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Sample records for resistance homeostasis model

  1. Childhood craniopharyngioma: greater hypothalamic involvement before surgery is associated with higher homeostasis model insulin resistance index

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    Trivin, Christine; Busiah, Kanetee; Mahlaoui, Nizar; Recasens, Christophe; Souberbielle, Jean-Claude; Zerah, Michel; Sainte-Rose, Christian; Brauner, Raja

    2009-01-01

    Background Obesity seems to be linked to the hypothalamic involvement in craniopharyngioma. We evaluated the pre-surgery relationship between the degree of this involvement on magnetic resonance imaging and insulin resistance, as evaluated by the homeostasis model insulin resistance index (HOMA). As insulin-like growth factor 1, leptin, soluble leptin receptor (sOB-R) and ghrelin may also be involved, we compared their plasma concentrations and their link to weight change. Methods 27 children with craniopharyngioma were classified as either grade 0 (n = 7, no hypothalamic involvement), grade 1 (n = 8, compression without involvement), or grade 2 (n = 12, severe involvement). Results Despite having similar body mass indexes (BMI), the grade 2 patients had higher glucose, insulin and HOMA before surgery than the grade 0 (P = 0.02, craniopharyngioma before surgery seems to determine the degree of insulin resistance, regardless of the BMI. The pre-surgery HOMA values were correlated with the post-surgery weight gain. This suggests that obesity should be prevented by reducing inn secretion in those cases with hypothalamic involvement. PMID:19341477

  2. Childhood craniopharyngioma: greater hypothalamic involvement before surgery is associated with higher homeostasis model insulin resistance index

    Directory of Open Access Journals (Sweden)

    Sainte-Rose Christian

    2009-04-01

    Full Text Available Abstract Background Obesity seems to be linked to the hypothalamic involvement in craniopharyngioma. We evaluated the pre-surgery relationship between the degree of this involvement on magnetic resonance imaging and insulin resistance, as evaluated by the homeostasis model insulin resistance index (HOMA. As insulin-like growth factor 1, leptin, soluble leptin receptor (sOB-R and ghrelin may also be involved, we compared their plasma concentrations and their link to weight change. Methods 27 children with craniopharyngioma were classified as either grade 0 (n = 7, no hypothalamic involvement, grade 1 (n = 8, compression without involvement, or grade 2 (n = 12, severe involvement. Results Despite having similar body mass indexes (BMI, the grade 2 patients had higher glucose, insulin and HOMA before surgery than the grade 0 (P = 0.02, The data for the whole population before and 6–18 months after surgery showed increases in BMI (P Conclusion The hypothalamic involvement by the craniopharyngioma before surgery seems to determine the degree of insulin resistance, regardless of the BMI. The pre-surgery HOMA values were correlated with the post-surgery weight gain. This suggests that obesity should be prevented by reducing inn secretion in those cases with hypothalamic involvement.

  3. Insulin resistance determined by Homeostasis Model Assessment (HOMA) and associations with metabolic syndrome among Chinese children and teenagers.

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    Yin, Jinhua; Li, Ming; Xu, Lu; Wang, Ying; Cheng, Hong; Zhao, Xiaoyuan; Mi, Jie

    2013-11-15

    The aim of this study is to assess the association between the degree of insulin resistance and the different components of the metabolic syndrome among Chinese children and adolescents. Moreover, to determine the cut-off values for homeostasis model assessment of insulin resistance (HOMA-IR) at MS risk. 3203 Chinese children aged 6 to 18 years were recruited. Anthropometric and biochemical parameters were measured. Metabolic syndrome (MS) was identified by a modified Adult Treatment Panel III (ATP III) definition. HOMA-IR index was calculated and the normal reference ranges were defined from the healthy participants. Receiver operating characteristic (ROC) analysis was used to find the optimal cutoff of HOMA-IR for diagnosis of MS. With the increase of insulin resistance (quintile of HOMA-IR value), the ORs of suffering MS or its related components were significantly increased. Participants in the highest quintile of HOMA-IR were about 60 times more likely to be classified with metabolic syndrome than those in the lowest quintile group. Similarly, the mean values of insulin and HOMA-IR increased with the number of MS components. The present HOMA-IR cutoff point corresponding to the 95th percentile of our healthy reference children was 3.0 for whole participants, 2.6 for children in prepubertal stage and 3.2 in pubertal period, respectively. The optimal point for diagnosis of MS was 2.3 in total participants, 1.7 in prepubertal children and 2.6 in pubertal adolescents, respectively, by ROC curve, which yielded high sensitivity and moderate specificity for a screening test. According to HOMA-IR > 3.0, the prevalence of insulin resistance in obese or MS children were 44.3% and 61.6% respectively. Our data indicates insulin resistance is common among Chinese obese children and adolescents, and is strongly related to MS risk, therefore requiring consideration early in life. As a reliable measure of insulin resistance and assessment of MS risk, the optimal HOMA-IR cut

  4. Homeostasis model assessment of insulin resistance in relation to the poor functional outcomes in nondiabetic patients with ischemic stroke

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    Li, Siou; Yin, Changhao; Zhao, Weina; Zhu, Haifu; Xu, Dan; Xu, Qing; Jiao, Yang; Wang, Xue; Qiao, Hong

    2018-01-01

    Whether insulin resistance (IR) predicts worse functional outcome in ischemic stroke is still a matter of debate. The aim of the present study is to determine the association between IR and risk of poor outcome in 173 Chinese nondiabetic patients with acute ischemic stroke. This is a prospective, population-based cohort study. Insulin sensitivity, expressed by the homeostasis model assessment (HOMA) of insulin sensitivity (HOMA index = (fasting insulin × fasting glucose)/22.5). IR was defined by HOMA-IR index in the top quartile (Q4). Functional impairment was evaluated at discharge using the modified Rankin scale (mRS). The median (interquartile range) HOMA-IR was 2.14 (1.17–2.83), and Q4 was at least 2.83. There was a significantly positive correlation between HOMA-IR and National Institutes of Health Stroke Scale (r = 0.408; PIR group were associated with a higher risk of poor functional outcome (odds ratio (OR) = 3.23; 95% confidence interval (CI) = 1.75–5.08; P=0.001). In multivariate models comparing the third and fourth quartiles against the first quartile of the HOMA-IR, levels of HOMA-IR were associated with poor outcome, and the adjusted risk of poor outcome increased by 207% (OR = 3.05 (95% CI 1.70–4.89), P=0.006) and 429% (5.29 (3.05–9.80), PHOMA-IR to clinical examination variables (P=0.02). High HOMA-IR index is associated with a poor functional outcome in nondiabetic patients with acute ischemic stroke. PMID:29588341

  5. Markers of insulin resistance and carotid atherosclerosis. A comparison of the homeostasis model assessment and triglyceride glucose index.

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    Irace, C; Carallo, C; Scavelli, F B; De Franceschi, M S; Esposito, T; Tripolino, C; Gnasso, A

    2013-07-01

    The present investigation was designed to test the association between carotid atherosclerosis and two simple markers of insulin resistance, i.e. HOMA-Index and TyG-Index. The study was performed in two different cohorts. In the first cohort, 330 individuals were enrolled. Blood pressure, lipids, glucose, waist and cigarette smoking were evaluated. HOMA-IR and TyG-Index were calculated as markers of prevalent hepatic and muscular insulin resistance respectively. Carotid atherosclerosis was assessed by Doppler ultrasonography. The association between cardiovascular risk factors, markers of insulin resistance and carotid atherosclerosis was assessed by multiple logistic regression analyses. In the second cohort, limited to the evaluation of TyG-Index, 1432 subjects were studied. In the first cohort, TyG-Index was significantly associated with carotid atherosclerosis in a model including age, sex, diabetes, cigarette smoking and LDL cholesterol, while HOMA-IR was not. When components of metabolic syndrome were added to the model as dichotomous variables (absent/present), TyG-Index retained its predictive power. The same result was obtained when the metabolic syndrome was added to the model (absence/presence). The association between TyG-Index and carotid atherosclerosis was confirmed in the second cohort. The present findings suggest that TyG-Index is better associated with carotid atherosclerosis than HOMA-IR. © 2013 John Wiley & Sons Ltd.

  6. Diagnostic Accuracies of Glycated Hemoglobin, Fructosamine, and Homeostasis Model Assessment of Insulin Resistance in Predicting Impaired Fasting Glucose, Impaired Glucose Tolerance, or New Onset Diabetes After Transplantation.

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    Rosettenstein, Kerri; Viecelli, Andrea; Yong, Kenneth; Nguyen, Hung Do; Chakera, Aron; Chan, Doris; Dogra, Gursharan; Lim, Ee Mun; Wong, Germaine; Lim, Wai H

    2016-07-01

    New onset diabetes after transplantation (NODAT) is associated with a 3-fold greater risk of cardiovascular disease events, with early identification and treatment potentially attenuating this risk. The optimal screening test to identify those with NODAT remains unclear, and the aim of this study was to examine the diagnostic accuracies of 4 screening tests in identifying impaired fasting glucose, impaired glucose tolerance (IGT), and NODAT. This is a single-center prospective cohort study of 83 nondiabetic kidney transplant recipients between 2008 and 2011. Oral glucose tolerance test was considered the gold standard in identifying IFG/IGT or NODAT. Diagnostic accuracies of random blood glucose, glycated hemoglobin (HBA1c), fructosamine, and Homeostasis Model Assessment-Insulin Resistance in predicting IFG/IGT or NODAT were assessed using the area under the receiver operating characteristic curve. Forty (48%) recipients had IFG/IGT or NODAT. Compared with HBA1c with adjusted area under the curve (AUC) of 0.88 (95% confidence interval [95% CI], 0.77-0.93), fructosamine was the most accurate test with adjusted AUC of 0.92 (95% CI, 0.83-0.96). The adjusted AUCs of random blood glucose and Homeostasis Model Assessment-Insulin Resistance in identifying IFG/IGT were between 0.81 and 0.85. Restricting to identifying IGT/NODAT using 2-hour oral glucose tolerance test (n = 66), fructosamine was the most accurate diagnostic test with adjusted AUC of 0.93 (95% CI, 0.84-0.99), but not statistically different to HBA1c with adjusted AUC of 0.88 (95% CI, 0.76-0.96). Although HBA1c is an acceptable and widely used screening test in detecting IFG/IGT or NODAT, fructosamine may be a more accurate diagnostic test but this needs to be further examined in larger cohorts.

  7. The Homeostasis Model Assessment-adiponectin (HOMA-AD) is the most sensitive predictor of insulin resistance in obese children.

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    Makni, Emna; Moalla, Wassim; Lac, Gérard; Aouichaoui, Chirine; Cannon, Daniel; Elloumi, Mohamed; Tabka, Zouhair

    2012-02-01

    The aim of this study was to examine the efficacy of three indices i.e. adiponectin/leptin ratio, HOMA-IR and HOMA-AD in assessing insulin resistance among obese children. One hundred and twenty-two obese children (57 girls, 65 boys): mean age 13.7±1.3 years, BMI 30.1±4.5kg/m(2), eight tanner stage I, 48 tanner stage II-III, 66 tanner stage IV-V, participated in this study. They were classified into four groups according to sex and the presence of metabolic syndrome characteristics: with metabolic syndrome (MS; 21 girls and 36 boys) and controls without metabolic syndrome (CON, 36 girls and 29 boys). The correlations between these three indices of insulin resistance and the MS criteria were analyzed using linear and multiple regressions and receiver operating characteristics (ROC) curves analysis. The majority of anthropometric and biological parameters as well as adiponectin/leptin ratio, HOMA-IR and HOMA-AD were significantly different between MS and CON in both sexes. Both HOMA-AD and HOMA-IR were significantly correlated with the majority of metabolic syndrome components than was the adiponectin/leptin ratio in MS of both sexes. In boys and girls with and without MS, multiple regression analyses highlighted that both HOMA-AD and adiponectin/leptin ratio (r=-0.99 and r=-0.54 for MS girls and boys respectively, 0.05HOMA-AD and HOMA-IR (r=0.66 and r=0.31 for MS girls and boys respectively, 0.05HOMA-IR. Additionally, the area under the ROC curves for predicting insulin resistance were 0.69 (CI 95%, 0.60-0.77), 0.68 (CI 95%, 0.59-0.76) and 0.71 (CI 95%, 0.62-0.79) for adiponectin/leptin ratio, HOMA-IR and HOMA-AD, respectively. The current study strengthens the validity of the HOMA-AD as an adequate tool for determining insulin resistance among obese children with MS. Copyright © 2012. Published by Elsevier Masson SAS.

  8. Clinical and Biochemical Profiles according to Homeostasis Model Assessment-insulin Resistance (HOMA-IR) in Korean Women with Polycystic Ovary Syndrome.

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    Lee, Da Eun; Park, Soo Yeon; Park, So Yun; Lee, Sa Ra; Chung, Hye Won; Jeong, Kyungah

    2014-12-01

    The aim of this study was to investigate the clinical and biochemical profiles according to homeostasis model assessment of insulin resistance (HOMA-IR) in Korean polycystic ovary syndrome (PCOS) patients. In 458 PCOS patients diagnosed by the Rotterdam European Society for Human Reproduction and Embryology (ESHRE) criteria, measurements of somatometry, blood test of hormones, glucose metabolic and lipid profiles, and transvaginal or transrectal ultrasonogram were carried out. HOMA-IR was then calculated and compared with the clinical and biochemical profiles related to PCOS. The patients were divided into 4 groups by quartiles of HOMA-IR. The mean level of HOMA-IR was 2.18 ± 1.73. Among the four groups separated according to HOMA-IR, body weight, body mass index (BMI), waist-to-hip ratio (WHR), triglyceride (TG), total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, lipid accumulation product (LAP) index, high-sensitivity C-reactive protein (hs-CRP), Apoprotein B, free testosterone, and sex hormone binding globulin (SHBG) were found to be significantly different. TG, LAP index, glucose metabolic profiles, and hs-CRP were positively correlated with HOMA-IR after adjustment for BMI. Our results suggest that the clinical and biochemical profiles which are applicable as cardiovascular risk factors are highly correlated with HOMA-IR in Korean women with PCOS.

  9. Evaluation of fasting plasma insulin concentration as an estimate of insulin action in nondiabetic individuals: comparison with the homeostasis model assessment of insulin resistance (HOMA-IR).

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    Abbasi, Fahim; Okeke, QueenDenise; Reaven, Gerald M

    2014-04-01

    Insulin-mediated glucose disposal varies severalfold in apparently healthy individuals, and approximately one-third of the most insulin resistant of these individuals is at increased risk to develop various adverse clinical syndromes. Since direct measurements of insulin sensitivity are not practical in a clinical setting, several surrogate estimates of insulin action have been proposed, including fasting plasma insulin (FPI) concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) calculated by a formula employing fasting plasma glucose (FPG) and FPI concentrations. The objective of this study was to compare FPI as an estimate of insulin-mediated glucose disposal with values generated by HOMA-IR in 758 apparently healthy nondiabetic individuals. Measurements were made of FPG, FPI, triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) concentrations, and insulin-mediated glucose uptake was quantified by determining steady-state plasma glucose (SSPG) concentration during the insulin suppression test. FPI and HOMA-IR were highly correlated (r = 0.98, P HOMA-IR (r = 0.64). Furthermore, the relationship between FPI and TG (r = 0.35) and HDL-C (r = -0.40) was comparable to that between HOMA-IR and TG (r = 0.39) and HDL-C (r = -0.41). In conclusion, FPI and HOMA-IR are highly correlated in nondiabetic individuals, with each estimate accounting for ~40% of the variability (variance) in a direct measure of insulin-mediated glucose disposal. Calculation of HOMA-IR does not provide a better surrogate estimate of insulin action, or of its associated dyslipidemia, than measurement of FPI.

  10. Fasting serum insulin and the homeostasis model of insulin resistance (HOMA-IR) in the monitoring of lifestyle interventions in obese persons.

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    Vogeser, Michael; König, Daniel; Frey, Ingrid; Predel, Hans-Georg; Parhofer, Klaus Georg; Berg, Aloys

    2007-09-01

    Lifestyle changes with increased physical activity and balanced energy intake are recognized as the principal interventions in obesity and insulin resistance. Only few prospective studies, however, have so far addressed the potential role of routine biochemical markers of insulin sensitivity in the monitoring of respective interventions. Fasting insulin and glucose was measured in 33 obese individuals undergoing a lifestyle modification program (MOBILIS) at baseline and after 1 year. The HOMA-IR index (homeostasis model of insulin resistance) was calculated as [fasting serum glucose*fasting serum insulin/22.5], with lower values indicating a higher degree of insulin sensitivity. While the median body mass index (BMI) and waist circumference decreased by 10% and 11%, respectively, the HOMA-IR index decreased in an over-proportional manner by 45% within 1 year (BMI baseline, median 35.7, interquartile range (IQR) 33.7-37.7; after 1 year, median 32.2, IQR 29.6-35.1. HOMA-IR baseline, median 2.9, IQR 1.5-4.6; after 1 year 1.6, IQR 0.9-2.7). In contrast to HOMA-IR and fasting serum insulin, no significant changes in fasting serum glucose were observed. Baseline and post-intervention HOMA-IR showed a high degree of inter-individual variation with eight individuals maintaining high HOMA-IR values despite weight loss after 1 year of intervention. Individual changes in the carbohydrate metabolism achieved by a lifestyle intervention program were displayed by fasting serum insulin concentrations and the HOMA-IR but not by fasting glucose measurement alone. Therefore, assessment of the HOMA-IR may help to individualize lifestyle interventions in obesity and to objectify improvements in insulin sensitivity after therapeutic lifestyle changes.

  11. Association between Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Components of Metabolic Syndrome in Young Chinese Men.

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    Ying, X; Song, Zh; Zhao, Ch; Jiang, Y

    2011-01-01

    To investigate the prevalence of metabolic syndrome (MetS) in young Chinese population and assess the association between HOMA-IR and different components of MetS in young Chinese men. Overall 5576 young Chinese subjects (age range [19-44 yr], 3636 men) were enrolled in, who visited our Health Care Center for a related health checkup from March to December 2008. The international diabetes federation (IDF) definition for MetS was used. The SPSS statistical package, version 11.5 was used for the statistical analysis. The prevalence of MetS was 21.81% in young men and 5.62% in young women. According to suffering from different numbers of MetS components, the male subjects were divided into four groups. Numbers of MetS components were more and HOMA-IR values were significantly higher. In this male population, the quartile of HOMA-IR was higher, values of triglyceride (TG), fasting plasma glucose (FBG), systolic blood pressure(SBP), diastolic blood pressure(DBP) and waist circumference (WC) were all significantly higher, as well as high density lipoprotein cholesterol (HDL-C) value was significantly lower (P= 0.000). In Spearman's correlation analysis, HOMA-IR was positively correlated with TG, FBG, SBP, DBP and WC, and negatively correlated with HDL-C (r= 0.460, 0.464, 0.362, 0.346, 0.586, -0.357, respectively, all P value= 0.000). The prevalence of MetS in these young Chinese men was obviously high. Insulin resistance played an important role in occurrence and development of MetS. Waist circumference was the best correlation with HOMA-IR among all components of MetS.

  12. Markers of Skeletal Muscle Mitochondrial Function and Lipid Accumulation Are Moderately Associated with the Homeostasis Model Assessment Index of Insulin Resistance in Obese Men

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    Samjoo, Imtiaz A.; Safdar, Adeel; Hamadeh, Mazen J.; Glover, Alexander W.; Mocellin, Nicholas J.; Santana, Jose; Little, Jonathan P.; Steinberg, Gregory R.; Raha, Sandeep; Tarnopolsky, Mark A.

    2013-01-01

    Lower skeletal muscle mitochondrial oxidative phosphorylation capacity (OXPHOS) and intramyocellular lipid (IMCL) accumulation have been implicated in the etiology of insulin resistance (IR) in obesity. The purpose of this study was to examine the impact of endurance exercise on biochemical and morphological measures of IMCL and mitochondrial content, and their relationship to IR in obese individuals. We examined mitochondrial content (subunit protein abundance and maximal activity of electron transport chain enzymes), IMCL/mitochondrial morphology in both subsarcolemmal (SS) and intermyofibrillar (IMF) regions by transmission electron microscopy, and intracellular lipid metabolites (diacylglycerol and ceramide) in vastus lateralis biopsies, as well as, the homeostasis model assessment index of IR (HOMA-IR) prior to and following twelve weeks of an endurance exercise regimen in healthy age- and physical activity-matched lean and obese men. Obese men did not show evidence of mitochondrial OXPHOS dysfunction, disproportionate IMCL content in sub-cellular regions, or diacylglycerol/ceramide accretion despite marked IR vs. lean controls. Endurance exercise increased OXPHOS and mitochondrial size and density, but not number of individual mitochondrial fragments, with moderate improvements in HOMA-IR. Exercise reduced SS IMCL content (size, number and density), increased IMF IMCL content, while increasing IMCL/mitochondrial juxtaposition in both regions. HOMA-IR was inversely associated with SS (r = −0.34; P = 0.051) and IMF mitochondrial density (r = −0.29; P = 0.096), IMF IMCL/mitochondrial juxtaposition (r = −0.30; P = 0.086), and COXII (r = −0.32; P = 0.095) and COXIV protein abundance (r = −0.35; P = 0.052); while positively associated with SS IMCL size (r = 0.28; P = 0.119) and SS IMCL density (r = 0.25; P = 0.152). Our findings suggest that once physical activity and cardiorespiratory fitness have

  13. Markers of skeletal muscle mitochondrial function and lipid accumulation are moderately associated with the homeostasis model assessment index of insulin resistance in obese men.

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    Imtiaz A Samjoo

    Full Text Available Lower skeletal muscle mitochondrial oxidative phosphorylation capacity (OXPHOS and intramyocellular lipid (IMCL accumulation have been implicated in the etiology of insulin resistance (IR in obesity. The purpose of this study was to examine the impact of endurance exercise on biochemical and morphological measures of IMCL and mitochondrial content, and their relationship to IR in obese individuals. We examined mitochondrial content (subunit protein abundance and maximal activity of electron transport chain enzymes, IMCL/mitochondrial morphology in both subsarcolemmal (SS and intermyofibrillar (IMF regions by transmission electron microscopy, and intracellular lipid metabolites (diacylglycerol and ceramide in vastus lateralis biopsies, as well as, the homeostasis model assessment index of IR (HOMA-IR prior to and following twelve weeks of an endurance exercise regimen in healthy age- and physical activity-matched lean and obese men. Obese men did not show evidence of mitochondrial OXPHOS dysfunction, disproportionate IMCL content in sub-cellular regions, or diacylglycerol/ceramide accretion despite marked IR vs. lean controls. Endurance exercise increased OXPHOS and mitochondrial size and density, but not number of individual mitochondrial fragments, with moderate improvements in HOMA-IR. Exercise reduced SS IMCL content (size, number and density, increased IMF IMCL content, while increasing IMCL/mitochondrial juxtaposition in both regions. HOMA-IR was inversely associated with SS (r = -0.34; P = 0.051 and IMF mitochondrial density (r = -0.29; P = 0.096, IMF IMCL/mitochondrial juxtaposition (r = -0.30; P = 0.086, and COXII (r = -0.32; P = 0.095 and COXIV protein abundance (r = -0.35; P = 0.052; while positively associated with SS IMCL size (r = 0.28; P = 0.119 and SS IMCL density (r = 0.25; P = 0.152. Our findings suggest that once physical activity and cardiorespiratory fitness have been

  14. A mathematical model of brain glucose homeostasis

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    Kimura Hidenori

    2009-11-01

    Full Text Available Abstract Background The physiological fact that a stable level of brain glucose is more important than that of blood glucose suggests that the ultimate goal of the glucose-insulin-glucagon (GIG regulatory system may be homeostasis of glucose concentration in the brain rather than in the circulation. Methods In order to demonstrate the relationship between brain glucose homeostasis and blood hyperglycemia in diabetes, a brain-oriented mathematical model was developed by considering the brain as the controlled object while the remaining body as the actuator. After approximating the body compartmentally, the concentration dynamics of glucose, as well as those of insulin and glucagon, are described in each compartment. The brain-endocrine crosstalk, which regulates blood glucose level for brain glucose homeostasis together with the peripheral interactions among glucose, insulin and glucagon, is modeled as a proportional feedback control of brain glucose. Correlated to the brain, long-term effects of psychological stress and effects of blood-brain-barrier (BBB adaptation to dysglycemia on the generation of hyperglycemia are also taken into account in the model. Results It is shown that simulation profiles obtained from the model are qualitatively or partially quantitatively consistent with clinical data, concerning the GIG regulatory system responses to bolus glucose, stepwise and continuous glucose infusion. Simulations also revealed that both stress and BBB adaptation contribute to the generation of hyperglycemia. Conclusion Simulations of the model of a healthy person under long-term severe stress demonstrated that feedback control of brain glucose concentration results in elevation of blood glucose level. In this paper, we try to suggest that hyperglycemia in diabetes may be a normal outcome of brain glucose homeostasis.

  15. [Homeostasis model assessment (HOMA) values in Chilean elderly subjects].

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    Garmendia, María Luisa; Lera, Lydia; Sánchez, Hugo; Uauy, Ricardo; Albala, Cecilia

    2009-11-01

    The homeostasis assessment model for insulin resistance (HOMA-IR) estimates insulin resistance using basal insulin and glucose values and has a good concordance with values obtained with the euglycemic clamp. However it has a high variability that depends on environmental, genetic and physiologic factors. Therefore it is imperative to establish normal HOMA values in different populations. To report HOMA-IR values in Chilean elderly subjects and to determine the best cutoff point to diagnose insulin resistance. Cross sectional study of 1003 subjects older than 60 years of whom 803 (71% women) did not have diabetes. In 154 subjects, an oral glucose tolerance test was also performed. Insulin resistance (IR) was defined as the HOMA value corresponding to percentile 75 of subjects without over or underweight. The behavior of HOMA-IR in metabolic syndrome was studied and receiver operating curves (ROC) were calculated, using glucose intolerance defined as a blood glucose over 140 mg/dl and hyperinsulinemia, defined as a serum insulin over 60 microU/ml, two hours after the glucose load. Median HOMA-IR values were 1.7. Percentile 75 in subjects without obesity or underweight was 2.57. The area under the ROC curve, when comparing HOMA-IR with glucose intolerance and hyperinsulinemia, was 0.8 (95% confidence values 0.72-0.87), with HOMA-IR values ranging from 2.04 to 2.33. HOMA-IR is a useful method to determine insulin resistance in epidemiological studies. The HOMA-IR cutoff point for insulin resistance defined in thi spopulation was 2.6.

  16. Definition of insulin resistance using the homeostasis model assessment (HOMA-IR) in IVF patients diagnosed with polycystic ovary syndrome (PCOS) according to the Rotterdam criteria.

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    Alebić, Miro Šimun; Bulum, Tomislav; Stojanović, Nataša; Duvnjak, Lea

    2014-11-01

    Polycystic ovary syndrome (PCOS) women are more insulin resistant than general population. Prevalence data on insulin resistance (IR) in PCOS vary depending on population characteristics and methodology used. The objectives of this study were to investigate whether IR in PCOS is exclusively associated with body mass and to assess the prevalence of IR in lean and overweight/obese PCOS. Study included 250 consecutive women who attended a Department of Human Reproduction diagnosed as having PCOS according to the Rotterdam criteria. Control group comprised 500 healthy women referred for male factor infertility evaluation during the same period as the PCOS women. PCOS women (n = 250) were more insulin resistant than controls (n = 500) even after adjustment for age and body mass index (BMI) (P = 0.03). Using logistic regression analysis, BMI ≥ 25 kg/m(2) (OR 6.0; 95 % CI 3.3-11.0), PCOS (OR 2.2; 95 % CI 1.4-3.5) and waist circumference ≥ 80 cm (OR 2.0; 95 % CI 1.1-3.8) were identified as independent determinants of IR (P IR was more prevalent in overweight/obese controls (n = 100) than in lean PCOS women (n = 150), 31 versus 9.3 %, but less prevalent than in overweight/obese PCOS (n = 100), 31 versus 57 %. The prevalence of IR between lean controls (5 %) and lean PCOS (9.3 %) did not significantly differ. Both PCOS-specific and obesity-related IR independently contribute to IR in PCOS. Using HOMA-IR cutoff value of 3.15 specific for Croatian women in our clinical setting, the assessed prevalence of IR in lean and overweight/obese PCOS women was 9.3 and 57 %, respectively.

  17. Optimal Cut-Offs of Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) to Identify Dysglycemia and Type 2 Diabetes Mellitus: A 15-Year Prospective Study in Chinese.

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    Lee, C H; Shih, A Z L; Woo, Y C; Fong, C H Y; Leung, O Y; Janus, E; Cheung, B M Y; Lam, K S L

    The optimal reference range of homeostasis model assessment of insulin resistance (HOMA-IR) in normal Chinese population has not been clearly defined. Here we address this issue using the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS), a prospective population-based cohort study with long-term follow-up. In this study, normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) were defined according to the 1998 World Health Organization criteria. Dysglycemia referred to IFG, IGT or T2DM. This study comprised two parts. Part one was a cross-sectional study involving 2,649 Hong Kong Chinese subjects, aged 25-74 years, at baseline CRISPS-1 (1995-1996). The optimal HOMA-IR cut-offs for dysglycemia and T2DM were determined by the receiver-operating characteristic (ROC) curve. Part two was a prospective study involving 872 subjects who had persistent NGT at CRISPS-4 (2010-2012) after 15 years of follow-up. At baseline, the optimal HOMA-IR cut-offs to identify dysglyceia and T2DM were 1.37 (AUC = 0.735; 95% confidence interval [CI] = 0.713-0.758; Sensitivity [Se] = 65.6%, Specificity [Sp] = 71.3%] and 1.97 (AUC = 0.807; 95% CI = 0.777-0.886; Se = 65.5%, Sp = 82.9%) respectively. These cut-offs, derived from the cross-sectional study at baseline, corresponded closely to the 75th (1.44) and 90th (2.03) percentiles, respectively, of the HOMA-IR reference range derived from the prospective study of subjects with persistent NGT. HOMA-IR cut-offs, of 1.4 and 2.0, which discriminated dysglycemia and T2DM respectively from NGT in Southern Chinese, can be usefully employed as references in clinical research involving the assessment of insulin resistance.

  18. Optimal cut-off values for the homeostasis model assessment of insulin resistance (HOMA-IR) and pre-diabetes screening: Developments in research and prospects for the future.

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    Tang, Qi; Li, Xueqin; Song, Peipei; Xu, Lingzhong

    2015-12-01

    Diabetes mellitus (DM) appears to be increasing rapidly, threatening to reduce life expectancy for humans around the globe. The International Diabetes Federation (IDF) has estimated that there will be 642 million people living with the disease by 2040 and half as many again who will be not diagnosed. This means that pre-DM screening is a critical issue. Insulin resistance (IR) has emerged as a major pathophysiological factor in the development and progression of DM since it is evident in susceptible individuals at the early stages of DM, and particularly type 2 DM (T2DM). Therefore, assessment of IR via the homeostasis model assessment of IR (HOMA-IR) is a key index for the primary prevention of DM and is thus found in guidelines for screening of high-risk groups. However, the cut-off values of HOMA-IR differ for different races, ages, genders, diseases, complications, etc. due to the complexity of IR. This hampers the determination of specific cut-off values of HOMA-IR in different places and in different situations. China has not published an official index to gauge IR for primary prevention of T2DM in the diabetic and non-diabetic population except for children and adolescents ages 6-12 years. Hence, this article summarizes developments in research on IR, HOMA-IR, and pre-DM screening in order to provide a reference for optimal cut-off values of HOMA-IR for the diagnosis of DM in the Chinese population.

  19. Orally disintegrating and oral standard olanzapine tablets similarly elevate the homeostasis model assessment of insulin resistance index and plasma triglyceride levels in 12 healthy men: a randomized crossover study.

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    Vidarsdottir, Solrun; Vlug, Pauline; Roelfsema, Ferdinand; Frölich, Marijke; Pijl, Hanno

    2010-09-01

    Treatment with olanzapine is associated with obesity, diabetes mellitus, and dyslipidemia. Reports have indicated that orally disintegrating tablets (ODT) cause less weight gain than oral standard tablets (OST). The aim of this study was to compare the effect of short-term treatment with these 2 distinct olanzapine formulations on glucose and lipid metabolism in healthy men. Twelve healthy men (mean ± SEM age: 25.1 ± 5.5 years) received olanzapine ODT (10 mg od, 8 days), olanzapine OST (10 mg od, 8 days), or no intervention in a randomized crossover design. At breakfast and dinner, glucose, insulin, free fatty acids (FFA), and triglyceride concentrations were measured at 10-minute intervals from 30 minutes prior to 2 hours after ingestion of standard meals. Leptin and adiponectin concentrations were measured at 20- and 30-minute intervals, respectively, between 0000h-1200h. Physical activity was assessed with an accelerometer. Fuel oxidation was measured in fasting condition by indirect calorimetry. The study was conducted from April 2006 through September 2006. Treatment with olanzapine ODT and OST equally elevated the homeostasis model assessment of insulin resistance (HOMA-IR) (P = .005). At breakfast, both formulations equally increased fasting and postprandial triglyceride concentrations (P = .013 and P = .005, respectively) while decreasing fasting and postprandial FFA concentrations (P = .004 and P = .009, respectively). Body weight, body composition, physical activity, or fuel oxidation did not differ between treatment modalities. Eight days of treatment with both olanzapine formulations similarly increased HOMA-IR and triglyceride concentrations and decreased FFA concentrations in response to standard meals without affecting anthropometrics or physical activity. These data suggest that olanzapine hampers insulin action via mechanistic routes other than body adiposity or physical inactivity. controlled-trials.com. Identifier: ISRCTN17632637. © Copyright

  20. Increase in homeostasis model assessment of insulin resistance (HOMA-IR) had a strong impact on the development of type 2 diabetes in Japanese individuals with impaired insulin secretion: the Saku study.

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    Morimoto, Akiko; Tatsumi, Yukako; Soyano, Fumie; Miyamatsu, Naomi; Sonoda, Nao; Godai, Kayo; Ohno, Yuko; Noda, Mitsuhiko; Deura, Kijyo

    2014-01-01

    Our aim was to assess the impact of increase in homeostasis model assessment of insulin resistance (HOMA-IR) on the development of type 2 diabetes in Japanese individuals with impaired insulin secretion (IIS). This study included 2,209 participants aged 30-69 without diabetes at baseline who underwent comprehensive medical check-ups between April 2006 and March 2007 at Saku Central Hospital. Participants were classified into eight groups according to the combination of baseline IIS status (non-IIS and IIS) and category of HOMA-IR change between the baseline and follow-up examinations (decrease, no change/small increase, moderate increase, and large increase). Type 2 diabetes was determined from fasting and 2 h post-load plasma glucose concentrations at the follow-up examination between April 2009 and March 2011. At baseline, 669 individuals (30.3%) were classified as having IIS. At follow-up, 74 individuals developed type 2 diabetes. After adjusting for confounding factors including baseline HOMA-IR values, the multivariable-adjusted odds ratios (95% confidence intervals) for type 2 diabetes in the non-IIS with a decrease (mean change in HOMA-IR: -0.47), non-IIS with a moderate increase (mean change in HOMA-IR: 0.28), non-IIS with a large increase (mean change in HOMA-IR: 0.83), IIS with a decrease (mean change in HOMA-IR: -0.36), IIS with no change/small increase (mean change in HOMA-IR: 0.08), IIS with a moderate increase (mean change in HOMA-IR: 0.27), and IIS with a large increase (mean change in HOMA-IR: 0.73) groups, relative to the non-IIS with no change/small increase (mean change in HOMA-IR: 0.08) group were 0.23 (0.04, 1.11), 1.22 (0.26, 5.72), 2.01 (0.70, 6.46), 1.37 (0.32, 4.28), 3.60 (0.83, 15.57), 5.24 (1.34, 20.52), and 7.01 (1.75, 24.18), respectively. Moderate and large increases in HOMA-IR had a strong impact on the development of type 2 diabetes among individuals with IIS in this Japanese population.

  1. The impact of transsphenoidal surgery on glucose homeostasis and insulin resistance in acromegaly.

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    Stelmachowska-Banaś, Maria; Zieliński, Grzegorz; Zdunowski, Piotr; Podgórski, Jan; Zgliczyński, Wocjiech

    2011-01-01

    Impaired glucose tolerance and overt diabetes mellitus are frequently associated with acro-megaly. The aim of this study was to find out whether these alterations could be reversed after transsphenoidal surgery. Two hundred and thirty-nine acromegalic patients were studied before and 6-12 months after transsphenoidal surgery. Diagnosis of active acromegaly was established on the basis of widely recognized criteria. In each patient, glucose and insulin concentrations were assessed during the 75 γ oral glucose tolerance test (OGTT). To estimate insulin resistance, we used homeostasis model assessment (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). At the moment of diagnosis, diabetes mellitus was present in 25% of the acromegalic patients. After surgery, the pre-valence of diabetes mellitus normalized to the level present in the general Polish population. We found a statistically significant reduction after surgery in plasma glucose levels both fasting (89.45 ± 13.92 mg/dL vs. 99.12 ± 17.33 mg/dL, p surgery compared to the moment of diagnosis (15.44 ± 8.80 mIU/mL vs. 23.40 ± 10.24 mIU/mL, p transsphenoidal surgery, there was a significant reduction in HOMA-IR (3.08 vs. 6.76, p surgery in fasting glucose and insulin levels between patients with controlled and in-adequately controlled disease. We conclude that in acromegalic patients glucose homeostasis alterations and insulin sensitivity can be normalized after transsphenoidal surgery, even if strict biochemical cure criteria are not fulfilled.

  2. Fibroblast Growth Factor 21 (FGF21, Free Fatty Acid (FFA, High Sensitivity C-reactive Protein (hsCRP and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR Among Indonesian Obese Non-Diabetic Males

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    Yani Lina

    2009-12-01

    Full Text Available BACKGROUND: Fibroblast growth factor-21 (FGF21 is known as an important endocrine and paracrine regulator of metabolic homeostasis. Recent studies have shown that FGF21 attenuates lipolysis in human adipocytes, which is suggested as a FGF21's mechanism as anti-hyperlipidemia, anti-hyperglycemia and anti-obesity. The aim of this study was to measure the correlation between FGF21, FFA, hsCRP and HOMA-IR among Indonesian obese non diabetic males. METHODS: The study was observational with cross sectional design. The analysis was done in 137 subjects aged 30-60 years with non diabetic abdominal obesity. We measured the biochemical markers FGF21, FFA, hsCRP, fasting insulin and fasting glucose. We also measured weight, height, waist circumrefence (WC, creatinine, serum glutamin oxaloacetic transaminase (SGOT, and serum glutamic pyruvic transaminase (SGPT, systolic blood pressure (SBP and diastolic blood pressure (DBP. Correlation between markers was measured using Pearson and Spearman's analysis. RESULTS: There were significant positive correlations between FGF21-HOMA-IR (r=0.314, p=0.000; FGF21-WC (r=0.173, p=0.043; FFA=hsCRP r=0.270, p=0.001; and WC-HOMA-IR (r=0.279, p=0.001. There was significant negative correlation between FGF21-FFA (r=-0.038, p=0.657 and FGF21-hsCRP (r=-0.061, p=0.482. CONCLUSIONS: In this study we found that although there was no significant correlation, FGF21 might act as an anti-lipolytic and anti-inflammation agent among Indonesian obese non-diabetic males. Our findings agree with results of previous studies that the positive correlation between FGF21-WC and FGF21-HOMA-IR might occur as a compensatory mechanism or resistance to FGF21 in obesity. KEYWORDS: obesity, FGF21, FFA, hsCRP, HOMA-IR.

  3. Calcineurin signaling and membrane lipid homeostasis regulates iron mediated multidrug resistance mechanisms in Candida albicans.

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    Saif Hameed

    2011-04-01

    Full Text Available We previously demonstrated that iron deprivation enhances drug susceptibility of Candida albicans by increasing membrane fluidity which correlated with the lower expression of ERG11 transcript and ergosterol levels. The iron restriction dependent membrane perturbations led to an increase in passive diffusion and drug susceptibility. The mechanisms underlying iron homeostasis and multidrug resistance (MDR, however, are not yet resolved. To evaluate the potential mechanisms, we used whole genome transcriptome and electrospray ionization tandem mass spectrometry (ESI-MS/MS based lipidome analyses of iron deprived Candida cells to examine the new cellular circuitry of the MDR of this pathogen. Our transcriptome data revealed a link between calcineurin signaling and iron homeostasis. Among the several categories of iron deprivation responsive genes, the down regulation of calcineurin signaling genes including HSP90, CMP1 and CRZ1 was noteworthy. Interestingly, iron deprived Candida cells as well as iron acquisition defective mutants phenocopied molecular chaperone HSP90 and calcineurin mutants and thus were sensitive to alkaline pH, salinity and membrane perturbations. In contrast, sensitivity to above stresses did not change in iron deprived DSY2146 strain with a hyperactive allele of calcineurin. Although, iron deprivation phenocopied compromised HSP90 and calcineurin, it was independent of protein kinase C signaling cascade. Notably, the phenotypes associated with iron deprivation in genetically impaired calcineurin and HSP90 could be reversed with iron supplementation. The observed down regulation of ergosterol (ERG1, ERG2, ERG11 and ERG25 and sphingolipid biosynthesis (AUR1 and SCS7 genes followed by lipidome analysis confirmed that iron deprivation not only disrupted ergosterol biosynthesis, but it also affected sphingolipid homeostasis in Candida cells. These lipid compositional changes suggested extensive remodeling of the membranes in iron

  4. Delineating the regulation of energy homeostasis using hypothalamic cell models.

    Science.gov (United States)

    Wellhauser, Leigh; Gojska, Nicole M; Belsham, Denise D

    2015-01-01

    Attesting to its intimate peripheral connections, hypothalamic neurons integrate nutritional and hormonal cues to effectively manage energy homeostasis according to the overall status of the system. Extensive progress in the identification of essential transcriptional and post-translational mechanisms regulating the controlled expression and actions of hypothalamic neuropeptides has been identified through the use of animal and cell models. This review will introduce the basic techniques of hypothalamic investigation both in vivo and in vitro and will briefly highlight the key advantages and challenges of their use. Further emphasis will be place on the use of immortalized models of hypothalamic neurons for in vitro study of feeding regulation, with a particular focus on cell lines proving themselves most fruitful in deciphering fundamental basics of NPY/AgRP, Proglucagon, and POMC neuropeptide function. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Coupling between phosphate and calcium homeostasis: a mathematical model.

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    Granjon, David; Bonny, Olivier; Edwards, Aurélie

    2017-12-01

    We developed a mathematical model of calcium (Ca) and phosphate (PO 4 ) homeostasis in the rat to elucidate the hormonal mechanisms that underlie the regulation of Ca and PO 4 balance. The model represents the exchanges of Ca and PO 4 between the intestine, plasma, kidneys, bone, and the intracellular compartment, and the formation of Ca-PO 4 -fetuin-A complexes. It accounts for the regulation of these fluxes by parathyroid hormone (PTH), vitamin D 3 , fibroblast growth factor 23, and Ca 2+ -sensing receptors. Our results suggest that the Ca and PO 4 homeostatic systems are robust enough to handle small perturbations in the production rate of either PTH or vitamin D 3 The model predicts that large perturbations in PTH or vitamin D 3 synthesis have a greater impact on the plasma concentration of Ca 2+ ([Ca 2+ ] p ) than on that of PO 4 ([PO 4 ] p ); due to negative feedback loops, [PO 4 ] p does not consistently increase when the production rate of PTH or vitamin D 3 is decreased. Our results also suggest that, following a large PO 4 infusion, the rapidly exchangeable pool in bone acts as a fast, transient storage PO 4 compartment (on the order of minutes), whereas the intracellular pool is able to store greater amounts of PO 4 over several hours. Moreover, a large PO 4 infusion rapidly lowers [Ca 2+ ] p owing to the formation of CaPO 4 complexes. A large Ca infusion, however, has a small impact on [PO 4 ] p , since a significant fraction of Ca binds to albumin. This mathematical model is the first to include all major regulatory factors of Ca and PO 4 homeostasis. Copyright © 2017 the American Physiological Society.

  6. Mathematical model of glucose-insulin homeostasis in healthy rats.

    Science.gov (United States)

    Lombarte, Mercedes; Lupo, Maela; Campetelli, German; Basualdo, Marta; Rigalli, Alfredo

    2013-10-01

    According to the World Health Organization there are over 220 million people in the world with diabetes and 3.4 million people died in 2004 as a consequence of this pathology. Development of an artificial pancreas would allow to restore control of blood glucose by coupling an infusion pump to a continuous glucose sensor in the blood. The design of such a device requires the development and application of mathematical models which represent the gluco-regulatory system. Models developed by other research groups describe very well the gluco-regulatory system but have a large number of mathematical equations and require complex methodologies for the estimation of its parameters. In this work we propose a mathematical model to study the homeostasis of glucose and insulin in healthy rats. The proposed model consists of three differential equations and 8 parameters that describe the variation of: blood glucose concentration, blood insulin concentration and amount of glucose in the intestine. All parameters were obtained by setting functions to the values of glucose and insulin in blood obtained after oral glucose administration. In vivo and in silico validations were performed. Additionally, a qualitative analysis has been done to verify the aforementioned model. We have shown that this model has a single, biologically consistent equilibrium point. This model is a first step in the development of a mathematical model for the type I diabetic rat. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Bistable dynamics underlying excitability of ion homeostasis in neuron models.

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    Niklas Hübel

    2014-05-01

    Full Text Available When neurons fire action potentials, dissipation of free energy is usually not directly considered, because the change in free energy is often negligible compared to the immense reservoir stored in neural transmembrane ion gradients and the long-term energy requirements are met through chemical energy, i.e., metabolism. However, these gradients can temporarily nearly vanish in neurological diseases, such as migraine and stroke, and in traumatic brain injury from concussions to severe injuries. We study biophysical neuron models based on the Hodgkin-Huxley (HH formalism extended to include time-dependent ion concentrations inside and outside the cell and metabolic energy-driven pumps. We reveal the basic mechanism of a state of free energy-starvation (FES with bifurcation analyses showing that ion dynamics is for a large range of pump rates bistable without contact to an ion bath. This is interpreted as a threshold reduction of a new fundamental mechanism of ionic excitability that causes a long-lasting but transient FES as observed in pathological states. We can in particular conclude that a coupling of extracellular ion concentrations to a large glial-vascular bath can take a role as an inhibitory mechanism crucial in ion homeostasis, while the Na⁺/K⁺ pumps alone are insufficient to recover from FES. Our results provide the missing link between the HH formalism and activator-inhibitor models that have been successfully used for modeling migraine phenotypes, and therefore will allow us to validate the hypothesis that migraine symptoms are explained by disturbed function in ion channel subunits, Na⁺/K⁺ pumps, and other proteins that regulate ion homeostasis.

  8. Modelling of Arabidopsis LAX3 expression suggests auxin homeostasis.

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    Mellor, Nathan; Péret, Benjamin; Porco, Silvana; Sairanen, Ilkka; Ljung, Karin; Bennett, Malcolm; King, John

    2015-02-07

    Emergence of new lateral roots from within the primary root in Arabidopsis has been shown to be regulated by the phytohormone auxin, via the expression of the auxin influx carrier LAX3, mediated by the ARF7/19 IAA14 signalling module (Swarup et al., 2008). A single cell model of the LAX3 and IAA14 auxin response was formulated and used to demonstrate that hysteresis and bistability may explain the experimentally observed 'all-or-nothing' LAX3 spatial expression pattern in cortical cells containing a gradient of auxin concentrations. The model was tested further by using a parameter fitting algorithm to match model output with qRT-PCR mRNA expression data following exogenous auxin treatment. It was found that the model is able to show good agreement with the data, but only when the exogenous auxin signal is degraded over time, at a rate higher than that measured in the experimental medium, suggesting the triggering of an endogenous auxin homeostasis mechanism. Testing the model over a more physiologically relevant range of extracellular auxin shows bistability and hysteresis still occur when using the optimised parameters, providing the rate of LAX3 active auxin transport is sufficiently high relative to passive diffusion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Endogenous cytokinin overproduction modulates ROS homeostasis and decreases salt stress resistance in Arabidopsis thaliana

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    Yanping eWang

    2015-11-01

    Full Text Available Cytokinins in plants are crucial for numerous biological processes, including seed germination, cell division and differentiation, floral initiation and adaptation to abiotic stresses. The salt stress can promote reactive oxygen species (ROS production in plants which are highly toxic and ultimately results in oxidative stress. However, the correlation between endogenous cytokinin production and ROS homeostasis in responding to salt stress is poorly understood. In this study, we analyzed the correlation of overexpressing the cytokinin biosynthetic gene AtIPT8 (adenosine phosphate-isopentenyl transferase 8 and the response of salt stress in Arabidopsis. Overproduction of cytokinins, which was resulted by the inducible overexpression of AtIPT8, significantly inhibited the primary root growth and true leaf emergence, especially under the conditions of exogenous salt, glucose and mannitol treatments. Upon cytokinin overproduction, the salt stress resistance was declined, and resulted in less survival rates and chlorophyll content. Interestingly, ROS production was obviously increased with the salt treatment, accompanied by endogenously overproduced cytokinins. The activities of CAT and SOD, which are responsible for scavenging ROS, were also affected. Transcription profiling revealed that the differential expressions of ROS-producing and scavenging related genes, the photosynthesis-related genes and stress responsive genes were existed in transgenic plants of overproducing cytokinins. Our results suggested that broken in the homeostasis of cytokinins in plant cells could modulate the salt stress responses through a ROS-mediated regulation in Arabidopsis.

  10. Molecular aspects of glucose homeostasis in skeletal muscle--A focus on the molecular mechanisms of insulin resistance.

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    Carnagarin, Revathy; Dharmarajan, Arun M; Dass, Crispin R

    2015-12-05

    Among all the varied actions of insulin, regulation of glucose homeostasis is the most critical and intensively studied. With the availability of glucose from nutrient metabolism, insulin action in muscle results in increased glucose disposal via uptake from the circulation and storage of excess, thereby maintaining euglycemia. This major action of insulin is executed by redistribution of the glucose transporter protein, GLUT4 from intracellular storage sites to the plasma membrane and storage of glucose in the form of glycogen which also involves modulation of actin dynamics that govern trafficking of all the signal proteins of insulin signal transduction. The cellular mechanisms responsible for these trafficking events and the defects associated with insulin resistance are largely enigmatic, and this review provides a consolidated overview of the various molecular mechanisms involved in insulin-dependent glucose homeostasis in skeletal muscle, as insulin resistance at this major peripheral site impacts whole body glucose homeostasis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Optimal cut-off of homeostasis model assessment of insulin resistance (HOMA-IR) for the diagnosis of metabolic syndrome: third national surveillance of risk factors of non-communicable diseases in Iran (SuRFNCD-2007).

    Science.gov (United States)

    Esteghamati, Alireza; Ashraf, Haleh; Khalilzadeh, Omid; Zandieh, Ali; Nakhjavani, Manouchehr; Rashidi, Armin; Haghazali, Mehrdad; Asgari, Fereshteh

    2010-04-07

    We have recently determined the optimal cut-off of the homeostatic model assessment of insulin resistance for the diagnosis of insulin resistance (IR) and metabolic syndrome (MetS) in non-diabetic residents of Tehran, the capital of Iran. The aim of the present study is to establish the optimal cut-off at the national level in the Iranian population with and without diabetes. Data of the third National Surveillance of Risk Factors of Non-Communicable Diseases, available for 3,071 adult Iranian individuals aging 25-64 years were analyzed. MetS was defined according to the Adult Treatment Panel III (ATPIII) and International Diabetes Federation (IDF) criteria. HOMA-IR cut-offs from the 50th to the 95th percentile were calculated and sensitivity, specificity, and positive likelihood ratio for MetS diagnosis were determined. The receiver operating characteristic (ROC) curves of HOMA-IR for MetS diagnosis were depicted, and the optimal cut-offs were determined by two different methods: Youden index, and the shortest distance from the top left corner of the curve. The area under the curve (AUC) (95%CI) was 0.650 (0.631-0.670) for IDF-defined MetS and 0.683 (0.664-0.703) with the ATPIII definition. The optimal HOMA-IR cut-off for the diagnosis of IDF- and ATPIII-defined MetS in non-diabetic individuals was 1.775 (sensitivity: 57.3%, specificity: 65.3%, with ATPIII; sensitivity: 55.9%, specificity: 64.7%, with IDF). The optimal cut-offs in diabetic individuals were 3.875 (sensitivity: 49.7%, specificity: 69.6%) and 4.325 (sensitivity: 45.4%, specificity: 69.0%) for ATPIII- and IDF-defined MetS, respectively. We determined the optimal HOMA-IR cut-off points for the diagnosis of MetS in the Iranian population with and without diabetes.

