain: prevalence and related variables].

    Science.gov (United States)

    Muñoz-Moreno, José A; Fuster-Ruiz de Apodaca, Maria J; Fumaz, Carmina R; Ferrer, Maria J; Molero, Fernando; Jaen, Àngels; Clotet, Bonaventura; Dalmau, David

    2014-05-20

    Cognitive complaints have been scarcely studied in people with HIV in Spain. The aim of this research was to know the prevalence of cognitive complaints in HIV-infected people, as well as its potential relationships with demographic, clinical and psychological variables, in the era of combination antiretroviral therapies. Observational multicenter study developed in 4 hospitals and 10 NGOs, in which 791 people with HIV in Spain participated. A self-reported questionnaire was used to evaluate demographic and clinical variables, and an assessment of cognitive complaints, emotional status and quality of life variables was also included. Descriptive and inferential tests were used for statistical analyses. Almost half of the sample (49.8%) referred cognitive complaints, in 72.1% of them an association with interference on daily living activities was found. Memory and attention were the areas most prevalently perceived as affected. The existence of cognitive complaints correlated with a longer HIV infection, lower CD4+ cell count, undetectable viral load and worse quality of life. A discriminant analysis determined that depression, anxiety, older age, living with no partner and low education level allowed to classify optimally HIV-infected people with cognitive complaints. Self-reported cognitive complaints are frequent in people infected with HIV in the current era of combination antiretroviral therapies. This fact is related to emotional disturbances and poor quality of life, but also to impaired immunological and virological status. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  1. In vitro screening for population variability in toxicity of pesticide-containing mixtures

    Science.gov (United States)

    Abdo, Nour; Wetmore, Barbara A.; Chappell, Grace A.; Shea, Damian; Wright, Fred A.; Rusyna, Ivan

    2016-01-01

    Population-based human in vitro models offer exceptional opportunities for evaluating the potential hazard and mode of action of chemicals, as well as variability in responses to toxic insults among individuals. This study was designed to test the hypothesis that comparative population genomics with efficient in vitro experimental design can be used for evaluation of the potential for hazard, mode of action, and the extent of population variability in responses to chemical mixtures. We selected 146 lymphoblast cell lines from 4 ancestrally and geographically diverse human populations based on the availability of genome sequence and basal RNA-seq data. Cells were exposed to two pesticide mixtures – an environmental surface water sample comprised primarily of organochlorine pesticides and a laboratory-prepared mixture of 36 currently used pesticides – in concentration response and evaluated for cytotoxicity. On average, the two mixtures exhibited a similar range of in vitro cytotoxicity and showed considerable inter-individual variability across screened cell lines. However, when in vitroto-in vivo extrapolation (IVIVE) coupled with reverse dosimetry was employed to convert the in vitro cytotoxic concentrations to oral equivalent doses and compared to the upper bound of predicted human exposure, we found that a nominally more cytotoxic chlorinated pesticide mixture is expected to have greater margin of safety (more than 5 orders of magnitude) as compared to the current use pesticide mixture (less than 2 orders of magnitude) due primarily to differences in exposure predictions. Multivariate genome-wide association mapping revealed an association between the toxicity of current use pesticide mixture and a polymorphism in rs1947825 in C17orf54. We conclude that a combination of in vitro human population-based cytotoxicity screening followed by dosimetric adjustment and comparative population genomics analyses enables quantitative evaluation of human health hazard

  2. Accounting for pH heterogeneity and variability in modelling human health risks from cadmium in contaminated land

    International Nuclear Information System (INIS)

    Gay, J. Rebecca; Korre, Anna

    2009-01-01

    The authors have previously published a methodology which combines quantitative probabilistic human health risk assessment and spatial statistical methods (geostatistics) to produce an assessment, incorporating uncertainty, of risks to human health from exposure to contaminated land. The model assumes a constant soil to plant concentration factor (CF veg ) when calculating intake of contaminants. This model is modified here to enhance its use in a situation where CF veg varies according to soil pH, as is the case for cadmium. The original methodology uses sequential indicator simulation (SIS) to map soil concentration estimates for one contaminant across a site. A real, age-stratified population is mapped across the contaminated area, and intake of soil contaminants by individuals is calculated probabilistically using an adaptation of the Contaminated Land Exposure Assessment (CLEA) model. The proposed improvement involves not only the geostatistical estimation of the contaminant concentration, but also that of soil pH, which in turn leads to a variable CF veg estimate which influences the human intake results. The results presented demonstrate that taking pH into account can influence the outcome of the risk assessment greatly. It is proposed that a similar adaptation could be used for other combinations of soil variables which influence CF veg .

  3. An Integrated Workflow To Assess Technical and Biological Variability of Cell Population Frequencies in Human Peripheral Blood by Flow Cytometry.

    Science.gov (United States)

    Burel, Julie G; Qian, Yu; Lindestam Arlehamn, Cecilia; Weiskopf, Daniela; Zapardiel-Gonzalo, Jose; Taplitz, Randy; Gilman, Robert H; Saito, Mayuko; de Silva, Aruna D; Vijayanand, Pandurangan; Scheuermann, Richard H; Sette, Alessandro; Peters, Bjoern

    2017-02-15

    In the context of large-scale human system immunology studies, controlling for technical and biological variability is crucial to ensure that experimental data support research conclusions. In this study, we report on a universal workflow to evaluate both technical and biological variation in multiparameter flow cytometry, applied to the development of a 10-color panel to identify all major cell populations and T cell subsets in cryopreserved PBMC. Replicate runs from a control donation and comparison of different gating strategies assessed the technical variability associated with each cell population and permitted the calculation of a quality control score. Applying our panel to a large collection of PBMC samples, we found that most cell populations showed low intraindividual variability over time. In contrast, certain subpopulations such as CD56 T cells and Temra CD4 T cells were associated with high interindividual variability. Age but not gender had a significant effect on the frequency of several populations, with a drastic decrease in naive T cells observed in older donors. Ethnicity also influenced a significant proportion of immune cell population frequencies, emphasizing the need to account for these covariates in immune profiling studies. We also exemplify the usefulness of our workflow by identifying a novel cell-subset signature of latent tuberculosis infection. Thus, our study provides a universal workflow to establish and evaluate any flow cytometry panel in systems immunology studies. Copyright © 2017 by The American Association of Immunologists, Inc.

  4. Variable epitope libraries: new vaccine immunogens capable of inducing broad human immunodeficiency virus type 1-neutralizing antibody response.

    Science.gov (United States)

    Charles-Niño, Claudia; Pedroza-Roldan, Cesar; Viveros, Monica; Gevorkian, Goar; Manoutcharian, Karen

    2011-07-18

    The extreme antigenic variability of human immunodeficiency virus (HIV) leads to immune escape of the virus, representing a major challenge in the design of effective vaccine. We have developed a novel concept for immunogen construction based on introduction of massive mutations within the epitopes targeting antigenically variable pathogens and diseases. Previously, we showed that these immunogens carrying large combinatorial libraries of mutated epitope variants, termed as variable epitope libraries (VELs), induce potent, broad and long lasting CD8+IFN-γ+ T-cell response. Moreover, we demonstrated that these T cells recognize more than 50% of heavily mutated variants (5 out of 10 amino acid positions were mutated in each epitope variant) of HIV-1 gp120 V3 loop-derived cytotoxic T lymphocyte epitope (RGPGRAFVTI) in mice. The constructed VELs had complexities of 10000 and 12500 individual members, generated as plasmid DNA or as M13 phage display combinatorial libraries, respectively, and with structural composition RGPGXAXXXX or XGXGXAXVXI, where X is any of 20 natural amino acids. Here, we demonstrated that sera from mice immunized with these VELs are capable of neutralizing 5 out of 10 viral isolates from Tier 2 reference panel of subtype B envelope clones, including HIV-1 isolates which are known to be resistant to neutralization by several potent monoclonal antibodies, described previously. These data indicate the feasibility of the application of immunogens based on VEL concept as an alternative approach for the development of molecular vaccines against antigenically variable pathogens. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Natural and human-induced variability in the composition of fish assemblages in the Northwestern Cuban shelf.

    Science.gov (United States)

    González-Sansón, Gaspar; Aguilar, Consuelo; Hernández, Ivet; Cabrera, Yureidy; Suarez-Montes, Noelis; Bretos, Fernando; Guggenheim, David

    2009-09-01

    The main goal of the study was to obtain field data to build a baseline of fish assemblage composition that can be used comparatively for future analyses of the impact of human actions in the region. A basic network of 68 sampling stations was defined for the entire region (4,050 km2). Fish assemblage species and size composition was estimated using visual census methods at three different spatial scales: a) entire region, b) inside the main reef area and c) along a human impact coastal gradient. Multivariate numerical analyses revealed habitat type as the main factor inducing spatial variability of fish community composition, while the level of human impact appears to play the main role in fish assemblage composition changes along the coast. A trend of decreasing fish size toward the east supports the theory of more severe human impact due to overfishing and higher urban pollution in that direction. This is the first detailed study along the northwest coast of Cuba that focuses on fish community structure and the natural and human-induced variations at different spatial scales for the entire NW shelf. This research also provides input for a more comprehensive understanding of coastal marine fish communities' status in the Gulf of Mexico basin.

  6. Characterization of Common Measures of Heart Period Variability in Healthy Human Subjects: Implications for Patient Monitoring

    Science.gov (United States)

    2010-01-01

    sports medicine and science. Sports Med 2000; 30: 1–15. 41. Eckberg DL. The human respiratory gate. J Physiol 2003; 548: 339–352. 42. Kamen PW, Krum H...in short-term HRV analysis. Biomed Tech 2006; 51: 190–193. 45. Hayano J, Taylor JA, Yamada A, et al. Continuous assessment of hemodynamic control by

  7. A general auditory bias for handling speaker variability in speech? Evidence in humans and songbirds

    NARCIS (Netherlands)

    Kriengwatana, B.; Escudero, P.; Kerkhoven, A.H.; ten Cate, C.

    2015-01-01

    Different speakers produce the same speech sound differently, yet listeners are still able to reliably identify the speech sound. How listeners can adjust their perception to compensate for speaker differences in speech, and whether these compensatory processes are unique only to humans, is still

  8. Human activities and climate variability drive fast-paced change across the world's estuarine-coastal ecosystems

    Science.gov (United States)

    Cloern, James E.; Abreu, Paulo C.; Carstensen, Jacob; Chauvaud, Laurent; Elmgren, Ragnar; Grall, Jacques; Greening, Holly; Johansson, John O.R.; Kahru, Mati; Sherwood, Edward T.; Xu, Jie; Yin, Kedong

    2016-01-01

    Time series of environmental measurements are essential for detecting, measuring and understanding changes in the Earth system and its biological communities. Observational series have accumulated over the past 2–5 decades from measurements across the world's estuaries, bays, lagoons, inland seas and shelf waters influenced by runoff. We synthesize information contained in these time series to develop a global view of changes occurring in marine systems influenced by connectivity to land. Our review is organized around four themes: (i) human activities as drivers of change; (ii) variability of the climate system as a driver of change; (iii) successes, disappointments and challenges of managing change at the sea-land interface; and (iv) discoveries made from observations over time. Multidecadal time series reveal that many of the world's estuarine–coastal ecosystems are in a continuing state of change, and the pace of change is faster than we could have imagined a decade ago. Some have been transformed into novel ecosystems with habitats, biogeochemistry and biological communities outside the natural range of variability. Change takes many forms including linear and nonlinear trends, abrupt state changes and oscillations. The challenge of managing change is daunting in the coastal zone where diverse human pressures are concentrated and intersect with different responses to climate variability over land and over ocean basins. The pace of change in estuarine–coastal ecosystems will likely accelerate as the human population and economies continue to grow and as global climate change accelerates. Wise stewardship of the resources upon which we depend is critically dependent upon a continuing flow of information from observations to measure, understand and anticipate future changes along the world's coastlines.

  9. Uncertainty versus variability in Monte Carlo simulations of human exposure through food pathways

    International Nuclear Information System (INIS)

    McKone, T.E.

    1994-01-01

    An important issue in both the risk characterization and subsequent risk management of contaminated soil is how precisely we can characterize the distribution among individuals of potential doses associated with chemical contaminants in soil and whether this level of precision favors the use of population distributions of exposure over the use of single scenario representations. For lipophilic contaminants, such as dioxins, furans, polychlorinated biphenyls, pesticides, and for metals such as lead and mercury, exposures through food have been demonstrated to be dominant contributors to total dose within non-occupationally exposed populations. However, overall uncertainties in estimating potential doses through food chains are much larger than uncertainties associated with other exposure pathways. A general model is described here for estimating the ratio of potential dose to contaminant concentration in soil for homegrown foods contaminated by lipophilic, nonionic organic chemicals. This model includes parameters describing homegrown food consumption rates, exposure duration, biotransfer factors, and partition factors. For the parameters needed in this model, the mean and variance are often the only moments of the parameter distribution available. Parameters are divided into three categories, uncertain parameters, variable parameters, and mixed uncertain/variable parameters. Using soils contaminated by hexachlorbenzene (HCB) and benzo(a)pyrene (BaP) as cases studies, a stepwise Monte Carlo analysis is used to develop a histogram that apportions variance in the outcome (ratio of potential dose by food pathways to soil concentration) to variance in each of the three input categories. The results represent potential doses in households consuming homegrown foods

  10. Scaling prediction errors to reward variability benefits error-driven learning in humans.

    Science.gov (United States)

    Diederen, Kelly M J; Schultz, Wolfram

    2015-09-01

    Effective error-driven learning requires individuals to adapt learning to environmental reward variability. The adaptive mechanism may involve decays in learning rate across subsequent trials, as shown previously, and rescaling of reward prediction errors. The present study investigated the influence of prediction error scaling and, in particular, the consequences for learning performance. Participants explicitly predicted reward magnitudes that were drawn from different probability distributions with specific standard deviations. By fitting the data with reinforcement learning models, we found scaling of prediction errors, in addition to the learning rate decay shown previously. Importantly, the prediction error scaling was closely related to learning performance, defined as accuracy in predicting the mean of reward distributions, across individual participants. In addition, participants who scaled prediction errors relative to standard deviation also presented with more similar performance for different standard deviations, indicating that increases in standard deviation did not substantially decrease "adapters'" accuracy in predicting the means of reward distributions. However, exaggerated scaling beyond the standard deviation resulted in impaired performance. Thus efficient adaptation makes learning more robust to changing variability. Copyright © 2015 the American Physiological Society.

  11. Hydrocortisone at stress-associated concentrations helps maintain human heart rate variability during subsequent endotoxin challenge.

    Science.gov (United States)

    Rassias, Athos J; Guyre, Paul M; Yeager, Mark P

    2011-12-01

    We evaluated the differential impact of stress-associated vs high pharmacologic concentrations of hydrocortisone pretreatment on heart rate variability (HRV) during a subsequent systemic inflammatory stimulus. Healthy volunteers were randomized to receive placebo (Control) and hydrocortisone at 1.5 μg/kg per minute (STRESS) or at 3.0 μg/kg per minute (PHARM) as a 6-hour infusion. The STRESS dose was chosen to replicate the condition of physiologic adrenal cortical output during acute systemic stress. The PHARM dose was chosen to induce a supraphysiologic concentration of cortisol. The next day, all subjects received 2 ng/kg Escherichia coli endotoxin (lipopolysaccharide). Heart rate variability was analyzed with the statistic approximate entropy (ApEn). A lower ApEn correlates with decreased HRV. At the 3-hour nadir, the decrease in ApEn in the STRESS group was significantly less compared to placebo (P statistically different. We also found that the maximal decrease in ApEn preceded maximal increase in heart rate in all groups. The decrease in R-R interval was maximal at 4 hours, whereas the ApEn nadir was 1 hour earlier at 3 hours. Pretreatment with a stress dose of hydrocortisone but not a higher pharmacologic dose maintained a significantly higher ApEn after endotoxin exposure when compared to a placebo. In addition, decreases in ApEn preceded increases in heart rate. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Probabilistic Tractography Recovers a Rostrocaudal Trajectory of Connectivity Variability in the Human Insular Cortex

    Science.gov (United States)

    Cerliani, Leonardo; Thomas, Rajat M; Jbabdi, Saad; Siero, Jeroen CW; Nanetti, Luca; Crippa, Alessandro; Gazzola, Valeria; D'Arceuil, Helen; Keysers, Christian

    2012-01-01

    The insular cortex of macaques has a wide spectrum of anatomical connections whose distribution is related to its heterogeneous cytoarchitecture. Although there is evidence of a similar cytoarchitectural arrangement in humans, the anatomical connectivity of the insula in the human brain has not yet been investigated in vivo. In the present work, we used in vivo probabilistic white-matter tractography and Laplacian eigenmaps (LE) to study the variation of connectivity patterns across insular territories in humans. In each subject and hemisphere, we recovered a rostrocaudal trajectory of connectivity variation ranging from the anterior dorsal and ventral insula to the dorsal caudal part of the long insular gyri. LE suggested that regional transitions among tractography patterns in the insula occur more gradually than in other brain regions. In particular, the change in tractography patterns was more gradual in the insula than in the medial premotor region, where a sharp transition between different tractography patterns was found. The recovered trajectory of connectivity variation in the insula suggests a relation between connectivity and cytoarchitecture in humans resembling that previously found in macaques: tractography seeds from the anterior insula were mainly found in limbic and paralimbic regions and in anterior parts of the inferior frontal gyrus, while seeds from caudal insular territories mostly reached parietal and posterior temporal cortices. Regions in the putative dysgranular insula displayed more heterogeneous connectivity patterns, with regional differences related to the proximity with either putative granular or agranular regions. Hum Brain Mapp 33:2005–2034, 2012. © 2011 Wiley Periodicals, Inc. PMID:21761507

  13. Climate variability, human wildlife conflict and population dynamics of lions Panthera leo

    Science.gov (United States)

    Trinkel, Martina

    2013-04-01

    Large carnivores are threatened by habitat loss, declining prey populations and direct persecution. Pride dynamics of eight lion prides in the centre of the Etosha National Park, Namibia are described during a 16-year study. Since the beginning of the 1980s, the number of adult and subadult lions declined continuously to two third of its initial population size, and reached a new equilibrium in the 1990s. Pride sizes decreased from 6.3 adult females in 1989 to 2.8 lionesses in 1997. While the number of adult females declined continuously, the number of adult males, subadult females and subadult males remained constant over the years. A severe drought period, lasting for more than 20 years, led to declining prey populations inside the lions' territory. Besides declining prey populations, conflict with humans at the border of Etosha puts substantial pressure onto the lion population: 82 % of all known lion mortalities were caused by humans, and most of these consisted of adult females (28 %) and subadult males (29 %). I postulate that the considerable decline in the lion population is a response to declining prey populations, and although the human predator conflict is severe, it does not seem to limit the size of Etosha's lion population.

  14. Human genetic basis of interindividual variability in the course of infection

    Science.gov (United States)

    Casanova, Jean-Laurent

    2015-01-01

    The key problem in human infectious diseases was posed at the turn of the 20th century: their pathogenesis. For almost any given virus, bacterium, fungus, or parasite, life-threatening clinical disease develops in only a small minority of infected individuals. Solving this infection enigma is important clinically, for diagnosis, prognosis, prevention, and treatment. Some microbes will inevitably remain refractory to, or escape vaccination, or chemotherapy, or both. The solution also is important biologically, because the emergence and evolution of eukaryotes alongside more rapidly evolving prokaryotes, archaea, and viruses posed immunological challenges of an ecological and evolutionary nature. We need to study these challenges in natural, as opposed to experimental, conditions, and also at the molecular and cellular levels. According to the human genetic theory of infectious diseases, inborn variants underlie life-threatening infectious diseases. Here I review the history of the field of human genetics of infectious diseases from the turn of the 19th century to the second half of the 20th century. This paper thus sets the scene, providing the background information required to understand and appreciate the more recently described monogenic forms of resistance or predisposition to specific infections discussed in a second paper in this issue. PMID:26621739

  15. Single genome retrieval of context-dependent variability in mutation rates for human germline.

    Science.gov (United States)

    Sahakyan, Aleksandr B; Balasubramanian, Shankar

    2017-01-13

    Accurate knowledge of the core components of substitution rates is of vital importance to understand genome evolution and dynamics. By performing a single-genome and direct analysis of 39,894 retrotransposon remnants, we reveal sequence context-dependent germline nucleotide substitution rates for the human genome. The rates are characterised through rate constants in a time-domain, and are made available through a dedicated program (Trek) and a stand-alone database. Due to the nature of the method design and the imposed stringency criteria, we expect our rate constants to be good estimates for the rates of spontaneous mutations. Benefiting from such data, we study the short-range nucleotide (up to 7-mer) organisation and the germline basal substitution propensity (BSP) profile of the human genome; characterise novel, CpG-independent, substitution prone and resistant motifs; confirm a decreased tendency of moieties with low BSP to undergo somatic mutations in a number of cancer types; and, produce a Trek-based estimate of the overall mutation rate in human. The extended set of rate constants we report may enrich our resources and help advance our understanding of genome dynamics and evolution, with possible implications for the role of spontaneous mutations in the emergence of pathological genotypes and neutral evolution of proteomes.

  16. Physical linkage of a human immunoglobulin heavy chain variable region gene segment to diversity and joining region elements

    International Nuclear Information System (INIS)

    Schroeder, H.W. Jr.; Walter, M.A.; Hofker, M.H.; Ebens, A.; Van Dijk, K.W.; Liao, L.C.; Cox, D.W.; Milner, E.C.B.; Perlmutter, R.M.

    1988-01-01

    Antibody genes are assembled from a series of germ-line gene segments that are juxtaposed during the maturation of B lymphocytes. Although diversification of the adult antibody repertoire results in large part from the combinatorial joining of these gene segments, a restricted set of antibody heavy chain variable (V H ), diversity (D H ), and joining (J H ) region gene segments appears preferentially in the human fetal repertoire. The authors report here that one of these early-expressed V H elements (termed V H 6) is the most 3' V H gene segment, positioned 77 kilobases on the 5' side of the J H locus and immediately adjacent to a set of previously described D H sequences. In addition to providing a physical map linking human V H , D H , and J H elements, these results support the view that the programmed development of the antibody V H repertoire is determined in part by the chromosomal position of these gene segments

  17. BALANCE CAPACITY WITH VARIABILITY CAUSED BY HUMAN FACTOR: AN APPLICATION IN A LINE WITH MONTE CARLO SIMULATION

    Directory of Open Access Journals (Sweden)

    Augusto Sandes Mendes

    2016-07-01

    Full Text Available The variation in processing times due to the human factor between the working stations of a production line can generate queues resulting in a higher cost to the productive process. The objective of this study was to apply Monte Carlo simulation to balance the capacity of a production line with stations suffering variability in processing time due to the human factor. Simulations of the current situation of the production line were performed by comparing it with a proposal to align capacity with the production restriction in order to reduce inventories process while maintaining full capacity of the line. To develop the study, the selection involves the case of a company’s production line in the metal industry that produces machinery and products for metalworking area. The results allowed pointing suggestions for the company to reduce in-process inventory, keeping then total capacity of the line.

  18. Human preference for air movement

    DEFF Research Database (Denmark)

    Toftum, Jørn; Melikov, Arsen Krikor; Tynel, A.

    2002-01-01

    Human preference for air movement was studied at slightly cool, neutral, and slightly warm overall thermal sensations and at temperatures ranging from 18 deg.C to 28 deg.C. Air movement preference depended on both thermal sensation and temperature, but large inter-individual differences existed...... between subjects. Preference for less air movement was linearly correlated with draught discomfort, but the percentage of subjects who felt draught was lower than the percentage who preferred less air movement....

  19. Natural and Human-Induced Variability in Barrier-Island Response to Sea Level Rise

    Science.gov (United States)

    Miselis, Jennifer L.; Lorenzo-Trueba, Jorge

    2017-12-01

    Storm-driven sediment fluxes onto and behind barrier islands help coastal barrier systems keep pace with sea level rise (SLR). Understanding what controls cross-shore sediment flux magnitudes is critical for making accurate forecasts of barrier response to increased SLR rates. Here, using an existing morphodynamic model for barrier island evolution, observations are used to constrain model parameters and explore potential variability in future barrier behavior. Using modeled drowning outcomes as a proxy for vulnerability to SLR, 0%, 28%, and 100% of the barrier is vulnerable to SLR rates of 4, 7, and 10 mm/yr, respectively. When only overwash fluxes are increased in the model, drowning vulnerability increases for the same rates of SLR, suggesting that future increases in storminess may increase island vulnerability particularly where sediment resources are limited. Developed sites are more vulnerable to SLR, indicating that anthropogenic changes to overwash fluxes and estuary depths could profoundly affect future barrier response to SLR.

  20. Source of variability in localized P-31 spectroscopy in human liver

    International Nuclear Information System (INIS)

    Wear, K.A.; Rajan, S.; Myers, K.J.; Grossman, L.W.; Garra, B.S.

    1990-01-01

    This paper reports on chemical shift imaging which is an emerging clinical tool. Variability in measurements potentially can arise from variations in diet and coil geometry. Factors with significant effects must be identified and controlled to reduce variance of measurements and hence enhance discrimination among disease classes. One-dimensional P-31 chemical shift images of seven healthy volunteers were generated. A 1.5-T Siemens Magnetom and a custom-built double-tuned surface coil were used. Volunteers were imaged once after 7 hours of fasting and again 2 hours following a meal containing abundant quantities of complex carbohydrates and sugar. Data were processed with a 100-Hz convolution difference filter and a 15-Hz exponential filter

  1. Wide Variability in Caloric Density of Expressed Human Milk Can Lead to Major Underestimation or Overestimation of Nutrient Content.

    Science.gov (United States)

    Sauer, Charles W; Boutin, Mallory A; Kim, Jae H

    2017-05-01

    Very-low-birth-weight infants continue to face significant difficulties with postnatal growth. Human milk is the optimal form of nutrition for infants but may exhibit variation in nutrient content. This study aimed to perform macronutrient analysis on expressed human milk from mothers whose babies are hospitalized in the neonatal intensive care unit. Up to five human milk samples per participant were analyzed for protein, carbohydrate, and fat content using reference chemical analyses (Kjeldahl for protein, high pressure liquid chromatography for carbohydrates, and Mojonnier for fat). Calorie content was calculated. A total of 64 samples from 24 participants was analyzed. Wide variability was found in calorie, protein, carbohydrate, and fat composition. The authors found an average of 17.9 kcal/ounce, with only 34% of samples falling within 10% of the expected caloric density. The assumption that human milk contains 20 kcal/ounce is no longer supported based on this study. This supports promoting an individualized nutrition strategy as a crucial aspect to optimal nutrition.

  2. Investigating Intergenerational Differences in Human PCB Exposure due to Variable Emissions and Reproductive Behaviors

    Science.gov (United States)

    Quinn, Cristina L.; Wania, Frank; Czub, Gertje; Breivik, Knut

    2011-01-01

    Background Reproductive behaviors—such as age of childbearing, parity, and breast-feeding prevalence—have changed over the same historical time period as emissions of polychlorinated biphenyls (PCB) and may produce intergenerational differences in human PCB exposure. Objectives Our goal in this study was to estimate prenatal, postnatal, and lifetime PCB exposures for women at different ages according to year of birth, and to evaluate the impact of reproductive characteristics on intergenerational differences in exposure. Methods We used the time-variant mechanistic model CoZMoMAN to calculate human bioaccumulation of PCBs, assuming both hypothetical constant and realistic time-variant emissions. Results Although exposure primarily depends on when an individual was born relative to the emission history of PCBs, reproductive behaviors can have a significant impact. Our model suggests that a mother’s reproductive history has a greater influence on the prenatal and postnatal exposures of her children than it does on her own cumulative lifetime exposure. In particular, a child’s birth order appears to have a strong influence on their prenatal exposure, whereas postnatal exposure is determined by the type of milk (formula or breast milk) fed to the infant. Conclusions Prenatal PCB exposure appears to be delayed relative to the time of PCB emissions, particularly among those born after the PCB production phaseout. Consequently, the health repercussions of environmental PCBs can be expected to persist for several decades, despite bans on their production for > 40 years. PMID:21156396

  3. Pharmacomicrobiomics : the impact of human microbiome variations on systems pharmacology and personalized therapeutics

    NARCIS (Netherlands)

    ElRakaiby, Marwa; Dutilh, Bas E; Rizkallah, Mariam R; Boleij, Annemarie; Cole, Jason N; Aziz, Ramy K

    The Human Microbiome Project (HMP) is a global initiative undertaken to identify and characterize the collection of human-associated microorganisms at multiple anatomic sites (skin, mouth, nose, colon, vagina), and to determine how intra-individual and inter-individual alterations in the microbiome

  4. Pharmacomicrobiomics: the impact of human microbiome variations on systems pharmacology and personalized therapeutics

    NARCIS (Netherlands)

    ElRakaiby, M.; Dutilh, B.E.; Rizkallah, M.R.; Boleij, A.; Cole, J.N.; Aziz, R.K.

    2014-01-01

    The Human Microbiome Project (HMP) is a global initiative undertaken to identify and characterize the collection of human-associated microorganisms at multiple anatomic sites (skin, mouth, nose, colon, vagina), and to determine how intra-individual and inter-individual alterations in the microbiome

  5. Culture of human dental pulp cells at variable times post-tooth extraction

    Directory of Open Access Journals (Sweden)

    BENÍCIO Daniela Ferreira Araújo

    2018-02-01

    Full Text Available Abstract The aim of this study was to investigate the viability of human dental pulp cells from extracted teeth kept at standard room temperature and atmospheric pressure for different periods of time. Twenty-one healthy permanent teeth were used. They were divided into five groups according to the expected time from extraction to processing. One group was tested immediately after extraction; the other groups were each tested at one of the following time points: 30 minutes, 1 hour, 2 hours, and 5 hours post-extraction. Cell morphology was analysed by light microscopy; cell proliferation was analysed using MTT assay and by counting the viable cells in a haemocytometer. Similar results were observed in all groups (p < 0.05. A delay of up to five hours for tooth processing and tissue collection does not preclude the establishment of dental pulp cell cultures, affect the morphology of these cells, or reduce their proliferative potential.

  6. The role of protozoa-driven selection in shaping human genetic variability.

    Science.gov (United States)

    Pozzoli, Uberto; Fumagalli, Matteo; Cagliani, Rachele; Comi, Giacomo P; Bresolin, Nereo; Clerici, Mario; Sironi, Manuela

    2010-03-01

    Protozoa exert a strong selective pressure in humans. The selection signatures left by these pathogens can be exploited to identify genetic modulators of infection susceptibility. We show that protozoa diversity in different geographic locations is a good measure of protozoa-driven selective pressure; protozoa diversity captured selection signatures at known malaria resistance loci and identified several selected single nucleotide polymorphisms in immune and hemolytic anemia genes. A genome-wide search enabled us to identify 5180 variants mapping to 1145 genes that are subjected to protozoa-driven selective pressure. We provide a genome-wide estimate of protozoa-driven selective pressure and identify candidate susceptibility genes for protozoa-borne diseases. Copyright 2010 Elsevier Ltd. All rights reserved.

  7. Primer sets for cloning the human repertoire of T cell Receptor Variable regions

    Directory of Open Access Journals (Sweden)

    Santoro Claudio

    2008-08-01

    Full Text Available Abstract Background Amplification and cloning of naïve T cell Receptor (TR repertoires or antigen-specific TR is crucial to shape immune response and to develop immuno-based therapies. TR variable (V regions are encoded by several genes that recombine during T cell development. The cloning of expressed genes as large diverse libraries from natural sources relies upon the availability of primers able to amplify as many V genes as possible. Results Here, we present a list of primers computationally designed on all functional TR V and J genes listed in the IMGT®, the ImMunoGeneTics information system®. The list consists of unambiguous or degenerate primers suitable to theoretically amplify and clone the entire TR repertoire. We show that it is possible to selectively amplify and clone expressed TR V genes in one single RT-PCR step and from as little as 1000 cells. Conclusion This new primer set will facilitate the creation of more diverse TR libraries than has been possible using currently available primer sets.

  8. Primer sets for cloning the human repertoire of T cell Receptor Variable regions.

    Science.gov (United States)

    Boria, Ilenia; Cotella, Diego; Dianzani, Irma; Santoro, Claudio; Sblattero, Daniele

    2008-08-29

    Amplification and cloning of naïve T cell Receptor (TR) repertoires or antigen-specific TR is crucial to shape immune response and to develop immuno-based therapies. TR variable (V) regions are encoded by several genes that recombine during T cell development. The cloning of expressed genes as large diverse libraries from natural sources relies upon the availability of primers able to amplify as many V genes as possible. Here, we present a list of primers computationally designed on all functional TR V and J genes listed in the IMGT, the ImMunoGeneTics information system. The list consists of unambiguous or degenerate primers suitable to theoretically amplify and clone the entire TR repertoire. We show that it is possible to selectively amplify and clone expressed TR V genes in one single RT-PCR step and from as little as 1000 cells. This new primer set will facilitate the creation of more diverse TR libraries than has been possible using currently available primer sets.

  9. Morphometric variability of precuneus in relation to gender and the hemisphere of human brain

    Directory of Open Access Journals (Sweden)

    Spasojević Goran

    2004-01-01

    Full Text Available Precuneus, a quadrangular gyrus of the medial surface of the human parietal lobe, is bound by three primary brain sulci and by superior hemispheric border. Precise encephalometric data about precuneus are important in the studies of brain lateralization, sex dimorphism, and brain functions in general. In this study, total and visible (exstrasulcal surface area of the precuneus were measured on 50 brains of the adult persons (31 male, and 29 female, together with the investigation of its relationship to the side (left/right and gender (sex dimorphism. The average total surface area of the precuneus was 16.07 cm2 on the right (males 16.44 cm2, females 15.27 cm2, and 15.44 cm2 on the left (males 15.67 cm2, females 14.62 cm2. The average visible (extrasulcal surface area of cortex of precuneus was 9.97 cm2 on the left (males 10.75 cm2, females 8.91 cm2, and 9.38 cm2 on the right (males 10.25 cm2, females 8.19 cm2. Exstrasulcal surface area of the left precuneus was larger, by 0.59 cm on the average, which was not statistically significant. Total surface area of precuneus of males was significantly larger on the right (16.44 cm2 (p<0.01 than on the left (15.67 cm2. In females it was also larger on the right (15.27 cm2 than on the left (14.62 cm2, but with no statistical significance. Visible (exstrasulcal surface area of both, (left and right precuneus of males was highly significantly larger in comparison with the females (p<0.001. The obtained results and other facts suggested that sex dimorphism of human brain, including precuneus, was present, but not always easily observable studied or proven in all the details.

  10. Variability of in vivo linear microcrack accumulation in the cortex of elderly human ribs

    Directory of Open Access Journals (Sweden)

    Amanda M. Agnew

    2017-06-01

    Full Text Available Excessive accumulation of microdamage in the skeleton in vivo is believed to contribute to fragility and risk of fracture, particularly in the elderly. Current knowledge of how much in vivo damage accrual varies between individuals, if at all, is lacking. In this study, paired sixth ribs from five male and five female elderly individuals (76–92 years, mean age = 84.7 years were examined using en bloc staining and fluorescent microcopy to quantify linear microcracks present at the time of death (i.e. in vivo microdamage. Crack number, crack length, crack density, and crack surface density were measured for each complete cross-section, with densities calculated using the variable of bone area (which accounts for the influence of porosity on the cortex, unlike the more frequently used cortical area, and analyzed using a two-way mixed model analysis of variance. Results indicate that while microcracks between individuals differ significantly, differences between the left and right corresponding pairs within individuals and the pleural and cutaneous cortices within each rib did not. These results suggest that systemic influences, such as differential metabolic activity, affect the accumulation of linear microcracks. Furthermore, variation in remodeling rates between individuals may be a major factor contributing to differential fracture risk in the elderly. Future work should expand to include a wider age range to examine differences in in vivo microdamage accumulation across the lifespan, as well as considering the influence of bisphosphonates on microdamage accumulation in the context of compromised remodeling rates in the elderly.

  11. Radial Pressure Pulse and Heart Rate Variability in Heat- and Cold-Stressed Humans

    Directory of Open Access Journals (Sweden)

    Chin-Ming Huang

    2011-01-01

    Full Text Available This study aims to explore the effects of heat and cold stress on the radial pressure pulse (RPP and heart rate variability (HRV. The subjects immersed their left hand into 45°C and 7°C water for 2 minutes. Sixty healthy subjects (age 25±4 yr; 29 men and 31 women were enrolled in this study. All subjects underwent the supine temperature measurements of the bilateral forearms, brachial arterial blood pressure, HRV and RPP with a pulse analyzer in normothermic conditions, and thermal stresses. The power spectral low-frequency (LF and high-frequency (HF components of HRV decreased in the heat test and increased in the cold test. The heat stress significantly reduced radial augmentation index (AIr (P<.05, but the cold stress significantly increased AIr (P<.01. The spectral energy of RPP did not show any statistical difference in 0∼10 Hz region under both conditions, but in the region of 10∼50 Hz, there was a significant increase (P<.01 in the heat test and a significant decrease in the cold test (P<.01. The changes in AIr induced by heat and cold stress were significantly negatively correlated with the spectral energy in the region of 10∼50 Hz (SE10−50 Hz but not in the region of 0∼10 Hz (SE0−10 Hz. The results demonstrated that the SE10−50 Hz, which only possessed a small percentage in total pulse energy, presented more physiological characteristics than the SE0−10 Hz under the thermal stresses.