  12. Involvement of the Pleiotropic Drug Resistance Response, Protein Kinase C Signaling, and Altered Zinc Homeostasis in Resistance of Saccharomyces cerevisiae to Diclofenac ▿

    Science.gov (United States)

    van Leeuwen, Jolanda S.; Vermeulen, Nico P. E.; Vos, J. Chris

    2011-01-01

    Diclofenac is a widely used analgesic drug that can cause serious adverse drug reactions. We used Saccharomyces cerevisiae as a model eukaryote with which to elucidate the molecular mechanisms of diclofenac toxicity and resistance. Although most yeast cells died during the initial diclofenac treatment, some survived and started growing again. Microarray analysis of the adapted cells identified three major processes involved in diclofenac detoxification and tolerance. In particular, pleiotropic drug resistance (PDR) genes and genes under the control of Rlm1p, a transcription factor in the protein kinase C (PKC) pathway, were upregulated in diclofenac-adapted cells. We tested if these processes or pathways were directly involved in diclofenac toxicity or resistance. Of the pleiotropic drug resistance gene products, the multidrug transporter Pdr5p was crucially important for diclofenac tolerance. Furthermore, deletion of components of the cell wall stress-responsive PKC pathway increased diclofenac toxicity, whereas incubation of cells with the cell wall stressor calcofluor white before the addition of diclofenac decreased its toxicity. Also, diclofenac induced flocculation, which might trigger the cell wall alterations. Genes involved in ribosome biogenesis and rRNA processing were downregulated, as were zinc-responsive genes. Paradoxically, deletion of the zinc-responsive transcription factor Zap1p or addition of the zinc chelator 1,10-phenanthroline significantly increased diclofenac toxicity, establishing a regulatory role for zinc in diclofenac resistance. In conclusion, we have identified three new pathways involved in diclofenac tolerance in yeast, namely, Pdr5p as the main contributor to the PDR response, cell wall signaling via the PKC pathway, and zinc homeostasis, regulated by Zap1p. PMID:21724882

  13. Diminished stress resistance and defective adaptive homeostasis in age-related diseases.

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    Lomeli, Naomi; Bota, Daniela A; Davies, Kelvin J A

    2017-11-01

    Adaptive homeostasis is defined as the transient expansion or contraction of the homeostatic range following exposure to subtoxic, non-damaging, signaling molecules or events, or the removal or cessation of such molecules or events ( Mol. Aspects Med. (2016) 49, 1-7 ). Adaptive homeostasis allows us to transiently adapt (and then de-adapt) to fluctuating levels of internal and external stressors. The ability to cope with transient changes in internal and external environmental stress, however, diminishes with age. Declining adaptive homeostasis may make older people more susceptible to many diseases. Chronic oxidative stress and defective protein homeostasis (proteostasis) are two major factors associated with the etiology of age-related disorders. In the present paper, we review the contribution of impaired responses to oxidative stress and defective adaptive homeostasis in the development of age-associated diseases. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  14. CONTACT RESISTANCE MODELING

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    S. V. LOSKUTOV

    2018-05-01

    Full Text Available Purpose. To determine the contribution of the real contact spots distribution in the total conductivity of the conductors contact. Methodology. The electrical contact resistance research was carried out on models. The experimental part of this work was done on paper with a graphite layer with membranes (the first type and conductive liquids with discrete partitions (the second type. Findings. It is shown that the contact electrical resistance is mainly determined by the real area of metal contact. The experimental dependence of the electrical resistance of the second type model on the distance between the electrodes and the potential distribution along the sample surface for the first type model were obtained. The theoretical model based on the principle of electric field superposition was considered. The dependences obtained experimentally and calculated by using the theoretical model are in good agreement. Originality. The regularity of the electrical contact resistance formation on a large number of membranes was researched for the first time. A new model of discrete electrical contact based on the liquid as the conducting environment with nuclear membrane partitions was developed. The conclusions of the additivity of contact and bulk electrical resistance were done. Practical value. Based on these researches, a new experimental method of kinetic macroidentation that as a parameter of the metal surface layer deformation uses the real contact area was developed. This method allows to determine the value of average contact stresses, yield point, change of the stress on the depth of deformation depending on the surface treatment.

  15. The resist diabetes trial: Rationale, design, and methods of a hybrid efficacy/effectiveness intervention trial for resistance training maintenance to improve glucose homeostasis in older prediabetic adults.

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    Marinik, Elaina L; Kelleher, Sarah; Savla, Jyoti; Winett, Richard A; Davy, Brenda M

    2014-01-01

    Advancing age is associated with reduced levels of physical activity, increased body weight and fat, decreased lean body mass, and a high prevalence of type 2 diabetes (T2D). Resistance training (RT) increases muscle strength and lean body mass, and reduces risk of T2D among older adults. The Resist Diabetes trial will determine if a social cognitive theory (SCT)-based intervention improves RT maintenance in older, prediabetic adults, using a hybrid efficacy/effectiveness approach. Sedentary, overweight/obese (BMI: 25-39.9 kg/m(2)) adults aged 50-69 (N = 170) with prediabetes (impaired fasting glucose and/or impaired glucose tolerance) completed a supervised 3-month RT (2×/wk) initiation phase and were then randomly assigned (N = 159; 94% retention) to one of two 6-month maintenance conditions: SCT or standard care. The SCT intervention consisted of faded contacts compared to standard care. Participants continue RT at an approved, self-selected community facility during maintenance. A subsequent 6-month period involves no contact for both conditions. Assessments occur at baseline and months 3 (post-initiation), 9 (post-intervention), and 15 (six months after no contact). Primary outcomes are prediabetes indices (i.e., impaired fasting and 2-hour glucose concentration) and strength. Secondary measures include insulin sensitivity, beta-cell responsiveness, and disposition index (oral glucose and C-peptide minimal model); adherence; body composition; and SCT measures. Resist Diabetes is the first trial to examine the effectiveness of a high fidelity SCT-based intervention for maintaining RT in older adults with prediabetes to improve glucose homeostasis. Successful application of SCT constructs for RT maintenance may support translation of our RT program for diabetes prevention into community settings. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity.

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    Giovanni Dalmasso

    Full Text Available Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis and the removal of damaged mitochondria by selective autophagy (mitophagy. While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1 mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2 restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3 maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4 our model suggests sources of, and stress conditions

  17. Consumption of added sugars from liquid but not solid sources predicts impaired glucose homeostasis and insulin resistance among youth at risk of obesity.

    Science.gov (United States)

    Wang, Jiawei; Light, Kelly; Henderson, Mélanie; O'Loughlin, Jennifer; Mathieu, Marie-Eve; Paradis, Gilles; Gray-Donald, Katherine

    2014-01-01

    Little is known about longitudinal associations between added sugar consumption (solid and liquid sources) and glucose-insulin homeostasis among youth. Caucasian children (8-10 y) with at least one obese biological parent were recruited in the QUébec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort (n = 630) and followed-up 2 y later (n = 564). Added sugars were assessed by 3 24-h dietary recalls at baseline. Two-year changes were examined in multivariate linear regression models, adjusting for baseline level, age, sex, Tanner stage, energy intake, fat mass (dual-energy X-ray absorptiometry), and physical activity (7 d accelerometer). Added sugar intake in either liquid or solid sources was not related to changes in adiposity measures (fat mass, body mass index, or waist circumference). However, a higher consumption (10 g/d) of added sugars from liquid sources was associated with 0.04 mmol/L higher fasting glucose, 2.3 pmol/L higher fasting insulin, 0.1 unit higher homeostasis model assessment of insulin resistance (HOMA-IR), and 0.4 unit lower Matsuda-insulin sensitivity index (Matsuda-ISI) in all participants (P added sugars from solid sources. Overweight/obese children at baseline had greater increases in adiposity indicators, fasting insulin, and HOMA-IR and decreases in Matsuda-ISI during those 2 y than normal-weight children. Consumption of added sugars from liquid or solid sources was not associated with changes in adiposity, but liquid added sugars were a risk factor for the development of impaired glucose homeostasis and insulin resistance over 2 y among youth at risk of obesity.

  18. Alterations in vitamin A/retinoic acid homeostasis in diet-induced obesity and insulin resistance.

    Science.gov (United States)

    Mody, Nimesh

    2017-11-01

    Vitamin A is an essential micronutrient for life and the phytochemical β-carotene, also known as pro-vitamin A, is an important dietary source of this vitamin. Vitamin A (retinol) is the parent compound of all bioactive retinoids but it is retinoic acid (RA) that is the active metabolite of vitamin A. The plasma concentration of retinol is maintained in a narrow range and its normal biological activities strictly regulated since excessive intake can lead to toxicity and thus also be detrimental to life. The present review will give an overview of how vitamin A homeostasis is maintained and move on to focus on the link between circulating vitamin A and metabolic disease states. Finally, we will examine how pharmacological or genetic alterations in vitamin A homeostasis and RA-signalling can influence body fat and blood glucose levels including a novel link to the liver secreted hormone fibroblast growth factor 21, an important metabolic regulator.

  19. Partial ablation of adult Drosophila insulin-producing neurons modulates glucose homeostasis and extends life span without insulin resistance.

    Science.gov (United States)

    Haselton, Aaron; Sharmin, Effat; Schrader, Janel; Sah, Megha; Poon, Peter; Fridell, Yih-Woei C

    2010-08-01

    In Drosophila melanogaster (D. melanogaster), neurosecretory insulin-like peptide-producing cells (IPCs), analogous to mammalian pancreatic beta cells are involved in glucose homeostasis. Extending those findings, we have developed in the adult fly an oral glucose tolerance test and demonstrated that IPCs indeed are responsible for executing an acute glucose clearance response. To further develop D. melanogaster as a relevant system for studying age-associated metabolic disorders, we set out to determine the impact of adult-specific partial ablation of IPCs (IPC knockdown) on insulin-like peptide (ILP) action, metabolic outcomes and longevity. Interestingly, while IPC knockdown flies are hyperglycemic and glucose intolerant, these flies remain insulin sensitive as measured by peripheral glucose disposal upon insulin injection and serine phosphorylation of a key insulin-signaling molecule, Akt. Significant increases in stored glycogen and triglyceride levels as well as an elevated level of circulating lipid measured in adult IPC knockdown flies suggest profound modulation in energy metabolism. Additional physiological outcomes measured in those flies include increased resistance to starvation and impaired female fecundity. Finally, increased life span and decreased mortality rates measured in IPC knockdown flies demonstrate that it is possible to modulate ILP action in adult flies to achieve life span extension without insulin resistance. Taken together, we have established and validated an invertebrate genetic system to further investigate insulin action, metabolic homeostasis and regulation of aging regulated by adult IPCs.

  20. Bayesian model discrimination for glucose-insulin homeostasis

    DEFF Research Database (Denmark)

    Andersen, Kim Emil; Brooks, Stephen P.; Højbjerre, Malene

    In this paper we analyse a set of experimental data on a number of healthy and diabetic patients and discuss a variety of models for describing the physiological processes involved in glucose absorption and insulin secretion within the human body. We adopt a Bayesian approach which facilitates...... as parameter uncertainty. Markov chain Monte Carlo methods are used, combining Metropolis Hastings, reversible jump and simulated tempering updates to provide rapidly mixing chains so as to provide robust inference. We demonstrate the methodology for both healthy and type II diabetic populations concluding...... that whilst both populations are well modelled by a common insulin model, their glucose dynamics differ considerably....

  1. A multi-scale model of hepcidin promoter regulation reveals factors controlling systemic iron homeostasis.

    Directory of Open Access Journals (Sweden)

    Guillem Casanovas

    2014-01-01

    Full Text Available Systemic iron homeostasis involves a negative feedback circuit in which the expression level of the peptide hormone hepcidin depends on and controls the iron blood levels. Hepcidin expression is regulated by the BMP6/SMAD and IL6/STAT signaling cascades. Deregulation of either pathway causes iron-related diseases such as hemochromatosis or anemia of inflammation. We quantitatively analyzed how BMP6 and IL6 control hepcidin expression. Transcription factor (TF phosphorylation and reporter gene expression were measured under co-stimulation conditions, and the promoter was perturbed by mutagenesis. Using mathematical modeling, we systematically analyzed potential mechanisms of cooperative and competitive promoter regulation by the transcription factors, and experimentally validated the model predictions. Our results reveal that hepcidin cross-regulation primarily occurs by combinatorial transcription factor binding to the promoter, whereas signaling crosstalk is insignificant. We find that the presence of two BMP-responsive elements enhances the steepness of the promoter response towards the iron-sensing BMP signaling axis, which promotes iron homeostasis in vivo. IL6 co-stimulation reduces the promoter sensitivity towards the BMP signal, because the SMAD and STAT transcription factors compete for recruiting RNA polymerase to the transcription start site. This may explain why inflammatory signals disturb iron homeostasis in anemia of inflammation. Taken together, our results reveal why the iron homeostasis circuit is sensitive to perturbations implicated in disease.

  2. Proliferation resistance modeling

    International Nuclear Information System (INIS)

    Bari, R.; Peterson, P.; Roglans, J.; Mladineo, S.; Nuclear Engineering Division; BNL; Univ. of California at Berkely; PNNL

    2004-01-01

    The National Nuclear Security Administration is developing methods for nonproliferation assessments. A working group on Nonproliferation Assessment Methodology (NPAM) assembled a toolbox of methods for various applications in the nonproliferation arena. One application of this methodology is to the evaluation of the proliferation resistance of Generation IV nuclear energy systems. This paper first summarizes the key results of the NPAM program and then provides results obtained thus far in the ongoing application, which is co-sponsored by the DOE Office of Nuclear Energy Science and Technology. In NPAM, a top-level measure of proliferation resistance for a fuel cycle system is developed from a hierarchy of metrics. The problem is decomposed into: metrics to be computed, barriers to proliferation, and a finite set of threats. The analyst models the process undertaken by the proliferant to overcome barriers to proliferation and evaluates the outcomes. In addition to proliferation resistance (PR) evaluation, the application also addresses physical protection (PP) evaluation against sabotage and theft. The Generation IV goal for future nuclear energy systems is to assure that they are very unattractive and the least desirable route for diversion or theft of weapons-usable materials, and provide increased physical protection against terrorism. An Expert Group, addressing this application, has identified six high-level measures for the PR goals (six measures have also been identified for the PP goals). Combined together, the complete set of measures provides information for program policy makers and system designers to compare specific system design features and integral system characteristics and to make choices among alternative options. The Group has developed a framework for a phased evaluation approach to analyzing PR and PP of system characteristics and to quantifying metrics and measures. This approach allows evaluations to become more detailed and representative

  3. The chronic effects of fish oil with exercise on postprandial lipaemia and chylomicron homeostasis in insulin resistant viscerally obese men

    Directory of Open Access Journals (Sweden)

    Slivkoff-Clark Karin M

    2012-02-01

    Full Text Available Abstract Background Visceral obesity and insulin resistance are associated with a postprandial accumulation of atherogenic chylomicron remnants that is difficult to modulate with lipid-lowering therapies. Dietary fish oil and exercise are cardioprotective interventions that can significantly modify the metabolism of TAG-rich lipoproteins. In this study, we investigated whether chronic exercise and fish oil act in combination to affect chylomicron metabolism in obese men with moderate insulin resistance. Methods The single blind study tested the effect of fish oil, exercise and the combined treatments on fasting and postprandial chylomicron metabolism. Twenty nine men with metabolic syndrome were randomly assigned to take fish oil or placebo for four weeks, before undertaking an additional 12 week walking program. At baseline and at the end of each treatment, subjects were tested for concentrations of fasting apo B48, plasma lipids and insulin. Postprandial apo B48 and TAG kinetics were also determined following ingestion of a fat enriched meal. Results Combining fish oil and exercise resulted in a significant reduction in the fasting apo B48 concentration, concomitant with attenuation of fasting TAG concentrations and the postprandial TAGIAUC response (p Conclusion Fish oil was shown to independently improve plasma TAG homeostasis but did not resolve hyper-chylomicronaemia. Instead, combining fish oil with chronic exercise reduced the plasma concentration of pro-atherogenic chylomicron remnants; in addition it reduced the fasting and postprandial TAG response in viscerally obese insulin resistant subjects.

  4. Vascular dysfunction in Chronic Mild Stress (CMS) induced depression model in rats: monoamine homeostasis and endothelial dysfunction

    DEFF Research Database (Denmark)

    Bouzinova, Elena; Wiborg, Ove; Aalkjær, Christian

    Major depression and cardiovascular diseases have strong co-morbidity but the reason for this is unknown. In CMS model of depression only some rats develop depression-like symptoms (i.e. anhedonia, measured by sucrose intake) while others are resilient to 8 weeks of CMS. Anhedonic rats have...... decreased cardiac output and unchanged blood pressure, suggesting increased total peripheral resistance. Small mesenteric and femoral arteries from CMS and non-stressed rats responded similarly to noradrenaline (NA) under control conditions but inhibition of neuronal reuptake with cocaine increased NA...... sensitivity stronger in anhedonic than in resilient and non-stressed groups. In contrast, corticosterone-sensitive extra-neuronal monoamine uptake was diminished in rats exposed to CMS. These changes in monoamine homeostasis were associated with upregulation neuronal NA transporter and reduced expression...

  5. DNA methylation regulates transcriptional homeostasis of algal endosymbiosis in the coral model Aiptasia

    KAUST Repository

    Li, Yong; Liew, Yi Jin; Cui, Guoxin; Cziesielski, Maha J; Zahran, Noura Ibrahim Omar; Michell, Craig T; Voolstra, Christian R.; Aranda, Manuel

    2017-01-01

    The symbiotic relationship between cnidarians and dinoflagellates is the cornerstone of coral reef ecosystems. Although research is focusing on the molecular mechanisms underlying this symbiosis, the role of epigenetic mechanisms, which have been implicated in transcriptional regulation and acclimation to environmental change, is unknown. To assess the role of DNA methylation in the cnidarian-dinoflagellate symbiosis, we analyzed genome-wide CpG methylation, histone associations, and transcriptomic states of symbiotic and aposymbiotic anemones in the model system Aiptasia. We find methylated genes are marked by histone H3K36me3 and show significant reduction of spurious transcription and transcriptional noise, revealing a role of DNA methylation in the maintenance of transcriptional homeostasis. Changes in DNA methylation and expression show enrichment for symbiosis-related processes such as immunity, apoptosis, phagocytosis recognition and phagosome formation, and unveil intricate interactions between the underlying pathways. Our results demonstrate that DNA methylation provides an epigenetic mechanism of transcriptional homeostasis during symbiosis.

  6. DNA methylation regulates transcriptional homeostasis of algal endosymbiosis in the coral model Aiptasia

    KAUST Repository

    Li, Yong

    2017-11-03

    The symbiotic relationship between cnidarians and dinoflagellates is the cornerstone of coral reef ecosystems. Although research is focusing on the molecular mechanisms underlying this symbiosis, the role of epigenetic mechanisms, which have been implicated in transcriptional regulation and acclimation to environmental change, is unknown. To assess the role of DNA methylation in the cnidarian-dinoflagellate symbiosis, we analyzed genome-wide CpG methylation, histone associations, and transcriptomic states of symbiotic and aposymbiotic anemones in the model system Aiptasia. We find methylated genes are marked by histone H3K36me3 and show significant reduction of spurious transcription and transcriptional noise, revealing a role of DNA methylation in the maintenance of transcriptional homeostasis. Changes in DNA methylation and expression show enrichment for symbiosis-related processes such as immunity, apoptosis, phagocytosis recognition and phagosome formation, and unveil intricate interactions between the underlying pathways. Our results demonstrate that DNA methylation provides an epigenetic mechanism of transcriptional homeostasis during symbiosis.

  7. Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis.

    Science.gov (United States)

    Haberzettl, Petra; McCracken, James P; Bhatnagar, Aruni; Conklin, Daniel J

    2016-06-01

    Exposure to fine particular matter (PM2.5) increases the risk of developing cardiovascular disease and Type 2 diabetes. Because blood vessels are sensitive targets of air pollutant exposure, we examined the effects of concentrated ambient PM2.5 (CAP) on vascular insulin sensitivity and circulating levels of endothelial progenitor cells (EPCs), which reflect cardiovascular health. We found that CAP exposure for 9 days decreased insulin-stimulated Akt phosphorylation in the aorta of mice maintained on control diet. This change was accompanied by the induction of IL-1β and increases in the abundance of cleaved IL-18 and p10 subunit of Casp-1, consistent with the activation of the inflammasome pathway. CAP exposure also suppressed circulating levels of EPCs (Flk-1(+)/Sca-1(+) cells), while enhancing the bone marrow abundance of these cells. Although similar changes in vascular insulin signaling and EPC levels were observed in mice fed high-fat diet, CAP exposure did not exacerbate diet-induced changes in vascular insulin resistance or EPC homeostasis. Treatment with an insulin sensitizer, metformin or rosiglitazone, prevented CAP-induced vascular insulin resistance and NF-κB and inflammasome activation and restored peripheral blood and bone marrow EPC levels. These findings suggest that PM2.5 exposure induces diet-independent vascular insulin resistance and inflammation and prevents EPC mobilization, and that this EPC mobilization defect could be mediated by vascular insulin resistance. Impaired vascular insulin sensitivity may be an important mechanism underlying PM2.5-induced vascular injury, and pharmacological sensitization to insulin action could potentially prevent deficits in vascular repair and mitigate vascular inflammation due to exposure to elevated levels of ambient air pollution. Copyright © 2016 the American Physiological Society.

  8. A mouse model of harlequin ichthyosis delineates a key role for Abca12 in lipid homeostasis.

    Directory of Open Access Journals (Sweden)

    Ian Smyth

    2008-09-01

    Full Text Available Harlequin Ichthyosis (HI is a severe and often lethal hyperkeratotic skin disease caused by mutations in the ABCA12 transport protein. In keratinocytes, ABCA12 is thought to regulate the transfer of lipids into small intracellular trafficking vesicles known as lamellar bodies. However, the nature and scope of this regulation remains unclear. As part of an original recessive mouse ENU mutagenesis screen, we have identified and characterised an animal model of HI and showed that it displays many of the hallmarks of the disease including hyperkeratosis, loss of barrier function, and defects in lipid homeostasis. We have used this model to follow disease progression in utero and present evidence that loss of Abca12 function leads to premature differentiation of basal keratinocytes. A comprehensive analysis of lipid levels in mutant epidermis demonstrated profound defects in lipid homeostasis, illustrating for the first time the extent to which Abca12 plays a pivotal role in maintaining lipid balance in the skin. To further investigate the scope of Abca12's activity, we have utilised cells from the mutant mouse to ascribe direct transport functions to the protein and, in doing so, we demonstrate activities independent of its role in lamellar body function. These cells have severely impaired lipid efflux leading to intracellular accumulation of neutral lipids. Furthermore, we identify Abca12 as a mediator of Abca1-regulated cellular cholesterol efflux, a finding that may have significant implications for other diseases of lipid metabolism and homeostasis, including atherosclerosis.

  9. Thermomechanical Modelling of Resistance Welding

    DEFF Research Database (Denmark)

    Bay, Niels; Zhang, Wenqi

    2007-01-01

    The present paper describes a generic programme for analysis, optimization and development of resistance spot and projection welding. The programme includes an electrical model determining electric current and voltage distribution as well as heat generation, a thermal model calculating heat...

  10. Quorum sensing in CD4+ T cell homeostasis: a hypothesis and a model.

    Directory of Open Access Journals (Sweden)

    Afonso R.M. Almeida

    2012-05-01

    Full Text Available Homeostasis of lymphocyte numbers is believed to be due to competition between cellular populations for a common niche of restricted size, defined by the combination of interactions and trophic factors required for cell survival. Here we propose a new mechanism: homeostasis of lymphocyte numbers could also be achieved by the ability of lymphocytes to perceive the density of their own populations. Such a mechanism would be reminiscent of the primordial quorum sensing systems used by bacteria, in which some bacteria sense the accumulation of bacterial metabolites secreted by other elements of the population, allowing them to count the number of cells present and adapt their growth accordingly. We propose that homeostasis of CD4+ T cell numbers may occur via a quorum-sensing-like mechanism, where IL-2 is produced by activated CD4+ T cells and sensed by a population of CD4+ Treg cells that expresses the high-affinity IL-2Rα-chain and can regulate the number of activated IL-2-producing CD4+ T cells and the total CD4+T cell population. In other words, CD4+ T cell populations can restrain their growth by monitoring the number of activated cells, thus preventing uncontrolled lymphocyte proliferation during immune responses. We hypothesize that malfunction of this quorum-sensing mechanism may lead to uncontrolled T cell activation and autoimmunity. Finally, we present a mathematical model that describes the role of IL-2 and quorum-sensing mechanisms in CD4+ T cell homeostasis during an immune response.

  11. Comparison of the Usefulness of the Updated Homeostasis Model Assessment (HOMA2) with the Original HOMA1 in the Prediction of Type 2 Diabetes Mellitus in Koreans

    OpenAIRE

    Song, Young Seok; Hwang, You-Cheol; Ahn, Hong-Yup; Park, Cheol-Young

    2016-01-01

    Background The original homeostasis model assessment (HOMA1) and the updated HOMA model (HOMA2) have been used to evaluate insulin resistance (IR) and ?-cell function, but little is known about the usefulness of HOMA2 for the prediction of diabetes in Koreans. The aim of this study was to demonstrate the usefulness of HOMA2 as a predictor of type 2 diabetes mellitus in Koreans without diabetes. Methods The study population consisted of 104,694 Koreans enrolled at a health checkup program and ...

  12. Comparison of the Usefulness of the Updated Homeostasis Model Assessment (HOMA2) with the Original HOMA1 in the Prediction of Type 2 Diabetes Mellitus in Koreans

    OpenAIRE

    Young Seok Song; You-Cheol Hwang; Hong-Yup Ahn; Cheol-Young Park

    2016-01-01

    BackgroundThe original homeostasis model assessment (HOMA1) and the updated HOMA model (HOMA2) have been used to evaluate insulin resistance (IR) and β-cell function, but little is known about the usefulness of HOMA2 for the prediction of diabetes in Koreans. The aim of this study was to demonstrate the usefulness of HOMA2 as a predictor of type 2 diabetes mellitus in Koreans without diabetes.MethodsThe study population consisted of 104,694 Koreans enrolled at a health checkup program and fol...

  13. ALTERATIONS OF FE HOMEOSTASIS IN RAT CARDIOVASCULAR DISEASE MODELS AND ITS CONTRIBUTION TO CARDIOPULMONARY TOXICITY

    Science.gov (United States)

    Introduction: Fe homeostasis can be disrupted in human cardiovascular diseases (CVD). We addressed how dysregulation of Fe homeostasis affected the pulmonary inflammation/oxidative stress response and disease progression after exposure to Libby amphibole (LA), an asbestifonn mine...

  14. An innovation resistance factor model

    Directory of Open Access Journals (Sweden)

    Siti Salwa Mohd Ishak

    2016-09-01

    Full Text Available The process and implementation strategy of information technology in construction is generally considered through the limiting prism of theoretical contexts generated from innovation diffusion and acceptance. This research argues that more attention should be given to understanding the positive effects of resistance. The study develops a theoretical framing for the Integrated Resistance Factor Model (IRFM. The framing uses a combination of diffusion of innovation theory, technology acceptance model and social network perspective. The model is tested to identify the most significant resistance factors using Partial Least Square (PLS technique. All constructs proposed in the model are found to be significant, valid and consistent with the theoretical framework. IRFM is shown to be an effective and appropriate model of user resistance factors. The most critical factors to influence technology resistance in the online project information management system (OPIMS context are: support from leaders and peers, complexity of the technology, compatibility with key work practices; and pre-trial of the technology before it is actually deployed. The study provides a new model for further research in technology innovation specific to the construction industry.

  15. Rolling Resistance Measurement and Model Development

    DEFF Research Database (Denmark)

    Andersen, Lasse Grinderslev; Larsen, Jesper; Fraser, Elsje Sophia

    2015-01-01

    There is an increased focus worldwide on understanding and modeling rolling resistance because reducing the rolling resistance by just a few percent will lead to substantial energy savings. This paper reviews the state of the art of rolling resistance research, focusing on measuring techniques, s......, surface and texture modeling, contact models, tire models, and macro-modeling of rolling resistance...

  16. Innate lymphoid cells: models of plasticity for immune homeostasis and rapid responsiveness in protection.

    Science.gov (United States)

    Almeida, F F; Belz, G T

    2016-09-01

    Innate lymphoid cells (ILCs) have stormed onto the immune landscape as "newly discovered" cell types. These tissue-resident sentinels are enriched at mucosal surfaces and engage in complex cross talk with elements of the adaptive immune system and microenvironment to orchestrate immune homeostasis. Many parallels exist between innate cells and T cells leading to the initial partitioning of ILCs into rather rigid subsets that reflect their "adaptive-like" effector cytokines profiles. ILCs themselves, however, have unique attributes that are only just beginning to be elucidated. These features result in complementarity with, rather than complete duplication of, functions of the adaptive immune system. Key transcription factors determine the pathway of differentiation of progenitors towards an ILC1, ILC2, or ILC3 subset. Once formed, flexibility in the responses of these subsets to stimuli unexpectedly allows transdifferentation between the different subsets and the acquisition of altered phenotypes and function. This provides a mechanism for rapid innate immune responsiveness. Here, we discuss the models of differentiation for maintenance and activation of tissue-resident ILCs in maintaining immune homeostasis and protection.

  17. Modeling the role of negative cooperativity in metabolic regulation and homeostasis.

    Directory of Open Access Journals (Sweden)

    Eliot C Bush

    Full Text Available A significant proportion of enzymes display cooperativity in binding ligand molecules, and such effects have an important impact on metabolic regulation. This is easiest to understand in the case of positive cooperativity. Sharp responses to changes in metabolite concentrations can allow organisms to better respond to environmental changes and maintain metabolic homeostasis. However, despite the fact that negative cooperativity is almost as common as positive, it has been harder to imagine what advantages it provides. Here we use computational models to explore the utility of negative cooperativity in one particular context: that of an inhibitor binding to an enzyme. We identify several factors which may contribute, and show that acting together they can make negative cooperativity advantageous.

  18. Metal Homeostasis Regulators Suppress FRDA Phenotypes in a Drosophila Model of the Disease.

    Directory of Open Access Journals (Sweden)

    Sirena Soriano

    Full Text Available Friedreich's ataxia (FRDA, the most commonly inherited ataxia in populations of European origin, is a neurodegenerative disorder caused by a decrease in frataxin levels. One of the hallmarks of the disease is the accumulation of iron in several tissues including the brain, and frataxin has been proposed to play a key role in iron homeostasis. We found that the levels of zinc, copper, manganese and aluminum were also increased in a Drosophila model of FRDA, and that copper and zinc chelation improve their impaired motor performance. By means of a candidate genetic screen, we identified that genes implicated in iron, zinc and copper transport and metal detoxification can restore frataxin deficiency-induced phenotypes. Taken together, these results demonstrate that the metal dysregulation in FRDA includes other metals besides iron, therefore providing a new set of potential therapeutic targets.

  19. Dimethyl amiloride improves glucose homeostasis in mouse models of type 2 diabetes.

    Science.gov (United States)

    Gunawardana, Subhadra C; Head, W Steven; Piston, David W

    2008-06-01

    Dimethyl amiloride (DMA) enhances insulin secretion in the pancreatic beta-cell. DMA also enhances time-dependent potentiation (TDP) and enables TDP to occur in situations where it is normally absent. As we have demonstrated before, these effects are mediated in part through inhibition of neuronal nitric oxide synthase (nNOS), resulting in increased availability of arginine. Thus both DMA and arginine have the potential to correct the secretory defect in diabetes by enabling or enhancing TDP. In the current study we have demonstrated the ability of these agents to improve blood glucose homeostasis in three mouse models of type 2 diabetes. The pattern of TDP under different conditions indicates that inhibition of NOS is not the only mechanism through which DMA exerts its positive effects. Thus we also have explored another possible mechanism through which DMA enables/enhances TDP, via the activation of mitochondrial alpha-ketoglutarate dehydrogenase.

  20. A generalized quantitative antibody homeostasis model: maintenance of global antibody equilibrium by effector functions.

    Science.gov (United States)

    Prechl, József

    2017-11-01

    The homeostasis of antibodies can be characterized as a balanced production, target-binding and receptor-mediated elimination regulated by an interaction network, which controls B-cell development and selection. Recently, we proposed a quantitative model to describe how the concentration and affinity of interacting partners generates a network. Here we argue that this physical, quantitative approach can be extended for the interpretation of effector functions of antibodies. We define global antibody equilibrium as the zone of molar equivalence of free antibody, free antigen and immune complex concentrations and of dissociation constant of apparent affinity: [Ab]=[Ag]=[AbAg]= K D . This zone corresponds to the biologically relevant K D range of reversible interactions. We show that thermodynamic and kinetic properties of antibody-antigen interactions correlate with immunological functions. The formation of stable, long-lived immune complexes correspond to a decrease of entropy and is a prerequisite for the generation of higher-order complexes. As the energy of formation of complexes increases, we observe a gradual shift from silent clearance to inflammatory reactions. These rules can also be applied to complement activation-related immune effector processes, linking the physicochemical principles of innate and adaptive humoral responses. Affinity of the receptors mediating effector functions shows a wide range of affinities, allowing the continuous sampling of antibody-bound antigen over the complete range of concentrations. The generation of multivalent, multicomponent complexes triggers effector functions by crosslinking these receptors on effector cells with increasing enzymatic degradation potential. Thus, antibody homeostasis is a thermodynamic system with complex network properties, nested into the host organism by proper immunoregulatory and effector pathways. Maintenance of global antibody equilibrium is achieved by innate qualitative signals modulating a

  1. Three-component homeostasis control

    Science.gov (United States)

    Xu, Jin; Hong, Hyunsuk; Jo, Junghyo

    2014-03-01

    Two reciprocal components seem to be sufficient to maintain a control variable constant. However, pancreatic islets adapt three components to control glucose homeostasis. They are α (secreting glucagon), β (insulin), and δ (somatostatin) cells. Glucagon and insulin are the reciprocal hormones for increasing and decreasing blood glucose levels, while the role of somatostatin is unknown. However, it has been known how each hormone affects other cell types. Based on the pulsatile hormone secretion and the cellular interactions, this system can be described as coupled oscillators. In particular, we used the Landau-Stuart model to consider both amplitudes and phases of hormone oscillations. We found that the presence of the third component, δ cell, was effective to resist under glucose perturbations, and to quickly return to the normal glucose level once perturbed. Our analysis suggested that three components are necessary for advanced homeostasis control.

  2. Platinum nanozymes recover cellular ROS homeostasis in an oxidative stress-mediated disease model

    Science.gov (United States)

    Moglianetti, Mauro; de Luca, Elisa; Pedone, Deborah; Marotta, Roberto; Catelani, Tiziano; Sartori, Barbara; Amenitsch, Heinz; Retta, Saverio Francesco; Pompa, Pier Paolo

    2016-02-01

    In recent years, the use of nanomaterials as biomimetic enzymes has attracted great interest. In this work, we show the potential of biocompatible platinum nanoparticles (Pt NPs) as antioxidant nanozymes, which combine abundant cellular internalization and efficient scavenging activity of cellular reactive oxygen species (ROS), thus simultaneously integrating the functions of nanocarriers and antioxidant drugs. Careful toxicity assessment and intracellular tracking of Pt NPs proved their cytocompatibility and high cellular uptake, with compartmentalization within the endo/lysosomal vesicles. We have demonstrated that Pt NPs possess strong and broad antioxidant properties, acting as superoxide dismutase, catalase, and peroxidase enzymes, with similar or even superior performance than natural enzymes, along with higher adaptability to the changes in environmental conditions. We then exploited their potent activity as radical scavenging materials in a cellular model of an oxidative stress-related disorder, namely human Cerebral Cavernous Malformation (CCM) disease, which is associated with a significant increase in intracellular ROS levels. Noteworthily, we found that Pt nanozymes can efficiently reduce ROS levels, completely restoring the cellular physiological homeostasis.In recent years, the use of nanomaterials as biomimetic enzymes has attracted great interest. In this work, we show the potential of biocompatible platinum nanoparticles (Pt NPs) as antioxidant nanozymes, which combine abundant cellular internalization and efficient scavenging activity of cellular reactive oxygen species (ROS), thus simultaneously integrating the functions of nanocarriers and antioxidant drugs. Careful toxicity assessment and intracellular tracking of Pt NPs proved their cytocompatibility and high cellular uptake, with compartmentalization within the endo/lysosomal vesicles. We have demonstrated that Pt NPs possess strong and broad antioxidant properties, acting as superoxide

  3. A Thermodynamic Model of Monovalent Cation Homeostasis in the Yeast Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Susanne Gerber

    2016-01-01

    Full Text Available Cationic and heavy metal toxicity is involved in a substantial number of diseases in mammals and crop plants. Therefore, the understanding of tightly regulated transporter activities, as well as conceiving the interplay of regulatory mechanisms, is of substantial interest. A generalized thermodynamic description is developed for the complex interplay of the plasma membrane ion transporters, membrane potential and the consumption of energy for maintaining and restoring specific intracellular cation concentrations. This concept is applied to the homeostasis of cation concentrations in the yeast cells of S. cerevisiae. The thermodynamic approach allows to model passive ion fluxes driven by the electrochemical potential differences, but also primary or secondary active transport processes driven by the inter- play of different ions (symport, antiport or by ATP consumption (ATPases. The model-confronted with experimental data-reproduces the experimentally observed potassium and proton fluxes induced by the external stimuli KCl and glucose. The estimated phenomenological constants combine kinetic parameters and transport coefficients. These are in good agreement with the biological understanding of the transporters thus providing a better understanding of the control exerted by the coupled fluxes. The model predicts the flux of additional ion species, like e.g. chloride, as a potential candidate for counterbalancing positive charges. Furthermore, the effect of a second KCl stimulus is simulated, predicting a reduced cellular response for cells that were first exposed to a high KCl stimulus compared to cells pretreated with a mild KCl stimulus. By describing the generalized forces that are responsible for a given flow, the model provides information and suggestions for new experiments. Furthermore, it can be extended to other systems such as e.g. Candida albicans, or selected plant cells.

  4. Dietary incorporation of whey proteins and galactooligosaccharides exhibits improvement in glucose homeostasis and insulin resistance in high fat diet fed mice

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Kavadi

    2017-09-01

    Full Text Available Background: The present study was planned to investigate the effectiveness of whey protein isolate (WPI of high purity and a galactooligosaccharides (GOS preparation on glucose homeostasis and insulin resistance under high fat diet (45.47% energy from fat fed conditions in C57BL/6 mice. The mRNA expression of genes related to gluconeogenesis was also examined. Methods: Fasting blood glucose level, serum insulin & GLP-1 (ELISA were measured; HOMA-IR determined in different treatment groups. mRNA expression of gluconeogenesis genes in liver and small intestine tissues analysed by qRT-PCR. Results: Dietary incorporation of WPI/GOS alone or in combination was observed to significantly resist (p [J Complement Med Res 2017; 6(3.000: 326-332

  5. Abnormal chloride homeostasis in the substancia nigra pars reticulata contributes to locomotor deficiency in a model of acute liver injury.

    Directory of Open Access Journals (Sweden)

    Yan-Ling Yang

    Full Text Available BACKGROUND: Altered chloride homeostasis has been thought to be a risk factor for several brain disorders, while less attention has been paid to its role in liver disease. We aimed to analyze the involvement and possible mechanisms of altered chloride homeostasis of GABAergic neurons within the substantia nigra pars reticulata (SNr in the motor deficit observed in a model of encephalopathy caused by acute liver failure, by using glutamic acid decarboxylase 67 - green fluorescent protein knock-in transgenic mice. METHODS: Alterations in intracellular chloride concentration in GABAergic neurons within the SNr and changes in the expression of two dominant chloride homeostasis-regulating genes, KCC2 and NKCC1, were evaluated in mice with hypolocomotion due to hepatic encephalopathy (HE. The effects of pharmacological blockade and/or activation of KCC2 and NKCC1 functions with their specific inhibitors and/or activators on the motor activity were assessed. RESULTS: In our mouse model of acute liver injury, chloride imaging indicated an increase in local intracellular chloride concentration in SNr GABAergic neurons. In addition, the mRNA and protein levels of KCC2 were reduced, particularly on neuronal cell membranes; in contrast, NKCC1 expression remained unaffected. Furthermore, blockage of KCC2 reduced motor activity in the normal mice and led to a further deteriorated hypolocomotion in HE mice. Blockade of NKCC1 was not able to normalize motor activity in mice with liver failure. CONCLUSION: Our data suggest that altered chloride homeostasis is likely involved in the pathophysiology of hypolocomotion following HE. Drugs aimed at restoring normal chloride homeostasis would be a potential treatment for hepatic failure.

  6. Homeostasis of exercise hyperpnea and optimal sensorimotor integration: the internal model paradigm.

    Science.gov (United States)

    Poon, Chi-Sang; Tin, Chung; Yu, Yunguo

    2007-10-15

    Homeostasis is a basic tenet of biomedicine and an open problem for many physiological control systems. Among them, none has been more extensively studied and intensely debated than the dilemma of exercise hyperpnea - a paradoxical homeostatic increase of respiratory ventilation that is geared to metabolic demands instead of the normal chemoreflex mechanism. Classical control theory has led to a plethora of "feedback/feedforward control" or "set point" hypotheses for homeostatic regulation, yet so far none of them has proved satisfactory in explaining exercise hyperpnea and its interactions with other respiratory inputs. Instead, the available evidence points to a far more sophisticated respiratory controller capable of integrating multiple afferent and efferent signals in adapting the ventilatory pattern toward optimality relative to conflicting homeostatic, energetic and other objectives. This optimality principle parsimoniously mimics exercise hyperpnea, chemoreflex and a host of characteristic respiratory responses to abnormal gas exchange or mechanical loading/unloading in health and in cardiopulmonary diseases - all without resorting to a feedforward "exercise stimulus". Rather, an emergent controller signal encoding the projected metabolic level is predicted by the principle as an exercise-induced 'mental percept' or 'internal model', presumably engendered by associative learning (operant conditioning or classical conditioning) which achieves optimality through continuous identification of, and adaptation to, the causal relationship between respiratory motor output and resultant chemical-mechanical afferent feedbacks. This internal model self-tuning adaptive control paradigm opens a new challenge and exciting opportunity for experimental and theoretical elucidations of the mechanisms of respiratory control - and of homeostatic regulation and sensorimotor integration in general.

  7. A composite computational model of liver glucose homeostasis. I. Building the composite model.

    Science.gov (United States)

    Hetherington, J; Sumner, T; Seymour, R M; Li, L; Rey, M Varela; Yamaji, S; Saffrey, P; Margoninski, O; Bogle, I D L; Finkelstein, A; Warner, A

    2012-04-07

    A computational model of the glucagon/insulin-driven liver glucohomeostasis function, focusing on the buffering of glucose into glycogen, has been developed. The model exemplifies an 'engineering' approach to modelling in systems biology, and was produced by linking together seven component models of separate aspects of the physiology. The component models use a variety of modelling paradigms and degrees of simplification. Model parameters were determined by an iterative hybrid of fitting to high-scale physiological data, and determination from small-scale in vitro experiments or molecular biological techniques. The component models were not originally designed for inclusion within such a composite model, but were integrated, with modification, using our published modelling software and computational frameworks. This approach facilitates the development of large and complex composite models, although, inevitably, some compromises must be made when composing the individual models. Composite models of this form have not previously been demonstrated.

  8. Farnesoid X Receptor Deficiency Improves Glucose Homeostasis in Mouse Models of Obesity

    NARCIS (Netherlands)

    Prawitt, Janne; Abdelkarim, Mouaadh; Stroeve, Johanna H. M.; Popescu, Iuliana; Duez, Helene; Velagapudi, Vidya R.; Dumont, Julie; Bouchaert, Emmanuel; van Dijk, Theo H.; Lucas, Anthony; Dorchies, Emilie; Daoudi, Mehdi; Lestavel, Sophie; Gonzalez, Frank J.; Oresic, Matej; Cariou, Bertrand; Kuipers, Folkert; Caron, Sandrine; Staels, Bart

    OBJECTIVE-Bile acids (BA) participate in the maintenance of metabolic homeostasis acting through different signaling pathways. The nuclear BA receptor farnesoid X receptor (FXR) regulates pathways in BA, lipid, glucose, and energy metabolism, which become dysregulated in obesity. However, the role

  9. Utility of Childhood Glucose Homeostasis Variables in Predicting Adult Diabetes and Related Cardiometabolic Risk Factors

    OpenAIRE

    Nguyen, Quoc Manh; Srinivasan, Sathanur R.; Xu, Ji-Hua; Chen, Wei; Kieltyka, Lyn; Berenson, Gerald S.

    2009-01-01

    OBJECTIVE This study examines the usefulness of childhood glucose homeostasis variables (glucose, insulin, and insulin resistance index [homeostasis model assessment of insulin resistance {HOMA-IR}]) in predicting pre-diabetes and type 2 diabetes and related cardiometabolic risk factors in adulthood. RESEARCH DESIGN AND METHODS This retrospective cohort study consisted of normoglycemic (n = 1,058), pre-diabetic (n = 37), and type 2 diabetic (n = 25) adults aged 19–39 years who were followed o...

  10. Acquired cisplatin resistance in human ovarian A2780 cancer cells correlates with shift in taurine homeostasis and ability to volume regulate

    DEFF Research Database (Denmark)

    Sørensen, Belinda Halling; Thorsteinsdottir, Unnur Arna; Lambert, Ian Henry

    2014-01-01

    Cisplatin resistance is a major challenge in the treatment of cancer and develops through reduced drug accumulation and an increased ability to avoid drug-induced cell damage, cell shrinkage, and hence initiation of apoptosis. Uptake and release of the semiessential amino acid taurine contribute...... to cell volume homeostasis, and taurine has been reported to have antiapoptotic effects. Here we find that volume-sensitive taurine release in cisplatin-sensitive [wild-type (WT)] human ovarian cancer A2780 cells is reduced in the presence of the phospholipase A2 inhibitor bromenol lactone, the 5......-induced cell death in RES A2780 cells correlates with an increased accumulation of taurine, due to an increased taurine uptake and a concomitant impairment of the volume-sensitive taurine release pathway, as well an inability to reduce cell volume after osmotic cell swelling. Downregulation of volume...

  11. Role of volume-regulated and calcium-activated anion channels in cell volume homeostasis, cancer and drug resistance

    DEFF Research Database (Denmark)

    Hoffmann, Else Kay; Sørensen, Belinda Halling; Sauter, Daniel Rafael Peter

    2015-01-01

    to be an essential component of both VRAC and VSOAC. Reduced VRAC and VSOAC activities are seen in drug resistant cancer cells. ANO1 is a calcium-activated chloride channel expressed on the plasma membrane of e.g. secretory epithelia. ANO1 is amplified and highly expressed in a large number of carcinomas. The gene...... functions as well as their role in cancer and drug resistance....

  12. A whole-body model for glycogen regulation reveals a critical role for substrate cycling in maintaining blood glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    Ke Xu

    2011-12-01

    Full Text Available Timely, and sometimes rapid, metabolic adaptation to changes in food supply is critical for survival as an organism moves from the fasted to the fed state, and vice versa. These transitions necessitate major metabolic changes to maintain energy homeostasis as the source of blood glucose moves away from ingested carbohydrates, through hepatic glycogen stores, towards gluconeogenesis. The integration of hepatic glycogen regulation with extra-hepatic energetics is a key aspect of these adaptive mechanisms. Here we use computational modeling to explore hepatic glycogen regulation under fed and fasting conditions in the context of a whole-body model. The model was validated against previous experimental results concerning glycogen phosphorylase a (active and glycogen synthase a dynamics. The model qualitatively reproduced physiological changes that occur during transition from the fed to the fasted state. Analysis of the model reveals a critical role for the inhibition of glycogen synthase phosphatase by glycogen phosphorylase a. This negative regulation leads to high levels of glycogen synthase activity during fasting conditions, which in turn increases substrate (futile cycling, priming the system for a rapid response once an external source of glucose is restored. This work demonstrates that a mechanistic understanding of the design principles used by metabolic control circuits to maintain homeostasis can benefit from the incorporation of mathematical descriptions of these networks into "whole-body" contextual models that mimic in vivo conditions.

  13. Descriptive Modeling of the Dynamical Systems and Determination of Feedback Homeostasis at Different Levels of Life Organization.

    Science.gov (United States)

    Zholtkevych, G N; Nosov, K V; Bespalov, Yu G; Rak, L I; Abhishek, M; Vysotskaya, E V

    2018-05-24

    The state-of-art research in the field of life's organization confronts the need to investigate a number of interacting components, their properties and conditions of sustainable behaviour within a natural system. In biology, ecology and life sciences, the performance of such stable system is usually related to homeostasis, a property of the system to actively regulate its state within a certain allowable limits. In our previous work, we proposed a deterministic model for systems' homeostasis. The model was based on dynamical system's theory and pairwise relationships of competition, amensalism and antagonism taken from theoretical biology and ecology. However, the present paper proposes a different dimension to our previous results based on the same model. In this paper, we introduce the influence of inter-component relationships in a system, wherein the impact is characterized by direction (neutral, positive, or negative) as well as its (absolute) value, or strength. This makes the model stochastic which, in our opinion, is more consistent with real-world elements affected by various random factors. The case study includes two examples from areas of hydrobiology and medicine. The models acquired for these cases enabled us to propose a convincing explanation for corresponding phenomena identified by different types of natural systems.

  14. Flaxseed Oil Alleviates Chronic HFD-Induced Insulin Resistance through Remodeling Lipid Homeostasis in Obese Adipose Tissue.

    Science.gov (United States)

    Yu, Xiao; Tang, Yuhan; Liu, Peiyi; Xiao, Lin; Liu, Liegang; Shen, Ruiling; Deng, Qianchun; Yao, Ping

    2017-11-08

    Emerging evidence suggests that higher circulating long-chain n-3 polyunsaturated fatty acids (n-3PUFA) levels were intimately associated with lower prevalence of obesity and insulin resistance. However, the understanding of bioactivity and potential mechanism of α-linolenic acid-rich flaxseed oil (ALA-FO) against insulin resistance was still limited. This study evaluated the effect of FO on high-fat diet (HFD)-induced insulin resistance in C57BL/6J mice focused on adipose tissue lipolysis. Mice after HFD feeding for 16 weeks (60% fat-derived calories) exhibited systemic insulin resistance, which was greatly attenuated by medium dose of FO (M-FO), paralleling with differential accumulation of ALA and its n-3 derivatives across serum lipid fractions. Moreover, M-FO was sufficient to effectively block the metabolic activation of adipose tissue macrophages (ATMs), thereby improving adipose tissue insulin signaling. Importantly, suppression of hypoxia-inducible factors HIF-1α and HIF-2α were involved in FO-mediated modulation of adipose tissue lipolysis, accompanied by specific reconstitution of n-3PUFA within adipose tissue lipid fractions.

  15. Growth hormone secretagogues prevent dysregulation of skeletal muscle calcium homeostasis in a rat model of cisplatin-induced cachexia.

    Science.gov (United States)

    Conte, Elena; Camerino, Giulia Maria; Mele, Antonietta; De Bellis, Michela; Pierno, Sabata; Rana, Francesco; Fonzino, Adriano; Caloiero, Roberta; Rizzi, Laura; Bresciani, Elena; Ben Haj Salah, Khoubaib; Fehrentz, Jean-Alain; Martinez, Jean; Giustino, Arcangela; Mariggiò, Maria Addolorata; Coluccia, Mauro; Tricarico, Domenico; Lograno, Marcello Diego; De Luca, Annamaria; Torsello, Antonio; Conte, Diana; Liantonio, Antonella

    2017-06-01

    vivo (forelimb force and muscle volume) outcomes in cachectic animals. Administration of hexarelin or JMV2894 markedly reduced the cisplatin-induced alteration of calcium homeostasis by both common as well as drug-specific mechanisms of action. This effect correlated with muscle function preservation as well as amelioration of various atrophic indexes, thus supporting the functional impact of GHS activity on calcium homeostasis. Our findings provide a direct evidence that a dysregulation of calcium homeostasis plays a key role in cisplatin-induced model of cachexia gaining insight into the etiopathogenesis of this form of muscle wasting. Furthermore, our demonstration that GHS administration efficaciously prevents cisplatin-induced calcium homeostasis alteration contributes to elucidate the mechanism of action through which GHS could potentially ameliorate chemotherapy-associated cachexia. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

  16. Studies on the effect of quercetin and nitrates on the redox homeostasis using in vitro model.

    Science.gov (United States)

    Kurzeja, Ewa; Stec, Małgorzata; Synowiec-Wojtarowicz, Agnieszka; Jowsa, Andrzej; Pawłowska-Góral, Katarzyna

    2014-07-01

    Antioxidants are widely considered to be a preventive measure for many diseases and beneficial for health. However, an increasing number of reports suggest a lack of any influence by antioxidants on health or even harmful pro-oxidative effects of antioxidants. In most cases, the research was conducted with respect to a chosen antioxidant, without considering the presence of other chemical substances present in food, with which these compounds may react. The aim of this work was to determine whether and to what extent the simultaneous presence of quercetin and sodium nitrate influences oxidative-reductive homeostasis in fibroblast cultures. Superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and nitric oxide synthase (NOS) activities were measured together with nitric oxide (NO) concentration and total antioxidant status (TAS). An increase in the activity of all the enzymes measured and in the NO concentration was determined compared with the control culture. The most prominent changes were observed at the highest quercetin concentration. These results indicate that the simultaneous presence of quercetin and sodium nitrate disrupts the oxidative-reductive homeostasis in fibroblasts. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Models to Study Colonisation and Colonisation Resistance

    OpenAIRE

    Boreau, H.; Hartmann, L.; Karjalainen, T.; Rowland, I.; Wilkinson, M. H. F.

    2011-01-01

    This review describes various in vivo animal models (humans; conventional animals administered antimicrobial agents and animals species used; gnotobiotic and germ-free animals), in vitro models (luminal and mucosal), and in silico and mathematicalmodels which have been developed to study colonisation and colonisation resistance and effects of gut flora on hosts. Where applicable, the advantages and disadvantages of each model are discussed.Keywords: colonisation, colonisation resistance, anim...

  18. Glucose homeostasis, insulin resistance and inflammatory biomarkers in patients with non-alcoholic fatty liver disease: Beneficial effects of supplementation with microalgae Chlorella vulgaris: A double-blind placebo-controlled randomized clinical trial.

    Science.gov (United States)

    Ebrahimi-Mameghani, Mehrangiz; Sadeghi, Zahra; Abbasalizad Farhangi, Mahdieh; Vaghef-Mehrabany, Elnaz; Aliashrafi, Soodabeh

    2017-08-01

    Chlorella vulgaris (C. vulgaris) is reported to improve dyslipidemia and hypertension; however, its effect on inflammatory biomarkers and insulin resistance has not been noticed thus far. Non-alcoholic fatty liver disease (NAFLD) as a hepatic symptom of metabolic syndrome is strongly associated with insulin resistance and inflammation. In the current interventional trial, we aimed to study the effects of C. vulgaris supplementation on glucose homeostasis, insulin resistance and inflammatory biomarkers in patients with NAFLD. Seventy NAFLD patients confirmed by ultra-sonographic findings were randomly assigned into intervention group (four 300 mg tablets of C. vulgaris) or placebo group (four 300 mg tablets of placebos) for 8 weeks. Anthropometric measurements, liver enzymes, fasting serum glucose (FSG), insulin, high sensitive C-reactive protein (hs-CRP) and tumor necrosis factor-alpha (TNF-α) were assessed and homeostatic model assessment (HOMA) score for insulin resistance was estimated before and after the intervention. Anthropometric measurements decreased significantly in both group (p vulgaris - treated group compared to placebo group. Serum concentrations of liver enzymes, FSG and hs-CRP also significantly decreased and serum insulin concentration and HOMA score increased significantly only in C. vulgaris-treated group (P vulgaris supplementation could be considered as an adjunctive therapy to decrease weight and improve glycemic status and reducing hs-CRP as well as improving liver function in patients with NAFLD. 201202233320N7. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  19. Insulin resistance in Nigerians with essential hypertension

    African Journals Online (AJOL)

    EB

    2013-09-03

    Sep 3, 2013 ... Keywords: Hypertension, Insulin resistance, Homeostasis model assessment ... worldwide and its prevalence is predicted to increase by 60% by 2025, when a ... model is derived from a mathematical assessment .... Drug type.