  12. Radial Pressure Pulse and Heart Rate Variability in Heat- and Cold-Stressed Humans

    Science.gov (United States)

    Huang, Chin-Ming; Chang, Hsien-Cheh; Kao, Shung-Te; Li, Tsai-Chung; Wei, Ching-Chuan; Chen, Chiachung; Liao, Yin-Tzu; Chen, Fun-Jou

    2011-01-01

    This study aims to explore the effects of heat and cold stress on the radial pressure pulse (RPP) and heart rate variability (HRV). The subjects immersed their left hand into 45°C and 7°C water for 2 minutes. Sixty healthy subjects (age 25 ± 4 yr; 29 men and 31 women) were enrolled in this study. All subjects underwent the supine temperature measurements of the bilateral forearms, brachial arterial blood pressure, HRV and RPP with a pulse analyzer in normothermic conditions, and thermal stresses. The power spectral low-frequency (LF) and high-frequency (HF) components of HRV decreased in the heat test and increased in the cold test. The heat stress significantly reduced radial augmentation index (AIr) (P < .05), but the cold stress significantly increased AIr (P < .01). The spectral energy of RPP did not show any statistical difference in 0 ~ 10 Hz region under both conditions, but in the region of 10 ~ 50 Hz, there was a significant increase (P < .01) in the heat test and a significant decrease in the cold test (P < .01). The changes in AIr induced by heat and cold stress were significantly negatively correlated with the spectral energy in the region of 10 ~ 50 Hz (SE10−50 Hz) but not in the region of 0 ~ 10 Hz (SE0−10 Hz). The results demonstrated that the SE10−50 Hz, which only possessed a small percentage in total pulse energy, presented more physiological characteristics than the SE0−10 Hz under the thermal stresses. PMID:21113292

  13. Platelet-rich plasma differs according to preparation method and human variability.

    Science.gov (United States)

    Mazzocca, Augustus D; McCarthy, Mary Beth R; Chowaniec, David M; Cote, Mark P; Romeo, Anthony A; Bradley, James P; Arciero, Robert A; Beitzel, Knut

    2012-02-15

    Varying concentrations of blood components in platelet-rich plasma preparations may contribute to the variable results seen in recently published clinical studies. The purposes of this investigation were (1) to quantify the level of platelets, growth factors, red blood cells, and white blood cells in so-called one-step (clinically used commercial devices) and two-step separation systems and (2) to determine the influence of three separate blood draws on the resulting components of platelet-rich plasma. Three different platelet-rich plasma (PRP) separation methods (on blood samples from eight subjects with a mean age [and standard deviation] of 31.6 ± 10.9 years) were used: two single-spin processes (PRPLP and PRPHP) and a double-spin process (PRPDS) were evaluated for concentrations of platelets, red and white blood cells, and growth factors. Additionally, the effect of three repetitive blood draws on platelet-rich plasma components was evaluated. The content and concentrations of platelets, white blood cells, and growth factors for each method of separation differed significantly. All separation techniques resulted in a significant increase in platelet concentration compared with native blood. Platelet and white blood-cell concentrations of the PRPHP procedure were significantly higher than platelet and white blood-cell concentrations produced by the so-called single-step PRPLP and the so-called two-step PRPDS procedures, although significant differences between PRPLP and PRPDS were not observed. Comparing the results of the three blood draws with regard to the reliability of platelet number and cell counts, wide variations of intra-individual numbers were observed. Single-step procedures are capable of producing sufficient amounts of platelets for clinical usage. Within the evaluated procedures, platelet numbers and numbers of white blood cells differ significantly. The intra-individual results of platelet-rich plasma separations showed wide variations in

  14. Blood pressure and heart rate variability analysis of orthostatic challenge in normal human pregnancies.

    Science.gov (United States)

    Heiskanen, Nonna; Saarelainen, Heli; Valtonen, Pirjo; Lyyra-Laitinen, Tiina; Laitinen, Tomi; Vanninen, Esko; Heinonen, Seppo

    2008-11-01

    The aim of the present study was to evaluate pregnancy-related changes in autonomic regulatory functions in healthy subjects. We studied cardiovascular autonomic responses to head-up tilt (HUT) in 28 pregnant women during the third trimester of pregnancy and 3 months after parturition. The maternal ECG and non-invasive beat-to-beat blood pressure were recorded in the horizontal position (left-lateral position) and during HUT in the upright position. Stroke volume was assessed from blood pressure signal by using the arterial pulse contour method. Heart rate variability (HRV) was analysed in frequency domain, and baroreflex sensitivity by the cross-spectral and the sequence methods. In the horizontal position, all frequency components of HRV were lower during pregnancy than 3 months after parturition (P pregnancy had no influence on normalized low frequency and high frequency powers. During pregnancy haemodynamics was well balanced with only minor changes in response to postural change while haemodynamic responses to HUT were more remarkable after parturition. In pregnant women HRV and especially its very low frequency component increased in response to HUT, whereas at 3 months after parturition the direction of these changes was opposite. Parasympathetic deactivation towards term is likely to contribute to increased heart rate and cardiac output at rest, whereas restored sympathetic modulation with modest responses may contribute stable peripheral resistance and sufficient placental blood supply under stimulated conditions. It is important to understand cardiovascular autonomic nervous system and haemodynamic control in normal pregnancy before being able to judge whether they are dysregulated in complicated pregnancies.

  15. Nonrandom variability in respiratory cycle parameters of humans during stage 2 sleep.

    Science.gov (United States)

    Modarreszadeh, M; Bruce, E N; Gothe, B

    1990-08-01

    We analyzed breath-to-breath inspiratory time (TI), expiratory time (TE), inspiratory volume (VI), and minute ventilation (Vm) from 11 normal subjects during stage 2 sleep. The analysis consisted of 1) fitting first- and second-order autoregressive models (AR1 and AR2) and 2) obtaining the power spectra of the data by fast-Fourier transform. For the AR2 model, the only coefficients that were statistically different from zero were the average alpha 1 (a1) for TI, VI, and Vm (a1 = 0.19, 0.29, and 0.15, respectively). However, the power spectra of all parameters often exhibited peaks at low frequency (less than 0.2 cycles/breath) and/or at high frequency (greater than 0.2 cycles/breath), indicative of periodic oscillations. After accounting for the corrupting effects of added oscillations on the a1 estimates, we conclude that 1) breath-to-breath fluctuations of VI, and to a lesser extent TI and Vm, exhibit a first-order autoregressive structure such that fluctuations of each breath are positively correlated with those of immediately preceding breaths and 2) the correlated components of variability in TE are mostly due to discrete high- and/or low-frequency oscillations with no underlying autoregressive structure. We propose that the autoregressive structure of VI, TI, and Vm during spontaneous breathing in stage 2 sleep may reflect either a central neural mechanism or the effects of noise in respiratory chemical feedback loops; the presence of low-frequency oscillations, seen more often in Vm, suggests possible instability in the chemical feedback loops. Mechanisms of high-frequency periodicities, seen more often in TE, are unknown.

  16. A study of genetic variability of human parainfluenza virus type 1 in Croatia, 2011-2014.

    Science.gov (United States)

    Košutić-Gulija, Tanja; Slovic, Anamarija; Ljubin-Sternak, Sunčanica; Mlinarić-Galinović, Gordana; Forčić, Dubravko

    2016-08-01

    Molecular epidemiology of human parainfluenza viruses type 1 (HPIV1) was investigated. Samples were collected from patients hospitalized in Croatia during the three consecutive epidemic seasons (2011-2014). Results indicated co-circulation of two major genetic clusters of HPIV1. Samples from the current study refer to clades II and III in a phylogenetic tree of haemagglutinin-neuraminidase (HN) gene. Additional phylogenetic trees of fusion (F) and phosphoprotein (P) genes confirmed the topology. Analysis of nucleotide diversity of entire P, F and HN genes demonstrated similar values: 0.0255, 0.0236 and 0.0237, respectively. However, amino acid diversity showed F protein to be the most conserved, while P protein was the most tolerant to mutations. Potential N- and O-glycosylation sites suggested that HPIV1 HN protein is abundantly glycosylated, and a specific N-glycosylation pattern could distinguish between clades II and III. Analysis of potential O-glycosylation sites in F protein indicated that samples from this study have two potential O-glycosylation sites, while publicly available sequences have five potential sites. This study provides data on the molecular characterization and epidemic pattern of HPIV1 in Croatia.

  17. Human movement stochastic variability leads to diagnostic biomarkers In Autism Spectrum Disorders (ASD)

    Science.gov (United States)

    Wu, Di; Torres, Elizabeth B.; Jose, Jorge V.

    2015-03-01

    ASD is a spectrum of neurodevelopmental disorders. The high heterogeneity of the symptoms associated with the disorder impedes efficient diagnoses based on human observations. Recent advances with high-resolution MEM wearable sensors enable accurate movement measurements that may escape the naked eye. It calls for objective metrics to extract physiological relevant information from the rapidly accumulating data. In this talk we'll discuss the statistical analysis of movement data continuously collected with high-resolution sensors at 240Hz. We calculated statistical properties of speed fluctuations within the millisecond time range that closely correlate with the subjects' cognitive abilities. We computed the periodicity and synchronicity of the speed fluctuations' from their power spectrum and ensemble averaged two-point cross-correlation function. We built a two-parameter phase space from the temporal statistical analyses of the nearest neighbor fluctuations that provided a quantitative biomarker for ASD and adult normal subjects and further classified ASD severity. We also found age related developmental statistical signatures and potential ASD parental links in our movement dynamical studies. Our results may have direct clinical applications.

  18. Variability in DNA repair capacity in the human population and its relationship to carcinogenic risk

    International Nuclear Information System (INIS)

    Nuzzo, F.; Stefanini, M.; Giulotto, E.; Falaschi, A.

    1980-01-01

    Several inherited diseases, all characterized by a high incidence of tumours in the homozygous patients, show pronounced defects in DNA repair mechanisms, thus confirming the relationship between the repair process and mutation induction, and indicating clearly that a fraction of the population is certainly much more exposed to cancer that the bulk of the human population. The basic molecular defects in such diseases are summarized. The estimated heterozygote frequency in tumour predisposing syndromes is considered and possible identification of heterozygotes discussed. A procedure to reveal DNA repair capacity at the cellular level would perhaps identify the cancer-prone fraction of the population. A simple assay for measuring repair synthesis is outlined which can be used to determine whether a given substance or treatment elicits repair synthesis and is hence harmful to DNA and potentially mutagenic and/or carcinogenic. It can also be used to assess the capacity of an individual to respond to a known DNA damaging agent. (Auth./C.F.)

  19. Human and bovine viruses and bacteria at three Great Lakes beaches: Environmental variable associations and health risk

    Science.gov (United States)

    Corsi, Steven R.; Borchardt, Mark A.; Carvin, Rebecca B.; Burch, Tucker R; Spencer, Susan K.; Lutz, Michelle A.; McDermott, Colleen M.; Busse, Kimberly M.; Kleinheinz, Gregory; Feng, Xiaoping; Zhu, Jun

    2016-01-01

    Waterborne pathogens were measured at three beaches in Lake Michigan, environmental factors for predicting pathogen concentrations were identified, and the risk of swimmer infection and illness was estimated. Waterborne pathogens were detected in 96% of samples collected at three Lake Michigan beaches in summer, 2010. Samples were quantified for 22 pathogens in four microbial categories (human viruses, bovine viruses, protozoa, and pathogenic bacteria). All beaches had detections of human and bovine viruses and pathogenic bacteria indicating influence of multiple contamination sources at these beaches. Occurrence ranged from 40 to 87% for human viruses, 65–87% for pathogenic bacteria, and 13–35% for bovine viruses. Enterovirus, adenovirus A, Salmonella spp., Campylobacter jejuni, bovine polyomavirus, and bovine rotavirus A were present most frequently. Variables selected in multiple regression models used to explore environmental factors that influence pathogens included wave direction, cloud cover, currents, and water temperature. Quantitative Microbial Risk Assessment was done for C. jejuni, Salmonella spp., and enteroviruses to estimate risk of infection and illness. Median infection risks for one-time swimming events were approximately 3 × 10–5, 7 × 10–9, and 3 × 10–7 for C. jejuni, Salmonella spp., and enteroviruses, respectively. Results highlight the importance of investigating multiple pathogens within multiple categories to avoid underestimating the prevalence and risk of waterborne pathogens.

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

    International Nuclear Information System (INIS)

    Yang, Xiaoxia; Doerge, Daniel R.; Teeguarden, Justin G.; Fisher, Jeffrey W.

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiaoxia, E-mail: xiaoxia.yang@fda.hhs.gov [Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Doerge, Daniel R. [Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Teeguarden, Justin G. [Health Effects and Exposure Science, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Fisher, Jeffrey W. [Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States)

    2015-12-15

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

  2. Quantifying the effects of climate variability and human activities on runoff for Kaidu River Basin in arid region of northwest China

    Science.gov (United States)

    Chen, Zhongsheng; Chen, Yaning; Li, Baofu

    2013-02-01

    Much attention has recently been focused on the effects that climate variability and human activities have had on runoff. In this study, data from the Kaidu River Basin in the arid region of northwest China were analyzed to investigate changes in annual runoff during the period of 1960-2009. The nonparametric Mann-Kendall test and the Mann-Kendall-Sneyers test were used to identify trend and step change point in the annual runoff. It was found that the basin had a significant increasing trend in annual runoff. Step change point in annual runoff was identified in the basin, which occurred in the year around 1993 dividing the long-term runoff series into a natural period (1960-1993) and a human-induced period (1994-2009). Then, the hydrologic sensitivity analysis method was employed to evaluate the effects of climate variability and human activities on mean annual runoff for the human-induced period based on precipitation and potential evapotranspiration. In 1994-2009, climate variability was the main factor that increased runoff with contribution of 90.5 %, while the increasing percentage due to human activities only accounted for 9.5 %, showing that runoff in the Kaidu River Basin is more sensitive to climate variability than human activities. This study quantitatively distinguishes the effects between climate variability and human activities on runoff, which can do duty for a reference for regional water resources assessment and management.

  3. Variable effects of cinder-cone eruptions on prehistoric agrarian human populations in the American southwest

    Science.gov (United States)

    Ort, Michael H.; Elson, Mark D.; Anderson, Kirk C.; Duffield, Wendell A.; Samples, Terry L.

    2008-10-01

    Two ˜ 900 BP cinder-cone eruptions in the American Southwest affected prehistoric human populations in different ways, mostly because of differences in the eruption styles and area affected. Primary pre-eruption cultural factors that may have led to successful adaptation to the eruptions include decision-making at the family or household level, low investment in site structures, dispersion of agricultural sites in varied environments, and settlement spread over a large area so that those who were less affected could shelter and feed evacuees. Sunset Crater, near Flagstaff, Arizona, produced about 8 km 2 lava flow fields and a ˜ 2300-km 2 tephra blanket in an area that had been settled by prehistoric groups for at least 1000 years. Local subsistence relied on agriculture, primarily maize, and > 30 cm tephra cover rendered 265 km 2 of prime land unfarmable. This area was apparently abandoned for at least several generations. A > 500-km 2 area was probably marked by collapsed roofs and other structural damage from the fallout. If the eruption occurred during the agricultural season, the fallout would also have significantly damaged crops. The eruption did have some benefits to local groups because lower elevation land, which had previously been too dry to farm, became agriculturally productive due to 3-8 cm of tephra 'mulch' and some temporary soil nutrient improvements. This previously uninhabited land became the site of significant year-round settlement and farming, eventually containing some of the largest pueblo structures ever built in the region. New agricultural techniques were developed to manage the fallout mulch. The eruption also affected ceramic production and trading patterns, and volcano-related ritual behavior - the production of maize-impressed lava-spatter agglutinate - was initiated. Little Springs Volcano, about 200 km northwest of Sunset Crater, is a small spatter rampart around a series of vents that produced about 5 km 2 of lava flow fields

  4. Hydrological Responses of Andean Lakes and Tropical Floodplains to Climate Variability and Human Intervention: an Integrative Modelling Framework

    Science.gov (United States)

    Hoyos, I. C.; González Morales, C.; Serna López, J. P.; Duque, C. L.; Canon Barriga, J. E.; Dominguez, F.

    2013-12-01

    Andean water bodies in tropical regions are significantly influenced by fluctuations associated with climatic and anthropogenic drivers, which implies long term changes in mountain snow peaks, land covers and ecosystems, among others. Our work aims at providing an integrative framework to realistically assess the possible future of natural water bodies with different degrees of human intervention. We are studying in particular the evolution of three water bodies in Colombia: two Andean lakes and a floodplain wetland. These natural reservoirs represent the accumulated effect of hydrological processes in their respective basins, which exhibit different patterns of climate variability and distinct human intervention and environmental histories. Modelling the hydrological responses of these local water bodies to climate variability and human intervention require an understanding of the strong linkage between geophysical and social factors. From the geophysical perspective, the challenge is how to downscale global climate projections in the local context: complex orography and relative lack of data. To overcome this challenge we combine the correlational and physically based analysis of several sources of spatially distributed biophysical and meteorological information to accurately determine aspects such as moisture sources and sinks and past, present and future local precipitation and temperature regimes. From the social perspective, the challenge is how to adequately represent and incorporate into the models the likely response of social agents whose water-related interests are diverse and usually conflictive. To deal with the complexity of these systems we develop interaction matrices, which are useful tools to holistically discuss and represent each environment as a complex system. Our goal is to assess partially the uncertainties of the hydrological balances in these intervened water bodies we establish climate/social scenarios, using hybrid models that combine

  5. Assessment of metabolic phenotypic variability in children’s urine using 1H NMR spectroscopy

    Science.gov (United States)

    Maitre, Léa; Lau, Chung-Ho E.; Vizcaino, Esther; Robinson, Oliver; Casas, Maribel; Siskos, Alexandros P.; Want, Elizabeth J.; Athersuch, Toby; Slama, Remy; Vrijheid, Martine; Keun, Hector C.; Coen, Muireann

    2017-04-01

    The application of metabolic phenotyping in clinical and epidemiological studies is limited by a poor understanding of inter-individual, intra-individual and temporal variability in metabolic phenotypes. Using 1H NMR spectroscopy we characterised short-term variability in urinary metabolites measured from 20 children aged 8-9 years old. Daily spot morning, night-time and pooled (50:50 morning and night-time) urine samples across six days (18 samples per child) were analysed, and 44 metabolites quantified. Intraclass correlation coefficients (ICC) and mixed effect models were applied to assess the reproducibility and biological variance of metabolic phenotypes. Excellent analytical reproducibility and precision was demonstrated for the 1H NMR spectroscopic platform (median CV 7.2%). Pooled samples captured the best inter-individual variability with an ICC of 0.40 (median). Trimethylamine, N-acetyl neuraminic acid, 3-hydroxyisobutyrate, 3-hydroxybutyrate/3-aminoisobutyrate, tyrosine, valine and 3-hydroxyisovalerate exhibited the highest stability with over 50% of variance specific to the child. The pooled sample was shown to capture the most inter-individual variance in the metabolic phenotype, which is of importance for molecular epidemiology study design. A substantial proportion of the variation in the urinary metabolome of children is specific to the individual, underlining the potential of such data to inform clinical and exposome studies conducted early in life.

  6. Association between the human herpesvirus 8 and the diffuse nodular lymphoid hyperplasia of the small intestine in common variable immunodeficiency

    International Nuclear Information System (INIS)

    Kokuina, Elena; Dominguez Alvarez, Carlos; Noa Pedroso, Guillermo; Martinez Rodriguez Pedro Ariel

    2009-01-01

    The common variable immunodeficiency (CVID) is the more frequent primary immunodeficiency in clinical field and its presentation forms are very variable. We describe the case of a women presenting with adult CVID with chronic diarrhea syndrome, weight loss and diffuse lymphadenopathies, where the more marked immunologic features were a deep hypogammaglobulinemia of the three major kinds of immunoglobulins and numerical decrease of B cells (CD19 +) and NK cells (CD3 -C D56 +) in peripheral blood. Biopsy of small intestine obtained by video-assisted panendoscope, showed the presence of a multinodular lymphoid hyperplasia with partial atrophy of hairinesses. Immunohistochemistry showed that nodules were high germinal centers with distribution of B cells (CD20 +) and T cells (CD3 +) , similar to that of normal follicle. There was not differential expression of the K and λ light chains. The real time polymerase chain reaction (QRT-PCR) method detected many copies from the genome of type 8 human herpesvirus (VHH-8) (133 copies/μL of DNA) in biopsy of intestinal nodule DNA. VHH-8 infection may to be a significant factor in pathogenesis of lymphoproliferative disorders in patients presenting with CVID

  7. From Human to Artificial Mouth, From Basics to Results

    International Nuclear Information System (INIS)

    Mielle, Patrick; Tarrega, Amparo; Salles, Christian; Gorria, Patrick; Liodenot, Jean Jacques; Liaboeuf, Joeel; Andrejewski, Jean-Luc

    2009-01-01

    Sensory perception of the flavor release during the eating of a food piece is highly dependent upon mouth parameters. Major limitations have been reported during in-vivo flavor release studies, such as marked intra- and inter-individual variability. To overcome these limitations, a chewing simulator has been developed to mimic the human mastication of food samples. The device faithfully reproduces most of the functions of the human mouth. The active cell comprises several mobile parts that can accurately reproduce shear and compression strengths and tongue functions in real-time, according to data previously collected in-vivo. The mechanical functionalities of the system were validated using peanuts, with a fair agreement with the human data. Flavor release can be monitored on-line using either API-MS or chemical sensors, or off-line using HPLC for non-volatile compounds. Couplings with API-MS detectors have shown differences in the kinetics of flavour release, as a function of the cheeses composition. Data were also collected for the analysis of taste compounds released during the human chewing but are not available yet for the Artificial Mouth.

  8. Effects of seasonal meteorological variables on E. coli persistence in livestock faeces and implications for environmental and human health.

    Science.gov (United States)

    Oliver, David M; Page, Trevor

    2016-11-15

    Agriculture contributes significant volumes of livestock faeces to land. Understanding how faecal microbes respond to shifts in meteorological patterns of contrasting seasons is important in order to gauge how environmental (and human health) risks may alter under a changing climate. The aim of this study was to: (i) quantify the temporal pattern of E. coli growth within dairy faeces post defecation; and (ii) derive E. coli seasonal population change profiles associated with contrasting environmental drivers. Evaluation of the die-off dynamics of E. coli revealed that a treatment mimicking drought and warming conditions significantly enhanced persistence relative to E. coli in faeces that were exposed to field conditions, and that this pattern was consistent across consecutive years. The internal temperature of faeces was important in driving the rate of change in the E. coli population in the immediate period post defecation, with most E. coli activity (as either die-off or growth) occurring at low dry matter content. This study highlighted that the use of seasonal E. coli persistence profiles should be approached with caution when modelling environmental and human health risks given the increased likelihood of atypical seasonal meteorological variables impacting on E. coli growth and die-off.

  9. Specific proliferation rates of human osteoblasts on calcium phosphate surfaces with variable concentrations of α-TCP

    International Nuclear Information System (INIS)

    Santos, Euler A. dos; Farina, Marcos; Soares, Gloria A.

    2007-01-01

    Ideally, ceramics used in the repair of bone defects need to be resorbed and replaced by newly formed bone in vivo. Tricalcium phosphate (TCP) has been widely used in association with hydroxyapatite (HA) due to its higher resorption kinetics when compared with HA alone. The aim of our study was to quantitatively investigate the effect of α-tricalcium phosphate (α-TCP) on human osteoblasts' adhesion and proliferation. Ceramic samples with variable concentrations of α-TCP and HA were produced by the calcination of calcium-deficient and stoichiometric HA. Human osteoblasts were cultured on the materials in three distinct experiments with different concentrations of cells. Numerical evaluation of cellular growth along time in culture was performed for each condition. The quantity of cells seeded onto the ceramics seems to influence the osteoblast behavior once proliferation was lower when more cells were seeded onto the samples. However, a smaller content of α-TCP in relation to that of HA did not significantly modify the specific proliferation rates of the osteoblasts. Only after a long time in culture, the increasing of the α-TCP content seems to change the cells' behavior

  10. Chemical variability of water and sediment over time and along a mountain river subjected to natural and human impact

    Directory of Open Access Journals (Sweden)

    Szarek-Gwiazda Ewa

    2018-01-01

    Full Text Available We studied the variability of physico-chemical parameters in water, and heavy metal contents in water and sediment over time and along the Carpathian Biała Tarnowska River (southern Poland and related them to catchment geology, human impact and the effect of barriers as a side aspect. The river water was well oxygenated, had pH 7.7–9.5 and was characterised by low and average flow. Temperature, pH and dissolved oxygen did not change significantly, while the contents of major ions, NO3−, NH4+, Mn and Fe increased gradually along the river. The major ion contents were negatively, and nitrate, Mn, and Fe positively, correlated with the flow. We recognise correlations between nitrate, Fe and Mn to be good indicators of soil erosion processes in the catchment. River sediment was unpolluted by most of the studied metals (slightly polluted by Ni and Cd. The differences in the values of some parameters (pH and NH4+, PO43−, HCO3−, Mn, Cd and Pb concentrations in the water, and heavy metals in the sediment upstream and downstream of some of the barriers were determined. Spatiotemporal changes in the values of studied parameters and the results of statistical calculation indicate the impact of human activity in the catchment basin (land use, wastewater on the water chemistry.

  11. SINGLE CHAIN VARIABLE FRAGMENTS OF ANTIBODIES AGAINST DIPHTHERIA TOXIN B-SUBUNIT ISOLATED FROM PHAGE DISPLAY HUMAN ANTIBODY LIBRARY

    Directory of Open Access Journals (Sweden)

    Oliinyk O. S.

    2014-02-01

    Full Text Available Diphtheria toxin is an exoantigen of Corynebacterium diphtheriae that inhibits protein synthesis and kills sensitive cells. The aim of this study was to obtain human recombinant single-chain variable fragment (scFv antibodies against receptor-binding B subunit of diphtheria toxin. 12 specific clones were selected after three rounds of a phage display naїve (unimmunized human antibody library against recombinant B-subunit. scFv DNA inserts from these 12 clones were digested with MvaI, and 6 unique restriction patterns were found. Single-chain antibodies were expressed in Escherichia coli XL1-blue. The recombinant proteins were characterized by immunoblotting of bacterial extracts and detection with an anti-E-tag antibody. The toxin B-subunit-binding function of the single-chain antibody was shown by ELISA. The affinity constants for different clones were found to be from 106 to 108 М–1. Due to the fact, that these antibody fragments recognized epitopes in the receptor-binding Bsubunit of diphtheria toxin, further studies are interesting to evaluate their toxin neutralization properties and potential for therapeutic applications. Obtained scFv-antibodies can also be used for detection and investigation of biological properties of diphtheria toxin.

  12. Plasticity, Variability and Age in Second Language Acquisition and Bilingualism.

    Science.gov (United States)

    Birdsong, David

    2018-01-01

    Much of what is known about the outcome of second language acquisition and bilingualism can be summarized in terms of inter-individual variability, plasticity and age. The present review looks at variability and plasticity with respect to their underlying sources, and at age as a modulating factor in variability and plasticity. In this context we consider critical period effects vs. bilingualism effects, early and late bilingualism, nativelike and non-nativelike L2 attainment, cognitive aging, individual differences in learning, and linguistic dominance in bilingualism. Non-uniformity is an inherent characteristic of both early and late bilingualism. This review shows how plasticity and age connect with biological and experiential sources of variability, and underscores the value of research that reveals and explains variability. In these ways the review suggests how plasticity, variability and age conspire to frame fundamental research issues in L2 acquisition and bilingualism, and provides points of reference for discussion of the present Frontiers in Psychology Research Topic.

  13. Isolation of primary microglia from the human post-mortem brain: effects of ante- and post-mortem variables.

    Science.gov (United States)

    Mizee, Mark R; Miedema, Suzanne S M; van der Poel, Marlijn; Adelia; Schuurman, Karianne G; van Strien, Miriam E; Melief, Jeroen; Smolders, Joost; Hendrickx, Debbie A; Heutinck, Kirstin M; Hamann, Jörg; Huitinga, Inge

    2017-02-17

    Microglia are key players in the central nervous system in health and disease. Much pioneering research on microglia function has been carried out in vivo with the use of genetic animal models. However, to fully understand the role of microglia in neurological and psychiatric disorders, it is crucial to study primary human microglia from brain donors. We have developed a rapid procedure for the isolation of pure human microglia from autopsy tissue using density gradient centrifugation followed by CD11b-specific cell selection. The protocol can be completed in 4 h, with an average yield of 450,000 and 145,000 viable cells per gram of white and grey matter tissue respectively. This method allows for the immediate phenotyping of microglia in relation to brain donor clinical variables, and shows the microglia population to be distinguishable from autologous choroid plexus macrophages. This protocol has been applied to samples from over 100 brain donors from the Netherlands Brain Bank, providing a robust dataset to analyze the effects of age, post-mortem delay, brain acidity, and neurological diagnosis on microglia yield and phenotype. Our data show that cerebrospinal fluid pH is positively correlated to microglial cell yield, but donor age and post-mortem delay do not negatively affect viable microglia yield. Analysis of CD45 and CD11b expression showed that changes in microglia phenotype can be attributed to a neurological diagnosis, and are not influenced by variation in ante- and post-mortem parameters. Cryogenic storage of primary microglia was shown to be possible, albeit with variable levels of recovery and effects on phenotype and RNA quality. Microglial gene expression substantially changed due to culture, including the loss of the microglia-specific markers, showing the importance of immediate microglia phenotyping. We conclude that primary microglia can be isolated effectively and rapidly from human post-mortem brain tissue, allowing for the study of the

  14. Physiologically based pharmacokinetic modeling of human exposure to perfluorooctanoic acid suggests historical non drinking-water exposures are important for predicting current serum concentrations.

    Science.gov (United States)

    Worley, Rachel Rogers; Yang, Xiaoxia; Fisher, Jeffrey

    2017-09-01

    Manufacturing of perfluorooctanoic acid (PFOA), a synthetic chemical with a long half-life in humans, peaked between 1970 and 2002, and has since diminished. In the United States, PFOA is detected in the blood of >99% of people tested, but serum concentrations have decreased since 1999. Much is known about exposure to PFOA in drinking water; however, the impact of non-drinking water PFOA exposure on serum PFOA concentrations is not well characterized. The objective of this research is to apply physiologically based pharmacokinetic (PBPK) modeling and Monte Carlo analysis to evaluate the impact of historic non-drinking water PFOA exposure on serum PFOA concentrations. In vitro to in vivo extrapolation was utilized to inform descriptions of PFOA transport in the kidney. Monte Carlo simulations were incorporated to evaluate factors that account for the large inter-individual variability of serum PFOA concentrations measured in individuals from North Alabama in 2010 and 2016, and the Mid-Ohio River Valley between 2005 and 2008. Predicted serum PFOA concentrations were within two-fold of experimental data. With incorporation of Monte Carlo simulations, the model successfully tracked the large variability of serum PFOA concentrations measured in populations from the Mid-Ohio River Valley. Simulation of exposure in a population of 45 adults from North Alabama successfully predicted 98% of individual serum PFOA concentrations measured in 2010 and 2016, respectively, when non-drinking water ingestion of PFOA exposure was included. Variation in serum PFOA concentrations may be due to inter-individual variability in the disposition of PFOA and potentially elevated historical non-drinking water exposures. Published by Elsevier Inc.

  15. Genetics of human body size and shape: body proportions and indices.

    Science.gov (United States)

    Livshits, Gregory; Roset, A; Yakovenko, K; Trofimov, S; Kobyliansky, E

    2002-01-01

    The study of the genetic component in morphological variables such as body height and weight, head and chest circumference, etc. has a rather long history. However, only a few studies investigated body proportions and configuration. The major aim of the present study was to evaluate the extent of the possible genetic effects on the inter-individual variation of a number of body configuration indices amenable to clear functional interpretation. Two ethnically different pedigree samples were used in the study: (1) Turkmenians (805 individuals) from Central Asia, and (2) Chuvasha (732 individuals) from the Volga riverside, Russian Federation. To achieve the aim of the present study we proposed three new indices, which were subjected to a statistical-genetic analysis using modified version of "FISHER" software. The proposed indices were: (1) an integral index of torso volume (IND#1), an index reflecting a predisposition of body proportions to maintain a balance in a vertical position (IND#2), and an index of skeletal extremities volume (IND#3). Additionally, the first two principal factors (PF1 and PF2) obtained on 19 measurements of body length and breadth were subjected to genetic analysis. Variance decomposition analysis that simultaneously assess the contribution of gender, age, additive genetic effects and effects of environment shared by the nuclear family members, was applied to fit variation of the above three indices, and PF1 and PF2. The raw familial correlation of all study traits and in both samples showed: (1) all marital correlations did not differ significantly from zero; (2) parent-offspring and sibling correlations were all positive and statistically significant. The parameter estimates obtained in variance analyses showed that from 40% to 75% of inter-individual variation of the studied traits (adjusted for age and sex) were attributable to genetic effects. For PF1 and PF2 in both samples, and for IND#2 (in Chuvasha pedigrees), significant common sib

  16. Studying variability in human brain aging in a population-based German cohort – Rationale and design of 1000BRAINS

    Directory of Open Access Journals (Sweden)

    Svenja eCaspers

    2014-07-01

    Full Text Available The ongoing 1000 brains study (1000BRAINS is an epidemiological and neuroscientific investigation of structural and functional variability in the human brain during aging. The two recruitment sources are the 10-year follow-up cohort of the German Heinz Nixdorf Recall (HNR Study, and the HNR MultiGeneration Study cohort, which comprises spouses and offspring of HNR subjects. The HNR is a longitudinal epidemiological investigation of cardiovascular risk factors, with a comprehensive collection of clinical, laboratory, socioeconomic, and environmental data from population-based subjects aged 45-75 years on inclusion. HNR subjects underwent detailed assessments in 2000, 2006, and 2011, and completed annual postal questionnaires on health status. 1000BRAINS accesses these HNR data and applies a separate protocol comprising: neuropsychological tests of attention, memory, executive functions & language; examination of motor skills; ratings of personality, life quality, mood & daily activities; analysis of laboratory and genetic data; and state-of-the-art magnetic resonance imaging (MRI, 3 Tesla of the brain. The latter includes (i 3D-T1- and 3D-T2-weighted scans for structural analyses and myelin mapping; (ii three diffusion imaging sequences optimized for diffusion tensor imaging, high-angular resolution diffusion imaging for detailed fibre tracking and for diffusion kurtosis imaging; (iii resting-state and task-based functional MRI; and (iv fluid-attenuated inversion recovery and MR angiography for the detection of vascular lesions and the mapping of white matter lesions. The unique design of 1000BRAINS allows: (i comprehensive investigation of various influences including genetics, environment and health status on variability in brain structure and function during aging; and (ii identification of the impact of selected influencing factors on specific cognitive subsystems and their anatomical correlates.

  17. Human activity and climate variability impacts on sediment discharge and runoff in the Yellow River of China

    Science.gov (United States)

    He, Yi; Wang, Fei; Mu, Xingmin; Guo, Lanqin; Gao, Peng; Zhao, Guangju

    2017-07-01

    We analyze the variability of sediment discharge and runoff in the Hekou-Longmen segment in the middle reaches of the Yellow River, China. Our analysis is based on Normalized Difference Vegetation Index (NDVI), sediment discharge, runoff, and monthly meteorological data (1961-2010). The climate conditions are controlled via monthly regional average precipitation and potential evapotranspiration (ET0) that are calculated with the Penman-Monteith method. Data regarding water and soil conservation infrastructure and their effects were investigated as causal factors of runoff and sediment discharge changes. The results indicated the following conclusions: (1) The sediment concentration, sediment discharge, and annual runoff, varied considerably during the study period and all of these factors exhibited larger coefficients of variation than ET0 and precipitation. (2) Sediment discharge, annual runoff, and sediment concentration significantly declined over the study period in a linear fashion. This was accompanied by an increase in ET0 and decline in precipitation that were not significant. (3) Within paired years with similar precipitation and potential evapotranspiration conditions (SPEC), all pairs showed a decline in runoff, sediment discharge, and sediment concentration. (4) Human impacts in this region were markedly high as indicated by NDVI, and soil and water measurements, and especially the soil and water conservation infrastructure resulting in an approximately 312 Mt year-1 of sediment deposition during 1960-1999.

  18. The impact of the matrix of red beet products and interindividual variability on betacyanins bioavailability in humans.

    Science.gov (United States)

    Wiczkowski, Wieslaw; Romaszko, Ewa; Szawara-Nowak, Dorota; Piskula, Mariusz K

    2018-06-01

    The influence of the matrix of red beetroot products and interindividual variability on betacyanins bioavailability in humans was studied. In a randomized crossover study 12 volunteers consumed red beet juice and crunchy slices containing betanin and isobetanin. Betalains were analyzed by the HPLC-DAD-MS. Urine samples examined after the consumption of both products contained not only native betacyanins but also their aglycones. In case of juice, the highest betacyanins urine excretion rate was observed within the first 2 h (64 nmol/h), while in case of crunchy slices within the period of 2-4 h (66 nmol/h). Among volunteers, the average total betacyanins excretion rate ranged from 18.54 to 67.96 nmol/h and, 13.15 to 63.58 nmol/h for red beet juice and crunchy slices, respectively. In total, approximately 0.3% of betacyanins (ranging from 0.12 to 0.58%) ingested from both products was excreted. The study showed that betacyanins bioavailability from juice and crunchy slices is similar, with the matrix of products consumed having an impact on betacyanins excretion profile, and the phenotype of volunteers affecting betacyanins excretion rate. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells.

    Science.gov (United States)

    Li, Jin; Jørgensen, Silje F; Maggadottir, S Melkorka; Bakay, Marina; Warnatz, Klaus; Glessner, Joseph; Pandey, Rahul; Salzer, Ulrich; Schmidt, Reinhold E; Perez, Elena; Resnick, Elena; Goldacker, Sigune; Buchta, Mary; Witte, Torsten; Padyukov, Leonid; Videm, Vibeke; Folseraas, Trine; Atschekzei, Faranaz; Elder, James T; Nair, Rajan P; Winkelmann, Juliane; Gieger, Christian; Nöthen, Markus M; Büning, Carsten; Brand, Stephan; Sullivan, Kathleen E; Orange, Jordan S; Fevang, Børre; Schreiber, Stefan; Lieb, Wolfgang; Aukrust, Pål; Chapel, Helen; Cunningham-Rundles, Charlotte; Franke, Andre; Karlsen, Tom H; Grimbacher, Bodo; Hakonarson, Hakon; Hammarström, Lennart; Ellinghaus, Eva

    2015-04-20

    Common variable immunodeficiency disorder (CVID) is the most common symptomatic primary immunodeficiency in adults, characterized by B-cell abnormalities and inadequate antibody response. CVID patients have considerable autoimmune comorbidity and we therefore hypothesized that genetic susceptibility to CVID may overlap with autoimmune disorders. Here, in the largest genetic study performed in CVID to date, we compare 778 CVID cases with 10,999 controls across 123,127 single-nucleotide polymorphisms (SNPs) on the Immunochip. We identify the first non-HLA genome-wide significant risk locus at CLEC16A (rs17806056, P=2.0 × 10(-9)) and confirm the previously reported human leukocyte antigen (HLA) associations on chromosome 6p21 (rs1049225, P=4.8 × 10(-16)). Clec16a knockdown (KD) mice showed reduced number of B cells and elevated IgM levels compared with controls, suggesting that CLEC16A may be involved in immune regulatory pathways of relevance to CVID. In conclusion, the CLEC16A associations in CVID represent the first robust evidence of non-HLA associations in this immunodeficiency condition.

  20. Towards the human colorectal cancer microbiome.

    Directory of Open Access Journals (Sweden)

    Julian R Marchesi

    Full Text Available Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is associated with human colorectal cancer (CRC. To this purpose, the microbiomes colonizing colon tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA sequencing. The results revealed striking differences in microbial colonization patterns between these two sites. Although inter-individual colonization in CRC patients was variable, tumors consistently formed a niche for Coriobacteria and other proposed probiotic bacterial species, while potentially pathogenic Enterobacteria were underrepresented in tumor tissue. As the intestinal microbiota is generally stable during adult life, these findings suggest that CRC-associated physiological and metabolic changes recruit tumor-foraging commensal-like bacteria. These microbes thus have an apparent competitive advantage in the tumor microenvironment and thereby seem to replace pathogenic bacteria that may be implicated in CRC etiology. This first glimpse of the CRC microbiome provides an important step towards full understanding of the dynamic interplay between intestinal microbial ecology and sporadic CRC, which may provide important leads towards novel microbiome-related diagnostic tools and therapeutic interventions.

  1. Determinants in the Ig Variable Domain of Human HAVCR1 (TIM-1) Are Required To Enhance Hepatitis C Virus Entry.

    Science.gov (United States)

    Kachko, Alla; Costafreda, Maria Isabel; Zubkova, Iryna; Jacques, Jerome; Takeda, Kazuyo; Wells, Frances; Kaplan, Gerardo; Major, Marian E

    2018-03-15

    Hepatitis C virus (HCV) is the leading cause of chronic hepatitis in humans. Several host molecules participate in HCV cell entry, but this process remains unclear. The complete unraveling of the HCV entry process is important to further understand viral pathogenesis and develop therapeutics. Human hepatitis A virus (HAV) cellular receptor 1 (HAVCR1), CD365, also known as TIM-1, functions as a phospholipid receptor involved in cell entry of several enveloped viruses. Here, we studied the role of HAVCR1 in HCV infection. HAVCR1 antibody inhibited entry in a dose-dependent manner. HAVCR1 soluble constructs neutralized HCV, which did not require the HAVCR1 mucinlike region and was abrogated by a mutation of N to A at position 94 (N94A) in the Ig variable (IgV) domain phospholipid-binding pocket, indicating a direct interaction of the HAVCR1 IgV domain with HCV virions. However, knockout of HAVCR1 in Huh7 cells reduced but did not prevent HCV growth. Interestingly, the mouse HAVCR1 ortholog, also a phospholipid receptor, did not enhance infection and a soluble form failed to neutralize HCV, although replacement of the mouse IgV domain with the human HAVCR1 IgV domain restored the enhancement of HCV infection. Mutations in the cytoplasmic tail revealed that direct HAVCR1 signaling is not required to enhance HCV infection. Our data show that the phospholipid-binding function and other determinant(s) in the IgV domain of human HAVCR1 enhance HCV infection. Although the exact mechanism is not known, it is possible that HAVCR1 facilitates entry by stabilizing or enhancing attachment, leading to direct interactions with specific receptors, such as CD81. IMPORTANCE Hepatitis C virus (HCV) enters cells through a multifaceted process. We identified the human hepatitis A virus cellular receptor 1 (HAVCR1), CD365, also known as TIM-1, as a facilitator of HCV entry. Antibody blocking and silencing or knockout of HAVCR1 in hepatoma cells reduced HCV entry. Our findings that the

  2. Natural and human-induced variability in the composition of fish assemblages in the Northwestern Cuban shelf

    Directory of Open Access Journals (Sweden)

    Gaspar González-Sansón

    2009-09-01

    Full Text Available The main goal of the study was to obtain field data to build a baseline of fish assemblage composition that can be used comparatively for future analyses of the impact of human actions in the region. A basic network of 68 sampling stations was defined for the entire region (4 050 km2. Fish assemblage species and size composition was estimated using visual census methods at three different spatial scales: a entire region, b inside the main reef area and c along a human impact coastal gradient. Multivariate numerical analyses revealed habitat type as the main factor inducing spatial variability of fish community composition, while the level of human impact appears to play the main role in fish assemblage composition changes along the coast. A trend of decreasing fish size toward the east supports the theory of more severe human impact due to overfishing and higher urban pollution in that direction. This is the first detailed study along the northwest coast of Cuba that focuses on fish community structure and the natural and human-induced variations at different spatial scales for the entire NW shelf. This research also provides input for a more comprehensive understanding of coastal marine fish communities’ status in the Gulf of Mexico basin. Rev. Biol. Trop. 57 (3: 721-740. Epub 2009 September 30.Se obtuvieron datos de campo para una línea base de la composición de la ictiofauna que pueda ser usada comparativamente para el análisis de impactos humanos futuros en la región. Se estableció una red básica de 68 estaciones de muestreo para la región completa (4 050 km2. La composición por especies y por tallas de la ictiofauna fue estimada utilizando métodos de censo visual en tres escalas espaciales diferentes: a La región completa, b dentro del área principal de arrecifes y c a lo largo de un gradiente costero de impacto humano. El tipo de hábitat es el factor principal que induce la variación espacial en la composición de la

  3. The "highs and lows" of the human brain on dopaminergics: Evidence from neuropharmacology.

    Science.gov (United States)

    Martins, Daniel; Mehta, Mitul A; Prata, Diana

    2017-09-01

    Rewards are appetitive events that elicit approach. Ground-breaking findings from neurophysiological experiments in animals, alongside neuropharmacology and neuroimaging research in human samples have identified dopamine as the main neurochemical messenger of global reward processing in the brain. However, dopamine's contribution to the different components of reward processing remains to be precisely defined. To facilitate the informed design and interpretation of reward studies in humans, we have systematically reviewed all existing human pharmacological studies investigating how drug manipulation of the dopamine system affects reward-related behaviour and its neural correlates. Pharmacological experiments in humans face methodological challenges in terms of the: 1) specificity and safety of the available drugs for administration in humans, 2) uncertainties about pre- or post-synaptic modes of action, and 3) possible interactions with inter-individual neuropsychological or genotypic variables. In order to circumvent some of these limitations, future research should rely on the combination of different levels of observation, in integrative pharmaco-genetics-neurobehavioral approaches, to more completely characterize dopamine's role in both general and modality-specific processing of reward. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Quantifying human disturbance in watersheds: Variable selection and performance of a GIS-based disturbance index for predicting the biological condition of perennial streams

    Science.gov (United States)

    Falcone, James A.; Carlisle, Daren M.; Weber, Lisa C.

    2010-01-01

    Characterizing the relative severity of human disturbance in watersheds is often part of stream assessments and is frequently done with the aid of Geographic Information System (GIS)-derived data. However, the choice of variables and how they are used to quantify disturbance are often subjective. In this study, we developed a number of disturbance indices by testing sets of variables, scoring methods, and weightings of 33 potential disturbance factors derived from readily available GIS data. The indices were calibrated using 770 watersheds located in the western United States for which the severity of disturbance had previously been classified from detailed local data by the United States Environmental Protection Agency (USEPA) Environmental Monitoring and Assessment Program (EMAP). The indices were calibrated by determining which variable or variable combinations and aggregation method best differentiated between least- and most-disturbed sites. Indices composed of several variables performed better than any individual variable, and best results came from a threshold method of scoring using six uncorrelated variables: housing unit density, road density, pesticide application, dam storage, land cover along a mainstem buffer, and distance to nearest canal/pipeline. The final index was validated with 192 withheld watersheds and correctly classified about two-thirds (68%) of least- and most-disturbed sites. These results provide information about the potential for using a disturbance index as a screening tool for a priori ranking of watersheds at a regional/national scale, and which landscape variables and methods of combination may be most helpful in doing so.

  5. Microchemical and structural regular variability of apatites in 'overbuilt' enamel and dentin of human molar teeth

    Energy Technology Data Exchange (ETDEWEB)

    Kuczumow, A., E-mail: kuczon@kul.lublin.pl [Department of Chemistry, Lublin Catholic University, 20-718 Lublin (Poland); Nowak, J. [Department of Chemistry, Lublin Catholic University, 20-718 Lublin (Poland); ChaLas, R. [Department of Conservative Medicine, Lublin Medical University, 20-081 Lublin (Poland)

    2011-10-15

    The aim of a recent paper was to recognize the chemical and structural changes in apatites, which form both the enamel and the dentin of the human tooth. The aim was achieved by scrutinizing the linear elemental profiles along the cross-sections of human molar teeth. Essentially, the task was accomplished with the application of the Electron Probe Microanalysis method and with some additional studies by Micro-Raman spectrometry. All the trends in linear profiles were strictly determined. In the enamel zone they were either increasing or decreasing curves of exponential character. The direction of the investigations was to start with the tooth surface and move towards the dentin-enamel junction (DEJ). The results of the elemental studies were more visible when the detected material was divided, in an arbitrary way, into the prevailing 'core' enamel ({approx}93.5% of the total mass) and the remaining 'overbuilt' enamel. The material in the 'core' enamel was fully stable, with clearly determined chemical and mechanical features. However, the case was totally different in the 'overbuilt enamel', with dynamic changes in the composition. In the 'overbuilt' layer Ca, P, Cl and F profiles present the decaying distribution curves, whereas Mg, Na, K and CO{sub 3}{sup 2-} present the growing ones. Close to the surface of the tooth the mixture of hydroxy-, chlor- and fluor-apatite is formed, which is much more resistant than the rest of the enamel. On passing towards the DEJ, the apatite is enriched with Na, Mg and CO{sub 3}{sup 2-}. In this location, three of six phosphate groups were substituted with carbonate groups. Simultaneously, Mg is associated with the hydroxyl groups around the hexad axis. In this way, the mechanisms of exchange reactions were established. The crystallographic structures were proposed for new phases located close to DEJ. In the dentin zone, the variability of elemental profiles looks different, with

  6. A pilot investigation of the effect of extremely low frequency pulsed electromagnetic fields on humans' heart rate variability.

    Science.gov (United States)

    Baldi, Emilio; Baldi, Claudio; Lithgow, Brian J

    2007-01-01

    The question whether pulsed electromagnetic field (PEMF) can affect the heart rhythm is still controversial. This study investigates the effects on the cardiocirculatory system of ELF-PEMFs. It is a follow-up to an investigation made of the possible therapeutic effect ELF-PEMFs, using a commercially available magneto therapeutic unit, had on soft tissue injury repair in humans. Modulation of heart rate (HR) or heart rate variability (HRV) can be detected from changes in periodicity of the R-R interval and/or from changes in the numbers of heart-beat/min (bpm), however, R-R interval analysis gives only a quantitative insight into HRV. A qualitative understanding of HRV can be obtained considering the power spectral density (PSD) of the R-R intervals Fourier transform. In this study PSD is the investigative tool used, more specifically the low frequency (LF) PSD and high frequency (HF) PSD ratio (LF/HF) which is an indicator of sympatho-vagal balance. To obtain the PSD value, variations of the R-R time intervals were evaluated from a continuously recorded ECG. The results show a HR variation in all the subjects when they are exposed to the same ELF-PEMF. This variation can be detected by observing the change in the sympatho-vagal equilibrium, which is an indicator of modulation of heart activity. Variation of the LF/HF PSD ratio mainly occurs at transition times from exposure to nonexposure, or vice versa. Also of interest are the results obtained during the exposure of one subject to a range of different ELF-PEMFs. This pilot study suggests that a full investigation into the effect of ELF-PEMFs on the cardiovascular system is justified.

  7. Characterizing synaptic protein development in human visual cortex enables alignment of synaptic age with rat visual cortex

    Science.gov (United States)

    Pinto, Joshua G. A.; Jones, David G.; Williams, C. Kate; Murphy, Kathryn M.

    2015-01-01

    Although many potential neuroplasticity based therapies have been developed in the lab, few have translated into established clinical treatments for human neurologic or neuropsychiatric diseases. Animal models, especially of the visual system, have shaped our understanding of neuroplasticity by characterizing the mechanisms that promote neural changes and defining timing of the sensitive period. The lack of knowledge about development of synaptic plasticity mechanisms in human cortex, and about alignment of synaptic age between animals and humans, has limited translation of neuroplasticity therapies. In this study, we quantified expression of a set of highly conserved pre- and post-synaptic proteins (Synapsin, Synaptophysin, PSD-95, Gephyrin) and found that synaptic development in human primary visual cortex (V1) continues into late childhood. Indeed, this is many years longer than suggested by neuroanatomical studies and points to a prolonged sensitive period for plasticity in human sensory cortex. In addition, during childhood we found waves of inter-individual variability that are different for the four proteins and include a stage during early development (visual cortex and identified a simple linear equation that provides robust alignment of synaptic age between humans and rats. Alignment of synaptic ages is important for age-appropriate targeting and effective translation of neuroplasticity therapies from the lab to the clinic. PMID:25729353

  8. Variability of femoral muscle attachments.

    Science.gov (United States)

    Duda, G N; Brand, D; Freitag, S; Lierse, W; Schneider, E

    1996-09-01

    Analytical and experimental models of the musculoskeletal system often assume single values rather than ranges for anatomical input parameters. The hypothesis of the present study was that anatomical variability significantly influences the results of biomechanical analyses, specifically regarding the moment arms of the various thigh muscles. Insertions and origins of muscles crossing or attaching to the femur were digitized in six specimens. Muscle volumes were measured; muscle attachment area and centroid location were computed. To demonstrate the influence of inter-individual anatomic variability on a mechanical modeling parameter, the corresponding range of muscle moment arms were calculated. Standard deviations, as a percentage of the mean, were about 70% for attachment area and 80% for muscle volume and attachment centroid location. The resulting moment arms of the m. gluteus maximus and m. rectus femoris were especially sensitive to anatomical variations (SD 65%). The results indicate that sensitivity to anatomical variations should be analyzed in any investigation simulating musculoskeletal interactions. To avoid misinterpretations, investigators should consider using several anatomical configurations rather than relying on a mean data set.

  9. Evidence for widespread changes in promoter methylation profile in human placenta in response to increasing gestational age and environmental/stochastic factors

    Directory of Open Access Journals (Sweden)

    Craig Jeffrey M

    2011-10-01

    Full Text Available Abstract Background The human placenta facilitates the exchange of nutrients, gas and waste between the fetal and maternal circulations. It also protects the fetus from the maternal immune response. Due to its role at the feto-maternal interface, the placenta is subject to many environmental exposures that can potentially alter its epigenetic profile. Previous studies have reported gene expression differences in placenta over gestation, as well as inter-individual variation in expression of some genes. However, the factors contributing to this variation in gene expression remain poorly understood. Results In this study, we performed a genome-wide DNA methylation analysis of gene promoters in placenta tissue from three pregnancy trimesters. We identified large-scale differences in DNA methylation levels between first, second and third trimesters, with an overall progressive increase in average methylation from first to third trimester. The most differentially methylated genes included many immune regulators, reflecting the change in placental immuno-modulation as pregnancy progresses. We also detected increased inter-individual variation in the third trimester relative to first and second, supporting an accumulation of environmentally induced (or stochastic changes in DNA methylation pattern. These highly variable genes were enriched for those involved in amino acid and other metabolic pathways, potentially reflecting the adaptation of the human placenta to different environments. Conclusions The identification of cellular pathways subject to drift in response to environmental influences provide a basis for future studies examining the role of specific environmental factors on DNA methylation pattern and placenta-associated adverse pregnancy outcomes.

  10. Human and methodological sources of variability in the measurement of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine

    DEFF Research Database (Denmark)

    Barregard, Lars; Møller, Peter; Henriksen, Trine

    2013-01-01

    Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to as...

  11. Phylotyping and functional analysis of two ancient human microbiomes.

    Directory of Open Access Journals (Sweden)

    Raúl Y Tito

    Full Text Available BACKGROUND: The Human Microbiome Project (HMP is one of the U.S. National Institutes of Health Roadmap for Medical Research. Primary interests of the HMP include the distinctiveness of different gut microbiomes, the factors influencing microbiome diversity, and the functional redundancies of the members of human microbiotas. In this present work, we contribute to these interests by characterizing two extinct human microbiotas. METHODOLOGY/PRINCIPAL FINDINGS: We examine two paleofecal samples originating from cave deposits in Durango Mexico and dating to approximately 1300 years ago. Contamination control is a serious issue in ancient DNA research; we use a novel approach to control contamination. After we determined that each sample originated from a different human, we generated 45 thousand shotgun DNA sequencing reads. The phylotyping and functional analysis of these reads reveals a signature consistent with the modern gut ecology. Interestingly, inter-individual variability for phenotypes but not functional pathways was observed. The two ancient samples have more similar functional profiles to each other than to a recently published profile for modern humans. This similarity could not be explained by a chance sampling of the databases. CONCLUSIONS/SIGNIFICANCE: We conduct a phylotyping and functional analysis of ancient human microbiomes, while providing novel methods to control for DNA contamination and novel hypotheses about past microbiome biogeography. We postulate that natural selection has more of an influence on microbiome functional profiles than it does on the species represented in the microbial ecology. We propose that human microbiomes were more geographically structured during pre-Columbian times than today.

  12. Pharmacomicrobiomics: The Impact of Human Microbiome Variations on Systems Pharmacology and Personalized Therapeutics

    OpenAIRE

    ElRakaiby, Marwa; Dutilh, Bas E.; Rizkallah, Mariam R.; Boleij, Annemarie; Cole, Jason N.; Aziz, Ramy K.

    2014-01-01

    The Human Microbiome Project (HMP) is a global initiative undertaken to identify and characterize the collection of human-associated microorganisms at multiple anatomic sites (skin, mouth, nose, colon, vagina), and to determine how intra-individual and inter-individual alterations in the microbiome influence human health, immunity, and different disease states. In this review article, we summarize the key findings and applications of the HMP that may impact pharmacology and personalized thera...

  13. Cardiac parasympathetic outflow during dynamic exercise in humans estimated from power spectral analysis of P-P interval variability.

    Science.gov (United States)

    Takahashi, Makoto; Nakamoto, Tomoko; Matsukawa, Kanji; Ishii, Kei; Watanabe, Tae; Sekikawa, Kiyokazu; Hamada, Hironobu

    2016-03-01

    What is the central question of this study? Should we use the high-frequency (HF) component of P-P interval as an index of cardiac parasympathetic nerve activity during moderate exercise? What is the main finding and its importance? The HF component of P-P interval variability remained even at a heart rate of 120-140 beats min(-1) and was further reduced by atropine, indicating incomplete cardiac vagal withdrawal during moderate exercise. The HF component of R-R interval is invalid as an estimate of cardiac parasympathetic outflow during moderate exercise; instead, the HF component of P-P interval variability should be used. The high-frequency (HF) component of R-R interval variability has been widely used as an indirect estimate of cardiac parasympathetic (vagal) outflow to the sino-atrial node of the heart. However, we have recently found that the variability of the R-R interval becomes much smaller during dynamic exercise than that of the P-P interval above a heart rate (HR) of ∼100 beats min(-1). We hypothesized that cardiac parasympathetic outflow during dynamic exercise with a higher intensity may be better estimated using the HF component of P-P interval variability. To test this hypothesis, the HF components of both P-P and R-R interval variability were analysed using a Wavelet transform during dynamic exercise. Twelve subjects performed ergometer exercise to increase HR from the baseline of 69 ± 3 beats min(-1) to three different levels of 100, 120 and 140 beats min(-1). We also examined the effect of atropine sulfate on the HF components in eight of the 12 subjects during exercise at an HR of 140 beats min(-1) . The HF component of P-P interval variability was significantly greater than that of R-R interval variability during exercise, especially at the HRs of 120 and 140 beats min(-1). The HF component of P-P interval variability was more reduced by atropine than that of R-R interval variability. We conclude that cardiac parasympathetic outflow to the

  14. Distribution of the Most Common Genetic Variants Associated with a Variable Drug Response in the Population of the Republic of Macedonia

    Directory of Open Access Journals (Sweden)

    Nestorovska Kapedanovska A.

    2014-12-01

    Full Text Available Genetic variation in the regulation, expression and activity of genes coding for Phase I, Phase II drug metabolizing enzymes (DMEs and drug targets, can be defining factors for the variability in both the effectiveness and occurrence of drug therapy side effects. Information regarding the geographic structure and multi-ethnic distribution of clinically relevant genetic variations is becoming increasingly useful for improving drug therapy and explaining inter-individual and inter-ethnic differences in drug response.

  15. Characterization of the porosity of human dental enamel and shear bond strength in vitro after variable etch times: initial findings using the BET method.

    Science.gov (United States)

    Nguyen, Trang T; Miller, Arthur; Orellana, Maria F

    2011-07-01

    (1) To quantitatively characterize human enamel porosity and surface area in vitro before and after etching for variable etching times; and (2) to evaluate shear bond strength after variable etching times. Specifically, our goal was to identify the presence of any correlation between enamel porosity and shear bond strength. Pore surface area, pore volume, and pore size of enamel from extracted human teeth were analyzed by Brunauer-Emmett-Teller (BET) gas adsorption before and after etching for 15, 30, and 60 seconds with 37% phosphoric acid. Orthodontic brackets were bonded with Transbond to the samples with variable etch times and were subsequently applied to a single-plane lap shear testing system. Pore volume and surface area increased after etching for 15 and 30 seconds. At 60 seconds, this increase was less pronounced. On the contrary, pore size appears to decrease after etching. No correlation was found between variable etching times and shear strength. Samples etched for 15, 30, and 60 seconds all demonstrated clinically viable shear strength values. The BET adsorption method could be a valuable tool in enhancing our understanding of enamel characteristics. Our findings indicate that distinct quantitative changes in enamel pore architecture are evident after etching. Further testing with a larger sample size would have to be carried out for more definitive conclusions to be made.

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

    Science.gov (United States)

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

    2014-01-01

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

  17. Study of the genetic variability of isolated belonging to the group B of the Respiratory Virus Human Sincicial

    International Nuclear Information System (INIS)

    Delfraro, A.

    1998-07-01

    The study allows analyzing the genetic variability of stumps belonging to the group B of the Breathing Virus Sincicial (Vrs), isolated in Uruguay among the years 1990 and 1996. They were evidenced by sequence the nucleotides changes and the changes were determined that take place at level of amino acids, the following ones were used technical: enzyme immunoassay, of extraction of viral RNA, of reverse transcription and Pcr, of purification of DNA and electrophoresis of nucleic acids. The result proven in the entirety of the isolated virus the genetic variability, enlarging and confirming the evolution pattern proposed by Sullender and collaborators, (1991) for the group B of Vrs [es

  18. Human choices and environmental constraints: deciphering the variability of large game procurement from Mousterian to Aurignacian times (MIS 5-3) in southwestern France

    Science.gov (United States)

    Discamps, Emmanuel; Jaubert, Jacques; Bachellerie, François

    2011-09-01

    The evolution in the selection of prey made by past humans, especially the Neandertals and the first anatomically modern humans, has been widely debated. Between Marine Isotope Stages (MIS) 5 and 3, the accuracy of absolute dating is still insufficient to precisely correlate paleoclimatic and archaeological data. It is often difficult, therefore, to estimate to what extent changes in species procurement are correlated with either climate fluctuations or deliberate cultural choices in terms of subsistence behavior. Here, the full development of archeostratigraphy and Bayesian statistical analysis of absolute dates allows the archeological and paleoclimatic chronologies to be compared. The variability in hunted fauna is investigated using multivariate statistical analysis of quantitative faunal lists of 148 assemblages from 39 archeological sequences from MIS 5 through MIS 3. Despite significant intra-technocomplex variability, it is possible to identify major shifts in the human diet during these stages. The integration of archeological data, paleoclimatic proxies and the ecological characteristics of the different species of prey shows that the shifts in large game hunting can be explained by an adaptation of the human groups to climatic fluctuations. However, even if Middle and Early Upper Paleolithic men adapted to changes in their environment and to contrasting landscapes, they ultimately belonged to the ecosystems of the past and were limited by environmental constraints.

  19. Correlation of Metabolic Variables with the Number of ORFs in Human Pathogenic and Phylogenetically Related Non- or Less-Pathogenic Bacteria.

    Science.gov (United States)

    Brambila-Tapia, Aniel Jessica Leticia; Poot-Hernández, Augusto Cesar; Garcia-Guevara, Jose Fernando; Rodríguez-Vázquez, Katya

    2016-06-01

    To date, a few works have performed a correlation of metabolic variables in bacteria; however specific correlations with these variables have not been reported. In this work, we included 36 human pathogenic bacteria and 18 non- or less-pathogenic-related bacteria and obtained all metabolic variables, including enzymes, metabolic pathways, enzymatic steps and specific metabolic pathways, and enzymatic steps of particular metabolic processes, from a reliable metabolic database (KEGG). Then, we correlated the number of the open reading frames (ORF) with these variables and with the proportions of these variables, and we observed a negative correlation with the proportion of enzymes (r = -0.506, p < 0.0001), metabolic pathways (r = -0.871, p < 00.0001), enzymatic reactions (r = -0.749, p < 00.0001), and with the proportions of central metabolism variables as well as a positive correlation with the proportions of multistep reactions (r = 0.650, p < 00.0001) and secondary metabolism variables. The proportion of multifunctional reactions (r: -0.114, p = 0.41) and the proportion of enzymatic steps (r: -0.205, p = 0.14) did not present a significant correlation. These correlations indicate that as the size of a genome (measured in the number of ORFs) increases, the proportion of genes that encode enzymes significantly diminishes (especially those related to central metabolism), suggesting that when essential metabolic pathways are complete, an increase in the number of ORFs does not require a similar increase in the metabolic pathways and enzymes, but only a slight increase is sufficient to cope with a large genome.

  20. The use of Chernobyl data to test model predictions for interindividual variability of 137Cs concentrations in humans

    International Nuclear Information System (INIS)

    Hoffman, F. Owen; Thiessen, Kathleen M.

    1996-01-01

    Data sets assembled in the aftermath of the Chernobyl accident as a part of the International Atomic Energy Agency's model testing program (VAMP) have provided a rare opportunity for 'blind-testing' predictions made with exposure assessment models. Measurements of Chernobyl-derived 137 Cs in Central Bohemia (Czech Republic) and southern Finland were used to test model predictions for a number of endpoints, including the distribution of whole-body concentrations of 137 Cs in adults in these regions at specified time points. This test endpoint required separation of uncertainty due to stochastic variability (aleatoric uncertainty) and uncertainty due to lack of knowledge about fixed but unknown values (epistemic uncertainty). Predictions of the distribution of whole-body 137 Cs concentrations were made by a minority of the participants in these model-testing exercises. Major reasons for misprediction included bias in the bioavailability of 137 Cs in soil and misestimation of the total intake of 137 Cs in the diet. Overestimation of the amount of interindividual variability often resulted from confusion of uncertainty with variability. The spreads of the distributions for parameters describing interindividual variability were frequently increased to compensate for lack of knowledge about the uptake and metabolism of 137 Cs in the population. Accurate results produced by participants are attributable both to a participant's access to additional site-specific data or choice of appropriate site-specific assumptions and to the effects of compensatory errors

  1. Pronounced between-subject and circadian variability in thymidylate synthase and dihydropyrimidine dehydrogenase enzyme activity in human volunteers

    NARCIS (Netherlands)

    Jacobs, Bart A W; Deenen, Maarten J; Pluim, Dick; van Hasselt, J G Coen; Krähenbühl, Martin D; van Geel, Robin M J M; de Vries, Niels; Rosing, Hilde; Meulendijks, Didier; Burylo, Artur M; Cats, Annemieke; Beijnen, Jos H; Huitema, Alwin D R; Schellens, Jan H M

    AIMS: The enzymatic activity of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are important for the tolerability and efficacy of the fluoropyrimidine drugs. In the present study, we explored between-subject variability (BSV) and circadian rhythmicity in DPD and TS activity in

  2. Climate variability and human impact on the environment in South America during the last 2000 years: synthesis and perspectives

    NARCIS (Netherlands)

    Flantua, S.G.A.; Hooghiemstra, H.; Vuillle, M.; Behling, H.; Carson, J.F.; Gosling, W.D.; Hoyos, I.; Ledru, M.P.; Montoya, E.; Mayle, F.; Maldonado, A.; Rull, V.; Tonello, M.S.; Whiyney, B.S.; González-Arango, C.

    2015-01-01

    An improved understanding of present-day climate variability and change relies on high-quality data sets from the past two millennia. Global efforts to reconstruct regional climate modes are in the process of validating and integrating paleo-proxies. For South America, however, the full potential of

  3. Intra-individual variability in tinnitus patients : current thoughts and perspectives.

    Science.gov (United States)

    Dauman, N; Erlandsson, S; Lundlin, L; Dauman, R

    2015-04-01

    Most tinnitus studies have attempted to compare groups of individuals, thus revealing inter-individuals differences, i.e., variations between compared subjects. For methodological reasons, inter-individual studies cannot take into account the variability of tinnitus experience, which has been known for decades to be relevant in daily practice with tinnitus patients. The concept of intra-individual variability has been promoted in the research literature, in order to shed light on this aspect of individual perception. In previous studies, unrelated to hearing, the concept of intra-individual variability implied inclusion of the environment (i.e., physical and social interactions) as a factor of individual performance. In tinnitus research, we believe that the concept of variability (within a person) could find a place beside the concept of variation (between groups of subjects). In this paper, four perspectives of tinnitus experiences from the clinical and research fields are described: (1) ENT consultation; (2) short-term group psychotherapy; (3) psychodynamic psychotherapy; and (4) clinical psychological research. Intra-individual variability stresses the importance of defining tinnitus in a dynamic way, contrary to the current definition of tinnitus as the perception of sound(s). In clinical practice, it is useful to embrace the perspective of the perceiver of tinnitus, and to include social and cultural circumstances as well as audiological/physical changes.

  4. Analysis of Human Resource Competency as Effort to Increase SMEs Economic Sector Productivity with Gender as Differentiating Variable

    OpenAIRE

    Wibawa, Dian Prihardini

    2018-01-01

    Competence is a very important factor in increasing work productivity. A qualified workforce will have a positive impact on improving business productivity. Thus, the level of corporate profitability also increased. Human resource improvement strategy is an excellent strategy apart from other factors such as technology improves. Increased strategy through human resource competence can be done with the improvement of ability, attitude, knowledge, and expertise. The purpose of this research is ...

  5. Variable Thumb Moment Arm Modeling and Thumb-Tip Force Production of a Human-Like Robotic Hand.

    Science.gov (United States)

    Niehues, Taylor D; Deshpande, Ashish D

    2017-10-01

    The anatomically correct testbed (ACT) hand mechanically simulates the musculoskeletal structure of the fingers and thumb of the human hand. In this work, we analyze the muscle moment arms (MAs) and thumb-tip force vectors in the ACT thumb in order to compare the ACT thumb's mechanical structure to the human thumb. Motion data are used to determine joint angle-dependent MA models, and thumb-tip three-dimensional (3D) force vectors are experimentally analyzed when forces are applied to individual muscles. Results are presented for both a nominal ACT thumb model designed to match human MAs and an adjusted model that more closely replicates human-like thumb-tip forces. The results confirm that the ACT thumb is capable of faithfully representing human musculoskeletal structure and muscle functionality. Using the ACT hand as a physical simulation platform allows us to gain a better understanding of the underlying biomechanical and neuromuscular properties of the human hand to ultimately inform the design and control of robotic and prosthetic hands.

  6. Biological variability dominates and influences analytical variance in HPLC-ECD studies of the human plasma metabolome

    Directory of Open Access Journals (Sweden)

    Willett Walter C

    2007-11-01

    Full Text Available Abstract Background Biomarker-based assessments of biological samples are widespread in clinical, pre-clinical, and epidemiological investigations. We previously developed serum metabolomic profiles assessed by HPLC-separations coupled with coulometric array detection that can accurately identify ad libitum fed and caloric-restricted rats. These profiles are being adapted for human epidemiology studies, given the importance of energy balance in human disease. Methods Human plasma samples were biochemically analyzed using HPLC separations coupled with coulometric electrode array detection. Results We identified these markers/metabolites in human plasma, and then used them to determine which human samples represent blinded duplicates with 100% accuracy (N = 30 of 30. At least 47 of 61 metabolites tested were sufficiently stable for use even after 48 hours of exposure to shipping conditions. Stability of some metabolites differed between individuals (N = 10 at 0, 24, and 48 hours, suggesting the influence of some biological factors on parameters normally considered as analytical. Conclusion Overall analytical precision (mean median CV, ~9% and total between-person variation (median CV, ~50–70% appear well suited to enable use of metabolomics markers in human clinical trials and epidemiological studies, including studies of the effect of caloric intake and balance on long-term cancer risk.

  7. A broad diversity of volatile carboxylic acids, released by a bacterial aminoacylase from axilla secretions, as candidate molecules for the determination of human-body odor type.

    Science.gov (United States)

    Natsch, Andreas; Derrer, Samuel; Flachsmann, Felix; Schmid, Joachim

    2006-01-01

    Human body odor is to a large part determined by secretions of glands in the axillary regions. Two key odoriferous principles, 3-methylhex-2-enoic acid (3MH2; 4/5) and 3-hydroxy-3-methylhexanoic acid (HMHA; 6) have been shown to be released from glutamine conjugates secreted in the axilla by a specific N(alpha)-acyl-glutamine aminoacylase (N-AGA) obtained from axilla isolates of Corynebacteria sp. However, the low number of different odorants reported in humans stands in contrast to the observed high inter-individual variability in body odors. Axilla secretions of individual donors were, therefore, analyzed in detail. The secretions were treated with N-AGA, analyzed by GC/MS, and compared to undigested controls. Over 28 different carboxylic acids were released by this enzyme from odorless axilla secretions (Table 1). Many of these body odorants have not been reported before from a natural source, and they include several aliphatic 3-hydroxy acids with 4-Me branches, 3,4-unsaturated, 4-Et-branched aliphatic acids, and a variety of degradation products of amino acids. The odor threshold of some of the acids was found to be in the range of 1 ng. Most of these compounds were present in all donors tested, but in highly variable relative amounts, and they are, thus, candidate molecules as key components of a 'compound odor' determining the individual types of human body odor.

  8. Variable Responses to Carbon Utilization between Planktonic and Biofilm Cells of a Human Carrier Strain of Salmonella enterica Serovar Typhi.

    Directory of Open Access Journals (Sweden)

    Kalaivani Kalai Chelvam

    Full Text Available Salmonella enterica serovar Typhi (S. Typhi is a foodborne pathogen that causes typhoid fever and infects only humans. The ability of S. Typhi to survive outside the human host remains unclear, particularly in human carrier strains. In this study, we have investigated the catabolic activity of a human carrier S. Typhi strain in both planktonic and biofilm cells using the high-throughput Biolog Phenotype MicroArray, Minimum Biofilm Eradication Concentration (MBEC biofilm inoculator (96-well peg lid and whole genome sequence data. Additional strains of S. Typhi were tested to further validate the variation of catabolism in selected carbon substrates in the different bacterial growth phases. The analyzes of the carbon utilization data indicated that planktonic cells of the carrier strain, S. Typhi CR0044 could utilize a broader range of carbon substrates compared to biofilm cells. Pyruvic acid and succinic acid which are related to energy metabolism were actively catabolised in the planktonic stage compared to biofilm stage. On the other hand, glycerol, L-fucose, L-rhamnose (carbohydrates and D-threonine (amino acid were more actively catabolised by biofilm cells compared to planktonic cells. Notably, dextrin and pectin could induce strong biofilm formation in the human carrier strain of S. Typhi. However, pectin could not induce formation of biofilm in the other S. Typhi strains. Phenome data showed the utilization of certain carbon substrates which was supported by the presence of the catabolism-associated genes in S. Typhi CR0044. In conclusion, the findings showed the differential carbon utilization between planktonic and biofilm cells of a S. Typhi human carrier strain. The differences found in the carbon utilization profiles suggested that S. Typhi uses substrates mainly found in the human biliary mucus glycoprotein, gallbladder, liver and cortex of the kidney of the human host. The observed diversity in the carbon catabolism profiles among

  9. Intra-individual metameric variation expressed at the enamel-dentine junction of lower post-canine dentition of South African fossil hominins and modern humans.

    Science.gov (United States)

    Pan, Lei; Thackeray, John Francis; Dumoncel, Jean; Zanolli, Clément; Oettlé, Anna; de Beer, Frikkie; Hoffman, Jakobus; Duployer, Benjamin; Tenailleau, Christophe; Braga, José

    2017-08-01

    The aim of this study is to compare the degree and patterning of inter- and intra-individual metameric variation in South African australopiths, early Homo and modern humans. Metameric variation likely reflects developmental and taxonomical issues, and could also be used to infer ecological and functional adaptations. However, its patterning along the early hominin postcanine dentition, particularly among South African fossil hominins, remains unexplored. Using microfocus X-ray computed tomography (µXCT) and geometric morphometric tools, we studied the enamel-dentine junction (EDJ) morphology and we investigated the intra- and inter-individual EDJ metameric variation among eight australopiths and two early Homo specimens from South Africa, as well as 32 modern humans. Along post-canine dentition, shape changes between metameres represented by relative positions and height of dentine horns, outlines of the EDJ occlusal table are reported in modern and fossil taxa. Comparisons of EDJ mean shapes and multivariate analyses reveal substantial variation in the direction and magnitude of metameric shape changes among taxa, but some common trends can be found. In modern humans, both the direction and magnitude of metameric shape change show increased variability in M 2 -M 3 compared to M 1 -M 2 . Fossil specimens are clustered together showing similar magnitudes of shape change. Along M 2 -M 3 , the lengths of their metameric vectors are not as variable as those of modern humans, but they display considerable variability in the direction of shape change. The distalward increase of metameric variation along the modern human molar row is consistent with the odontogenetic models of molar row structure (inhibitory cascade model). Though much remains to be tested, the variable trends and magnitudes in metamerism in fossil hominins reported here, together with differences in the scale of shape change between modern humans and fossil hominins may provide valuable information

  10. Mapping human skeletal muscle perforator vessels using a quantum well infrared photodetector (QWIP) might explain the variability of NIRS and LDF measurements

    International Nuclear Information System (INIS)

    Binzoni, T; Leung, T; Delpy, D T; Fauci, M A; Ruefenacht, D

    2004-01-01

    Near-infrared spectroscopy (NIRS) and laser Doppler flowmetry (LDF) have become the techniques of choice allowing the non-invasive study of local human skeletal muscle metabolism and blood perfusion on a small tissue volume (a few cm 3 ). However, it has been shown that both NIRS and LDF measurements may show a large spatial variability depending on the position of the optodes over the investigated muscle. This variability may be due to local morphologic and/or metabolic characteristics of the muscle and makes the data interpretation and comparison difficult. In the present work, we use a third method to investigate this problem which permits fast, non-invasive mapping of the intramuscular vessel distribution in the human vastus lateralis muscle. This method uses an advanced, passive, infrared imaging sensor called a QWIP (quantum well infrared photodetector). We demonstrate, using a recovery-enhanced infrared imaging technique, that there is a significant presence of perforator vessels in the region of interest of ∼30 x 18 cm (the number of vessels being: 14, 9, 8, 33, 17 and 18 for each subject, respectively). The presence of these vessels makes the skeletal muscle highly inhomogeneous, and may explain the observed NIRS and LDF spatial variability. We conclude that accurate comparison of the metabolic activity of two different muscle regions is not possible without reliable maps of vascular 'singularities' such as the perforator vessels, and that the QWIP-based imaging system is one method to obtain this information. (note)

  11. Analysis of the variability of human normal urine by 2D-GE reveals a "public" and a "private" proteome.

    Science.gov (United States)

    Molina, Laurence; Salvetat, Nicolas; Ameur, Randa Ben; Peres, Sabine; Sommerer, Nicolas; Jarraya, Fayçal; Ayadi, Hammadi; Molina, Franck; Granier, Claude

    2011-12-10

    The characterization of the normal urinary proteome is steadily progressing and represents a major interest in the assessment of clinical urinary biomarkers. To estimate quantitatively the variability of the normal urinary proteome, urines of 20 healthy people were collected. We first evaluated the impact of the sample conservation temperature on urine proteome integrity. Keeping the urine sample at RT or at +4°C until storage at -80°C seems the best way for long-term storage of samples for 2D-GE analysis. The quantitative variability of the normal urinary proteome was estimated on the 20 urines mapped by 2D-GE. The occurrence of the 910 identified spots was analysed throughout the gels and represented in a virtual 2D gel. Sixteen percent of the spots were found to occur in all samples and 23% occurred in at least 90% of urines. About 13% of the protein spots were present only in 10% or less of the samples, thus representing the most variable part of the normal urinary proteome. Twenty proteins corresponding to a fraction of the fully conserved spots were identified by mass spectrometry. In conclusion, a "public" urinary proteome, common to healthy individuals, seems to coexist with a "private" urinary proteome, which is more specific to each individual. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Functional variability of snake venom metalloproteinases: adaptive advantages in targeting different prey and implications for human envenomation.