  20. Osmotic homeostasis and NKLy lymphoma cells radiosensitivity

    International Nuclear Information System (INIS)

    Tishchenko, V.V.; Magda, I.N.

    1992-01-01

    In experiments with cells of ascites NKLy lymphoma differing in ploidy and position in the cell cycle, a study was made of the radiosensitivity, osmotic homeostasis peculiarities and thermoradiation changes in potassium content. It was shown that the resistance of osmotic homeostasis of NKLy cells to thermoradiation correlated with their radioresistance

  1. Tumour resistance to cisplatin: a modelling approach

    International Nuclear Information System (INIS)

    Marcu, L; Bezak, E; Olver, I; Doorn, T van

    2005-01-01

    Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure

  2. Tumour resistance to cisplatin: a modelling approach

    Energy Technology Data Exchange (ETDEWEB)

    Marcu, L [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia); Bezak, E [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia); Olver, I [Faculty of Medicine, University of Adelaide, North Terrace, SA 5000 (Australia); Doorn, T van [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia)

    2005-01-07

    Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure.

  3. RodZ and PgsA play intertwined roles in membrane homeostasis of Bacillus subtilis and resistance to weak organic acid stress

    Directory of Open Access Journals (Sweden)

    Johan Willem Albertus Van Beilen

    2016-10-01

    Full Text Available Weak organic acids like sorbic and acetic acid are widely used to prevent growth of spoilage organisms such as Bacilli. To identify genes involved in weak acid stress tolerance we screened a transposon mutant library of Bacillus subtilis for sorbic acid sensitivity. Mutants of the rodZ (ymfM gene were found to be hypersensitive to the lipophilic weak organic acid. RodZ is involved in determining the cell’s rod-shape and believed to interact with the bacterial actin-like MreB cytoskeleton. Since rodZ lies upstream in the genome of the essential gene pgsA (phosphatidylglycerol phosphate synthase we hypothesized that expression of the latter might also be affected in rodZ mutants and hence contribute to the phenotype observed. We show that both genes are co-transcribed and that both the rodZ::mini-Tn10 mutant and a conditional pgsA mutant, under conditions of minimal pgsA expression, were sensitive to sorbic and acetic acid. Both strains displayed a severely altered membrane composition. Compared to the wild-type strain, phosphatidylglycerol and cardiolipin levels were lowered and the average acyl chain length was elongated. Induction of rodZ expression from a plasmid in our transposon mutant led to no recovery of weak acid susceptibility comparable to wild-type levels. However, pgsA overexpression in the same mutant partly restored sorbic acid susceptibility and fully restored acetic acid sensitivity. A construct containing both rodZ and pgsA as on the genome led to some restored growth as well. We propose that RodZ and PgsA play intertwined roles in membrane homeostasis and resistance to weak organic acid stress.

  4. Effects of probiotics and antibiotics on the intestinal homeostasis in a computer controlled model of the large intestine

    Directory of Open Access Journals (Sweden)

    Rehman Ateequr

    2012-03-01

    Full Text Available Abstract Background Antibiotic associated diarrhea and Clostridium difficile infection are frequent complications of broad spectrum antibiotic therapy. Probiotic bacteria are used as therapeutic and preventive agents in these disorders, but the exact functional mechanisms and the mode of action are poorly understood. The effects of clindamycin and the probiotic mixture VSL#3 (containing the 8 bacterial strains Streptococcus thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei and Lactobacillus delbrueckii subsp. Bulgaricus consecutively or in combination were investigated and compared to controls without therapy using a standardized human fecal microbiota in a computer-controlled in vitro model of large intestine. Microbial metabolites (short chain fatty acids, lactate, branched chain fatty acids, and ammonia and the intestinal microbiota were analyzed. Results Compared to controls and combination therapy, short chain fatty acids and lactate, but also ammonia and branched chain fatty acids, were increased under probiotic therapy. The metabolic pattern under combined therapy with antibiotics and probiotics had the most beneficial and consistent effect on intestinal metabolic profiles. The intestinal microbiota showed a decrease in several indigenous bacterial groups under antibiotic therapy, there was no significant recovery of these groups when the antibiotic therapy was followed by administration of probiotics. Simultaneous application of anti- and probiotics had a stabilizing effect on the intestinal microbiota with increased bifidobacteria and lactobacilli. Conclusions Administration of VSL#3 parallel with the clindamycin therapy had a beneficial and stabilizing effect on the intestinal metabolic homeostasis by decreasing toxic metabolites and protecting the endogenic microbiota from destruction. Probiotics could be a reasonable

  5. Genetic models rule out a major role of beta cell glycogen in the control of glucose homeostasis.

    Science.gov (United States)

    Mir-Coll, Joan; Duran, Jordi; Slebe, Felipe; García-Rocha, Mar; Gomis, Ramon; Gasa, Rosa; Guinovart, Joan J

    2016-05-01

    Glycogen accumulation occurs in beta cells of diabetic patients and has been proposed to partly mediate glucotoxicity-induced beta cell dysfunction. However, the role of glycogen metabolism in beta cell function and its contribution to diabetes pathophysiology remain poorly understood. We investigated the function of beta cell glycogen by studying glucose homeostasis in mice with (1) defective glycogen synthesis in the pancreas; and (2) excessive glycogen accumulation in beta cells. Conditional deletion of the Gys1 gene and overexpression of protein targeting to glycogen (PTG) was accomplished by Cre-lox recombination using pancreas-specific Cre lines. Glucose homeostasis was assessed by determining fasting glycaemia, insulinaemia and glucose tolerance. Beta cell mass was determined by morphometry. Glycogen was detected histologically by periodic acid-Schiff's reagent staining. Isolated islets were used for the determination of glycogen and insulin content, insulin secretion, immunoblots and gene expression assays. Gys1 knockout (Gys1 (KO)) mice did not exhibit differences in glucose tolerance or basal glycaemia and insulinaemia relative to controls. Insulin secretion and gene expression in isolated islets was also indistinguishable between Gys1 (KO) and controls. Conversely, despite effective glycogen overaccumulation in islets, mice with PTG overexpression (PTG(OE)) presented similar glucose tolerance to controls. However, under fasting conditions they exhibited lower glycaemia and higher insulinaemia. Importantly, neither young nor aged PTG(OE) mice showed differences in beta cell mass relative to age-matched controls. Finally, a high-fat diet did not reveal a beta cell-autonomous phenotype in either model. Glycogen metabolism is not required for the maintenance of beta cell function. Glycogen accumulation in beta cells alone is not sufficient to trigger the dysfunction or loss of these cells, or progression to diabetes.

  6. Mathematical model reveals role of nucleotide signaling in airway surface liquid homeostasis and its dysregulation in cystic fibrosis.

    Science.gov (United States)

    Sandefur, Conner I; Boucher, Richard C; Elston, Timothy C

    2017-08-29

    Mucociliary clearance is composed of three components (i.e., mucin secretion, airway surface hydration, and ciliary-activity) which function coordinately to clear inhaled microbes and other foreign particles from airway surfaces. Airway surface hydration is maintained by water fluxes driven predominantly by active chloride and sodium ion transport. The ion channels that mediate electrogenic ion transport are regulated by extracellular purinergic signals that signal through G protein-coupled receptors. These purinoreceptors and the signaling pathways they activate have been identified as possible therapeutic targets for treating lung disease. A systems-level description of airway surface liquid (ASL) homeostasis could accelerate development of such therapies. Accordingly, we developed a mathematical model to describe the dynamic coupling of ion and water transport to extracellular purinergic signaling. We trained our model from steady-state and time-dependent experimental measurements made using normal and cystic fibrosis (CF) cultured human airway epithelium. To reproduce CF conditions, reduced chloride secretion, increased potassium secretion, and increased sodium absorption were required. The model accurately predicted ASL height under basal normal and CF conditions and the collapse of surface hydration due to the accelerated nucleotide metabolism associated with CF exacerbations. Finally, the model predicted a therapeutic strategy to deliver nucleotide receptor agonists to effectively rehydrate the ASL of CF airways.

  7. Effect of Inquiry-Based Computer Simulation Modeling on Pre-Service Teachers' Understanding of Homeostasis and Their Perceptions of Design Features

    Science.gov (United States)

    Chabalengula, Vivien; Fateen, Rasheta; Mumba, Frackson; Ochs, Laura Kathryn

    2016-01-01

    This study investigated the effect of an inquiry-based computer simulation modeling (ICoSM) instructional approach on pre-service science teachers' understanding of homeostasis and its related concepts, and their perceived design features of the ICoSM and simulation that enhanced their conceptual understanding of these concepts. Fifty pre-service…

  8. (+-Rutamarin as a dual inducer of both GLUT4 translocation and expression efficiently ameliorates glucose homeostasis in insulin-resistant mice.

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    Full Text Available Glucose transporter 4 (GLUT4 is a principal glucose transporter in response to insulin, and impaired translocation or decreased expression of GLUT4 is believed to be one of the major pathological features of type 2 diabetes mellitus (T2DM. Therefore, induction of GLUT4 translocation or/and expression is a promising strategy for anti-T2DM drug discovery. Here we report that the natural product (+-Rutamarin (Rut functions as an efficient dual inducer on both insulin-induced GLUT4 translocation and expression. Rut-treated 3T3-L1 adipocytes exhibit efficiently enhanced insulin-induced glucose uptake, while diet-induced obese (DIO mice based assays further confirm the Rut-induced improvement of glucose homeostasis and insulin sensitivity in vivo. Subsequent investigation of Rut acting targets indicates that as a specific protein tyrosine phosphatase 1B (PTP1B inhibitor Rut induces basal GLUT4 translocation to some extent and largely enhances insulin-induced GLUT4 translocation through PI3 kinase-AKT/PKB pathway, while as an agonist of retinoid X receptor α (RXRα, Rut potently increases GLUT4 expression. Furthermore, by using molecular modeling and crystallographic approaches, the possible binding modes of Rut to these two targets have been also determined at atomic levels. All our results have thus highlighted the potential of Rut as both a valuable lead compound for anti-T2DM drug discovery and a promising chemical probe for GLUT4 associated pathways exploration.

  9. Mice with an Oncogenic HRAS Mutation are Resistant to High-Fat Diet-Induced Obesity and Exhibit Impaired Hepatic Energy Homeostasis

    Directory of Open Access Journals (Sweden)

    Daiju Oba

    2018-01-01

    Full Text Available Costello syndrome is a “RASopathy” that is characterized by growth retardation, dysmorphic facial appearance, hypertrophic cardiomyopathy and tumor predisposition. >80% of patients with Costello syndrome harbor a heterozygous germline G12S mutation in HRAS. Altered metabolic regulation has been suspected because patients with Costello syndrome exhibit hypoketotic hypoglycemia and increased resting energy expenditure, and their growth is severely retarded. To examine the mechanisms of energy reprogramming by HRAS activation in vivo, we generated knock-in mice expressing a heterozygous Hras G12S mutation (HrasG12S/+ mice as a mouse model of Costello syndrome. On a high-fat diet, HrasG12S/+ mice developed a lean phenotype with microvesicular hepatic steatosis, resulting in early death compared with wild-type mice. Under starvation conditions, hypoketosis and elevated blood levels of long-chain fatty acylcarnitines were observed, suggesting impaired mitochondrial fatty acid oxidation. Our findings suggest that the oncogenic Hras mutation modulates energy homeostasis in vivo.

  10. Parenteral nutrition dysregulates bile salt homeostasis in a rat model of parenteral nutrition-associated liver disease.

    Science.gov (United States)

    Koelfat, Kiran V K; Schaap, Frank G; Hodin, Caroline M J M; Visschers, Ruben G J; Svavarsson, Björn I; Lenicek, Martin; Shiri-Sverdlov, Ronit; Lenaerts, Kaatje; Olde Damink, Steven W M

    2017-10-01

    Parenteral nutrition (PN), a lifesaving therapy in patients with intestinal failure, has been associated with hepatobiliary complications including steatosis, cholestasis and fibrosis, collectively known as parenteral nutrition-associated liver disease (PNALD). To date, the pathogenesis of PNALD is poorly understood and therapeutic options are limited. Impaired bile salt homeostasis has been proposed to contribute PNALD. The objective of this study was to establish a PNALD model in rats and to evaluate the effects of continuous parenteral nutrition (PN) on bile salt homeostasis. Rats received either PN via the jugular vein or received normal diet for 3, 7 or 14 days. Serum biochemistry, hepatic triglycerides, circulating bile salts and C4, IL-6 and TNF-alpha, and lipogenic and bile salt homeostatic gene expression in liver and ileum were assessed. PN increased hepatic triglycerides already after 3 days of administration, and resulted in conjugated bilirubin elevation after 7 or more days. This indicates PN-induced steatosis and impaired canalicular secretion of bilirubin, the latter which is in line with reduced hepatic expression of Mrp2 mRNA. There was no histological evidence for liver inflammation after PN administration, and circulating levels of pro-inflammatory cytokines IL-6 and TNF-α, were comparable in all groups. Hepatic expression of Fxr mRNA was decreased after 7 days of PN, without apparent effect on expression of Fxr targets Bsep and Shp. Nonetheless, Cyp7a1 expression was reduced after 7 days of PN, indicative for lowered bile salt synthesis. Circulating levels of C4 (marker of bile salt synthesis) were also decreased after 3, 7 and 14 days of PN. Levels of circulating bile salts were not affected by PN. This study showed that PN in rats caused early mild steatosis and cholestasis, while hepatic and systemic inflammation were not present. The onset of these abnormalities was associated with alterations in bile salt synthesis and transport. This

  11. A population-based Bayesian approach to the minimal model of glucose and insulin homeostasis

    DEFF Research Database (Denmark)

    Andersen, Kim Emil; Højbjerre, Malene

    2005-01-01

    -posed estimation problem, where the reconstruction most often has been done by non-linear least squares techniques separately for each entity. The minmal model was originally specified for a single individual and does not combine several individuals with the advantage of estimating the metabolic portrait...... to a population-based model. The estimation of the parameters are efficiently implemented in a Bayesian approach where posterior inference is made through the use of Markov chain Monte Carlo techniques. Hereby we obtain a powerful and flexible modelling framework for regularizing the ill-posed estimation problem...

  12. Task-Difficulty Homeostasis in Car Following Models: Experimental Validation Using Self-Paced Visual Occlusion.

    Directory of Open Access Journals (Sweden)

    Jami Pekkanen

    Full Text Available Car following (CF models used in traffic engineering are often criticized for not incorporating "human factors" well known to affect driving. Some recent work has addressed this by augmenting the CF models with the Task-Capability Interface (TCI model, by dynamically changing driving parameters as function of driver capability. We examined assumptions of these models experimentally using a self-paced visual occlusion paradigm in a simulated car following task. The results show strong, approximately one-to-one, correspondence between occlusion duration and increase in time headway. The correspondence was found between subjects and within subjects, on aggregate and individual sample level. The long time scale aggregate results support TCI-CF models that assume a linear increase in time headway in response to increased distraction. The short time scale individual sample level results suggest that drivers also adapt their visual sampling in response to transient changes in time headway, a mechanism which isn't incorporated in the current models.

  13. Dynamic optimal control of homeostasis: an integrative system approach for modeling of the central nitrogen metabolism in Saccharomyces cerevisiae.

    Science.gov (United States)

    van Riel, N A; Giuseppin, M L; Verrips, C T

    2000-01-01

    The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system encountered in advanced metabolic engineering. The CNM is the source of the cellular amino acids and proteins, including flavors and potentially valuable biomolecules; therefore, it is also of industrial interest. In the DOMC approach the cell is regarded as an optimally controlled system. Given the metabolic genotype, the cell faces a control problem to maintain an optimal flux distribution in a changing environment. The regulation is based on strategies and balances feedback control of homeostasis and feedforward regulation for adaptation. The DOMC approach is an integrative, holistic approach, not based on mechanistic descriptions and (therefore) not biased by the variation present in biochemical and molecular biological data. It is an effective tool to structure the rapidly increasing amount of data on the function of genes and pathways. The DOMC model is used successfully to predict the responses of pulses of ammonia and glutamine to nitrogen-limited continuous cultures of a wild-type strain and a glutamine synthetase-negative mutant. The simulation results are validated with experimental data.

  14. MODELS OF INSULIN RESISTANCE AND HEART FAILURE

    Science.gov (United States)

    Velez, Mauricio; Kohli, Smita; Sabbah, Hani N.

    2013-01-01

    The incidence of heart failure (HF) and diabetes mellitus is rapidly increasing and is associated with poor prognosis. In spite of the advances in therapy, HF remains a major health problem with high morbidity and mortality. When HF and diabetes coexist, clinical outcomes are significantly worse. The relationship between these two conditions has been studied in various experimental models. However, the mechanisms for this interrelationship are complex, incompletely understood, and have become a matter of considerable clinical and research interest. There are only few animal models that manifest both HF and diabetes. However, the translation of results from these models to human disease is limited and new models are needed to expand our current understanding of this clinical interaction. In this review, we discuss mechanisms of insulin signaling and insulin resistance, the clinical association between insulin resistance and HF and its proposed pathophysiologic mechanisms. Finally, we discuss available animal models of insulin resistance and HF and propose requirements for future new models. PMID:23456447

  15. Theoretical modeling of mechanical homeostasis of a mammalian cell under gravity-directed vector.

    Science.gov (United States)

    Zhou, Lüwen; Zhang, Chen; Zhang, Fan; Lü, Shouqin; Sun, Shujin; Lü, Dongyuan; Long, Mian

    2018-02-01

    Translocation of dense nucleus along gravity vector initiates mechanical remodeling of a eukaryotic cell. In our previous experiments, we quantified the impact of gravity vector on cell remodeling by placing an MC3T3-E1 cell onto upward (U)-, downward (D)-, or edge-on (E)- orientated substrate. Our experimental data demonstrate that orientation dependence of nucleus longitudinal translocation is positively correlated with cytoskeletal (CSK) remodeling of their expressions and structures and also is associated with rearrangement of focal adhesion complex (FAC). However, the underlying mechanism how CSK network and FACs are reorganized in a mammalian cell remains unclear. In this paper, we developed a theoretical biomechanical model to integrate the mechanosensing of nucleus translocation with CSK remodeling and FAC reorganization induced by a gravity vector. The cell was simplified as a nucleated tensegrity structure in the model. The cell and CSK filaments were considered to be symmetrical. All elements of CSK filaments and cytomembrane that support the nucleus were simplified as springs. FACs were simplified as an adhesion cluster of parallel bonds with shared force. Our model proposed that gravity vector-directed translocation of the cell nucleus is mechanically balanced by CSK remodeling and FAC reorganization induced by a gravitational force. Under gravity, dense nucleus tends to translocate and exert additional compressive or stretching force on the cytoskeleton. Finally, changes of the tension force acting on talin by microfilament alter the size of FACs. Results from our model are in qualitative agreement with those from experiments.

  16. Localized Sympathectomy Reduces Mechanical Hypersensitivity by Restoring Normal Immune Homeostasis in Rat Models of Inflammatory Pain.

    Science.gov (United States)

    Xie, Wenrui; Chen, Sisi; Strong, Judith A; Li, Ai-Ling; Lewkowich, Ian P; Zhang, Jun-Ming

    2016-08-17

    Some forms of chronic pain are maintained or enhanced by activity in the sympathetic nervous system (SNS), but attempts to model this have yielded conflicting findings. The SNS has both pro- and anti-inflammatory effects on immunity, confounding the interpretation of experiments using global sympathectomy methods. We performed a "microsympathectomy" by cutting the ipsilateral gray rami where they entered the spinal nerves near the L4 and L5 DRG. This led to profound sustained reductions in pain behaviors induced by local DRG inflammation (a rat model of low back pain) and by a peripheral paw inflammation model. Effects of microsympathectomy were evident within one day, making it unlikely that blocking sympathetic sprouting in the local DRGs or hindpaw was the sole mechanism. Prior microsympathectomy greatly reduced hyperexcitability of sensory neurons induced by local DRG inflammation observed 4 d later. Microsympathectomy reduced local inflammation and macrophage density in the affected tissues (as indicated by paw swelling and histochemical staining). Cytokine profiling in locally inflamed DRG showed increases in pro-inflammatory Type 1 cytokines and decreases in the Type 2 cytokines present at baseline, changes that were mitigated by microsympathectomy. Microsympathectomy was also effective in reducing established pain behaviors in the local DRG inflammation model. We conclude that the effect of sympathetic fibers in the L4/L5 gray rami in these models is pro-inflammatory. This raises the possibility that therapeutic interventions targeting gray rami might be useful in some chronic inflammatory pain conditions. Sympathetic blockade is used for many pain conditions, but preclinical studies show both pro- and anti-nociceptive effects. The sympathetic nervous system also has both pro- and anti-inflammatory effects on immune tissues and cells. We examined effects of a very localized sympathectomy. By cutting the gray rami to the spinal nerves near the lumbar sensory

  17. Epidermal Homeostasis and Radiation Responses in a Multiscale Tissue Modeling Framework

    Science.gov (United States)

    Hu, Shaowen; Cucinotta, Francis A.

    2013-01-01

    The surface of skin is lined with several thin layers of epithelial cells that are maintained throughout life time by a small population of stem cells. High dose radiation exposures could injure and deplete the underlying proliferative cells and induce cutaneous radiation syndrome. In this work we propose a multiscale computational model for skin epidermal dynamics that links phenomena occurring at the subcellular, cellular, and tissue levels of organization, to simulate the experimental data of the radiation response of swine epidermis, which is closely similar to human epidermis. Incorporating experimentally measured histological and cell kinetic parameters, we obtain results of population kinetics and proliferation indexes comparable to observations in unirradiated and acutely irradiated swine experiments. At the sub-cellular level, several recently published Wnt signaling controlled cell-cycle models are applied and the roles of key components and parameters are analyzed. Based on our simulation results, we demonstrate that a moderate increase of proliferation rate for the survival proliferative cells is sufficient to fully repopulate the area denuded by high dose radiation, as long as the integrity of underlying basement membrane is maintained. Our work highlights the importance of considering proliferation kinetics as well as the spatial organization of tissues when conducting in vivo investigations of radiation responses. This integrated model allow us to test the validity of several basic biological rules at the cellular level and sub-cellular mechanisms by qualitatively comparing simulation results with published research, and enhance our understanding of the pathophysiological effects of ionizing radiation on skin.

  18. The effect of low dose ionizing radiation on homeostasis and functional integrity in an organotypic human skin model

    Energy Technology Data Exchange (ETDEWEB)

    Neubeck, Claere von [German Cancer Consortium DKTK partner site Dresden, OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden (Germany); German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Geniza, Matthew J. [Molecular and Cellular Biology Program, Oregon State University, Corvallis OR 97331 (United States); Kauer, Paula M.; Robinson, R. Joe; Chrisler, William B. [Health Impacts and Exposure Science, Pacific Northwest National Laboratory, Richland WA 99352 (United States); Sowa, Marianne B., E-mail: marianne.sowa@pnnl.gov [Health Impacts and Exposure Science, Pacific Northwest National Laboratory, Richland WA 99352 (United States)

    2015-05-15

    Highlights: • Low doses of high LET radiation influence skin homeostasis. • Effects on proliferation and differentiation profiles are LET dependent. • Skin barrier function is not compromised following low dose exposure. - Abstract: Outside the protection of Earth's atmosphere, astronauts are exposed to low doses of high linear energy transfer (LET) radiation. Future NASA plans for deep space missions or a permanent settlement on the moon are limited by the health risks associated with space radiation exposures. There is a paucity of direct epidemiological data for low dose exposures to space radiation-relevant high LET ions. Health risk models are used to estimate the risk for such exposures, though these models are based on high dose experiments. There is increasing evidence, however, that low and high dose exposures result in different signaling events at the molecular level, and may involve different response mechanisms. Further, despite their low abundance, high LET particles have been identified as the major contributor to health risk during manned space flight. The human skin is exposed in every external radiation scenario, making it an ideal epithelial tissue model in which to study radiation induced effects. Here, we exposed an in vitro three dimensional (3-D) human organotypic skin tissue model to low doses of high LET oxygen (O), silicon (Si) and iron (Fe) ions. We measured proliferation and differentiation profiles in the skin tissue and examined the integrity of the skin's barrier function. We discuss the role of secondary particles in changing the proportion of cells receiving a radiation dose, emphasizing the possible impact on radiation-induced health issues in astronauts.

  19. Perinatal Polyunstaurated Fatty Acids Supplementation Causes Alterations in Fuel Homeostasis in Adult Male Rats but does not Offer Resistance Against STZ-induced Diabetes

    NARCIS (Netherlands)

    van Dijk, G.; Kacsandi, A.; Kobor-Nyakas, D. E.; Hogyes, E.; Nyakas, C.; Hőgyes, E.

    2011-01-01

    Maternal factors can have major imprinting effects on homeostatic mechanisms in the developing fetus and newborn. Here we studied whether supplemented perinatal polyunsaturated fatty acids (PUFAs) influence energy balance and fuel homeostasis later in life. Between day 10 after conception and day 10

  20. The Association of Unintentional Changes in Weight, Body Composition, and Homeostasis Model Assessment Index with Glycemic Progression in Non-Diabetic Healthy Subjects

    Directory of Open Access Journals (Sweden)

    Eun-Jung Rhee

    2011-04-01

    Full Text Available BackgroundWe performed a retrospective longitudinal study on the effects of changes in weight, body composition, and homeostasis model assessment (HOMA indices on glycemic progression in subjects without diabetes during a four-year follow-up period in a community cohort without intentional intervention.MethodsFrom 28,440 non-diabetic subjects who participated in a medical check-up program in 2004, data on anthropometric and metabolic parameters were obtained after four years in 2008. Body composition analyses were performed with a bioelectrical impedance analyzer. Skeletal muscle index (SMI, % was calculated with lean mass/weight×100. Subjects were divided into three groups according to weight change status in four years: weight loss (≤-5.0%, stable weight (-5.0 to 5.0%, weight gain (≥5.0%. Progressors were defined as the subjects who progressed to impaired fasting glucose or diabetes.ResultsProgressors showed worse baseline metabolic profiles compared with non-progressors. In logistic regression analyses, the increase in changes of HOMA-insulin resistance (HOMA-IR in four years presented higher odds ratios for glycemic progression compared with other changes during that period. Among the components of body composition, a change in waist-hip ratio was the strongest predictor, and SMI change in four years was a significant negative predictor for glycemic progression. Changes in HOMA β-cell function in four years was a negative predictor for glycemic progression.ConclusionIncreased interval changes in HOMA-IR, weight gain and waist-hip ratio was associated with glycemic progression during a four-year period without intentional intervention in non-diabetic Korean subjects.

  1. Tim-3/galectin-9 regulate the homeostasis of hepatic NKT cells in a murine model of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Tang, Zhao-Hui; Liang, Shuwen; Potter, James; Jiang, Xuan; Mao, Hai-Quan; Li, Zhiping

    2013-02-15

    T cell Ig and mucin domain (Tim)-3 is well known to interact with its natural ligand, Galectin-9 (Gal-9), to regulate T cell function. However, little is known about the function of Tim-3/Gal-9 signaling in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) mediated by hepatic NKT cells that also express Tim-3. In the current study, we define the role and the mechanism of Tim-3/Gal-9 signaling in hepatic NKT cell regulation in a mouse model of diet-induced NAFLD. Adult male wild-type or CD1d knockout C57BL/6 mice were fed a high-fat diet to induce steatosis. Some of the mice also received one or a combination of Gal-9, anti-IL-15R/IL-15 mAb, rIL-15, α-galactosylceramide, and multilamellar liposomes containing Cl(2)MDP. The expression of Tim-3 and various markers reflecting cell proliferation, activation, cytokine production, and apoptosis was analyzed. Liver histology, steatosis grade, and hepatic triglyceride content were also evaluated. In the liver, Tim-3(+) NKT cells are in an activated state, and Gal-9 directly induces Tim-3(+) NKT cell apoptosis and contributes to the depletion of NKT cells in diet-induced steatosis. However, Gal-9 also interacts with Tim-3-expressing Kupffer cells to induce secretion of IL-15, thus promoting NKT cell proliferation. Exogenous administration of Gal-9 significantly ameliorates diet-induced steatosis by modulating hepatic NKT cell function. In summary, the Tim-3/Gal-9-signaling pathway plays a critical role in the homeostasis of hepatic NKT cells through activation-induced apoptosis and secondary proliferation and, thus, contributes to the pathogenesis of NAFLD.

  2. Tim-3/Galectin-9 Regulate the Homeostasis of Hepatic NKT Cells in a Murine Model of Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Liang, Shuwen; Potter, James; Jiang, Xuan; Mao, Hai-Quan

    2013-01-01

    T cell Ig and mucin domain (Tim)-3 is well known to interact with its natural ligand, Galectin-9 (Gal-9), to regulate T cell function. However, little is known about the function of Tim-3/Gal-9 signaling in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) mediated by hepatic NKT cells that also express Tim-3. In the current study, we define the role and the mechanism of Tim-3/Gal-9 signaling in hepatic NKT cell regulation in a mouse model of diet-induced NAFLD. Adult male wild-type or CD1d knockout C57BL/6 mice were fed a high-fat diet to induce steatosis. Some of the mice also received one or a combination of Gal-9, anti–IL-15R/IL-15 mAb, rIL-15, α-galactosylceramide, and multilamellar liposomes containing Cl2MDP. The expression of Tim-3 and various markers reflecting cell proliferation, activation, cytokine production, and apoptosis was analyzed. Liver histology, steatosis grade, and hepatic triglyceride content were also evaluated. In the liver, Tim-3+ NKT cells are in an activated state, and Gal-9 directly induces Tim-3+ NKT cell apoptosis and contributes to the depletion of NKT cells in diet-induced steatosis. However, Gal-9 also interacts with Tim-3–expressing Kupffer cells to induce secretion of IL-15, thus promoting NKT cell proliferation. Exogenous administration of Gal-9 significantly ameliorates diet-induced steatosis by modulating hepatic NKT cell function. In summary, the Tim-3/Gal-9–signaling pathway plays a critical role in the homeostasis of hepatic NKT cells through activation-induced apoptosis and secondary proliferation and, thus, contributes to the pathogenesis of NAFLD. PMID:23296703

  3. Spike Pattern Structure Influences Synaptic Efficacy Variability Under STDP and Synaptic Homeostasis. I: Spike Generating Models on Converging Motifs

    Directory of Open Access Journals (Sweden)

    Zedong eBi

    2016-02-01

    Full Text Available In neural systems, synaptic plasticity is usually driven by spike trains. Due to the inherent noises of neurons and synapses as well as the randomness of connection details, spike trains typically exhibit variability such as spatial randomness and temporal stochasticity, resulting in variability of synaptic changes under plasticity, which we call efficacy variability. How the variability of spike trains influences the efficacy variability of synapses remains unclear. In this paper, we try to understand this influence under pair-wise additive spike-timing dependent plasticity (STDP when the mean strength of plastic synapses into a neuron is bounded (synaptic homeostasis. Specifically, we systematically study, analytically and numerically, how four aspects of statistical features, i.e. synchronous firing, burstiness/regularity, heterogeneity of rates and heterogeneity of cross-correlations, as well as their interactions influence the efficacy variability in converging motifs (simple networks in which one neuron receives from many other neurons. Neurons (including the post-synaptic neuron in a converging motif generate spikes according to statistical models with tunable parameters. In this way, we can explicitly control the statistics of the spike patterns, and investigate their influence onto the efficacy variability, without worrying about the feedback from synaptic changes onto the dynamics of the post-synaptic neuron. We separate efficacy variability into two parts: the drift part (DriftV induced by the heterogeneity of change rates of different synapses, and the diffusion part (DiffV induced by weight diffusion caused by stochasticity of spike trains. Our main findings are: (1 synchronous firing and burstiness tend to increase DiffV, (2 heterogeneity of rates induces DriftV when potentiation and depression in STDP are not balanced, and (3 heterogeneity of cross-correlations induces DriftV together with heterogeneity of rates. We anticipate our

  4. Analysis and modeling of resistive switching mechanisms oriented to resistive random-access memory

    International Nuclear Information System (INIS)

    Huang Da; Wu Jun-Jie; Tang Yu-Hua

    2013-01-01

    With the progress of the semiconductor industry, the resistive random-access memory (RAM) has drawn increasing attention. The discovery of the memristor has brought much attention to this study. Research has focused on the resistive switching characteristics of different materials and the analysis of resistive switching mechanisms. We discuss the resistive switching mechanisms of different materials in this paper and analyze the differences of those mechanisms from the view point of circuitry to establish their respective circuit models. Finally, simulations are presented. We give the prospect of using different materials in resistive RAM on account of their resistive switching mechanisms, which are applied to explain their resistive switchings

  5. Cadm2 regulates body weight and energy homeostasis in mice

    Directory of Open Access Journals (Sweden)

    Xin Yan

    2018-02-01

    Full Text Available Objective: Obesity is strongly linked to genes regulating neuronal signaling and function, implicating the central nervous system in the maintenance of body weight and energy metabolism. Genome-wide association studies identified significant associations between body mass index (BMI and multiple loci near Cell adhesion molecule2 (CADM2, which encodes a mediator of synaptic signaling enriched in the brain. Here we sought to further understand the role of Cadm2 in the pathogenesis of hyperglycemia and weight gain. Methods: We first analyzed Cadm2 expression in the brain of both human subjects and mouse models and subsequently characterized a loss-of-function mouse model of Cadm2 for alterations in glucose and energy homeostasis. Results: We show that the risk variant rs13078960 associates with increased CADM2 expression in the hypothalamus of human subjects. Increased Cadm2 expression in several brain regions of Lepob/ob mice was ameliorated after leptin treatment. Deletion of Cadm2 in obese mice (Cadm2/ob resulted in reduced adiposity, systemic glucose levels, and improved insulin sensitivity. Cadm2-deficient mice exhibited increased locomotor activity, energy expenditure rate, and core body temperature identifying Cadm2 as a potent regulator of systemic energy homeostasis. Conclusions: Together these data illustrate that reducing Cadm2 expression can reverse several traits associated with the metabolic syndrome including obesity, insulin resistance, and impaired glucose homeostasis. Keywords: Cadm2/SynCAM2, Energy homeostasis, Insulin sensitivity, Genome-wide association studies, Leptin signaling

  6. Serum uric acid levels are associated with homeostasis model assessment in obese nondiabetic patients: HOMA and uric acid.

    Science.gov (United States)

    Elizalde-Barrera, Cesar I; Estrada-García, Teresa; Lozano-Nuevo, Jose J; Garro-Almendaro, Ana K; López-Saucedo, Catalina; Rubio-Guerra, Alberto F

    2017-10-01

    Hyperuricemia leads to insulin resistance, whereas insulin resistance decreases renal excretion of uric acid. The aim of this study was to evaluate whether there is a correlation between serum uric acid levels with homeostatic model assessment (HOMA) 1 in nondiabetic patients. We evaluated 88 nondiabetic patients, in whom uric acid levels were measured, in all of them HOMA of β-cell function (HOMA 1B) and HOMA of insulin resistance (HOMA 1IR) scores were performed. Uric acid and the HOMA 1 values were correlated using the Pearson coefficient. We did not find any correlation between uric acid levels with both HOMA 1B ( r = 0.102, p = 0.343), nor with HOMA 1IR ( r = 0.158, p = 0.117). When patients were analyzed by sex, we found a significant correlation with HOMA 1IR (0.278, p = 0.01), but not with HOMA 1B (0.138, p = 0.257) in women. We found a correlation with HOMA 1B in men ( r = 0.37, p = 0.044), but not with HOMA 1IR: 0.203, p = 0.283. The analysis performed based on body mass index did not show correlation in the patients with normal weight, (HOMA 1B r = 0.08, p = 0.5, HOMA 1IR = 0.034, p = 0.793), nor in the patients who were overweight (HOMA 1B: r = 0.05, p = 0.76, HOMA 1IR r = 0.145, p = 0.43). However, a significant correlation between uricemia with both HOMA 1B (0.559, p uric acid levels seem to be associated with insulin resistance in women, and in obese patients, but not in nonobese men. Uric acid also modifies β-cell function in men and in obese patients.

  7. Comparison of the Usefulness of the Updated Homeostasis Model Assessment (HOMA2 with the Original HOMA1 in the Prediction of Type 2 Diabetes Mellitus in Koreans

    Directory of Open Access Journals (Sweden)

    Young Seok Song

    2016-05-01

    Full Text Available BackgroundThe original homeostasis model assessment (HOMA1 and the updated HOMA model (HOMA2 have been used to evaluate insulin resistance (IR and β-cell function, but little is known about the usefulness of HOMA2 for the prediction of diabetes in Koreans. The aim of this study was to demonstrate the usefulness of HOMA2 as a predictor of type 2 diabetes mellitus in Koreans without diabetes.MethodsThe study population consisted of 104,694 Koreans enrolled at a health checkup program and followed up from 2001 to 2012. Participants were divided into a normal glucose tolerance (NGT group and a pre-diabetes group according to fasting glucose and glycosylated hemoglobin levels. Anthropometric and laboratory data were measured at the baseline checkup, and HOMA values were calculated at the baseline and follow-up checkups. The hazard ratios (HRs of the HOMA1 and HOMA2 values and the prevalence of diabetes at follow-up were evaluated using a multivariable Cox proportional hazards model and Kaplan-Meier analysis.ResultsAfter adjusting for several diabetes risk factors, all of the HOMA values except 1/HOMA1-β and 1/HOMA2-β in the NGT group were significant predictors of the progression to diabetes. In the NGT group, there was no significant difference in HOMA1-IR (HR, 1.09; 95% confidence interval [CI], 1.04 to 1.14 and HOMA2-IR (HR, 1.11; 95% CI, 1.04 to 1.19. However, in the pre-diabetes group, 1/HOMA2-β was a more powerful marker (HR, 1.29; 95% CI, 1.26 to 1.31 than HOMA1-IR (HR, 1.23; 95% CI, 1.19 to 1.28 or 1/HOMA1-β (HR, 1.14; 95% CI, 1.12 to 1.16. In the non-diabetic group (NGT+pre-diabetes, 1/HOMA2-β was also a stronger predictor of diabetes (HR, 1.27; 95% CI, 1.25 to 1.29 than HOMA1-IR (HR, 1.14; 95% CI, 1.12 to 1.15 or 1/HOMA1-β (HR, 1.13; 95% CI, 1.11 to 1.14.ConclusionHOMA2 is more predictive than HOMA1 for the progression to diabetes in pre-diabetes or non-diabetic Koreans.

  8. Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Wu, C-W.; Biggar, K.K.; Storey, K.B. [Carleton University, Department of Biology, Institute of Biochemistry, Ottawa, ON (Canada)

    2013-01-28

    An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of research. As such, a unique model providing insight into the mechanisms of reversible insulin resistance is mammalian hibernation. Hibernators, such as ground squirrels and bats, are excellent examples of animals exhibiting reversible insulin resistance, for which a rapid increase in body weight is required prior to entry into dormancy. Hibernator studies have shown differential regulation of specific molecular pathways involved in reversible resistance to insulin. The present review focuses on this growing area of research and the molecular mechanisms that regulate glucose homeostasis, and explores the roles of the Akt signaling pathway during hibernation. Here, we propose a link between hibernation, a well-documented response to periods of environmental stress, and reversible insulin resistance, potentially facilitated by key alterations in the Akt signaling network, PPAR-γ/PGC-1α regulation, and non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during insulin resistance in human type 2 diabetes. Hence, the molecular networks that may regulate reversible insulin resistance in hibernating mammals represent a novel approach by providing insight into medical treatment of insulin resistance in humans.

  9. Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

    International Nuclear Information System (INIS)

    Wu, C-W.; Biggar, K.K.; Storey, K.B.

    2013-01-01

    An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of research. As such, a unique model providing insight into the mechanisms of reversible insulin resistance is mammalian hibernation. Hibernators, such as ground squirrels and bats, are excellent examples of animals exhibiting reversible insulin resistance, for which a rapid increase in body weight is required prior to entry into dormancy. Hibernator studies have shown differential regulation of specific molecular pathways involved in reversible resistance to insulin. The present review focuses on this growing area of research and the molecular mechanisms that regulate glucose homeostasis, and explores the roles of the Akt signaling pathway during hibernation. Here, we propose a link between hibernation, a well-documented response to periods of environmental stress, and reversible insulin resistance, potentially facilitated by key alterations in the Akt signaling network, PPAR-γ/PGC-1α regulation, and non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during insulin resistance in human type 2 diabetes. Hence, the molecular networks that may regulate reversible insulin resistance in hibernating mammals represent a novel approach by providing insight into medical treatment of insulin resistance in humans

  10. Modeling physiological resistance in bacterial biofilms.

    Science.gov (United States)

    Cogan, N G; Cortez, Ricardo; Fauci, Lisa

    2005-07-01

    A mathematical model of the action of antimicrobial agents on bacterial biofilms is presented. The model includes the fluid dynamics in and around the biofilm, advective and diffusive transport of two chemical constituents and the mechanism of physiological resistance. Although the mathematical model applies in three dimensions, we present two-dimensional simulations for arbitrary biofilm domains and various dosing strategies. The model allows the prediction of the spatial evolution of bacterial population and chemical constituents as well as different dosing strategies based on the fluid motion. We find that the interaction between the nutrient and the antimicrobial agent can reproduce survival curves which are comparable to other model predictions as well as experimental results. The model predicts that exposing the biofilm to low concentration doses of antimicrobial agent for longer time is more effective than short time dosing with high antimicrobial agent concentration. The effects of flow reversal and the roughness of the fluid/biofilm are also investigated. We find that reversing the flow increases the effectiveness of dosing. In addition, we show that overall survival decreases with increasing surface roughness.

  11. Brain glycogen and its role in supporting glutamate and GABA homeostasis in a type 2 diabetes rat model

    DEFF Research Database (Denmark)

    Sickmann, Helle Mark; Waagepetersen, Helle S.; Schousboe, Arne

    2012-01-01

    -(13)C]glucose was used to monitor metabolism. Brain levels of (13)C labeling in glucose, lactate, alanine, glutamate, GABA, glutamine and aspartate were determined. Our results show that inhibition of brain glycogen metabolism reduced the amounts of glutamate in both the control and type 2 diabetes......The number of people suffering from diabetes is hastily increasing and the condition is associated with altered brain glucose homeostasis. Brain glycogen is located in astrocytes and being a carbohydrate reservoir it contributes to glucose homeostasis. Furthermore, glycogen has been indicated...... to be important for proper neurotransmission under normal conditions. Previous findings from our laboratory suggested that glucose metabolism was reduced in type 2 diabetes, and thus we wanted to investigate more specifically how brain glycogen metabolism contributes to maintain energy status in the type 2...

  12. Tau causes synapse loss without disrupting calcium homeostasis in the rTg4510 model of tauopathy.

    Directory of Open Access Journals (Sweden)

    Katherine J Kopeikina

    Full Text Available Neurofibrillary tangles (NFTs of tau are one of the defining hallmarks of Alzheimer's disease (AD, and are closely associated with neuronal degeneration. Although it has been suggested that calcium dysregulation is important to AD pathogenesis, few studies have probed the link between calcium homeostasis, synapse loss and pathological changes in tau. Here we test the hypothesis that pathological changes in tau are associated with changes in calcium by utilizing in vivo calcium imaging in adult rTg4510 mice that exhibit severe tau pathology due to over-expression of human mutant P301L tau. We observe prominent dendritic spine loss without disruptions in calcium homeostasis, indicating that tangles do not disrupt this fundamental feature of neuronal health, and that tau likely induces spine loss in a calcium-independent manner.

  13. Atypical antipsychotics and glucose homeostasis.

    Science.gov (United States)

    Bergman, Richard N; Ader, Marilyn

    2005-04-01

    Persistent reports have linked atypical antipsychotics with diabetes, yet causative mechanisms responsible for this linkage are unclear. Goals of this review are to outline the pathogenesis of nonimmune diabetes and to survey the available literature related to why antipsychotics may lead to this disease. We accessed the literature regarding atypical antipsychotics and glucose homeostasis using PubMed. The search included English-language publications from 1990 through October 2004. Keywords used included atypical antipsychotics plus one of the following: glucose, insulin, glucose tolerance, obesity, or diabetes. In addition, we culled information from published abstracts from several national and international scientific meetings for the years 2001 through 2004, including the American Diabetes Association, the International Congress on Schizophrenia Research, and the American College of Neuropsychopharmacology. The latter search was necessary because of the paucity of well-controlled prospective studies. We examined publications with significant new data or publications that contributed to the overall comprehension of the impact of atypical antipsychotics on glucose metabolism. We favored original peer-reviewed articles and were less likely to cite single case studies and/or anecdotal information. Approximately 75% of the fewer than 150 identified articles were examined and included in this review. Validity of data was evaluated using the existence of peer-review status as well as our own experience with methodology described in the specific articles. The metabolic profile caused by atypical antipsychotic treatment resembles type 2 diabetes. These agents cause weight gain in treated subjects and may induce obesity in both visceral and subcutaneous depots, as occurs in diabetes. Insulin resistance, usually associated with obesity, occurs to varying degrees with different antipsychotics, although more comparative studies with direct assessment of resistance are

  14. The resistive tearing instability for generalized resistivity models: Applications

    International Nuclear Information System (INIS)

    Birk, G.T.; Otto, A.

    1991-01-01

    The dispersion relation for the resistive tearing mode is investigated with a general form of the resistivity that allows for evaluating the dependence of the mode on the anomalous dissipation caused by the lower-hybrid-drift turbulence and the ion-acoustic turbulence. The coupling of the plasma dynamic and radiative processes due to a temperature-dependent Spitzer resistivity are also discussed. The dispersion relation is solved numerically for two-dimensional equilibrium configurations with applications to the Earth's magnetosphere and the solar corona. In the case of the parameter regimes of the magnetopause and the solar corona, growth rates that result in realistic time scales for the respective dynamic processes as flux transfer events and solar flares were found. Moreover, the influence of a nonvanishing component of the magnetic field normal to the current sheet on the dispersion relation is examined. The normal field component leads to overstable modes and the growth rate of the pure tearing mode is not altered, whereas the radiative tearing mode is damped effectively

  15. A Wheat SIMILAR TO RCD-ONE Gene Enhances Seedling Growth and Abiotic Stress Resistance by Modulating Redox Homeostasis and Maintaining Genomic Integrity[C][W

    Science.gov (United States)

    Liu, Shuantao; Liu, Shuwei; Wang, Mei; Wei, Tiandi; Meng, Chen; Wang, Meng; Xia, Guangmin

    2014-01-01

    Plant growth inhibition is a common response to salinity. Under saline conditions, Shanrong No. 3 (SR3), a bread wheat (Triticum aestivum) introgression line, performs better than its parent wheat variety Jinan 177 (JN177) with respect to both seedling growth and abiotic stress tolerance. Furthermore, the endogenous reactive oxygen species (ROS) was also elevated in SR3 relative to JN177. The SR3 allele of sro1, a gene encoding a poly(ADP ribose) polymerase (PARP) domain protein, was identified to be crucial for both aspects of its superior performance. Unlike RADICAL-INDUCED CELL DEATH1 and other Arabidopsis thaliana SIMILAR TO RCD-ONE (SRO) proteins, sro1 has PARP activity. Both the overexpression of Ta-sro1 in wheat and its heterologous expression in Arabidopsis promote the accumulation of ROS, mainly by enhancing the activity of NADPH oxidase and the expression of NAD(P)H dehydrogenase, in conjunction with the suppression of alternative oxidase expression. Moreover, it promotes the activity of ascorbate-GSH cycle enzymes and GSH peroxidase cycle enzymes, which regulate ROS content and cellular redox homeostasis. sro1 is also found to be involved in the maintenance of genomic integrity. We show here that the wheat SRO has PARP activity; such activity could be manipulated to improve the growth of seedlings exposed to salinity stress by modulating redox homeostasis and maintaining genomic stability. PMID:24443520

  16. Effect of non-surgical periodontal therapy on insulin resistance in patients with type II diabetes mellitus and chronic periodontitis, as assessed by C-peptide and the Homeostasis Assessment Index.

    Science.gov (United States)

    Mammen, Jerry; Vadakkekuttical, Rosamma Joseph; George, Joseraj Manaloor; Kaziyarakath, Jaishid Ahadal; Radhakrishnan, Chandni

    2017-08-01

    A bidirectional relationship exists between diabetes and periodontitis. In the present clinical trial, we evaluated the effects of non-surgical periodontal therapy (NSPT) on insulin resistance in patients with type II diabetes mellitus (DM) and chronic periodontitis. Forty chronic periodontitis patients with type II DM were selected and equally allocated to case and control groups. All patients were assessed for periodontal parameters and systemic parameters. The case group received NSPT, and both groups were re-evaluated after 3 months. All periodontal parameters were found to be significantly improved in the case group compared to the control group 3 months after NSPT. The mean differences in systemic parameters, such as fasting serum C-peptide, Homeostasis Assessment (HOMA) Index-insulin resistance, and HOMA-insulin sensitivity, from baseline to 3 months for the case group were 0.544 ± 0.73, 0.54 ± 0.63, and -25.44 ± 36.81, respectively; for the control group, they were significant at -1.66 ± 1.89, -1.48 ± 1.86, and 31.42 ± 38.82 respectively (P periodontal inflammation could affect glycemic control and insulin resistance. Effective periodontal therapy reduced insulin resistance and improved periodontal health status and insulin sensitivity in patients with type II DM and chronic periodontitis. © 2016 John Wiley & Sons Australia, Ltd.

  17. Evaluation of the Genetic and Nutritional Control of Obesity and Type 2 Diabetes in a Novel Mouse Model on Chromosome 7: An Insight into Insulin Signaling and Glucose Homeostasis

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, S.; Dhar, M.

    2003-01-01

    Obesity is the main cause of type 2 diabetes, accounting for 90-95% of all diabetes cases in the US. Human obesity is a complex trait and can be studied using appropriate mouse models. A novel polygenic mouse model for studying the genetic and environmental contributions to and the physiological ramifications of obesity and related phenotypes is found in specific lines of mice bred and maintained at Oak Ridge National Laboratory. Heterozygous mice with a maternally inherited copy of two radiation-induced deletions in the p region of mouse chromosome 7, p23DFioD and p30PUb, have significantly greater body fat and show hyperinsulinemia compared to the wild-type. A single gene, Atp10c, maps to this critical region and codes for a putative aminophospholipid translocase. Biochemical and molecular studies were initiated to gain insight into obesity and glucose homeostasis in these animals and to study the biological role of Atp10c in creating these phenotypes. Glucose and insulin tolerance tests were standardized for the heterozygous p23DFioD and control mice on a custom-made diet containing 20% protein, 70% carbohydrate, and 10% fat (kcal). Atp10c expression profiles were also generated using Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR). Heterozygous p23DFioD animals showed insulin resistance after receiving a dose of either 0.375 or 0.75 U/kg Illetin R insulin. RT-PCR data also shows differences in Atp10c expression in the mutants versus control mice. Using these standardized biochemical assays, future studies will further the understanding of genetic and nutritional controls of glucose homeostasis and obesity in animal models and subsequently in human populations.

  18. Studies of axon-glial cell interactions and periaxonal K+ homeostasis--II. The effect of axonal stimulation, cholinergic agents and transport inhibitors on the resistance in series with the axon membrane.

    Science.gov (United States)

    Hassan, S; Lieberman, E M

    1988-06-01

    The small electrical resistance in series with the axon membrane is generally modeled as the intercellular pathway for current flow through the periaxonal glial (Schwann cell) sheath. The series resistance of the medial giant axon of the crayfish, Procambarus clarkii, was found to vary with conditions known to affect the electrical properties of the periaxonal glia. Series resistance was estimated from computer analysed voltage waveforms generated by axial wire-constant current and space clamp techniques. The average series resistance for all axons was 6.2 +/- 0.5 omega cm2 (n = 128). Values ranged between 1 and 30 omega cm2. The series resistance of axons with low resting membrane resistance (less than 1500 omega cm2) increased an average of 30% when stimulated for 45 s to 7 min (50 Hz) whereas the series resistance of high membrane resistance (greater than 1500 omega cm2) axons decreased an average of 10%. Carbachol (10(-7) M) caused the series resistance of low membrane resistance axons to decrease during stimulation but had no effect on high membrane resistance axons. d-Tubocurare (10(-8) M) caused the series resistance of high membrane resistance axons to increase during stimulation but had no effect on low membrane resistance axons. Bumetanide, a Na-K-Cl cotransport inhibitor and low [K+]o, prevented the stimulation-induced increase in series resistance of low membrane resistance axons but had no effect on the high membrane resistance axons. The results suggest that the series resistance of axons varies in response to the activity of the glial K+ uptake mechanisms stimulated by the appearance of K+ in the periaxonal space during action potential generation.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Studies of acid-base homeostasis during simulated weightlessness: Application of the water immersion model to man

    Science.gov (United States)

    Epstein, M.

    1975-01-01

    The effects of water immersion on acid-base homeostasis were investigated under carefully controlled conditions. Studies of renal acidification were carried out on seven healthy male subjects, each consuming a diet containing 150 meq sodium and 100 meq potassium. Control and immersion studies were carried out on each subject on the fourth and sixth days, respectively, of dietary equilibration, by which time all subjects had achieved sodium balance. The experimental protocols on study days were similar (except for the amount of water administered).

  20. Receiver Expectations: Toward a New Model of Resistance to Persuasion.

    Science.gov (United States)

    Miller, Michael D.; Burgoon, Michael

    Communication research long has noted how pretreatment strategies ("inoculations") induce resistance to persuasion, but a new model proposes that resistance is an integral part of the persuasion process. Using the inoculation framework, researchers showed the importance of threats to an individual's attitudes in developing resistance to…

  1. Epidemiological models for the spread of anti-malarial resistance

    Directory of Open Access Journals (Sweden)

    Antia R

    2003-02-01

    Full Text Available Abstract Background The spread of drug resistance is making malaria control increasingly difficult. Mathematical models for the transmission dynamics of drug sensitive and resistant strains can be a useful tool to help to understand the factors that influence the spread of drug resistance, and they can therefore help in the design of rational strategies for the control of drug resistance. Methods We present an epidemiological framework to investigate the spread of anti-malarial resistance. Several mathematical models, based on the familiar Macdonald-Ross model of malaria transmission, enable us to examine the processes and parameters that are critical in determining the spread of resistance. Results In our simplest model, resistance does not spread if the fraction of infected individuals treated is less than a threshold value; if drug treatment exceeds this threshold, resistance will eventually become fixed in the population. The threshold value is determined only by the rates of infection and the infectious periods of resistant and sensitive parasites in untreated and treated hosts, whereas the intensity of transmission has no influence on the threshold value. In more complex models, where hosts can be infected by multiple parasite strains or where treatment varies spatially, resistance is generally not fixed, but rather some level of sensitivity is often maintained in the population. Conclusions The models developed in this paper are a first step in understanding the epidemiology of anti-malarial resistance and evaluating strategies to reduce the spread of resistance. However, specific recommendations for the management of resistance need to wait until we have more data on the critical parameters underlying the spread of resistance: drug use, spatial variability of treatment and parasite migration among areas, and perhaps most importantly, cost of resistance.

  2. Two cation transporters Ena1 and Nha1 cooperatively modulate ion homeostasis, antifungal drug resistance, and virulence of Cryptococcus neoformans via the HOG pathway

    Science.gov (United States)

    Jung, Kwang-Woo; Strain, Anna K; Nielsen, Kirsten; Jung, Kwang-Hwan; Bahn, Yong-Sun

    2012-01-01

    Maintenance of cation homeostasis is essential for survival of all living organisms in their biological niches. It is also important for the survival of human pathogenic fungi in the host, where cation concentrations and pH will vary depending on different anatomical sites. However, the exact role of diverse cation transporters and ion channels in virulence of fungal pathogens remains elusive. In this study we functionally characterized ENA1 and NHA1, encoding a putative Na+/ATPase and Na+/H+ antiporter, respectively, in Cryptococcus neoformans, a basidiomycete fungal pathogen which causes fatal meningoencephalitis. Expression of NHA1 and ENA1 is induced in response to salt and osmotic shock mainly in a Hog1-dependent manner. Phenotypic analysis of the ena1, nha1, and ena1 nha1 mutants revealed that Ena1 controls cellular levels of toxic cations, such as Na+ and Li+ whereas both Ena1 and Nha1 are important for controlling less toxic K+ ions. Under alkaline conditions, Ena1 was highly induced and required for growth in the presence of low levels of Na+ or K+ salt and Nha1 played a role in survival under K+ stress. In contrast, Nha1, but not Ena1, was essential for survival at acidic conditions (pH 4.5) under high K+ stress. In addition, Ena1 and Nha1 were required for maintenance of plasma membrane potential and stability, which appeared to modulate antifungal drug susceptibility. Perturbation of ENA1 and NHA1 enhanced capsule production and melanin synthesis. However, Nha1 was dispensable for virulence of C. neoformans although Ena1 was essential. In conclusion, Ena1 and Nha1 play redundant and discrete roles in cation homeostasis, pH regulation, membrane potential, and virulence in C. neoformans, suggesting that these transporters could be novel antifungal drug targets for treatment of cryptococcosis. PMID:22343280

  3. Model for evaluating nuclear strategies with proliferation resistance

    International Nuclear Information System (INIS)

    Shay, M.R.; Hardie, R.W.; Omberg, R.P.

    1979-03-01

    A model was developed at HEDL to specifically analyze proliferation resistant strategies. The model was not designed to predict the future, but rather to provide a method for estimating the consequences of decisions affecting proliferation resistance in a rational and plausible manner. The characteristics of the model are described

  4. Effect of Rolling Resistance in Dem Models With Spherical Bodies

    Directory of Open Access Journals (Sweden)

    Dubina Radek

    2016-12-01

    Full Text Available The rolling resistance is an artificial moment arising on the contact of two discrete elements which mimics resistance of two grains of complex shape in contact rolling relatively to each other. The paper investigates the influence of rolling resistance on behaviour of an assembly of spherical discrete elements. Besides the resistance to rolling, the contacts between spherical particles obey the Hertzian law in normal straining and Coulomb model of friction in shear.

  5. Lactobacillus rhamnosus GG treatment improves intestinal permeability and modulates inflammatory response and homeostasis of spleen and colon in experimental model of Pseudomonas aeruginosa pneumonia.

    Science.gov (United States)

    Khailova, Ludmila; Baird, Christine H; Rush, Aubri A; Barnes, Christopher; Wischmeyer, Paul E

    2017-12-01

    Recent clinical trials and in vivo models demonstrate probiotic administration can reduce occurrence and improve outcome of pneumonia and sepsis, both major clinical challenges worldwide. Potential probiotic benefits include maintenance of gut epithelial barrier homeostasis and prevention of downstream organ dysfunction due to systemic inflammation. However, mechanism(s) of probiotic-mediated protection against pneumonia remain poorly understood. This study evaluated potential mechanistic targets in the maintenance of gut barrier homeostasis following Lactobacillus rhamnosus GG (LGG) treatment in a mouse model of pneumonia. Studies were performed in 6-8 week old FVB/N mice treated (o.g.) with or without LGG (10 9  CFU/ml) and intratracheally injected with Pseudomonas aeruginosa or saline. At 4, 12, and 24 h post-bacterial treatment spleen and colonic tissue were collected for analysis. Pneumonia significantly increased intestinal permeability and gut claudin-2. LGG significantly attenuated increased gut permeability and claudin-2 following pneumonia back to sham control levels. As mucin expression is key to gut barrier homeostasis we demonstrate that LGG can enhance goblet cell expression and mucin barrier formation versus control pneumonia animals. Further as Muc2 is a key gut mucin, we show LGG corrected deficient Muc2 expression post-pneumonia. Apoptosis increased in both colon and spleen post-pneumonia, and this increase was significantly attenuated by LGG. Concomitantly, LGG corrected pneumonia-mediated loss of cell proliferation in colon and significantly enhanced cell proliferation in spleen. Finally, LGG significantly reduced pro-inflammatory cytokine gene expression in colon and spleen post-pneumonia. These data demonstrate LGG can maintain intestinal barrier homeostasis by enhancing gut mucin expression/barrier formation, reducing apoptosis, and improving cell proliferation. This was accompanied by reduced pro-inflammatory cytokine expression in the

  6. Disruption of redox homeostasis in liver function and activation of apoptosis on consumption of aspartame in folate deficient rat model

    Directory of Open Access Journals (Sweden)

    Ashok Iyaswamy

    2017-06-01

    Full Text Available This study assesses the effect of long-term intake of aspartame on liver function and apoptosis signaling pathway in the Wistar albino rats. Several reports have suggested that methanol is one of the major metabolites of Aspartame. Non-primate animals are usually resistant to methanol-induced metabolic acidosis due to high levels of hepatic folate content; hence a folate deficiency model was induced by treating animals with methotrexate (MTX prior to aspartame exposure. The aspartame treated MTX animals exhibited a marked significant increase in hepatic alanine transaminase (ALT, aspartate transaminase (AST, alkaline phosphatase (ALP and lactic acid dehydrogenase (LDH activity compared to controls. Aspartame treated MTX animals additionally exhibited down-regulation of genes namely B-cell lymphoma 2 (Bcl2 expression and up-regulation of Bcl-2-associated X protein (Bax, Fas-associated protein with death domain (FADD and Caspase 3, 9 genes and apoptotic protein expression, indicating the augmentation of hepatic apoptosis. Nuclear condensation, micro vacuole formation in the cytoplasm and necrosis were observed in the liver of the aspartame treated animals on histopathology evaluation. Additionally, Immunohistochemical analysis revealed a significant increase in positive cells expressing Fas, FADD, Bax and Caspase 9 protein, indicating an increase in apoptotic protein expression in the liver. Thus, Aspartame may act as a chemical stressor which alters the functional status of liver, leading to hepatotoxicity.

  7. Model of pulmonary fluid traffic homeostasis based on respiratory cycle pressure, bidirectional bronchiolo-pulmonar shunting and water evaporation.

    Science.gov (United States)

    Kurbel, Sven; Kurbel, Beatrica; Gulam, Danijela; Spajić, Borislav

    2010-06-01

    The main puzzle of the pulmonary circulation is how the alveolar spaces remain dry over a wide range of pulmonary vascular pressures and blood flows. Although normal hydrostatic pressure in pulmonary capillaries is probably always below 10 mmHg, well bellow plasma colloid pressure of 25 mmHg, most textbooks state that some fluid filtration through capillary walls does occur, while the increased lymph drainage prevents alveolar fluid accumulation. The lack of a measurable pressure drop along pulmonary capillaries makes the classic description of Starling forces unsuitable to the low pressure, low resistance pulmonary circulation. Here presented model of pulmonary fluid traffic describes lungs as a matrix of small vascular units, each consisting of alveoli whose capillaries are anastomotically linked to the bronchiolar capillaries perfused by a single bronchiolar arteriole. It proposes that filtration and absorption in pulmonary and in bronchiolar capillaries happen as alternating periods of low and of increased perfusion pressures. The model is based on three levels of filtration control: short filtration phases due to respiratory cycle of the whole lung are modulated by bidirectional bronchiolo-pulmonar shunting independently in each small vascular unit, while fluid evaporation from alveolar groups further tunes local filtration. These mechanisms are used to describe a self-sustaining regulator that allows optimal fluid traffic in different settings. The proposed concept is used to describe development of pulmonary edema in several clinical entities (exercise in wet or dry climate, left heart failure, people who rapidly move to high altitudes, acute cyanide and carbon monoxide poisoning, large pulmonary embolisms). .

  8. An Empirical Test of a Model of Resistance to Persuasion.

    Science.gov (United States)

    And Others; Burgoon, Michael

    1978-01-01

    Tests a model of resistance to persuasion based upon variables not considered by earlier congruity and inoculation models. Supports the prediction that the kind of critical response set induced and the target of the criticism are mediators of resistance to persuasion. (JMF)

  9. Gliadin affects glucose homeostasis and intestinal metagenome in C57BL/6 mice fed and high-fat diet

    DEFF Research Database (Denmark)

    Zhang, Li; Hansen, Axel Kornerup; Bahl, Martin Iain

    time, with a borderline significance of higher HOMA-IR (homeostasis model assessment of insulin resistance) after 22 weeks. Sequencing of the V3 region of the bacterial 16S rRNA genes showed that gliadin changed the abundance of 81 bacterial taxa, separating the intestinal microbial profile...

  10. Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease.

    Directory of Open Access Journals (Sweden)

    Susanne C Beck

    Full Text Available Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms that induce progression into severe adult disease. The goal of this study was the comprehensive analysis of the long-term effects of the absence of Norrin on vascular homeostasis and retinal function. In a mouse model of Norrie disease retinal vascular morphology and integrity were studied by means of in vivo angiography; the vascular constituents were assessed in detailed histological analyses using quantitative retinal morphometry. Finally, electroretinographic analyses were performed to assess the retinal function in adult Norrin deficient animals. We could show that the primary developmental defects not only persisted but developed into further vascular abnormalities and microangiopathies. In particular, the overall vessel homeostasis, the vascular integrity, and also the cellular constituents of the vascular wall were affected in the adult Norrin deficient retina. Moreover, functional analyses indicated to persistent hypoxia in the neural retina which was suggested as one of the major driving forces of disease progression. In summary, our data provide evidence that the key to adult Norrie disease are ongoing vascular modifications, driven by the persistent hypoxic conditions, which are ineffective to compensate for the primary Norrin-dependent defects.

  11. Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease.

    Science.gov (United States)

    Beck, Susanne C; Feng, Yuxi; Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Tanimoto, Naoyuki; Acar, Niyazi; Shan, Shenliang; Seebauer, Britta; Berger, Wolfgang; Hammes, Hans-Peter; Seeliger, Mathias W

    2017-01-01

    Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms that induce progression into severe adult disease. The goal of this study was the comprehensive analysis of the long-term effects of the absence of Norrin on vascular homeostasis and retinal function. In a mouse model of Norrie disease retinal vascular morphology and integrity were studied by means of in vivo angiography; the vascular constituents were assessed in detailed histological analyses using quantitative retinal morphometry. Finally, electroretinographic analyses were performed to assess the retinal function in adult Norrin deficient animals. We could show that the primary developmental defects not only persisted but developed into further vascular abnormalities and microangiopathies. In particular, the overall vessel homeostasis, the vascular integrity, and also the cellular constituents of the vascular wall were affected in the adult Norrin deficient retina. Moreover, functional analyses indicated to persistent hypoxia in the neural retina which was suggested as one of the major driving forces of disease progression. In summary, our data provide evidence that the key to adult Norrie disease are ongoing vascular modifications, driven by the persistent hypoxic conditions, which are ineffective to compensate for the primary Norrin-dependent defects.

  12. [Effects of telmisartan on resistin expression in a rat model of nonalcoholic steatohepatitis and insulin resistance].

    Science.gov (United States)

    Zhang, Qiuzan; Wang, Yanrong; Liu, Yingli; Yang, Qian; Wang, Xiuru; Wang, Qiang; Zhang, Chenming; Wang, Bangmao

    2015-04-01

    To investigate the effects of telmisartan on expression of resistin in serum and liver under conditions of nonalcoholic steatohepatitis (NASH) and insulin resistance using a rat model system. Forty-five male Sprague-Dawley rats were randomly divided into a normal control group (NC, n=10), a model control group (MC, n=15), a polyene phosphatidylcholine prevention group (PP, n=10), and a telmisartan prevention group (TP, n=10). The NC group was given a standard diet and the other groups were given a high-fat diet for 16 weeks in order to induce NASH. At the end of week 12, 5 rats in the MC group were sacrificed for pathology confirmation of the NASH model. At the end of week 12, the TP group was given telmisartan (8.0 mg/kg/d) and the PP group was given polyene phosphatidylcholine (8.4 mg/kg/d) for an additional 4 weeks by intragastric administration. At the end of week 16, all rats were sacrificed and body weights recorded. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), resistin, insulin and fasting blood glucose were measured. The insulin resistance value, HOMA-IR, was assessed by homeostasis mode assessment. Liver expression of the resistin protein was detected by western blotting and of the resistin mRNA was detected by RT-PCR. The F test and LSD test were used for statistical analyses. Compared to the NC group, the body weight and HOMA-IR of rats in the MC group were significantly increased (Pinsulin resistance were significantly lower in the TP group than in the MC group of rats (all Pinsulin resistance in NASH rats by decreasing the expression of serum resistin, and liver resistin protein and mRNA.

  13. Statistical models of a gas diffusion electrode: II. Current resistent

    Energy Technology Data Exchange (ETDEWEB)

    Proksch, D B; Winsel, O W

    1965-07-01

    The authors describe an apparatus for measuring the flow resistance of gas diffusion electrodes which is a mechanical analog of the Wheatstone bridge for measuring electric resistance. The flow resistance of a circular DSK electrode sheet, consisting of two covering layers and a working layer between them, was measured as a function of the gas pressure. While the pressure first was increased and then decreased, a hysteresis occurred, which is discussed and explained by a statistical model of a porous electrode.

  14. Filamentary model in resistive switching materials

    Science.gov (United States)

    Jasmin, Alladin C.

    2017-12-01

    The need for next generation computer devices is increasing as the demand for efficient data processing increases. The amount of data generated every second also increases which requires large data storage devices. Oxide-based memory devices are being studied to explore new research frontiers thanks to modern advances in nanofabrication. Various oxide materials are studied as active layers for non-volatile memory. This technology has potential application in resistive random-access-memory (ReRAM) and can be easily integrated in CMOS technologies. The long term perspective of this research field is to develop devices which mimic how the brain processes information. To realize such application, a thorough understanding of the charge transport and switching mechanism is important. A new perspective in the multistate resistive switching based on current-induced filament dynamics will be discussed. A simple equivalent circuit of the device gives quantitative information about the nature of the conducting filament at different resistance states.

  15. Validation of insulin resistance indexes in a stable renal transplant population

    NARCIS (Netherlands)

    Oterdoom, Leendert H.; de Vries, Aiko P. J.; van Son, Willem J.; Homan van der Heide, Jaap J.; Ploeg, Rutger J.; Gansevoort, Ron T.; de Jong, Paul E.; Gans, Rijk O. B.; Bakker, Stephan J. L.

    2005-01-01

    The purpose of this study was to investigate the validity of established insulin resistance indexes, based on fasting blood parameters, in a stable renal transplant population. Fasting insulin, homeostasis model assessment (HOMA), the quantitative insulin sensitivity check index (QUICKI), and

  16. Validation of insulin resistance indexes in a stable renal transplant population

    NARCIS (Netherlands)

    Oterdoom, LH; De Vries, APJ; Van Son, WJ; Van Der Heide, JJH; Ploeg, RJ; Gansevoort, RT; De Jong, PE; Gans, ROB; Bakker, SJL

    2005-01-01

    OBJECTIVE - The purpose of this study was to investigate the validity of established insulin resistance indexes, based on fasting blood parameters, in a stable renal transplant population. RESEARCH DESIGN AND METHODS - Fasting insulin, homeostasis model assessment (HOMA), the quantitative insulin

  17. Mathematical modeling and computational prediction of cancer drug resistance.

    Science.gov (United States)

    Sun, Xiaoqiang; Hu, Bin

    2017-06-23

    Diverse forms of resistance to anticancer drugs can lead to the failure of chemotherapy. Drug resistance is one of the most intractable issues for successfully treating cancer in current clinical practice. Effective clinical approaches that could counter drug resistance by restoring the sensitivity of tumors to the targeted agents are urgently needed. As numerous experimental results on resistance mechanisms have been obtained and a mass of high-throughput data has been accumulated, mathematical modeling and computational predictions using systematic and quantitative approaches have become increasingly important, as they can potentially provide deeper insights into resistance mechanisms, generate novel hypotheses or suggest promising treatment strategies for future testing. In this review, we first briefly summarize the current progress of experimentally revealed resistance mechanisms of targeted therapy, including genetic mechanisms, epigenetic mechanisms, posttranslational mechanisms, cellular mechanisms, microenvironmental mechanisms and pharmacokinetic mechanisms. Subsequently, we list several currently available databases and Web-based tools related to drug sensitivity and resistance. Then, we focus primarily on introducing some state-of-the-art computational methods used in drug resistance studies, including mechanism-based mathematical modeling approaches (e.g. molecular dynamics simulation, kinetic model of molecular networks, ordinary differential equation model of cellular dynamics, stochastic model, partial differential equation model, agent-based model, pharmacokinetic-pharmacodynamic model, etc.) and data-driven prediction methods (e.g. omics data-based conventional screening approach for node biomarkers, static network approach for edge biomarkers and module biomarkers, dynamic network approach for dynamic network biomarkers and dynamic module network biomarkers, etc.). Finally, we discuss several further questions and future directions for the use of

  18. Testing and Modeling of Machine Properties in Resistance Welding

    DEFF Research Database (Denmark)

    Wu, Pei

    The objective of this work has been to test and model the machine properties including the mechanical properties and the electrical properties in resistance welding. The results are used to simulate the welding process more accurately. The state of the art in testing and modeling machine properties...... as real projection welding tests, is easy to realize in industry, since tests may be performed in situ. In part II, an approach of characterizing the electrical properties of AC resistance welding machines is presented, involving testing and mathematical modelling of the weld current, the firing angle...... in resistance welding has been described based on a comprehensive literature study. The present thesis has been subdivided into two parts: Part I: Mechanical properties of resistance welding machines. Part II: Electrical properties of resistance welding machines. In part I, the electrode force in the squeeze...

  19. The common inhaled anesthetic isoflurane increases aggregation of huntingtin and alters calcium homeostasis in a cell model of Huntington's disease

    International Nuclear Information System (INIS)

    Wang Qiujun; Liang Ge; Yang Hui; Wang Shouping; Eckenhoff, Maryellen F.; Wei Huafeng

    2011-01-01

    Isoflurane is known to increase β-amyloid aggregation and neuronal damage. We hypothesized that isoflurane will have similar effects on the polyglutamine huntingtin protein and will cause alterations in intracellular calcium homeostasis. We tested this hypothesis in striatal cells from the expanded glutamine huntingtin knock-in mouse (STHdh Q111/Q111 ) and wild type (STHdh Q7/Q7 ) striatal neurons. The primary cultured neurons were exposed for 24 h to equipotent concentrations of isoflurane, sevoflurane, and desflurane in the presence or absence of extracellular calcium and with or without xestospongin C, a potent endoplasmic reticulum inositol 1,4,5-trisphosphate (InsP 3 ) receptor antagonist. Aggregation of huntingtin protein, cell viability, and calcium concentrations were measured. Isoflurane, sevoflurane, and desflurane all increased the aggregation of huntingtin in STHdh Q111/Q111 cells, with isoflurane having the largest effect. Isoflurane induced greater calcium release from the ER and relatively more cell damage in the STHdh Q111/Q111 huntingtin cells than in the wild type STHdh Q7/Q7 striatal cells. However, sevoflurane and desflurane caused less calcium release from the ER and less cell damage. Xestospongin C inhibited the isoflurane-induced calcium release from the ER, aggregation of huntingtin, and cell damage in the STHdh Q111/Q111 cells. In summary, the Q111 form of huntingtin increases the vulnerability of striatal neurons to isoflurane neurotoxicity through combined actions on the ER IP 3 receptors. Calcium release from the ER contributes to the anesthetic induced huntingtin aggregation in STHdh Q111/Q111 striatal cells.

  20. Testing and Modeling of Contact Problems in Resistance Welding

    DEFF Research Database (Denmark)

    Song, Quanfeng

    together two or three cylindrical parts as well as disc-ring pairs of dissimilar metals. The tests have demonstrated the effectiveness of the model. A theoretical and experimental study is performed on the contact resistance aiming at a more reliable model for numerical simulation of resistance welding......As a part of the efforts towards a professional and reliable numerical tool for resistance welding engineers, this Ph.D. project is dedicated to refining the numerical models related to the interface behavior. An FE algorithm for the contact problems in resistance welding has been developed...... for the formulation, and the interfaces are treated in a symmetric pattern. The frictional sliding contact is also solved employing the constant friction model. The algorithm is incorporated into the finite element code. Verification is carried out in some numerical tests as well as experiments such as upsetting...

  1. Analysis and modeling of resistive switching mechanism oriented to fault tolerance of resistive memory based on memristor

    International Nuclear Information System (INIS)

    Huang Da; Wu Jun-Jie; Tang Yu-Hua

    2014-01-01

    With the progress of the semiconductor industry, resistive memories, especially the memristor, have drawn increasing attention. The resistive memory based on memrsitor has not been commercialized mainly because of data error. Currently, there are more studies focused on fault tolerance of resistive memory. This paper studies the resistive switching mechanism which may have time-varying characteristics. Resistive switching mechanism is analyzed and its respective circuit model is established based on the memristor Spice model

  2. pH and Ion Homeostasis on Plant Endomembrane Dynamics: Insights from structural models and mutants of K+/H+ antiporters.

    Science.gov (United States)

    Sze, Heven; Chanroj, Salil

    2018-04-24

    Plants remodel their cells through the dynamic endomembrane system. Intracellular pH is important for membrane trafficking, but the determinants of pH homeostasis are poorly defined in plants. Electrogenic proton (H+) pumps depend on counter-ion fluxes to establish transmembrane pH gradients at the plasma membrane and endomembranes. Vacuolar-type H+-ATPase-mediated acidification of the trans-Golgi network (TGN) is crucial for secretion and membrane recycling. Pump and counter-ion fluxes are unlikely to fine-tune pH; rather, alkali cation/H+ antiporters, which can alter pH and/or cation homeostasis locally and transiently, are prime candidates. Plants have a large family of predicted cation/H+ exchangers (CHX) of obscure function, in addition to the well-studied K+(Na+)/H+ exchangers (NHX). Here, we review the regulation of cytosolic and vacuolar pH, highlighting the similarities and distinctions of NHX and CHX members. In planta, alkalinization of the TGN or vacuole by NHXs promotes membrane trafficking, endocytosis, cell expansion, and growth. CHXs localize to endomembranes and/or the plasma membrane, contribute to male fertility, pollen tube guidance, pollen wall construction, stomatal opening, and in soybean (Glycine max), tolerance to salt stress. Three-dimensional structural models and mutagenesis of Arabidopsis thaliana genes have allowed us to infer that AtCHX17 and AtNHX1 share a global architecture and a translocation core like bacterial Na+/H+ antiporters. Yet the presence of distinct residues suggests some CHXs differ from NHXs in pH sensing and electrogenicity. How H+ pumps, counter-ion fluxes, and cation/H+ antiporters are linked with signaling and membrane trafficking to remodel membranes and cell walls awaits further investigation. {copyright, serif} 2018 American Society of Plant Biologists. All rights reserved.

  3. Violation of homeostasis of the main types of exchange and immune resistance status in children with subclinical hypovitaminosis in conditions of exposure to chemical environmental factors

    Directory of Open Access Journals (Sweden)

    A.M. Yambulatov

    2016-03-01

    Full Text Available The study of the chemical substances’ content of anthropogenic origin in children with subclinical polyhypovitaminosis was conducted. It was found that a deficiency of vitamins A, C, E, B6 and B12 increases the risk of developing of elevated concentrations of organic substances of technogenic origin in blood in 1.4–6.9 times. In children with subclinical polyhypovitaminosis and high blood phenol, formaldehyde, aromatic hydrocarbons, and organ chlorine compounds increases the tension of erythropoiesis, decreases the activity of proliferating processes of lympfomonocytic germ cell factors of nonspecific resistance. Even subclinical forms of polyhypovitaminosis on the background of high content of organic compounds in the blood of children are accompanied by a slowdown of protein and carbohydrate metabolism, depletion of antioxidant defense system of reserves and shortage of energy metabolism. Developing disorders of fat metabolism in children with subclinical polyhypovitaminosis occur against a background of strained reactions of hormonal regulation that, in case of the progressive course may pose a threat to the early development of cardiovascular disease in older age groups.

  4. Glucose Homeostasis Variables in Pregnancy versus Maternal and Infant Body Composition

    Directory of Open Access Journals (Sweden)

    Pontus Henriksson

    2015-07-01

    Full Text Available Intrauterine factors influence infant size and body composition but the mechanisms involved are to a large extent unknown. We studied relationships between the body composition of pregnant women and variables related to their glucose homeostasis, i.e., glucose, HOMA-IR (homeostasis model assessment-insulin resistance, hemoglobin A1c and IGFBP-1 (insulin-like growth factor binding protein-1, and related these variables to the body composition of their infants. Body composition of 209 women in gestational week 32 and of their healthy, singleton and full-term one-week-old infants was measured using air displacement plethysmography. Glucose homeostasis variables were assessed in gestational week 32. HOMA-IR was positively related to fat mass index and fat mass (r2 = 0.32, p < 0.001 of the women. Maternal glucose and HOMA-IR values were positively (p ≤ 0.006 associated, while IGFBP-1was negatively (p = 0.001 associated, with infant fat mass. HOMA-IR was positively associated with fat mass of daughters (p < 0.001, but not of sons (p = 0.65 (Sex-interaction: p = 0.042. In conclusion, glucose homeostasis variables of pregnant women are related to their own body composition and to that of their infants. The results suggest that a previously identified relationship between fat mass of mothers and daughters is mediated by maternal insulin resistance.

  5. SPICE compatible behavioural modelling of resistive sensors

    International Nuclear Information System (INIS)

    Nandi, Prajit; Dhar, Anindya Sundar; Das, Soumen; Sahu, Debashis

    2014-01-01

    In this paper, a modelling technique for anisotropic magneto-resistors (AMRs) and piezo-resistors has been developed. These models are then used to model sensors using such elements. The motivation is to develop a platform which will help in the analysis of different performance parameters of such sensors and optimally design electronic systems for such sensor applications. Non-idealistic behaviour such as temperature and nonlinearity, hysteresis, mismatch, noise, etc have been considered while developing the model. The proposed technique helps us to study each of these non-idealities individually as well as understand the holistic sensor response. Root-cause analysis can, thus, be performed. Model parameters are derived from different product specifications and various characterization reports. The sensor's response predicted from the model is compared with the performance of these products. Response of the model is seen to closely follow the response of the actual product. (paper)

  6. Birinci trimesterde homeostasis model assessment -insulin resistance (HOMA-IR) indeksi tayini ile gestasyonel diabetes mellitus'un prediksiyonu

    OpenAIRE

    GÜMÜŞ, Yeliz

    2012-01-01

    Gestasyonel diabetes mellitus gebelikle birlikte ortaya çıkan veya ilk olarak gebelikte tanısı konan karbonhidrat intoleransı olarak tanımlanmaktadır. Toplumlardaki ağırlık artışı ve obezite oranlarının giderek yükselmesine paralel olarak GDM prevalansı da artmaktadır. Makrozomi, omuz distosisi, doğum esnasında fiziksel yaralanma, hipoglisemi, hiperbilirubinemi, solunum problemleri ve çocukluk çağında obezite gibi fetal ve neonatal risklerin yanı sıra, preeklampsi, sezaryen ile doğum...

  7. Thermodynamic and kinetic modelling: creep resistant materials

    DEFF Research Database (Denmark)

    Hald, John; Korcakova, L.; Danielsen, Hilmar Kjartansson

    2008-01-01

    The use of thermodynamic and kinetic modelling of microstructure evolution in materials exposed to high temperatures in power plants is demonstrated with two examples. Precipitate stability in martensitic 9–12%Cr steels is modelled including equilibrium phase stability, growth of Laves phase part...

  8. Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Yuan-Horng [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan (China); Charles, Chou C.-K. [Research Center for Environmental Changes, Academia Sinica, Taipei, Taiwan (China); Wang, Jyh-Seng [Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Tung, Chun-Liang [Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan (China); Li, Ya-Ru; Lo, Kai [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Cheng, Tsun-Jen, E-mail: tcheng@ntu.edu.tw [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan (China)

    2014-12-01

    Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM{sub 2.5} exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), to continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24 h/day, 7 days/week, for a total of 16 weeks. The average concentrations (mean [SD]) of PM{sub 2.5} in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05] μg/m{sup 3}, respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P < 0.05). Interleukin 6 and fibrinogen levels were significantly increased after PM exposure. PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney (tubular damage index: 1.76 [0.77] vs. 1.15 [0.36], P < 0.001). PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation. - Highlights: • The study demonstrated cardiovascular and renal effects of PM in a rat model of DM. • TAPES is a continuous, real world, long-term PM exposure system. • HbA1c, a marker of glycemic

  9. Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model

    International Nuclear Information System (INIS)

    Yan, Yuan-Horng; Charles, Chou C.-K.; Wang, Jyh-Seng; Tung, Chun-Liang; Li, Ya-Ru; Lo, Kai; Cheng, Tsun-Jen

    2014-01-01

    Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM 2.5 exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), to continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24 h/day, 7 days/week, for a total of 16 weeks. The average concentrations (mean [SD]) of PM 2.5 in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05] μg/m 3 , respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P < 0.05). Interleukin 6 and fibrinogen levels were significantly increased after PM exposure. PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney (tubular damage index: 1.76 [0.77] vs. 1.15 [0.36], P < 0.001). PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation. - Highlights: • The study demonstrated cardiovascular and renal effects of PM in a rat model of DM. • TAPES is a continuous, real world, long-term PM exposure system. • HbA1c, a marker of glycemic homeostasis, was

  10. A model of antibiotic-resistant bacterial epidemics in hospitals

    OpenAIRE

    Webb, Glenn F.; D'Agata, Erika M. C.; Magal, Pierre; Ruan, Shigui

    2005-01-01

    The emergence of drug-resistant strains of bacteria is an increasing threat to society, especially in hospital settings. Many antibiotics that were formerly effective in combating bacterial infections in hospital patients are no longer effective because of the evolution of resistant strains, which compromises medical care worldwide. In this article, we formulate a two-level population model to quantify key elements in nosocomial (hospital-acquired) infections. At the bacteria level, patients ...

  11. Mathematical Modeling of Contact Resistance in Silicon Photovoltaic Cells

    KAUST Repository

    Black, J. P.

    2013-10-22

    In screen-printed silicon-crystalline solar cells, the contact resistance of a thin interfacial glass layer between the silicon and the silver electrode plays a limiting role for electron transport. We analyze a simple model for electron transport across this layer, based on the driftdiffusion equations. We utilize the size of the current/Debye length to conduct asymptotic techniques to simplify the model; we solve the model numerically to find that the effective contact resistance may be a monotonic increasing, monotonic decreasing, or nonmonotonic function of the electron flux, depending on the values of the physical parameters. © 2013 Society for Industrial and Applied Mathematics.

  12. Mathematical Modeling of Contact Resistance in Silicon Photovoltaic Cells

    KAUST Repository

    Black, J. P.; Breward, C. J. W.; Howell, P. D.; Young, R. J. S.

    2013-01-01

    across this layer, based on the driftdiffusion equations. We utilize the size of the current/Debye length to conduct asymptotic techniques to simplify the model; we solve the model numerically to find that the effective contact resistance may be a

  13. The brain acid-base homeostasis and serotonin: A perspective on the use of carbon dioxide as human and rodent experimental model of panic.

    Science.gov (United States)

    Leibold, N K; van den Hove, D L A; Esquivel, G; De Cort, K; Goossens, L; Strackx, E; Buchanan, G F; Steinbusch, H W M; Lesch, K P; Schruers, K R J

    2015-06-01

    Panic attacks (PAs), the core feature of panic disorder, represent a common phenomenon in the general adult population and are associated with a considerable decrease in quality of life and high health care costs. To date, the underlying pathophysiology of PAs is not well understood. A unique feature of PAs is that they represent a rare example of a psychopathological phenomenon that can be reliably modeled in the laboratory in panic disorder patients and healthy volunteers. The most effective techniques to experimentally trigger PAs are those that acutely disturb the acid-base homeostasis in the brain: inhalation of carbon dioxide (CO2), hyperventilation, and lactate infusion. This review particularly focuses on the use of CO2 inhalation in humans and rodents as an experimental model of panic. Besides highlighting the different methodological approaches, the cardio-respiratory and the endocrine responses to CO2 inhalation are summarized. In addition, the relationships between CO2 level, changes in brain pH, the serotonergic system, and adaptive physiological and behavioral responses to CO2 exposure are presented. We aim to present an integrated psychological and neurobiological perspective. Remaining gaps in the literature and future perspectives are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Preference, resistance to change, and the cumulative decision model.

    Science.gov (United States)

    Grace, Randolph C

    2018-01-01

    According to behavioral momentum theory (Nevin & Grace, 2000a), preference in concurrent chains and resistance to change in multiple schedules are independent measures of a common construct representing reinforcement history. Here I review the original studies on preference and resistance to change in which reinforcement variables were manipulated parametrically, conducted by Nevin, Grace and colleagues between 1997 and 2002, as well as more recent research. The cumulative decision model proposed by Grace and colleagues for concurrent chains is shown to provide a good account of both preference and resistance to change, and is able to predict the increased sensitivity to reinforcer rate and magnitude observed with constant-duration components. Residuals from fits of the cumulative decision model to preference and resistance to change data were positively correlated, supporting the prediction of behavioral momentum theory. Although some questions remain, the learning process assumed by the cumulative decision model, in which outcomes are compared against a criterion that represents the average outcome value in the current context, may provide a plausible model for the acquisition of differential resistance to change. © 2018 Society for the Experimental Analysis of Behavior.

  15. Insulin Signaling, Resistance, and the Metabolic Syndrome: Insights from Mouse Models to Disease Mechanisms

    Science.gov (United States)

    Guo, Shaodong

    2014-01-01

    Insulin resistance is a major underlying mechanism for the “metabolic syndrome”, which is also known as insulin resistance syndrome. Metabolic syndrome is increasing at an alarming rate, becoming a major public and clinical problem worldwide. Metabolic syndrome is represented by a group of interrelated disorders, including obesity, hyperglycemia, hyperlipidemia, and hypertension. It is also a significant risk factor for cardiovascular disease and increased morbidity and mortality. Animal studies demonstrate that insulin and its signaling cascade normally control cell growth, metabolism and survival through activation of mitogen-activated protein kinases (MAPKs) and phosphotidylinositide-3-kinase (PI3K), of which activation of PI-3K-associated with insulin receptor substrate-1 and -2 (IRS1, 2) and subsequent Akt→Foxo1 phosphorylation cascade has a central role in control of nutrient homeostasis and organ survival. Inactivation of Akt and activation of Foxo1, through suppression IRS1 and IRS2 in different organs following hyperinsulinemia, metabolic inflammation, and over nutrition may provide the underlying mechanisms for metabolic syndrome in humans. Targeting the IRS→Akt→Foxo1 signaling cascade will likely provide a strategy for therapeutic intervention in the treatment of type 2 diabetes and its complications. This review discusses the basis of insulin signaling, insulin resistance in different mouse models, and how a deficiency of insulin signaling components in different organs contributes to the feature of the metabolic syndrome. Emphasis will be placed on the role of IRS1, IRS2, and associated signaling pathways that couple to Akt and the forkhead/winged helix transcription factor Foxo1. PMID:24281010

  16. Association of SSTR2 Polymorphisms and Glucose Homeostasis Phenotypes

    OpenAIRE

    Sutton, Beth S.; Palmer, Nicholette D.; Langefeld, Carl D.; Xue, Bingzhong; Proctor, Alexandria; Ziegler, Julie T.; Haffner, Steven M.; Norris, Jill M.; Bowden, Donald W.

    2009-01-01

    OBJECTIVE This study evaluated the influence of somatostatin receptor type 2 (SSTR2) polymorphisms on measures of glucose homeostasis in the Insulin Resistance Atherosclerosis Family Study (IRASFS). SSTR2 is a G-protein?coupled receptor that, in response to somatostatin, mediates inhibition of insulin, glucagon, and growth hormone release and thus may affect glucose homeostasis. RESEARCH DESIGN AND METHODS Ten single nucleotide polymorphisms (SNPs) spanning the gene were chosen using a SNP de...

  17. WNIN/GR-Ob - an insulin-resistant obese rat model from inbred WNIN strain.

    Science.gov (United States)

    Harishankar, N; Vajreswari, A; Giridharan, N V

    2011-09-01

    WNIN/GR-Ob is a mutant obese rat strain with impaired glucose tolerance (IGT) developed at the National Institute of Nutrition (NIN), Hyderabad, India, from the existing 80 year old Wistar rat (WNIN) stock colony. The data presented here pertain to its obese nature along with IGT trait as evidenced by physical, physiological and biochemical parameters. The study also explains its existence, in three phenotypes: homozygous lean (+/+), heterozygous carrier (+/-) and homozygous obese (-/-). Thirty animals (15 males and 15 females) from each phenotype (+/+, +/-, -/-) and 24 lean and obese (6 males and 6 females) rats were taken for growth and food intake studies respectively. Twelve adult rats from each phenotype were taken for body composition measurement by total body electrical conductivity (TOBEC); 12 rats of both genders from each phenotype at different ages were taken for clinical chemistry parameters. Physiological indices of insulin resistance were calculated according to the homeostasis model assessment for insulin resistance (HOMA-IR) and also by studying U¹⁴C 2-deoxy glucose uptake (2DG). WNINGR-Ob mutants had high growth, hyperphagia, polydipsia, polyurea, glycosuria, and significantly lower lean body mass, higher fat mass as compared with carrier and lean rats. These mutants, at 50 days of age displayed abnormal response to glucose load (IGT), hyperinsulinaemia, hypertriglyceridaemia, hypercholesterolaemia and hyperleptinaemia. Basal and insulin-stimulated glucose uptakes by diaphragm were significantly decreased in obese rats as compared with lean rats. Obese rats of the designated WNIN/GR-Ob strain showed obesity with IGT, as adjudged by physical, physiological and biochemical indices. These indices varied among the three phenotypes, being lowest in lean, highest in obese and intermediate in carrier phenotypes thereby suggesting that obesity is inherited as autosomal incomplete dominant trait in this strain. This mutant obese rat model is easy to

  18. Exploring emergent properties in cellular homeostasis using OnGuard to model K+ and other ion transport in guard cells.

    Science.gov (United States)

    Blatt, Michael R; Wang, Yizhou; Leonhardt, Nathalie; Hills, Adrian

    2014-05-15

    It is widely recognized that the nature and characteristics of transport across eukaryotic membranes are so complex as to defy intuitive understanding. In these circumstances, quantitative mathematical modeling is an essential tool, both to integrate detailed knowledge of individual transporters and to extract the properties emergent from their interactions. As the first, fully integrated and quantitative modeling environment for the study of ion transport dynamics in a plant cell, OnGuard offers a unique tool for exploring homeostatic properties emerging from the interactions of ion transport, both at the plasma membrane and tonoplast in the guard cell. OnGuard has already yielded detail sufficient to guide phenotypic and mutational studies, and it represents a key step toward 'reverse engineering' of stomatal guard cell physiology, based on rational design and testing in simulation, to improve water use efficiency and carbon assimilation. Its construction from the HoTSig libraries enables translation of the software to other cell types, including growing root hairs and pollen. The problems inherent to transport are nonetheless challenging, and are compounded for those unfamiliar with conceptual 'mindset' of the modeler. Here we set out guidelines for the use of OnGuard and outline a standardized approach that will enable users to advance quickly to its application both in the classroom and laboratory. We also highlight the uncanny and emergent property of OnGuard models to reproduce the 'communication' evident between the plasma membrane and tonoplast of the guard cell. Copyright © 2014 The Authors. Published by Elsevier GmbH.. All rights reserved.

  19. Sodium homeostasis is preserved in a global 11β-hydroxysteroid dehydrogenase type 1 knockout mouse model

    DEFF Research Database (Denmark)

    Christensen, Thorbjørn H; Bailey, Matthew A; Kenyon, Christopher J

    2015-01-01

    hypothesized that loss of renal 11βHSD1 would result in salt wasting and tested this in a knockout mouse model in which 11βHSD1 was deleted in all body tissues. In balance studies, 11βHSD1 deletion had no effect on water, sodium or potassium metabolism; transition to a low-sodium diet did not reveal...... that global deletion of 11βHSD1 in the mouse would give rise to a salt-wasting renal phenotype. What is the main finding and its importance? We subjected a mouse model of global 11βHSD1 deletion to studies of water and electrolyte balance, renal clearance, urinary steroid excretion, renin-angiotensin system...... a natriuretic phenotype. Renal clearance studies demonstrated identical haemodynamic parameters (arterial blood pressure, renal blood flow and glomerular filtration rate) in knockout and wild-type mice, but revealed an augmented kaliuretic response to thiazides in 11βHSD1 knockout animals. There was no effect...

  20. Neuronal and molecular mechanisms of sleep homeostasis.

    Science.gov (United States)

    Donlea, Jeffrey M

    2017-12-01

    Sleep is necessary for survival, and prolonged waking causes a homeostatic increase in the need for recovery sleep. Homeostasis is a core component of sleep regulation and has been tightly conserved across evolution from invertebrates to man. Homeostatic sleep regulation was first identified among insects in cockroaches several decades ago, but the characterization of sleep rebound in Drosophila melanogaster opened the use of insect model species to understand homeostatic functions and regulation of sleep. This review describes circuits in two neuropil structures, the central complex and mushroom bodies, that influence sleep homeostasis and neuromodulatory systems that influence the accrual of homeostatic sleep need. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Scenario Evaluator for Electrical Resistivity survey pre-modeling tool

    Science.gov (United States)

    Terry, Neil; Day-Lewis, Frederick D.; Robinson, Judith L.; Slater, Lee D.; Halford, Keith J.; Binley, Andrew; Lane, John W.; Werkema, Dale D.

    2017-01-01

    Geophysical tools have much to offer users in environmental, water resource, and geotechnical fields; however, techniques such as electrical resistivity imaging (ERI) are often oversold and/or overinterpreted due to a lack of understanding of the limitations of the techniques, such as the appropriate depth intervals or resolution of the methods. The relationship between ERI data and resistivity is nonlinear; therefore, these limitations depend on site conditions and survey design and are best assessed through forward and inverse modeling exercises prior to field investigations. In this approach, proposed field surveys are first numerically simulated given the expected electrical properties of the site, and the resulting hypothetical data are then analyzed using inverse models. Performing ERI forward/inverse modeling, however, requires substantial expertise and can take many hours to implement. We present a new spreadsheet-based tool, the Scenario Evaluator for Electrical Resistivity (SEER), which features a graphical user interface that allows users to manipulate a resistivity model and instantly view how that model would likely be interpreted by an ERI survey. The SEER tool is intended for use by those who wish to determine the value of including ERI to achieve project goals, and is designed to have broad utility in industry, teaching, and research.

  2. Large-scale 3-D modeling by integration of resistivity models and borehole data through inversion

    DEFF Research Database (Denmark)

    Foged, N.; Marker, Pernille Aabye; Christiansen, A. V.

    2014-01-01

    resistivity and the clay fraction. Through inversion we use the lithological data and the resistivity data to determine the optimum spatially distributed translator function. Applying the translator function we get a 3-D clay fraction model, which holds information from the resistivity data set...... and the borehole data set in one variable. Finally, we use k-means clustering to generate a 3-D model of the subsurface structures. We apply the procedure to the Norsminde survey in Denmark, integrating approximately 700 boreholes and more than 100 000 resistivity models from an airborne survey...

  3. Amyloid and immune homeostasis.

    Science.gov (United States)

    Wang, Ying-Hui; Zhang, Yu-Gen

    2018-03-01

    Extracellular amyloid deposition defines a range of amyloidosis and amyloid-related disease. Addition to primary and secondary amyloidosis, amyloid-related disease can be observed in different tissue/organ that sharing the common pathogenesis based on the formation of amyloid deposition. Currently, both Alzheimer's disease and type 2 diabetes can be diagnosed with certainly only based on the autopsy results, by which amyloidosis of the associative tissue/organ is observed. Intriguingly, since it demonstrated that amyloid deposits trigger inflammatory reaction through the activation of cascaded immune response, wherein several lines of evidence implies a protective role of amyloid in preventing autoimmunity. Furthermore, attempts for preventing amyloid formation and/or removing amyloid deposits from the brain have caused meningoencephalitis and consequent deaths among the subjects. Hence, it is important to note that amyloid positively participates in maintaining immune homeostasis and contributes to irreversible inflammatory response. In this review, we will focus on the interactive relationship between amyloid and the immune system, discussing the potential functional roles of amyloid in immune tolerance and homeostasis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  4. Ageing and water homeostasis

    Science.gov (United States)

    Robertson, David; Jordan, Jens; Jacob, Giris; Ketch, Terry; Shannon, John R.; Biaggioni, Italo

    2002-01-01

    This review outlines current knowledge concerning fluid intake and volume homeostasis in ageing. The physiology of vasopressin is summarized. Studies have been carried out to determine orthostatic changes in plasma volume and to assess the effect of water ingestion in normal subjects, elderly subjects, and patients with dysautonomias. About 14% of plasma volume shifts out of the vasculature within 30 minutes of upright posture. Oral ingestion of water raises blood pressure in individuals with impaired autonomic reflexes and is an important source of noise in blood pressure trials in the elderly. On the average, oral ingestion of 16 ounces (473ml) of water raises blood pressure 11 mmHg in elderly normal subjects. In patients with autonomic impairment, such as multiple system atrophy, strikingly exaggerated pressor effects of water have been seen with blood pressure elevations greater than 75 mmHg not at all uncommon. Ingestion of water is a major determinant of blood pressure in the elderly population. Volume homeostasis is importantly affected by posture and large changes in plasma volume may occur within 30 minutes when upright posture is assumed.

  5. Model for nuclear proliferation resistance analysis using decision making tools

    International Nuclear Information System (INIS)

    Ko, Won Il; Kim, Ho Dong; Yang, Myung Seung

    2003-06-01

    The nuclear proliferation risks of nuclear fuel cycles is being considered as one of the most important factors in assessing advanced and innovative nuclear systems in GEN IV and INPRO program. They have been trying to find out an appropriate and reasonable method to evaluate quantitatively several nuclear energy system alternatives. Any reasonable methodology for integrated analysis of the proliferation resistance, however, has not yet been come out at this time. In this study, several decision making methods, which have been used in the situation of multiple objectives, are described in order to see if those can be appropriately used for proliferation resistance evaluation. Especially, the AHP model for quantitatively evaluating proliferation resistance is dealt with in more detail. The theoretical principle of the method and some examples for the proliferation resistance problem are described. For more efficient applications, a simple computer program for the AHP model is developed, and the usage of the program is introduced here in detail. We hope that the program developed in this study could be useful for quantitative analysis of the proliferation resistance involving multiple conflict criteria

  6. Model for nuclear proliferation resistance analysis using decision making tools

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Won Il; Kim, Ho Dong; Yang, Myung Seung

    2003-06-01

    The nuclear proliferation risks of nuclear fuel cycles is being considered as one of the most important factors in assessing advanced and innovative nuclear systems in GEN IV and INPRO program. They have been trying to find out an appropriate and reasonable method to evaluate quantitatively several nuclear energy system alternatives. Any reasonable methodology for integrated analysis of the proliferation resistance, however, has not yet been come out at this time. In this study, several decision making methods, which have been used in the situation of multiple objectives, are described in order to see if those can be appropriately used for proliferation resistance evaluation. Especially, the AHP model for quantitatively evaluating proliferation resistance is dealt with in more detail. The theoretical principle of the method and some examples for the proliferation resistance problem are described. For more efficient applications, a simple computer program for the AHP model is developed, and the usage of the program is introduced here in detail. We hope that the program developed in this study could be useful for quantitative analysis of the proliferation resistance involving multiple conflict criteria.

  7. Modeling HIV-1 drug resistance as episodic directional selection.

    Science.gov (United States)

    Murrell, Ben; de Oliveira, Tulio; Seebregts, Chris; Kosakovsky Pond, Sergei L; Scheffler, Konrad

    2012-01-01

    The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance.

  8. Modeling HIV-1 drug resistance as episodic directional selection.

    Directory of Open Access Journals (Sweden)

    Ben Murrell

    Full Text Available The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance.

  9. Error modelling of quantum Hall array resistance standards

    Science.gov (United States)

    Marzano, Martina; Oe, Takehiko; Ortolano, Massimo; Callegaro, Luca; Kaneko, Nobu-Hisa

    2018-04-01

    Quantum Hall array resistance standards (QHARSs) are integrated circuits composed of interconnected quantum Hall effect elements that allow the realization of virtually arbitrary resistance values. In recent years, techniques were presented to efficiently design QHARS networks. An open problem is that of the evaluation of the accuracy of a QHARS, which is affected by contact and wire resistances. In this work, we present a general and systematic procedure for the error modelling of QHARSs, which is based on modern circuit analysis techniques and Monte Carlo evaluation of the uncertainty. As a practical example, this method of analysis is applied to the characterization of a 1 MΩ QHARS developed by the National Metrology Institute of Japan. Software tools are provided to apply the procedure to other arrays.

  10. Induction and direct resistance heating theory and numerical modeling

    CERN Document Server

    Lupi, Sergio; Aliferov, Aleksandr

    2015-01-01

    This book offers broad, detailed coverage of theoretical developments in induction and direct resistance heating and presents new material on the solution of problems in the application of such heating. The physical basis of induction and conduction heating processes is explained, and electromagnetic phenomena in direct resistance and induction heating of flat workpieces and cylindrical bodies are examined in depth. The calculation of electrical and energetic characteristics of induction and conduction heating systems is then thoroughly reviewed. The final two chapters consider analytical solutions and numerical modeling of problems in the application of induction and direct resistance heating, providing industrial engineers with the knowledge needed in order to use numerical tools in the modern design of installations. Other engineers, scientists, and technologists will find the book to be an invaluable reference that will assist in the efficient utilization of electrical energy.

  11. Pain emotion and homeostasis.

    Science.gov (United States)

    Panerai, Alberto E

    2011-05-01

    Pain has always been considered as part of a defensive strategy, whose specific role is to signal an immediate, active danger. This definition partially fits acute pain, but certainly not chronic pain, that is maintained also in the absence of an active noxa or danger and that nowadays is considered a disease by itself. Moreover, acute pain is not only an automatic alerting system, but its severity and characteristics can change depending on the surrounding environment. The affective, emotional components of pain have been and are the object of extensive attention and research by psychologists, philosophers, physiologists and also pharmacologists. Pain itself can be considered to share the same genesis as emotions and as a specific emotion in contributing to the maintenance of the homeostasis of each unique subject. Interestingly, this role of pain reaches its maximal development in the human; some even argue that it is specific for the human primate.

  12. Testing and Modeling of Mechanical Characteristics of Resistance Welding Machines

    DEFF Research Database (Denmark)

    Wu, Pei; Zhang, Wenqi; Bay, Niels

    2003-01-01

    for both upper and lower electrode systems. This has laid a foundation for modeling the welding process and selecting the welding parameters considering the machine factors. The method is straightforward and easy to be applied in industry since the whole procedure is based on tests with no requirements......The dynamic mechanical response of resistance welding machine is very important to the weld quality in resistance welding especially in projection welding when collapse or deformation of work piece occurs. It is mainly governed by the mechanical parameters of machine. In this paper, a mathematical...... model for characterizing the dynamic mechanical responses of machine and a special test set-up called breaking test set-up are developed. Based on the model and the test results, the mechanical parameters of machine are determined, including the equivalent mass, damping coefficient, and stiffness...

  13. An approach to ductile fracture resistance modelling in pipeline steels

    Energy Technology Data Exchange (ETDEWEB)

    Pussegoda, L.N.; Fredj, A. [BMT Fleet Technology Ltd., Kanata (Canada)

    2009-07-01

    Ductile fracture resistance studies of high grade steels in the pipeline industry often included analyses of the crack tip opening angle (CTOA) parameter using 3-point bend steel specimens. The CTOA is a function of specimen ligament size in high grade materials. Other resistance measurements may include steady state fracture propagation energy, critical fracture strain, and the adoption of damage mechanisms. Modelling approaches for crack propagation were discussed in this abstract. Tension tests were used to calibrate damage model parameters. Results from the tests were then applied to the crack propagation in a 3-point bend specimen using modern 1980 vintage steels. Limitations and approaches to overcome the difficulties associated with crack propagation modelling were discussed.

  14. Normalization of Hepatic Homeostasis in the Npc1nmf164 Mouse Model of Niemann-Pick Type C Disease Treated with the Histone Deacetylase Inhibitor Vorinostat.