    Directory of Open Access Journals (Sweden)

    Juliana L Bernardoni

    Full Text Available Snake venom metalloproteinases (SVMPs are major components in most viperid venoms that induce disturbances in the hemostatic system and tissues of animals envenomated by snakes. These disturbances are involved in human pathology of snake bites and appear to be essential for the capture and digestion of snake's prey and avoidance of predators. SVMPs are a versatile family of venom toxins acting on different hemostatic targets which are present in venoms in distinct structural forms. However, the reason why a large number of different SVMPs are expressed in some venoms is still unclear. In this study, we evaluated the interference of five isolated SVMPs in blood coagulation of humans, birds and small rodents. P-III class SVMPs (fractions Ic, IIb and IIc possess gelatinolytic and hemorrhagic activities, and, of these, two also show fibrinolytic activity. P-I class SVMPs (fractions IVa and IVb are only fibrinolytic. P-III class SVMPs reduced clotting time of human plasma. Fraction IIc was characterized as prothrombin activator and fraction Ic as factor X activator. In the absence of Ca2+, a firm clot was observed in chicken blood samples with fractions Ic, IIb and partially with fraction IIc. In contrast, without Ca2+, only fraction IIc was able to induce a firm clot in rat blood. In conclusion, functionally distinct forms of SVMPs were found in B. neuwiedi venom that affect distinct mechanisms in the coagulation system of humans, birds and small rodents. Distinct SVMPs appear to be more specialized to rat or chicken blood, strengthening the current hypothesis that toxin diversity enhances the possibilities of the snakes for hunting different prey or evading different predators. This functional diversity also impacts the complexity of human envenoming since different hemostatic mechanisms will be targeted by SVMPs accounting for the complexity of the response of humans to venoms.

  13. Deciphering long-term records of natural variability and human impact as recorded in lake sediments: a palaeolimnological puzzle

    DEFF Research Database (Denmark)

    Mills, Keely; Schillereff, Daniel; Saulnier-Talbot, Émilie

    2017-01-01

    that is particularly acute when considering management options for aquatic ecosystems. The duration and timing of human impacts on lake systems varies geographically, with some regions of the world (such as Africa and South America) having a longer legacy of human impact than others (e.g., New Zealand). A wide array...... of techniques (biological, chemical, physical and statistical) is available to palaeolimnologists to allow the deciphering of complex sedimentary records. Lake sediments are an important archive of how drivers have changed through time, and how these impacts manifest in lake systems. With a paucity of ‘real...

  14. Three Experiments Examining the Use of Electroencephalogram,Event-Related Potentials, and Heart-Rate Variability for Real-Time Human-Centered Adaptive Automation Design

    Science.gov (United States)

    Prinzel, Lawrence J., III; Parasuraman, Raja; Freeman, Frederick G.; Scerbo, Mark W.; Mikulka, Peter J.; Pope, Alan T.

    2003-01-01

    Adaptive automation represents an advanced form of human-centered automation design. The approach to automation provides for real-time and model-based assessments of human-automation interaction, determines whether the human has entered into a hazardous state of awareness and then modulates the task environment to keep the operator in-the-loop , while maintaining an optimal state of task engagement and mental alertness. Because adaptive automation has not matured, numerous challenges remain, including what the criteria are, for determining when adaptive aiding and adaptive function allocation should take place. Human factors experts in the area have suggested a number of measures including the use of psychophysiology. This NASA Technical Paper reports on three experiments that examined the psychophysiological measures of event-related potentials, electroencephalogram, and heart-rate variability for real-time adaptive automation. The results of the experiments confirm the efficacy of these measures for use in both a developmental and operational role for adaptive automation design. The implications of these results and future directions for psychophysiology and human-centered automation design are discussed.

  15. Dosimetry of nasal uptake of soluble and reactive gases: A first study of inter-human variability (Journal Article)

    Science.gov (United States)

    Anatomically accurate human child and adult nasal tract models will be used in concert with computationally simulated air flow information to investigate the influence of age-related differences in anatomy on inhalation dosimetry in the upper and lower airways. The findings of t...

  16. On the variability of the salting-out curves of proteins of normal human plasma and serum

    NARCIS (Netherlands)

    Steyn-Parvé, Elizabeth P.; Hout, A.J. van den

    1953-01-01

    Salting-out curves of proteins of normal human plasma reflect the influence of a number of other factors besides the protein composition: the manner of obtaining the blood, the nature of the anti-coagulant used, the non-protein components of the plasma. Diagrams of serum and plasma obtained from

  17. Contact variables for exposure to avian influenza H5N1 virus at the human-animal interface.

    Science.gov (United States)

    Rabinowitz, P; Perdue, M; Mumford, E

    2010-06-01

    Although the highly pathogenic avian influenza H5N1 virus continues to cause infections in both avian and human populations, the specific zoonotic risk factors remain poorly understood. This review summarizes available evidence regarding types of contact associated with transmission of H5N1 virus at the human-animal interface. A systematic search of the published literature revealed five analytical studies and 15 case reports describing avian influenza transmission from animals to humans for further review. Risk factors identified in analytical studies were compared, and World Health Organization-confirmed cases, identified in case reports, were classified according to type of contact reported using a standardized algorithm. Although cases were primarily associated with direct contact with sick/unexpectedly dead birds, some cases reported only indirect contact with birds or contaminated environments or contact with apparently healthy birds. Specific types of contacts or activities leading to exposure could not be determined from data available in the publications reviewed. These results support previous reports that direct contact with sick birds is not the only means of human exposure to avian influenza H5N1 virus. To target public health measures and disease awareness messaging for reducing the risk of zoonotic infection with avian influenza H5N1 virus, the specific types of contacts and activities leading to transmission need to be further understood. The role of environmental virus persistence, shedding of virus by asymptomatic poultry and disease pathophysiology in different avian species relative to human zoonotic risk, as well as specific modes of zoonotic transmission, should be determined.

  18. Discovering human germ cell mutagens with whole genome sequencing: Insights from power calculations reveal the importance of controlling for between-family variability.

    Science.gov (United States)

    Webster, R J; Williams, A; Marchetti, F; Yauk, C L

    2018-07-01

    Mutations in germ cells pose potential genetic risks to offspring. However, de novo mutations are rare events that are spread across the genome and are difficult to detect. Thus, studies in this area have generally been under-powered, and no human germ cell mutagen has been identified. Whole Genome Sequencing (WGS) of human pedigrees has been proposed as an approach to overcome these technical and statistical challenges. WGS enables analysis of a much wider breadth of the genome than traditional approaches. Here, we performed power analyses to determine the feasibility of using WGS in human families to identify germ cell mutagens. Different statistical models were compared in the power analyses (ANOVA and multiple regression for one-child families, and mixed effect model sampling between two to four siblings per family). Assumptions were made based on parameters from the existing literature, such as the mutation-by-paternal age effect. We explored two scenarios: a constant effect due to an exposure that occurred in the past, and an accumulating effect where the exposure is continuing. Our analysis revealed the importance of modeling inter-family variability of the mutation-by-paternal age effect. Statistical power was improved by models accounting for the family-to-family variability. Our power analyses suggest that sufficient statistical power can be attained with 4-28 four-sibling families per treatment group, when the increase in mutations ranges from 40 to 10% respectively. Modeling family variability using mixed effect models provided a reduction in sample size compared to a multiple regression approach. Much larger sample sizes were required to detect an interaction effect between environmental exposures and paternal age. These findings inform study design and statistical modeling approaches to improve power and reduce sequencing costs for future studies in this area. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  19. Quantifying the ocean, freshwater and human effects on year-to-year variability of one-sea-winter Atlantic salmon angled in multiple Norwegian rivers.

    Science.gov (United States)

    Otero, Jaime; Jensen, Arne J; L'Abée-Lund, Jan Henning; Stenseth, Nils Chr; Storvik, Geir O; Vøllestad, Leif Asbjørn

    2011-01-01

    Many Atlantic salmon, Salmo salar, populations are decreasing throughout the species' distributional range probably due to several factors acting in concert. A number of studies have documented the influence of freshwater and ocean conditions, climate variability and human impacts resulting from impoundment and aquaculture. However, most previous research has focused on analyzing single or only a few populations, and quantified isolated effects rather than handling multiple factors in conjunction. By using a multi-river mixed-effects model we estimated the effects of oceanic and river conditions, as well as human impacts, on year-to-year and between-river variability across 60 time series of recreational catch of one-sea-winter salmon (grilse) from Norwegian rivers over 29 years (1979-2007). Warm coastal temperatures at the time of smolt entrance into the sea and increased water discharge during upstream migration of mature fish were associated with higher rod catches of grilse. When hydropower stations were present in the course of the river systems the strength of the relationship with runoff was reduced. Catches of grilse in the river increased significantly following the reduction of the harvesting of this life-stage at sea. However, an average decreasing temporal trend was still detected and appeared to be stronger in the presence of salmon farms on the migration route of smolts in coastal/fjord areas. These results suggest that both ocean and freshwater conditions in conjunction with various human impacts contribute to shape interannual fluctuations and between-river variability of wild Atlantic salmon in Norwegian rivers. Current global change altering coastal temperature and water flow patterns might have implications for future grilse catches, moreover, positioning of aquaculture facilities as well as the implementation of hydropower schemes or other encroachments should be made with care when implementing management actions and searching for solutions to

  20. Quantifying the ocean, freshwater and human effects on year-to-year variability of one-sea-winter Atlantic salmon angled in multiple Norwegian rivers.

    Directory of Open Access Journals (Sweden)

    Jaime Otero

    Full Text Available Many Atlantic salmon, Salmo salar, populations are decreasing throughout the species' distributional range probably due to several factors acting in concert. A number of studies have documented the influence of freshwater and ocean conditions, climate variability and human impacts resulting from impoundment and aquaculture. However, most previous research has focused on analyzing single or only a few populations, and quantified isolated effects rather than handling multiple factors in conjunction. By using a multi-river mixed-effects model we estimated the effects of oceanic and river conditions, as well as human impacts, on year-to-year and between-river variability across 60 time series of recreational catch of one-sea-winter salmon (grilse from Norwegian rivers over 29 years (1979-2007. Warm coastal temperatures at the time of smolt entrance into the sea and increased water discharge during upstream migration of mature fish were associated with higher rod catches of grilse. When hydropower stations were present in the course of the river systems the strength of the relationship with runoff was reduced. Catches of grilse in the river increased significantly following the reduction of the harvesting of this life-stage at sea. However, an average decreasing temporal trend was still detected and appeared to be stronger in the presence of salmon farms on the migration route of smolts in coastal/fjord areas. These results suggest that both ocean and freshwater conditions in conjunction with various human impacts contribute to shape interannual fluctuations and between-river variability of wild Atlantic salmon in Norwegian rivers. Current global change altering coastal temperature and water flow patterns might have implications for future grilse catches, moreover, positioning of aquaculture facilities as well as the implementation of hydropower schemes or other encroachments should be made with care when implementing management actions and searching

  1. Phenotypic variability in LQT3 human induced pluripotent stem cell-derived cardiomyocytes and their response to antiarrhythmic pharmacologic therapy: An in silico approach.

    Science.gov (United States)

    Paci, Michelangelo; Passini, Elisa; Severi, Stefano; Hyttinen, Jari; Rodriguez, Blanca

    2017-11-01

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are in vitro models with the clear advantages of their human origin and suitability for human disease investigations. However, limitations include their incomplete characterization and variability reported in different cell lines and laboratories. The purpose of this study was to investigate in silico ionic mechanisms potentially explaining the phenotypic variability of hiPSC-CMs in long QT syndrome type 3 (LQT3) and their response to antiarrhythmic drugs. Populations of in silico hiPSC-CM models were constructed and calibrated for control (n = 1,463 models) and LQT3 caused by I NaL channelopathy (n = 1,401 models), using experimental recordings for late sodium current (I NaL ) and action potentials (APs). Antiarrhythmic drug therapy was evaluated by simulating mexiletine and ranolazine multichannel effects. As in experiments, LQT3 hiPSC-CMs yield prolonged action potential duration at 90% repolarization (APD 90 ) (+34.3% than controls) and large electrophysiological variability. LQT3 hiPSC-CMs with symptomatic APs showed overexpression of I CaL , I K1 , and I NaL , underexpression of I Kr , and increased sensitivity to both drugs compared to asymptomatic LQT3 models. Simulations showed that both mexiletine and ranolazine corrected APD prolongation in the LQT3 population but also highlighted differences in drug response. Mexiletine stops spontaneous APs in more LQT3 hiPSC-CMs models than ranolazine (784/1,401 vs 53/1,401) due to its stronger action on I Na . In silico simulations demonstrate our ability to recapitulate variability in LQT3 and control hiPSC-CM phenotypes, and the ability of mexiletine and ranolazine to reduce APD prolongation, in agreement with experiments. The in silico models also identify potential ionic mechanisms of phenotypic variability in LQT3 hiPSC-CMs, explaining APD prolongation in symptomatic vs asymptomatic LQT3 hiPSC-CMs. Copyright © 2017 The Authors. Published by

  2. Determination of supplier-to-supplier and lot-to-lot variability in glycation of recombinant human serum albumin expressed in Oryza sativa.

    Directory of Open Access Journals (Sweden)

    Grant E Frahm

    Full Text Available The use of different expression systems to produce the same recombinant human protein can result in expression-dependent chemical modifications (CMs leading to variability of structure, stability and immunogenicity. Of particular interest are recombinant human proteins expressed in plant-based systems, which have shown particularly high CM variability. In studies presented here, recombinant human serum albumins (rHSA produced in Oryza sativa (Asian rice (OsrHSA from a number of suppliers have been extensively characterized and compared to plasma-derived HSA (pHSA and rHSA expressed in yeast (Pichia pastoris and Saccharomyces cerevisiae. The heterogeneity of each sample was evaluated using size exclusion chromatography (SEC, reversed-phase high-performance liquid chromatography (RP-HPLC and capillary electrophoresis (CE. Modifications of the samples were identified by liquid chromatography-mass spectrometry (LC-MS. The secondary and tertiary structure of the albumin samples were assessed with far U/V circular dichroism spectropolarimetry (far U/V CD and fluorescence spectroscopy, respectively. Far U/V CD and fluorescence analyses were also used to assess thermal stability and drug binding. High molecular weight aggregates in OsrHSA samples were detected with SEC and supplier-to-supplier variability and, more critically, lot-to-lot variability in one manufactures supplied products were identified. LC-MS analysis identified a greater number of hexose-glycated arginine and lysine residues on OsrHSA compared to pHSA or rHSA expressed in yeast. This analysis also showed supplier-to-supplier and lot-to-lot variability in the degree of glycation at specific lysine and arginine residues for OsrHSA. Both the number of glycated residues and the degree of glycation correlated positively with the quantity of non-monomeric species and the chromatographic profiles of the samples. Tertiary structural changes were observed for most OsrHSA samples which

  3. Clinical and molecular characterization of duplications encompassing the human SHOX gene reveal a variable effect on stature.

    Science.gov (United States)

    Thomas, N Simon; Harvey, John F; Bunyan, David J; Rankin, Julia; Grigelioniene, Giedre; Bruno, Damien L; Tan, Tiong Y; Tomkins, Susan; Hastings, Robert

    2009-07-01

    Deletions of the SHOX gene are well documented and cause disproportionate short stature and variable skeletal abnormalities. In contrast interstitial SHOX duplications limited to PAR1 appear to be very rare and the clinical significance of the only case report in the literature is unclear. Mapping of this duplication has now shown that it includes the entire SHOX gene but little flanking sequence and so will not encompass any of the long-range enhancers required for SHOX transcription. We now describe the clinical and molecular characterization of three additional cases. The duplications all included the SHOX coding sequence but varied in the amount of flanking sequence involved. The probands were ascertained for a variety of reasons: hypotonia and features of Asperger syndrome, Leri-Weill dyschondrosteosis (LWD), and a family history of cleft palate. However, the presence of a duplication did not correlate with any of these features or with evidence of skeletal abnormality. Remarkably, the proband with LWD had inherited both a SHOX deletion and a duplication. The effect of the duplications on stature was variable: height appeared to be elevated in some carriers, particularly in those with the largest duplications, but was still within the normal range. SHOX duplications are likely to be under ascertained and more cases need to be identified and characterized in detail in order to accurately determine their phenotypic consequences.

  4. Ability of human oral microbiota to produce wine odorant aglycones from odourless grape glycosidic aroma precursors.

    Science.gov (United States)

    Muñoz-González, Carolina; Cueva, Carolina; Ángeles Pozo-Bayón, M; Victoria Moreno-Arribas, M

    2015-11-15

    Grape aroma precursors are odourless glycosides that represent a natural reservoir of potential active odorant molecules in wines. Since the first step of wine consumption starts in the oral cavity, the processing of these compounds in the mouth could be an important factor in influencing aroma perception. Therefore, the objective of this work has been to evaluate the ability of human oral microbiota to produce wine odorant aglycones from odourless grape glycosidic aroma precursors previously isolated from white grapes. To do so, two methodological approaches involving the use of typical oral bacteria or the whole oral microbiota isolated from human saliva were followed. Odorant aglycones released in the culture mediums were isolated and analysed by HS-SPME-GC/MS. Results showed the ability of oral bacteria to hydrolyse grape aroma precursors, releasing different types of odorant molecules (terpenes, benzenic compounds and lipid derivatives). The hydrolytic activity seemed to be bacteria-dependent and was subject to large inter-individual variability. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Potency testing of mesenchymal stromal cell growth expanded in human platelet lysate from different human tissues.

    Science.gov (United States)

    Fazzina, R; Iudicone, P; Fioravanti, D; Bonanno, G; Totta, P; Zizzari, I G; Pierelli, L

    2016-08-25

    Mesenchymal stromal cells (MSCs) have been largely investigated, in the past decade, as potential therapeutic strategies for various acute and chronic pathological conditions. MSCs isolated from different sources, such as bone marrow (BM), umbilical cord tissue (UCT) and adipose tissue (AT), share many biological features, although they may show some differences on cumulative yield, proliferative ability and differentiation potential. The standardization of MSCs growth and their functional amplification is a mandatory objective of cell therapies. The aim of this study was to evaluate the cumulative yield and the ex vivo amplification potential of MSCs obtained from various sources and different subjects, using defined culture conditions with a standardized platelet lysate (PL) as growth stimulus. MSCs isolated from BM, UCT and AT and expanded in human PL were compared in terms of cumulative yield and growth potential per gram of starting tissue. MSCs morphology, phenotype, differentiation potential, and immunomodulatory properties were also investigated to evaluate their biological characteristics. The use of standardized PL-based culture conditions resulted in a very low variability of MSC growth. Our data showed that AT has the greater capacity to generate MSC per gram of initial tissue, compared to BM and UCT. However, UCT-MSCs replicated faster than AT-MSCs and BM-MSCs, revealing a greater proliferation capacity of this source irrespective of its lower MSC yield. All MSCs exhibited the typical MSC phenotype and the ability to differentiate into all mesodermal lineages, while BM-MSCs showed the most prominent immunosuppressive effect in vitro. The adoption of standardized culture conditions may help researchers and clinicians to reveal particular characteristics and inter-individual variability of MSCs sourced from different tissues. These data will be beneficial to set the standards for tissue collection and MSCs clinical-scale expansion both for cell banking

  6. Natural climate variability inferred from cosmogenic isotopes and other geophysical data and its impact on human activity

    International Nuclear Information System (INIS)

    Creer, K.M.

    2001-01-01

    The way how natural climate changes may have influenced anthropological development is discussed. The main characteristics of solar variability are reviewed: (1) as measured in detail over recent decades by instruments on-board artificial satellites; (2) as recorded in historical documents on the time-scale of centuries; and (3) as inferred on millennial time-scales from archived records of the cosmogenically generated isotopes 14 C and 10 Be. The older, proxy data comprise temperature changes reconstructed from tree ring studies and environmental changes deduced from multi-disciplinary studies of lake sediments. The effects of changes in ocean circulation and the sporadic influence of volcanic activity are also considered briefly. (author)

  7. Comparison of Variable-Number Tandem-Repeat Markers typing and IS1245 Restriction Fragment Length Polymorphism fingerprinting of Mycobacterium avium subsp. hominissuis from human and porcine origins

    Directory of Open Access Journals (Sweden)

    Marttila Harri

    2010-03-01

    Full Text Available Abstract Background Animal mycobacterioses are regarded as a potential zoonotic risk and cause economical losses world wide. M. avium subsp. hominissuis is a slow-growing subspecies found in mycobacterial infected humans and pigs and therefore rapid and discriminatory typing methods are needed for epidemiological studies. The genetic similarity of M. avium subsp. hominissuis from human and porcine origins using two different typing methods have not been studied earlier. The objective of this study was to compare the IS1245 RFLP pattern and MIRU-VNTR typing to study the genetic relatedness of M. avium strains isolated from slaughter pigs and humans in Finland with regard to public health aspects. Methods A novel PCR-based genotyping method, variable number tandem repeat (VNTR typing of eight mycobacterial interspersed repetitive units (MIRUs, was evaluated for its ability to characterize Finnish Mycobacterium avium subsp. hominissuis strains isolated from pigs (n = 16 and humans (n = 13 and the results were compared with those obtained by the conventional IS1245 RFLP method. Results The MIRU-VNTR results showed a discriminatory index (DI of 0,92 and the IS1245 RFLP resulted in DI 0,98. The combined DI for both methods was 0,98. The MIRU-VNTR test has the advantages of being simple, reproducible, non-subjective, which makes it suitable for large-scale screening of M. avium strains. Conclusions Both typing methods demonstrated a high degree of similarity between the strains of human and porcine origin. The parallel application of the methods adds epidemiological value to the comparison of the strains and their origins. The present approach and results support the hypothesis that there is a common source of M. avium subsp. hominissuis infection for pigs and humans or alternatively one species may be the infective source to the other.

  8. Time since death and decomposition of the human body: variables and observations in case and experimental field studies.

    Science.gov (United States)

    Mann, R W; Bass, W M; Meadows, L

    1990-01-01

    Much of the difficulty in determining the time since death stems from the lack of systematic observation and research on the decomposition rate of the human body. Continuing studies conducted at the University of Tennessee, Knoxville, provide useful information on the impact of carrion insect activity, ambient temperature, rainfall, clothing, burial and depth, carnivores, bodily trauma, body weight, and the surface with which the body is in contact. This paper reports findings and observations accumulated during eight years of research and case studies that may clarify some of the questions concerning bodily decay.

  9. Epidemiology and genetic variability of human metapneumovirus during a 4-year-long study in Southeastern Brazil.

    Science.gov (United States)

    Oliveira, Danielle B L; Durigon, Edison L; Carvalho, Ariane C L; Leal, Andréa L; Souza, Thereza S; Thomazelli, Luciano M; Moraes, Claudia T P; Vieira, Sandra E; Gilio, Alfredo E; Stewien, Klaus E

    2009-05-01

    Epidemiological and molecular characteristics of human metapneumovirus (hMPV) were compared with human respiratory syncytial virus (hRSV) in infants and young children admitted for acute lower respiratory tract infections in a prospective study during four consecutive years in subtropical Brazil. GeneScan polymerase chain assays (GeneScan RT-PCR) were used to detect hMPV and hRSV in nasopharyngeal aspirates of 1,670 children during January 2003 to December 2006. hMPV and hRSV were detected, respectively, in 191 (11.4%) and in 702 (42%) of the children admitted with acute lower respiratory tract infections at the Sao Paulo University Hospital. Sequencing data of the hMPV F gene revealed that two groups of the virus, each divided into two subgroups, co-circulated during three consecutive years. It was also shown that a clear dominance of genotype B1 occurred during the years 2004 and 2005, followed by genotype A2 during 2006. Copyright 2009 Wiley-Liss, Inc.

  10. ICP-MS/MS-Based Ionomics: A Validated Methodology to Investigate the Biological Variability of the Human Ionome.

    Science.gov (United States)

    Konz, Tobias; Migliavacca, Eugenia; Dayon, Loïc; Bowman, Gene; Oikonomidi, Aikaterini; Popp, Julius; Rezzi, Serge

    2017-05-05

    We here describe the development, validation and application of a quantitative methodology for the simultaneous determination of 29 elements in human serum using state-of-the-art inductively coupled plasma triple quadrupole mass spectrometry (ICP-MS/MS). This new methodology offers high-throughput elemental profiling using simple dilution of minimal quantity of serum samples. We report the outcomes of the validation procedure including limits of detection/quantification, linearity of calibration curves, precision, recovery and measurement uncertainty. ICP-MS/MS-based ionomics was used to analyze human serum of 120 older adults. Following a metabolomic data mining approach, the generated ionome profiles were subjected to principal component analysis revealing gender and age-specific differences. The ionome of female individuals was marked by higher levels of calcium, phosphorus, copper and copper to zinc ratio, while iron concentration was lower with respect to male subjects. Age was associated with lower concentrations of zinc. These findings were complemented with additional readouts to interpret micronutrient status including ceruloplasmin, ferritin and inorganic phosphate. Our data supports a gender-specific compartmentalization of the ionome that may reflect different bone remodelling in female individuals. Our ICP-MS/MS methodology enriches the panel of validated "Omics" approaches to study molecular relationships between the exposome and the ionome in relation with nutrition and health.

  11. Modular Construction of Large Non-Immune Human Antibody Phage-Display Libraries from Variable Heavy and Light Chain Gene Cassettes.

    Science.gov (United States)

    Lee, Nam-Kyung; Bidlingmaier, Scott; Su, Yang; Liu, Bin

    2018-01-01

    Monoclonal antibodies and antibody-derived therapeutics have emerged as a rapidly growing class of biological drugs for the treatment of cancer, autoimmunity, infection, and neurological diseases. To support the development of human antibodies, various display techniques based on antibody gene repertoires have been constructed over the last two decades. In particular, scFv-antibody phage display has been extensively utilized to select lead antibodies against a variety of target antigens. To construct a scFv phage display that enables efficient antibody discovery, and optimization, it is desirable to develop a system that allows modular assembly of highly diverse variable heavy chain and light chain (Vκ and Vλ) repertoires. Here, we describe modular construction of large non-immune human antibody phage-display libraries built on variable gene cassettes from heavy chain and light chain repertoires (Vκ- and Vλ-light can be made into independent cassettes). We describe utility of such libraries in antibody discovery and optimization through chain shuffling.

  12. Immunoglobulin variable region sequences of two human monoclonal antibodies directed to an onco-developmental carbohydrate antigen, lactotetraosylceramide (LcOse4Cer).

    Science.gov (United States)

    Yago, K; Zenita, K; Ohwaki, I; Harada, R; Nozawa, S; Tsukazaki, K; Iwamori, M; Endo, N; Yasuda, N; Okuma, M

    1993-11-01

    A human monoclonal antibody, 11-50, was generated and was shown to recognize an onco-developmental carbohydrate antigen, LcOse4Cer. The isotype of this antibody was IgM, lambda, similar to the previously known human anti-LcOse4 antibodies, such as IgMWOO and HMST-1. We raised a murine anti-idiotypic antibody G3 (IgG1, kappa) against 11-50, and tested its reactivity towards the affinity purified human polyclonal anti-LcOse4 antibodies prepared from pooled human sera using a Gal beta 1-->3GlcNAc beta-immobilized column. The results indicated that at least a part of the human polyclonal anti-LcOse4 antibodies shared the G3 idiotype with 11-50. We further analyzed the sequence of variable regions of the two anti-LcOse4 antibodies, 11-50 and HMST-1. Sequence analysis of the heavy chain variable regions indicated that the VH regions of these two antibodies were highly homologous to each other (93.5% at the nucleic acid level), and these antibodies utilized the germline genes VH1.9III and hv3005f3 as the VH segments, which are closely related germline genes of the VHIII family. It was noted that these germline VH genes are frequently utilized in fetal B cells. The JH region of both antibodies was encoded by the JH4 gene. For the light chain, the V lambda segments of the two antibodies were 96.3% homologous to each other at the nucleic acid level. The V lambda segments of both antibodies showed the highest homology to the rearranged V lambda gene called V lambda II.DS among reported V lambda genes, while the exact germline V lambda genes encoding the two antibodies were not yet registered in available sequence databanks. The amino acid sequences of the J lambda segments of both antibodies were identical. These results indicate that the two human antibodies recognizing the onco-developmental carbohydrate antigen Lc4 are encoded by the same or very homologous germline genes.

  13. Variability and situatedness of human emotions. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

    Science.gov (United States)

    Nadal, Marcos; Rosselló, Jaume

    2015-06-01

    We commend Koelsch and colleagues [14] for developing a broad and integrative explanation of the neurobiological foundations of emotions. We especially welcome this framework's emphasis on the interaction between language and emotion, and its focus on the characteristically human moral emotions. Emotions elicited by art and aesthetics also seem to be distinctively human, but comparatively little research has been devoted to understanding these. This is probably because they are usually viewed as atypical in several respects. William James [12], for instance, regarded emotional responses to artworks and aesthetic qualities as subtler emotions, because they lacked the strong bodily changes and adaptive value characteristic of coarser emotions, such as joy, anger, or fear. This view is still predominant today, and aesthetic emotions are often distinguished from everyday emotions [13]. However, the notion of a class of aesthetic emotions, separate from everyday emotions, rests on the questionable assumption that artistic and aesthetic experiences and activities are different in essence from everyday experiences and activities. The discontinuity between "aesthetic experience [and] normal processes of living" [9, p. 10], however, is the product of social and cultural developments in Europe during the 18th century [7,15,20]. Distinctions that oppose art to craft, or aesthetic to practical, in reference to objects, behaviors, experiences, and emotions, make little sense in a broader historic and geographic context [1,7,20], and hinder empirical research [7].

  14. Time course of changes in sperm morphometry and semen variables during testosterone-induced suppression of human spermatogenesis.

    Science.gov (United States)

    Garrett, C; Liu, D Y; McLachlan, R I; Baker, H W G

    2005-11-01

    Quantification of changes in semen may give insight into the testosterone (T)-induced disruption of spermatogenesis in man. A model analogous to flushing of sperm from the genital tract after vasectomy was used to quantify the time course of semen changes in subjects participating in male contraceptive trials using 800 mg T-implant (n = 25) or 200 mg weekly intramuscular injection (IM-T; n = 33). A modified exponential decay model allowed for delayed onset and incomplete disruption to spermatogenesis. Semen variables measured weekly during a 91-day period after initial treatment were fitted to the model. Sperm concentration, total count, motility and morphometry exhibited similar average decay rates (5 day half-life). The mean delay to onset of decline in concentration was 15 (IM-T) and 18 (T-implant) days. The significantly longer (P sperm viability (43 and 55 days), and the change of morphometry to smaller more compact sperm heads are consistent with sperm being progressively cleared from the genital tract rather than continued shedding of immature or abnormal sperm by the seminiferous epithelium. A significant negative relationship was found between lag time and baseline sperm concentration, consistent with longer sperm-epididymal transit times associated with lower daily production rates.

  15. EMG Versus Torque Control of Human-Machine Systems: Equalizing Control Signal Variability Does not Equalize Error or Uncertainty.

    Science.gov (United States)

    Johnson, Reva E; Kording, Konrad P; Hargrove, Levi J; Sensinger, Jonathon W

    2017-06-01

    In this paper we asked the question: if we artificially raise the variability of torque control signals to match that of EMG, do subjects make similar errors and have similar uncertainty about their movements? We answered this question using two experiments in which subjects used three different control signals: torque, torque+noise, and EMG. First, we measured error on a simple target-hitting task in which subjects received visual feedback only at the end of their movements. We found that even when the signal-to-noise ratio was equal across EMG and torque+noise control signals, EMG resulted in larger errors. Second, we quantified uncertainty by measuring the just-noticeable difference of a visual perturbation. We found that for equal errors, EMG resulted in higher movement uncertainty than both torque and torque+noise. The differences suggest that performance and confidence are influenced by more than just the noisiness of the control signal, and suggest that other factors, such as the user's ability to incorporate feedback and develop accurate internal models, also have significant impacts on the performance and confidence of a person's actions. We theorize that users have difficulty distinguishing between random and systematic errors for EMG control, and future work should examine in more detail the types of errors made with EMG control.

  16. Positive selection in the chromosome 16 VKORC1 genomic region has contributed to the variability of anticoagulant response in humans.

    Directory of Open Access Journals (Sweden)

    Blandine Patillon

    Full Text Available VKORC1 (vitamin K epoxide reductase complex subunit 1, 16p11.2 is the main genetic determinant of human response to oral anticoagulants of antivitamin K type (AVK. This gene was recently suggested to be a putative target of positive selection in East Asian populations. In this study, we genotyped the HGDP-CEPH Panel for six VKORC1 SNPs and downloaded chromosome 16 genotypes from the HGDP-CEPH database in order to characterize the geographic distribution of footprints of positive selection within and around this locus. A unique VKORC1 haplotype carrying the promoter mutation associated with AVK sensitivity showed especially high frequencies in all the 17 HGDP-CEPH East Asian population samples. VKORC1 and 24 neighboring genes were found to lie in a 505 kb region of strong linkage disequilibrium in these populations. Patterns of allele frequency differentiation and haplotype structure suggest that this genomic region has been submitted to a near complete selective sweep in all East Asian populations and only in this geographic area. The most extreme scores of the different selection tests are found within a smaller 45 kb region that contains VKORC1 and three other genes (BCKDK, MYST1 (KAT8, and PRSS8 with different functions. Because of the strong linkage disequilibrium, it is not possible to determine if VKORC1 or one of the three other genes is the target of this strong positive selection that could explain present-day differences among human populations in AVK dose requirement. Our results show that the extended region surrounding a presumable single target of positive selection should be analyzed for genetic variation in a wide range of genetically diverse populations in order to account for other neighboring and confounding selective events and the hitchhiking effect.

  17. Inter- and Intra-individual Variability in Response to Transcranial Direct Current Stimulation (tDCS) at Varying Current Intensities.

    Science.gov (United States)

    Chew, Taariq; Ho, Kerrie-Anne; Loo, Colleen K

    2015-01-01

    Translation of transcranial direct current stimulation (tDCS) from research to clinical practice is hindered by a lack of consensus on optimal stimulation parameters, significant inter-individual variability in response, and in sufficient intra-individual reliability data. Inter-individual differences in response to anodal tDCS at a range of current intensities were explored. Intra-individual reliability in response to anodal tDCS across two identical sessions was also investigated. Twenty-nine subjects participated in a crossover study. Anodal-tDCS using four different current intensities (0.2, 0.5, 1 and 2 mA), with an anode size of 16 cm2, was tested. The 0.5 mA condition was repeated to assess intra-individual variability. TMS was used to elicit 40 motor-evoked potentials (MEPs) before 10 min of tDCS, and 20 MEPs at four time-points over 30 min following tDCS. ANOVA revealed no main effect of TIME for all conditions except the first 0.5 mA condition, and no differences in response between the four current intensities. Cluster analysis identified two clusters for the 0.2 and 2 mA conditions only. Frequency distributions based on individual subject responses (excitatory, inhibitory or no response) to each condition indicate possible differential responses between individuals to different current intensities. Test-retest reliability was negligible (ICC(2,1) = -0.50). Significant inter-individual variability in response to tDCS across a range of current intensities was found. 2 mA and 0.2 mA tDCS were most effective at inducing a distinct response. Significant intra-individual variability in response to tDCS was also found. This has implications for interpreting results of single-session tDCS experiments. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  18. Toward hydro-social modeling: Merging human variables and the social sciences with climate-glacier runoff models (Santa River, Peru)

    Science.gov (United States)

    Carey, Mark; Baraer, Michel; Mark, Bryan G.; French, Adam; Bury, Jeffrey; Young, Kenneth R.; McKenzie, Jeffrey M.

    2014-10-01

    Glacier shrinkage caused by climate change is likely to trigger diminished and less consistent stream flow in glacier-fed watersheds worldwide. To understand, model, and adapt to these climate-glacier-water changes, it is vital to integrate the analysis of both water availability (the domain of hydrologists) and water use (the focus for social scientists). Drawn from a case study of the Santa River watershed below Peru’s glaciated Cordillera Blanca mountain range, this paper provides a holistic hydro-social framework that identifies five major human variables critical to hydrological modeling because these forces have profoundly influenced water use over the last 60 years: (1) political agendas and economic development; (2) governance: laws and institutions; (3) technology and engineering; (4) land and resource use; and (5) societal responses. Notable shifts in Santa River water use-including major expansions in hydroelectricity generation, large-scale irrigation projects, and other land and resource-use practices-did not necessarily stem from changing glacier runoff or hydrologic shifts, but rather from these human variables. Ultimately, then, water usage is not predictable based on water availability alone. Glacier runoff conforms to certain expected trends predicted by models of progressively reduced glacier storage. However, societal forces establish the legal, economic, political, cultural, and social drivers that actually shape water usage patterns via human modification of watershed dynamics. This hydro-social framework has widespread implications for hydrological modeling in glaciated watersheds from the Andes and Alps to the Himalaya and Tien Shan, as well as for the development of climate change adaptation plans.