    Science.gov (United States)

    Munkacsi, Andrew B; Hammond, Natalie; Schneider, Remy T; Senanayake, Dinindu S; Higaki, Katsumi; Lagutin, Kirill; Bloor, Stephen J; Ory, Daniel S; Maue, Robert A; Chen, Fannie W; Hernandez-Ono, Antonio; Dahlson, Nicole; Repa, Joyce J; Ginsberg, Henry N; Ioannou, Yiannis A; Sturley, Stephen L

    2017-03-17

    Niemann-Pick type C (NP-C) disease is a fatal genetic lipidosis for which there is no Food and Drug Administration (FDA)-approved therapy. Vorinostat, an FDA-approved inhibitor of histone deacetylases, ameliorates lysosomal lipid accumulation in cultured NP-C patient fibroblasts. To assess the therapeutic potential of histone deacetylase inhibition, we pursued these in vitro observations in two murine models of NP-C disease. Npc1 nmf164 mice, which express a missense mutation in the Npc1 gene, were treated intraperitoneally, from weaning, with the maximum tolerated dose of vorinostat (150 mg/kg, 5 days/week). Disease progression was measured via gene expression, liver function and pathology, serum and tissue lipid levels, body weight, and life span. Transcriptome analyses of treated livers indicated multiple changes consistent with reversal of liver dysfunction that typifies NP-C disease. Significant improvements in liver pathology and function were achieved by this treatment regimen; however, NPC1 protein maturation and levels, disease progression, weight loss, and animal morbidity were not detectably altered. Vorinostat concentrations were >200 μm in the plasma compartment of treated animals but were almost 100-fold lower in brain tissue. Apolipoprotein B metabolism and the expression of key components of lipid homeostasis in primary hepatocytes from null ( Npc1 -/- ) and missense ( Npc1 nmf164 ) mutant mice were altered by vorinostat treatment, consistent with a response by these cells independent of the status of the Npc1 locus. These results suggest that HDAC inhibitors have utility to treat visceral NP-C disease. However, it is clear that improved blood-brain barrier penetration will be required to alleviate the neurological symptoms of human NP-C disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Normalization of Hepatic Homeostasis in the Npc1nmf164 Mouse Model of Niemann-Pick Type C Disease Treated with the Histone Deacetylase Inhibitor Vorinostat*

    Science.gov (United States)

    Munkacsi, Andrew B.; Hammond, Natalie; Schneider, Remy T.; Senanayake, Dinindu S.; Higaki, Katsumi; Lagutin, Kirill; Bloor, Stephen J.; Ory, Daniel S.; Maue, Robert A.; Chen, Fannie W.; Hernandez-Ono, Antonio; Dahlson, Nicole; Repa, Joyce J.; Ginsberg, Henry N.; Ioannou, Yiannis A.; Sturley, Stephen L.

    2017-01-01

    Niemann-Pick type C (NP-C) disease is a fatal genetic lipidosis for which there is no Food and Drug Administration (FDA)-approved therapy. Vorinostat, an FDA-approved inhibitor of histone deacetylases, ameliorates lysosomal lipid accumulation in cultured NP-C patient fibroblasts. To assess the therapeutic potential of histone deacetylase inhibition, we pursued these in vitro observations in two murine models of NP-C disease. Npc1nmf164 mice, which express a missense mutation in the Npc1 gene, were treated intraperitoneally, from weaning, with the maximum tolerated dose of vorinostat (150 mg/kg, 5 days/week). Disease progression was measured via gene expression, liver function and pathology, serum and tissue lipid levels, body weight, and life span. Transcriptome analyses of treated livers indicated multiple changes consistent with reversal of liver dysfunction that typifies NP-C disease. Significant improvements in liver pathology and function were achieved by this treatment regimen; however, NPC1 protein maturation and levels, disease progression, weight loss, and animal morbidity were not detectably altered. Vorinostat concentrations were >200 μm in the plasma compartment of treated animals but were almost 100-fold lower in brain tissue. Apolipoprotein B metabolism and the expression of key components of lipid homeostasis in primary hepatocytes from null (Npc1−/−) and missense (Npc1nmf164) mutant mice were altered by vorinostat treatment, consistent with a response by these cells independent of the status of the Npc1 locus. These results suggest that HDAC inhibitors have utility to treat visceral NP-C disease. However, it is clear that improved blood-brain barrier penetration will be required to alleviate the neurological symptoms of human NP-C disease. PMID:28031458

  16. Common genetic determinants of glucose homeostasis in healthy children

    DEFF Research Database (Denmark)

    Kelliny, Clara; Ekelund, Ulf; Andersen, Lars Bo

    2009-01-01

    ) were genotyped in 2,025 healthy European children aged 9-11 and 14-16 years. Associations with fasting glucose, insulin, homeostasis model assessment (HOMA)-insulin resistance (IR) and HOMA-B were investigated along with those observed for type 2 diabetes variants available in this study (CDKN2A/B, IGF....... A similar but weaker trend was observed for GCK (0.028 [-0.006 to 0.06] mmol/l, P = 0.11). All three variants were associated with lower beta-cell function (HOMA-B P = 9.38 x 10(-5), 0.004, and 0.04, respectively). SLC30A8 (rs13266634) was the only type 2 diabetes variant associated with higher fasting...

  17. A Physiologist's View of Homeostasis

    Science.gov (United States)

    Modell, Harold; Cliff, William; Michael, Joel; McFarland, Jenny; Wenderoth, Mary Pat; Wright, Ann

    2015-01-01

    Homeostasis is a core concept necessary for understanding the many regulatory mechanisms in physiology. Claude Bernard originally proposed the concept of the constancy of the "milieu interieur," but his discussion was rather abstract. Walter Cannon introduced the term "homeostasis" and expanded Bernard's notion of…

  18. Model for the resistive critical current transition in composite superconductors

    International Nuclear Information System (INIS)

    Warnes, W.H.

    1988-01-01

    Much of the research investigating technological type-II superconducting composites relies on the measurement of the resistive critical current transition. We have developed a model for the resistive transition which improves on older models by allowing for the very different nature of monofilamentary and multifilamentary composite structures. The monofilamentary model allows for axial current flow around critical current weak links in the superconducting filament. The multifilamentary model incorporates an additional radial current transfer between neighboring filaments. The development of both models is presented. It is shown that the models are useful for extracting more information from the experimental data than was formerly possible. Specific information obtainable from the experimental voltage-current characteristic includes the distribution of critical currents in the composite, the average critical current of the distribution, the range of critical currents in the composite, the field and temperature dependence of the distribution, and the fraction of the composite dissipating energy in flux flow at any current. This additional information about the distribution of critical currents may be helpful in leading toward a better understanding of flux pinning in technological superconductors. Comparison of the models with several experiments is given and shown to be in reasonable agreement. Implications of the models for the measurement of critical currents in technological composites is presented and discussed with reference to basic flux pinning studies in such composites

  19. Nonlinear Stochastic Modelling of Antimicrobial resistance in Bacterial Populations

    DEFF Research Database (Denmark)

    Philipsen, Kirsten Riber

    -mutator population. The growth rates of the two populations were initially compared by a maximum likelihood approach and the growth rates were found to be equal. Thereafter a model for the competing growth was developed. The models showthat mutatorswill obtain a higher fitness by adapting faster to an environment...... an important role for the evolution of resistance. When growing under stressed conditions, such as in the presence of antibiotics, mutators are considered to have an advantages in comparison to non-mutators. This has been supported by a mathematical model for competing growth between a mutator and a non...

  20. Distinguishing Antimicrobial Models with Different Resistance Mechanisms via Population Pharmacodynamic Modeling.

    Directory of Open Access Journals (Sweden)

    Matthieu Jacobs

    2016-03-01

    Full Text Available Semi-mechanistic pharmacokinetic-pharmacodynamic (PK-PD modeling is increasingly used for antimicrobial drug development and optimization of dosage regimens, but systematic simulation-estimation studies to distinguish between competing PD models are lacking. This study compared the ability of static and dynamic in vitro infection models to distinguish between models with different resistance mechanisms and support accurate and precise parameter estimation. Monte Carlo simulations (MCS were performed for models with one susceptible bacterial population without (M1 or with a resting stage (M2, a one population model with adaptive resistance (M5, models with pre-existing susceptible and resistant populations without (M3 or with (M4 inter-conversion, and a model with two pre-existing populations with adaptive resistance (M6. For each model, 200 datasets of the total bacterial population were simulated over 24h using static antibiotic concentrations (256-fold concentration range or over 48h under dynamic conditions (dosing every 12h; elimination half-life: 1h. Twelve-hundred random datasets (each containing 20 curves for static or four curves for dynamic conditions were generated by bootstrapping. Each dataset was estimated by all six models via population PD modeling to compare bias and precision. For M1 and M3, most parameter estimates were unbiased (<10% and had good imprecision (<30%. However, parameters for adaptive resistance and inter-conversion for M2, M4, M5 and M6 had poor bias and large imprecision under static and dynamic conditions. For datasets that only contained viable counts of the total population, common statistical criteria and diagnostic plots did not support sound identification of the true resistance mechanism. Therefore, it seems advisable to quantify resistant bacteria and characterize their MICs and resistance mechanisms to support extended simulations and translate from in vitro experiments to animal infection models and

  1. Mathematical model of temephos resistance in Aedes aegypti mosquito population

    Science.gov (United States)

    Aldila, D.; Nuraini, N.; Soewono, E.; Supriatna, A. K.

    2014-03-01

    Aedes aegypti is the main vector of dengue disease in many tropical and sub-tropical countries. Dengue became major public concern in these countries due to the unavailability of vaccine or drugs for dengue disease in the market. Hence, the only way to control the spread of DF and DHF is by controlling the vectors carrying the disease, for instance with fumigation, temephos or genetic manipulation. Many previous studies conclude that Aedes aegypti may develop resistance to many kind of insecticide, including temephos. Mathematical model for transmission of temephos resistance in Aedes aegypti population is discussed in this paper. Nontrivial equilibrium point of the system and the corresponding existence are shown analytically. The model analysis have shown epidemiological trends condition that permits the coexistence of nontrivial equilibrium is given analytically. Numerical results are given to show parameter sensitivity and some cases of worsening effect values for illustrating possible conditions in the field.

  2. Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis.

    Science.gov (United States)

    Klose, Christoph S N; Artis, David

    2016-06-21

    Research over the last 7 years has led to the formal identification of innate lymphoid cells (ILCs), increased the understanding of their tissue distribution and has established essential functions of ILCs in diverse physiological processes. These include resistance to pathogens, the regulation of autoimmune inflammation, tissue remodeling, cancer and metabolic homeostasis. Notably, many ILC functions appear to be regulated by mechanisms distinct from those of other innate and adaptive immune cells. In this Review, we focus on how group 2 ILC (ILC2) and group 3 ILC (ILC3) responses are regulated and how these cells interact with other immune and non-immune cells to mediate their functions. We highlight experimental evidence from mouse models and patient-based studies that have elucidated the effects of ILCs on the maintenance of tissue homeostasis and the consequences for health and disease.

  3. Impact of intermittent fasting on glucose homeostasis.

    Science.gov (United States)

    Varady, Krista A

    2016-07-01

    This article provides an overview of the most recent human trials that have examined the impact of intermittent fasting on glucose homeostasis. Our literature search retrieved one human trial of alternate day fasting, and three trials of Ramadan fasting published in the past 12 months. Current evidence suggests that 8 weeks of alternate day fasting that produces mild weight loss (4% from baseline) has no effect on glucose homeostasis. As for Ramadan fasting, decreases in fasting glucose, insulin, and insulin resistance have been noted after 4 weeks in healthy normal weight individuals with mild weight loss (1-2% from baseline). However, Ramadan fasting may have little impact on glucoregulatory parameters in women with polycystic ovarian syndrome who failed to observe weight loss. Whether intermittent fasting is an effective means of regulating glucose homeostasis remains unclear because of the scarcity of studies in this area. Large-scale, longer-term randomized controlled trials will be required before the use of fasting can be recommended for the prevention and treatment of metabolic diseases.

  4. Regulation of energy homeostasis via GPR120

    Directory of Open Access Journals (Sweden)

    Atsuhiko eIchimura

    2014-07-01

    Full Text Available Free fatty acids (FFAs are fundamental units of key nutrients. FFAs exert various biological functions, depending on the chain length and degree of desaturation. Recent studies have shown that several FFAs act as ligands of G-protein-coupled receptors (GPCRs, activate intracellular signaling and exert physiological functions via these GPCRs. GPR120 (also known as free fatty acid receptor 4, FFAR4 is activated by unsaturated medium- to long-chain FFAs and has a critical role in various physiological homeostasis mechanisms such as incretin hormone secretion, food preference, anti-inflammation and adipogenesis. Recent studies showed that a lipid sensor GPR120 has a key role in sensing dietary fat in white adipose tissue and regulates the whole body energy homeostasis in both humans and rodents. Genetic study in human identified the loss-of-functional mutation of GPR120 associated with obesity and insulin resistance. In addition, dysfunction of GPR120 has been linked as a novel risk factor for diet-induced obesity. This review aims to provide evidence from the recent development in physiological function of GPR120 and discusses its functional roles in regulation of energy homeostasis and its potential as drug targets.

  5. Pseudomonas aeruginosa Trent and zinc homeostasis.

    Science.gov (United States)

    Davies, Corey B; Harrison, Mark D; Huygens, Flavia

    2017-09-01

    Pseudomonas aeruginosa is a Gram-negative pathogen and the major cause of mortality in patients with cystic fibrosis. The mechanisms that P. aeruginosa strains use to regulate intracellular zinc have an effect on infection, antibiotic resistance and the propensity to form biofilms. However, zinc homeostasis in P. aeruginosa strains of variable infectivity has not been compared. In this study, zinc homeostasis in P. aeruginosa Trent, a highly infectious clinical strain, was compared to that of a laboratory P. aeruginosa strain, ATCC27853. Trent was able to tolerate higher concentrations of additional zinc in rich media than ATCC27853. Further, pre-adaptation to additional zinc enhanced the growth of Trent at non-inhibitory concentrations but the impact of pre-adaption on the growth of ATCC27853 under the same conditions was minimal. The results establish clear differences in zinc-induced responses in Trent and ATCC27853, and how zinc homeostasis can be a promising target for the development of novel antimicrobial strategies for P. aeruginosa infection in cystic fibrosis patients. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Iron homeostasis during pregnancy.

    Science.gov (United States)

    Fisher, Allison L; Nemeth, Elizabeta

    2017-12-01

    During pregnancy, iron needs to increase substantially to support fetoplacental development and maternal adaptation to pregnancy. To meet these iron requirements, both dietary iron absorption and the mobilization of iron from stores increase, a mechanism that is in large part dependent on the iron-regulatory hormone hepcidin. In healthy human pregnancies, maternal hepcidin concentrations are suppressed in the second and third trimesters, thereby facilitating an increased supply of iron into the circulation. The mechanism of maternal hepcidin suppression in pregnancy is unknown, but hepcidin regulation by the known stimuli (i.e., iron, erythropoietic activity, and inflammation) appears to be preserved during pregnancy. Inappropriately increased maternal hepcidin during pregnancy can compromise the iron availability for placental transfer and impair the efficacy of iron supplementation. The role of fetal hepcidin in the regulation of placental iron transfer still remains to be characterized. This review summarizes the current understanding and addresses the gaps in knowledge about gestational changes in hematologic and iron variables and regulatory aspects of maternal, fetal, and placental iron homeostasis. © 2017 American Society for Nutrition.

  7. INTRACELLULAR Ca2+ HOMEOSTASIS

    Directory of Open Access Journals (Sweden)

    Shahdevi Nandar Kurniawan

    2015-01-01

    Full Text Available Ca2+ signaling functions to regulate many cellular processes. Dynamics of Ca2+ signaling or homeostasis is regulated by the interaction between ON and OFF reactions that control Ca2+ flux in both the plasma membrane and internal organelles such as the endoplasmic reticulum (ER and mitochondria. External stimuli activate the ON reactions, which include Ca2+ into the cytoplasm either through channels in the plasma membrane or from internal storage like in ER. Most of the cells utilize both channels/sources, butthere area few cells using an external or internal source to control certain processes. Most of the Ca2+ entering the cytoplasm adsorbed to the buffer, while a smaller part activate effect or to stimulate cellular processes. Reaction OFF is pumping of cytoplasmic Ca2+ using a combination mechanism of mitochondrial and others. Changes in Ca2+ signal has been detected in various tissues isolated from animals induced into diabetes as well as patients with diabetes. Ca2+ signal interference is also found in sensory neurons of experimental animals with diabetes. Ca2+ signaling is one of the main signaling systems in the cell.

  8. Thin stillage fractionation using ultrafiltration: resistance in series model.

    Science.gov (United States)

    Arora, Amit; Dien, Bruce S; Belyea, Ronald L; Wang, Ping; Singh, Vijay; Tumbleson, M E; Rausch, Kent D

    2009-02-01

    The corn based dry grind process is the most widely used method in the US for fuel ethanol production. Fermentation of corn to ethanol produces whole stillage after ethanol is removed by distillation. It is centrifuged to separate thin stillage from wet grains. Thin stillage contains 5-10% solids. To concentrate solids of thin stillage, it requires evaporation of large amounts of water and maintenance of evaporators. Evaporator maintenance requires excess evaporator capacity at the facility, increasing capital expenses, requiring plant slowdowns or shut downs and results in revenue losses. Membrane filtration is one method that could lead to improved value of thin stillage and may offer an alternative to evaporation. Fractionation of thin stillage using ultrafiltration was conducted to evaluate membranes as an alternative to evaporators in the ethanol industry. Two regenerated cellulose membranes with molecular weight cut offs of 10 and 100 kDa were evaluated. Total solids (suspended and soluble) contents recovered through membrane separation process were similar to those from commercial evaporators. Permeate flux decline of thin stillage using a resistance in series model was determined. Each of the four components of total resistance was evaluated experimentally. Effects of operating variables such as transmembrane pressure and temperature on permeate flux rate and resistances were determined and optimum conditions for maximum flux rates were evaluated. Model equations were developed to evaluate the resistance components that are responsible for fouling and to predict total flux decline with respect to time. Modeling results were in agreement with experimental results (R(2) > 0.98).

  9. Contact Modelling in Resistance Welding, Part II: Experimental Validation

    DEFF Research Database (Denmark)

    Song, Quanfeng; Zhang, Wenqi; Bay, Niels

    2006-01-01

    Contact algorithms in resistance welding presented in the previous paper are experimentally validated in the present paper. In order to verify the mechanical contact algorithm, two types of experiments, i.e. sandwich upsetting of circular, cylindrical specimens and compression tests of discs...... with a solid ring projection towards a flat ring, are carried out at room temperature. The complete algorithm, involving not only the mechanical model but also the thermal and electrical models, is validated by projection welding experiments. The experimental results are in satisfactory agreement...

  10. Achieving fast reconnection in resistive MHD models via turbulent means

    Directory of Open Access Journals (Sweden)

    G. Lapenta

    2012-04-01

    Full Text Available Astrophysical fluids are generally turbulent and this preexisting turbulence must be taken into account for models of magnetic reconnection in astrophysical, solar or heliospheric environments. In addition, reconnection itself induces turbulence which provides an important feedback on the reconnection process. In this paper we discuss both the theoretical model and numerical evidence that magnetic reconnection becomes fast in the approximation of resistive MHD. We consider the relation between the Lazarian and Vishniac turbulent reconnection theory and Lapenta's numerical experiments testifying of the spontaneous onset of turbulent reconnection in systems which are initially laminar.

  11. Periodontitis contributes to adipose tissue inflammation through the NF-B, JNK and ERK pathways to promote insulin resistance in a rat model.

    Science.gov (United States)

    Huang, Yanli; Zeng, Jin; Chen, Guoqing; Xie, Xudong; Guo, Weihua; Tian, Weidong

    2016-12-01

    This study aimed to investigate the mechanism by which periodontitis affects the inflammatory response and systemic insulin resistance in the white adipose and liver tissues in an obese rat model. The obese model was generated by feeding rats a high fat diet. The periodontitis model was induced by ligatures and injection of "red complex", which consisted of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, for two weeks. When compared with rats without periodontitis, fasting glucose levels and homeostasis model assessment index were significantly increased in rats with periodontitis, suggesting that periodontitis promotes the development of insulin resistance in obese rats. Gene and protein expression analysis in white adipose and liver tissue revealed that experimental periodontitis stimulated the expression of inflammatory cytokines, such as tumor necrosis factors-alpha, interleukin-1 beta, toll-like receptor 2 and toll-like receptor 4. Signals associated with inflammation and insulin resistance, including nuclear factor- B, c-Jun amino-terminal kinase and extracellular-signal regulated kinase were significantly activated in the white adipose tissue from obese rats with periodontitis compared to obese rats without periodontitis. Taken together, these findings suggest that periodontitis plays an important role in aggravating the development of local white adipose inflammation and systemic insulin resistance in rat models. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  12. Adaptive mechanisms of homeostasis disorders

    Directory of Open Access Journals (Sweden)

    Anna Maria Dobosiewicz

    2017-08-01

    Full Text Available The ability to preserve a permanent level of internal environment in a human organism, against internal and external factors, which could breach the consistency, can be define as homeostasis. Scientific proven influence on the homeostasis has the periodicity of biological processes, which is also called circadian rhythm. The effect of circadian rhythm is also to see in the functioning of autonomic nervous system and cardiovascular system. Sleep deprivation is an example of how the disorders in circadian rhythm could have the influence on the homeostasis.

  13. Global Current Circuit Structure in a Resistive Pulsar Magnetosphere Model

    Science.gov (United States)

    Kato, Yugo. E.

    2017-12-01

    Pulsar magnetospheres have strong magnetic fields and large amounts of plasma. The structures of these magnetospheres are studied using force-free electrodynamics. To understand pulsar magnetospheres, discussions must include their outer region. However, force-free electrodynamics is limited in it does not handle dissipation. Therefore, a resistive pulsar magnetic field model is needed. To break the ideal magnetohydrodynamic (MHD) condition E\\cdot B=0, Ohm’s law is used. This work introduces resistivity depending upon the distance from the star and obtain a self-consistent steady state by time integration. Poloidal current circuits form in the magnetosphere while the toroidal magnetic field region expands beyond the light cylinder and the Poynting flux radiation appears. High electric resistivity causes a large space scale poloidal current circuit and the magnetosphere radiates a larger Poynting flux than the linear increase outside of the light cylinder radius. The formed poloidal-current circuit has width, which grows with the electric conductivity. This result contributes to a more concrete dissipative pulsar magnetosphere model.

  14. Copper Homeostasis in Escherichia coli and Other Enterobacteriaceae.

    Science.gov (United States)

    Rensing, Christopher; Franke, Sylvia

    2007-04-01

    An interesting model for studying environmental influences shaping microbial evolution is provided by a multitude of copper resistance and copper homeostasis determinants in enteric bacteria. This review describes these determinants and tries to relate their presence to the habitat of the respective organism, as a current hypothesis predicts that the environment should determine an organism's genetic makeup. In Escherichia coli there are four regulons that are induced in the presence of copper. Two, the CueR and the CusR regulons, are described in detail. A central component regulating intracellular copper levels, present in all free-living enteric bacteria whose genomes have so far been sequenced, is a Cu(I)translocating P-type ATPase. The P-type ATPase superfamily is a ubiquitous group of proteins involved in the transport of charged substrates across biological membranes. Whereas some components involved in copper homeostasis can be found in both anaerobes and aerobes, multi-copper oxidases (MCOs) implicated in copper tolerance in E. coli, such as CueO and the plasmid-based PcoA, can be found only in aerobic organisms. Several features indicate that CueO, PcoA, and other related MCOs are specifically adapted to combat copper-mediated oxidative damage. In addition to these well-characterized resistance operons, there are numerous other genes that appear to be involved in copper binding and trafficking that have not been studied in great detail. SilE and its homologue PcoE, for example, are thought to effect the periplasmic binding and sequestration of silver and copper, respectively.

  15. Basic models modeling resistance training: an update for basic scientists interested in study skeletal muscle hypertrophy.

    Science.gov (United States)

    Cholewa, Jason; Guimarães-Ferreira, Lucas; da Silva Teixeira, Tamiris; Naimo, Marshall Alan; Zhi, Xia; de Sá, Rafaele Bis Dal Ponte; Lodetti, Alice; Cardozo, Mayara Quadros; Zanchi, Nelo Eidy

    2014-09-01

    Human muscle hypertrophy brought about by voluntary exercise in laboratorial conditions is the most common way to study resistance exercise training, especially because of its reliability, stimulus control and easy application to resistance training exercise sessions at fitness centers. However, because of the complexity of blood factors and organs involved, invasive data is difficult to obtain in human exercise training studies due to the integration of several organs, including adipose tissue, liver, brain and skeletal muscle. In contrast, studying skeletal muscle remodeling in animal models are easier to perform as the organs can be easily obtained after euthanasia; however, not all models of resistance training in animals displays a robust capacity to hypertrophy the desired muscle. Moreover, some models of resistance training rely on voluntary effort, which complicates the results observed when animal models are employed since voluntary capacity is something theoretically impossible to measure in rodents. With this information in mind, we will review the modalities used to simulate resistance training in animals in order to present to investigators the benefits and risks of different animal models capable to provoke skeletal muscle hypertrophy. Our second objective is to help investigators analyze and select the experimental resistance training model that best promotes the research question and desired endpoints. © 2013 Wiley Periodicals, Inc.

  16. Empirical validation of landscape resistance models: insights from the Greater Sage-Grouse (Centrocercus urophasianus)

    Science.gov (United States)

    Andrew J. Shirk; Michael A. Schroeder; Leslie A. Robb; Samuel A. Cushman

    2015-01-01

    The ability of landscapes to impede species’ movement or gene flow may be quantified by resistance models. Few studies have assessed the performance of resistance models parameterized by expert opinion. In addition, resistance models differ in terms of spatial and thematic resolution as well as their focus on the ecology of a particular species or more generally on the...

  17. Within-host selection of drug resistance in a mouse model reveals dose-dependent selection of atovaquone resistance mutations

    NARCIS (Netherlands)

    Nuralitha, Suci; Murdiyarso, Lydia S.; Siregar, Josephine E.; Syafruddin, Din; Roelands, Jessica; Verhoef, Jan; Hoepelman, Andy I.M.; Marzuki, Sangkot

    2017-01-01

    The evolutionary selection of malaria parasites within an individual host plays a critical role in the emergence of drug resistance. We have compared the selection of atovaquone resistance mutants in mouse models reflecting two different causes of failure of malaria treatment, an inadequate

  18. Metal ion transporters and homeostasis.

    OpenAIRE

    Nelson, N

    1999-01-01

    Transition metals are essential for many metabolic processes and their homeostasis is crucial for life. Aberrations in the cellular metal ion concentrations may lead to cell death and severe diseases. Metal ion transporters play a major role in maintaining the correct concentrations of the various metal ions in the different cellular compartments. Recent studies of yeast mutants revealed key elements in metal ion homeostasis, including novel transport systems. Several of the proteins discover...

  19. Innate immunity orchestrates adipose tissue homeostasis.

    Science.gov (United States)

    Lin, Yi-Wei; Wei, Li-Na

    2017-06-23

    Obesity is strongly associated with multiple diseases including insulin resistance, type 2 diabetes, cardiovascular diseases, fatty liver disease, neurodegenerative diseases and cancers, etc. Adipose tissue (AT), mainly brown AT (BAT) and white AT (WAT), is an important metabolic and endocrine organ that maintains whole-body homeostasis. BAT contributes to non-shivering thermogenesis in a cold environment; WAT stores energy and produces adipokines that fine-tune metabolic and inflammatory responses. Obesity is often characterized by over-expansion and inflammation of WAT where inflammatory cells/mediators are abundant, especially pro-inflammatory (M1) macrophages, resulting in chronic low-grade inflammation and leading to insulin resistance and metabolic complications. Macrophages constitute the major component of innate immunity and can be activated as a M1 or M2 (anti-inflammatory) phenotype in response to environmental stimuli. Polarized M1 macrophage causes AT inflammation, whereas polarized M2 macrophage promotes WAT remodeling into the BAT phenotype, also known as WAT browning/beiging, which enhances insulin sensitivity and metabolic health. This review will discuss the regulation of AT homeostasis in relation to innate immunity.

  20. A matching-allele model explains host resistance to parasites.

    Science.gov (United States)

    Luijckx, Pepijn; Fienberg, Harris; Duneau, David; Ebert, Dieter

    2013-06-17

    The maintenance of genetic variation and sex despite its costs has long puzzled biologists. A popular idea, the Red Queen Theory, is that under rapid antagonistic coevolution between hosts and their parasites, the formation of new rare host genotypes through sex can be advantageous as it creates host genotypes to which the prevailing parasite is not adapted. For host-parasite coevolution to lead to an ongoing advantage for rare genotypes, parasites should infect specific host genotypes and hosts should resist specific parasite genotypes. The most prominent genetics capturing such specificity are matching-allele models (MAMs), which have the key feature that resistance for two parasite genotypes can reverse by switching one allele at one host locus. Despite the lack of empirical support, MAMs have played a central role in the theoretical development of antagonistic coevolution, local adaptation, speciation, and sexual selection. Using genetic crosses, we show that resistance of the crustacean Daphnia magna against the parasitic bacterium Pasteuria ramosa follows a MAM. Simulation results show that the observed genetics can explain the maintenance of genetic variation and contribute to the maintenance of sex in the facultatively sexual host as predicted by the Red Queen Theory. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Resistive switching near electrode interfaces: Estimations by a current model

    Science.gov (United States)

    Schroeder, Herbert; Zurhelle, Alexander; Stemmer, Stefanie; Marchewka, Astrid; Waser, Rainer

    2013-02-01

    The growing resistive switching database is accompanied by many detailed mechanisms which often are pure hypotheses. Some of these suggested models can be verified by checking their predictions with the benchmarks of future memory cells. The valence change memory model assumes that the different resistances in ON and OFF states are made by changing the defect density profiles in a sheet near one working electrode during switching. The resulting different READ current densities in ON and OFF states were calculated by using an appropriate simulation model with variation of several important defect and material parameters of the metal/insulator (oxide)/metal thin film stack such as defect density and its profile change in density and thickness, height of the interface barrier, dielectric permittivity, applied voltage. The results were compared to the benchmarks and some memory windows of the varied parameters can be defined: The required ON state READ current density of 105 A/cm2 can only be achieved for barriers smaller than 0.7 eV and defect densities larger than 3 × 1020 cm-3. The required current ratio between ON and OFF states of at least 10 requests defect density reduction of approximately an order of magnitude in a sheet of several nanometers near the working electrode.

  2. Analytic modeling of the feedback stabilization of resistive wall modes

    International Nuclear Information System (INIS)

    Pustovitov, Vladimir D.

    2003-01-01

    Feedback suppression of resistive wall modes (RWM) is studied analytically using a model based on a standard cylindrical approximation. Optimal choice of the input signal for the feedback, effects related to the geometry of the feedback active coils, RWM suppression in a configuration with ITER-like double wall, are considered here. The widespread opinion that the feedback with poloidal sensors is better than that with radial sensors is discussed. It is shown that for an ideal feedback system the best input signal would be a combination of radial and poloidal perturbations measured inside the vessel. (author)

  3. Simulation of variation of apparent resistivity in resistivity surveys using finite difference modelling with Monte Carlo analysis

    Science.gov (United States)

    Aguirre, E. E.; Karchewski, B.

    2017-12-01

    DC resistivity surveying is a geophysical method that quantifies the electrical properties of the subsurface of the earth by applying a source current between two electrodes and measuring potential differences between electrodes at known distances from the source. Analytical solutions for a homogeneous half-space and simple subsurface models are well known, as the former is used to define the concept of apparent resistivity. However, in situ properties are heterogeneous meaning that simple analytical models are only an approximation, and ignoring such heterogeneity can lead to misinterpretation of survey results costing time and money. The present study examines the extent to which random variations in electrical properties (i.e. electrical conductivity) affect potential difference readings and therefore apparent resistivities, relative to an assumed homogeneous subsurface model. We simulate the DC resistivity survey using a Finite Difference (FD) approximation of an appropriate simplification of Maxwell's equations implemented in Matlab. Electrical resistivity values at each node in the simulation were defined as random variables with a given mean and variance, and are assumed to follow a log-normal distribution. The Monte Carlo analysis for a given variance of electrical resistivity was performed until the mean and variance in potential difference measured at the surface converged. Finally, we used the simulation results to examine the relationship between variance in resistivity and variation in surface potential difference (or apparent resistivity) relative to a homogeneous half-space model. For relatively low values of standard deviation in the material properties (<10% of mean), we observed a linear correlation between variance of resistivity and variance in apparent resistivity.

  4. Transcranial electrical stimulation accelerates human sleep homeostasis.

    Directory of Open Access Journals (Sweden)

    Davide Reato

    Full Text Available The sleeping brain exhibits characteristic slow-wave activity which decays over the course of the night. This decay is thought to result from homeostatic synaptic downscaling. Transcranial electrical stimulation can entrain slow-wave oscillations (SWO in the human electro-encephalogram (EEG. A computational model of the underlying mechanism predicts that firing rates are predominantly increased during stimulation. Assuming that synaptic homeostasis is driven by average firing rates, we expected an acceleration of synaptic downscaling during stimulation, which is compensated by a reduced drive after stimulation. We show that 25 minutes of transcranial electrical stimulation, as predicted, reduced the decay of SWO in the remainder of the night. Anatomically accurate simulations of the field intensities on human cortex precisely matched the effect size in different EEG electrodes. Together these results suggest a mechanistic link between electrical stimulation and accelerated synaptic homeostasis in human sleep.

  5. The fitness of drug-resistant malaria parasites in a rodent model: multiplicity of infection

    OpenAIRE

    Huijben, Silvie; Sim, Derek G.; Nelson, William, A.; Read, Andrew F.

    2011-01-01

    Malaria infections normally consist of more than one clonally-replicating lineage. Within-host interactions between sensitive and resistant parasites can have profound effects on the evolution of drug resistance. Here, using the Plasmodium chabaudi mouse malaria model, we ask whether the costs and benefits of resistance are affected by the number of co-infecting strains competing with a resistant clone. We found strong competitive suppression of resistant parasites in untreated infections and...

  6. Computational modeling of drug-resistant bacteria. Final report

    International Nuclear Information System (INIS)

    2015-01-01

    Initial proposal summary: The evolution of antibiotic-resistant mutants among bacteria (superbugs) is a persistent and growing threat to public health. In many ways, we are engaged in a war with these microorganisms, where the corresponding arms race involves chemical weapons and biological targets. Just as advances in microelectronics, imaging technology and feature recognition software have turned conventional munitions into smart bombs, the long-term objectives of this proposal are to develop highly effective antibiotics using next-generation biomolecular modeling capabilities in tandem with novel subatomic feature detection software. Using model compounds and targets, our design methodology will be validated with correspondingly ultra-high resolution structure-determination methods at premier DOE facilities (single-crystal X-ray diffraction at Argonne National Laboratory, and neutron diffraction at Oak Ridge National Laboratory). The objectives and accomplishments are summarized.

  7. Computational modeling of drug-resistant bacteria. Final report

    Energy Technology Data Exchange (ETDEWEB)

    MacDougall, Preston [Middle Tennessee State Univ., Murfreesboro, TN (United States)

    2015-03-12

    Initial proposal summary: The evolution of antibiotic-resistant mutants among bacteria (superbugs) is a persistent and growing threat to public health. In many ways, we are engaged in a war with these microorganisms, where the corresponding arms race involves chemical weapons and biological targets. Just as advances in microelectronics, imaging technology and feature recognition software have turned conventional munitions into smart bombs, the long-term objectives of this proposal are to develop highly effective antibiotics using next-generation biomolecular modeling capabilities in tandem with novel subatomic feature detection software. Using model compounds and targets, our design methodology will be validated with correspondingly ultra-high resolution structure-determination methods at premier DOE facilities (single-crystal X-ray diffraction at Argonne National Laboratory, and neutron diffraction at Oak Ridge National Laboratory). The objectives and accomplishments are summarized.

  8. High-fat diet based on dried bovine brain: an effective animal model of dyslipidemia and insulin resistance.

    Science.gov (United States)

    Araújo, Tiago Gomes; Leite, Ana Catarina Rezende; Martins da Fonseca, Caíque Silveira; Carvalho, Bruno Melo; Schuler, Alexandre Ricardo Pereira; Lima, Vera Lúcia de Menezes

    2011-09-01

    Currently, there are no reports in the literature demonstrating any animal model that ingests one of the fattiest animal food source, the bovine brain. We hypothesized that a high-fat diet (HFD), based on dried bovine brain, could be used to develop an animal model possessing a spectrum of insulin resistance-related features. The HFD was formulated with 40% dried bovine brain plus 16.4% butter fat, prepared in-house. Furthermore, the diet contained 52% calories as fat and 73% of total fatty acids were saturated. Swiss mice weighing about 40 g were assigned to two dietary groups (n=6/group), one group received a standard chow diet and the other was given HFD for 3 months. The body weight and biochemical parameters of the animals were measured initially and at monthly intervals until the end of the experiment. Animals fed on a HFD showed a significant increase in the body and adipose tissue weight, serum total cholesterol and triglyceride levels, when compared with mice fed on the control diet. Additionally, the HFD group showed higher circulating levels of liver transaminases, such as alanine aminotransferase and aspartate aminotransferase, compared with the control group. Finally, to illustrate the usefulness of this model, we report that the HFD induced mild hyperglycemia, fasting hyperinsulinemia, and increased the homeostasis model of assessment (HOMA-IR), in comparison with the control group. In conclusion, our results show that HFD, based on dried bovine brain, causes insulin resistance-related metabolic disturbances. Thus, this may be a suitable model to study disturbances in energy metabolism and their consequences.

  9. Insulin resistance in Nigerians with essential hypertension | Akande ...

    African Journals Online (AJOL)

    Homeostasis model assessment (HOMA) was used to determine insulin resistance (IR). Results: The hypertensive subjects had significantly higher fasting insulin and HOMA-IR compared with normotensives (p =0.02 and 0.04) respectively. There were significant correlations between HOMA-IR, BMI, waist and hip ...

  10. Glucocorticoid receptor polymorphism in obesity and glucose homeostasis.

    Science.gov (United States)

    Majer-Łobodzińska, Agnieszka; Adamiec-Mroczek, Joanna

    2017-01-01

    Glucocorticoid receptor (GR) activity plays a significant role in the etiology of obesity and is essential for glucose homeostasis, the development of hyperinsulinaemia and subsequent increased fat deposition. Several polymorphisms in the GR gene have been described, and at least three of them seem to be associated with altered glucocorticoid sensitivity and changes in glucose homeostasis, and other metabolic parameters. The N363S polymorphism has been associated with increased sensitivity to glucocorticoides, increased insulin response to dexamethasone and increased plasma glucose level. BclI polymorphism is associated with increased abdominal obesity, hyperinsulinaemia and increased insulin resistance. Another polymorphism, ER22/23EK, in contrast to the others, is associated with relative resistance to glucocoricides actions and more beneficial metabolic profile-lower insulin resistance level, decreased lower cardiovascular risk and subseuent prolongation of life time. More research is still needed to understand the mechanisms behind these associations at the molecular level.

  11. Pyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparum

    Science.gov (United States)

    Vaidya, Akhil B.; Morrisey, Joanne M.; Zhang, Zhongsheng; Das, Sudipta; Daly, Thomas M.; Otto, Thomas D.; Spillman, Natalie J.; Wyvratt, Matthew; Siegl, Peter; Marfurt, Jutta; Wirjanata, Grennady; Sebayang, Boni F.; Price, Ric N.; Chatterjee, Arnab; Nagle, Advait; Stasiak, Marcin; Charman, Susan A.; Angulo-Barturen, Iñigo; Ferrer, Santiago; Belén Jiménez-Díaz, María; Martínez, María Santos; Gamo, Francisco Javier; Avery, Vicky M.; Ruecker, Andrea; Delves, Michael; Kirk, Kiaran; Berriman, Matthew; Kortagere, Sandhya; Burrows, Jeremy; Fan, Erkang; Bergman, Lawrence W.

    2014-01-01

    The quest for new antimalarial drugs, especially those with novel modes of action, is essential in the face of emerging drug-resistant parasites. Here we describe a new chemical class of molecules, pyrazoleamides, with potent activity against human malaria parasites and showing remarkably rapid parasite clearance in an in vivo model. Investigations involving pyrazoleamide-resistant parasites, whole-genome sequencing and gene transfers reveal that mutations in two proteins, a calcium-dependent protein kinase (PfCDPK5) and a P-type cation-ATPase (PfATP4), are necessary to impart full resistance to these compounds. A pyrazoleamide compound causes a rapid disruption of Na+ regulation in blood-stage Plasmodium falciparum parasites. Similar effect on Na+ homeostasis was recently reported for spiroindolones, which are antimalarials of a chemical class quite distinct from pyrazoleamides. Our results reveal that disruption of Na+ homeostasis in malaria parasites is a promising mode of antimalarial action mediated by at least two distinct chemical classes. PMID:25422853

  12. A New Prediction Model for Evaluating Treatment-Resistant Depression.

    Science.gov (United States)

    Kautzky, Alexander; Baldinger-Melich, Pia; Kranz, Georg S; Vanicek, Thomas; Souery, Daniel; Montgomery, Stuart; Mendlewicz, Julien; Zohar, Joseph; Serretti, Alessandro; Lanzenberger, Rupert; Kasper, Siegfried

    2017-02-01

    Despite a broad arsenal of antidepressants, about a third of patients suffering from major depressive disorder (MDD) do not respond sufficiently to adequate treatment. Using the data pool of the Group for the Study of Resistant Depression and machine learning, we intended to draw new insights featuring 48 clinical, sociodemographic, and psychosocial predictors for treatment outcome. Patients were enrolled starting from January 2000 and diagnosed according to DSM-IV. Treatment-resistant depression (TRD) was defined by a 17-item Hamilton Depression Rating Scale (HDRS) score ≥ 17 after at least 2 antidepressant trials of adequate dosage and length. Remission was defined by an HDRS score depressive episode, age at first antidepressant treatment, response to first antidepressant treatment, severity, suicidality, melancholia, number of lifetime depressive episodes, patients' admittance type, education, occupation, and comorbid diabetes, panic, and thyroid disorder. While single predictors could not reach a prediction accuracy much different from random guessing, by combining all predictors, we could detect resistance with an accuracy of 0.737 and remission with an accuracy of 0.850. Consequently, 65.5% of predictions for TRD and 77.7% for remission can be expected to be accurate. Using machine learning algorithms, we could demonstrate success rates of 0.737 for predicting TRD and 0.850 for predicting remission, surpassing predictive capabilities of clinicians. Our results strengthen data mining and suggest the benefit of focus on interaction-based statistics. Considering that all predictors can easily be obtained in a clinical setting, we hope that our model can be tested by other research groups. © Copyright 2017 Physicians Postgraduate Press, Inc.

  13. Phosphatidyl inositol 3-kinase signaling in hypothalamic proopiomelanocortin neurons contributes to the regulation of glucose homeostasis.

    Science.gov (United States)

    Hill, Jennifer W; Xu, Yong; Preitner, Frederic; Fukuda, Makota; Cho, You-Ree; Luo, Ji; Balthasar, Nina; Coppari, Roberto; Cantley, Lewis C; Kahn, Barbara B; Zhao, Jean J; Elmquist, Joel K

    2009-11-01

    Recent studies demonstrated a role for hypothalamic insulin and leptin action in the regulation of glucose homeostasis. This regulation involves proopiomelanocortin (POMC) neurons because suppression of phosphatidyl inositol 3-kinase (PI3K) signaling in these neurons blunts the acute effects of insulin and leptin on POMC neuronal activity. In the current study, we investigated whether disruption of PI3K signaling in POMC neurons alters normal glucose homeostasis using mouse models designed to both increase and decrease PI3K-mediated signaling in these neurons. We found that deleting p85alpha alone induced resistance to diet-induced obesity. In contrast, deletion of the p110alpha catalytic subunit of PI3K led to increased weight gain and adipose tissue along with reduced energy expenditure. Independent of these effects, increased PI3K activity in POMC neurons improved insulin sensitivity, whereas decreased PI3K signaling resulted in impaired glucose regulation. These studies show that activity of the PI3K pathway in POMC neurons is involved in not only normal energy regulation but also glucose homeostasis.

  14. Modeling and experimental study of resistive switching in vertically aligned carbon nanotubes

    Science.gov (United States)

    Ageev, O. A.; Blinov, Yu F.; Ilina, M. V.; Ilin, O. I.; Smirnov, V. A.

    2016-08-01

    Model of the resistive switching in vertically aligned carbon nanotube (VA CNT) taking into account the processes of deformation, polarization and piezoelectric charge accumulation have been developed. Origin of hysteresis in VA CNT-based structure is described. Based on modeling results the VACNTs-based structure has been created. The ration resistance of high-resistance to low-resistance states of the VACNTs-based structure amounts 48. The correlation the modeling results with experimental studies is shown. The results can be used in the development nanoelectronics devices based on VA CNTs, including the nonvolatile resistive random-access memory.

  15. Modeling and experimental study of resistive switching in vertically aligned carbon nanotubes

    International Nuclear Information System (INIS)

    Ageev, O A; Blinov, Yu F; Ilina, M V; Ilin, O I; Smirnov, V A

    2016-01-01

    Model of the resistive switching in vertically aligned carbon nanotube (VA CNT) taking into account the processes of deformation, polarization and piezoelectric charge accumulation have been developed. Origin of hysteresis in VA CNT-based structure is described. Based on modeling results the VACNTs-based structure has been created. The ration resistance of high-resistance to low-resistance states of the VACNTs-based structure amounts 48. The correlation the modeling results with experimental studies is shown. The results can be used in the development nanoelectronics devices based on VA CNTs, including the nonvolatile resistive random-access memory. (paper)

  16. INFLUENCE OF INTERMITTENT CYCLIC LOADING ON REINFORCED CONCRETE RESISTANCE MODEL

    Directory of Open Access Journals (Sweden)

    Vasyl Karpiuk

    2017-01-01

    Full Text Available This article describes the study of reinforced concrete span bending structures under conditions of high-level cyclic loading. Previous studies on the development of physical models of bending reinforced concrete element fatigue resistance, cyclic effect of lateral forces, and methods of calculation, are important and appropriate owing to certain features and the essential specificity of the mentioned loading type. These primarily include the nonlinearity of deformation, damage accumulation in the form of fatigue micro- and macro-cracks, and exhausting destruction of construction materials. In this paper, key expressions determining the endurance limits of concrete, longitudinal reinforcement, and anchoring longitudinal reinforcement, which contribute to endurance throughout the entire construction, are considered. Establishing a link between stresses in the elements and deformations in the element under conditions of cyclic loading action is of equal importance because of the presence of cyclic stress-induced creep deformation.

  17. Screening the banana biodiversity for drought tolerance: can an in vitro growth model and proteomics be used as a tool to discover tolerant varieties and understand homeostasis.

    Science.gov (United States)

    Vanhove, Anne-Catherine; Vermaelen, Wesley; Panis, Bart; Swennen, Rony; Carpentier, Sebastien C

    2012-01-01

    There is a great need for research aimed at understanding drought tolerance, screening for drought tolerant varieties and breeding crops with an improved water use efficiency. Bananas and plantains are a major staple food and export product with a worldwide production of over 135 million tonnes per year. Water however is the most limiting abiotic factor in banana production. A screening of the Musa biodiversity has not yet been performed. We at KU Leuven host the Musa International Germplasm collection with over 1200 accessions. To screen the Musa biodiversity for drought tolerant varieties, we developed a screening test for in vitro plants. Five varieties representing different genomic constitutions in banana (AAAh, AAA, AAB, AABp, and ABB) were selected and subjected to a mild osmotic stress. The ABB variety showed the smallest stress induced growth reduction. To get an insight into the acclimation and the accomplishment of homeostasis, the leaf proteome of this variety was characterized via 2D DIGE. After extraction of the leaf proteome of six control and six stressed plants, 2600 spots could be distinguished. A PCA analysis indicates that control and stressed plants can blindly be classified based on their proteome. One hundred and twelve proteins were significantly more abundant in the stressed plants and 18 proteins were significantly more abundant in control plants (FDR α 0.05). Twenty four differential proteins could be identified. The proteome analysis clearly shows that there is a new balance in the stressed plants and that the respiration, metabolism of ROS and several dehydrogenases involved in NAD/NADH homeostasis play an important role.

  18. A model for temperature dependent resistivity of metallic superlattices

    Directory of Open Access Journals (Sweden)

    J. I. Uba

    2015-11-01

    Full Text Available The temperature dependent resistivity of metallic superlattices, to first order approximation, is assumed to have same form as bulk metal, ρ(T = ρo + aT, which permits describing these structures as linear atomic chain. The assumption is, substantiated with the derivation of the above expression from the standard magnetoresistance equation, in which the second term, a Bragg scattering factor, is a correction to the usual model involving magnon and phonon scatterings. Fitting the model to Fe/Cr data from literature shows that Bragg scattering is dominant at T < 50 K and magnon and phonon coefficients are independent of experiment conditions, with typical values of 4.7 × 10−4 μΩcmK−2 and −8 ± 0.7 × 10−7μΩcmK−3. From the linear atomic chain model, the dielectric constant ε q , ω = 8 . 33 × 10 − 2 at Debye frequency for all materials and acoustic speed and Thomas – Fermi screening length are pressure dependent with typical values of 1.53 × 104 m/s and 1.80 × 109 m at 0.5 GPa pressure for an Fe/Cr structure.

  19. Mathematical modeling for corrosion environment estimation based on concrete resistivity measurement directly above reinforcement

    International Nuclear Information System (INIS)

    Lim, Young-Chul; Lee, Han-Seung; Noguchi, Takafumi

    2009-01-01

    This study aims to formulate a resistivity model whereby the concrete resistivity expressing the environment of steel reinforcement can be directly estimated and evaluated based on measurement immediately above reinforcement as a method of evaluating corrosion deterioration in reinforced concrete structures. It also aims to provide a theoretical ground for the feasibility of durability evaluation by electric non-destructive techniques with no need for chipping of cover concrete. This Resistivity Estimation Model (REM), which is a mathematical model using the mirror method, combines conventional four-electrode measurement of resistivity with geometric parameters including cover depth, bar diameter, and electrode intervals. This model was verified by estimation using this model at areas directly above reinforcement and resistivity measurement at areas unaffected by reinforcement in regard to the assessment of the concrete resistivity. Both results strongly correlated, proving the validity of this model. It is expected to be applicable to laboratory study and field diagnosis regarding reinforcement corrosion. (author)

  20. Association between insulin resistance and plasma amino acid profile in non-diabetic Japanese subjects

    OpenAIRE

    Yamada, Chizumi; Kondo, Masumi; Kishimoto, Noriaki; Shibata, Takeo; Nagai, Yoko; Imanishi, Tadashi; Oroguchi, Takashige; Ishii, Naoaki; Nishizaki, Yasuhiro

    2015-01-01

    Aims/Introduction Elevation of the branched-chain amino acids (BCAAs), valine, leucine and isoleucine; and the aromatic amino acids, tyrosine and phenylalanine, has been observed in obesity-related insulin resistance. However, there have been few studies on Asians, who are generally less obese and less insulin-resistant than Caucasian or African-Americans. In the present study, we investigated the relationship between homeostasis model assessment of insulin resistance (HOMA-IR) and plasma ami...

  1. Gliadin affects glucose homeostasis and intestinal metagenome in C57BL6 mice fed a high-fat diet

    DEFF Research Database (Denmark)

    Zhang, Li; Hansen, Axel Kornerup; Bahl, Martin Iain

    limited. The aim of this study was to investigate the effect of gliadin on glucose homeostasis and intestinal ecology in the mouse. Forty male C57BL/6 mice were fed a high-fat diet containing either 4% gliadin or no gliadin for 22 weeks. Gliadin consumption significantly increased the HbA1c level over......Dietary gluten and its component gliadin are well-known environmental triggers of celiac disease and important actors in type-1 diabetes, and are reported to induce alterations in the intestinal microbiota. However, research on the impact of gluten on type-2 diabetes in non-celiac subjects is more...... time, with a borderline significance of higher HOMA-IR (homeostasis model assessment of insulin resistance) after 22 weeks. Sequencing of the V3 region of the bacterial 16S rRNA genes showed that gliadin altered the abundance of 81 bacterial taxa, separating the intestinal microbial profile...

  2. Towards predictive resistance models for agrochemicals by combining chemical and protein similarity via proteochemometric modelling.

    Science.gov (United States)

    van Westen, Gerard J P; Bender, Andreas; Overington, John P

    2014-10-01

    Resistance to pesticides is an increasing problem in agriculture. Despite practices such as phased use and cycling of 'orthogonally resistant' agents, resistance remains a major risk to national and global food security. To combat this problem, there is a need for both new approaches for pesticide design, as well as for novel chemical entities themselves. As summarized in this opinion article, a technique termed 'proteochemometric modelling' (PCM), from the field of chemoinformatics, could aid in the quantification and prediction of resistance that acts via point mutations in the target proteins of an agent. The technique combines information from both the chemical and biological domain to generate bioactivity models across large numbers of ligands as well as protein targets. PCM has previously been validated in prospective, experimental work in the medicinal chemistry area, and it draws on the growing amount of bioactivity information available in the public domain. Here, two potential applications of proteochemometric modelling to agrochemical data are described, based on previously published examples from the medicinal chemistry literature.

  3. Antibiotic Resistances in Livestock: A Comparative Approach to Identify an Appropriate Regression Model for Count Data

    Directory of Open Access Journals (Sweden)

    Anke Hüls

    2017-05-01

    Full Text Available Antimicrobial resistance in livestock is a matter of general concern. To develop hygiene measures and methods for resistance prevention and control, epidemiological studies on a population level are needed to detect factors associated with antimicrobial resistance in livestock holdings. In general, regression models are used to describe these relationships between environmental factors and resistance outcome. Besides the study design, the correlation structures of the different outcomes of antibiotic resistance and structural zero measurements on the resistance outcome as well as on the exposure side are challenges for the epidemiological model building process. The use of appropriate regression models that acknowledge these complexities is essential to assure valid epidemiological interpretations. The aims of this paper are (i to explain the model building process comparing several competing models for count data (negative binomial model, quasi-Poisson model, zero-inflated model, and hurdle model and (ii to compare these models using data from a cross-sectional study on antibiotic resistance in animal husbandry. These goals are essential to evaluate which model is most suitable to identify potential prevention measures. The dataset used as an example in our analyses was generated initially to study the prevalence and associated factors for the appearance of cefotaxime-resistant Escherichia coli in 48 German fattening pig farms. For each farm, the outcome was the count of samples with resistant bacteria. There was almost no overdispersion and only moderate evidence of excess zeros in the data. Our analyses show that it is essential to evaluate regression models in studies analyzing the relationship between environmental factors and antibiotic resistances in livestock. After model comparison based on evaluation of model predictions, Akaike information criterion, and Pearson residuals, here the hurdle model was judged to be the most appropriate

  4. The homeostasis solution – Mechanical homeostasis in architecturally homeostatic buildings

    International Nuclear Information System (INIS)

    Wang, Lin-Shu; Ma, Peizheng

    2016-01-01

    Highlights: • Architectural homeostatic buildings (AHBs) make sense because of the laws of physics. • However, high efficiency can be obtained only with AHBs and equipment considered as systems. • Mechanical homeostasis facilitates AHB-equipment system synergy with heat extraction. • Entropically speaking a building needs neither energy nor a fixed amount of heat, but its homeostatic existence. • Homeostatic buildings can reduce building energy consumption from 80% to 90%. - Abstract: We already know, for energy-saving potential, the necessary architectural features in well-designed buildings: high performance building envelope, sufficient interior thermal mass, and hydronic-network activated radiant surfaces for cooling and heating. Buildings with these features may be referred to as architecturally homeostatic buildings (AHBs); such a building-system is thermally semi-autonomous in the sense that its temperature variation stays within a certain range even without conditioning equipment, and, with conditioning equipment in operation, its thermal regulation is handled by its hydronic heat-distribution-network for controlling the temperature level of the building. At the present time conventional HVAC equipment is used for maintaining the heat-distribution-network: this arrangement, however, has resulted in great energy saving only for AHBs with accessible natural water bodies. In operation of general AHBs, a case is made here for a new kind of mechanical equipment having the attribute of mechanical homeostasis (MH). MH is a new energy transformation concept in a triadic framework. Superlative energy efficiency is predicted as a result of combined improvements in higher triadCOPs and lower total (inducted + removed) heat rates—evincing existence of synergy in architectural and mechanical homeostasis, which together will be referred to as the homeostasis solution.

  5. Impact of metal ion homeostasis of genetically modified Escherichia coli Nissle 1917 and K12 (W3110) strains on colonization properties in the murine intestinal tract.

    Science.gov (United States)

    Kupz, Andreas; Fischer, André; Nies, Dietrich H; Grass, Gregor; Göbel, Ulf B; Bereswill, Stefan; Heimesaat, Markus M

    2013-09-01

    Metal ions are integral parts of pro- as well as eukaryotic cell homeostasis. Escherichia coli proved a valuable in vitro model organism to elucidate essential mechanisms involved in uptake, storage, and export of metal ions. Given that E. coli Nissle 1917 is able to overcome murine colonization resistance, we generated several E. coli Nissle 1917 mutants with defects in zinc, iron, copper, nickel, manganese homeostasis and performed a comprehensive survey of the impact of metal ion transport and homeostasis for E. coli colonization capacities within the murine intestinal tract. Seven days following peroral infection of conventional mice with E. coli Nissle 1917 strains exhibiting defined defects in zinc or iron uptake, the respective mutant and parental strains could be cultured at comparable, but low levels from the colonic lumen. We next reassociated gnotobiotic mice in which the microbiota responsible for colonization resistance was abrogated by broad-spectrum antibiotics with six different E. coli K12 (W3110) mutants. Seven days following peroral challenge, each mutant and parental strain stably colonized duodenum, ileum, and colon at comparable levels. Taken together, defects in zinc, iron, copper, nickel, and manganese homeostasis do not compromise colonization capacities of E. coli in the murine intestinal tract.

  6. Induced mutations for horizontal resistance. A model study using leaf rust resistance in wheat

    International Nuclear Information System (INIS)

    Chopra, V.L.; Sawhney, R.N.; Kumar, R.

    1983-01-01

    A mutant with seemingly non-specific resistance to leaf rust was obtained some time ago from the wheat variety Kharchia Local treated with NMH. This mutant is being studied genetically and in its disease reaction by laboratories in Australia, Canada and India in co-operation. The mutant showed a dominant inheritance of resistance in F 1 , but different segregation in F 2 and F 3 . This peculiar genetic behaviour has so far not been explained. (author)

  7. Associations between depressive symptoms and insulin resistance

    DEFF Research Database (Denmark)

    Adriaanse, M C; Dekker, J M; Nijpels, G

    2006-01-01

    AIMS/HYPOTHESIS: The association between depression and insulin resistance has been investigated in only a few studies, with contradictory results reported. The aim of this study was to determine whether the association between symptoms of depression and insulin resistance varies across glucose...... established type 2 diabetes mellitus. Main outcome measures were insulin resistance defined by the homeostasis model assessment for insulin resistance (HOMA-IR) and symptoms of depression using the Centre for Epidemiologic Studies Depression Scale (CES-D). RESULTS: In the total sample, we found a weak.......942). The association between depressive symptoms and insulin resistance was similar for men and women. CONCLUSIONS/INTERPRETATION: We found only weak associations between depressive symptoms and insulin resistance, which did not differ among different glucose metabolism subgroups or between men and women....

  8. Recovery of immune competence following sublethal X irradiation of young and old mice: a model for studying age-related loss of immunologic homeostasis

    International Nuclear Information System (INIS)

    Peterson, W.J.; Perkins, E.H.; Makinodan, T.

    1982-01-01

    Age-related alteration in lymphohematopoietic homeostasis was assessed kinetically by determining immunologic and stem-cell regenerating capacities of young (5-7 months), middle-aged (13 months), and old (23-24 months) C3H and C57BL/6 mice following their exposure to 500 R. Immunologic activities were based on the ability of spleen cells to respond to sheep erythrocytes, phytohemagglutinin, and bacterial lipopolysaccharide. Stem-cell activity was based on the ability of splenic and bone marrow cells to form colonies in vivo. Reflective of age-related homeostatic imbalance was alteration in the (a) time of recovery, (b) rate of regeneration, and (c) capacity of the regenerating system to overshoot the preirradition steady-state level. Most of the immunologic parameters showed a delay in the time of recovery in old mice. In contrast, the time of recovery of stem cells in old mice was equal to or faster than that in young mice. Furthermore, the magnitude of regeneration of stem cells was greater in old than young mice. These results suggest that recovery of immunologic activities in old mice is delayed partly because of the inability of their stem cells to rapidly generate immunocompetent progenies

  9. Energy Homeostasis in Monotremes

    Directory of Open Access Journals (Sweden)

    Stewart C. Nicol

    2017-04-01

    Full Text Available In 1803, the French anatomist Étienne Geoffroy Saint-Hilaire decided that the newly described echidna and platypus should be placed in a separate order, the monotremes, intermediate between reptiles and mammals. The first physiological observations showed monotremes had low body temperatures and metabolic rates, and the consensus was that they were at a stage of physiological development intermediate between “higher mammals” and “lower vertebrates.” Subsequent studies demonstrated that platypuses and echidnas are capable of close thermoregulation in the cold although less so under hot conditions. Because the short-beaked echidna Tachyglossus aculeatus, may show very large daily variations in body temperature, as well as seasonal hibernation, it has been suggested that it may provide a useful model of protoendotherm physiology. Such analysis is complicated by the very significant differences in thermal relations between echidnas from different climates. In all areas female echidnas regulate Tb within 1°C during egg incubation. The lactation period is considered to be the most energetically expensive time for most female mammals but lactating echidnas showed no measurable difference in field metabolic rate from non-lactating females, while the lactation period is more than 200 days for Kangaroo Island echidnas but only 150 days in Tasmania. In areas with mild winters echidnas show reduced activity and shallow torpor in autumn and early winter, but in areas with cold winters echidnas enter true hibernation with Tb falling as low as 4.5°C. Monotremes do not possess brown adipose tissue and maximum rates of rewarming from hibernation in echidnas were only half those of marmots of the same mass. Although echidnas show very large seasonal variations in fat stores associated with hibernation there is no relationship between plasma leptin and adiposity. Leptin levels are lowest during post-reproductive fattening, supporting suggestions that in

  10. Validation of HOMA-IR in a model of insulin-resistance induced by a high-fat diet in Wistar rats.

    Science.gov (United States)

    Antunes, Luciana C; Elkfury, Jessica L; Jornada, Manoela N; Foletto, Kelly C; Bertoluci, Marcello C

    2016-04-01

    Objective The present study aimed to validate homeostasis model assessment of insulin resistance (HOMA-IR) in relation to the insulin tolerance test (ITT) in a model of insulin-resistance in Wistar rats induced by a 19-week high-fat diet. Materials and methods A total of 30 male Wistar rats weighing 200-300 g were allocated into a high-fat diet group (HFD) (55% fat-enriched chow, ad lib, n = 15) and a standard-diet group (CD) standard chow, ad lib, n = 15), for 19 weeks. ITT was determined at baseline and in the 19th week. HOMA-IR was determined between the 18-19th week in three different days and the mean was considered for analysis. Area under the curve (AUC-ITT) of the blood glucose excursion along 120 minutes after intra-peritoneal insulin injection was determined and correlated with the corresponding fasting values for HOMA-IR. Results AUC-ITT and HOMA-IR were significantly greater after 19th week in HFD compared to CD (p HOMA-IR was strongly correlated (Pearson's) with AUC-ITT r = 0.637; p HOMA-IR and AUC-ITT showed similar sensitivity and specificity. Conclusion HOMA-IR is a valid measure to determine insulin-resistance in Wistar rats. Arch Endocrinol Metab. 2016;60(2):138-42.

  11. The Role of Angiopoietin-like 4 in Lipid Homeostasis

    OpenAIRE

    Gray, Nora

    2012-01-01

    AbstractThe Role of Angiopoietin-like 4 in Lipid HomeostasisbyNora Elizabeth Forbes GrayDoctor of Philosophy in Molecular and Biochemical NutritionUniversity of California, BerkeleyProfessor Jen-Chywan Wang, ChairAlterations in the regulation of lipid homeostasis are major causes of metabolic diseases like obesity, insulin resistance and the metabolic syndrome. These diseases affect millions of people and therefore constitute a pressing public health concern. The mobilization of lipids is a k...

  12. Modeling deployment of Pierce’s disease resistant grapevines

    Science.gov (United States)

    Deployment of Pierce’s disease resistant grapevines is a key solution to mitigating economic losses caused by Xylella fastidiosa. While Pierce’s disease resistant grapevines under development display mild symptoms and have lower bacterial populations than susceptible varieties, all appear to remain ...

  13. Airflow resistivity of models of fibrous acoustic materials

    DEFF Research Database (Denmark)

    Tarnow, Viggo

    1996-01-01

    A new way of calculating the airflow resistivity of randomly placed parallel cylinders is presented. The calculation is based on Voronoi polygons, and the resistivity is given by the mean spacing between the fibers, their diameters, and the physical properties of air. New explicit formulas...

  14. Modeling polyolefin deformation resistance in a growing microparticle

    NARCIS (Netherlands)

    Agarwal, U.S.

    2004-01-01

    When polyolefins are produced on heterogeneous catalysts, they encapsulate the catalyst fragments and present diffusional resistance to further monomer transport to the catalyst fragments. In addition, the deposited polymer layer brings in viscoelastic resistance, since it must be deformed to make

  15. Telomere Homeostasis: Interplay with Magnesium

    Directory of Open Access Journals (Sweden)

    Donogh Maguire

    2018-01-01

    Full Text Available Telomere biology, a key component of the hallmarks of ageing, offers insight into dysregulation of normative ageing processes that accompany age-related diseases such as cancer. Telomere homeostasis is tightly linked to cellular metabolism, and in particular with mitochondrial physiology, which is also diminished during cellular senescence and normative physiological ageing. Inherent in the biochemistry of these processes is the role of magnesium, one of the main cellular ions and an essential cofactor in all reactions that use ATP. Magnesium plays an important role in many of the processes involved in regulating telomere structure, integrity and function. This review explores the mechanisms that maintain telomere structure and function, their influence on circadian rhythms and their impact on health and age-related disease. The pervasive role of magnesium in telomere homeostasis is also highlighted.

  16. Marine Natural Products as Models to Circumvent Multidrug Resistance

    Directory of Open Access Journals (Sweden)

    Solida Long

    2016-07-01

    Full Text Available Multidrug resistance (MDR to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC transporter P-glycoprotein (P-gp, which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds.

  17. Sleep Homeostasis and Synaptic Plasticity

    Science.gov (United States)

    2017-06-01

    Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202...circuit (a homeostat) that operates in concert with the circadian circuitry or does sleep drive accumulate everywhere in the brain? To answer these...neurons is capable of generating sleep drive. RNAi-mediated knockdown of insomniac in R2 neurons abolished sleep homeostasis without affecting baseline

  18. EGb761, an extract of Ginkgo biloba leaves, reduces insulin resistance in a high-fat-fed mouse model

    Directory of Open Access Journals (Sweden)

    Wei-na Cong

    2011-06-01

    Full Text Available EGb761, a standardized and well-defined product extract of Ginkgo biloba leaves, has beneficial effects on the treatment of multiple diseases, including diabetes and dyslipidemia. However, it is still unclear whether EGb761 can increase insulin sensitivity. The objectives of the present study are to evaluate the effects of EGb761 on insulin sensitivity in an obese and insulin-resistant mouse model, established through chronic feeding of C57BL/6J mice with a high-fat diet (HFD, and to explore potential mechanisms. Mice fed with HFD for 18 weeks (starting from 4 weeks of age developed obesity, dyslipidemia (as indicated by biochemical measurements of blood glucose, triglyceride (TG, total cholesterol (TC, and free fatty acids (FFA, and insulin resistance (as determined by the oral glucose tolerance test (OGTT and the homeostasis model assessment of insulin resistance (HOMA-IR index, compared to control mice fed with a standard laboratory chow. Oral treatment of the HFD-fed mice with EGb761, at low (100 mg/kg, medium (200 mg/kg, or high (400 mg/kg doses, via oral gavage (once daily for 8 weeks (starting from 26 weeks of age dose-dependently enhanced glucose tolerance in OGTT, and decreased both the insulin levels (by 29%, 55%, and 70%, respectively, and the HOMA-IR index values (by 50%, 69%, and 80%, respectively. EGb761 treatment also ameliorated HFD-induced obesity, dyslipidemia, and liver injury, as indicated by decreases in body weight (by 4%, 11%, and 16%, respectively, blood TC levels (by 23%, 32%, and 37%, respectively, blood TG levels (by 17%, 23%, and 33%, respectively, blood FAA levels (by 35%, 38%, and 46%, respectively, and liver index (liver weight/body weight values (by 12.8%, 25%, and 28%, respectively in the low, medium, and high EGb761 dose groups, respectively. In further mechanism studies, EGb761 was found to protect hepatic insulin receptor β and insulin receptor substrate 1 from HFD-induced degradation, and to keep the AMP

  19. Cry1F resistance among lepidopteran pests: a model for improved resistance management?

    Science.gov (United States)

    Vélez, Ana M; Vellichirammal, Neetha Nanoth; Jurat-Fuentes, Juan Luis; Siegfried, Blair D

    2016-06-01

    The Cry1Fa protein from the bacterium Bacillus thuringiensis (Bt) is known for its potential to control lepidopteran pests, especially through transgenic expression in maize and cotton. The maize event TC1507 expressing the cry1Fa toxin gene became commercially available in the United States in 2003 for the management of key lepidopteran pests including the European corn borer, Ostrinia nubilalis, and the fall armyworm, Spodoptera frugiperda. A high-dose/refuge strategy has been widely adopted to delay evolution of resistance to event TC1507 and other transgenic Bt crops. Efficacy of this strategy depends on the crops expressing a high dose of the Bt toxin to targeted pests and adjacent refuges of non-Bt host plants serving as a source of abundant susceptible insects. While this strategy has proved effective in delaying O. nubilalis resistance, field-evolved resistance to event TC1507 has been reported in S. frugiperda populations in Puerto Rico, Brazil, and the southeastern United States. This paper examines available information on resistance to Cry1Fa in O. nubilalis and S. frugiperda and discusses how this information identifies opportunities to refine resistance management recommendations for Bt maize. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Regulation of calcium homeostasis in activated human neutrophils ...

    African Journals Online (AJOL)

    Objectives. The objectives of the current study were to: (i) present an integrated model for the restoration of calcium homeostasis in activated human neutrophils based on current knowledge and recent research; and (ii) identify potential targets for the modulation of calcium fluxes in activated neutrophils based on this model ...

  1. On the applicability of nearly free electron model for resistivity calculations in liquid metals

    International Nuclear Information System (INIS)

    Gorecki, J.; Popielawski, J.

    1982-09-01

    The calculations of resistivity based on the nearly free electron model are presented for many noble and transition liquid metals. The triple ion correlation is included in resistivity formula according to SCQCA approximation. Two different methods for describing the conduction band are used. The problem of applicability of the nearly free electron model for different metals is discussed. (author)

  2. Comparison of different initiation protocols in the resistant hepatocyte model

    International Nuclear Information System (INIS)

    Espandiari, Parvaneh; Robertson, Larry W.; Srinivasan, Cidambi; Glauert, Howard P.

    2005-01-01

    Several models in rat liver have been developed to study multistage carcinogenesis, including the Solt-Farber resistant hepatocyte model. In this model, initiation consists of either a necrogenic dose of a hepatocarcinogen or a non-necrogenic dose in conjunction with partial hepatectomy (PH). As an alternative to PH, we investigated two different procedures: fasting for 96 h followed by refeeding, or the use of one-day-old neonates. Male Fisher 344 rats were injected p.o. with diethylnitrosamine (DEN) (0, 20, or 100 mg/kg) 24 h after refeeding or PH (controls received DEN alone with no proliferative stimulus). For the neonatal group, male and female Fisher 344 rats were treated with DEN (0 or 20 mg/kg, i.p.) at one day of age. All initiated animals were treated at the same age (11 weeks) with the following selection agents: three daily doses of 2-acetylaminofluorene (AAF) (30 mg/kg), followed by a single dose of carbon tetrachloride (2 ml/kg), followed by three additional daily treatments of AAF (30 mg/kg). Rats were euthanized 2 weeks after the last AAF injection. The PH, neonatal male, and neonatal female groups receiving DEN developed more γ-glutamyl transpeptidase (GGT)-positive foci per cubic centimeter and foci per liver as compared to untreated rats receiving the same proliferative stimulus, whereas the fasting/refeeding group and the group receiving no proliferative stimulus did not. All DEN-treated groups receiving one of the proliferative stimuli had more foci per cubic centimeter than the DEN-treated group receiving no proliferative stimulus. The volume fractions of GGT-positive foci in the PH/DEN and neonatal male/DEN groups were higher than those of both the DEN-treated group receiving no proliferative stimulus and the groups receiving the same proliferative stimulus without DEN. In neonatal females-receiving DEN, the volume fraction was not different from either neonatal females not receiving DEN or DEN-treated rats receiving no proliferative

  3. Defecto en la homeostasis del óxido nítrico: Mecanismo común subyacente de la insulino-resistencia, la hiperactividad simpática y la morbi-mortalidad cardiovascular Defective nitric oxide homeostasis: Common underlying mechanism between insulin resistance, sympathetic overactivity and cardiovascular morbidity and mortality

    Directory of Open Access Journals (Sweden)

    Marcos Schwab

    2008-06-01

    Full Text Available La incidencia de la obesidad y de la resistencia a la insulina con sus complicaciones asociadas, como la hipertensión arterial y el aumento de la morbi-mortalidad cardiovascular, alcanzan hoy en día proporciones epidémicas y representan un problema mayor de salud pública. En los últimos años se ha demostrado que la administración de insulina, además de sus efectos metabólicos, posee efectos cardiovasculares importantes. El sistema nervioso simpático y el sistema L-arginina - óxido nítrico son los mediadores centrales de estas acciones cardiovasculares de la insulina. Mostramos, gracias a estudios realizados en animales y en humanos, que no sólo un déficit de la síntesis del óxido nítrico (NO, sino también un aumento exagerado en su producción representan un defecto subyacente central de las anomalías metabólicas, cardiovasculares y del sistema nervioso simpático que caracterizan a la insulino resistencia. Mostramos cómo estos resultados establecen el fundamento científico para la utilización de sustancias farmacológicas capaces de liberar de manera prolongada cantidades fisiológicas de NO o de inhibidores de su sobreproducción como futuros tratamientos para la resistencia a la insulina y sus complicaciones asociadas.Obesity, insulin resistance and associated cardiovascular complications are reaching epidemic proportions worldwide and represent a major public health problem. Over the past decade, evidence has accumulated indicating that insulin administration, in addition to its metabolic effects, also has important cardiovascular actions. The sympathetic nervous system and the L-arginine-nitric oxide pathway are the central players in the mediation of insulin's cardiovascular actions. Based on recent animal and human research, we demonstrate that both defective and augmented NO synthesis represent a central defect triggering many of the metabolic, vascular and sympathetic abnormalities characteristic of insulin-resistant

  4. Mid-gestational serum uric acid concentration effect on neonate birth weight and insulin resistance in pregnant women

    OpenAIRE

    Nasri, Khadijeh; Razavi, Maryamsadat; Rezvanfar, Mohammad Reza; Mashhadi, Esmat; Chehrei, Ali; Mohammadbeigi, Abolfazl

    2015-01-01

    Objective To investigate the relationship between mid-gestational serum uric acid and birth weight in diabetic pregnant women with or without insulin resistance. Methods: In a prospective cohort study, fasting uric acid, blood glucose, and serum insulin were measured in 247 pregnant women between 20-22 weeks of gestational period. Insulin resistance was estimated using the homeostasis model assessment-insulin resistance (HOMA-IR). Stratification analysis and independent t-test was used to ass...

  5. 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue and prospective changes in body weight and insulin resistance

    DEFF Research Database (Denmark)

    Koska, Juraj; de Courten, Barbora; Wake, Deborah J

    2006-01-01

    Increased mRNA and activity levels of 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in human adipose tissue (AT) are associated with obesity and insulin resistance. The aim of our study was to investigate whether 11betaHSD1 expression or activity in abdominal subcutaneous AT of non-diab......-diabetic subjects are associated with subsequent changes in body weight and insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)]....

  6. A New Nonlinear Model of Body Resistance in Nanometer PD SOI MOSFETs

    Directory of Open Access Journals (Sweden)

    Arash Daghighi

    2011-01-01

    Full Text Available In this paper, a nonlinear model for the body resistance of a 45nm PD SOI MOSFET is developed. This model verified on the base of the small signal three-dimensional simulation results. In this paper by using the three-dimensional simulation of ISE-TCAD software, the indicating factors of body resistance in nanometer transistors and then are shown, using the surface potential model. A mathematical relation to calculat the body resistance incorporating device width and body potential was derived. Excellent agreement was obtained by comparing the model outputs and three-dimensional simulation results.

  7. Analysis of mutational resistance to trimethoprim in Staphylococcus aureus by genetic and structural modelling techniques.

    Science.gov (United States)

    Vickers, Anna A; Potter, Nicola J; Fishwick, Colin W G; Chopra, Ian; O'Neill, Alex J

    2009-06-01

    This study sought to expand knowledge on the molecular mechanisms of mutational resistance to trimethoprim in Staphylococcus aureus, and the fitness costs associated with resistance. Spontaneous trimethoprim-resistant mutants of S. aureus SH1000 were recovered in vitro, resistance genotypes characterized by DNA sequencing of the gene encoding the drug target (dfrA) and the fitness of mutants determined by pair-wise growth competition assays with SH1000. Novel resistance genotypes were confirmed by ectopic expression of dfrA alleles in a trimethoprim-sensitive S. aureus strain. Molecular models of S. aureus dihydrofolate reductase (DHFR) were constructed to explore the structural basis of trimethoprim resistance, and to rationalize the observed in vitro fitness of trimethoprim-resistant mutants. In addition to known amino acid substitutions in DHFR mediating trimethoprim resistance (F(99)Y and H(150)R), two novel resistance polymorphisms (L(41)F and F(99)S) were identified among the trimethoprim-resistant mutants selected in vitro. Molecular modelling of mutated DHFR enzymes provided insight into the structural basis of trimethoprim resistance. Calculated binding energies of the substrate (dihydrofolate) for the mutant and wild-type enzymes were similar, consistent with apparent lack of fitness costs for the resistance mutations in vitro. Reduced susceptibility to trimethoprim of DHFR enzymes carrying substitutions L(41)F, F(99)S, F(99)Y and H(150)R appears to result from structural changes that reduce trimethoprim binding to the enzyme. However, the mutations conferring trimethoprim resistance are not associated with fitness costs in vitro, suggesting that the survival of trimethoprim-resistant strains emerging in the clinic may not be subject to a fitness disadvantage.

  8. Physical model of the contact resistivity of metal-graphene junctions

    International Nuclear Information System (INIS)

    Chaves, Ferney A.; Jiménez, David; Cummings, Aron W.; Roche, Stephan

    2014-01-01

    While graphene-based technology shows great promise for a variety of electronic applications, including radio-frequency devices, the resistance of the metal-graphene contact is a technological bottleneck for the realization of viable graphene electronics. One of the most important factors in determining the resistance of a metal-graphene junction is the contact resistivity. Despite the large number of experimental works that exist in the literature measuring the contact resistivity, a simple model of it is still lacking. In this paper, we present a comprehensive physical model for the contact resistivity of these junctions, based on the Bardeen Transfer Hamiltonian method. This model unveils the role played by different electrical and physical parameters in determining the specific contact resistivity, such as the chemical potential of interaction, the work metal-graphene function difference, and the insulator thickness between the metal and graphene. In addition, our model reveals that the contact resistivity is strongly dependent on the bias voltage across the metal-graphene junction. This model is applicable to a wide variety of graphene-based electronic devices and thus is useful for understanding how to optimize the contact resistance in these systems

  9. Physical model of the contact resistivity of metal-graphene junctions

    Energy Technology Data Exchange (ETDEWEB)

    Chaves, Ferney A., E-mail: ferneyalveiro.chaves@uab.cat; Jiménez, David [Departament d' Enginyeria Electrònica, Escola d' Enginyeria, Universitat Autònoma de Barcelona, Campus UAB, 08193 Bellaterra, Barcelona (Spain); Cummings, Aron W. [ICN2–Institut Català de Nanociència i Nanotecnologia, Campus UAB, 08193 Bellaterra, Barcelona (Spain); Roche, Stephan [ICN2–Institut Català de Nanociència i Nanotecnologia, Campus UAB, 08193 Bellaterra, Barcelona (Spain); ICREA, Institució Catalana de Recerca i Estudis Avançats, 08070 Barcelona (Spain)

    2014-04-28

    While graphene-based technology shows great promise for a variety of electronic applications, including radio-frequency devices, the resistance of the metal-graphene contact is a technological bottleneck for the realization of viable graphene electronics. One of the most important factors in determining the resistance of a metal-graphene junction is the contact resistivity. Despite the large number of experimental works that exist in the literature measuring the contact resistivity, a simple model of it is still lacking. In this paper, we present a comprehensive physical model for the contact resistivity of these junctions, based on the Bardeen Transfer Hamiltonian method. This model unveils the role played by different electrical and physical parameters in determining the specific contact resistivity, such as the chemical potential of interaction, the work metal-graphene function difference, and the insulator thickness between the metal and graphene. In addition, our model reveals that the contact resistivity is strongly dependent on the bias voltage across the metal-graphene junction. This model is applicable to a wide variety of graphene-based electronic devices and thus is useful for understanding how to optimize the contact resistance in these systems.

  10. The rising impact of mathematical modelling in epidemiology: antibiotic resistance research as a case study

    Science.gov (United States)

    TEMIME, L.; HEJBLUM, G.; SETBON, M.; VALLERON, A. J.

    2008-01-01

    SUMMARY Mathematical modelling of infectious diseases has gradually become part of public health decision-making in recent years. However, the developing status of modelling in epidemiology and its relationship with other relevant scientific approaches have never been assessed quantitatively. Herein, using antibiotic resistance as a case study, 60 published models were analysed. Their interactions with other scientific fields are reported and their citation impact evaluated, as well as temporal trends. The yearly number of antibiotic resistance modelling publications increased significantly between 1990 and 2006. This rise cannot be explained by the surge of interest in resistance phenomena alone. Moreover, modelling articles are, on average, among the most frequently cited third of articles from the journal in which they were published. The results of this analysis, which might be applicable to other emerging public health problems, demonstrate the growing interest in mathematical modelling approaches to evaluate antibiotic resistance. PMID:17767792

  11. Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors.

    Directory of Open Access Journals (Sweden)

    Winyoo Chowanadisai

    Full Text Available The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05 (S2 Table. Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition.

  12. A Novel Method of Modeling the Deformation Resistance for Clad Sheet

    International Nuclear Information System (INIS)

    Hu Jianliang; Yi Youping; Xie Mantang

    2011-01-01

    Because of the excellent thermal conductivity, the clad sheet (3003/4004/3003) of aluminum alloy is extensively used in various heat exchangers, such as radiator, motorcar air conditioning, evaporator, and so on. The deformation resistance model plays an important role in designing the process parameters of hot continuous rolling. However, the complex behaviors of the plastic deformation of the clad sheet make the modeling very difficult. In this work, a novel method for modeling the deformation resistance of clad sheet was proposed by combining the finite element analysis with experiments. The deformation resistance model of aluminum 3003 and 4004 was proposed through hot compression test on the Gleeble-1500 thermo-simulation machine. And the deformation resistance model of clad sheet was proposed through finite element analysis using DEFORM-2D software. The relationship between cladding ratio and the deformation resistance was discussed in detail. The results of hot compression simulation demonstrate that the cladding ratio has great effects on the resistance of the clad sheet. Taking the cladding ratio into consideration, the mathematical model of the deformation resistance for clad sheet has been proved to have perfect forecasting precision of different cladding ratio. Therefore, the presented model can be used to predict the rolling force of clad sheet during the hot continuous rolling process.

  13. Prion protein misfolding affects calcium homeostasis and sensitizes cells to endoplasmic reticulum stress.

    Directory of Open Access Journals (Sweden)

    Mauricio Torres

    2010-12-01

    Full Text Available Prion-related disorders (PrDs are fatal neurodegenerative disorders characterized by progressive neuronal impairment as well as the accumulation of an abnormally folded and protease resistant form of the cellular prion protein, termed PrP(RES. Altered endoplasmic reticulum (ER homeostasis is associated with the occurrence of neurodegeneration in sporadic, infectious and familial forms of PrDs. The ER operates as a major intracellular calcium store, playing a crucial role in pathological events related to neuronal dysfunction and death. Here we investigated the possible impact of PrP misfolding on ER calcium homeostasis in infectious and familial models of PrDs. Neuro2A cells chronically infected with scrapie prions showed decreased ER-calcium content that correlated with a stronger upregulation of UPR-inducible chaperones, and a higher sensitivity to ER stress-induced cell death. Overexpression of the calcium pump SERCA stimulated calcium release and increased the neurotoxicity observed after exposure of cells to brain-derived infectious PrP(RES. Furthermore, expression of PrP mutants that cause hereditary Creutzfeldt-Jakob disease or fatal familial insomnia led to accumulation of PrP(RES and their partial retention at the ER, associated with a drastic decrease of ER calcium content and higher susceptibility to ER stress. Finally, similar results were observed when a transmembrane form of PrP was expressed, which is proposed as a neurotoxic intermediate. Our results suggest that alterations in calcium homeostasis and increased susceptibility to ER stress are common pathological features of both infectious and familial PrD models.

  14. The study of cell homeostasis state of the gastric mucosa of rats on model of rheumatoid arthritis , treatment with ibuprofen and its combination with vinboron

    Directory of Open Access Journals (Sweden)

    F. V. Hladkykh

    2016-01-01

     of Ki-67 and CPP32 showed that the basis of gastroprotective effect of vinboron with ibuprofen-induced gastropathy in rats with adjuvant arthritis is its ability to enhance the regenerative properties of the gastric epithelium by restoring the proliferative activity. In addition vinboron is able to inhibit apoptosis induced by ibuprofen epithelial cells of the stomach, which helps to maintain cellular homeostasis of the gastric mucosa.

  15. Homeostasis, inflammation, and disease susceptibility.

    Science.gov (United States)

    Kotas, Maya E; Medzhitov, Ruslan

    2015-02-26

    While modernization has dramatically increased lifespan, it has also witnessed the increasing prevalence of diseases such as obesity, hypertension, and type 2 diabetes. Such chronic, acquired diseases result when normal physiologic control goes awry and may thus be viewed as failures of homeostasis. However, while nearly every process in human physiology relies on homeostatic mechanisms for stability, only some have demonstrated vulnerability to dysregulation. Additionally, chronic inflammation is a common accomplice of the diseases of homeostasis, yet the basis for this connection is not fully understood. Here we review the design of homeostatic systems and discuss universal features of control circuits that operate at the cellular, tissue, and organismal levels. We suggest a framework for classification of homeostatic signals that is based on different classes of homeostatic variables they report on. Finally, we discuss how adaptability of homeostatic systems with adjustable set points creates vulnerability to dysregulation and disease. This framework highlights the fundamental parallels between homeostatic and inflammatory control mechanisms and provides a new perspective on the physiological origin of inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. (HbA1c) levels with Iinsulin resistance in obese children.

    African Journals Online (AJOL)

    Objectives: We investigated the relationship between insulin resistance reflected by homeostasis model assessment (HOMA-IR) index and serum HbA1c levels of obese children. Material and Methods: This study included 70 obese and 60 normal weight healthy children between the ages of 3 and 15. Anthropometric ...

  17. The establishment of insulin resistance model in FL83B and L6 cell

    Science.gov (United States)

    Liu, Lanlan; Han, Jizhong; Li, Haoran; Liu, Mengmeng; Zeng, Bin

    2017-10-01

    The insulin resistance models of mouse liver epithelial and rat myoblasts cells were induced by three kinds of inducers: dexamethasone, high insulin and high glucose. The purpose is to select the optimal insulin resistance model, to provide a simple and reliable TR cell model for the study of the pathogenesis of TR and the improvement of TR drugs and functional foods. The MTT method is used for toxicity screening of three compounds, selecting security and suitable concentration. We performed a Glucose oxidase peroxidase (GOD-POD) method involving FL83B and L6 cell with dexamethasone, high insulin and high glucose-induced insulin resistance. Results suggested that FL83B cells with dexamethasone-induced (0.25uM) were established insulin resistance and L6 cells with high-glucose (30mM) and dexamethasone-induced (0.25uM) were established insulin resistance.

  18. Grain-Boundary Resistance in Copper Interconnects: From an Atomistic Model to a Neural Network

    Science.gov (United States)

    Valencia, Daniel; Wilson, Evan; Jiang, Zhengping; Valencia-Zapata, Gustavo A.; Wang, Kuang-Chung; Klimeck, Gerhard; Povolotskyi, Michael

    2018-04-01

    Orientation effects on the specific resistance of copper grain boundaries are studied systematically with two different atomistic tight-binding methods. A methodology is developed to model the specific resistance of grain boundaries in the ballistic limit using the embedded atom model, tight- binding methods, and nonequilibrium Green's functions. The methodology is validated against first-principles calculations for thin films with a single coincident grain boundary, with 6.4% deviation in the specific resistance. A statistical ensemble of 600 large, random structures with grains is studied. For structures with three grains, it is found that the distribution of specific resistances is close to normal. Finally, a compact model for grain-boundary-specific resistance is constructed based on a neural network.

  19. Testing a Model of Resistance to Peer Pressure among Mexican-Origin Adolescents

    Science.gov (United States)

    Bamaca, Mayra Y.; Umana-Taylor, Adriana J.

    2006-01-01

    This study examined the factors associated with resistance to peer pressure toward antisocial behaviors among a sample of Mexican-origin adolescents (n=564) living in a large Southwestern city in the U.S. A model examining the influence of generational status, emotional autonomy from parents, and self-esteem on resistance to peer pressure was…

  20. Resistance and support to electronic government, building a model of innovation

    NARCIS (Netherlands)

    Ebbers, Wolfgang E.; van Dijk, Johannes A.G.M.

    2007-01-01

    In several countries forces that resist e-government innovations apparently override those that support them. A first step is taken in order to identify organizational processes of resistance and support to e-government innovations. A multi-disciplinary and non-linear innovation model is proposed

  1. Chatty Mitochondria: Keeping Balance in Cellular Protein Homeostasis.

    Science.gov (United States)

    Topf, Ulrike; Wrobel, Lidia; Chacinska, Agnieszka

    2016-08-01

    Mitochondria are multifunctional cellular organelles that host many biochemical pathways including oxidative phosphorylation (OXPHOS). Defective mitochondria pose a threat to cellular homeostasis and compensatory responses exist to curtail the source of stress and/or its consequences. The mitochondrial proteome comprises proteins encoded by the nuclear and mitochondrial genomes. Disturbances in protein homeostasis may originate from mistargeting of nuclear encoded mitochondrial proteins. Defective protein import and accumulation of mistargeted proteins leads to stress that triggers translation alterations and proteasomal activation. These cytosolic pathways are complementary to the mitochondrial unfolded protein response (UPRmt) that aims to increase the capacity of protein quality control mechanisms inside mitochondria. They constitute putative targets for interventions aimed at increasing the fitness, stress resistance, and longevity of cells and organisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Electrical Resistance Based Damage Modeling of Multifunctional Carbon Fiber Reinforced Polymer Matrix Composites

    Science.gov (United States)

    Hart, Robert James

    In the current thesis, the 4-probe electrical resistance of carbon fiber-reinforced polymer (CFRP) composites is utilized as a metric for sensing low-velocity impact damage. A robust method has been developed for recovering the directionally dependent electrical resistivities using an experimental line-type 4-probe resistance method. Next, the concept of effective conducting thickness was uniquely applied in the development of a brand new point-type 4-probe method for applications with electrically anisotropic materials. An extensive experimental study was completed to characterize the 4-probe electrical resistance of CFRP specimens using both the traditional line-type and new point-type methods. Leveraging the concept of effective conducting thickness, a novel method was developed for building 4-probe electrical finite element (FE) models in COMSOL. The electrical models were validated against experimental resistance measurements and the FE models demonstrated predictive capabilities when applied to CFRP specimens with varying thickness and layup. These new models demonstrated a significant improvement in accuracy compared to previous literature and could provide a framework for future advancements in FE modeling of electrically anisotropic materials. FE models were then developed in ABAQUS for evaluating the influence of prescribed localized damage on the 4-probe resistance. Experimental data was compiled on the impact response of various CFRP laminates, and was used in the development of quasi- static FE models for predicting presence of impact-induced delamination. The simulation-based delamination predictions were then integrated into the electrical FE models for the purpose of studying the influence of realistic damage patterns on electrical resistance. When the size of the delamination damage was moderate compared to the electrode spacing, the electrical resistance increased by less than 1% due to the delamination damage. However, for a specimen with large

  3. Verification, Validation and Credibility Assessment of a Computational Model of the Advanced Resistive Exercise Device (ARED)

    Science.gov (United States)

    Werner, C. R.; Humphreys, B. T.; Mulugeta, L.

    2014-01-01

    The Advanced Resistive Exercise Device (ARED) is the resistive exercise device used by astronauts on the International Space Station (ISS) to mitigate bone loss and muscle atrophy due to extended exposure to microgravity (micro g). The Digital Astronaut Project (DAP) has developed a multi-body dynamics model of biomechanics models for use in spaceflight exercise physiology research and operations. In an effort to advance model maturity and credibility of the ARED model, the DAP performed verification, validation and credibility (VV and C) assessment of the analyses of the model in accordance to NASA-STD-7009 'Standards for Models and Simulations'.

  4. Alterations in Adiposity and Glucose Homeostasis in Adult Gasp-1 Overexpressing Mice

    Directory of Open Access Journals (Sweden)

    Luce Périè

    2017-12-01

    Full Text Available Background/Aims: Myostatin is known as a powerful negative regulator of muscle growth playing a key role in skeletal muscle homeostasis. Recent studies revealed that myostatin-deficient mice lead to an increase of insulin sensitivity, a decrease of adiposity and a resistance to obesity, showing that myostatin can also impact on metabolism. Thus, myostatin appeared as a potential therapeutic target to treat insulin resistance. Methods: We generated transgenic mice overexpressing Gasp-1, a myostatin inhibitor. Results: Surprisingly, we found that these mice gained weight with age due to an increase in fat mass associated with ectopic fat accumulation. In addition, these mice developed an adipocyte hypertrophy, hyperglycemia, hyperinsulinemia, muscle and hepatic insulin resistance. Understanding the molecular networks controlling this insulin resistance responsiveness in overexpressing Gasp-1 mice is essential. Molecular analyses revealed a deregulation of adipokines and muscle cytokines expression, but also an increase in plasma myostatin levels. The increase in myostatin bioactivity by a positive feedback mechanism in the Tg(Gasp-1 transgenic mice could lead to this combination of phenotypes. Conclusion: Altogether, these data suggested that overexpressing Gasp-1 mice develop most of the symptoms associated with metabolic syndrome and could be a relevant model for the study of obesity or type 2 diabetes.

  5. Computational methods for structural load and resistance modeling

    Science.gov (United States)

    Thacker, B. H.; Millwater, H. R.; Harren, S. V.

    1991-01-01

    An automated capability for computing structural reliability considering uncertainties in both load and resistance variables is presented. The computations are carried out using an automated Advanced Mean Value iteration algorithm (AMV +) with performance functions involving load and resistance variables obtained by both explicit and implicit methods. A complete description of the procedures used is given as well as several illustrative examples, verified by Monte Carlo Analysis. In particular, the computational methods described in the paper are shown to be quite accurate and efficient for a material nonlinear structure considering material damage as a function of several primitive random variables. The results show clearly the effectiveness of the algorithms for computing the reliability of large-scale structural systems with a maximum number of resolutions.

  6. Model development for quantitative evaluation of proliferation resistance of nuclear fuel cycles

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Won Il; Kim, Ho Dong; Yang, Myung Seung

    2000-07-01

    This study addresses the quantitative evaluation of the proliferation resistance which is important factor of the alternative nuclear fuel cycle system. In this study, model was developed to quantitatively evaluate the proliferation resistance of the nuclear fuel cycles. The proposed models were then applied to Korean environment as a sample study to provide better references for the determination of future nuclear fuel cycle system in Korea. In order to quantify the proliferation resistance of the nuclear fuel cycle, the proliferation resistance index was defined in imitation of an electrical circuit with an electromotive force and various electrical resistance components. The analysis on the proliferation resistance of nuclear fuel cycles has shown that the resistance index as defined herein can be used as an international measure of the relative risk of the nuclear proliferation if the motivation index is appropriately defined. It has also shown that the proposed model can include political issues as well as technical ones relevant to the proliferation resistance, and consider all facilities and activities in a specific nuclear fuel cycle (from mining to disposal). In addition, sensitivity analyses on the sample study indicate that the direct disposal option in a country with high nuclear propensity may give rise to a high risk of the nuclear proliferation than the reprocessing option in a country with low nuclear propensity.

  7. Model development for quantitative evaluation of proliferation resistance of nuclear fuel cycles

    International Nuclear Information System (INIS)

    Ko, Won Il; Kim, Ho Dong; Yang, Myung Seung

    2000-07-01

    This study addresses the quantitative evaluation of the proliferation resistance which is important factor of the alternative nuclear fuel cycle system. In this study, model was developed to quantitatively evaluate the proliferation resistance of the nuclear fuel cycles. The proposed models were then applied to Korean environment as a sample study to provide better references for the determination of future nuclear fuel cycle system in Korea. In order to quantify the proliferation resistance of the nuclear fuel cycle, the proliferation resistance index was defined in imitation of an electrical circuit with an electromotive force and various electrical resistance components. The analysis on the proliferation resistance of nuclear fuel cycles has shown that the resistance index as defined herein can be used as an international measure of the relative risk of the nuclear proliferation if the motivation index is appropriately defined. It has also shown that the proposed model can include political issues as well as technical ones relevant to the proliferation resistance, and consider all facilities and activities in a specific nuclear fuel cycle (from mining to disposal). In addition, sensitivity analyses on the sample study indicate that the direct disposal option in a country with high nuclear propensity may give rise to a high risk of the nuclear proliferation than the reprocessing option in a country with low nuclear propensity

  8. The effect of acetaminophen on ubiquitin homeostasis in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Angelina Huseinovic

    Full Text Available Acetaminophen (APAP, although considered a safe drug, is one of the major causes of acute liver failure by overdose, and therapeutic chronic use can cause serious health problems. Although the reactive APAP metabolite N-acetyl-p-benzoquinoneimine (NAPQI is clearly linked to liver toxicity, toxicity of APAP is also found without drug metabolism of APAP to NAPQI. To get more insight into mechanisms of APAP toxicity, a genome-wide screen in Saccharomyces cerevisiae for APAP-resistant deletion strains was performed. In this screen we identified genes related to the DNA damage response. Next, we investigated the link between genotype and APAP-induced toxicity or resistance by performing a more detailed screen with a library containing mutants of 1522 genes related to nuclear processes, like DNA repair and chromatin remodelling. We identified 233 strains that had an altered growth rate relative to wild type, of which 107 showed increased resistance to APAP and 126 showed increased sensitivity. Gene Ontology analysis identified ubiquitin homeostasis, regulation of transcription of RNA polymerase II genes, and the mitochondria-to-nucleus signalling pathway to be associated with APAP resistance, while histone exchange and modification, and vesicular transport were connected to APAP sensitivity. Indeed, we observed a link between ubiquitin levels and APAP resistance, whereby ubiquitin deficiency conferred resistance to APAP toxicity while ubiquitin overexpression resulted in sensitivity. The toxicity profile of various chemicals, APAP, and its positional isomer AMAP on a series of deletion strains with ubiquitin deficiency showed a unique resistance pattern for APAP. Furthermore, exposure to APAP increased the level of free ubiquitin and influenced the ubiquitination of proteins. Together, these results uncover a role for ubiquitin homeostasis in APAP-induced toxicity.

  9. Nutrition and protein energy homeostasis in elderly.

    Science.gov (United States)

    Boirie, Yves; Morio, Béatrice; Caumon, Elodie; Cano, Noël J

    2014-01-01

    Protein-energy homeostasis is a major determinant of healthy aging. Inadequate nutritional intakes and physical activity, together with endocrine disturbances are associated with of sarcopenia and frailty. Guidelines from scientific societies mainly address the quantitative aspects of protein and energy nutrition in elderly. Besides these quantitative aspects of protein load, perspective strategies to promote muscle protein synthesis and prevent sarcopenia include pulse feeding, the use of fast proteins and the addition of leucine or citrulline to dietary protein. An integrated management of sarcopenia, taking into account the determinants of muscle wasting, i.e. nutrition, physical activity, anabolic factors such as androgens, vitamin D and n-3 polyunsaturated fatty acids status, needs to be tested in the prevention and treatment of sarcopenia. The importance of physical activity, specifically resistance training, is emphasized, not only in order to facilitate muscle protein anabolism but also to increase appetite and food intake in elderly people at risk of malnutrition. According to present data, healthy nutrition in elderly should respect the guidelines for protein and energy requirement, privilege a Mediterranean way of alimentation, and be associated with a regular physical activity. Further issues relate to the identification of the genetics determinants of protein energy wasting in elderly. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. CHF: circulatory homeostasis gone awry.

    Science.gov (United States)

    Weber, Karl T; Burlew, Brad S; Davis, Richard C; Newman, Kevin P; D'Cruz, Ivan A; Hawkins, Ralph G; Wall, Barry M; Parker, Robert B

    2002-01-01

    The role of the renin-angiotensin-aldosterone system (RAAS) is integral to salt and water retention, particularly by the kidneys. Over time, positive sodium balance leads first to intra- and then to extravascular volume expansion, with subsequent symptomatic heart failure. This report examines the role of the RAAS in regulating a less well recognized component essential to circulatory homeostasis--central blood volume. The regulation of central blood volume draws on integrative cardiorenal physiology and a key role played by the RAAS in its regulation. In presenting insights into the role of the RAAS in regulating central blood volume, this review also addresses other sodium-retaining states with a predisposition to edema formation, such as cirrhosis and nephrosis. (c)2002 CHF, Inc

  11. [Bone homeostasis and Mechano biology.

    Science.gov (United States)

    Nakashima, Tomoki

    The weight-bearing exercises help to build bones and to maintain them strength. Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication between bone component cells such as osteoclasts, osteoblasts and osteocytes. An imbalance of this process is often linked to various bone diseases. During bone remodeling, resorption by osteoclasts precedes bone formation by osteoblasts. Based on the osteocyte location within the bone matrix and the cellular morphology, it is proposed that osteocytes potentially contribute to the regulation of bone remodeling in response to mechanical and endocrine stimuli.

  12. Phloretin Prevents High-Fat Diet-Induced Obesity and Improves Metabolic Homeostasis.

    Science.gov (United States)

    Alsanea, Sary; Gao, Mingming; Liu, Dexi

    2017-05-01

    Reactive oxygen species generated as a by-product in metabolism play a central role in the development of obesity and obesity-related metabolic complications. The objective of the current study is to explore the possibility to block obesity and improve metabolic homeostasis via phloretin, a natural antioxidant product from apple tree leaves and Manchurian apricot. Both preventive and therapeutic activities of phloretin were assessed using a high-fat diet-induced obesity mouse model. Phloretin was injected intraperitoneally twice weekly into regular and obese mice fed a high-fat diet. The effects of phloretin treatment on body weight and composition, fat content in the liver, glucose and lipid metabolism, and insulin resistance were monitored and compared to the control animals. Phloretin treatment significantly blocks high-fat diet-induced weight gain but did not induce weight loss in obese animals. Phloretin improved glucose homeostasis and insulin sensitivity and alleviated hepatic lipid accumulation. RT-PCR analysis showed that phloretin treatment suppresses expression of macrophage markers (F4/80 and Cd68) and pro-inflammatory genes (Mcp-1 and Ccr2) and enhances adiponectin gene expression in white adipose tissue. In addition, phloretin treatment elevated the expression of fatty acid oxidation genes such as carnitine palmitoyltransferase 1a and 1b (Cpt1a and Cpt1b) and reduced expression of monocyte chemoattractant protein-1 (Mcp-1), de novo lipogenesis transcriptional factor peroxisome proliferator-activated receptor-γ 2 (Pparγ2), and its target monoacylglycerol O-acyltransferase (Mgat-1) genes. These results provide direct evidence to support a possible use of phloretin for mitigation of obesity and maintenance of metabolic homeostasis.

  13. The practical use of resistance modelling to interpret the gas separation properties of hollow fiber membranes

    International Nuclear Information System (INIS)

    Ahmad Fauzi Ismail; Shilton, S.J.

    2000-01-01

    A simple resistance modelling methodology is presented for gas transport through asymmetric polymeric membranes. The methodology allows fine structural properties such as active layer thickness and surface porosity, to be determined from experimental gas permeation data. This paper, which could be regarded as a practical guide, shows that resistance modeling, if accompanied by realistic working assumptions, need not be difficult and can provide a valuable insight into the relationships between the membrane fabrication conditions and performance of gas separation membranes. (Author)

  14. Modeling the electrical resistance of gold film conductors on uniaxially stretched elastomeric substrates

    Science.gov (United States)

    Cao, Wenzhe; Görrn, Patrick; Wagner, Sigurd

    2011-05-01

    The electrical resistance of gold film conductors on polydimethyl siloxane substrates at stages of uniaxial stretching is measured and modeled. The surface area of a gold conductor is assumed constant during stretching so that the exposed substrate takes up all strain. Sheet resistances are calculated from frames of scanning electron micrographs by numerically solving for the electrical potentials of all pixels in a frame. These sheet resistances agree sufficiently well with values measured on the same conductors to give credence to the model of a stretchable network of gold links defined by microcracks.

  15. Sleep duration and sleep quality are associated differently with alterations of glucose homeostasis.

    Science.gov (United States)

    Byberg, S; Hansen, A-L S; Christensen, D L; Vistisen, D; Aadahl, M; Linneberg, A; Witte, D R

    2012-09-01

    Studies suggest that inadequate sleep duration and poor sleep quality increase the risk of impaired glucose regulation and diabetes. However, associations with specific markers of glucose homeostasis are less well explained. The objective of this study was to explore possible associations of sleep duration and sleep quality with markers of glucose homeostasis and glucose tolerance status in a healthy population-based study sample. The study comprised 771 participants from the Danish, population-based cross-sectional 'Health2008' study. Sleep duration and sleep quality were measured by self-report. Markers of glucose homeostasis were derived from a 3-point oral glucose tolerance test and included fasting plasma glucose, 2-h plasma glucose, HbA(1c), two measures of insulin sensitivity (the insulin sensitivity index(0,120) and homeostasis model assessment of insulin sensitivity), the homeostasis model assessment of β-cell function and glucose tolerance status. Associations of sleep duration and sleep quality with markers of glucose homeostasis and tolerance were analysed by multiple linear and logistic regression. A 1-h increment in sleep duration was associated with a 0.3 mmol/mol (0.3%) decrement in HbA(1c) and a 25% reduction in the risk of having impaired glucose regulation. Further, a 1-point increment in sleep quality was associated with a 2% increase in both the insulin sensitivity index(0,120) and homeostasis model assessment of insulin sensitivity, as well as a 1% decrease in homeostasis model assessment of β-cell function. In the present study, shorter sleep duration was mainly associated with later alterations in glucose homeostasis, whereas poorer sleep quality was mainly associated with earlier alterations in glucose homeostasis. Thus, adopting healthy sleep habits may benefit glucose metabolism in healthy populations. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  16. Regulation of glucose homeostasis by KSR1 and MARK2.

    Directory of Open Access Journals (Sweden)

    Paula J Klutho

    Full Text Available Protein scaffolds control the intensity and duration of signaling and dictate the specificity of signaling through MAP kinase pathways. KSR1 is a molecular scaffold of the Raf/MEK/ERK MAP kinase cascade that regulates the intensity and duration of ERK activation. Relative to wild-type mice, ksr1⁻/⁻ mice are modestly glucose intolerant, but show a normal response to exogenous insulin. However, ksr1⁻/⁻ mice also demonstrate a three-fold increase in serum insulin levels in response to a glucose challenge, suggesting a role for KSR1 in insulin secretion. The kinase MARK2 is closely related to C-TAK1, a known regulator of KSR1. Mice lacking MARK2 have an increased rate of glucose disposal in response to exogenous insulin, increased glucose tolerance, and are resistant to diet-induced obesity. mark2⁻/⁻ksr1⁻/⁻ (DKO mice were compared to wild type, mark2⁻/⁻, and ksr1⁻/⁻ mice for their ability to regulate glucose homeostasis. Here we show that disruption of KSR1 in mark2⁻/⁻ mice reverses the increased sensitivity to exogenous insulin resulting from MARK2 deletion. DKO mice respond to exogenous insulin similarly to wild type and ksr1⁻/⁻ mice. These data suggest a model whereby MARK2 negatively regulates insulin sensitivity in peripheral tissue through inhibition of KSR1. Consistent with this model, we found that MARK2 binds and phosphorylates KSR1 on Ser392. Phosphorylation of Ser392 is a critical regulator of KSR1 stability, subcellular location, and ERK activation. These data reveal an unexpected role for the molecular scaffold KSR1 in insulin-regulated glucose metabolism.