  19. Spatial variability in selenium and mercury interactions in a key recreational fish species: Implications for human health and environmental monitoring

    International Nuclear Information System (INIS)

    Jones, H.J.; Butler, E.C.V.; Macleod, C.K.

    2013-01-01

    Highlights: • THg and Se concentrations in fish varied between estuary regions but all maintained positive Se:Hg ratios. • Regional negative selenium health benefit values (Se HBVs) were evident suggesting increased Hg toxicity risk. • Single all-encompassing Se HBV for any given species may not be appropriate when there is strong site fidelity. • The results highlight the importance of including Se in assessments of seafood safety. -- Abstract: Selenium’s (Se) protective effects against mercury (Hg) toxicity have been demonstrated; however, this is seldom considered in health assessments, where dietary exposure is still evaluated by Hg concentration alone. Se:Hg ratios and selenium health benefit values (Se HBVs) offer a more comprehensive seafood safety model. Here we describe total mercury (THg), methylmercury (MeHg) and Se concentrations in fish from a Hg-polluted estuary. Spatial variation in THg, MeHg and Se was evident, though all regions maintained Se:Hg ratio values >1. Se HBV varied between regions and in one region mean negative values (−5.17) were evident. This study provides the first evidence that quoting a single all-encompassing Se HBV is not appropriate when species demonstrate strong site fidelity. It highlights the need for research into Se–Hg relationships in environments with established Hg pollution and reinforces the assertion that Se concentration be considered in assessments of human health risk to Hg exposure

  20. Effect of silica nanoparticles with variable size and surface functionalization on human endothelial cell viability and angiogenic activity

    Science.gov (United States)

    Guarnieri, Daniela; Malvindi, Maria Ada; Belli, Valentina; Pompa, Pier Paolo; Netti, Paolo

    2014-02-01

    Silica nanoparticles could be promising delivery vehicles for drug targeting or gene therapy. However, few studies have been undertaken to determine the biological behavior effects of silica nanoparticles on primary endothelial cells. Here we investigated uptake, cytotoxicity and angiogenic properties of silica nanoparticle with positive and negative surface charge and sizes ranging from 25 to 115 nm in primary human umbilical vein endothelial cells. Dynamic light scattering measurements and nanoparticle tracking analysis were used to estimate the dispersion status of nanoparticles in cell culture media, which was a key aspect to understand the results of the in vitro cellular uptake experiments. Nanoparticles were taken up by primary endothelial cells in a size-dependent manner according to their degree of agglomeration occurring after transfer in cell culture media. Functionalization of the particle surface with positively charged groups enhanced the in vitro cellular uptake, compared to negatively charged nanoparticles. However, this effect was contrasted by the tendency of particles to form agglomerates, leading to lower internalization efficiency. Silica nanoparticle uptake did not affect cell viability and cell membrane integrity. More interestingly, positively and negatively charged 25 nm nanoparticles did not influence capillary-like tube formation and angiogenic sprouting, compared to controls. Considering the increasing interest in nanomaterials for several biomedical applications, a careful study of nanoparticle-endothelial cells interactions is of high relevance to assess possible risks associated to silica nanoparticle exposure and their possible applications in nanomedicine as safe and effective nanocarriers for vascular transport of therapeutic agents.

  1. Effects of subsidized predators, resource variability, and human population density on desert tortoise populations in the Mojave Desert, USA

    Science.gov (United States)

    Esque, Todd C.; Nussear, Kenneth E.; Drake, K. Kristina; Walde, Andrew D.; Berry, Kristin H.; Averill-Murray, Roy C.; Woodman, A. Peter; Boarman, William I.; Medica, Phil A.; Mack, Jeremy S.; Heaton, Jill S.

    2010-01-01

    Understanding predator–prey relationships can be pivotal in the conservation of species. For 2 decades, desert tortoise Gopherus agassizii populations have declined, yet quantitative evidence regarding the causes of declines is scarce. In 2005, Ft. Irwin National Training Center, California, USA, implemented a translocation project including 2 yr of baseline monitoring of desert tortoises. Unusually high predation on tortoises was observed after translocation occurred. We conducted a retrospective analysis of predation and found that translocation did not affect the probability of predation: translocated, resident, and control tortoises all had similar levels of predation. However, predation rates were higher near human population concentrations, at lower elevation sites, and for smaller tortoises and females. Furthermore, high mortality rates were not limited to the National Training Center. In 2008, elevated mortality (as high as 43%) occurred throughout the listed range of the desert tortoise. Although no temporal prey base data are available for analysis from any of the study sites, we hypothesize that low population levels of typical coyote Canis latrans prey (i.e. jackrabbits Lepus californicus and other small animals) due to drought conditions influenced high predation rates in previous years. Predation may have been exacerbated in areas with high levels of subsidized predators. Many historical reports of increased predation, and our observation of a range-wide pattern, may indicate that high predation rates are more common than generally considered and may impact recovery of the desert tortoise throughout its range.

  2. Genetic variability of aryl hydrocarbon receptor (AhR)-mediated regulation of the human UDP glucuronosyltransferase (UGT) 1A4 gene

    Energy Technology Data Exchange (ETDEWEB)

    Erichsen, Thomas J; Ehmer, Ursula; Kalthoff, Sandra; Lankisch, Tim O; Mueller, Tordis M [Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Medical School, Hannover (Germany); Munzel, Peter A [Department of Toxicology, Institute of Pharmacology and Toxicology, University of Tubingen, Tubingen (Germany); Manns, Michael P [Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Medical School, Hannover (Germany); Strassburg, Christian P. [Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Medical School, Hannover (Germany)], E-mail: strassburg.christian@mh-hannover.de

    2008-07-15

    UDP glucuronosyltransferases (UGTs) play an important role for drug detoxification and toxicity. UGT function is genetically modulated by single nucleotide polymorphisms (SNPs) which lead to the expression of functionally altered protein, or altered expression levels. UGT1A4 activity includes anticonvulsants, antidepressants and environmental mutagens. In this study the induction of the human UGT1A4 gene and a potential influence of genetic variation in its promoter region were analyzed. SNPs at bp - 219 and - 163 occurred in 9% among 109 blood donors reducing UGT1A4 transcription by 40%. UGT1A4 transcription was dioxin inducible. Reporter gene experiments identified 2 xenobiotic response elements (XRE), which were functionally confirmed by mutagenesis analyses, and binding was demonstrated by electromobility shift assays. Constitutive human UGT1A4 gene expression and induction was aryl hydrocarbon receptor (AhR)-dependent, and reduced in the presence of SNPs at bp - 219 and - 163. AhR-mediated regulation of the human UGT1A4 gene by two XRE and a modulation by naturally occurring genetic variability by SNPs is demonstrated, which indicates gene-environment interaction with potential relevance for drug metabolism.

  3. Genetic variability of aryl hydrocarbon receptor (AhR)-mediated regulation of the human UDP glucuronosyltransferase (UGT) 1A4 gene

    International Nuclear Information System (INIS)

    Erichsen, Thomas J.; Ehmer, Ursula; Kalthoff, Sandra; Lankisch, Tim O.; Mueller, Tordis M.; Munzel, Peter A.; Manns, Michael P.; Strassburg, Christian P.

    2008-01-01

    UDP glucuronosyltransferases (UGTs) play an important role for drug detoxification and toxicity. UGT function is genetically modulated by single nucleotide polymorphisms (SNPs) which lead to the expression of functionally altered protein, or altered expression levels. UGT1A4 activity includes anticonvulsants, antidepressants and environmental mutagens. In this study the induction of the human UGT1A4 gene and a potential influence of genetic variation in its promoter region were analyzed. SNPs at bp - 219 and - 163 occurred in 9% among 109 blood donors reducing UGT1A4 transcription by 40%. UGT1A4 transcription was dioxin inducible. Reporter gene experiments identified 2 xenobiotic response elements (XRE), which were functionally confirmed by mutagenesis analyses, and binding was demonstrated by electromobility shift assays. Constitutive human UGT1A4 gene expression and induction was aryl hydrocarbon receptor (AhR)-dependent, and reduced in the presence of SNPs at bp - 219 and - 163. AhR-mediated regulation of the human UGT1A4 gene by two XRE and a modulation by naturally occurring genetic variability by SNPs is demonstrated, which indicates gene-environment interaction with potential relevance for drug metabolism

  4. A theoretical approach to the deposition and clearance of fibers with variable size in the human respiratory tract

    International Nuclear Information System (INIS)

    Sturm, Robert; Hofmann, Werner

    2009-01-01

    In the study presented here, a mathematical approach for the deposition and clearance of rigid and chemically stable fibers in the human respiratory tract (HRT) is described in detail. For the simulation of fiber transport and deposition in lung airways an advanced concept of the aerodynamic diameter is applied to a stochastic lung model with individual particle trajectories computed according to a random walk algorithm. Interception of fibrous material at airway bifurcations is considered by implementation of correction factors obtained from previously published numerical approaches to fiber deposition in short bronchial sequences. Fiber clearance is simulated on the basis of a multicompartment model, within which separate clearance scenarios are assumed for the alveolar, bronchiolar, and bronchial lung region and evacuation of fibrous material commonly takes place via the airway and extrathoracic path to the gastrointestinal tract (GIT) or via the transepithelial path to the lymph nodes and blood vessels. Deposition of fibrous particles in the HRT is controlled by the fiber aspect ratio β in as much as particles with diameters <0.1 μm deposit less effectively with increasing β, while larger particles exhibit a positive correlation between their deposition efficiencies and β. A change from sitting to light-work breathing conditions causes only insignificant modifications of total fiber deposition in the HRT, whereas alveolar and, above all, tubular deposition of fibrous particles with a diameter ≥0.1 μm are affected remarkably. For these particles enhancement of the inhalative flow rate results in an increase of the extrathoracic and bronchial deposition fractions. Concerning the clearance of fibers from the HRT, 24-h retention is noticeably influenced by β and, not less important, by the preferential deposition sites of the simulated particles. The significance of β with respect to particle size may be regarded as similar to that determined for the

  5. Transcriptome association analysis identifies miR-375 as a major determinant of variable acetaminophen glucuronidation by human liver.

    Science.gov (United States)

    Papageorgiou, Ioannis; Freytsis, Marina; Court, Michael H

    2016-10-01

    Acetaminophen is the leading cause of acute liver failure (ALF) in many countries including the United States. Hepatic glucuronidation by UDP-glucuronosyltransferase (UGT) 1A subfamily enzymes is the major route of acetaminophen elimination. Reduced glucuronidation may predispose some individuals to acetaminophen-induced ALF, but mechanisms underlying reduced glucuronidation are poorly understood. We hypothesized that specific microRNAs (miRNAs) may reduce UGT1A activity by direct effects on the UGT1A 3'-UTR shared by all UGT1A enzyme transcripts, or by indirect effects on transcription factors regulating UGT1A expression. We performed an unbiased miRNA whole transcriptome association analysis using a bank of human livers with known acetaminophen glucuronidation activities. Of 754 miRNAs evaluated, 9 miRNAs were identified that were significantly overexpressed (p2-fold) in livers with low acetaminophen glucuronidation activities compared with those with high activities. miR-375 showed the highest difference (>10-fold), and was chosen for further mechanistic validation. We demonstrated using in silico analysis and luciferase reporter assays that miR-375 has a unique functional binding site in the 3'-UTR of the aryl hydrocarbon receptor (AhR) gene. Furthermore overexpression of miR-375 in LS180 cells demonstrated significant repression of endogenous AhR protein (by 40%) and mRNA (by 10%), as well as enzyme activity and/or mRNA of AhR regulated enzymes including UGT1A1, UGT1A6, and CYP1A2, without affecting UGT2B7, which is not regulated by AhR. Thus miR-375 is identified as a novel repressor of UGT1A-mediated hepatic acetaminophen glucuronidation through reduced AhR expression, which could predispose some individuals to increased risk for acetaminophen-induced ALF. Published by Elsevier Inc.

  6. Variability of human immunodeficiency virus-1 in the female genital reservoir during genital reactivation of herpes simplex virus type 2.

    Science.gov (United States)

    LeGoff, J; Roques, P; Jenabian, M-A; Charpentier, C; Brochier, C; Bouhlal, H; Gresenguet, G; Frost, E; Pepin, J; Mayaud, P; Belec, L

    2015-09-01

    Clinical and subclinical genital herpes simplex virus type 2 (HSV-2) reactivations have been associated with increases in human immunodeficiency virus (HIV)-1 genital shedding. Whether HSV-2 shedding contributes to the selection of specific genital HIV-1 variants remains unknown. We evaluated the genetic diversity of genital and blood HIV-1 RNA and DNA in 14 HIV-1/HSV-2-co-infected women, including seven with HSV-2 genital reactivation, and seven without as controls. HIV-1 DNA and HIV-1 RNA env V1-V3 sequences in paired blood and genital samples were compared. The HSV-2 selection pressure on HIV was estimated according to the number of synonymous substitutions (dS), the number of non-synonymous substitutions (dN) and the dS/dN ratio within HIV quasi-species. HIV-1 RNA levels in cervicovaginal secretions were higher in women with HSV-2 replication than in controls (p0.02). Plasma HIV-1 RNA and genital HIV-1 RNA and DNA were genetically compartmentalized. No differences in dS, dN and the dS/dN ratio were observed between the study groups for either genital HIV-1 RNA or plasma HIV-1 RNA. In contrast, dS and dN in genital HIV-1 DNA were significantly higher in patients with HSV-2 genital reactivation (p genital HIV-1 DNA was slightly higher in patients with HSV-2 genital replication, indicating a trend for purifying selection (p 0.056). HSV-2 increased the genetic diversity of genital HIV-1 DNA. These observations confirm molecular interactions between HSV-2 and HIV-1 at the genital tract level. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  7. Variability of protein level and phosphorylation status caused by biopsy protocol design in human skeletal muscle analyses

    Directory of Open Access Journals (Sweden)

    Caron Marc-André

    2011-11-01

    Full Text Available Abstract Background Bergström needle biopsy is widely used to sample skeletal muscle in order to study cell signaling directly in human tissue. Consequences of the biopsy protocol design on muscle protein quantity and quality remain unclear. The aim of the present study was to assess the impact of different events surrounding biopsy protocol on the stability of the Western blot signal of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1, Akt, glycogen synthase kinase-3β (GSK-3β, muscle RING finger protein 1 (MuRF1 and p70 S6 kinase (p70 S6K. Six healthy subjects underwent four biopsies of the vastus lateralis, distributed into two distinct visits spaced by 48 hrs. At visit 1, a basal biopsy in the right leg was performed in the morning (R1 followed by a second in the left leg in the afternoon (AF. At visit 2, a second basal biopsy (R2 was collected from the right leg. Low intensity mobilization (3 × 20 right leg extensions was performed and a final biopsy (Mob was collected using the same incision site as R2. Results Akt and p70 S6K phosphorylation levels were increased by 83% when AF biopsy was compared to R1. Mob condition induced important phosphorylation of p70 S6K when compared to R2. Comparison of R1 and R2 biopsies revealed a relative stability of the signal for both total and phosphorylated proteins. Conclusions This study highlights the importance to standardize muscle biopsy protocols in order to minimize the method-induced variation when analyzing Western blot signals.

  8. Late Holocene forest dynamics in the Gulf of Gaeta (central Mediterranean) in relation to NAO variability and human impact

    Science.gov (United States)

    Di Rita, Federico; Lirer, Fabrizio; Bonomo, Sergio; Cascella, Antonio; Ferraro, Luciana; Florindo, Fabio; Insinga, Donatella Domenica; Lurcock, Pontus Conrad; Margaritelli, Giulia; Petrosino, Paola; Rettori, Roberto; Vallefuoco, Mattia; Magri, Donatella

    2018-01-01

    A new high-resolution pollen record, spanning the last five millennia, is presented from the Gulf of Gaeta (Tyrrhenian Sea, central Italy), with the aim of verifying if any vegetation change occurred in the central Mediterranean region in relation to specific well-known global and/or regional climate events, including the 4.2 ka event, the Medieval Climate Anomaly (MCA) and the Little Ice Age (LIA), and to detect possible vegetation changes related to still under-investigated climate signals, for example the so-called "Bond 2" cold event around 2.8 ka BP. The vegetation dynamics of the Gaeta record shows a recurrent pattern of forest increase and decline punctuating the mid- and late Holocene. When the timing of these patterns is compared with the climate proxy data available from the same core (planktonic foraminifera assemblages and oxygen stable isotope record) and with the NAO (North Atlantic Oscillation) index, it clearly appears that the main driver for the forest fluctuations is climate, which may even overshadow the effects of human activity. We have found a clear correspondence between phases with negative NAO index and forest declines. In particular, around 4200 cal BP, a drop in AP (Arboreal Pollen) confirms the clearance recorded in many sites in Italy south of 43°N. Around 2800 cal BP, a vegetation change towards open conditions is found at a time when the NAO index clearly shows negative values. Between 800 and 1000 AD, a remarkable forest decline, coeval with a decrease in the frequencies of both Castanea and Olea, matches a shift in the oxygen isotope record towards positive values, indicating cooler temperatures, and a negative NAO. Between 1400-1850 AD, in the time period chronologically corresponding to the LIA (Little Ice Age), the Gaeta record shows a clear decline of the forest cover, particularly evident after 1550 AD, once again in correspondence with negative NAO index.

  9. Laterality and grip strength influence hand bone micro-architecture in modern humans, an HRpQCT study.

    Science.gov (United States)

    Reina, Nicolas; Cavaignac, Etienne; Trousdale, William H; Laffosse, Jean-Michel; Braga, José

    2017-06-01

    It is widely hypothesized that mechanical loading, specifically repetitive low-intensity tasks, influences the inner structure of cancellous bone. As such, there is likely a relationship between handedness and bone morphology. The aim of this study is to determine patterns in trabecular bone between dominant and non-dominant hands in modern humans. Seventeen healthy patients between 22 and 32 years old were included in the study. Radial carpal bones (lunate, capitate, scaphoid, trapezium, trapezoid, 1st, 2nd and 3rd metacarpals) were analyzed with high-resolution micro-computed tomography. Additionally, crush and pinch grip were recorded. Factorial analysis indicated that bone volume ratio, trabeculae number (Tb.N), bone surface to volume ratio (BS.BV), body weight, stature and crush grip were all positively correlated with principal components 1 and 2 explaining 78.7% of the variance. Volumetric and trabecular endostructural parameters (BV/TV, BS/BV or Tb.Th, Tb.N) explain the observed inter-individual variability better than anthropometric or clinical parameters. Factors analysis regressions showed correlations between these parameters and the dominant side for crush strength for the lunate (r 2 = 0.640, P modern human wrist. © 2017 Anatomical Society.

  10. An analysis on half century morphological changes in the Changjiang Estuary: Spatial variability under natural processes and human intervention

    Science.gov (United States)

    Zhao, Jie; Guo, Leicheng; He, Qing; Wang, Zheng Bing; van Maren, D. S.; Wang, Xianye

    2018-05-01

    Examination of large scale, alluvial estuarine morphology and associated time evolution is of particular importance regarding management of channel navigability, ecosystem, etc. In this work, we analyze morphological evolution and changes of the channel-shoal system in the Changjiang Estuary, a river- and tide-controlled coastal plain estuary, based on bathymetric data between 1958 and 2016. We see that its channel-shoal pattern is featured by meandering and bifurcated channels persisting over decades. In the vertical direction, hypsometry curves show that the sand bars and shoals are continuously accreted while the deep channels are eroded, leading to narrower and deeper estuarine channels. Intensive human activities in terms of reclamation, embankment, and dredging play a profound role in controlling the decadal morphological evolution by stabilizing coastlines and narrowing channels. Even though, the present Changjiang Estuary is still a pretty wide and shallow system with channel width-to-depth ratios >1000, much larger than usual fluvial rivers and small estuaries. In-depth analysis suggests that the Changjiang Estuary as a whole exhibited an overall deposition trend over 59 years, i.e., a net deposition volume of 8.3 × 108 m3. Spatially, the pan-South Branch was net eroded by 9.7 × 108 m3 whereas the mouth bar zone was net deposited by 18 × 108 m3, suggesting that the mouth bar zone is a major sediment sink. Over time there is no directional deposition or erosion trend in the interval though riverine sediment supply has decreased by 2/3 since the mid-1980s. We infer that the pan-South Branch is more fluvial-controlled therefore its morphology responds to riverine sediment load reduction fast while the mouth bar zone is more controlled by both river and tides that its morphological response lags to riverine sediment supply changes at a time scale >10 years, which is an issue largely ignored in previous studies. We argue that the time lag effect needs

  11. Taming Human Genetic Variability: Transcriptomic Meta-Analysis Guides the Experimental Design and Interpretation of iPSC-Based Disease Modeling

    Directory of Open Access Journals (Sweden)

    Pierre-Luc Germain

    2017-06-01

    Full Text Available Both the promises and pitfalls of the cell reprogramming research platform rest on human genetic variation, making the measurement of its impact one of the most urgent issues in the field. Harnessing large transcriptomics datasets of induced pluripotent stem cells (iPSC, we investigate the implications of this variability for iPSC-based disease modeling. In particular, we show that the widespread use of more than one clone per individual in combination with current analytical practices is detrimental to the robustness of the findings. We then proceed to identify methods to address this challenge and leverage multiple clones per individual. Finally, we evaluate the specificity and sensitivity of different sample sizes and experimental designs, presenting computational tools for power analysis. These findings and tools reframe the nature of replicates used in disease modeling and provide important resources for the design, analysis, and interpretation of iPSC-based studies.

  12. Genetic variability of attachment (G and Fusion (F protein genes of human metapneumovirus strains circulating during 2006-2009 in Kolkata, Eastern India

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    Chawla-Sarkar Mamta

    2011-02-01

    Full Text Available Abstract Background Human metapneumovirus (hMPV is associated with the acute respiratory tract infection (ARTI in all the age groups. However, there is limited information on prevalence and genetic diversity of human metapneumovirus (hMPV strains circulating in India. Objective To study prevalence and genomic diversity of hMPV strains among ARTI patients reporting in outpatient departments of hospitals in Kolkata, Eastern India. Methods Nasal and/or throat swabs from 2309 patients during January 2006 to December 2009, were screened for the presence of hMPV by RT-PCR of nucleocapsid (N gene. The G and F genes of representative hMPV positive samples were sequenced. Results 118 of 2309 (5.11% clinical samples were positive for hMPV. The majority (≈80% of the positive cases were detected during July−November all through the study period. Genetic analysis revealed that 77% strains belong to A2 subgroup whereas rest clustered in B1 subgroup. G sequences showed higher diversity at the nucleotide and amino acid level. In contrast, less than 10% variation was observed in F gene of representative strains of all four years. Sequence analysis also revealed changes in the position of stop codon in G protein, which resulted in variable length (217-231 aa polypeptides. Conclusion The study suggests that approximately 5% of ARTI in the region were caused by hMPV. This is the first report on the genetic variability of G and F gene of hMPV strains from India which clearly shows that the G protein of hMPV is continuously evolving. Though the study partially fulfills lacunae of information, further studies from other regions are necessary for better understanding of prevalence, epidemiology and virus evolution in Indian subcontinent.

  13. A study of the relationship between variables from the model of human occupation and subjective well-being among university students in jordan.

    Science.gov (United States)

    Yazdani, Farzaneh; Jibril, Musa; Kielhofner, Gary

    2008-01-01

    The occupational role of a university student can create challenges that negatively affect subjective well-being. Cultural factors can make these problems particularly acute for students from Arab backgrounds. This study examined the relationship between variables derived from the Model of Human Occupation (MOHO) and Jordanian university students' subjective well-being. Using cluster sampling, a total of 670 participants were recruited from the undergraduate student body at the University of Jordan. Data were collected from these students using the Role checklist, the Occupational Self-Assessment, the Affectometer 2, and the Satisfaction with Life Scale. As hypothesized, reported roles, valuation of roles, perceived competence in volition, habituation, performance capacity/skills, and the environment were significantly correlated with subjective well-being. A discriminant analysis using the most strongly correlated items significantly classified students into known groups of high and low subjective well-being. Overall, MOHO-based variables offered an effective explanation of factors that influence subjective well-being in Jordanian university students.

  14. Magneto encephalography (MEG: perspectives of speech areas functional mapping in human subjects

    Directory of Open Access Journals (Sweden)

    Butorina A. V.

    2012-06-01

    Full Text Available One of the main problems in clinical practice and academic research is how to localize speech zones in the human brain. Two speech areas (Broca and Wernicke areas that are responsible for language production and for understanding of written and spoken language have been known since the past century. Their location and even hemispheric lateralization have a substantial inter-individual variability, especially in neurosurgery patients. Wada test is one of the most frequently used invasive methodology for speech hemispheric lateralization in neurosurgery patients. However, besides relatively high-risk of Wada test for patient's health, it has its own limitation, e. g. low reliability of Wada-based evidence of verbal memory brain lateralization. Therefore, there is an urgent need for non-invasive, reliable methods of speech zones mapping.The current review summarizes the recent experimental evidence from magnitoencephalographic (MEG research suggesting that speech areas are included in the speech processing within the first 200 ms after the word onset. The electro-magnetic response to deviant word, mismatch negativity wave with latency of 100—200 ms, can be recorded from auditory cortex within the oddball-paradigm. We provide the arguments that basic features of this brain response, such as its automatic, pre-attentive nature, high signal to noise ratio, source localization at superior temporal sulcus, make it a promising vehicle for non-invasive MEG-based speech areas mapping in neurosurgery.

  15. Adaptive response induced by low doses of ionizing radiation in human lymphocytes

    International Nuclear Information System (INIS)

    Frati, Diego Libkind; Bunge, Maria M.

    2001-01-01

    The term adaptive response (AR) applies to the phenomenon of protection or enhanced repair induced by a small dose of a mutagenic agent. In order to determine the existence of AR in human lymphocytes for two different irradiation schemes, microcultures of blood from 4 donors were irradiated. Samples were exposed 24 hours (hr) after phytohemagglutinin stimulation to an adapting dose of 0,01 Gy and to a challenging dose of 1,5 Gy either 6 or 24 hr later (irradiation scheme 24+30 or 24+48, respectively). Gamma radiation from a 2,5 MeV Linac was used in all experiments. A cytogenetic analysis of unstable chromosome aberrations was applied as the endpoint. High inter-individual variability was found for the first irradiation scheme: one expressed AR, two did not and the last showed an apparent synergistic response. For the second irradiation scheme, low mitotic indices (MI) were found, suggesting a G2 arrest. When a series of harvesting times were applied for the last donor, normal MI were obtained only harvesting after 58 hr. An AR was found when harvesting at 72 hr but not at 58 hr. (author)

  16. Mechanistic understanding of time-dependent oral absorption based on gastric motor activity in humans.

    Science.gov (United States)

    Higaki, Kazutaka; Choe, Sally Y; Löbenberg, Raimar; Welage, Lynda S; Amidon, Gordon L

    2008-09-01

    The relationship of gastric motor activity and gastric emptying of 0.7 mm caffeine pellets with their absorption was investigated in the fed state in healthy human subjects by simultaneous monitoring of antral motility and plasma concentrations. A kinetic model for gastric emptying-dependent absorption yielded multiple phases of gastric emptying and rate constants (k(g)) with large inter-individual differences and large variability in onset of gastric emptying (50-175 min). The model suggests that 50% of the dose is emptied in 1-2h and over 90% emptied by 3.5h following dosing, in all subjects. The maximum values of k(g) (k(g)(max)) were much greater than those reported for emptying of liquids in the fasted state and were comparable to k(g) values in the late Phase II/III of the migrating motor complex (MMC). The model described the observed irregular absorption rate-time and plasma concentration-time profiles adequately but not in detail. The model was more successful at simulating double-peak phenomena in absorption rate profiles and onset of caffeine absorption. The results suggest that gastric emptying regulates drug absorption of small particles in the fed state. Further, estimates of k(a) derived using the time-dependent absorption model were closer to the intrinsic absorption rate constant for caffeine.

  17. Genetic variability in G2 and F2 region between biological clones of human respiratory syncytial virus with or without host immune selection pressure

    Directory of Open Access Journals (Sweden)

    Claudia Trigo Pedroso Moraes

    2015-02-01

    Full Text Available Human respiratory syncytial virus (HRSV is an important respiratory pathogens among children between zero-five years old. Host immunity and viral genetic variability are important factors that can make vaccine production difficult. In this work, differences between biological clones of HRSV were detected in clinical samples in the absence and presence of serum collected from children in the convalescent phase of the illness and from their biological mothers. Viral clones were selected by plaque assay in the absence and presence of serum and nucleotide sequences of the G2 and F2 genes of HRSV biological clones were compared. One non-synonymous mutation was found in the F gene (Ile5Asn in one clone of an HRSV-B sample and one non-synonymous mutation was found in the G gene (Ser291Pro in four clones of the same HRSV-B sample. Only one of these clones was obtained after treatment with the child's serum. In addition, some synonymous mutations were determined in two clones of the HRSV-A samples. In conclusion, it is possible that minor sequences could be selected by host antibodies contributing to the HRSV evolutionary process, hampering the development of an effective vaccine, since we verify the same codon alteration in absence and presence of human sera in individual clones of BR-85 sample.

  18. Genetic variability in G2 and F2 region between biological clones of human respiratory syncytial virus with or without host immune selection pressure.

    Science.gov (United States)

    Moraes, Claudia Trigo Pedroso; Oliveira, Danielle Bruna Leal; Campos, Angelica Cristine Almeida; Bosso, Patricia Alves; Lima, Hildener Nogueira; Stewien, Klaus Eberhard; Gilio, Alfredo Elias; Vieira, Sandra Elisabete; Botosso, Viviane Fongaro; Durigon, Edison Luiz

    2015-02-01

    Human respiratory syncytial virus (HRSV) is an important respiratory pathogens among children between zero-five years old. Host immunity and viral genetic variability are important factors that can make vaccine production difficult. In this work, differences between biological clones of HRSV were detected in clinical samples in the absence and presence of serum collected from children in the convalescent phase of the illness and from their biological mothers. Viral clones were selected by plaque assay in the absence and presence of serum and nucleotide sequences of the G2 and F2 genes of HRSV biological clones were compared. One non-synonymous mutation was found in the F gene (Ile5Asn) in one clone of an HRSV-B sample and one non-synonymous mutation was found in the G gene (Ser291Pro) in four clones of the same HRSV-B sample. Only one of these clones was obtained after treatment with the child's serum. In addition, some synonymous mutations were determined in two clones of the HRSV-A samples. In conclusion, it is possible that minor sequences could be selected by host antibodies contributing to the HRSV evolutionary process, hampering the development of an effective vaccine, since we verify the same codon alteration in absence and presence of human sera in individual clones of BR-85 sample.

  19. Effects of Moxa (Folium Artemisiae argyi Smoke Exposure on Heart Rate and Heart Rate Variability in Healthy Young Adults: A Randomized, Controlled Human Study

    Directory of Open Access Journals (Sweden)

    Yingxue Cui

    2013-01-01

    Full Text Available Objective. To determine the effects of the moxa smoke on human heart rate (HR and heart rate variability (HRV. Methods. Fifty-five healthy young adults were randomly divided into experimental (n=28 and control (n=27 groups. Experimental subjects were exposed to moxa smoke (2.5 ± 0.5 mg/m3 twice for 25 minutes in one week. ECG monitoring was performed before, during, and after exposure. Control subjects were exposed to normal indoor air in a similar environment and similarly monitored. Followup was performed the following week. Short-term (5 min HRV parameters were analyzed with HRV analysis software. SPSS software was used for statistical analysis. Results. During and after the first exposure, comparison of percentage changes or changes in all parameters between groups showed no significant differences. During the second exposure, percentage decrease in HR, percentage increases in lnTP, lnHF, lnLF, and RMSSD, and increase in PNN50 were significantly greater in the experimental group than in control. Conclusion. No significant adverse HRV effects were associated with this clinically routine 25-minute exposure to moxa smoke, and the data suggests that short-term exposure to moxa smoke might have positive regulating effects on human autonomic function. Further studies are warranted to confirm these findings.

  20. Behavioral Correlations Associated with Fear of Humans Differ between Rural and Urban Burrowing Owls

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    Martina Carrete

    2017-05-01

    Full Text Available Behavioral studies are fundamental to understanding how animal populations face global change. Although much research has centered upon the idea that individuals can adaptively modify their behaviors to cope with environmental changes, recent evidence supports the existence of individual differences in suites of correlated behaviors. However, little is known about how selection can change these behavioral structures in populations subject to different environmental constraints. The colonization of urban environments by birds has been related to their inter-individual variability in their fear of humans, measured as their flight initiation distance to an approaching human, such that urban life would select for fearless individuals. This behavior has been demonstrated to be heritable and highly consistent throughout the adult lifespan of burrowing owls (Athene cunicularia. Here, we experimentally assessed, in field conditions, whether urban life involves changes in other behaviors such as exploration and antipredatory response through their correlation with fear of humans. Breeding urban birds were more fearless toward humans and were quicker to explore a new food resource and defend their nests from predators than their rural counterparts. However, while fear of humans positively correlated with exploration and antipredatory response in the rural population, it only correlated with exploration in the urban one. Predator release in urban environments could relax—and even counterselect—antipredator behaviors, thus dismantling the behavioral correlation existent in natural populations. Altogether, our results suggest that rural and urban animals may differ in some behavioral aspects, may be as a consequence of the selection processes acting during the colonization of urban areas as well as the different ecological environments encountered by individuals.

  1. Variability Bugs:

    DEFF Research Database (Denmark)

    Melo, Jean

    . Although many researchers suggest that preprocessor-based variability amplifies maintenance problems, there is little to no hard evidence on how actually variability affects programs and programmers. Specifically, how does variability affect programmers during maintenance tasks (bug finding in particular......)? How much harder is it to debug a program as variability increases? How do developers debug programs with variability? In what ways does variability affect bugs? In this Ph.D. thesis, I set off to address such issues through different perspectives using empirical research (based on controlled...... experiments) in order to understand quantitatively and qualitatively the impact of variability on programmers at bug finding and on buggy programs. From the program (and bug) perspective, the results show that variability is ubiquitous. There appears to be no specific nature of variability bugs that could...

  2. Effect of genetic homogeneity on behavioural variability in an object recognition test in cloned Göttingen minipigs

    DEFF Research Database (Denmark)

    Søndergaard, Lene Vammen; Herskin, Mette S.; Ladewig, Jan

    2012-01-01

    effects of genetic homogeneity on variability of cloned minipigs compared with non-cloned controls regarding behavioural variables in a cognitive test, namely the spontaneous object recognition test. Significant differences in the variability between the cloned and control pigs were found in five out...... was numerically greater for the control group compared to the cloned group, indicating that variation may be less in cloned animals, but not demonstrable with the small group size of the present study (n = 6 for each of the two groups tested). Overall, this study failed to show unambiguously that variability......The number of animals used in research should be limited as much as possible. Among cloned animals, genetic variation is minimal and to the extent that behaviour is genetically determined inter-individual variability is expected to be higher among naturally bred animals. However, the cloning...

  3. Selenium and mercury molar ratios in saltwater fish from New Jersey: Individual and species variability complicate use in human health fish consumption advisories☆

    Science.gov (United States)

    Burger, Joanna; Gochfeld, Michael

    2014-01-01

    Balancing risk versus benefits to humans and other organisms from consuming fish is a national concern in the USA, as well as in many other parts of the world. Protecting public health is both a federal and state responsibility, and states respond by issuing fish consumption advisories, particularly for mercury. Recently it has been emphasized that the protective role of selenium against mercury toxicity depends on their molar ratios, which should be evaluated as an indication of selenium’s protective capacity, and incorporated in risk assessments for fish consumption. However, there is no single “protective” ratio agreed upon. In this paper we examine the selenium:mercury (Se:Hg) molar ratios in a wide range of saltwater fish caught and eaten by recreational fishers along the New Jersey coast. We were particularly interested in interspecific and intraspecific variability, and whether the molar ratios were consistent within a species, allowing for its use in managing risk. The selenium–mercury molar ratio showed significant variation among and within fish species. The molar ratio decreased with the size of the fish species, decreased with the mercury levels, and within a fish species, the selenium:mercury ratio decreased with fish size. As an essential element, selenium undergoes some homeostatic regulation, but it is also highly toxic. Within species, mercury level tends to increase with size, accounting for the negative relationship between size and ratio. This variability may make it difficult to use the selenium:mercury molar ratio in risk assessment, risk management, and risk communication at this time, and more information is needed on how mercury and selenium actually interact and on the relationship between the molar ratios and health outcomes. PMID:22405995

  4. Simultaneous determination of nine β-lactam antibiotics in human plasma by an ultrafast hydrophilic-interaction chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Abdulla, Alan; Bahmany, Soma; Wijma, Rixt A; van der Nagel, Bart C H; Koch, Birgit C P

    2017-08-15

    Contemporary β-lactam antibiotic dosing is debatable in severely ill patients, since the occurrence of pathophysiological changes in critical illness can result in great inter-individual variability. Therapeutic drug monitoring (TDM) is a commonly used dosing strategy to optimize exposure and thereby minimize toxicity and maximize the efficacy. Currently, TDM of β-lactam antibiotics is rarely performed, due to poor availability in clinical practice. We describe an ultrafast Hydrophilic-Interaction Chromatography (HILIC) based UPLC-MS/MS method for the determination of amoxicillin, benzylpenicillin, cefotaxime, cefuroxime, ceftazidime, flucloxacillin, imipenem, meropenem and piperacillin in human plasma. This method involves simple sample preparation steps and was comprehensively validated according to standard FDA guidelines. For all analytes, mean accuracy and precision values were within the acceptance value. The lower and upper limits of quantification were found to be sufficient to cover the therapeutic range for all antibiotics. Finally, the method was successfully applied in a large pharmacokinetic study performed in the intensive care setting, and the feasibility of the analytical procedure was demonstrated in routine clinical practice. To the best of our knowledge, we report here the first HILIC-based UPLC-MS/MS assay for the determination of β-lactam antibiotics in human plasma. This simple, sensitive and ultrafast assay requires small-volume samples and can easily be implemented in clinical laboratories to promote the TDM of β-lactam antibiotics. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Variations of Histone Modification Patterns: Contributions of Inter-plant Variability and Technical Factors

    Directory of Open Access Journals (Sweden)

    Sylva Brabencová

    2017-12-01

    Full Text Available Inter-individual variability of conspecific plants is governed by differences in their genetically determined growth and development traits, environmental conditions, and adaptive responses under epigenetic control involving histone post-translational modifications. The apparent variability in histone modifications among plants might be increased by technical variation introduced in sample processing during epigenetic analyses. Thus, to detect true variations in epigenetic histone patterns associated with given factors, the basal variability among samples that is not associated with them must be estimated. To improve knowledge of relative contribution of biological and technical variation, mass spectrometry was used to examine histone modification patterns (acetylation and methylation among Arabidopsis thaliana plants of ecotypes Columbia 0 (Col-0 and Wassilewskija (Ws homogenized by two techniques (grinding in a cryomill or with a mortar and pestle. We found little difference in histone modification profiles between the ecotypes. However, in comparison of the biological and technical components of variability, we found consistently higher inter-individual variability in histone mark levels among Ws plants than among Col-0 plants (grown from seeds collected either from single plants or sets of plants. Thus, more replicates of Ws would be needed for rigorous analysis of epigenetic marks. Regarding technical variability, the cryomill introduced detectably more heterogeneity in the data than the mortar and pestle treatment, but mass spectrometric analyses had minor apparent effects. Our study shows that it is essential to consider inter-sample variance and estimate suitable numbers of biological replicates for statistical analysis for each studied organism when investigating changes in epigenetic histone profiles.