  17. Dietary Patterns, Insulin Resistance, and Incidence of Type 2 Diabetes in the Whitehall II Study

    OpenAIRE

    McNaughton, Sarah A.; Mishra, Gita D.; Brunner, Eric J.

    2008-01-01

    OBJECTIVE?The aim of this study was to identify a dietary pattern associated with insulin resistance and investigate whether this pattern was prospectively associated with type 2 diabetes. RESEARCH DESIGN AND METHODS?Analysis was based on 7,339 participants of the Whitehall II study. Dietary intake was measured using a 127-item food frequency questionnaire. We used the reduced rank regression method to determine dietary patterns using the homeostasis model assessment of insulin resistance as ...

  18. Association of insulin resistance and coronary artery remodeling: an intravascular ultrasound study

    OpenAIRE

    Kim, Sang-Hoon; Moon, Jae-Youn; Lim, Yeong Min; Kim, Kyung Ho; Yang, Woo-In; Sung, Jung-Hoon; Yoo, Seung Min; Kim, In Jai; Lim, Sang-Wook; Cha, Dong-Hun; Cho, Seung-Yun

    2015-01-01

    Background There are few studies that investigated the correlation between insulin resistance (IR) and the coronary artery remodeling. The aim of the study is to investigate the association of IR measured by homeostasis model assessment of insulin resistance (HOMA-IR) and coronary artery remodeling evaluated by intravascular ultrasound (IVUS). Methods A total of 298 consecutive patients who received percutaneous coronary interventions under IVUS guidance were retrospectively enrolled. The val...

  19. Severely altered guanidino compound levels, disturbed body weight homeostasis and impaired fertility in a mouse model of guanidinoacetate N-methyltransferase (GAMT) deficiency.

    NARCIS (Netherlands)

    Schmidt, A.; Marescau, B.; Boehm, E.A.; Renema, W.K.J.; Peco, R.; Das, A.; Steinfeld, R.; Chan, S.; Wallis, J.; Davidoff, M.; Ullrich, K.; Waldschutz, R.; Heerschap, A.; Deyn, P.P. de; Neubauer, S.; Isbrandt, D.

    2004-01-01

    We generated a knockout mouse model for guanidinoacetate N-methyltransferase (GAMT) deficiency (MIM 601240), the first discovered human creatine deficiency syndrome, by gene targeting in embryonic stem cells. Disruption of the open reading frame of the murine GAMT gene in the first exon resulted in

  20. Changes in action potentials and intracellular ionic homeostasis in a ventricular cell model related to a persistent sodium current in SCN5A mutations underlying LQT3

    Czech Academy of Sciences Publication Activity Database

    Christé, G.; Chahine, M.; Chevalier, P.; Pásek, Michal

    2008-01-01

    Roč. 96, - (2008), s. 281-293 ISSN 0079-6107 Institutional research plan: CEZ:AV0Z20760514 Keywords : cardiac cell * SCN5A mutation * Long QT syndrome * quantitative modelling Subject RIV: BO - Biophysics Impact factor: 6.388, year: 2008

  1. Robust stator resistance identification of an IM drive using model reference adaptive system

    International Nuclear Information System (INIS)

    Madadi Kojabadi, Hossein; Abarzadeh, Mostafa; Aghaei Farouji, Said

    2013-01-01

    Highlights: ► We estimate the stator resistance and rotor speed of the IM. ► We proposed a new quantity to estimate the speed and stator resistance of IM. ► The proposed algorithm is robust to rotor resistance variations. ► We estimate the IM speed and stator resistance simultaneously to avoid speed error. - Abstract: Model reference adaptive system (MRAS) based robust stator resistance estimator for sensorless induction motor (IM) drive is proposed. The MRAS is formed with a semi-active power quantity. The proposed identification method can be achieved with on-line tuning of the stator resistance with robustness against rotor resistance variations. Stable and efficient estimation of IM speed at low region will be guaranteed by simultaneous identification of IM speed and stator resistance. The stability of proposed stator resistance estimator is checked through Popov’s hyperstability theorem. Simulation and experimental results are given to highlight the feasibility, the simplicity, and the robustness of the proposed method.

  2. Resistive RAM: Simulation and Modeling for Reliable Design

    OpenAIRE

    García Redondo, Fernando

    2017-01-01

    Las tecnologías emergentes de resistencia variable o resistencia-commutativa, Resistive-Switching (RS) technologies, están consideradas como una de las alternativas más prometedoras para el futuro de aplicaciones electrónicas de almacenamiento y sistemas de computación. Características tales como su no-volatilidad, alta densidad de integración, bajo consumo, así como su compatibilidad con circuitos CMOS tradicionales, despierta el interés de fabricantes de dispositivos, diseñadores de circuit...

  3. Use of mathematical modelling to assess the impact of vaccines on antibiotic resistance.

    Science.gov (United States)

    Atkins, Katherine E; Lafferty, Erin I; Deeny, Sarah R; Davies, Nicholas G; Robotham, Julie V; Jit, Mark

    2017-11-13

    Antibiotic resistance is a major global threat to the provision of safe and effective health care. To control antibiotic resistance, vaccines have been proposed as an essential intervention, complementing improvements in diagnostic testing, antibiotic stewardship, and drug pipelines. The decision to introduce or amend vaccination programmes is routinely based on mathematical modelling. However, few mathematical models address the impact of vaccination on antibiotic resistance. We reviewed the literature using PubMed to identify all studies that used an original mathematical model to quantify the impact of a vaccine on antibiotic resistance transmission within a human population. We reviewed the models from the resulting studies in the context of a new framework to elucidate the pathways through which vaccination might impact antibiotic resistance. We identified eight mathematical modelling studies; the state of the literature highlighted important gaps in our understanding. Notably, studies are limited in the range of pathways represented, their geographical scope, and the vaccine-pathogen combinations assessed. Furthermore, to translate model predictions into public health decision making, more work is needed to understand how model structure and parameterisation affects model predictions and how to embed these predictions within economic frameworks. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. A model of directional selection applied to the evolution of drug resistance in HIV-1.

    Science.gov (United States)

    Seoighe, Cathal; Ketwaroo, Farahnaz; Pillay, Visva; Scheffler, Konrad; Wood, Natasha; Duffet, Rodger; Zvelebil, Marketa; Martinson, Neil; McIntyre, James; Morris, Lynn; Hide, Winston

    2007-04-01

    Understanding how pathogens acquire resistance to drugs is important for the design of treatment strategies, particularly for rapidly evolving viruses such as HIV-1. Drug treatment can exert strong selective pressures and sites within targeted genes that confer resistance frequently evolve far more rapidly than the neutral rate. Rapid evolution at sites that confer resistance to drugs can be used to help elucidate the mechanisms of evolution of drug resistance and to discover or corroborate novel resistance mutations. We have implemented standard maximum likelihood methods that are used to detect diversifying selection and adapted them for use with serially sampled reverse transcriptase (RT) coding sequences isolated from a group of 300 HIV-1 subtype C-infected women before and after single-dose nevirapine (sdNVP) to prevent mother-to-child transmission. We have also extended the standard models of codon evolution for application to the detection of directional selection. Through simulation, we show that the directional selection model can provide a substantial improvement in sensitivity over models of diversifying selection. Five of the sites within the RT gene that are known to harbor mutations that confer resistance to nevirapine (NVP) strongly supported the directional selection model. There was no evidence that other mutations that are known to confer NVP resistance were selected in this cohort. The directional selection model, applied to serially sampled sequences, also had more power than the diversifying selection model to detect selection resulting from factors other than drug resistance. Because inference of selection from serial samples is unlikely to be adversely affected by recombination, the methods we describe may have general applicability to the analysis of positive selection affecting recombining coding sequences when serially sampled data are available.

  5. Hot electron transport modelling in fast ignition relevant targets with non-Spitzer resistivity

    Energy Technology Data Exchange (ETDEWEB)

    Chapman, D A; Hoarty, D J; Swatton, D J R [Plasma Physics Department, AWE, Aldermaston, Reading, Berkshire, RG7 4PR (United Kingdom); Hughes, S J, E-mail: david.chapman@awe.co.u [Computational Physics Group, AWE, Aldermaston, Reading, Berkshire, RG7 4PR (United Kingdom)

    2010-08-01

    The simple Lee-More model for electrical resistivity is implemented in the hybrid fast electron transport code THOR. The model is shown to reproduce experimental data across a wide range of temperatures using a small number of parameters. The effect of this model on the heating of simple Al targets by a short-pulse laser is studied and compared to the predictions of the classical Spitzer-Haerm resistivity. The model is then used in simulations of hot electron transport experiments using buried layer targets.

  6. A carrier transport model in the high-resistance state of lead-methylamine iodide-based resistive memory devices

    Directory of Open Access Journals (Sweden)

    Yongwoo Kwon

    2017-08-01

    Full Text Available Methylamine lead iodide (CH3NH3PbI3, which has recently been in the spotlight as a solar cell material, has also recently shown promise for use as an active material in resistive memory cells with ultralow operation voltages, good transparencies, and flexibilities. The material’s defects, which govern its properties, differ vastly depending on the fabrication process. However, the defect chemistry is not yet entirely understood. We have therefore established a macroscopic transport model with defect-related model parameters, such as trap density, trap energy level, and Fermi level, in order to estimate these parameters for fabricated samples based on their electrical data. Our model will serve as an efficient way to analyze the properties of the active material.

  7. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on liver phosphoenolpyruvate carboxykinase (PEPCK) activity, glucose homeostasis and plasma amino acid concentrations in the most TCDD-susceptible and the most TCDD-resistant rat strains

    Energy Technology Data Exchange (ETDEWEB)

    Viluksela, M.; Pohjanvirta, R.; Tuomisto, J.T.; Tuomisto, J. (National Public Health Inst., Laboratory of Toxicology, Kuopio (Finland)); Unkila, M. (Department of Pharmacology and Toxicology, Univ. of Kuopio (Finland)); Stahl, B.U.; Rozman, K.K. (Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States) Section of Environmental Toxicology, GSF-Institut fuer Toxikologie, Neuherberg (Germany))

    1999-08-01

    Reduced gluconeogenesis due to decreased activity of key gluconeogenic enzymes in liver, together with feed refusal, has been suggested to play an important role in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced lethality in rats. This study was carried out to further analyse the toxicological significance of reduced gluconeogenesis by comparing dose-responses and time-courses of effects of TCDD on the activity of phosphoenolpyruvate carboxykinase (PEPCK) in liver, liver glycogen concentration as well as plasma concentrations of glucose and amino acids in both genders of TCDD-sensitive Long-Evans (L-E) rats and TCDD-resistant Han/Wistar (H/W) rats. A dose-dependent decrease in PEPCK activity was observed in H/W rats, but in L-E rats the activity was not decreased. However, TCDD impaired the strong increase in liver PEPCK activity observed in pair-fed controls of the L-E strain. Liver glycogen concentrations were severely decreased in L-E rats and moderately in H/W rats. This effect seems to be secondary to reduced feed intake, since a similar decrease was seen in pair-fed controls. Decreases in plasma glucose concentrations were also more profound in L-E rats than in H/W rats, but pair-fed controls were generally less affected. Circulating concentrations of amino acids were markedly increased in TCDD-treated L-E rats, which is likely to reflect increased mobilization of amino acids and their decreased metabolism in liver. Reduction of liver PEPCK activity cannot account for the sensitivity difference of these two strains of rats in terms of mortality. Nevertheless, the response of both strains of TCDD-treated rats regarding gluconeogenesis is different from that seen in pair-fed controls and suggesting that impairment of this pathway contributes to the development of the wasting syndrome. (orig.) With 7 figs., 2 tabs., 47 refs.

  8. Influence of multidrug resistance on 18F-FCH cellular uptake in a glioblastoma model

    International Nuclear Information System (INIS)

    Vanpouille, Claire; Jeune, Nathalie le; Clotagatide, Anthony; Dubois, Francis; Kryza, David; Janier, Marc; Perek, Nathalie

    2009-01-01

    Multidrug resistance, aggressiveness and accelerated choline metabolism are hallmarks of malignancy and have motivated the development of new PET tracers like 18 F-FCH, an analogue of choline. Our aim was to study the relationship of multidrug resistance of cultured glioma cell lines and 18 F-FCH tracer uptake. We used an in vitro multidrug-resistant (MDR) glioma model composed of sensitive parental U87MG and derived resistant cells U87MG-CIS and U87MG-DOX. Aggressiveness, choline metabolism and transport were studied, particularly the expression of choline kinase (CK) and high-affinity choline transporter (CHT1). FCH transport studies were assessed in our glioblastoma model. As expected, the resistant cell lines express P-glycoprotein (Pgp), multidrug resistance-associated protein isoform 1 (MRP1) and elevated glutathione (GSH) content and are also more mobile and more invasive than the sensitive U87MG cells. Our results show an overexpression of CK and CHT1 in the resistant cell lines compared to the sensitive cell lines. We found an increased uptake of FCH (in % of uptake per 200,000 cells) in the resistant cells compared to the sensitive ones (U87MG: 0.89±0.14; U87MG-CIS: 1.27±0.18; U87MG-DOX: 1.33±0.13) in line with accelerated choline metabolism and aggressive phenotype. FCH uptake is not influenced by the two ATP-dependant efflux pumps: Pgp and MRP1. FCH would be an interesting probe for glioma imaging which would not be effluxed from the resistant cells by the classic MDR ABC transporters. Our results clearly show that FCH uptake reflects accelerated choline metabolism and is related to tumour aggressiveness and drug resistance. (orig.)

  9. Lifespan extension by preserving proliferative homeostasis in Drosophila.

    Directory of Open Access Journals (Sweden)

    Benoît Biteau

    2010-10-01

    Full Text Available Regenerative processes are critical to maintain tissue homeostasis in high-turnover tissues. At the same time, proliferation of stem and progenitor cells has to be carefully controlled to prevent hyper-proliferative diseases. Mechanisms that ensure this balance, thus promoting proliferative homeostasis, are expected to be critical for longevity in metazoans. The intestinal epithelium of Drosophila provides an accessible model in which to test this prediction. In aging flies, the intestinal epithelium degenerates due to over-proliferation of intestinal stem cells (ISCs and mis-differentiation of ISC daughter cells, resulting in intestinal dysplasia. Here we show that conditions that impair tissue renewal lead to lifespan shortening, whereas genetic manipulations that improve proliferative homeostasis extend lifespan. These include reduced Insulin/IGF or Jun-N-terminal Kinase (JNK signaling activities, as well as over-expression of stress-protective genes in somatic stem cell lineages. Interestingly, proliferative activity in aging intestinal epithelia correlates with longevity over a range of genotypes, with maximal lifespan when intestinal proliferation is reduced but not completely inhibited. Our results highlight the importance of the balance between regenerative processes and strategies to prevent hyperproliferative disorders and demonstrate that promoting proliferative homeostasis in aging metazoans is a viable strategy to extend lifespan.

  10. A Simple Model of Tetracycline Antibiotic Resistance in the Aquatic Environment (with Application to the Poudre River

    Directory of Open Access Journals (Sweden)

    Sarah Sanchez

    2011-02-01

    Full Text Available Antibiotic resistance is a major concern, yet it is unclear what causes the relatively high densities of resistant bacteria in the anthropogenically impacted environment. There are various possible scenarios (hypotheses: (A Input of resistant bacteria from wastewater and agricultural sources is significant, but they do not grow in the environment; (B Input of resistant bacteria is negligible, but the resistant bacteria (exogenous or endogenous grow due to the selection pressure of the antibiotic; (C Exogenous bacteria transfer the resistance to the endogenous bacteria and those grow. This paper presents a simple mechanistic model of tetracycline resistance in the aquatic environment. It includes state variables for tetracyclines, susceptible and resistant bacteria, and particulate and dissolved organic matter in the water column and sediment bed. The antibiotic partitions between freely dissolved, dissolved organic matter (DOM-bound and solids-bound phases, and decays. Bacteria growth is limited by DOM, inhibited by the antibiotic (susceptible bacteria only and lower due to the metabolic cost of carrying the resistance (resistant bacteria only. Resistant bacteria can transfer resistance to the susceptible bacteria (conjugation and lose the resistance (segregation. The model is applied to the Poudre River and can reproduce the major observed (literature data patterns of antibiotic concentration and resistance. The model suggests observed densities of resistant bacteria in the sediment bed cannot be explained by input (scenario A, but require growth (scenarios B or C.

  11. Simple and accurate model for voltage-dependent resistance of metallic carbon nanotube interconnects: An ab initio study

    International Nuclear Information System (INIS)

    Yamacli, Serhan; Avci, Mutlu

    2009-01-01

    In this work, development of a voltage dependent resistance model for metallic carbon nanotubes is aimed. Firstly, the resistance of metallic carbon nanotube interconnects are obtained from ab initio simulations and then the voltage dependence of the resistance is modeled through regression. Self-consistent non-equilibrium Green's function formalism combined with density functional theory is used for calculating the voltage dependent resistance of metallic carbon nanotubes. It is shown that voltage dependent resistances of carbon nanotubes can be accurately modeled as a polynomial function which enables rapid integration of carbon nanotube interconnect models into electronic design automation tools.

  12. Protein synthesis controls phosphate homeostasis.

    Science.gov (United States)

    Pontes, Mauricio H; Groisman, Eduardo A

    2018-01-01

    Phosphorus is an essential element assimilated largely as orthophosphate (Pi). Cells respond to Pi starvation by importing Pi from their surroundings. We now report that impaired protein synthesis alone triggers a Pi starvation response even when Pi is plentiful in the extracellular milieu. In the bacterium Salmonella enterica serovar Typhimurium , this response entails phosphorylation of the regulatory protein PhoB and transcription of PhoB-dependent Pi transporter genes and is eliminated upon stimulation of adenosine triphosphate (ATP) hydrolysis. When protein synthesis is impaired due to low cytoplasmic magnesium (Mg 2+ ), Salmonella triggers the Pi starvation response because ribosomes are destabilized, which reduces ATP consumption and thus free cytoplasmic Pi. This response is transient because low cytoplasmic Mg 2+ promotes an uptake in Mg 2+ and a decrease in ATP levels, which stabilizes ribosomes, resulting in ATP consumption and Pi increase, thus ending the response. Notably, pharmacological inhibition of protein synthesis also elicited a Pi starvation response in the bacterium Escherichia coli and the yeast Saccharomyces cerevisiae Our findings identify a regulatory connection between protein synthesis and Pi homeostasis that is widespread in nature. © 2018 Pontes and Groisman; Published by Cold Spring Harbor Laboratory Press.

  13. [Matematical modeling of antibiotic resistance: perspectives from a meta-analysys].

    Science.gov (United States)

    Fresnadillo-Martínez, M J; García-Sánchez, E; García-Merino, E; Martín-Del-Rey, A; Rodríguez-Encinas, A; Rodríguez-Sánchez, G; García-Sánchez, J E

    2012-09-01

    The antibiotic resistance is one of the greatest challenges of the international health community. The study of antibiotic resistance must be a multidisciplinary task and, in this sense, the main goal of this work is to analyze the role that Mathematical Modeling can play in this scenario. A qualitative and cuantitative analysis of the works published in the scientific literature is done by means of a search in the most important databases: MEDLINE, SCOPUS and ISI Web of Science. Consequently, there are few papers related to our topic but the existing works have been published in high-quality and impact international journals. Moreover, we can state that mathematical models are a very important and useful tool to analyze and study both the treatments protocols for resistance prevention and the assesment of control strategies in hospital environtment, or the prediction of the evolution of diseases due to resistant strains.

  14. Resistance to Antiangiogenic Therapies by Metabolic Symbiosis in Renal Cell Carcinoma PDX Models and Patients

    Directory of Open Access Journals (Sweden)

    Gabriela Jiménez-Valerio

    2016-05-01

    Full Text Available Antiangiogenic drugs are used clinically for treatment of renal cell carcinoma (RCC as a standard first-line treatment. Nevertheless, these agents primarily serve to stabilize disease, and resistance eventually develops concomitant with progression. Here, we implicate metabolic symbiosis between tumor cells distal and proximal to remaining vessels as a mechanism of resistance to antiangiogenic therapies in patient-derived RCC orthoxenograft (PDX models and in clinical samples. This metabolic patterning is regulated by the mTOR pathway, and its inhibition effectively blocks metabolic symbiosis in PDX models. Clinically, patients treated with antiangiogenics consistently present with histologic signatures of metabolic symbiosis that are exacerbated in resistant tumors. Furthermore, the mTOR pathway is also associated in clinical samples, and its inhibition eliminates symbiotic patterning in patient samples. Overall, these data support a mechanism of resistance to antiangiogenics involving metabolic compartmentalization of tumor cells that can be inhibited by mTOR-targeted drugs.

  15. Effects of Low-Molecular-Weight Fucoidan and High Stability Fucoxanthin on Glucose Homeostasis, Lipid Metabolism, and Liver Function in a Mouse Model of Type II Diabetes

    Directory of Open Access Journals (Sweden)

    Hong-Ting Victor Lin

    2017-04-01

    Full Text Available The combined effects of low-molecular-weight fucoidan (LMF and fucoxanthin (Fx in terms of antihyperglycemic, antihyperlipidemic, and hepatoprotective activities were investigated in a mouse model of type II diabetes. The intake of LMF, Fx, and LMF + Fx lowered the blood sugar and fasting blood sugar levels, and increased serum adiponectin levels. The significant decrease in urinary sugar was only observed in LMF + Fx supplementation. LMF and Fx had ameliorating effects on the hepatic tissue of db/db mice by increasing hepatic glycogen and antioxidative enzymes, and LMF was more effective than Fx at improving hepatic glucose metabolism. As for glucose and lipid metabolism in the adipose tissue, the expression of insulin receptor substrate (IRS-1, glucose transporter (GLUT, peroxisome proliferator-activated receptor gamma (PPARγ, and uncoupling protein (UCP-1 mRNAs in the adipose tissue of diabetic mice was significantly upregulated by Fx and LMF + Fx, and levels of inflammatory adipocytokines, such as adiponectin, tumor necrosis factor-α (TNF-α, and interleukin-6 (IL-6, were significantly modulated only by LMF + Fx supplementation. The efficacy of LMF + Fx supplementation on the decrease in urinary sugar and on glucose and lipid metabolism in the white adipose tissue of db/db mice was better than that of Fx or LMF alone, indicating the occurrence of a synergistic effect of LMF and Fx.

  16. Insulin Resistance in Alzheimer's Disease

    Science.gov (United States)

    Dineley, Kelly T; Jahrling, Jordan B; Denner, Larry

    2014-01-01

    Insulin is a key hormone regulating metabolism. Insulin binding to cell surface insulin receptors engages many signaling intermediates operating in parallel and in series to control glucose, energy, and lipids while also regulating mitogenesis and development. Perturbations in the function of any of these intermediates, which occur in a variety of diseases, cause reduced sensitivity to insulin and insulin resistance with consequent metabolic dysfunction. Chronic inflammation ensues which exacerbates compromised metabolic homeostasis. Since insulin has a key role in learning and memory as well as directly regulating ERK, a kinase required for the type of learning and memory compromised in early Alzheimer's disease (AD), insulin resistance has been identified as a major risk factor for the onset of AD. Animal models of AD or insulin resistance or both demonstrate that AD pathology and impaired insulin signaling form a reciprocal relationship. Of note are human and animal model studies geared toward improving insulin resistance that have led to the identification of the nuclear receptor and transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) as an intervention tool for early AD. Strategic targeting of alternate nodes within the insulin signaling network has revealed disease-stage therapeutic windows in animal models that coalesce with previous and ongoing clinical trial approaches. Thus, exploiting the connection between insulin resistance and AD provides powerful opportunities to delineate therapeutic interventions that slow or block the pathogenesis of AD. PMID:25237037

  17. A mathematical model of insulin resistance in Parkinson's disease.

    Science.gov (United States)

    Braatz, Elise M; Coleman, Randolph A

    2015-06-01

    This paper introduces a mathematical model representing the biochemical interactions between insulin signaling and Parkinson's disease. The model can be used to examine the changes that occur over the course of the disease as well as identify which processes would be the most effective targets for treatment. The model is mathematized using biochemical systems theory (BST). It incorporates a treatment strategy that includes several experimental drugs along with current treatments. In the past, BST models of neurodegeneration have used power law analysis and simulation (PLAS) to model the system. This paper recommends the use of MATLAB instead. MATLAB allows for more flexibility in both the model itself and in data analysis. Previous BST analyses of neurodegeneration began treatment at disease onset. As shown in this model, the outcomes of delayed, realistic treatment and full treatment at disease onset are significantly different. The delayed treatment strategy is an important development in BST modeling of neurodegeneration. It emphasizes the importance of early diagnosis, and allows for a more accurate representation of disease and treatment interactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Spread of anti-malarial drug resistance: Mathematical model with implications for ACT drug policies

    Directory of Open Access Journals (Sweden)

    Dondorp Arjen M

    2008-11-01

    Full Text Available Abstract Background Most malaria-endemic countries are implementing a change in anti-malarial drug policy to artemisinin-based combination therapy (ACT. The impact of different drug choices and implementation strategies is uncertain. Data from many epidemiological studies in different levels of malaria endemicity and in areas with the highest prevalence of drug resistance like borders of Thailand are certainly valuable. Formulating an appropriate dynamic data-driven model is a powerful predictive tool for exploring the impact of these strategies quantitatively. Methods A comprehensive model was constructed incorporating important epidemiological and biological factors of human, mosquito, parasite and treatment. The iterative process of developing the model, identifying data needed, and parameterization has been taken to strongly link the model to the empirical evidence. The model provides quantitative measures of outcomes, such as malaria prevalence/incidence and treatment failure, and illustrates the spread of resistance in low and high transmission settings. The model was used to evaluate different anti-malarial policy options focusing on ACT deployment. Results The model predicts robustly that in low transmission settings drug resistance spreads faster than in high transmission settings, and treatment failure is the main force driving the spread of drug resistance. In low transmission settings, ACT slows the spread of drug resistance to a partner drug, especially at high coverage rates. This effect decreases exponentially with increasing delay in deploying the ACT and decreasing rates of coverage. In the high transmission settings, however, drug resistance is driven by the proportion of the human population with a residual drug level, which gives resistant parasites some survival advantage. The spread of drug resistance could be slowed down by controlling presumptive drug use and avoiding the use of combination therapies containing drugs with

  19. Nonlinear inversion of resistivity sounding data for 1-D earth models using the Neighbourhood Algorithm

    Science.gov (United States)

    Ojo, A. O.; Xie, Jun; Olorunfemi, M. O.

    2018-01-01

    To reduce ambiguity related to nonlinearities in the resistivity model-data relationships, an efficient direct-search scheme employing the Neighbourhood Algorithm (NA) was implemented to solve the 1-D resistivity problem. In addition to finding a range of best-fit models which are more likely to be global minimums, this method investigates the entire multi-dimensional model space and provides additional information about the posterior model covariance matrix, marginal probability density function and an ensemble of acceptable models. This provides new insights into how well the model parameters are constrained and make assessing trade-offs between them possible, thus avoiding some common interpretation pitfalls. The efficacy of the newly developed program is tested by inverting both synthetic (noisy and noise-free) data and field data from other authors employing different inversion methods so as to provide a good base for comparative performance. In all cases, the inverted model parameters were in good agreement with the true and recovered model parameters from other methods and remarkably correlate with the available borehole litho-log and known geology for the field dataset. The NA method has proven to be useful whilst a good starting model is not available and the reduced number of unknowns in the 1-D resistivity inverse problem makes it an attractive alternative to the linearized methods. Hence, it is concluded that the newly developed program offers an excellent complementary tool for the global inversion of the layered resistivity structure.

  20. Relativistic fluid model of the resistive hose instability

    International Nuclear Information System (INIS)

    Siambis, J.G.

    1992-01-01

    A systematic analysis of the hose instability using the relativistic fluid formulation is reported. In its basic nature, the hose instability is a macroscopic, low-frequency instability, hence a fluid model should, in principle, give an accurate account of the hose instability. It has been found that for zeroth-order beam displacements, giving rise to rigid beam displacements, the fluid wave equation and resulting dispersion relation are identical to the spread-mass model and the energy-group model results. When first-order fluid displacements are included as well, giving rise to compressible, nonfrozen displacements in the axial direction and beam cross-section distortion in the radial direction, then there is obtained a wave equation similar, but not identical to the multicomponent model. The dispersion relation is solved for numerically. The hose instability growth rate is found to be similar to the multicomponent model result, over part of the beam frame, real hose frequency range

  1. Examination of the effects of arsenic on glucose homeostasis in cell culture and animal studies: Development of a mouse model for arsenic-induced diabetes

    International Nuclear Information System (INIS)

    Paul, David S.; Hernandez-Zavala, Araceli; Walton, Felecia S.; Adair, Blakely M.; Dedina, Jiri; Matousek, Tomas; Styblo, Miroslav

    2007-01-01

    Previous epidemiologic studies found increased prevalences of type 2 diabetes mellitus in populations exposed to high levels of inorganic arsenic (iAs) in drinking water. Although results of epidemiologic studies in low-exposure areas or occupational settings have been inconclusive, laboratory research has shown that exposures to iAs can produce effects that are consistent with type 2 diabetes. The current paper reviews the results of laboratory studies that examined the effects of iAs on glucose metabolism and describes new experiments in which the diabetogenic effects of iAs exposure were reproduced in a mouse model. Here, weanling male C57BL/6 mice drank deionized water with or without the addition of arsenite (25 or 50 ppm As) for 8 weeks. Intraperitoneal glucose tolerance tests revealed impaired glucose tolerance in mice exposed to 50 ppm As, but not to 25 ppm As. Exposure to 25 and 50 ppm As in drinking-water resulted in proportional increases in the concentration of iAs and its metabolites in the liver and in organs targeted by type 2 diabetes, including pancreas, skeletal muscle and adipose tissue. Dimethylarsenic was the predominant form of As in the tissues of mice in both 25 and 50 ppm groups. Notably, the average concentration of total speciated arsenic in livers from mice in the 50 ppm group was comparable to the highest concentration of total arsenic reported in the livers of Bangladeshi residents who had consumed water with an order of magnitude lower level of iAs. These data suggest that mice are less susceptible than humans to the diabetogenic effects of chronic exposure to iAs due to a more efficient clearance of iAs or its metabolites from target tissues

  2. Nutrient sensing and insulin signaling in neuropeptide-expressing immortalized, hypothalamic neurons: A cellular model of insulin resistance.

    Science.gov (United States)

    Fick, Laura J; Belsham, Denise D

    2010-08-15

    Obesity and type 2 diabetes mellitus represent a significant global health crisis. These two interrelated diseases are typified by perturbed insulin signaling in the hypothalamus. Using novel hypothalamic cell lines, we have begun to elucidate the molecular and intracellular mechanisms involved in the hypothalamic control of energy homeostasis and insulin resistance. In this review, we present evidence of insulin and glucose signaling pathways that lead to changes in neuropeptide gene expression. We have identified some of the molecular mechanisms involved in the control of de novo hypothalamic insulin mRNA expression. And finally, we have defined key mechanisms involved in the etiology of cellular insulin resistance in hypothalamic neurons that may play a fundamental role in cases of high levels of insulin or saturated fatty acids, often linked to the exacerbation of obesity and diabetes.

  3. Resistive transition for two-dimensional superconductors: Comparison between experiments and Coulomb-gas-model predictions

    International Nuclear Information System (INIS)

    Minnhagen, P.

    1983-01-01

    The Coulomb-gas model of vortex fluctuations leads to scaling relations for the resistive transition which can be directly tested by experiments. By analyzing published resistance data, it is shown that there is experimental evidence for the Coulomb-gas scaling relation in the absence of a perpendicular magnetic field. It is also shown that there exists some suggestive support for the Coulomb-gas predictions in the presence of a magnetic field

  4. Deciphering Mineral Homeostasis in Barley Seed Transfer Cells at Transcriptional Level.

    Directory of Open Access Journals (Sweden)

    Behrooz Darbani

    Full Text Available In addition to the micronutrient inadequacy of staple crops for optimal human nutrition, a global downtrend in crop-quality has emerged from intensive breeding for yield. This trend will be aggravated by elevated levels of the greenhouse gas carbon dioxide. Therefore, crop biofortification is inevitable to ensure a sustainable supply of minerals to the large part of human population who is dietary dependent on staple crops. This requires a thorough understanding of plant-mineral interactions due to the complexity of mineral homeostasis. Employing RNA sequencing, we here communicate transfer cell specific effects of excess iron and zinc during grain filling in our model crop plant barley. Responding to alterations in mineral contents, we found a long range of different genes and transcripts. Among them, it is worth to highlight the auxin and ethylene signaling factors Arfs, Abcbs, Cand1, Hps4, Hac1, Ecr1, and Ctr1, diurnal fluctuation components Sdg2, Imb1, Lip1, and PhyC, retroelements, sulfur homeostasis components Amp1, Hmt3, Eil3, and Vip1, mineral trafficking components Med16, Cnnm4, Aha2, Clpc1, and Pcbps, and vacuole organization factors Ymr155W, RabG3F, Vps4, and Cbl3. Our analysis introduces new interactors and signifies a broad spectrum of regulatory levels from chromatin remodeling to intracellular protein sorting mechanisms active in the plant mineral homeostasis. The results highlight the importance of storage proteins in metal ion toxicity-resistance and chelation. Interestingly, the protein sorting and recycling factors Exoc7, Cdc1, Sec23A, and Rab11A contributed to the response as well as the polar distributors of metal-transporters ensuring the directional flow of minerals. Alternative isoform switching was found important for plant adaptation and occurred among transcripts coding for identical proteins as well as transcripts coding for protein isoforms. We also identified differences in the alternative-isoform preference between

  5. Deciphering Mineral Homeostasis in Barley Seed Transfer Cells at Transcriptional Level.

    Science.gov (United States)

    Darbani, Behrooz; Noeparvar, Shahin; Borg, Søren

    2015-01-01

    In addition to the micronutrient inadequacy of staple crops for optimal human nutrition, a global downtrend in crop-quality has emerged from intensive breeding for yield. This trend will be aggravated by elevated levels of the greenhouse gas carbon dioxide. Therefore, crop biofortification is inevitable to ensure a sustainable supply of minerals to the large part of human population who is dietary dependent on staple crops. This requires a thorough understanding of plant-mineral interactions due to the complexity of mineral homeostasis. Employing RNA sequencing, we here communicate transfer cell specific effects of excess iron and zinc during grain filling in our model crop plant barley. Responding to alterations in mineral contents, we found a long range of different genes and transcripts. Among them, it is worth to highlight the auxin and ethylene signaling factors Arfs, Abcbs, Cand1, Hps4, Hac1, Ecr1, and Ctr1, diurnal fluctuation components Sdg2, Imb1, Lip1, and PhyC, retroelements, sulfur homeostasis components Amp1, Hmt3, Eil3, and Vip1, mineral trafficking components Med16, Cnnm4, Aha2, Clpc1, and Pcbps, and vacuole organization factors Ymr155W, RabG3F, Vps4, and Cbl3. Our analysis introduces new interactors and signifies a broad spectrum of regulatory levels from chromatin remodeling to intracellular protein sorting mechanisms active in the plant mineral homeostasis. The results highlight the importance of storage proteins in metal ion toxicity-resistance and chelation. Interestingly, the protein sorting and recycling factors Exoc7, Cdc1, Sec23A, and Rab11A contributed to the response as well as the polar distributors of metal-transporters ensuring the directional flow of minerals. Alternative isoform switching was found important for plant adaptation and occurred among transcripts coding for identical proteins as well as transcripts coding for protein isoforms. We also identified differences in the alternative-isoform preference between the treatments

  6. A multiple-field coupled resistive transition model for superconducting Nb3Sn

    Directory of Open Access Journals (Sweden)

    Lin Yang

    2016-12-01

    Full Text Available A study on the superconducting transition width as functions of the applied magnetic field and strain is performed in superconducting Nb3Sn. A quantitative, yet universal phenomenological resistivity model is proposed. The numerical simulation by the proposed model shows predicted resistive transition characteristics under variable magnetic fields and strain, which in good agreement with the experimental observations. Furthermore, a temperature-modulated magnetoresistance transition behavior in filamentary Nb3Sn conductors can also be well described by the given model. The multiple-field coupled resistive transition model is helpful for making objective determinations of the high-dimensional critical surface of Nb3Sn in the multi-parameter space, offering some preliminary information about the basic vortex-pinning mechanisms, and guiding the design of the quench protection system of Nb3Sn superconducting magnets.

  7. A multiple-field coupled resistive transition model for superconducting Nb3Sn

    Science.gov (United States)

    Yang, Lin; Ding, He; Zhang, Xin; Qiao, Li

    2016-12-01

    A study on the superconducting transition width as functions of the applied magnetic field and strain is performed in superconducting Nb3Sn. A quantitative, yet universal phenomenological resistivity model is proposed. The numerical simulation by the proposed model shows predicted resistive transition characteristics under variable magnetic fields and strain, which in good agreement with the experimental observations. Furthermore, a temperature-modulated magnetoresistance transition behavior in filamentary Nb3Sn conductors can also be well described by the given model. The multiple-field coupled resistive transition model is helpful for making objective determinations of the high-dimensional critical surface of Nb3Sn in the multi-parameter space, offering some preliminary information about the basic vortex-pinning mechanisms, and guiding the design of the quench protection system of Nb3Sn superconducting magnets.

  8. The lytic transglycosylase MltB connects membrane homeostasis and in vivo fitness of Acinetobacter baumannii.

    Science.gov (United States)

    Crépin, Sébastien; Ottosen, Elizabeth N; Peters, Katharina; Smith, Sara N; Himpsl, Stephanie D; Vollmer, Waldemar; Mobley, Harry L T

    2018-06-08

    Acinetobacter baumannii has emerged as a leading nosocomial pathogen, infecting a wide range of anatomic sites including the respiratory tract and the bloodstream. In addition to being multi-drug resistant, little is known about the molecular basis of A. baumannii pathogenesis. To better understand A. baumannii virulence, a combination of a transposon-sequencing (TraDIS) screen and the neutropenic mouse model of bacteremia was used to identify the full set of fitness genes required during bloodstream infection. The lytic transglycosylase MltB was identified as a critical fitness factor. MltB cleaves the MurNAc-GlcNAc bond of peptidoglycan, which leads to cell wall remodeling. Here we show that MltB is part of a complex network connecting resistance to stresses, membrane homeostasis, biogenesis of pili and in vivo fitness. Indeed, inactivation of mltB not only impaired resistance to serum complement, cationic antimicrobial peptides and oxygen species, but also altered the cell envelope integrity, activated the envelope stress response, drastically reduced the number of pili at the cell surface and finally, significantly decreased colonization of both the bloodstream and the respiratory tract. This article is protected by copyright. All rights reserved. © 2018 John Wiley & Sons Ltd.

  9. Bariatric surgery improves the cavernosal neuronal, vasorelaxation, and contraction mechanisms for erectile dysfunction as result of amelioration of glucose homeostasis in a diabetic rat model.

    Directory of Open Access Journals (Sweden)

    Yong Sun Choi

    Full Text Available Bariatric surgery is an effective treatment option for both obesity and obesity-related type 2 diabetes mellitus (T2DM. However, little is known regarding the effects of bariatric surgery on erectile dysfunction among patients with T2DM. Therefore, we investigated whether bariatric surgery would lead to structural and biochemical changes in the corpus cavernosum.Twenty-five male Otsuka Long-Evans Tokushima Fatty rats were assigned to either a control group (sham operation, n = 10 or a bariatric surgery group (gastric bypass surgery, n = 15. Four weeks after the operation, each group of rats was evaluated with an oral glucose tolerance test (OGTT. The penile intracavernous pressure was measured for erectile functional analysis. Histologic evaluation of the tissue was performed with Masson's trichrome staining. Endothelial nitric oxide synthase (eNOS, neuronal nitric oxide synthase (nNOS, Rho kinase, and 8-hydroxy-2-deoxyguanosine (8-OHdG levels in the corpus cavernosum were assayed by using western blot and ELISA.The mean body weight of the bariatric surgery group was lower than the control group (p = 0.002. The postoperative OGTT result was lower in the bariatric surgery group than in the control group (p = 0.014, and this was lower than the preoperative value (p = 0.037. The intracavernous pressure/mean arterial pressure ratio was higher in the bariatric surgery group compared to the control group (p = 0.021, and a higher cavernosum smooth muscle/collagen ratio was observed in the bariatric surgery group compared to the control group (p = 0.025. Likewise, the expression of eNOS and nNOS was higher in bariatric surgery group than in the control group (p = 0.027 and p = 0.008, respectively. Decreased expression of Rho kinase and levels of 8-OHdG were observed in the bariatric surgery group (p = 0.032.In this animal model, bariatric surgery appears to ameliorate T2DM-related metabolic dysfunction leading to

  10. Bariatric surgery improves the cavernosal neuronal, vasorelaxation, and contraction mechanisms for erectile dysfunction as result of amelioration of glucose homeostasis in a diabetic rat model.

    Science.gov (United States)

    Choi, Yong Sun; Lee, Sang Kuon; Bae, Woong Jin; Kim, Su Jin; Cho, Hyuk Jin; Hong, Sung-Hoo; Lee, Ji Youl; Hwang, Tae-Kon; Kim, Sae Woong

    2014-01-01

    Bariatric surgery is an effective treatment option for both obesity and obesity-related type 2 diabetes mellitus (T2DM). However, little is known regarding the effects of bariatric surgery on erectile dysfunction among patients with T2DM. Therefore, we investigated whether bariatric surgery would lead to structural and biochemical changes in the corpus cavernosum. Twenty-five male Otsuka Long-Evans Tokushima Fatty rats were assigned to either a control group (sham operation, n = 10) or a bariatric surgery group (gastric bypass surgery, n = 15). Four weeks after the operation, each group of rats was evaluated with an oral glucose tolerance test (OGTT). The penile intracavernous pressure was measured for erectile functional analysis. Histologic evaluation of the tissue was performed with Masson's trichrome staining. Endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), Rho kinase, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in the corpus cavernosum were assayed by using western blot and ELISA. The mean body weight of the bariatric surgery group was lower than the control group (p = 0.002). The postoperative OGTT result was lower in the bariatric surgery group than in the control group (p = 0.014), and this was lower than the preoperative value (p = 0.037). The intracavernous pressure/mean arterial pressure ratio was higher in the bariatric surgery group compared to the control group (p = 0.021), and a higher cavernosum smooth muscle/collagen ratio was observed in the bariatric surgery group compared to the control group (p = 0.025). Likewise, the expression of eNOS and nNOS was higher in bariatric surgery group than in the control group (p = 0.027 and p = 0.008, respectively). Decreased expression of Rho kinase and levels of 8-OHdG were observed in the bariatric surgery group (p = 0.032). In this animal model, bariatric surgery appears to ameliorate T2DM-related metabolic dysfunction leading to

  11. Plausible carrier transport model in organic-inorganic hybrid perovskite resistive memory devices

    Science.gov (United States)

    Park, Nayoung; Kwon, Yongwoo; Choi, Jaeho; Jang, Ho Won; Cha, Pil-Ryung

    2018-04-01

    We demonstrate thermally assisted hopping (TAH) as an appropriate carrier transport model for CH3NH3PbI3 resistive memories. Organic semiconductors, including organic-inorganic hybrid perovskites, have been previously speculated to follow the space-charge-limited conduction (SCLC) model. However, the SCLC model cannot reproduce the temperature dependence of experimental current-voltage curves. Instead, the TAH model with temperature-dependent trap densities and a constant trap level are demonstrated to well reproduce the experimental results.

  12. A human model of dietary saturated fatty acid induced insulin resistance.

    Science.gov (United States)

    Koska, Juraj; Ozias, Marlies K; Deer, James; Kurtz, Julie; Salbe, Arline D; Harman, S Mitchell; Reaven, Peter D

    2016-11-01

    Increased consumption of high-fat diets is associated with the development of insulin resistance and type 2 diabetes. Current models to study the mechanisms of high-fat diet-induced IR in humans are limited by their long duration or low efficacy. In the present study we developed and characterized an acute dietary model of saturated fatty acid-enriched diet induced insulin resistance. High caloric diets enriched with saturated fatty acids (SFA) or carbohydrates (CARB) were evaluated in subjects with normal and impaired glucose tolerance (NGT or IGT). Both diets were compared to a standard eucaloric American Heart Association (AHA) control diet in a series of crossover studies. Whole body insulin resistance was estimated as steady state plasma glucose (SSPG) concentrations during the last 30min of a 3-h insulin suppression test. SSPG was increased after a 24-h SFA diet (by 83±74% vs. control, n=38) in the entire cohort, which was comprised of participants with NGT (92±82%, n=22) or IGT (65±55%, n=16) (all pinsulin resistance in both NGT and IGT subjects. Insulin resistance persisted overnight after the last SFA meal and was attenuated by one day of a healthy diet. This model offers opportunities for identifying early mechanisms and potential treatments of dietary saturated fat induced insulin resistance. Published by Elsevier Inc.

  13. Comparing Novel Multi-Gap Resistive Plate Chamber Models

    Science.gov (United States)

    Stien, Haley; EIC PID Consortium Collaboration

    2016-09-01

    Investigating nuclear structure has led to the fundamental theory of Quantum Chromodynamics. An Electron Ion Collider (EIC) is a proposed accelerator that would further these investigations. In order to prepare for the EIC, there is an active detector research and development effort. One specific goal is to achieve better particle identification via improved Time of Flight (TOF) detectors. A promising option is the Multi-Gap Resistive Plate Chamber (mRPC). These detectors are similar to the more traditional RPCs, but their active gas gaps have dividers to form several thinner gas gaps. These very thin and accurately defined gas gaps improve the timing resolution of the chamber, so the goal is to build an mRPC with the thinnest gaps to achieve the best possible timing resolution. Two different construction techniques have been employed to make two mRPCs. The first technique is to physically separate the gas gaps with sheets of glass that are .2mm thick. The second technique is to 3D print the layered gas gaps. A comparison of these mRPCs and their performances will be discussed and the latest data presented. This research was supported by US DOE MENP Grant DE-FG02-03ER41243.

  14. Friction correction for model ship resistance and propulsion tests in ice at NRC's OCRE-RC

    Directory of Open Access Journals (Sweden)

    Michael Lau

    2018-05-01

    Full Text Available This paper documents the result of a preliminary analysis on the influence of hull-ice friction coefficient on model resistance and power predictions and their correlation to full-scale measurements. The study is based on previous model-scale/full-scale correlations performed on the National Research Council - Ocean, Coastal, and River Engineering Research Center's (NRC/OCRE-RC model test data. There are two objectives for the current study: (1 to validate NRC/OCRE-RC's modeling standards in regarding to its practice of specifying a CFC (Correlation Friction Coefficient of 0.05 for all its ship models; and (2 to develop a correction methodology for its resistance and propulsion predictions when the model is prepared with an ice friction coefficient slightly deviated from the CFC of 0.05. The mean CFC of 0.056 and 0.050 for perfect correlation as computed from the resistance and power analysis, respectively, have justified NRC/OCRE-RC's selection of 0.05 for the CFC of all its models. Furthermore, a procedure for minor friction corrections is developed. Keywords: Model test, Ice resistance, Power, Friction correction, Correlation friction coefficient

  15. Model of the coronary circulation based on pressure dependence of coronary resistance and compliance

    NARCIS (Netherlands)

    Bruinsma, P.; Arts, T.; Dankelman, J.; Spaan, J. A.

    1988-01-01

    The effect of pressure-dependent changes in vascular volume, resistance and capacitance in the coronary micro-circulation, has been studied by a distributed mathematical model of the coronary micro-vasculature in the left ventricular wall. The model does not include regulation of coronary blood flow

  16. Steel corrosion resistance in model solutions and reinforced mortar containing wastes

    NARCIS (Netherlands)

    Koleva, D.A.; Van Breugel, K.

    2012-01-01

    This work reports on the corrosion resistance of steel in alkaline model solutions and in cement-based materials (mortar). The model solutions and the mortar specimens were Ordinary Portland Cement (OPC) based. Further, hereby discussed is the implementation of an eco-friendly approach of waste

  17. Effect of high-dose pitavastatin on glucose homeostasis in patients at elevated risk of new-onset diabetes: insights from the CAPITAIN and PREVAIL-US studies.

    Science.gov (United States)

    Chapman, M J; Orsoni, A; Robillard, P; Hounslow, N; Sponseller, C A; Giral, P

    2014-05-01

    Statin treatment may impair glucose homeostasis and increase the risk of new-onset diabetes mellitus, although this may depend on the statin, dose and patient population. We evaluated the effects of pitavastatin 4 mg/day on glucose homeostasis in patients with metabolic syndrome in the CAPITAIN trial. Findings were validated in a subset of patients enrolled in PREVAIL-US. Participants with a well defined metabolic syndrome phenotype were recruited to CAPITAIN to reduce the influence of confounding factors. Validation and comparison datasets were selected comprising phenotypically similar subsets of individuals enrolled in PREVAIL-US and treated with pitavastatin or pravastatin, respectively. Mean change from baseline in parameters of glucose homeostasis (fasting plasma glucose [FPG], glycated hemoglobin [HbA1c], insulin, quantitative insulin-sensitivity check index [QUICKI] and homeostasis model of assessment-insulin resistance [HOMA-IR]) and plasma lipid profile were assessed at 6 months (CAPITAIN) and 3 months (PREVAIL-US) after initiating treatment. In CAPITAIN (n = 12), no significant differences from baseline in HbA1c, insulin, HOMA-IR and QUICKI were observed at day 180 in patients treated with pitavastatin. A small (4%) increase in FPG from baseline to day 180 (P  0.05). Similar results were observed for pravastatin in the comparison dataset (n = 14). Other than a small change in FPG in the CAPITAIN study, neutral effects of pitavastatin on glucose homeostasis were observed in two cohorts of patients with metabolic syndrome, independent of its efficacy in reducing levels of atherogenic lipoproteins. The small number of patients and relatively short follow-up period represent limitations of the study. Nevertheless, these data suggest that statin-induced diabetogenesis may not represent a class effect.

  18. Prediction of microsegregation and pitting corrosion resistance of austenitic stainless steel welds by modelling

    Energy Technology Data Exchange (ETDEWEB)

    Vilpas, M. [VTT Manufacturing Technology, Espoo (Finland). Materials and Structural Integrity

    1999-07-01

    The present study focuses on the ability of several computer models to accurately predict the solidification, microsegregation and pitting corrosion resistance of austenitic stainless steel weld metals. Emphasis was given to modelling the effect of welding speed on solute redistribution and ultimately to the prediction of weld pitting corrosion resistance. Calculations were experimentally verified by applying autogenous GTA- and laser processes over the welding speed range of 0.1 to 5 m/min for several austenitic stainless steel grades. Analytical and computer aided models were applied and linked together for modelling the solidification behaviour of welds. The combined use of macroscopic and microscopic modelling is a unique feature of this work. This procedure made it possible to demonstrate the effect of weld pool shape and the resulting solidification parameters on microsegregation and pitting corrosion resistance. Microscopic models were also used separately to study the role of welding speed and solidification mode in the development of microsegregation and pitting corrosion resistance. These investigations demonstrate that the macroscopic model can be implemented to predict solidification parameters that agree well with experimentally measured values. The linked macro-micro modelling was also able to accurately predict segregation profiles and CPT-temperatures obtained from experiments. The macro-micro simulations clearly showed the major roles of weld composition and welding speed in determining segregation and pitting corrosion resistance while the effect of weld shape variations remained negligible. The microscopic dendrite tip and interdendritic models were applied to welds with good agreement with measured segregation profiles. Simulations predicted that weld inhomogeneity can be substantially decreased with increasing welding speed resulting in a corresponding improvement in the weld pitting corrosion resistance. In the case of primary austenitic

  19. Analysis and Modelling of Electrode Wear in Resistance Spot Welding

    DEFF Research Database (Denmark)

    Madsen, Anders; Pedersen, Kim; Friis, Kasper Storgaard

    2010-01-01

    A model describing electrode wear as a function of weld number, initial tip diameter, truncated cone angle, welding current and electrode force is proposed. Excellent agreement between the model and experimental results is achieved, showing that the model can describe the change in electrode tip...... diameter with increasing weld number at different weld settings. Furthermore a method for measuring the worn tip diameter in a fast and robust manner is developed. The method relies on a well-known technique for capturing the electrode tip area by the use of carbon imprints and a new developed image...... a central cavity is formed and one where smaller pits are formed randomly across the electrode face. The influence of these two types of surface pits on the nugget size are investigated using the FE code SORPAS, revealing ring welds and undersized weld nuggets....

  20. Venom Resistance as a Model for Understanding the Molecular Basis of Complex Coevolutionary Adaptations.

    Science.gov (United States)

    Holding, Matthew L; Drabeck, Danielle H; Jansa, Sharon A; Gibbs, H Lisle

    2016-11-01

    SynopsisVenom and venom resistance are molecular phenotypes widely considered to have diversified through coevolution between predators and prey. However, while evolutionary and functional studies on venom have been extensive, little is known about the molecular basis, variation, and complexity of venom resistance. We review known mechanisms of venom resistance and relate these mechanisms to their predicted impact on coevolutionary dynamics with venomous enemies. We then describe two conceptual approaches which can be used to examine venom/resistance systems. At the intraspecific level, tests of local adaptation in venom and resistance phenotypes can identify the functional mechanisms governing the outcomes of coevolution. At deeper evolutionary timescales, the combination of phylogenetically informed analyses of protein evolution coupled with studies of protein function promise to elucidate the mode and tempo of evolutionary change on potentially coevolving genes. We highlight case studies that use each approach to extend our knowledge of these systems as well as address larger questions about coevolutionary dynamics. We argue that resistance and venom are phenotypic traits which hold exceptional promise for investigating the mechanisms, dynamics, and outcomes of coevolution at the molecular level. Furthermore, extending the understanding of single gene-for-gene interactions to the whole resistance and venom phenotypes may provide a model system for examining the molecular and evolutionary dynamics of complex multi-gene interactions. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  1. Gut Homeostasis, Microbial Dysbiosis, and Opioids.

    Science.gov (United States)

    Wang, Fuyuan; Roy, Sabita

    2017-01-01

    Gut homeostasis plays an important role in maintaining animal and human health. The disruption of gut homeostasis has been shown to be associated with multiple diseases. The mutually beneficial relationship between the gut microbiota and the host has been demonstrated to maintain homeostasis of the mucosal immunity and preserve the integrity of the gut epithelial barrier. Currently, rapid progress in the understanding of the host-microbial interaction has redefined toxicological pathology of opioids and their pharmacokinetics. However, it is unclear how opioids modulate the gut microbiome and metabolome. Our study, showing opioid modulation of gut homeostasis in mice, suggests that medical interventions to ameliorate the consequences of drug use/abuse will provide potential therapeutic and diagnostic strategies for opioid-modulated intestinal infections. The study of morphine's modulation of the gut microbiome and metabolome will shed light on the toxicological pathology of opioids and its role in the susceptibility to infectious diseases.