  6. Variations of Histone Modification Patterns: Contributions of Inter-plant Variability and Technical Factors.

    Science.gov (United States)

    Brabencová, Sylva; Ihnatová, Ivana; Potěšil, David; Fojtová, Miloslava; Fajkus, Jiří; Zdráhal, Zbyněk; Lochmanová, Gabriela

    2017-01-01

    Inter-individual variability of conspecific plants is governed by differences in their genetically determined growth and development traits, environmental conditions, and adaptive responses under epigenetic control involving histone post-translational modifications. The apparent variability in histone modifications among plants might be increased by technical variation introduced in sample processing during epigenetic analyses. Thus, to detect true variations in epigenetic histone patterns associated with given factors, the basal variability among samples that is not associated with them must be estimated. To improve knowledge of relative contribution of biological and technical variation, mass spectrometry was used to examine histone modification patterns (acetylation and methylation) among Arabidopsis thaliana plants of ecotypes Columbia 0 (Col-0) and Wassilewskija (Ws) homogenized by two techniques (grinding in a cryomill or with a mortar and pestle). We found little difference in histone modification profiles between the ecotypes. However, in comparison of the biological and technical components of variability, we found consistently higher inter-individual variability in histone mark levels among Ws plants than among Col-0 plants (grown from seeds collected either from single plants or sets of plants). Thus, more replicates of Ws would be needed for rigorous analysis of epigenetic marks. Regarding technical variability, the cryomill introduced detectably more heterogeneity in the data than the mortar and pestle treatment, but mass spectrometric analyses had minor apparent effects. Our study shows that it is essential to consider inter-sample variance and estimate suitable numbers of biological replicates for statistical analysis for each studied organism when investigating changes in epigenetic histone profiles.

  7. Intra-individual variability as a predictor of learning

    Directory of Open Access Journals (Sweden)

    Matija Svetina

    2004-05-01

    Full Text Available Learning is one of the most important aspects of children's behaviour. A new theory that emerged from evolutionary principles and information-processing models assumes learning to be run by two basic mechanisms: variability and selection. The theory is based on the underlying assumption that intra-individual variability of strategies that children use to solve a problem, is a core mechanism of learning change. This assumption was tested in the case of multiple classification (MC task. 30 6-year-old children were tested for intelligence, short-term memory, and MC. Procedure followed classical pre-test/learning/post-test scheme. Amount of learning was measured through percentage of correct answers before and after learning sessions, whereas intra-individual variability was assessed through children's explanations of their answers on MC problems. The results yielded intra-individual variability to explain learning changes beyond inter-individual differences in intelligence or short-term memory. Although the results rose some new questions to be considered in further research, the data supported the hypothesis of intra-individual variability as predictor of learning change.

  8. A method to evaluate the perceived ease of use of human-machine interface in agricultural tractors equipped with Continuously Variable Transmission (CVT)

    International Nuclear Information System (INIS)

    Caffaro, F.; Bisaglia, C.; Cutini, M.; Cremasco, M.M.; Cavallo, E.

    2017-01-01

    At the end of the 20th century the adoption of the Continuously Variable Transmission (CVT) was one of the disruptive technological advances in agricultural tractors. Several changes in the Human Machine Interface (HMI) of the tractor cab have been introduced to accommodate this technology. HMIs are known to raise issues about their ease of use; however, this topic has been under-investigated in the agricultural sector. The present study introduces a method to investigate the perceived ease of use of the HMI of agricultural tractors equipped with technological innovations. The HMI required to manage a CVT tractor was evaluated by sixteen tractor drivers (8 novices and 8 experts). During the first contact with the machine and after having performed two targeted tasks with the tractor, participants filled in a questionnaire about the ease of use of the controls and of the touch-screen display, and evaluated the general perception of ease of use, safety, quality and solidity of the machine. The trial pointed out some significant differences between novices and experts, thus confirming the validity of the proposed method. In particular, novice users showed some difficulties when interacting for the first time with the HMI of the CVT tractor working station, whereas experts did not report similar difficulties. Thus, expertise seems to play a role in determining the quality of the interaction with the HMI. Training interventions should be designed to help novices in increasing their expertise effectively, avoiding effort and errors and improving user’s comfort and system performance.

  9. A method to evaluate the perceived ease of use of human-machine interface in agricultural tractors equipped with Continuously Variable Transmission (CVT)

    Energy Technology Data Exchange (ETDEWEB)

    Caffaro, F.; Bisaglia, C.; Cutini, M.; Cremasco, M.M.; Cavallo, E.

    2017-07-01

    At the end of the 20th century the adoption of the Continuously Variable Transmission (CVT) was one of the disruptive technological advances in agricultural tractors. Several changes in the Human Machine Interface (HMI) of the tractor cab have been introduced to accommodate this technology. HMIs are known to raise issues about their ease of use; however, this topic has been under-investigated in the agricultural sector. The present study introduces a method to investigate the perceived ease of use of the HMI of agricultural tractors equipped with technological innovations. The HMI required to manage a CVT tractor was evaluated by sixteen tractor drivers (8 novices and 8 experts). During the first contact with the machine and after having performed two targeted tasks with the tractor, participants filled in a questionnaire about the ease of use of the controls and of the touch-screen display, and evaluated the general perception of ease of use, safety, quality and solidity of the machine. The trial pointed out some significant differences between novices and experts, thus confirming the validity of the proposed method. In particular, novice users showed some difficulties when interacting for the first time with the HMI of the CVT tractor working station, whereas experts did not report similar difficulties. Thus, expertise seems to play a role in determining the quality of the interaction with the HMI. Training interventions should be designed to help novices in increasing their expertise effectively, avoiding effort and errors and improving user’s comfort and system performance.

  10. The Influence of New Colored Light Stimulation Methods on Heart Rate Variability, Temperature, and Well-Being: Results of a Pilot Study in Humans

    Directory of Open Access Journals (Sweden)

    Daniela Litscher

    2013-01-01

    Full Text Available Changes of light intensity of different colors can shift many physiological parameters and conditions like melatonin, alertness, body temperature, heart rate (HR, and heart rate variability (HRV. The aim of this pilot study was to investigate acute temperature, HR, HRV, and state of mind reactivities after illumination with red (631 nm and blue (456 nm light (illuminance 140 lux for both. Seven healthy volunteers (5 females, 2 males; mean age ± SD 34.1 ± 11.9 years were investigated at the Medical University of Graz, using new color light panels. Significant decreases were found only after 10 min blue light stimulation in nose temperature (P=0.046, HR (P<0.05, and total HRV (P=0.029, in association with a significant alteration of the emotional state (stress level score, P=0.006. However, red light stimulation of the same persons did not induce the same effects in these parameters. The effect of blue light as environmental stimulation on human health is not clarified in detail and needs further investigations.

  11. Comparison of variable region 3 sequences of human immunodeficiency virus type 1 from infected children with the RNA and DNA sequences of the virus populations of their mothers.

    Science.gov (United States)

    Scarlatti, G; Leitner, T; Halapi, E; Wahlberg, J; Marchisio, P; Clerici-Schoeller, M A; Wigzell, H; Fenyö, E M; Albert, J; Uhlén, M

    1993-01-01

    We have compared the variable region 3 sequences from 10 human immunodeficiency virus type 1 (HIV-1)-infected infants to virus sequences from the corresponding mothers. The sequences were derived from DNA of uncultured peripheral blood mononuclear cells (PBMC), DNA of cultured PBMC, and RNA from serum collected at or shortly after delivery. The infected infants, in contrast to the mothers, harbored homogeneous virus populations. Comparison of sequences from the children and clones derived from DNA of the corresponding mothers showed that the transmitted virus represented either a minor or a major virus population of the mother. In contrast to an earlier study, we found no evidence of selection of minor virus variants during transmission. Furthermore, the transmitted virus variant did not show any characteristic molecular features. In some cases the transmitted virus was more related to the virus RNA population of the mother and in other cases it was more related to the virus DNA population. This suggests that either cell-free or cell-associated virus may be transmitted. These data will help AIDS researchers to understand the mechanism of transmission and to plan strategies for prevention of transmission. PMID:8446584

  12. Improving resolution of public health surveillance for human Salmonella enterica serovar Typhimurium infection: 3 years of prospective multiple-locus variable-number tandem-repeat analysis (MLVA

    Directory of Open Access Journals (Sweden)

    Sintchenko Vitali

    2012-03-01

    Full Text Available Abstract Background Prospective typing of Salmonella enterica serovar Typhimurium (STM by multiple-locus variable-number tandem-repeat analysis (MLVA can assist in identifying clusters of STM cases that might otherwise have gone unrecognised, as well as sources of sporadic and outbreak cases. This paper describes the dynamics of human STM infection in a prospective study of STM MLVA typing for public health surveillance. Methods During a three-year period between August 2007 and September 2010 all confirmed STM isolates were fingerprinted using MLVA as part of the New South Wales (NSW state public health surveillance program. Results A total of 4,920 STM isolates were typed and a subset of 4,377 human isolates was included in the analysis. The STM spectrum was dominated by a small number of phage types, including DT170 (44.6% of all isolates, DT135 (13.9%, DT9 (10.8%, DT44 (4.5% and DT126 (4.5%. There was a difference in the discriminatory power of MLVA types within endemic phage types: Simpson's index of diversity ranged from 0.109 and 0.113 for DTs 9 and 135 to 0.172 and 0.269 for DTs 170 and 44, respectively. 66 distinct STM clusters were observed ranging in size from 5 to 180 cases and in duration from 4 weeks to 25 weeks. 43 clusters had novel MLVA types and 23 represented recurrences of previously recorded MLVA types. The diversity of the STM population remained relatively constant over time. The gradual increase in the number of STM cases during the study was not related to significant changes in the number of clusters or their size. 667 different MLVA types or patterns were observed. Conclusions Prospective MLVA typing of STM allows the detection of community outbreaks and demonstrates the sustained level of STM diversity that accompanies the increasing incidence of human STM infections. The monitoring of novel and persistent MLVA types offers a new benchmark for STM surveillance. A part of this study was presented at the MEEGID

  13. The Role of Information Technology as Moderating Variable and Internal Control Effectiveness as intervening in the Relationship between Human Resource Competency and Internal Auditor Service Quality on of Report

    OpenAIRE

    Haliah, Hamid,Irdam

    2015-01-01

    in general, this research is intended to investigate factors that effect quality of report of local government in west Sulawesi province, Indonesia. Human resource competence and quality of services of internal auditor have indirect effect through the effectiveness of internal control to the quality of the report. These results indicate that the effectiveness of internal control serves as an intervening variable on the relationship of competence of human resources and internal auditor service...

  14. The Toll-like receptor gene family is integrated into human DNA damage and p53 networks.

    Directory of Open Access Journals (Sweden)

    Daniel Menendez

    2011-03-01

    Full Text Available In recent years the functions that the p53 tumor suppressor plays in human biology have been greatly extended beyond "guardian of the genome." Our studies of promoter response element sequences targeted by the p53 master regulatory transcription factor suggest a general role for this DNA damage and stress-responsive regulator in the control of human Toll-like receptor (TLR gene expression. The TLR gene family mediates innate immunity to a wide variety of pathogenic threats through recognition of conserved pathogen-associated molecular motifs. Using primary human immune cells, we have examined expression of the entire TLR gene family following exposure to anti-cancer agents that induce the p53 network. Expression of all TLR genes, TLR1 to TLR10, in blood lymphocytes and alveolar macrophages from healthy volunteers can be induced by DNA metabolic stressors. However, there is considerable inter-individual variability. Most of the TLR genes respond to p53 via canonical as well as noncanonical promoter binding sites. Importantly, the integration of the TLR gene family into the p53 network is unique to primates, a recurrent theme raised for other gene families in our previous studies. Furthermore, a polymorphism in a TLR8 response element provides the first human example of a p53 target sequence specifically responsible for endogenous gene induction. These findings-demonstrating that the human innate immune system, including downstream induction of cytokines, can be modulated by DNA metabolic stress-have many implications for health and disease, as well as for understanding the evolution of damage and p53 responsive networks.

  15. Pulsating variables

    International Nuclear Information System (INIS)

    1989-01-01

    The study of stellar pulsations is a major route to the understanding of stellar structure and evolution. At the South African Astronomical Observatory (SAAO) the following stellar pulsation studies were undertaken: rapidly oscillating Ap stars; solar-like oscillations in stars; 8-Scuti type variability in a classical Am star; Beta Cephei variables; a pulsating white dwarf and its companion; RR Lyrae variables and galactic Cepheids. 4 figs

  16. Human-induced river runoff overlapping natural climate variability over the last 150 years: Palynological evidence (Bay of Brest, NW France)

    Science.gov (United States)

    Lambert, Clément; Penaud, Aurélie; Vidal, Muriel; Klouch, Khadidja; Gregoire, Gwendoline; Ehrhold, Axel; Eynaud, Frédérique; Schmidt, Sabine; Ragueneau, Olivier; Siano, Raffaele

    2018-01-01

    For the first time a very high resolution palynological study (mean resolution of 1 to 5 years) was carried out over the last 150 years in a French estuarine environment (Bay of Brest; NW France), allowing direct comparison between the evolution of landscapes, surface water, and human practices on Bay of Brest watersheds, through continental (especially pollen grains) and marine (phytoplanktonic microalgae: cysts of dinoflagellates or dinocysts) microfossils. Thanks to the small size of the watersheds and the close proximity of the depositional environment to the mainland, the Bay of Brest represents an ideal case study for palynological investigations. Palynological data were then compared to published palaeo-genetic analyses conducted on the same core and to various available instrumental data, allowing us to better characterize past environmental variability since the second half of the 19th century in Western Brittany. We provide evidence of some clues of recent eutrophication and/or pollution that affected phytoplankton communities and which appears linked with increased runoff (higher precipitations, higher percentages of riparian forest pollen, decline of salt marsh-type indicators, and higher values of the XRF Ti/Ca signal), mainly explained by the evolution of agricultural practices since 1945 superimposed on the warming climate trend. We assume that the significant relay observed between dinocyst taxa: Lingulodinium machaerophorum and Spiniferites bentorii around 1965 then followed by Spiniferites membranaceus after 1985, attests to a strong and recent eutrophication of Bay of Brest surface waters induced by high river runoff combined with abnormally elevated air temperatures, especially obvious in the data from 1990. The structure of the dinocyst community has thus been deeply altered, accompanied by an unprecedented increase of Alexandrium minutum toxic form at the same period, as confirmed by the genetic quantification. Despite this recent major

  17. Human mesenchymal stem cells cultured on silk hydrogels with variable stiffness and growth factor differentiate into mature smooth muscle cell phenotype.

    Science.gov (United States)

    Floren, Michael; Bonani, Walter; Dharmarajan, Anirudh; Motta, Antonella; Migliaresi, Claudio; Tan, Wei

    2016-02-01

    Cell-matrix and cell-biomolecule interactions play critical roles in a diversity of biological events including cell adhesion, growth, differentiation, and apoptosis. Evidence suggests that a concise crosstalk of these environmental factors may be required to direct stem cell differentiation toward matured cell type and function. However, the culmination of these complex interactions to direct stem cells into highly specific phenotypes in vitro is still widely unknown, particularly in the context of implantable biomaterials. In this study, we utilized tunable hydrogels based on a simple high pressure CO2 method and silk fibroin (SF) the structural protein of Bombyx mori silk fibers. Modification of SF protein starting water solution concentration results in hydrogels of variable stiffness while retaining key structural parameters such as matrix pore size and β-sheet crystallinity. To further resolve the complex crosstalk of chemical signals with matrix properties, we chose to investigate the role of 3D hydrogel stiffness and transforming growth factor (TGF-β1), with the aim of correlating the effects on the vascular commitment of human mesenchymal stem cells. Our data revealed the potential to upregulate matured vascular smooth muscle cell phenotype (myosin heavy chain expression) of hMSCs by employing appropriate matrix stiffness and growth factor (within 72h). Overall, our observations suggest that chemical and physical stimuli within the cellular microenvironment are tightly coupled systems involved in the fate decisions of hMSCs. The production of tunable scaffold materials that are biocompatible and further specialized to mimic tissue-specific niche environments will be of considerable value to future tissue engineering platforms. This article investigates the role of silk fibroin hydrogel stiffness and transforming growth factor (TGF-β1), with the aim of correlating the effects on the vascular commitment of human mesenchymal stem cells. Specifically, we

  18. Cognitive Variability

    Science.gov (United States)

    Siegler, Robert S.

    2007-01-01

    Children's thinking is highly variable at every level of analysis, from neural and associative levels to the level of strategies, theories, and other aspects of high-level cognition. This variability exists within people as well as between them; individual children often rely on different strategies or representations on closely related problems…

  19. Salivary Proteome Patterns Affecting Human Salt Taste Sensitivity.

    Science.gov (United States)

    Stolle, Theresa; Grondinger, Freya; Dunkel, Andreas; Meng, Chen; Médard, Guillaume; Kuster, Bernhard; Hofmann, Thomas

    2017-10-25

    To investigate the role of perireceptor events in inter-individual variability in salt taste sensitivity, 31 volunteers were monitored in their detection functions for sodium chloride (NaCl) and classified into sensitive (0.6-1.7 mmol/L), medium-sensitive (1.8-6.9 mmol/L), and nonsensitive (7.0-11.2 mmol/L) subjects. Chemosensory intervention of NaCl-sensitive (S + ) and nonsensitive (S - ) panellists with potassium chloride, ammonium chloride, and sodium gluconate showed the salt taste sensitivity to be specific for NaCl. As no significant differences were found between S + and S - subjects in salivary sodium and protein content, salivary proteome differences and their stimulus-induced dynamic changes were analyzed by tryptic digestion, iTRAQ labeling, and liquid chromatography-tandem mass spectrometry analysis. Differences in the salivary proteome between S + and S - subjects were found primarily in resting saliva and were largely independent of the dynamic alterations observed upon salt stimulation. Gene ontology enrichment analysis of key proteins, i.e., immunoglobulin heavy constant y1, myeloblastin, cathepsin G, and kallikrein, revealed significantly increased serine-type endopeptidase activity for the S + group, while the S - group exhibited augmented cysteine-type endopeptidase inhibitor activity by increased abundances in lipocalin-1 and cystatin-D, -S, and -SN, respectively. As proteases have been suggested to facilitate transepithelial sodium transport by cleaving the y-subunit of the epithelial sodium channel (ENaC) and protease inhibitors have been shown to reduce ENaC-mediated sodium transport, the differentially modulated proteolytic activity patterns observed in vivo for S + and S - subjects show evidence of them playing a crucial role in affecting human NaCl sensitivity.

  20. A method to evaluate the perceived ease of use of human-machine interface in agricultural tractors equipped with Continuously Variable Transmission (CVT

    Directory of Open Access Journals (Sweden)

    Federica Caffaro

    2018-02-01

    Full Text Available At the end of the 20th century the adoption of the Continuously Variable Transmission (CVT was one of the disruptive technological advances in agricultural tractors. Several changes in the Human Machine Interface (HMI of the tractor cab have been introduced to accommodate this technology. HMIs are known to raise issues about their ease of use; however, this topic has been under-investigated in the agricultural sector. The present study introduces a method to investigate the perceived ease of use of the HMI of agricultural tractors equipped with technological innovations. The HMI required to manage a CVT tractor was evaluated by sixteen tractor drivers (8 novices and 8 experts. During the first contact with the machine and after having performed two targeted tasks with the tractor, participants filled in a questionnaire about the ease of use of the controls and of the touch-screen display, and evaluated the general perception of ease of use, safety, quality and solidity of the machine. The trial pointed out some significant differences between novices and experts, thus confirming the validity of the proposed method. In particular, novice users showed some difficulties when interacting for the first time with the HMI of the CVT tractor working station, whereas experts did not report similar difficulties. Thus, expertise seems to play a role in determining the quality of the interaction with the HMI. Training interventions should be designed to help novices in increasing their expertise effectively, avoiding effort and errors and improving user’s comfort and system performance.

  1. Genetic variability of human respiratory syncytial virus A strains circulating in Ontario: a novel genotype with a 72 nucleotide G gene duplication.

    Directory of Open Access Journals (Sweden)

    Alireza Eshaghi

    Full Text Available Human respiratory syncytial virus (HRSV is the main cause of acute lower respiratory infections in children under 2 years of age and causes repeated infections throughout life. We investigated the genetic variability of RSV-A circulating in Ontario during 2010-2011 winter season by sequencing and phylogenetic analysis of the G glycoprotein gene.Among the 201 consecutive RSV isolates studied, RSV-A (55.7% was more commonly observed than RSV-B (42.3%. 59.8% and 90.1% of RSV-A infections were among children ≤12 months and ≤5 years old, respectively. On phylogenetic analysis of the second hypervariable region of the 112 RSV-A strains, 110 (98.2% clustered within or adjacent to the NA1 genotype; two isolates were GA5 genotype. Eleven (10% NA1-related isolates clustered together phylogenetically as a novel RSV-A genotype, named ON1, containing a 72 nucleotide duplication in the C-terminal region of the attachment (G glycoprotein. The predicted polypeptide is lengthened by 24 amino acids and includes a23 amino acid duplication. Using RNA secondary structural software, a possible mechanism of duplication occurrence was derived. The 23 amino acid ON1 G gene duplication results in a repeat of 7 potential O-glycosylation sites including three O-linked sugar acceptors at residues 270, 275, and 283. Using Phylogenetic Analysis by Maximum Likelihood analysis, a total of 19 positively selected sites were observed among Ontario NA1 isolates; six were found to be codons which reverted to the previous state observed in the prototype RSV-A2 strain. The tendency of codon regression in the G-ectodomain may infer a decreased avidity of antibody to the current circulating strains. Further work is needed to document and further understand the emergence, virulence, pathogenicity and transmissibility of this novel RSV-A genotype with a72 nucleotide G gene duplication.

  2. A review on architecture of the gag-pol ribosomal frameshifting RNA in human immunodeficiency virus: a variability survey of virus genotypes.

    Science.gov (United States)

    Qiao, Qi; Yan, Yanhua; Guo, Jinmei; Du, Shuqiang; Zhang, Jiangtao; Jia, Ruyue; Ren, Haimin; Qiao, Yuanbiao; Li, Qingshan

    2017-06-01

    Programmed '-1' ribosomal frameshifting is necessary for expressing the pol gene overlapped from a gag of human immunodeficiency virus. A viral RNA structure that requires base pairing across the overlapping sequence region suggests a mechanism of regulating ribosome and helicase traffic during expression. To get precise roles of an element around the frameshift site, a review on architecture of the frameshifting RNA is performed in combination of reported information with augments of a representative set of 19 viral samples. In spite of a different length for the viral RNAs, a canonical comparison on the element sequence allocation is performed for viewing variability associations between virus genotypes. Additionally, recent and historical insights recognized in frameshifting regulation are looked back as for indel and single nucleotide polymorphism of RNA. As specially noted, structural changes at a frameshift site, the spacer sequence, and a three-helix junction element, as well as two Watson-Crick base pairs near a bulge and a C-G pair close a loop, are the most vital strategies for the virus frameshifting regulations. All of structural changes, which are dependent upon specific sequence variations, facilitate an elucidation about the RNA element conformation-dependent mechanism for frameshifting. These facts on disrupting base pair interactions also allow solving the problem of competition between ribosome and helicase on a same RNA template, common to single-stranded RNA viruses. In a broad perspective, each new insight of frameshifting regulation in the competition systems introduced by the RNA element construct changes will offer a compelling target for antiviral therapy.

  3. Variability in EIT Images of Lung Ventilation as a Function of Electrode Planes and Body Positions.

    Science.gov (United States)

    Zhang, Jie; Patterson, Robert

    2014-01-01

    This study is aimed at investigating the variability in resistivity changes in the lung region as a function of air volume, electrode plane and body position. Six normal subjects (33.8 ± 4.7 years, range from 26 to 37 years) were studied using the Sheffield Electrical Impedance Tomography (EIT) portable system. Three transverse planes at the level of second intercostal space, the level of the xiphisternal joint, and midway between upper and lower locations were chosen for measurements. For each plane, sixteen electrodes were uniformly positioned around the thorax. Data were collected with the breath held at end expiration and after inspiring 0.5, 1.0, or 1.5 liters of air from end expiration, with the subject in both the supine and sitting position. The average resistivity change in five regions, two 8x8 pixel local regions in the right lung, entire right, entire left and total lung regions, were calculated. The results show the resistivity change averaged over electrode positions and subject positions was 7-9% per liter of air, with a slightly larger resistivity change of 10 % per liter air in the lower electrode plane. There was no significant difference (p>0.05) between supine and sitting. The two 8x8 regions show a larger inter individual variability (coefficient of variation, CV, is from 30% to 382%) compared to the entire left, entire right and total lung (CV is from 11% to 51%). The results for the global regions are more consistent. The large inter individual variability appears to be a problem for clinical applications of EIT, such as regional ventilation. The variability may be mitigated by choosing appropriate electrode plane, body position and region of interest for the analysis.

  4. Individual Movement Variability Magnitudes Are Explained by Cortical Neural Variability.

    Science.gov (United States)

    Haar, Shlomi; Donchin, Opher; Dinstein, Ilan

    2017-09-13

    Humans exhibit considerable motor variability even across trivial reaching movements. This variability can be separated into specific kinematic components such as extent and direction that are thought to be governed by distinct neural processes. Here, we report that individual subjects (males and females) exhibit different magnitudes of kinematic variability, which are consistent (within individual) across movements to different targets and regardless of which arm (right or left) was used to perform the movements. Simultaneous fMRI recordings revealed that the same subjects also exhibited different magnitudes of fMRI variability across movements in a variety of motor system areas. These fMRI variability magnitudes were also consistent across movements to different targets when performed with either arm. Cortical fMRI variability in the posterior-parietal cortex of individual subjects explained their movement-extent variability. This relationship was apparent only in posterior-parietal cortex and not in other motor system areas, thereby suggesting that individuals with more variable movement preparation exhibit larger kinematic variability. We therefore propose that neural and kinematic variability are reliable and interrelated individual characteristics that may predispose individual subjects to exhibit distinct motor capabilities. SIGNIFICANCE STATEMENT Neural activity and movement kinematics are remarkably variable. Although intertrial variability is rarely studied, here, we demonstrate that individual human subjects exhibit distinct magnitudes of neural and kinematic variability that are reproducible across movements to different targets and when performing these movements with either arm. Furthermore, when examining the relationship between cortical variability and movement variability, we find that cortical fMRI variability in parietal cortex of individual subjects explained their movement extent variability. This enabled us to explain why some subjects

  5. The Intersection of Environmental Variability, Policy, and Human Values: International Treaties, Yukon River Salmon, and Food Security in a Changing Arctic (Invited)

    Science.gov (United States)

    Gerlach, S.; Loring, P. A.; Murray, M. S.

    2009-12-01

    2009 was a particularly devastating year for rural communities of the Yukon River in Alaska. For a number of reasons, including annual variability in Chinook and Chum salmon runs, imperfect monitoring and information, “best practices” management decisions by regulatory agencies, and international treaty obligations related to conservation and total allowable catch allocation, the smokehouses and freezers of many Alaska Native families, particularly those in up-river communities in the Yukon Flats region, are empty; a problem that has prompted Alaska’s Governor Sean Parnell to ask the US Federal Government to declare a disaster. However, depending on whom you ask, this year’s management of these resources, which provide food security and enable self-reliance in rural communities, may be evaluated as a failure or as a success. How can we reconcile an institutional assessment that claims success as defined in terms of internationally-agreed upon conservation and escapement goals, with the negative economic and health impacts on communities? We use this case to illustrate how the whole Yukon River watershed and drainage, including Alaska and Canada, provides an elegant, geographic context for the discussion and analysis of the human dimensions of environmental change and regional sustainability. Policymakers have arguably gone to great lengths to reconcile competing ‘uses’ of the Yukon River, including commercial and subsistence uses as well as conservation goals, but while managers continue to strive to be ‘adaptive learners’ in their approach to balancing these goals, the impacts on rural communities are immediate and cumulative, synergistic, temporally and spatially scaled, and directly related to rural livelihoods, community health, well-being and sustainability. The cost of this ‘adaptive’ process may be too high, both for the ecosystem and for the people who live there. Are we asking too much of the Yukon River? Are we asking too much of the

  6. Vaccine induced antibodies to the first variable loop of human immunodeficiency virus type 1 gp120, mediate antibody-dependent virus inhibition in macaques.

    Science.gov (United States)

    Bialuk, Izabela; Whitney, Stephen; Andresen, Vibeke; Florese, Ruth H; Nacsa, Janos; Cecchinato, Valentina; Valeri, Valerio W; Heraud, Jean-Michel; Gordon, Shari; Parks, Robyn Washington; Montefiori, David C; Venzon, David; Demberg, Thorsten; Guroff, Marjorie Robert-; Landucci, Gary; Forthal, Donald N; Franchini, Genoveffa

    2011-12-09

    The role of antibodies directed against the hyper variable envelope region V1 of human immunodeficiency virus type 1 (HIV-1), has not been thoroughly studied. We show that a vaccine able to elicit strain-specific non-neutralizing antibodies to this region of gp120 is associated with control of highly pathogenic chimeric SHIV(89.6P) replication in rhesus macaques. The vaccinated animal that had the highest titers of antibodies to the amino terminus portion of V1, prior to challenge, had secondary antibody responses that mediated cell killing by antibody-dependent cellular cytotoxicity (ADCC), as early as 2 weeks after infection and inhibited viral replication by antibody-dependent cell-mediated virus inhibition (ADCVI), by 4 weeks after infection. There was a significant inverse correlation between virus level and binding antibody titers to the envelope protein, (R=-0.83, p=0.015), and ADCVI (R=-0.84 p=0.044). Genotyping of plasma virus demonstrated in vivo selection of three SHIV(89.6P) variants with changes in potential N-linked glycosylation sites in V1. We found a significant inverse correlation between virus levels and titers of antibodies that mediated ADCVI against all the identified V1 virus variants. A significant inverse correlation was also found between neutralizing antibody titers to SHIV(89.6) and virus levels (R=-0.72 p=0.0050). However, passive inoculation of purified immunoglobulin from animal M316, the macaque that best controlled virus, to a naïve macaque, resulted in a low serum neutralizing antibodies and low ADCVI activity that failed to protect from SHIV(89.6P) challenge. Collectively, while our data suggest that anti-envelope antibodies with neutralizing and non-neutralizing Fc(R-dependent activities may be important in the control of SHIV replication, they also demonstrate that low levels of these antibodies alone are not sufficient to protect from infection. Published by Elsevier Ltd.

  7. Reduced variability and execution time to reach a target with a needle GPS system: Comparison between physicians, residents and nurse anaesthetists.

    Science.gov (United States)

    Fevre, Marie-Cécile; Vincent, Caroline; Picard, Julien; Vighetti, Arnaud; Chapuis, Claire; Detavernier, Maxime; Allenet, Benoît; Payen, Jean-François; Bosson, Jean-Luc; Albaladejo, Pierre

    2018-02-01

    Ultrasound (US) guided needle positioning is safer than anatomical landmark techniques for central venous access. Hand-eye coordination and execution time depend on the professional's ability, previous training and personal skills. Needle guidance positioning systems (GPS) may theoretically reduce execution time and facilitate needle positioning in specific targets, thus improving patient comfort and safety. Three groups of healthcare professionals (41 anaesthesiologists and intensivists, 41 residents in anaesthesiology and intensive care, 39 nurse anaesthetists) were included and required to perform 3 tasks (positioning the tip of a needle in three different targets in a silicon phantom) by using successively a conventional US-guided needle positioning and a needle GPS. We measured execution times to perform the tasks, hand-eye coordination and the number of repositioning occurrences or errors in handling the needle or the probe. Without the GPS system, we observed a significant inter-individual difference for execution time (Pgaming were found to be independent factors associated with a shorter execution time. Use of GPS attenuated the inter-individual and group variability. We observed a reduced execution time and improved hand-eye coordination in all groups as compared to US without GPS. Neither US training, video gaming nor demographic personal or professional factors were found to be significantly associated with reduced execution time when GPS was used. US associated with GPS systems may improve safety and decrease execution time by reducing inter-individual variability between professionals for needle-handling procedures. Copyright © 2016 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

  8. Complex variables

    CERN Document Server

    Fisher, Stephen D

    1999-01-01

    The most important topics in the theory and application of complex variables receive a thorough, coherent treatment in this introductory text. Intended for undergraduates or graduate students in science, mathematics, and engineering, this volume features hundreds of solved examples, exercises, and applications designed to foster a complete understanding of complex variables as well as an appreciation of their mathematical beauty and elegance. Prerequisites are minimal; a three-semester course in calculus will suffice to prepare students for discussions of these topics: the complex plane, basic

  9. Use of multiple-locus variable-number of tandem repeats analysis (MLVA) to investigate genetic diversity of Salmonella enterica subsp. enterica serovar Typhimurium isolates from human, food, and veterinary sources

    DEFF Research Database (Denmark)

    Mateva, Gergana; Pedersen, Karl; Sørensen, Gitte

    2017-01-01

    -locus variable-number of tandem repeats analysis (MLVA) and compared results with antimicrobial resistance (AMR) determinations for 100 S. Typhimurium strains isolated in Bulgaria during 2008-2012 (50 veterinary/food and 50 human isolates). Results showed that isolates were divided into 80 and 34 groups using......). No clustering of isolates related to susceptibility/resistance to antimicrobials, source of isolation, or year of isolation was observed. Some MLVA types were found in both human and veterinary/food isolates, indicating a possible route of transmission. A majority (83%) of the isolates were found...

  10. Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

    Directory of Open Access Journals (Sweden)

    Claudia Mastroeni

    Full Text Available Repetitive transcranial magnetic stimulation (rTMS of the human motor hand area (M1HAND can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val(66met polymorphism in the brain-derived neurotrophic factor (BDNF gene. Here we used theta burst stimulation (TBS to examine whether the BDNF val(66met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS usually inducing a lasting increase and continuous TBS (cTBS a lasting decrease in corticospinal excitability. In three separate sessions, healthy val(66met (n = 12 and val(66val (n = 17 carriers received neuronavigated cTBS followed by cTBS (n = 27, cTBS followed by iTBS (n = 29, and iTBS followed by iTBS (n = 28. Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS and increase (iTBS in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val(66met carriers and val(66val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val(66met polymorphism, our results do not support the notion that the BDNF val(66met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.

  11. Brain-Derived Neurotrophic Factor – A Major Player in Stimulation-Induced Homeostatic Metaplasticity of Human Motor Cortex?

    Science.gov (United States)

    Rizzo, Vincenzo; Ritter, Christoph; Klein, Christine; Pohlmann, Ines; Brueggemann, Norbert; Quartarone, Angelo; Siebner, Hartwig Roman

    2013-01-01

    Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val66met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val66met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val66met (n = 12) and val66val (n = 17) carriers received neuronavigated cTBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val66met carriers and val66val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val66met polymorphism, our results do not support the notion that the BDNF val66met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND. PMID:23469118

  12. Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

    Science.gov (United States)

    Mastroeni, Claudia; Bergmann, Til Ole; Rizzo, Vincenzo; Ritter, Christoph; Klein, Christine; Pohlmann, Ines; Brueggemann, Norbert; Quartarone, Angelo; Siebner, Hartwig Roman

    2013-01-01

    Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val(66)met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val(66)met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val(66)met (n = 12) and val(66)val (n = 17) carriers received neuronavigated cTBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val(66)met carriers and val(66)val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val(66)met polymorphism, our results do not support the notion that the BDNF val(66)met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.

  13. Variable stars

    International Nuclear Information System (INIS)

    Feast, M.W.; Wenzel, W.; Fernie, J.D.; Percy, J.R.; Smak, J.; Gascoigne, S.C.B.; Grindley, J.E.; Lovell, B.; Sawyer Hogg, H.B.; Baker, N.; Fitch, W.S.; Rosino, L.; Gursky, H.

    1976-01-01

    A critical review of variable stars is presented. A fairly complete summary of major developments and discoveries during the period 1973-1975 is given. The broad developments and new trends are outlined. Essential problems for future research are identified. (B.R.H. )

  14. Habitual dietary fibre intake influences gut microbiota response to an inulin-type fructan prebiotic: a randomised, double-blind, placebo-controlled, cross-over, human intervention study.

    Science.gov (United States)

    Healey, Genelle; Murphy, Rinki; Butts, Christine; Brough, Louise; Whelan, Kevin; Coad, Jane

    2018-01-01

    Dysbiotic gut microbiota have been implicated in human disease. Diet-based therapeutic strategies have been used to manipulate the gut microbiota towards a more favourable profile. However, it has been demonstrated that large inter-individual variability exists in gut microbiota response to a dietary intervention. The primary objective of this study was to investigate whether habitually low dietary fibre (LDF) v. high dietary fibre (HDF) intakes influence gut microbiota response to an inulin-type fructan prebiotic. In this randomised, double-blind, placebo-controlled, cross-over study, thirty-four healthy participants were classified as LDF or HDF consumers. Gut microbiota composition (16S rRNA bacterial gene sequencing) and SCFA concentrations were assessed following 3 weeks of daily prebiotic supplementation (Orafti® Synergy 1; 16 g/d) or placebo (Glucidex® 29 Premium; 16 g/d), as well as after 3 weeks of the alternative intervention, following a 3-week washout period. In the LDF group, the prebiotic intervention led to an increase in Bifidobacterium (P=0·001). In the HDF group, the prebiotic intervention led to an increase in Bifidobacterium (Pgut microbiota response and are therefore more likely to benefit from an inulin-type fructan prebiotic than those with LDF intakes. Future studies aiming to modulate the gut microbiota and improve host health, using an inulin-type fructan prebiotic, should take habitual dietary fibre intake into account.

  15. Methodological principles for the evaluation of impact of the variability and the climatic change in the human health, a statistical focus

    International Nuclear Information System (INIS)

    Ortiz Bulto, Paulo Lazaro; Vladimir Guevara, Antonio; Ulloa, Jacqueline; Aparicio, Marilyn

    2001-01-01

    Signal detection of climate variability or change and the evaluation of its specific effects, requires an understanding of the variations in the observed data, which describe the natural climate variability and change signals. It is also necessary to understand the complex interactions that make up the climate system. In the present work, an unusual methodological approach is taken to evaluate the effects and impacts of climate variability and change on the behaviour of different diseases, on the basis of practical experience of its application in four countries of the Caribbean, Central and South America: Cuba, Panama, Bolivia and Paraguay. For the determination of the climate signal change multivariate analysis techniques (empirical orthogonal functions) were used, combined with robust methods of time series decomposition (decomposition by median). They allowed us to describe the changes observed in the seasonal patterns of climate and epidemiological diseases for the period 1991-1999, with respect to the period 1961-1990. These results were used to build an autoregressive model with non-constant variance, with a climate index based on the signals obtained from the decompositions, which enters the model as an exogenous variable in order to make projections of the diseases

  16. Assessment of Human Ambulatory Speed by Measuring Near-Body Air Flow

    Directory of Open Access Journals (Sweden)

    Stefano Salati

    2010-09-01

    Full Text Available Accurate measurements of physical activity are important for the diagnosis of the exacerbation of chronic diseases. Accelerometers have been widely employed in clinical research for measuring activity intensity and investigating the association between physical activity and adverse health conditions. However, the ability of accelerometers in assessing physical activity intensity such as walking speed has been constrained by the inter-individual variability in sensor output and by the necessity of developing unobtrusive low-power monitoring systems. This paper will present a study aimed at investigating the accuracy of a wearable measuring system of near-body air flow to determine ambulatory speed in the field.

  17. Soil variability in mountain areas

    OpenAIRE

    Zanini, E.; Freppaz, M.; Stanchi, S.; Bonifacio, E.; Egli, M.

    2015-01-01

    The high spatial variability of soils is a relevant issue at local and global scales, and determines the complexity of soil ecosystem functions and services. This variability derives from strong dependencies of soil ecosystems on parent materials, climate, relief and biosphere, including human impact. Although present in all environments, the interactions of soils with these forming factors are particularly striking in mountain areas.

  18. Assessing human variability in kinetics for exposures to multiple environmental chemicals: a physiologically based pharmacokinetic modeling case study with dichloromethane, benzene, toluene, ethylbenzene, and m-xylene.

    Science.gov (United States)

    Valcke, Mathieu; Haddad, Sami

    2015-01-01

    The objective of this study was to compare the magnitude of interindividual variability in internal dose for inhalation exposure to single versus multiple chemicals. Physiologically based pharmacokinetic models for adults (AD), neonates (NEO), toddlers (TODD), and pregnant women (PW) were used to simulate inhalation exposure to "low" (RfC-like) or "high" (AEGL-like) air concentrations of benzene (Bz) or dichloromethane (DCM), along with various levels of toluene alone or toluene with ethylbenzene and xylene. Monte Carlo simulations were performed and distributions of relevant internal dose metrics of either Bz or DCM were computed. Area under the blood concentration of parent compound versus time curve (AUC)-based variability in AD, TODD, and PW rose for Bz when concomitant "low" exposure to mixtures of increasing complexities occurred (coefficient of variation (CV) = 16-24%, vs. 12-15% for Bz alone), but remained unchanged considering DCM. Conversely, AUC-based CV in NEO fell (15 to 5% for Bz; 12 to 6% for DCM). Comparable trends were observed considering production of metabolites (AMET), except for NEO's CYP2E1-mediated metabolites of Bz, where an increased CV was observed (20 to 71%). For "high" exposure scenarios, Cmax-based variability of Bz and DCM remained unchanged in AD and PW, but decreased in NEO (CV= 11-16% to 2-6%) and TODD (CV= 12-13% to 7-9%). Conversely, AMET-based variability for both substrates rose in every subpopulation. This study analyzed for the first time the impact of multiple exposures on interindividual variability in toxicokinetics. Evidence indicates that this impact depends upon chemical concentrations and biochemical properties, as well as the subpopulation and internal dose metrics considered.

  19. Complex variables

    CERN Document Server

    Flanigan, Francis J

    2010-01-01

    A caution to mathematics professors: Complex Variables does not follow conventional outlines of course material. One reviewer noting its originality wrote: ""A standard text is often preferred [to a superior text like this] because the professor knows the order of topics and the problems, and doesn't really have to pay attention to the text. He can go to class without preparation."" Not so here-Dr. Flanigan treats this most important field of contemporary mathematics in a most unusual way. While all the material for an advanced undergraduate or first-year graduate course is covered, discussion

  20. Characterizing uncertainty and population variability in the toxicokinetics of trichloroethylene and metabolites in mice, rats, and humans using an updated database, physiologically based pharmacokinetic (PBPK) model, and Bayesian approach

    International Nuclear Information System (INIS)

    Chiu, Weihsueh A.; Okino, Miles S.; Evans, Marina V.

    2009-01-01

    We have developed a comprehensive, Bayesian, PBPK model-based analysis of the population toxicokinetics of trichloroethylene (TCE) and its metabolites in mice, rats, and humans, considering a wider range of physiological, chemical, in vitro, and in vivo data than any previously published analysis of TCE. The toxicokinetics of the 'population average,' its population variability, and their uncertainties are characterized in an approach that strives to be maximally transparent and objective. Estimates of experimental variability and uncertainty were also included in this analysis. The experimental database was expanded to include virtually all available in vivo toxicokinetic data, which permitted, in rats and humans, the specification of separate datasets for model calibration and evaluation. The total combination of these approaches and PBPK analysis provides substantial support for the model predictions. In addition, we feel confident that the approach employed also yields an accurate characterization of the uncertainty in metabolic pathways for which available data were sparse or relatively indirect, such as GSH conjugation and respiratory tract metabolism. Key conclusions from the model predictions include the following: (1) as expected, TCE is substantially metabolized, primarily by oxidation at doses below saturation; (2) GSH conjugation and subsequent bioactivation in humans appear to be 10- to 100-fold greater than previously estimated; and (3) mice had the greatest rate of respiratory tract oxidative metabolism as compared to rats and humans. In a situation such as TCE in which there is large database of studies coupled with complex toxicokinetics, the Bayesian approach provides a systematic method of simultaneously estimating model parameters and characterizing their uncertainty and variability. However, care needs to be taken in its implementation to ensure biological consistency, transparency, and objectivity.

  1. The variability of translocator protein signal in brain and blood of genotyped healthy humans using in vivo 123I-CLINDE SPECT imaging

    DEFF Research Database (Denmark)

    Feng, Ling; Jensen, Per; Thomsen, Gerda

    2017-01-01

    123I-CLINDE is a radiotracer developed for SPECT and targets the 18-kDa translocator protein (TSPO). TSPO is upregulated in glial cells and used as a measure of neuroinflammation in a variety of central nervous system diseases. The aim of this study was to examine the test-retest variability of 123...... subjects and a population-based approach in combination with individual whole-blood time-activity curves in the other 8 subjects. Seven brain volumes of interest were extracted and quantified by SUVs and by 2-tissue-compartment modeling for calculation of distribution volumes (VT). Test-retest variability...... was measured by percentage difference (PD), the absolute PD, intraclass correlation coefficient (ICC), and coefficient of variation. Results: The absolute PD of brain SUV and the VT had similar values. The ICC values were higher for VTs than for brain SUVs, which were both moderate to high; however, lower ICC...

  2. Classic and Golli Myelin Basic Protein have distinct developmental trajectories in human visual cortex.

    Science.gov (United States)

    Siu, Caitlin R; Balsor, Justin L; Jones, David G; Murphy, Kathryn M

    2015-01-01

    Traditionally, myelin is viewed as insulation around axons, however, more recent studies have shown it also plays an important role in plasticity, axonal metabolism, and neuroimmune signaling. Myelin is a complex multi-protein structure composed of hundreds of proteins, with Myelin Basic Protein (MBP) being the most studied. MBP has two families: Classic-MBP that is necessary for activity driven compaction of myelin around axons, and Golli-MBP that is found in neurons, oligodendrocytes, and T-cells. Furthermore, Golli-MBP has been called a "molecular link" between the nervous and immune systems. In visual cortex specifically, myelin proteins interact with immune processes to affect experience-dependent plasticity. We studied myelin in human visual cortex using Western blotting to quantify Classic- and Golli-MBP expression in post-mortem tissue samples ranging in age from 20 days to 80 years. We found that Classic- and Golli-MBP have different patterns of change across the lifespan. Classic-MBP gradually increases to 42 years and then declines into aging. Golli-MBP has early developmental changes that are coincident with milestones in visual system sensitive period, and gradually increases into aging. There are three stages in the balance between Classic- and Golli-MBP expression, with Golli-MBP dominating early, then shifting to Classic-MBP, and back to Golli-MBP in aging. Also Golli-MBP has a wave of high inter-individual variability during childhood. These results about cortical MBP expression are timely because they compliment recent advances in MRI techniques that produce high resolution maps of cortical myelin in normal and diseased brain. In addition, the unique pattern of Golli-MBP expression across the lifespan suggests that it supports high levels of neuroimmune interaction in cortical development and in aging.

  3. Co-encapsulation of human serum albumin and superparamagnetic iron oxide in PLGA nanoparticles: Part II. Effect of process variables on protein model drug encapsulation efficiency

    Czech Academy of Sciences Publication Activity Database

    Shubhra, Q. T. H.; Feczkó, T.; Kardos, A. F.; Tóth, J.; Macková, Hana; Horák, Daniel; Dósa, G.; Gyenis, J.

    2014-01-01

    Roč. 31, č. 2 (2014), s. 156-165 ISSN 0265-2048 R&D Projects: GA AV ČR(CZ) KAN401220801 Institutional support: RVO:61389013 Keywords : encapsulation efficiency * experimental design * human serum albumin Subject RIV: JB - Sensors, Measurment, Regulation Impact factor: 1.585, year: 2014

  4. Spherical aberration and other higher-order aberrations in the human eye : from summary wave-front analysis data to optical variables relevant to visual perception

    NARCIS (Netherlands)

    Jansonius, Nomdo M.

    Wave-front analysis data from the human eye are commonly presented using the aberration coefficient c(4)(0) (primary spherical aberration) together with an overall measure of all higher-order aberrations. If groups of subjects are compared, however, the relevance of an observed difference cannot

  5. Quantification, Variability, and Reproducibility of Basal Skeletal Muscle Glucose Uptake in Healthy Humans Using 18F-FDG PET/CT.

    Science.gov (United States)

    Gheysens, Olivier; Postnov, Andrey; Deroose, Christophe M; Vandermeulen, Corinne; de Hoon, Jan; Declercq, Ruben; Dennie, Justin; Mixson, Lori; De Lepeleire, Inge; Van Laere, Koen; Klimas, Michael; Chakravarthy, Manu V

    2015-10-01

    The quantification and variability of skeletal muscle glucose utilization (SMGU) in healthy subjects under basal (low insulin) conditions are poorly known. This information is essential early in clinical drug development to effectively interrogate novel pharmacologic interventions that modulate glucose uptake. The aim of this study was to determine test-retest characteristics and variability of SMGU within and between healthy subjects under basal conditions. Furthermore, different kinetic modeling strategies were evaluated to find the best-fitting model to assess SMGU studied by 18F-FDG. Six healthy male volunteers underwent 2 dynamic 18F-FDG PET/CT scans with an interval of 24 h. Subjects were admitted to the clinical unit to minimize variability in daily activities and food intake and restrict physical activity. 18F-FDG PET/CT scans of gluteal and quadriceps muscle area were obtained with arterial input. Regions of interest were drawn over the muscle area to obtain time-activity curves and standardized uptake values (SUVs) between 60 and 90 min. Spectral analysis of the data and kinetic modeling was performed using 2-tissue-irreversible (2T3K), 2-tissue-reversible, and 3-tissue-sequential-irreversible (3T5KS) models. Reproducibility was assessed by intraclass correlation coefficients (ICCs) and within-subject coefficient of variation (WSCV). SUVs in gluteal and quadriceps areas were 0.56±0.09 and 0.64±0.07. ICCs (with 90% confidence intervals in parentheses) were 0.88 (0.64-0.96) and 0.96 (0.82-0.99), respectively, for gluteal and quadriceps muscles, and WSCV for gluteal and quadriceps muscles was 2.2% and 3.6%, respectively. The rate of glucose uptake into muscle was 0.0016±0.0004 mL/mL⋅min, with an ICC of 0.94 (0.93-0.95) and WSCV of 6.6% for the 3T5KS model, whereas an ICC of 0.98 (0.92-1.00) and WSCV of 2.8% was obtained for the 2T3K model. 3T5KS demonstrated the best fit to the measured experimental points. Minimal variability in skeletal muscle glucose

  6. Intra and Inter-Individual Differences in Social Intelligence of Portuguese Students

    Directory of Open Access Journals (Sweden)

    Joana Carneiro Pinto

    2015-08-01

    Full Text Available Social intelligence is a favorable condition for career decision-making and development. The social intelligence indices of Portuguese students in school years prior to a career transition are characterized and intra and interindividual differences are analyzed. Participants were 1095 students (552, 50.4% women with a mean age of 14.78 years (SD = 1.86, in the 8th (542, 49.5%, 10th (295, 26.9% and 11th (258, 23.6% grades. The Cognitive Test of Social Intelligence (PCIS was administered at two moments, six months apart. Results indicate that the 8th grade obtained higher average scores in Problem Solving, Motivation and Self-confidence (time 1, while the 10th grade obtained better results in Problem Solving, Motivation and Familiarity (time 2. Between the assessment moments, all school years register an increase in Problem Solving and Self-confidence in social situations. These results constitute favorable psychological conditions for the promotion of ethical questioning in career guidance interventions.

  7. Behavioural plasticity across social contexts is regulated by the directionality of inter-individual differences.

    Science.gov (United States)

    Guayasamin, Olivia L; Couzin, Iain D; Miller, Noam Y

    2017-08-01

    An individual's behavioural phenotype is a combination of its unique behavioural propensities and its responsiveness to environmental variation, also known as behavioural plasticity. In social species, we must not only explore how individuals respond to variations in the physical environment but also how they react to changes in their social environment. A growing body of work has demonstrated that the behavioural heterogeneity of a group can alter its responsiveness, decision making, and fitness. Whether an individual is more or less extreme than a partner - what we term its 'relative personality' - may also alter individual behavioural responses. We determined exploratory tendencies of individual zebrafish (Danio rerio) and then constructed pairs with varying differences in 'relative personality' to determine the effect of differences between partners on behavioural plasticity. We find that relative personality, but not the magnitude of the difference between partners, is the most important determinant of behavioural plasticity across social treatments. Despite this overall effect, pairs of fish exhibited no predictable leader-follower interactions, suggesting that details of the experimental paradigm may be important in shaping social dynamics. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Partial diel migration: A facultative migration underpinned by long-term inter-individual variation.

    Science.gov (United States)

    Harrison, Philip M; Gutowsky, Lee F G; Martins, Eduardo G; Patterson, David A; Cooke, Steven J; Power, Michael

    2017-09-01

    The variations in migration that comprise partial diel migrations, putatively occur entirely as a consequence of behavioural flexibility. However, seasonal partial migrations are increasingly recognised to be mediated by a combination of reversible plasticity in response to environmental variation and individual variation due to genetic and environmental effects. Here, we test the hypothesis that while partial diel migration heterogeneity occurs primarily due to short-term within-individual flexibility in behaviour, long-term individual differences in migratory behaviour also underpin this migration variation. Specifically, we use a hierarchical behavioural reaction norm approach to partition within- and among-individual variation in depth use and diel plasticity in depth use, across short- and long-term time-scales, in a group of 47 burbot (Lota lota) tagged with depth-sensing acoustic telemetry transmitters. We found that within-individual variation at the among-dates-within-seasons and among-seasons scale, explained the dominant proportion of phenotypic variation. However, individuals also repeatedly differed in their expression of migration behaviour over the 2 year study duration. These results reveal that diel migration variation occurs primarily due to short-term within-individual flexibility in depth use and diel migration behaviour. However, repeatable individual differences also played a key role in mediating partial diel migration. These findings represent a significant advancement of our understanding of the mechanisms generating the important, yet poorly understood phenomena of partial diel migration. Moreover, given the pervasive occurrence of diel migrations across aquatic taxa, these findings indicate that individual differences have an important, yet previously unacknowledged role in structuring the temporal and vertical dynamics of aquatic ecosystems. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

  9. Inter-individual inequality in BMI: An analysis of Indonesian Family Life Surveys (1993–2007

    Directory of Open Access Journals (Sweden)

    Masoud Vaezghasemi

    2016-12-01

    Full Text Available Widening inequalities in mean Body Mass Index (BMI between social and economic groups are well documented. However, whether changes in mean BMI are followed by changes in dispersion (or variance and whether these inequalities are also occurring within social groups or across individuals remain understudied. In addition, a substantial body of literature exists on the global increase in mean BMI and prevalence of overweight and obesity. However, whether this weight gain is shared proportionately across the whole spectrum of BMI distribution, also remains understudied. We examined changes in the distribution of BMI at the population level over time to understand how changes in the dispersion reflect between-group compared to within-group inequalities in weight gain. Moreover, we investigated the entire distribution of BMI to determine in which percentiles the most weight gain is occurring over time. Utilizing four waves (from 1993 to 2007 of Indonesian Family Life Surveys (IFLS, we estimated changes in the mean and the variance of BMI over time and across various socioeconomic groups based on education and households’ expenditure per capita in 53,648 men and women aged 20–50 years. An increase in mean and standard deviation was observed among men (by 4.3% and 25%, respectively and women (by 7.3% and 20%, respectively over time. Quantile-Quantile plots showed that higher percentiles had greater increases in BMI compared to the segment of the population at lower percentiles. While between socioeconomic group differences decreased over time, within-group differences increased and were more prominent among individuals with poor education and lower per capita expenditures. Population changes in BMI cannot be fully described by average trends or single parameters such as the mean BMI. Moreover, greater increases in within-group dispersion compared with between-group differences imply that growing inequalities are not merely driven by these socioeconomic factors at the population level. Keywords: Body mass index, Distributional change, Health inequalities, Obesity, Socioeconomic status, Indonesian Family Life Survey

  10. Landscaping: teamwork and integration into inter-individual coordination as a learning situation.

    Science.gov (United States)

    Mayen, Patrick; Olry, Paul

    2012-01-01

    One of the dimensions of work that is not well known in training is teamwork and the work of the team leader. The team leader is the personne who provides local supervision. Teachers and trainers, as well as business employers aknowledge the place and importance of teamwork and the role of the team leader. However, most consider themselves, insufficiently prepared to offer training in line with these elements. This paper thus aims to present the results of an analysis of group work in the field of landscaping conducted from the perspective of team work and team leader learning and training.

  11. The Impact of Disappointment in Decision Making: Inter-Individual Differences and Electrical Neuroimaging

    Science.gov (United States)

    Tzieropoulos, Hélène; de Peralta, Rolando Grave; Bossaerts, Peter; Andino, Sara L. Gonzalez

    2011-01-01

    Disappointment, the emotion experienced when faced to reward prediction errors (RPEs), considerably impacts decision making (DM). Individuals tend to modify their behavior in an often unpredictable way just to avoid experiencing negative emotions. Despite its importance, disappointment remains much less studied than regret and its impact on upcoming decisions largely unexplored. Here, we adapted the Trust Game to effectively elicit, quantify, and isolate disappointment by relying on the formal definition provided by Bell's in economics. We evaluated the effects of experienced disappointment and elation on future cooperation and trust as well as the rationality and utility of the different behavioral and neural mechanisms used to cope with disappointment. All participants in our game trusted less and particularly expected less from unknown opponents as a result of disappointing outcomes in the previous trial but not necessarily after elation indicating that behavioral consequences of positive and negative RPEs are not the same. A large variance in the tolerance to disappointment was observed across subjects, with some participants needing only a small disappointment to impulsively bias their subsequent decisions. As revealed by high-density EEG recordings the most tolerant individuals – who thought twice before making a decision and earned more money – relied on different neural generators to contend with neutral and unexpected outcomes. This study thus provides some support to the idea that different neural systems underlie reflexive and reflective decisions within the same individuals as predicted by the dual-system theory of social judgment and DM. PMID:21258645

  12. The impact of disappointment in decision making: Inter-individual differences and electrical neuroimaging

    Directory of Open Access Journals (Sweden)

    Helène eTzieropoulos

    2011-01-01

    Full Text Available Disappointment, the emotion experienced when faced to reward prediction errors, considerably impact decision making. Individuals tend to modify their behavior in an often unpredictable way just to avoid experiencing negative emotions. Despite its importance, disappointment remains much less studied than regret and its impact on upcoming decisions largely unexplored. Here, we adapted the Trust Game to effectively elicit, quantify and isolate disappointment by relying on the formal definition provided by Bell’s in economics. We evaluated the effects of experienced disappointment and elation on future cooperation and trust as well as the rationality and utility of the different behavioral and neural mechanisms used to cope with disappointment. All participants in our game trusted less and particularly expected less from unknown opponents as a result of disappointing outcomes in the previous trial but not necessarily after elation indicating that behavioral consequences of positive and negative reward prediction errors are not the same. A large variance in the tolerance to disappointment was observed across subjects, with some participants needing only a small disappointment to impulsively bias their subsequent decisions. As revealed by high-density EEG recordings the most tolerant individuals - who thought twice before making a decision and earned more money – relied on different neural generators to contend with neutral and unexpected outcomes. This study thus provide some support to the idea that different neural systems underlie reflexive and reflective decisions within the same individuals as predicted by the dual-system theory of social judgment and decision making.

  13. The impact of disappointment in decision making: inter-individual differences and electrical neuroimaging.

    Science.gov (United States)

    Tzieropoulos, Hélène; de Peralta, Rolando Grave; Bossaerts, Peter; Gonzalez Andino, Sara L

    2011-01-01

    Disappointment, the emotion experienced when faced to reward prediction errors (RPEs), considerably impacts decision making (DM). Individuals tend to modify their behavior in an often unpredictable way just to avoid experiencing negative emotions. Despite its importance, disappointment remains much less studied than regret and its impact on upcoming decisions largely unexplored. Here, we adapted the Trust Game to effectively elicit, quantify, and isolate disappointment by relying on the formal definition provided by Bell's in economics. We evaluated the effects of experienced disappointment and elation on future cooperation and trust as well as the rationality and utility of the different behavioral and neural mechanisms used to cope with disappointment. All participants in our game trusted less and particularly expected less from unknown opponents as a result of disappointing outcomes in the previous trial but not necessarily after elation indicating that behavioral consequences of positive and negative RPEs are not the same. A large variance in the tolerance to disappointment was observed across subjects, with some participants needing only a small disappointment to impulsively bias their subsequent decisions. As revealed by high-density EEG recordings the most tolerant individuals - who thought twice before making a decision and earned more money - relied on different neural generators to contend with neutral and unexpected outcomes. This study thus provides some support to the idea that different neural systems underlie reflexive and reflective decisions within the same individuals as predicted by the dual-system theory of social judgment and DM.

  14. Dose optimization of gadolinium DTPA. An inter-individual study of patients with intracranial tumours

    International Nuclear Information System (INIS)

    Schubeus, P.; Schoerner, W.; Haustein, J.; Hosten, N.; Niendorf, H.P.; Felix, R.; Schering AG, Berlin

    1990-01-01

    The diagnostic value of various doses of Gd-DTPA was compared intraindividually. Thirty-three patients with cerebral tumours were randomly allocated to three groups. Group 1 was given a dose of 0.025, group 2 a dose of 0.05 and group 3 a dose of 0.1 mmol GD-DTPA/kg body weight. Following administration of Gd-DTPA the average tumor/brain contrast in group 1 was -4.5%, in group 2 +8.4% and in group 3 +43.0%. Diagnostically useful tumour delineation was obtained in two out of 11 in group 1, in seven out of 11 in group 2 and in 10 out of 11 in group 3. A further increase in the dose to 0.2 mmol/kg body weight in group 3 resulted in a further increase in tumour/brain contrast of +62.5% and improved tumour deliniation in one case. As a result of these findings a dose of 0.1 mmol Gd-DTPA/kg body weight is reommended for the routine investigation of intracranial tumours. (orig.) [de

  15. Case fatality as an indicator for the human toxicity of pesticides - a systematic review on the availability and variability of severity indicators of pesticide poisoning

    OpenAIRE

    Moebus, Susanne; Boedeker, Wolfgang

    2017-01-01

    Objective: To investigate if case fatality and other indicators of severity of human pesticide poisonings can be used to prioritize pesticides of public health concern. To study the heterogeneity of data across countries, cause of poisonings, and treatment facilities. Methods: We searched literature databases as well as the internet for studies on case-fatality and severity scores of pesticide poisoning. Studies published between 1990 and 2014 providing information on active ingredients in pe...

  16. Spontaneous flocking in human groups.

    Science.gov (United States)

    Belz, Michael; Pyritz, Lennart W; Boos, Margarete

    2013-01-01

    Flocking behaviour, as a type of self-organised collective behaviour, is described as the spatial formation of groups without global control and explicit inter-individual recruitment signals. It can be observed in many animals, such as bird flocks, shoals or herds of ungulates. Spatial attraction between humans as the central component of flocking behaviour has been simulated in a number of seminal models but it has not been detected experimentally in human groups so far. The two other sub-processes of this self-organised collective movement - collision avoidance and alignment - are excluded or held constant respectively in this study. We created a computer-based, multi-agent game where human players, represented as black dots, moved on a virtual playground. The participants were deprived of social cues about each other and could neither communicate verbally nor nonverbally. They played two games: (1) Single Game, where other players were invisible, and (2) Joint Game, where each player could see players' positions in a local radius around himself/herself. We found that individuals approached their neighbours spontaneously if their positions were visible, leading to less spatial dispersion of the whole group compared to moving alone. We conclude that human groups show the basic component of flocking behaviour without being explicitly instructed or rewarded to do so. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Inter-subject variability modulates phonological advance planning in the production of adjective-noun phrases.

    Science.gov (United States)

    Michel Lange, Violaine; Laganaro, Marina

    2014-01-01

    The literature on advance phonological planning in adjective-noun phrases (NPs) presents diverging results: while many experimental studies suggest that the entire NP is encoded before articulation, other results favor a span of encoding limited to the first word. Although cross-linguistic differences in the structure of adjective-NPs may account for some of these contrasting results, divergences have been reported even among similar languages and syntactic structures. Here we examined whether inter-individual differences account for variability in the span of phonological planning in the production of French NPs, where previous results indicated encoding limited to the first word. The span of phonological encoding is tested with the picture-word interference (PWI) paradigm using phonological distractors related to the noun or to the adjective of the NPs. In Experiment 1, phonological priming effects were limited to the first word in adjective NPs whichever the position of the adjective (pre-nominal or post-nominal). Crucially, phonological priming effects on the second word interacted with speakers' production speed suggesting different encoding strategies for participants. In Experiment 2, we tested this hypothesis further with a larger group of participants. Results clearly showed that slow and fast initializing participants presented different phonological priming patterns on the last element of adjective-NPs: while the first word was primed by a distractor for all speakers, only the slow speaker group presented a priming effect on the second element of the NP. These results show that the span of phonological encoding is modulated by inter-individual strategies: in experimental paradigms some speakers plan word by word whereas others encode beyond the initial word. We suggest that the diverging results reported in the literature on advance phonological planning may partly be reconciled in light of the present results.

  18. Variable collimator

    International Nuclear Information System (INIS)

    Richey, J.B.; McBride, T.R.; Covic, J.

    1979-01-01

    This invention describes an automatic variable collimator which controls the width and thickness of X-ray beams in X-ray diagnostic medical equipment, and which is particularly adapted for use with computerized axial tomographic scanners. A two-part collimator is provided which shapes an X-ray beam both prior to its entering an object subject to radiographic analysis and after the attenuated beam has passed through the object. Interposed between a source of radiation and the object subject to radiographic analysis is a first or source collimator. The source collimator causes the X-ray beam emitted by the source of radiation to be split into a plurality of generally rectangular shaped beams. Disposed within the source collimator is a movable aperture plate which may be used to selectively vary the thickness of the plurality of generally rectangular shaped beams transmitted through the source collimator. A second or receiver collimator is interposed between the object subject to radiographic analysis and a series of radiation detectors. The receiver collimator is disposed to receive the attenuated X-ray beams passing through the object subject to radiographic analysis. Located within the receiver collimator are a plurality of movable aperture plates adapted to be displaced relative to a plurality of fixed aperture plates for the purpose of varying the width and thickness of the attenuated X-ray beams transmitted through the object subject to radiographic analysis. The movable aperture plates of the source and receiver collimators are automatically controlled by circuitry which is provided to allow remote operation of the movable aperture plates

  19. Effect of partial and complete variable loop deletions of the human immunodeficiency virus type 1 envelope glycoprotein on the breadth of gp160-specific immune responses

    International Nuclear Information System (INIS)

    Gzyl, Jaroslaw; Bolesta, Elizabeth; Wierzbicki, Andrew; Kmieciak, Dariusz; Naito, Toshio; Honda, Mitsuo; Komuro, Katsutoshi; Kaneko, Yutaro; Kozbor, Danuta

    2004-01-01

    Induction of cross-reactive cellular and humoral responses to the HIV-1 envelope (env) glycoprotein was examined after DNA immunization of BALB/c mice with gp140 89.6 -derived constructs exhibiting partial or complete deletions of the V1, V2, and V3 domains. It was demonstrated that specific modification of the V3 loop (mV3) in combination with the V2-modified (mV2) or V1/V2-deleted (ΔV1/V2) region elicited increased levels of cross-reactive CD8 + T cell responses. Mice immunized with the mV2/mV3 or ΔV1/V2/mV3 gp140 89.6 plasmid DNA were greater than 50-fold more resistant to challenge with recombinant vaccinia virus (rVV) expressing heterologous env gene products than animals immunized with the wild-type (WT) counterpart. Sera from mV2/mV3- and ΔV1/V2/mV3-immunized mice exhibited the highest cross-neutralizing activity and displayed intermediate antibody avidity values which were further enhanced by challenge with rVV expressing the homologous gp160 glycoprotein. In contrast, complete deletion of the variable regions had little or no effect on the cross-reactive antibody responses. The results of these experiments indicate that the breadth of antibody responses to the HIV-1 env glycoprotein may not be increased by removal of the variable domains. Instead, partial deletions within these regions may redirect specific responses toward conserved epitopes and facilitate approaches for boosting cross-reactive cellular and antibody responses to the env glycoprotein

  20. A review on environmental factors regulating arsenic methylation in humans

    International Nuclear Information System (INIS)

    Tseng, C.-H.

    2009-01-01

    Subjects exposed to arsenic show significant inter-individual variation in urinary patterns of arsenic metabolites but insignificant day-to-day intra-individual variation. The inter-individual variation in arsenic methylation can be partly responsible for the variation in susceptibility to arsenic toxicity. Wide inter-ethnic variation and family correlation in urinary arsenic profile suggest a genetic effect on arsenic metabolism. In this paper the environmental factors affecting arsenic metabolism are reviewed. Methylation capacity might reduce with increasing dosage of arsenic exposure. Furthermore, women, especially at pregnancy, have better methylation capacity than their men counterparts, probably due to the effect of estrogen. Children might have better methylation capacity than adults and age shows inconsistent relevance in adults. Smoking and alcohol consumption might be associated with a poorer methylation capacity. Nutritional status is important in the methylation capacity and folate may facilitate the methylation and excretion of arsenic. Besides, general health conditions and medications might influence the arsenic methylation capacity; and technical problems can cause biased estimates. The consumption of seafood, seaweed, rice and other food with high arsenic contents and the extent of cooking and arsenic-containing water used in food preparation may also interfere with the presentation of the urinary arsenic profile. Future studies are necessary to clarify the effects of the various arsenic metabolites including the trivalent methylated forms on the development of arsenic-induced human diseases with the consideration of the effects of confounding factors and the interactions with other effect modifiers

  1. Phenotype-genotype variability in the human CYP3A locus as assessed by the probe drug quinine and analyses of variant CYP3A4 alleles

    International Nuclear Information System (INIS)

    Rodriguez-Antona, Cristina; Sayi, Jane G.; Gustafsson, Lars L.; Bertilsson, Leif; Ingelman-Sundberg, Magnus

    2005-01-01

    The human cytochrome P450 3A (CYP3A) enzymes, which metabolize 50% of currently used therapeutic drugs, exhibit great interindividual differences in activity that have a major impact on drug treatment outcome, but hitherto no genetic background importantly contributing to this variation has been identified. In this study we show that CYP3A4 mRNA and hnRNA contents with a few exceptions vary in parallel in human liver, suggesting that mechanisms affecting CYP3A4 transcription, such as promoter polymorphisms, are relevant for interindividual differences in CYP3A4 expression. Tanzanian (n = 143) healthy volunteers were phenotyped using quinine as a CYP3A probe and the results were used for association studies with CYP3A4 genotypes. Carriers of CYP3A4*1B had a significantly lower activity than those with CYP3A4*1 whereas no differences were seen for five other SNPs investigated. Nuclear proteins from the B16A2 hepatoma cells were found to bind with less affinity to the CYP3A4*1B element around -392 bp as compared to CYP3A4*1. The data indicate the existence of a genetic CYP3A4 polymorphism with functional importance for interindividual differences in enzyme expression

  2. Testing the variability of PSA expression by different human prostate cancer cell lines by means of a new potentiometric device employing molecularly antibody assembled on graphene surface

    International Nuclear Information System (INIS)

    Rebelo, Tânia S.C.R.; Noronha, João P.; Galésio, Marco; Santos, Hugo; Diniz, Mário; Sales, M. Goreti F.; Fernandes, Maria H.; Costa-Rodrigues, João

    2016-01-01

    Prostate Specific Antigen (PSA) is widely used as a biomarker for prostate cancer. Recently, an electrochemical biosensor for PSA detection by means of molecularly imprinted polymers (MIPs) was developed. This work evaluated the performance and the effectiveness of that PSA biosensor in screening the biomarker PSA in biological media with complex composition, collected from different human prostate cell line cultures. For that, the prostate cancer LNCaP and PC3 cells, and the non-cancerous prostate cell line PNT2 were cultured for 2, 7 and 14 days in either α-MEM or RPMI in the presence of 10% or 30% fetal bovine serum. Human gingival fibroblasts were used as a non-cancerous non-prostatic control. The different culture conditions modulated cellular proliferation and the expression of several prostate markers, including PSA. The electrochemical biosensor was able to specifically detect PSA in the culture media and values obtained were similar to those achieved by a commercial Enzyme-Linked Immunosorbent Assay (ELISA) kit, the most commonly used method for PSA quantification in prostate cancer diagnosis. Thus, the tested biosensor may represent a useful alternative as a diagnostic tool for PSA determination in biological samples. - Highlights: • PSA quantification was performed in prostate cancer cell culture media. • Culture media composition and culture period significantly affect PSA production. • The PSA biosensor detected a wide range of PSA levels in complex media. • A high data correlation was observed between the biosensor and the ELISA analysis.

  3. Determination of a method for extraction of coenzyme Q10 in human plasma: optimization of the use of surfactants and other variables

    Directory of Open Access Journals (Sweden)

    Claudia Cristina Ferreiro-Barros

    2012-06-01

    Full Text Available Objective: To establish a routine for the extraction of the total levelsof CoQ10 in human plasma through the Ultra High Performance LiquidChromatography (UHPLC. Methods: Two extraction protocolswere tested: a methanol: hexane and b 1-propanol. The followingparameters were analyzed: extraction temperature (19ºC and 4ºC,extraction tubes (glass and polypropylene, and surfactants (SDS,Triton X-100, Tween-20 at different concentrations, i.e., 1%,3%, 5% and 10%. Results: The results showed that the methodof extraction of CoQ10 in a sample of human plasma at 4ºC, usingsolvents methanol: hexane (85:15, v/v in the presence of surfactantTween-20 at 3% and polypropylene tubes showed better efficiencyand reproducibility when compared to the method with 1-propanol.Conclusion: By the analyses performed, it was possible to observethat the addition of the surfactant Tween-20 promoted an increasein the recovery of CoQ10 by the methanol:hexane extraction method.This method showed good reproducibility, with a low coefficient ofvariation and high sensitivity, since CoQ10 was detected in samplesof plasma of a control individual using a UV-type detector. The useof UHPLC equipment allowed a total analysis with total run time of3.5 minutes, enabling the rapid achievement of results, consideredmandatory for laboratory routines.

  4. Testing the variability of PSA expression by different human prostate cancer cell lines by means of a new potentiometric device employing molecularly antibody assembled on graphene surface

    Energy Technology Data Exchange (ETDEWEB)

    Rebelo, Tânia S.C.R. [BioMark-CINTESIS/ISEP, Instituto Superior de Engenharia do Instituto Politécnico do Porto (Portugal); LAQV, REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica (Portugal); Laboratory for Bone Metabolism and Regeneration, Faculdade de Medicina Dentária, Universidade do Porto, Porto (Portugal); Noronha, João P.; Galésio, Marco; Santos, Hugo; Diniz, Mário [LAQV, REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica (Portugal); Sales, M. Goreti F. [BioMark-CINTESIS/ISEP, Instituto Superior de Engenharia do Instituto Politécnico do Porto (Portugal); Fernandes, Maria H. [Laboratory for Bone Metabolism and Regeneration, Faculdade de Medicina Dentária, Universidade do Porto, Porto (Portugal); Costa-Rodrigues, João, E-mail: jrodrigues@fmd.up.pt [Laboratory for Bone Metabolism and Regeneration, Faculdade de Medicina Dentária, Universidade do Porto, Porto (Portugal); ESTSP — Escola Superior de Tecnologia da Saúde do Porto, Instituto Politécnico do Porto (Portugal)

    2016-02-01

    Prostate Specific Antigen (PSA) is widely used as a biomarker for prostate cancer. Recently, an electrochemical biosensor for PSA detection by means of molecularly imprinted polymers (MIPs) was developed. This work evaluated the performance and the effectiveness of that PSA biosensor in screening the biomarker PSA in biological media with complex composition, collected from different human prostate cell line cultures. For that, the prostate cancer LNCaP and PC3 cells, and the non-cancerous prostate cell line PNT2 were cultured for 2, 7 and 14 days in either α-MEM or RPMI in the presence of 10% or 30% fetal bovine serum. Human gingival fibroblasts were used as a non-cancerous non-prostatic control. The different culture conditions modulated cellular proliferation and the expression of several prostate markers, including PSA. The electrochemical biosensor was able to specifically detect PSA in the culture media and values obtained were similar to those achieved by a commercial Enzyme-Linked Immunosorbent Assay (ELISA) kit, the most commonly used method for PSA quantification in prostate cancer diagnosis. Thus, the tested biosensor may represent a useful alternative as a diagnostic tool for PSA determination in biological samples. - Highlights: • PSA quantification was performed in prostate cancer cell culture media. • Culture media composition and culture period significantly affect PSA production. • The PSA biosensor detected a wide range of PSA levels in complex media. • A high data correlation was observed between the biosensor and the ELISA analysis.

  5. Role of Climate Variability and Human Activity on Poopó Lake Droughts between 1990 and 2015 Assessed Using Remote Sensing Data

    Directory of Open Access Journals (Sweden)

    Frédéric Satgé

    2017-02-01

    Full Text Available In 2015, an emergency state was declared in Bolivia when Poopó Lake dried up. Climate variability and the increasing need for water are potential factors responsible for this situation. Because field data are missing over the region, no statements are possible about the influence of mentioned factors. This study is a preliminary step toward the understanding of Poopó Lake drought using remote sensing data. First, atmospheric corrections for Landsat (FLAASH and L8SR, seven satellite derived indexes for extracting water bodies, MOD16 evapotranspiration, PERSIANN-CDR and MSWEP rainfall products potentiality were assessed. Then, the fluctuations of Poopó Lake extent over the last 26 years are presented for the first time jointly, with the mean regional annual rainfall. Three main droughts are highlighted between 1990 and 2015: two are associated with negative annual rainfall anomalies in 1994 and 1995 and one associated with positive annual rainfall anomaly in 2015. This suggests that other factors than rainfall influenced the recent disappearance of the lake. The regional evapotranspiration increased by 12.8% between 2000 and 2014. Evapotranspiration increase is not homogeneous over the watershed but limited over the main agriculture regions. Agriculture activity is one of the major factors contributing to the regional desertification and recent disappearance of Poopó Lake.

  6. Isolation of a Reassortant H1N2 Swine Flu Strain of Type “Swine-Human-Avian” and Its Genetic Variability Analysis

    Directory of Open Access Journals (Sweden)

    Long-Bai Wang

    2018-01-01

    Full Text Available We isolated an influenza strain named A/Swine/Fujian/F1/2010 (H1N2 from a pig suspected to be infected with swine flu. The results of electron microscopy, hemagglutination (HA assay, hemagglutination inhibition (HI assay, and whole genome sequencing analysis suggest that it was a reassortant virus of swine (H1N1 subtype, human (H3N2 subtype, and avian influenza viruses. To further study the genetic evolution of A/Swine/Fujian/F1/2010 (H1N2, we cloned its whole genome fragments using RT-PCR and performed phylogenetic analysis on the eight genes. As a result, the nucleotide sequences of HA, NA, PB1, PA, PB2, NP, M, and NS gene are similar to those of A/Swine/Shanghai/1/2007(H1N2 with identity of 98.9%, 98.9%, 99.0%, 98.6%, 99.0%, 98.9%, 99.3%, and 99.3%, respectively. Similar to A/Swine/Shanghai/1/2007(H1N2, we inferred that the HA, NP, M, and NS gene fragments of A/Swine/Fujian/F1/2010 (H1N2 strain were derived from classical swine influenza H3N2 subtype, NA and PB1 were derived from human swine influenza H3N2 subtype, and PB2 and PA genes were derived from avian influenza virus. This further validates the role of swine as a “mixer” for influenza viruses.

  7. A new perspective on human health risk assessment: Development of a time dependent methodology and the effect of varying exposure durations

    International Nuclear Information System (INIS)

    Siirila, Erica R.; Maxwell, Reed M.

    2012-01-01

    We present a new Time Dependent Risk Assessment (TDRA) that stochastically considers how joint uncertainty and inter-individual variability (JUV) associated with human health risk change as a function of time. In contrast to traditional, time independent assessments of risk, this new formulation relays information on when the risk occurs, how long the duration of risk is, and how risk changes with time. Because the true exposure duration (ED) is often uncertain in a risk assessment, we also investigate how varying the magnitude of fixed size durations (ranging between 5 and 70 years) of this parameter affects the distribution of risk in both the time independent and dependent methodologies. To illustrate this new formulation and to investigate these mechanisms for sensitivity, an example of arsenic contaminated groundwater is used in conjunction with two scenarios of different environmental concentration signals resulting from rate dependencies in geochemical reactions. Cancer risk is computed and compared using environmental concentration ensembles modeled with sorption as 1) a linear equilibrium assumption (LEA) and 2) first order kinetics (Kin). Results show that the information attained in the new time dependent methodology reveals how the uncertainty in other time-dependent processes in the risk assessment may influence the uncertainty in risk. We also show that individual susceptibility also affects how risk changes in time, information that would otherwise be lost in the traditional, time independent methodology. These results are especially pertinent for forecasting risk in time, and for risk managers who are assessing the uncertainty of risk. - Highlights: ► A human health, Time Dependent Risk Assessment (TDRA) methodology is presented. ► TDRA relays information on the magnitude, duration, and fluxes of risk in time. ► Kinetic and equilibrium concentration signals show sensitivity in TDRA results. ► In the TDRA results, individual susceptibility

  8. Revisiting the role of individual variability in population persistence and stability.

    Directory of Open Access Journals (Sweden)

    Andrew Morozov

    Full Text Available Populations often exhibit a pronounced degree of individual variability and this can be important when constructing ecological models. In this paper, we revisit the role of inter-individual variability in population persistence and stability under predation pressure. As a case study, we consider interactions between a structured population of zooplankton grazers and their predators. Unlike previous structured population models, which only consider variability of individuals according to the age or body size, we focus on physiological and behavioural structuring. We first experimentally demonstrate a high degree of variation of individual consumption rates in three dominant species of herbivorous copepods (Calanus finmarchicus, Calanus glacialis, Calanus euxinus and show that this disparity implies a pronounced variation in the consumption capacities of individuals. Then we construct a parsimonious predator-prey model which takes into account the intra-population variability of prey individuals according to behavioural traits: effectively, each organism has a 'personality' of its own. Our modelling results show that structuring of prey according to their growth rate and vulnerability to predation can dampen predator-prey cycles and enhance persistence of a species, even if the resource stock for prey is unlimited. The main mechanism of efficient top-down regulation is shown to work by letting the prey population become dominated by less vulnerable individuals when predator densities are high, while the trait distribution recovers when the predator densities are low.

  9. Tamoxifen Forms DNA Adducts In Human Colon After Administration Of A Single [14C]-Labeled Therapeutic Dose.

    Energy Technology Data Exchange (ETDEWEB)

    Brown, K; Tompkins, E M; Boocock, D J; Martin, E A; Farmer, P B; Turteltaub, K W; Ubick, E; Hemingway, D; Horner-Glister, E; White, I H

    2007-05-23

    Tamoxifen is widely prescribed for the treatment of breast cancer and is also licensed in the U.S. for the prevention of this disease. However, tamoxifen therapy is associated with an increased occurrence of endometrial cancer in women and there is also evidence that it may elevate the risk of colorectal cancer. The underlying mechanisms responsible for tamoxifen-induced carcinogenesis in women have not yet been elucidated but much interest has focussed on the role of DNA adduct formation. We investigated the propensity of tamoxifen to bind irreversibly to colorectal DNA when given to ten women as a single [{sup 14}C]-labeled therapeutic (20 mg) dose, {approx}18 h prior to undergoing colon resections. Using the sensitive technique of accelerator mass spectrometry, coupled with HPLC separation of enzymatically digested DNA, a peak corresponding to authentic dG-N{sup 2}-tamoxifen adduct was detected in samples from three patients, at levels ranging from 1-7 adducts/10{sup 9} nucleotides. No [{sup 14}C]-radiolabel associated with tamoxifen or its major metabolites was detected. The presence of detectable CYP3A4 protein in all colon samples suggests this tissue has the potential to activate tamoxifen to {alpha}-hydroxytamoxifen, in addition to that occurring in the systemic circulation, and direct interaction of this metabolite with DNA could account for the binding observed. Although the level of tamoxifeninduced damage displayed a degree of inter-individual variability, when present it was {approx}10-100 times higher than that reported for other suspect human colon carcinogens such as PhIP. These findings provide a mechanistic basis through which tamoxifen could increase the incidence of colon cancers in women.

  10. Quantification of glutathione transverse relaxation time T2 using echo time extension with variable refocusing selectivity and symmetry in the human brain at 7 Tesla

    Science.gov (United States)

    Swanberg, Kelley M.; Prinsen, Hetty; Coman, Daniel; de Graaf, Robin A.; Juchem, Christoph

    2018-05-01

    Glutathione (GSH) is an endogenous antioxidant implicated in numerous biological processes, including those associated with multiple sclerosis, aging, and cancer. Spectral editing techniques have greatly facilitated the acquisition of glutathione signal in living humans via proton magnetic resonance spectroscopy, but signal quantification at 7 Tesla is still hampered by uncertainty about the glutathione transverse decay rate T2 relative to those of commonly employed quantitative references like N-acetyl aspartate (NAA), total creatine, or water. While the T2 of uncoupled singlets can be derived in a straightforward manner from exponential signal decay as a function of echo time, similar estimation of signal decay in GSH is complicated by a spin system that involves both weak and strong J-couplings as well as resonances that overlap those of several other metabolites and macromolecules. Here, we extend a previously published method for quantifying the T2 of GABA, a weakly coupled system, to quantify T2 of the strongly coupled spin system glutathione in the human brain at 7 Tesla. Using full density matrix simulation of glutathione signal behavior, we selected an array of eight optimized echo times between 72 and 322 ms for glutathione signal acquisition by J-difference editing (JDE). We varied the selectivity and symmetry parameters of the inversion pulses used for echo time extension to further optimize the intensity, simplicity, and distinctiveness of glutathione signals at chosen echo times. Pairs of selective adiabatic inversion pulses replaced nonselective pulses at three extended echo times, and symmetry of the time intervals between the two extension pulses was adjusted at one extended echo time to compensate for J-modulation, thereby resulting in appreciable signal-to-noise ratio and quantifiable signal shapes at all measured points. Glutathione signal across all echo times fit smooth monoexponential curves over ten scans of occipital cortex voxels in nine

  11. Simultaneous quantification of acetaminophen and five acetaminophen metabolites in human plasma and urine by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry: Method validation and application to a neonatal pharmacokinetic study.

    Science.gov (United States)

    Cook, Sarah F; King, Amber D; van den Anker, John N; Wilkins, Diana G

    2015-12-15

    Drug metabolism plays a key role in acetaminophen (paracetamol)-induced hepatotoxicity, and quantification of acetaminophen metabolites provides critical information about factors influencing susceptibility to acetaminophen-induced hepatotoxicity in clinical and experimental settings. The aims of this study were to develop, validate, and apply high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) methods for simultaneous quantification of acetaminophen, acetaminophen-glucuronide, acetaminophen-sulfate, acetaminophen-glutathione, acetaminophen-cysteine, and acetaminophen-N-acetylcysteine in small volumes of human plasma and urine. In the reported procedures, acetaminophen-d4 and acetaminophen-d3-sulfate were utilized as internal standards (IS). Analytes and IS were recovered from human plasma (10μL) by protein precipitation with acetonitrile. Human urine (10μL) was prepared by fortification with IS followed only by sample dilution. Calibration concentration ranges were tailored to literature values for each analyte in each biological matrix. Prepared samples from plasma and urine were analyzed under the same HPLC-ESI-MS/MS conditions, and chromatographic separation was achieved through use of an Agilent Poroshell 120 EC-C18 column with a 20-min run time per injected sample. The analytes could be accurately and precisely quantified over 2.0-3.5 orders of magnitude. Across both matrices, mean intra- and inter-assay accuracies ranged from 85% to 112%, and intra- and inter-assay imprecision did not exceed 15%. Validation experiments included tests for specificity, recovery and ionization efficiency, inter-individual variability in matrix effects, stock solution stability, and sample stability under a variety of storage and handling conditions (room temperature, freezer, freeze-thaw, and post-preparative). The utility and suitability of the reported procedures were illustrated by analysis of pharmacokinetic samples

  12. Preanalytical and analytical variation of surface-enhanced laser desorption-ionization time-of-flight mass spectrometry of human serum

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Bøgebo, Rikke; Olsen, Jesper

    2006-01-01

    BACKGROUND: Surface-enhanced laser desorption-ionization time-of-flight (SELDI-TOF) mass spectrometry of human serum is a potential diagnostic tool in human diseases. In the present study, the preanalytical and analytical variation of SELDI-TOF mass spectrometry of serum was assessed in healthy...... was 18% (6%-34%, n=4) for 16 peaks, and inter-individual CV was 38% (16%-56%, n=16) for 20 peaks. CONCLUSIONS: The pre-analytical and analytical conditions of SELDI-TOF mass spectrometry of serum have a significant impact on the protein peaks, with the number of peaks low and the assay variation high...

  13. Genetic variation in lipid desaturases and its impact on the development of human disease.

    Science.gov (United States)

    Merino, Diana M; Ma, David W L; Mutch, David M

    2010-06-18

    Perturbations in lipid metabolism characterize many of the chronic diseases currently plaguing our society, such as obesity, diabetes, and cardiovascular disease. Thus interventions that target plasma lipid levels remain a primary goal to manage these diseases. The determinants of plasma lipid levels are multi-factorial, consisting of both genetic and lifestyle components. Recent evidence indicates that fatty acid desaturases have an important role in defining plasma and tissue lipid profiles. This review will highlight the current state-of-knowledge regarding three desaturases (Scd-1, Fads1 and Fads2) and their potential roles in disease onset and development. Although research in rodent models has provided invaluable insight into the regulation and functions of these desaturases, the extent to which murine research can be translated to humans remains unclear. Evidence emerging from human-based research demonstrates that genetic variation in human desaturase genes affects enzyme activity and, consequently, disease risk factors. Moreover, this genetic variation may have a trans-generational effect via breastfeeding. Therefore inter-individual variation in desaturase function is attributed to both genetic and lifestyle components. As such, population-based research regarding the role of desaturases on disease risk is challenged by this complex gene-lifestyle paradigm. Unravelling the contribution of each component is paramount for understanding the inter-individual variation that exists in plasma lipid profiles, and will provide crucial information to develop personalized strategies to improve health management.

  14. Variability of Heart Rate in Primitive Horses and Their Relatives as an Indicator of Stress Level, Behavioural Conduct Towards Humans and Adaptation to Living in Wild

    Directory of Open Access Journals (Sweden)

    Pluta Michał

    2014-10-01

    Full Text Available The aim of the study was to evaluate the possibility of using heart rate (HR as a metric parameter that can be used for the characterisation of behaviour of primitive horses and their relatives, related to reactions to the stress resulting from the contact with humans and adaptation to living in various conditions, including natural environment. This characterisation served the authors to expand the knowledge of such behaviour of primitive horses, and to assess the impact of the environmental and genetic factors. Studies were conducted in three populations of horses: two herds of Polish Konik and one herd of Biłgoraj horses. The studies were performed between 1993 and 2010. They concerned the behaviour of horses during grooming - breeding procedures (hooves clearing, body measurements performed cyclically and the daily observations when HR was monitored continuously. HR results for the respective age categories, during particular grooming - breeding procedures and reserve observations indicate that Polish Konik horses, closely related to the primitive Tarpan breed, are genetically better adapted to living in conditions similar to the natural (reserve than the Biłgoraj horses. They show less stress symptoms, which are evidenced by HR values noted during inhabiting the natural environment.

  15. The shunt from the cyclooxygenase to lipoxygenase pathway in human osteoarthritic subchondral osteoblasts is linked with a variable expression of the 5-lipoxygenase-activating protein.

    Science.gov (United States)

    Maxis, Kelitha; Delalandre, Aline; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Duval, Nicolas; Lajeunesse, Daniel

    2006-01-01

    Osteoarthritis (OA) is characterized by articular cartilage degradation and hypertrophic bone changes with osteophyte formation and abnormal bone remodeling. Two groups of OA patients were identified via the production of variable and opposite levels of prostaglandin E2 (PGE2) or leukotriene B4 (LTB4) by subchondral osteoblasts, PGE2 levels discriminating between low and high subgroups. We studied whether the expression of 5-lipoxygenase (5-LO) or 5-LO-activating protein (FLAP) is responsible for the shunt from prostaglandins to leukotrienes. FLAP mRNA levels varied in low and high OA groups compared with normal, whereas mRNA levels of 5-LO were similar in all osteoblasts. Selective inhibition of cyclooxygenase-2 (COX-2) with NS-398-stimulated FLAP expression in the high OA osteoblasts subgroup, whereas it was without effect in the low OA osteoblasts subgroup. The addition of PGE2 to the low OA osteoblasts subgroup decreased FLAP expression but failed to affect it in the high OA osteoblasts subgroup. LTB4 levels in OA osteoblasts were stimulated about twofold by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plus transforming growth factor-beta (TGF-beta), a situation corresponding to their effect on FLAP mRNA levels. Treatments with 1,25(OH)2D3 and TGF-beta also modulated PGE2 production. TGF-beta stimulated PGE2 production in both OA osteoblast groups, whereas 1,25(OH)2D3 alone had a limited effect but decreased the effect of TGF-beta in the low OA osteoblasts subgroup. This modulation of PGE2 production was mirrored by the synthesis of COX-2. IL-18 levels were only slightly increased in a subgroup of OA osteoblasts compared with normal; however, no relationship was observed overall between IL-18 and PGE2 levels in normal and OA osteoblasts. These results suggest that the shunt from the production of PGE2 to LTB4 is through regulation of the expression of FLAP, not 5-LO, in OA osteoblasts. The expression of FLAP in OA osteoblasts is also modulated differently by 1,25(OH

  16. Reduction of hexavalent chromium by fasted and fed human gastric fluid. II. Ex vivo gastric reduction modeling

    Energy Technology Data Exchange (ETDEWEB)

    Kirman, Christopher R., E-mail: ckirman@summittoxicology.com [Summit Toxicology, Orange Village, OH, 44022 (United States); Suh, Mina, E-mail: msuh@toxstrategies.com [ToxStrategies, Inc., Mission Viejo, CA, 92692 (United States); Hays, Sean M., E-mail: shays@summittoxicology.com [Summit Toxicology, Allenspark, CO, 8040 (United States); Gürleyük, Hakan, E-mail: hakan@brooksrand.com [Brooks Applied Labs, Bothell, WA, 98011 (United States); Gerads, Russ, E-mail: russ@brooksrand.com [Brooks Applied Labs, Bothell, WA, 98011 (United States); De Flora, Silvio, E-mail: sdf@unige.it [Department of Health Sciences, University of Genoa, 16132 Genoa (Italy); Parker, William, E-mail: william.parker@duke.edu [Duke University Medical Center, Department of Surgery, Durham, NC, 27710 (United States); Lin, Shu, E-mail: shu.lin@duke.edu [Duke University Medical Center, Department of Surgery, Durham, NC, 27710 (United States); Haws, Laurie C., E-mail: lhaws@toxstrategies.com [ToxStrategies, Inc., Katy, TX, 77494 (United States); Harris, Mark A., E-mail: mharris@toxstrategies.com [ToxStrategies, Inc., Austin, TX, 78751 (United States); Proctor, Deborah M., E-mail: dproctor@toxstrategies.com [ToxStrategies, Inc., Mission Viejo, CA, 92692 (United States)

    2016-09-01

    model is used to characterize inter-individual variability in Cr(VI) gastric reduction capacity.

  17. Effect of diet on the human gut microbiota

    DEFF Research Database (Denmark)

    Bahl, Martin Iain

    The gut microbiota plays an important role for humans in both health and disease. It is therefore important to understand how and to what extent choice of diet may influence the microbial community and the effects this has on the host. The variation in the normal human gut microbiota may however...... impede the discovery of correlations between dietary changes and compositional shifts in the microbiota by masking such effects. Although specific functional food ingredients, such as prebiotics, are known to have measurable effects on e.g. abundance of bifidobacteria, it is nevertheless clear...... that induced shifts in gut microbiota show large inter-individual variations. It thus seems plausible that knowing the microbiota composition could facilitate predictions as to how the community will react to dietary interventions thus moving towards some degree of personalised dietary recommendations. During...

  18. Self-renewal and differentiation capabilities are variable between human embryonic stem cell lines I3, I6 and BG01V

    Directory of Open Access Journals (Sweden)

    Rao Mahendra S

    2009-06-01

    Full Text Available Abstract Background A unique and essential property of embryonic stem cells is the ability to self-renew and differentiate into multiple cell lineages. However, the possible differences in proliferation and differentiation capabilities among independently-derived human embryonic stem cells (hESCs are not well known because of insufficient characterization. To address this question, a side-by-side comparison of 1 the ability to maintain an undifferentiated state and to self-renew under standard conditions; 2 the ability to spontaneously differentiate into three primary embryonic germ lineages in differentiating embryoid bodies; and 3 the responses to directed neural differentiation was made between three NIH registered hES cell lines I3 (TE03, I6 (TE06 and BG01V. Lines I3 and I6 possess normal XX and a normal XY karyotype while BG01V is a variant cell line with an abnormal karyotype derived from the karyotypically normal cell line BG01. Results Using immunocytochemistry, flow cytometry, qRT-PCR and MPSS, we found that all three cell lines actively proliferated and expressed similar "stemness" markers including transcription factors POU5F1/Oct3/4 and NANOG, glycolipids SSEA4 and TRA-1-81, and alkaline phosphatase activity. All cell lines differentiated into three embryonic germ lineages in embryoid bodies and into neural cell lineages when cultured in neural differentiation medium. However, a profound variation in colony morphology, growth rate, BrdU incorporation, and relative abundance of gene expression in undifferentiated and differentiated states of the cell lines was observed. Undifferentiated I3 cells grew significantly slower but their differentiation potential was greater than I6 and BG01V. Under the same neural differentiation-promoting conditions, the ability of each cell line to differentiate into neural progenitors varied. Conclusion Our comparative analysis provides further evidence for similarities and differences between three h

  19. A module of human peripheral blood mononuclear cell transcriptional network containing primitive and differentiation markers is related to specific cardiovascular health variables.

    Directory of Open Access Journals (Sweden)

    Leni Moldovan

    Full Text Available Peripheral blood mononuclear cells (PBMCs, including rare circulating stem and progenitor cells (CSPCs, have important yet poorly understood roles in the maintenance and repair of blood vessels and perfused organs. Our hypothesis was that the identities and functions of CSPCs in cardiovascular health could be ascertained by analyzing the patterns of their co-expressed markers in unselected PBMC samples. Because gene microarrays had failed to detect many stem cell-associated genes, we performed quantitative real-time PCR to measure the expression of 45 primitive and tissue differentiation markers in PBMCs from healthy and hypertensive human subjects. We compared these expression levels to the subjects' demographic and cardiovascular risk factors, including vascular stiffness. The tested marker genes were expressed in all of samples and organized in hierarchical transcriptional network modules, constructed by a bottom-up approach. An index of gene expression in one of these modules (metagene, defined as the average standardized relative copy numbers of 15 pluripotency and cardiovascular differentiation markers, was negatively correlated (all p<0.03 with age (R2 = -0.23, vascular stiffness (R2 = -0.24, and central aortic pressure (R2 = -0.19 and positively correlated with body mass index (R2 = 0.72, in women. The co-expression of three neovascular markers was validated at the single-cell level using mRNA in situ hybridization and immunocytochemistry. The overall gene expression in this cardiovascular module was reduced by 72±22% in the patients compared with controls. However, the compactness of both modules was increased in the patients' samples, which was reflected in reduced dispersion of their nodes' degrees of connectivity, suggesting a more primitive character of the patients' CSPCs. In conclusion, our results show that the relationship between CSPCs and vascular function is encoded in modules of the PBMCs transcriptional

  20. Context matters! sources of variability in weekend physical activity among families: a repeated measures study

    Directory of Open Access Journals (Sweden)

    Robert J. Noonan

    2017-04-01

    Full Text Available Abstract Background Family involvement is an essential component of effective physical activity (PA interventions in children. However, little is known about the PA levels and characteristics of PA among families. This study used a repeated measures design and multiple data sources to explore the variability and characteristics of weekend PA among families. Methods Families (including a ‘target’ child aged 9–11 years, their primary caregiver(s and siblings aged 6–8 years were recruited through primary schools in Liverpool, UK. Participants completed a paper-based PA diary and wore an ActiGraph GT9X accelerometer on their left wrist for up to 16 weekend days. ActiGraph.csv files were analysed using the R-package GGIR version 1.1–4. Mean minutes of moderate-to-vigorous PA (MVPA for each weekend of measurement were calculated using linear mixed models, and variance components were estimated for participant (inter-individual, weekend of measurement, and residual error (intra-individual. Intraclass correlation coefficients (ICC were calculated from the proportion of total variance accounted for by inter-individual sources, and used as a measure of reliability. Diary responses were summed to produce frequency counts. To offer contextual insight into weekend PA among family units, demographic, accelerometer, and diary data were combined to form two case studies representative of low and high active families. Results Twenty-five participants from 7 families participated, including 7 ‘target’ children (mean age 9.3 ± 1.1 years, 4 boys, 6 siblings (mean age 7.2 ± 0.7 years; 4 boys and 12 adults (7 mothers and 5 fathers. There was a high degree of variability in target children’s (ICC = 0.55, siblings (ICC = 0.38, and mothers’ MVPA (ICC = 0.58, but not in fathers’ MVPA (ICC = 0.83. Children’s weekend PA was mostly unstructured in nature and undertaken with friends, whereas a greater proportion of parents’ weekend

  1. Variability of activity profile during medium-sided games in professional soccer.

    Science.gov (United States)

    Rago, Vincenzo; Silva, João R; Mohr, Magni; Barreira, Daniel; Krustrup, Peter; Rebelo, António N

    2018-04-24

    In Southern European countries it is very frequent to perform medium-sized games (MSG) as last training drill. We analyzed the individual variability and changes in activity patterns during MSG throughout the preseason. Activity profile during MSGs (10v10+goalkeepers, duration: 10-min, field length: 50 m, width: 90 m, area per player: 204.5 m2) was quantified using a GPS in 14 professional male players (6 defenders, 5 midfielders 5 and attackers). Inter-individual variability was higher for high-intensity (HIR), very-high speed (VHS), maximum acceleration (Accmax) and maximum deceleration (Decmax) distance (CV=25.2 to 43.3%), compared to total distance (TD), total acceleration (Acctot) and total deceleration (Dectot) distance (CV= 8.3 to 18.3 %). Defenders showed higher variability in TD, HIR, VHS, Acctot and Dectot (ES= 1.30 to 11.28) compared to the other field positions, whereas attackers showed higher variability in HIR, VHS Accmax and Decmax (ES=-4.92 to 2.07) than other the field positions. Variability in TD regularly increased (ES= -2.13 to -0.91) towards the end of the preseason, while HIR and VHS variability tended to increase over the 3rd and the 4th preseason week (ES=-0.94 to -3.05). However, the behavior of variability across the preseason period was more unpredictable for Acctot and Dectot, both decreasing in the 3rd week (ES= 0.70 to 1.20), while Decmax increased in the 4th week (ES=-0.91±0.59). During MSGs, individual variability of activity differs among field positions, and tends to increase with either speed or acceleration intensity, underlining the need of an individualized approach for training load monitoring.

  2. Biologic variability and correlation of platelet function testing in healthy dogs.

    Science.gov (United States)

    Blois, Shauna L; Lang, Sean T; Wood, R Darren; Monteith, Gabrielle

    2015-12-01

    Platelet function tests are influenced by biologic variability, including inter-individual (CVG ) and intra-individual (CVI ), as well as analytic (CVA ) variability. Variability in canine platelet function testing is unknown, but if excessive, would make it difficult to interpret serial results. Additionally, the correlation between platelet function tests is poor in people, but not well described in dogs. The aims were to: (1) identify the effect of variation in preanalytic factors (venipuncture, elapsed time until analysis) on platelet function tests; (2) calculate analytic and biologic variability of adenosine diphosphate (ADP) and arachidonic acid (AA)-induced thromboelastograph platelet mapping (TEG-PM), ADP-, AA-, and collagen-induced whole blood platelet aggregometry (WBA), and collagen/ADP and collagen/epinephrine platelet function analysis (PFA-CADP, PFA-CEPI); and (3) determine the correlation between these variables. In this prospective observational trial, platelet function was measured once every 7 days, for 4 consecutive weeks, in 9 healthy dogs. In addition, CBC, TEG-PM, WBA, and PFA were performed. Overall coefficients of variability ranged from 13.3% to 87.8% for the platelet function tests. Biologic variability was highest for AA-induced maximum amplitude generated during TEG-PM (MAAA; CVG = 95.3%, CVI = 60.8%). Use of population-based reference intervals (RI) was determined appropriate only for PFA-CADP (index of individuality = 10.7). There was poor correlation between most platelet function tests. Use of population-based RI appears inappropriate for most platelet function tests, and tests poorly correlate with one another. Future studies on biologic variability and correlation of platelet function tests should be performed in dogs with platelet dysfunction and those treated with antiplatelet therapy. © 2015 American Society for Veterinary Clinical Pathology.

  3. Single-cell systems level analysis of human Toll-Like-Receptor activation defines a chemokine signature in Systemic Lupus Erythematosus

    Science.gov (United States)

    O'Gorman, William E.; Hsieh, Elena W.Y.; Savig, Erica S.; Gherardini, Pier Federico; Hernandez, Joseph D.; Hansmann, Leo; Balboni, Imelda M.; Utz, Paul J.; Bendall, Sean C.; Fantl, Wendy J.; Lewis, David B.; Nolan, Garry P.; Davis, Mark M.

    2015-01-01

    Background Activation of Toll-Like Receptors (TLRs) induces inflammatory responses involved in immunity to pathogens and autoimmune pathogenesis, such as in Systemic Lupus Erythematosus (SLE). Although TLRs are differentially expressed across the immune system, a comprehensive analysis of how multiple immune cell subsets respond in a system-wide manner has previously not been described. Objective To characterize TLR activation across multiple immune cell subsets and individuals, with the goal of establishing a reference framework against which to compare pathological processes. Methods Peripheral whole blood samples were stimulated with TLR ligands, and analyzed by mass cytometry simultaneously for surface marker expression, activation states of intracellular signaling proteins, and cytokine production. We developed a novel data visualization tool to provide an integrated view of TLR signaling networks with single-cell resolution. We studied seventeen healthy volunteer donors and eight newly diagnosed untreated SLE patients. Results Our data revealed the diversity of TLR-induced responses within cell types, with TLR ligand specificity. Subsets of NK and T cells selectively induced NF-κB in response to TLR2 ligands. CD14hi monocytes exhibited the most polyfunctional cytokine expression patterns, with over 80 distinct cytokine combinations. Monocytic TLR-induced cytokine patterns were shared amongst a group of healthy donors, with minimal intra- and inter- individual variability. Furthermore, autoimmune disease altered baseline cytokine production, as newly diagnosed untreated SLE patients shared a distinct monocytic chemokine signature, despite clinical heterogeneity. Conclusion Mass cytometry analysis defined a systems-level reference framework for human TLR activation, which can be applied to study perturbations in inflammatory disease, such as SLE. PMID:26037552

  4. Estimating the reliability of glycemic index values and potential sources of methodological and biological variability.

    Science.gov (United States)

    Matthan, Nirupa R; Ausman, Lynne M; Meng, Huicui; Tighiouart, Hocine; Lichtenstein, Alice H

    2016-10-01

    The utility of glycemic index (GI) values for chronic disease risk management remains controversial. Although absolute GI value determinations for individual foods have been shown to vary significantly in individuals with diabetes, there is a dearth of data on the reliability of GI value determinations and potential sources of variability among healthy adults. We examined the intra- and inter-individual variability in glycemic response to a single food challenge and methodologic and biological factors that potentially mediate this response. The GI value for white bread was determined by using standardized methodology in 63 volunteers free from chronic disease and recruited to differ by sex, age (18-85 y), and body mass index [BMI (in kg/m 2 ): 20-35]. Volunteers randomly underwent 3 sets of food challenges involving glucose (reference) and white bread (test food), both providing 50 g available carbohydrates. Serum glucose and insulin were monitored for 5 h postingestion, and GI values were calculated by using different area under the curve (AUC) methods. Biochemical variables were measured by using standard assays and body composition by dual-energy X-ray absorptiometry. The mean ± SD GI value for white bread was 62 ± 15 when calculated by using the recommended method. Mean intra- and interindividual CVs were 20% and 25%, respectively. Increasing sample size, replication of reference and test foods, and length of blood sampling, as well as AUC calculation method, did not improve the CVs. Among the biological factors assessed, insulin index and glycated hemoglobin values explained 15% and 16% of the variability in mean GI value for white bread, respectively. These data indicate that there is substantial variability in individual responses to GI value determinations, demonstrating that it is unlikely to be a good approach to guiding food choices. Additionally, even in healthy individuals, glycemic status significantly contributes to the variability in GI value

  5. The human gut microbiome, a taxonomic conundrum.

    Science.gov (United States)

    Sankar, Senthil Alias; Lagier, Jean-Christophe; Pontarotti, Pierre; Raoult, Didier; Fournier, Pierre-Edouard

    2015-06-01

    From culture to metagenomics, within only 130 years, our knowledge of the human microbiome has considerably improved. With >1000 microbial species identified to date, the gastro-intestinal microbiota is the most complex of human biotas. It is composed of a majority of Bacteroidetes and Firmicutes and, although exhibiting great inter-individual variations according to age, geographic origin, disease or antibiotic uptake, it is stable over time. Metagenomic studies have suggested associations between specific gut microbiota compositions and a variety of diseases, including irritable bowel syndrome, Crohn's disease, colon cancer, type 2 diabetes and obesity. However, these data remain method-dependent, as no consensus strategy has been defined to decipher the complexity of the gut microbiota. High-throughput culture-independent techniques have highlighted the limitations of culture by showing the importance of uncultured species, whereas modern culture methods have demonstrated that metagenomics underestimates the microbial diversity by ignoring minor populations. In this review, we highlight the progress and challenges that pave the way to a complete understanding of the human gastrointestinal microbiota and its influence on human health. Copyright © 2015 Elsevier GmbH. All rights reserved.

  6. Inter- and Intra-individual variability following intermittent theta burst stimulation: implications for rehabilitation and recovery.

    Science.gov (United States)

    Hinder, Mark R; Goss, Emily L; Fujiyama, Hakuei; Canty, Alison J; Garry, Michael I; Rodger, Jennifer; Summers, Jeffery J

    2014-01-01

    The continued refinement of non-invasive brain stimulation (NBS) techniques is indicative of promising clinical and rehabilitative interventions that are able to modulate cortical excitability. Intermittent theta burst stimulation (iTBS) is one such technique that can increase cortical excitability, purportedly via LTP-like mechanisms. While iTBS may have the capacity to promote recovery after neurological injury, and to combat cognitive and motor decline, recent reports observed highly variable effects across individuals, questioning the efficacy of iTBS as a clinical tool. The aim of this study was to examine intra-individual reliability and inter-individual variability in responses to iTBS. Thirty healthy participants completed two experimental sessions of the iTBS protocol 1-3 weeks apart. Motor evoked potentials in response to single pulse TMS were used to assess corticospinal excitability prior to, and up to 36 min following, iTBS. At the group level, iTBS evoked statistically significant increases in motor cortical excitability across both sessions (P iTBS is capable of inducing relatively robust and consistent effects within and between young individuals. As such, the capacity for iTBS to be exploited in clinical and rehabilitative interventions should continue to be explored. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Variability in prescription opioid intake and reinforcement amongst 129 substrains.

    Science.gov (United States)

    Jimenez, S M; Healy, A F; Coelho, M A; Brown, C N; Kippin, T E; Szumlinski, K K

    2017-09-01

    Opioid abuse in the United States has reached epidemic proportions, with treatment admissions and deaths associated with prescription opioid abuse quadrupling over the past 10 years. Although genetics are theorized to contribute substantially to inter-individual variability in the development, severity and treatment outcomes of opioid abuse/addiction, little direct preclinical study has focused on the behavioral genetics of prescription opioid reinforcement and drug-taking. Herein, we employed different 129 substrains of mice currently available from The Jackson Laboratory (129S1/SvlmJ, 129X1/SvJ, 129S4/SvJaeJ and 129P3/J) as a model system of genetic variation and assayed mice for oral opioid intake and reinforcement, as well as behavioral and somatic signs of dependence. All substrains exhibited a dose-dependent increase in oral oxycodone and heroin preference and intake under limited-access procedures and all, but 129S1/SvlmJ mice, exhibited oxycodone reinforcement. Relative to the other substrains, 129P3/J mice exhibited higher heroin and oxycodone intake. While 129X1/SvJ exhibited the highest anxiety-like behavior during natural opioid withdrawal, somatic and behavior signs of precipitated withdrawal were most robust in 129P3/J mice. These results demonstrate the feasibility and relative sensitivity of our oral opioid self-administration procedures for detecting substrain differences in drug reinforcement/intake among 129 mice, of relevance to the identification of genetic variants contributing to high vs. low oxycodone reinforcement and intake. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  8. Long-range autocorrelations of CpG islands in the human genome.

    Directory of Open Access Journals (Sweden)

    Benjamin Koester

    Full Text Available In this paper, we use a statistical estimator developed in astrophysics to study the distribution and organization of features of the human genome. Using the human reference sequence we quantify the global distribution of CpG islands (CGI in each chromosome and demonstrate that the organization of the CGI across a chromosome is non-random, exhibits surprisingly long range correlations (10 Mb and varies significantly among chromosomes. These correlations of CGI summarize functional properties of the genome that are not captured when considering variation in any particular separate (and local feature. The demonstration of the proposed methods to quantify the organization of CGI in the human genome forms the basis of future studies. The most illuminating of these will assess the potential impact on phenotypic variation of inter-individual variation in the organization of the functional features of the genome within and among chromosomes, and among individuals for particular chromosomes.

  9. A Systematic Review and Meta-Analysis of the Effects of Flavanol-Containing Tea, Cocoa and Apple P