  2. Air pollution particles and iron homeostasis

    Science.gov (United States)

    Background: The mechanism underlying biological effects of particles deposited in the lung has not been defined. Major Conclusions: A disruption in iron homeostasis follows exposure of cells to all particulate matter including air pollution particles. Following endocytosis, fun...

  3. Neuronal regulation of homeostasis by nutrient sensing.

    Science.gov (United States)

    Lam, Tony K T

    2010-04-01

    In type 2 diabetes and obesity, the homeostatic control of glucose and energy balance is impaired, leading to hyperglycemia and hyperphagia. Recent studies indicate that nutrient-sensing mechanisms in the body activate negative-feedback systems to regulate energy and glucose homeostasis through a neuronal network. Direct metabolic signaling within the intestine activates gut-brain and gut-brain-liver axes to regulate energy and glucose homeostasis, respectively. In parallel, direct metabolism of nutrients within the hypothalamus regulates food intake and blood glucose levels. These findings highlight the importance of the central nervous system in mediating the ability of nutrient sensing to maintain homeostasis. Futhermore, they provide a physiological and neuronal framework by which enhancing or restoring nutrient sensing in the intestine and the brain could normalize energy and glucose homeostasis in diabetes and obesity.

  4. A study on the radionuclide transport through fractured porous media based on the network resistance model

    International Nuclear Information System (INIS)

    Hwang, Ki Ha

    2000-02-01

    Before the actual construction of radioactive waste repository, analysis of radionuclide transport is required to predict the radiological effect on public and environment. Many models have been developed to predict the realistic radionuclide transport through the repository. In this study, Network Resistance Model (NRM) that is similar to electrical circuit network is adopted to simulate the radionuclide transport. NRM assume the media of repository as the resistance of the radionuclide transport and describes the transport phenomena of radionuclide by connecting the resistance as network. NRM is easy to apply to describe complex system and take less calculation time compared to the other model. The object of this study is to develop the fast, simple and efficient calculation method to simulate the radionuclide with the newly adopted concept using network resistance. New system configuration specially focused on rock edge region is introduced by dividing the rock matrix. By dividing the rock edge from the main rock matrix region, the rock edge region is more carefully analyzed and compared. Rock edge region can accelerate radionuclide transport due to the reducing effect on the total resistivity of rock matrix. Therefore, increased radioactive dose is expected when we apply NRM methodology in the performance assessment of the repository. Result of the performance assessment can be more conservative and reliable. NRM can be applied to other system configuration and for more complex pathways. NRM is simple to us e and easy to modify than any other modeling method

  5. CFD investigation of pentamaran ship model with chine hull form on the resistance characteristics

    Science.gov (United States)

    Yanuar; Sulistyawati, W.

    2018-03-01

    This paper presents an investigation of pentamaran hull form with chine hull form to the effects of outriggers position, asymmetry, and deadrise angles on the resistance characteristics. The investigation to the resistance characteristics by modelling pentamaran hull form using chine with symmetrical main hull and asymmetric outboard on the variation deadrise angles: 25°, 30°, 35° and Froude number 0,1 to 0,7. On calm water resistance characteristics of six pentamaran models with chine-hull form examined by variation of deadrise angles by using CFD. Comparation with Wigley hull form, the maximum resistance drag reduction of the chine hull form was reduced by 15.81% on deadrise 25°, 13.8% on deadrise 30°, and 20.38% on deadrise 35°. While the smallest value of total resistance coefficient was generated from chine 35° at R/L:1/14 and R/L:1/7. Optimum hull form for minimum resistance has been obtained, so it is interesting to continue with angle of entrance and stem angle of hull for further research.

  6. Persistent hepatitis virus infection and immune homeostasis

    OpenAIRE

    ZHOU Yun

    2014-01-01

    Homeostasis between the host and viruses is naturally maintained. On the one hand, the immune system activates the immune response to kill or eliminate viruses; on the other hand, the immune system controls the immune response to maintain immune homeostasis. The cause of persistent infections with hepatitis viruses such as HBV and HCV is that viral molecules damage the immune system of the host and their variants escape immune clearance. Long-term coexistence of the host and viruses is the pr...

  7. Neuroimmune regulation during intestinal development and homeostasis.

    Science.gov (United States)

    Veiga-Fernandes, Henrique; Pachnis, Vassilis

    2017-02-01

    Interactions between the nervous system and immune system are required for organ function and homeostasis. Evidence suggests that enteric neurons and intestinal immune cells share common regulatory mechanisms and can coordinate their responses to developmental challenges and environmental aggressions. These discoveries shed light on the physiology of system interactions and open novel perspectives for therapy designs that target underappreciated neurological-immunological commonalities. Here we highlight findings that address the importance of neuroimmune cell units (NICUs) in intestinal development, homeostasis and disease.

  8. A role of the adaptive immune system in glucose homeostasis.

    Science.gov (United States)

    Bronsart, Laura L; Contag, Christopher H

    2016-01-01

    The immune system, including the adaptive immune response, has recently been recognized as having a significant role in diet-induced insulin resistance. In this study, we aimed to determine if the adaptive immune system also functions in maintaining physiological glucose homeostasis in the absence of diet-induced disease. SCID mice and immunocompetent control animals were phenotypically assessed for variations in metabolic parameters and cytokine profiles. Additionally, the glucose tolerance of SCID and immunocompetent control animals was assessed following introduction of a high-fat diet. SCID mice on a normal chow diet were significantly insulin resistant relative to control animals despite having less fat mass. This was associated with a significant increase in the innate immunity-stimulating cytokines granulocyte colony-stimulating factor, monocyte chemoattractant protein 1 (MCP1), and MCP3. Additionally, the SCID mouse phenotype was exacerbated in response to a high-fat diet as evidenced by the further significant progression of glucose intolerance. These results support the notion that the adaptive immune system plays a fundamental biological role in glucose homeostasis, and that the absence of functional B and T cells results in disruption in the concentrations of various cytokines associated with macrophage proliferation and recruitment. Additionally, the absence of functional B and T cells is not protective against diet-induced pathology.

  9. Modelling the influence of steel fibres on the electrical resistivity of cementitious composites

    DEFF Research Database (Denmark)

    Solgaard, Anders Ole Stubbe; Michel, Alexander; Stang, Henrik

    2009-01-01

    One of the governing factors on the corrosion of embedded reinforcement is the electrical resistivity of the concrete. The combination of steel fibres and conventional reinforcement bars has been used in a number of structures. However, the addition of electrical con-ductive fibres might influence...... of steel fibre reinforced concrete (SFRC). The parameters investigated in the following are the fibre geometry, the fibre volume and the transitional resistance. On basis of the experimental results, a model, taking the resistivity of the fibres and the concrete matrix into account is proposed....... the overall resistivity of the material and thereby the corrosion rate of the embedded reinforcement. To the knowledge of the authors, only preliminary studies have been made on the influence of corrosion of the reinforcement bars from the addition of the electrical conductive steel fibres. Thus the present...

  10. Pharmacokinetic-Pharmacodynamic Model To Evaluate Intramuscular Tetracycline Treatment Protocols To Prevent Antimicrobial Resistance in Pigs

    DEFF Research Database (Denmark)

    Ahmad, Amais; Græsbøll, Kaare; Christiansen, Lasse Engbo

    2015-01-01

    High instances of antimicrobial resistance are linked to both routine and excessive antimicrobial use, but excessive or inappropriate use represents an unnecessary risk. The competitive growth advantages of resistant bacteria may be amplified by the strain dynamics; in particular, the extent...... to which resistant strains outcompete susceptible strains under antimicrobial pressure may depend not only on the antimicrobial treatment strategies but also on the epidemiological parameters, such as the composition of the bacterial strains in a pig. This study evaluated how variation in the dosing...... protocol for intramuscular administration of tetracycline and the composition of bacterial strains in a pig affect the level of resistance in the intestine of a pig. Predictions were generated by a mathematical model of competitive growth of Escherichia coli strains in pigs under specified plasma...

  11. Pharmacokinetic-Pharmacodynamic Model To Evaluate Intramuscular Tetracycline Treatment Protocols To Prevent Antimicrobial Resistance in Pigs

    DEFF Research Database (Denmark)

    Ahmad, Amais; Græsbøll, Kaare; Christiansen, Lasse Engbo

    2015-01-01

    protocol for intramuscular administration of tetracycline and the composition of bacterial strains in a pig affect the level of resistance in the intestine of a pig. Predictions were generated by a mathematical model of competitive growth of Escherichia coli strains in pigs under specified plasma......High instances of antimicrobial resistance are linked to both routine and excessive antimicrobial use, but excessive or inappropriate use represents an unnecessary risk. The competitive growth advantages of resistant bacteria may be amplified by the strain dynamics; in particular, the extent...... to which resistant strains outcompete susceptible strains under antimicrobial pressure may depend not only on the antimicrobial treatment strategies but also on the epidemiological parameters, such as the composition of the bacterial strains in a pig. This study evaluated how variation in the dosing...

  12. Multistrain models predict sequential multidrug treatment strategies to result in less antimicrobial resistance than combination treatment

    DEFF Research Database (Denmark)

    Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo

    2016-01-01

    generated by a mathematical model of the competitive growth of multiple strains of Escherichia coli.Results: Simulation studies showed that sequential use of tetracycline and ampicillin reduced the level of double resistance, when compared to the combination treatment. The effect of the cycling frequency...... frequency did not play a role in suppressing the growth of resistant strains, but the specific order of the two antimicrobials did. Predictions made from the study could be used to redesign multidrug treatment strategies not only for intramuscular treatment in pigs, but also for other dosing routes.......Background: Combination treatment is increasingly used to fight infections caused by bacteria resistant to two or more antimicrobials. While multiple studies have evaluated treatment strategies to minimize the emergence of resistant strains for single antimicrobial treatment, fewer studies have...

  13. An ETP model (exclusion-tolerance-progression for multi drug resistance

    Directory of Open Access Journals (Sweden)

    Kannan Subburaj

    2005-04-01

    Full Text Available Abstract Background It is known that sensitivity or resistance of tumor cells to a given chemotherapeutic agent is an acquired characteristic(s, depending on the heterogeneity of the tumor mass subjected to the treatment. The clinical success of a chemotherapeutic regimen depends on the ratio of sensitive to resistant cell populations. Results Based on findings from clinical and experimental studies, a unifying model is proposed to delineate the potential mechanism by which tumor cells progress towards multi drug resistance, resulting in failure of chemotherapy. Conclusion It is suggested that the evolution of multi drug resistance is a developmentally orchestrated event. Identifying stage-specific time windows during this process would help to identify valid therapeutic targets for the effective elimination of malignancy.

  14. Thermal Conductivity in Soil: Theoretical Approach by 3D Infinite Resistance Grid Model

    Science.gov (United States)

    Changjan, A.; Intaravicha, N.

    2018-05-01

    Thermal conductivity in soil was elementary characteristic of soil that conduct heat, measured in terms of Fourier’s Law for heat conduction and useful application in many fields: such as Utilizing underground cable for transmission and distribution systems, the rate of cooling of the cable depends on the thermal properties of the soil surrounding the cable. In this paper, we investigated thermal conductivity in soil by infinite three dimensions (3D) electrical resistance circuit concept. Infinite resistance grid 3D was the grid of resistors that extends to infinity in all directions. Model of thermal conductivity in soil of this research was generated from this concept: comparison between electrical resistance and thermal resistance in soil. Finally, we investigated the analytical form of thermal conductivity in soil which helpful for engineering and science students that could exhibit education with a principle of physics that applied to real situations.

  15. Maintaining homeostasis by decision-making.

    Directory of Open Access Journals (Sweden)

    Christoph W Korn

    2015-05-01

    Full Text Available Living organisms need to maintain energetic homeostasis. For many species, this implies taking actions with delayed consequences. For example, humans may have to decide between foraging for high-calorie but hard-to-get, and low-calorie but easy-to-get food, under threat of starvation. Homeostatic principles prescribe decisions that maximize the probability of sustaining appropriate energy levels across the entire foraging trajectory. Here, predictions from biological principles contrast with predictions from economic decision-making models based on maximizing the utility of the endpoint outcome of a choice. To empirically arbitrate between the predictions of biological and economic models for individual human decision-making, we devised a virtual foraging task in which players chose repeatedly between two foraging environments, lost energy by the passage of time, and gained energy probabilistically according to the statistics of the environment they chose. Reaching zero energy was framed as starvation. We used the mathematics of random walks to derive endpoint outcome distributions of the choices. This also furnished equivalent lotteries, presented in a purely economic, casino-like frame, in which starvation corresponded to winning nothing. Bayesian model comparison showed that--in both the foraging and the casino frames--participants' choices depended jointly on the probability of starvation and the expected endpoint value of the outcome, but could not be explained by economic models based on combinations of statistical moments or on rank-dependent utility. This implies that under precisely defined constraints biological principles are better suited to explain human decision-making than economic models based on endpoint utility maximization.

  16. Narcissistic Force Meets Systemic Resistance: The Energy Clash Model.

    Science.gov (United States)

    Sedikides, Constantine; Campbell, W Keith

    2017-05-01

    This article focuses on the interplay between narcissistic leaders and organizations. It attempts to capture the gist of this interplay with a model outlining the narcissistic organizational trajectory. The Energy Clash Model borrows and adapts a phase/state physics metaphor to conceptualize narcissism as a force that enters or emerges in a stable system (i.e., organization) as a leader, destabilizes it, and stabilizes it at a different state or is expelled. The model consists of three time-contingent phases: perturbation, conflict, and resolution. Narcissists create instability through waves of excitement, proposed reforms, and an inspiring vision for organization's future ( perturbation). With the passage of time, though, systemic awareness and alertness intensify, as organizational costs-in terms of human resources and monetary losses-accrue. Narcissistic energy clashes directly with the organization ( conflict), a clash likely to restabilize the system eventually. The conflict may provoke the exit of the narcissistic leader or his or her accommodation, that is, steps or controls negotiated between the system and the leader ( resolution). Although narcissism is subject to organizational liability, narcissistic energy, when managed and directed properly, may contribute to organizational innovation and evolution. Thus, several interventions for working with narcissistic leaders are discussed.

  17. Exploring electrical resistance: a novel kinesthetic model helps to resolve some misconceptions

    Science.gov (United States)

    Cottle, Dan; Marshall, Rick

    2016-09-01

    A simple ‘hands on’ physical model is described which displays analogous behaviour to some aspects of the free electron theory of metals. Using it students can get a real feel for what is going on inside a metallic conductor. Ohms Law, the temperature dependence of resistivity, the dependence of resistance on geometry, how the conduction electrons respond to a potential difference and the concepts of mean free path and drift speed of the conduction electrons can all be explored. Some quantitative results obtained by using the model are compared with the predictions of Drude’s free electron theory of electrical conduction.

  18. Within-host selection of drug resistance in a mouse model of repeated interrupted treatment of Plasmodium yoelii infection

    NARCIS (Netherlands)

    Nuralitha, Suci; Siregar, Josephine E; Syafruddin, Din; Hoepelman, Andy I M; Marzuki, Sangkot

    2017-01-01

    BACKGROUND: To study within-host selection of resistant parasites, an important factor in the development of resistance to anti-malarial drugs, a mouse model of repeated interrupted malaria treatment (RIT) has been developed. The characteristics of within host selection of resistance to atovaquone

  19. Development of a programming model for radiation-resistant software

    International Nuclear Information System (INIS)

    Eichhorn, G.; Piercey, R.B.

    1984-01-01

    The adverse effects of ionizing radiation on microelectronic systems include cumulative dosage effects, single-event upsets (SEU's) and latch-up. Most frequent, especially when the radiation environment includes heavy ions, are SEU's. Unfortunately SEU's are difficult to detect since they can be read (in RAM or ROM) as valid addresses. They can however be handled in software by proper techniques. The authors refer to their method as MRS - Maximally Redundant Software. The MRS programming model which the authors are developing uses multiply redundant boot blocks, majority voting, periodic refresh, and error recovery techniques to minimize the deleterious effects of SEU's. 1 figure

  20. Characteristics and contributions of hyperandrogenism to insulin resistance and other metabolic profiles in polycystic ovary syndrome.

    Science.gov (United States)

    Huang, Rong; Zheng, Jun; Li, Shengxian; Tao, Tao; Ma, Jing; Liu, Wei

    2015-05-01

    To investigate the different characteristics in Chinese Han women with polycystic ovary syndrome, and to analyze the significance of hyperandrogenism in insulin resistance and other metabolic profiles. A cross-sectional study. Medical university hospital. A total of 229 women with polycystic ovary syndrome aged 18-45 years. Women with polycystic ovary syndrome, diagnosed by Rotterdam criteria, were divided into four groups according to the quartile intervals of free androgen index levels. Comparisons between groups were performed using one-way analysis of variance. Stepwise logistic regression analysis was performed to investigate the association between homeostasis model assessment-insulin resistance and independent variables. Within the four phenotypes, women with phenotype 1 (hyperandrogenism, oligo/anovulation, and polycystic ovaries) exhibited higher total testosterone, free androgen index, androstenedione, low-density lipoprotein, and lower quantitative insulin sensitivity check index (p polycystic ovaries) showed lower total cholesterol, low-density lipoprotein, and homeostasis model assessment-insulin resistance, but higher high-density lipoprotein (p < 0.05). The levels of triglycerides, total cholesterol, low-density lipoprotein, and homeostasis model assessment-insulin resistance significantly increased, but high-density lipoprotein and quantitative insulin sensitivity check index decreased with the elevation of free androgen index intervals. After adjustment for lipid profiles, free androgen index was significantly associated with homeostasis model assessment-insulin resistance in both lean and overweight/obese women (odds ratio 1.302, p = 0.039 in lean vs. odds ratio 1.132, p = 0.036 in overweight/obese). Phenotypes 1 and 4 represent groups with the most and least severe metabolic profiles, respectively. Hyperandrogenism, particularly with elevated free androgen index, is likely a key contributing factor for insulin resistance and for the aggravation

  1. Zinc and the modulation of redox homeostasis

    Science.gov (United States)

    Oteiza, Patricia I.

    2012-01-01

    Zinc, a redox inactive metal, has been long viewed as a component of the antioxidant network, and growing evidence points to its involvement in redox-regulated signaling. These actions are exerted through several mechanisms based on the unique chemical and functional properties of zinc. Overall, zinc contributes to maintain the cell redox balance through different mechanisms including: i) the regulation of oxidant production and metal-induced oxidative damage; ii) the dynamic association of zinc with sulfur in protein cysteine clusters, from which the metal can be released by nitric oxide, peroxides, oxidized glutathione and other thiol oxidant species; iii) zinc-mediated induction of the zinc-binding protein metallothionein, which releases the metal under oxidative conditions and act per se scavenging oxidants; iv) the involvement of zinc in the regulation of glutathione metabolism and of the overall protein thiol redox status; and v) a direct or indirect regulation of redox signaling. Findings of oxidative stress, altered redox signaling, and associated cell/tissue disfunction in cell and animal models of zinc deficiency, stress the relevant role of zinc in the preservation of cell redox homeostasis. However, while the participation of zinc in antioxidant protection, redox sensing, and redox-regulated signaling is accepted, the involved molecules, targets and mechanisms are still partially known and the subject of active research. PMID:22960578

  2. Classical and quantum stochastic models of resistive and memristive circuits

    Science.gov (United States)

    Gough, John E.; Zhang, Guofeng

    2017-07-01

    The purpose of this paper is to examine stochastic Markovian models for circuits in phase space for which the drift term is equivalent to the standard circuit equations. In particular, we include dissipative components corresponding to both a resistor and a memristor in series. We obtain a dilation of the problem which is canonical in the sense that the underlying Poisson bracket structure is preserved under the stochastic flow. We do this first of all for standard Wiener noise but also treat the problem using a new concept of symplectic noise, where the Poisson structure is extended to the noise as well as the circuit variables, and in particular where we have canonically conjugate noises. Finally, we construct a dilation which describes the quantum mechanical analogue.

  3. Application of DOI index to analysis of selected examples of resistivity imaging models in Quaternary sediments

    Directory of Open Access Journals (Sweden)

    Glazer Michał

    2014-12-01

    Full Text Available Interpretation of resistivity cross sections may be in many cases unreliable due to the presence of artifacts left by the inversion process. One way to avoid erroneous conclusions about geological structure is creation of Depth of Investigation (DOI index maps, which describe durability of prepared model with respect to variable parameters of inversion. To assess the usefulness of this interpretation methodology in resistivity imaging method over quaternary sediments, it has been used to one synthetic data set and three investigation sites. Two of the study areas were placed in the Upper Silesian Industrial District region: Bytom - Karb, Chorzów - Chorzow Stary; and one in the Southern Pomeranian Lake District across Piława River Valley. Basing on the available geological information the results show high utility of DOI index in analysis of received resistivity models, on which areas poorly constrained by data has been designated.

  4. Leveraging Resistance to Change and the Skunk Works Model of Innovation

    DEFF Research Database (Denmark)

    Fosfuri, Andrea; Rønde, Thomas

    We study a situation in which an R&D department promotes the introduction of an innovation, which results in costly re-adjustments for production workers. In response, the production department tries to resist change by improving the existing technology. We show that firms balancing the strengths...... of the two departments perform better. This principle is employed to derive several implications concerning the hiring of talents, monetary incentives, and technology investment policies. As a negative effect, resistance to change might distort the R&D department's effort away from radical innovations....... The firm can solve this problem by implementing the so-called "skunk works model" of innovation where the R&D department is isolated from the rest of the organization. Resistance to change, innovation, skunk works model, contest....

  5. Evaluation of seismic reliability of steel moment resisting frames rehabilitated by concentric braces with probabilistic models

    Directory of Open Access Journals (Sweden)

    Fateme Rezaei

    2017-08-01

    Full Text Available Probability of structure failure which has been designed by "deterministic methods" can be more than the one which has been designed in similar situation using probabilistic methods and models considering "uncertainties". The main purpose of this research was to evaluate the seismic reliability of steel moment resisting frames rehabilitated with concentric braces by probabilistic models. To do so, three-story and nine-story steel moment resisting frames were designed based on resistant criteria of Iranian code and then they were rehabilitated based on controlling drift limitations by concentric braces. Probability of frames failure was evaluated by probabilistic models of magnitude, location of earthquake, ground shaking intensity in the area of the structure, probabilistic model of building response (based on maximum lateral roof displacement and probabilistic methods. These frames were analyzed under subcrustal source by sampling probabilistic method "Risk Tools" (RT. Comparing the exceedance probability of building response curves (or selected points on it of the three-story and nine-story model frames (before and after rehabilitation, seismic response of rehabilitated frames, was reduced and their reliability was improved. Also the main effective variables in reducing the probability of frames failure were determined using sensitivity analysis by FORM probabilistic method. The most effective variables reducing the probability of frames failure are  in the magnitude model, ground shaking intensity model error and magnitude model error

  6. Mapping the resistance-associated mobilome of a carbapenem-resistant Klebsiella pneumoniae strain reveals insights into factors shaping these regions and facilitates generation of a 'resistance-disarmed' model organism.

    Science.gov (United States)

    Bi, Dexi; Jiang, Xiaofei; Sheng, Zi-Ke; Ngmenterebo, David; Tai, Cui; Wang, Minggui; Deng, Zixin; Rajakumar, Kumar; Ou, Hong-Yu

    2015-10-01

    This study aims to investigate the landscape of the mobile genome, with a focus on antibiotic resistance-associated factors in carbapenem-resistant Klebsiella pneumoniae. The mobile genome of the completely sequenced K. pneumoniae HS11286 strain (an ST11, carbapenem-resistant, near-pan-resistant, clinical isolate) was annotated in fine detail. The identified mobile genetic elements were mapped to the genetic contexts of resistance genes. The blaKPC-2 gene and a 26 kb region containing 12 clustered antibiotic resistance genes and one biocide resistance gene were deleted, and the MICs were determined again to ensure that antibiotic resistance had been lost. HS11286 contains six plasmids, 49 ISs, nine transposons, two separate In2-related integron remnants, two integrative and conjugative elements (ICEs) and seven prophages. Sixteen plasmid-borne resistance genes were identified, 14 of which were found to be directly associated with Tn1721-, Tn3-, Tn5393-, In2-, ISCR2- and ISCR3-derived elements. IS26 appears to have actively moulded several of these genetic regions. The deletion of blaKPC-2, followed by the deletion of a 26 kb region containing 12 clustered antibiotic resistance genes, progressively decreased the spectrum and level of resistance exhibited by the resultant mutant strains. This study has reiterated the role of plasmids as bearers of the vast majority of resistance genes in this species and has provided valuable insights into the vital role played by ISs, transposons and integrons in shaping the resistance-coding regions in this important strain. The 'resistance-disarmed' K. pneumoniae ST11 strain generated in this study will offer a more benign and readily genetically modifiable model organism for future extensive functional studies. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. A Dual-Sensing Receptor Confers Robust Cellular Homeostasis

    Directory of Open Access Journals (Sweden)

    Hannah Schramke

    2016-06-01

    Full Text Available Cells have evolved diverse mechanisms that maintain intracellular homeostasis in fluctuating environments. In bacteria, control is often exerted by bifunctional receptors acting as both kinase and phosphatase to regulate gene expression, a design known to provide robustness against noise. Yet how such antagonistic enzymatic activities are balanced as a function of environmental change remains poorly understood. We find that the bifunctional receptor that regulates K+ uptake in Escherichia coli is a dual sensor, which modulates its autokinase and phosphatase activities in response to both extracellular and intracellular K+ concentration. Using mathematical modeling, we show that dual sensing is a superior strategy for ensuring homeostasis when both the supply of and demand for a limiting resource fluctuate. By engineering standards, this molecular control system displays a strikingly high degree of functional integration, providing a reference for the vast numbers of receptors for which the sensing strategy remains elusive.

  8. Unaltered Prion Pathogenesis in a Mouse Model of High-Fat Diet-Induced Insulin Resistance.

    Directory of Open Access Journals (Sweden)

    Caihong Zhu

    Full Text Available Epidemiological, clinical, and experimental animal studies suggest a strong correlation between insulin resistance and Alzheimer's disease. In fact, type-2 diabetes is considered an important risk factor of developing Alzheimer's disease. In addition, impaired insulin signaling in the Alzheimer's disease brain may promote Aβ production, impair Aβ clearance and induce tau hyperphosphorylation, thereby leading to deterioration of the disease. The pathological prion protein, PrPSc, deposits in the form of extracellular aggregates and leads to dementia, raising the question as to whether prion pathogenesis may also be affected by insulin resistance. We therefore established high-fat diet-induced insulin resistance in tga20 mice, which overexpress the prion protein. We then inoculated the insulin-resistant mice with prions. We found that insulin resistance in tga20 mice did not affect prion disease progression, PrPSc deposition, astrogliosis or microglial activation, and had no effect on survival. Our study demonstrates that in a mouse model, insulin resistance does not significantly contribute to prion pathogenesis.

  9. Diversity of fecal coliforms and their antimicrobial resistance patterns in wastewater treatment model plant.

    Science.gov (United States)

    Luczkiewicz, A; Fudala-Ksiazek, S; Jankowska, K; Quant, B; Olańczuk-Neyman, K

    2010-01-01

    The occurrence of resistance patterns among wastewater fecal coliforms was determined in the study. Susceptibility of the isolates was tested against 19 antimicrobial agents: aminoglycosides, aztreonam, carbapenems, cephalosporines, beta-lactam/beta-lactamase inhibitors, penicillines, tetracycline, trimethoprim/sulfamethoxazole, and fluoroquinolones. Additionally the removal of resistant isolates was evaluated in the laboratory-scale wastewater treatment model plant (M-WWTP), continuously supplied with the wastewater obtained from the full-scale WWTP. Number of fecal coliforms in raw (after mechanical treatment) and treated wastewater, as well as in aerobic chamber effluent was determined using selective medium. The selected strains were identified and examined for antibiotic resistance using Phoenix Automated Microbiology System (BD Biosciences, USA). The strains were identified as Escherichia coli (n=222), Klebsiella pneumoniae ssp. ozaenae (n=9), and Pantoea agglomerans (n=1). The isolate of P. agglomerans as well as 48% of E. coli isolates were sensitive to all antimicrobials tested. The most frequent resistance patterns were found for ampicillin: 100% of K. pneumoniae ssp. ozaenae and 41% of E. coli isolates. Among E. coli isolates 12% was regarded as multiple antimicrobial resistant (MAR). In the studied M-WWTP, the applied activated sludge processes reduced considerably the number of fecal coliforms, but increased the ratio of antimicrobial-resistant E. coli isolates to sensitive ones, especially among strains with MAR patterns.

  10. Ambient air pollution, adipokines, and glucose homeostasis: The Framingham Heart Study.

    Science.gov (United States)

    Li, Wenyuan; Dorans, Kirsten S; Wilker, Elissa H; Rice, Mary B; Kloog, Itai; Schwartz, Joel D; Koutrakis, Petros; Coull, Brent A; Gold, Diane R; Meigs, James B; Fox, Caroline S; Mittleman, Murray A

    2018-02-01

    To examine associations of proximity to major roadways, sustained exposure to fine particulate matter (PM 2.5 ), and acute exposure to ambient air pollutants with adipokines and measures of glucose homeostasis among participants living in the northeastern United States. We included 5958 participants from the Framingham Offspring cohort examination cycle 7 (1998-2001) and 8 (2005-2008) and Third Generation cohort examination cycle 1 (2002-2005) and 2 (2008-2011), who did not have type 2 diabetes at the time of examination visit. We calculated 2003 annual average PM 2.5 at participants' home address, residential distance to the nearest major roadway, and daily PM 2.5 , black carbon (BC), sulfate, nitrogen oxides (NO x ), and ozone concentrations. We used linear mixed effects models for fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) which were measured up to twice, and used linear regression models for adiponectin, resistin, leptin, and hemoglobin A1c (HbA1c) which were measured only once, adjusting for demographics, socioeconomic position, lifestyle, time, and seasonality. The mean age was 51years and 55% were women. Participants who lived 64m (25th percentile) from a major roadway had 0.28% (95% CI: 0.05%, 0.51%) higher fasting plasma glucose than participants who lived 413m (75th percentile) away, and the association appeared to be driven by participants who lived within 50m from a major roadway. Higher exposures to 3- to 7-day moving averages of BC and NO x were associated with higher glucose whereas the associations for ozone were negative. The associations otherwise were generally null and did not differ by median age, sex, educational attainment, obesity status, or prediabetes status. Living closer to a major roadway or acute exposure to traffic-related air pollutants were associated with dysregulated glucose homeostasis but not with adipokines among participants from the Framingham Offspring and Third Generation

  11. Cooperation between brain and islet in glucose homeostasis and diabetes

    Science.gov (United States)

    Schwartz, Michael W.; Seeley, Randy J.; Tschöp, Matthias H.; Woods, Stephen C.; Morton, Gregory J.; Myers, Martin G.; D'Alessio, David

    2014-01-01

    Although a prominent role for the brain in glucose homeostasis was proposed by scientists in the nineteenth century, research throughout most of the twentieth century focused on evidence that the function of pancreatic islets is both necessary and sufficient to explain glucose homeostasis, and that diabetes results from defects of insulin secretion, action or both. However, insulin-independent mechanisms, referred to as ‘glucose effectiveness’, account for roughly 50% of overall glucose disposal, and reduced glucose effectiveness also contributes importantly to diabetes pathogenesis. Although mechanisms underlying glucose effectiveness are poorly understood, growing evidence suggests that the brain can dynamically regulate this process in ways that improve or even normalize glycaemia in rodent models of diabetes. Here we present evidence of a brain-centred glucoregulatory system (BCGS) that can lower blood glucose levels via both insulin-dependent and -independent mechanisms, and propose a model in which complex and highly coordinated interactions between the BCGS and pancreatic islets promote normal glucose homeostasis. Because activation of either regulatory system can compensate for failure of the other, defects in both may be required for diabetes to develop. Consequently, therapies that target the BCGS in addition to conventional approaches based on enhancing insulin effects may have the potential to induce diabetes remission, whereas targeting just one typically does not. PMID:24201279

  12. Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype.

    Science.gov (United States)

    Ngo, Kevin; Patil, Prashanti; McGowan, Sara J; Niedernhofer, Laura J; Robbins, Paul D; Kang, James; Sowa, Gwendolyn; Vo, Nam

    2017-09-01

    Aging greatly increases the risk for intervertebral disc degeneration (IDD) as a result of proteoglycan loss due to reduced synthesis and enhanced degradation of the disc matrix proteoglycan (PG). How disc matrix PG homeostasis becomes perturbed with age is not known. The goal of this study is to determine whether cellular senescence is a source of this perturbation. We demonstrated that disc cellular senescence is dramatically increased in the DNA repair-deficient Ercc1 -/Δ mouse model of human progeria. In these accelerated aging mice, increased disc cellular senescence is closely associated with the rapid loss of disc PG. We also directly examine PG homeostasis in oxidative damage-induced senescent human cells using an in vitro cell culture model system. Senescence of human disc cells treated with hydrogen peroxide was confirmed by growth arrest, senescence-associated β-galactosidase activity, γH2AX foci, and acquisition of senescence-associated secretory phenotype. Senescent human disc cells also exhibited perturbed matrix PG homeostasis as evidenced by their decreased capacity to synthesize new matrix PG and enhanced degradation of aggrecan, a major matrix PG. of the disc. Our in vivo and in vitro findings altogether suggest that disc cellular senescence is an important driver of PG matrix homeostatic perturbation and PG loss. Published by Elsevier B.V.

  13. Osteoarthritis: Control of human cartilage hypertrophic differentiation. Research highlight van: Gremlin1, frizzled-related protein, and Dkk-1 are key regulators of human articular cartilage homeostasis

    NARCIS (Netherlands)

    Buckland, J.; Leijten, Jeroen Christianus Hermanus; van Blitterswijk, Clemens; Karperien, Hermanus Bernardus Johannes

    2012-01-01

    Disruption of articular cartilage homeostasis is important in osteoarthritis (OA) pathogenesis, key to which is activation of articular chondrocyte hypertrophic differentiation. Healthy articular cartilage is resistant to hypertrophic differentiation, whereas growth-plate cartilage is destined to

  14. Modeling evolution of resistance of sugarcane borer (Lepidoptera: Crambidae) to transgenic Bt corn.

    Science.gov (United States)

    Kang, J; Huang, F; Onstad, D W

    2014-08-01

    Diatraea saccharalis (F.) (Lepidoptera: Crambidae) is a target pest of transgenic corn expressing Bacillus thuringiensis (Bt) protein, and the first evidence of resistance by D. saccharalis to Cry1Ab corn was detected in a field population in northeast Louisiana in 2004. We used a model of population dynamics and genetics of D. saccharalis to 1) study the effect of interfield dispersal, the first date that larvae enter diapause for overwintering, toxin mortality, the proportion of non-Bt corn in the corn patch, and the area of a crop patch on Bt resistance evolution; and 2) to identify gaps in empirical knowledge for managing D. saccharalis resistance to Bt corn. Increasing, the proportion of corn refuge did not always improve the durability of Bt corn if the landscape also contained sugarcane, sorghum, or rice. In the landscape, which consisted of 90% corn area, 5% sorghum area, and 5% rice area, the durability of single-protein Bt corn was 40 yr when the proportion of corn refuge was 0.2 but 16 yr when the proportion of corn refuge was 0.5. The Bt resistance evolution was sensitive to a change (from Julian date 260 to 272) in the first date larvae enter diapause for overwintering and moth movement. In the landscapes with Bt corn, non-Bt corn, sugarcane, sorghum, and rice, the evolution of Bt resistance accelerated when larvae entered diapause for overwintering early. Intermediate rates of moth movement delayed evolution of resistance more than either extremely low or high rates. This study suggested that heterogeneity in the agrolandscapes may complicate the strategy for managing Bt resistance in D. saccharalis, and designing a Bt resistance management strategy for D. saccharalis is challenging because of a lack of empirical data about overwintering and moth movement.

  15. Homology modelling of Drosophila cytochrome P450 enzymes associated with insecticide resistance.

    Science.gov (United States)

    Jones, Robert T; Bakker, Saskia E; Stone, Deborah; Shuttleworth, Sally N; Boundy, Sam; McCart, Caroline; Daborn, Phillip J; ffrench-Constant, Richard H; van den Elsen, Jean M H

    2010-10-01

    Overexpression of the cytochrome P450 gene Cyp6g1 confers resistance against DDT and a broad range of other insecticides in Drosophila melanogaster Meig. In the absence of crystal structures of CYP6G1 or complexes with its substrates, structural studies rely on homology modelling and ligand docking to understand P450-substrate interactions. Homology models are presented for CYP6G1, a P450 associated with resistance to DDT and neonicotinoids, and two other enzymes associated with insecticide resistance in D. melanogaster, CYP12D1 and CYP6A2. The models are based on a template of the X-ray structure of the phylogenetically related human CYP3A4, which is known for its broad substrate specificity. The model of CYP6G1 has a much smaller active site cavity than the template. The cavity is also 'V'-shaped and is lined with hydrophobic residues, showing high shape and chemical complementarity with the molecular characteristics of DDT. Comparison of the DDT-CYP6G1 complex and a non-resistant CYP6A2 homology model implies that tight-fit recognition of this insecticide is important in CYP6G1. The active site can accommodate differently shaped substrates ranging from imidacloprid to malathion but not the pyrethroids permethrin and cyfluthrin. The CYP6G1, CYP12D1 and CYP6A2 homology models can provide a structural insight into insecticide resistance in flies overexpressing P450 enzymes with broad substrate specificities.

  16. Modeling and control of a DC upset resistance butt welding process

    NARCIS (Netherlands)

    Naus, G.J.L.; Meulenberg, R.; Molengraft, van de M.J.G.

    2007-01-01

    This paper presents the analysis and synthesis of modeling and control of the DC upset resistance butt welding process used in rim production lines. A new control strategy is developed, enabling active control of the welding seam temperature and the upset size. As a result, set-up times and energy

  17. Design of squat shear walls using continuous strut-and-tie resistant models

    International Nuclear Information System (INIS)

    Santos, S.H. de C; Silva, R.E. da

    1993-01-01

    A new approach is presented for designing squat shear walls, subjected to seismic loading. In this approach, the strut-and-tie resistant models, proposed by Schlaich et al., are generalized in order to analyze continuous fields of compression and tension stresses. The application of the presented methodology is illustrated through numerical examples. (author)

  18. Are Available Models Reliable for Predicting the FRP Contribution to the Shear Resistance of RC Beams?

    DEFF Research Database (Denmark)

    Sas, G.; Täljsten, Björn; Barros, J.

    2009-01-01

    In this paper the trustworthiness of the existing theory for predicting the fiber-reinforced plastic contribution to the shear resistance of reinforced concrete beams is discussed. The most well-known shear models for external bonded reinforcement are presented, commented on, and compared...

  19. Safety Analysis of the Patch Load Resistance of Plate Girders: Influence of Model Error and Variability

    Directory of Open Access Journals (Sweden)

    Farzad Shahabian

    2013-12-01

    Full Text Available This study aims to undertake a statistical study to evaluate the accuracy of nine models that have been previously proposed for estimating the ultimate resistance of plate girders subjected to patch loading. For each model, mean errors and standard errors, as well as the probability of underestimating or overestimating patch load resistance, are estimated and the resultant values are compared one to another. Prior to that, the models are initially calibrated in order to improve interaction formulae using an experimental data set collected from the literature. The models are then analyzed by computing design factors associated with a target risk level (probability of exceedance. These models are compared one to another considering uncertainties existed in material and geometrical properties. The Monte Carlo simulation method is used to generate random variables. The statistical parameters of the calibrated models are calculated for various coefficients of variations regardless of their correlation with the random resistance variables. These probabilistic results are very useful for evaluating the stochastic sensitivity of the calibrated models.

  20. Modeling the Responses to Resistance Training in an Animal Experiment Study

    Directory of Open Access Journals (Sweden)

    Antony G. Philippe

    2015-01-01

    Full Text Available The aim of the present study was to test whether systems models of training effects on performance in athletes can be used to explore the responses to resistance training in rats. 11 Wistar Han rats (277 ± 15 g underwent 4 weeks of resistance training consisting in climbing a ladder with progressive loads. Training amount and performance were computed from total work and mean power during each training session. Three systems models relating performance to cumulated training bouts have been tested: (i with a single component for adaptation to training, (ii with two components to distinguish the adaptation and fatigue produced by exercise bouts, and (iii with an additional component to account for training-related changes in exercise-induced fatigue. Model parameters were fitted using a mixed-effects modeling approach. The model with two components was found to be the most suitable to analyze the training responses (R2=0.53; P<0.001. In conclusion, the accuracy in quantifying training loads and performance in a rodent experiment makes it possible to model the responses to resistance training. This modeling in rodents could be used in future studies in combination with biological tools for enhancing our understanding of the adaptive processes that occur during physical training.

  1. Discourse in Action: Parents' use of medical and social models to resist disability stigma.

    Science.gov (United States)

    Manago, Bianca; Davis, Jenny L; Goar, Carla

    2017-07-01

    For parents of children with disabilities, stigmatization is part of everyday life. To resist the negative social and emotional consequences of stigma, parents both challenge and deflect social devaluations. Challenges work to upend the stigmatizing structure, while deflections maintain the interaction order. We examine how parents of children with disabilities deploy deflections and challenges, and how their stigma resistance strategies combine with available models of disability discourse. Disability discourse falls into two broad categories: medical and social. The medical model emphasizes diagnostic labels and treats impairment as an individual deficit, while the social model centralizes unaccommodating social structures. The social model's activist underpinnings make it a logical frame for parents to use as they challenge disability stigma. In turn, the medical model's focus on individual "improvement" seems to most closely align with stigma deflections. However, the relationship between stigma resistance strategies and models of disability is an empirical question not yet addressed in the literature. In this study, we examine 117 instances of stigmatization from 40 interviews with 43 parents, and document how parents respond. We find that challenges and deflections do not map cleanly onto the social or medical models. Rather, parents invoke medical and social meanings in ways that serve diverse ends, sometimes centralizing a medical label to challenge stigma, and sometimes recognizing disabling social structures, but deflecting stigma nonetheless. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Acquired MET expression confers resistance to EGFR inhibition in a mouse model of glioblastoma multiforme.

    Science.gov (United States)

    Jun, H J; Acquaviva, J; Chi, D; Lessard, J; Zhu, H; Woolfenden, S; Bronson, R T; Pfannl, R; White, F; Housman, D E; Iyer, L; Whittaker, C A; Boskovitz, A; Raval, A; Charest, A

    2012-06-21

    Glioblastoma multiforme (GBM) is an aggressive brain tumor for which there is no cure. Overexpression of wild-type epidermal growth factor receptor (EGFR) and loss of the tumor suppressor genes Ink4a/Arf and PTEN are salient features of this deadly cancer. Surprisingly, targeted inhibition of EGFR has been clinically disappointing, demonstrating an innate ability for GBM to develop resistance. Efforts at modeling GBM in mice using wild-type EGFR have proven unsuccessful to date, hampering endeavors at understanding molecular mechanisms of therapeutic resistance. Here, we describe a unique genetically engineered mouse model of EGFR-driven gliomagenesis that uses a somatic conditional overexpression and chronic activation of wild-type EGFR in cooperation with deletions in the Ink4a/Arf and PTEN genes in adult brains. Using this model, we establish that chronic activation of wild-type EGFR with a ligand is necessary for generating tumors with histopathological and molecular characteristics of GBMs. We show that these GBMs are resistant to EGFR kinase inhibition and we define this resistance molecularly. Inhibition of EGFR kinase activity using tyrosine kinase inhibitors in GBM tumor cells generates a cytostatic response characterized by a cell cycle arrest, which is accompanied by a substantial change in global gene expression levels. We demonstrate that an important component of this pattern is the transcriptional activation of the MET receptor tyrosine kinase and that pharmacological inhibition of MET overcomes the resistance to EGFR inhibition in these cells. These findings provide important new insights into mechanisms of resistance to EGFR inhibition and suggest that inhibition of multiple targets will be necessary to provide therapeutic benefit for GBM patients.

  3. Stability Analysis of an HIV/AIDS Dynamics Model with Drug Resistance

    Directory of Open Access Journals (Sweden)

    Qianqian Li

    2012-01-01

    Full Text Available A mathematical model of HIV/AIDS transmission incorporating treatment and drug resistance was built in this study. We firstly calculated the threshold value of the basic reproductive number (R0 by the next generation matrix and then analyzed stability of two equilibriums by constructing Lyapunov function. When R0<1, the system was globally asymptotically stable and converged to the disease-free equilibrium. Otherwise, the system had a unique endemic equilibrium which was also globally asymptotically stable. While an antiretroviral drug tried to reduce the infection rate and prolong the patients’ survival, drug resistance was neutralizing the effects of treatment in fact.

  4. Mechanistic characterization and molecular modeling of hepatitis B virus polymerase resistance to entecavir.

    Science.gov (United States)

    Walsh, Ann W; Langley, David R; Colonno, Richard J; Tenney, Daniel J

    2010-02-12

    Entecavir (ETV) is a deoxyguanosine analog competitive inhibitor of hepatitis B virus (HBV) polymerase that exhibits delayed chain termination of HBV DNA. A high barrier to entecavir-resistance (ETVr) is observed clinically, likely due to its potency and a requirement for multiple resistance changes to overcome suppression. Changes in the HBV polymerase reverse-transcriptase (RT) domain involve lamivudine-resistance (LVDr) substitutions in the conserved YMDD motif (M204V/I +/- L180M), plus an additional ETV-specific change at residues T184, S202 or M250. These substitutions surround the putative dNTP binding site or primer grip regions of the HBV RT. To determine the mechanistic basis for ETVr, wildtype, lamivudine-resistant (M204V, L180M) and ETVr HBVs were studied using in vitro RT enzyme and cell culture assays, as well as molecular modeling. Resistance substitutions significantly reduced ETV incorporation and chain termination in HBV DNA and increased the ETV-TP inhibition constant (K(i)) for HBV RT. Resistant HBVs exhibited impaired replication in culture and reduced enzyme activity (k(cat)) in vitro. Molecular modeling of the HBV RT suggested that ETVr residue T184 was adjacent to and stabilized S202 within the LVDr YMDD loop. ETVr arose through steric changes at T184 or S202 or by disruption of hydrogen-bonding between the two, both of which repositioned the loop and reduced the ETV-triphosphate (ETV-TP) binding pocket. In contrast to T184 and S202 changes, ETVr at primer grip residue M250 was observed during RNA-directed DNA synthesis only. Experimentally, M250 changes also impacted the dNTP-binding site. Modeling suggested a novel mechanism for M250 resistance, whereby repositioning of the primer-template component of the dNTP-binding site shifted the ETV-TP binding pocket. No structural data are available to confirm the HBV RT modeling, however, results were consistent with phenotypic analysis of comprehensive substitutions of each ETVr position

  5. Mechanistic characterization and molecular modeling of hepatitis B virus polymerase resistance to entecavir.

    Directory of Open Access Journals (Sweden)

    Ann W Walsh

    Full Text Available BACKGROUND: Entecavir (ETV is a deoxyguanosine analog competitive inhibitor of hepatitis B virus (HBV polymerase that exhibits delayed chain termination of HBV DNA. A high barrier to entecavir-resistance (ETVr is observed clinically, likely due to its potency and a requirement for multiple resistance changes to overcome suppression. Changes in the HBV polymerase reverse-transcriptase (RT domain involve lamivudine-resistance (LVDr substitutions in the conserved YMDD motif (M204V/I +/- L180M, plus an additional ETV-specific change at residues T184, S202 or M250. These substitutions surround the putative dNTP binding site or primer grip regions of the HBV RT. METHODS/PRINCIPAL FINDINGS: To determine the mechanistic basis for ETVr, wildtype, lamivudine-resistant (M204V, L180M and ETVr HBVs were studied using in vitro RT enzyme and cell culture assays, as well as molecular modeling. Resistance substitutions significantly reduced ETV incorporation and chain termination in HBV DNA and increased the ETV-TP inhibition constant (K(i for HBV RT. Resistant HBVs exhibited impaired replication in culture and reduced enzyme activity (k(cat in vitro. Molecular modeling of the HBV RT suggested that ETVr residue T184 was adjacent to and stabilized S202 within the LVDr YMDD loop. ETVr arose through steric changes at T184 or S202 or by disruption of hydrogen-bonding between the two, both of which repositioned the loop and reduced the ETV-triphosphate (ETV-TP binding pocket. In contrast to T184 and S202 changes, ETVr at primer grip residue M250 was observed during RNA-directed DNA synthesis only. Experimentally, M250 changes also impacted the dNTP-binding site. Modeling suggested a novel mechanism for M250 resistance, whereby repositioning of the primer-template component of the dNTP-binding site shifted the ETV-TP binding pocket. No structural data are available to confirm the HBV RT modeling, however, results were consistent with phenotypic analysis of

  6. Excitation block in a nerve fibre model owing to potassium-dependent changes in myelin resistance

    DEFF Research Database (Denmark)

    Brazhe, Alexey; Maksimov, G. V.; Mosekilde, Erik

    2011-01-01

    . Uptake of potassium leads to Schwann cell swelling and myelin restructuring that impacts the electrical properties of the myelin. In order to further understand the dynamic interaction that takes place between the myelin and the axon, we have modelled submyelin potassium accumulation and related changes...... in myelin resistance during prolonged high-frequency stimulation. We predict that potassium-mediated decrease in myelin resistance leads to a functional excitation block with various patterns of altered spike trains. The patterns are found to depend on stimulation frequency and amplitude and to range from...

  7. Within-host selection of drug resistance in a mouse model of repeated interrupted treatment of Plasmodium yoelii infection

    OpenAIRE

    Nuralitha, Suci; Siregar, Josephine E; Syafruddin, Din; Hoepelman, Andy I M; Marzuki, Sangkot

    2017-01-01

    BACKGROUND: To study within-host selection of resistant parasites, an important factor in the development of resistance to anti-malarial drugs, a mouse model of repeated interrupted malaria treatment (RIT) has been developed. The characteristics of within host selection of resistance to atovaquone and pyrimethamine in Plasmodium yoelii was examined in such a model. METHODS: Treatment of P. yoelii infected mice, with atovaquone or pyrimethamine, was started at parasitaemia level of 3-5%, inter...

  8. Plausible carrier transport model in organic-inorganic hybrid perovskite resistive memory devices

    Directory of Open Access Journals (Sweden)

    Nayoung Park

    2018-04-01

    Full Text Available We demonstrate thermally assisted hopping (TAH as an appropriate carrier transport model for CH3NH3PbI3 resistive memories. Organic semiconductors, including organic-inorganic hybrid perovskites, have been previously speculated to follow the space-charge-limited conduction (SCLC model. However, the SCLC model cannot reproduce the temperature dependence of experimental current-voltage curves. Instead, the TAH model with temperature-dependent trap densities and a constant trap level are demonstrated to well reproduce the experimental results.

  9. 2D and 3D modelling of magnetic and resistivity data from Aespoe

    International Nuclear Information System (INIS)

    Mattsson, Haakan

    2011-05-01

    This report presents results from modelling of geophysical data. Ground magnetic and geo electric data were collected in 1988 as part of the pre-investigations carried out before the construction of the Aespoe Hard Rock Laboratory (HRL). The work presented in this report is an evaluation of the magnetic and geo electric data with the focus on estimating variations in geometry and dip of some of the possible deformation zones indicated in lineament interpretations presented earlier. This was done by 2D forward magnetic modelling, 2D forward resistivity modelling and 3D inversion of the magnetic data. The specific aims of this work are: 1. Produce magnetic 2D forward models across 12 selected linked lineaments. 2. Produce a 3D susceptibility model of the entire data set of Aespoe. 3. Use 2D forward resistivity modelling to produce electric anomaly response diagrams for a dipole-dipole survey across low resistivity zones with various dips. The results of the modelling work will mainly be used as supportive information for deterministic geological modelling of deformation zones and rock units in the vicinity of the Aespoe HRL. The results of the 2D forward modelling of magnetic data show geologically reasonable solutions, and in most cases it is possible to make reliable estimates of the width and orientation of the cause of the targeted lineament. The possible deformation zones generally dip steeply (80 deg-90 deg) and have a width of c. 30-50 m. In some cases the modelled lineament has a diffuse character with low amplitude, which makes the model solution uncertain. Two 3D susceptibility models were created by use of inversion of the ground magnetic data; one coarse model of the entire Island of Aespoe and one more detailed model of the south-eastern peninsula of the Island, covering the volume of the Aespoe HRL. The two models fit nicely to the measured data and they are geologically realistic. It is possible to identify well-defined bodies (rock volumes) of

  10. [Economic efficiency of renal denervation in patients with resistant hypertension: results of Markov modeling].

    Science.gov (United States)

    Kontsevaia, A V; Suvorova, E I; Khudiakov, M B

    2014-01-01

    Aim of this study was to evaluate the cost-effectiveness of renal denervation (RD) in resistant arterial hypertension (AH) in Russia. Modeling of Markov conducted economic impact of RD on the Russian population of patients with resistant hypertension in combination with optimal medical therapy (OMT) compared with OMT using a model developed by American researchers based on the results of international research. The model contains data on Russian mortality, and costs of major complications of hypertension. The simulation results showed a significant reduction in relative risk reduction of adverse outcomes in patients with resistant hypertension for 10 years (risk of stroke is reduced by 30%, myocardial infarction - 32%). RD saves 0.9 years of quality-adjusted life (QALY) by an average of 1 patient with resistant hypertension. Costs for 1 year stored in the application of quality of life amounted to RD 203 791.6 rubles. Which is below the 1 gross domestic product and therefore indicates the feasibility of this method in Russia.

  11. Modeling of electric and heat processes in spot resistance welding of cross-wire steel bars

    Science.gov (United States)

    Iatcheva, Ilona; Darzhanova, Denitsa; Manilova, Marina

    2018-03-01

    The aim of this work is the modeling of coupled electric and heat processes in a system for spot resistance welding of cross-wire reinforced steel bars. The real system geometry, dependences of material properties on the temperature, and changes of contact resistance and released power during the welding process have been taken into account in the study. The 3D analysis of the coupled AC electric and transient thermal field distributions is carried out using the finite element method. The novel feature is that the processes are modeled for several successive time stages, corresponding to the change of contact area, related contact resistance, and reduction of the released power, occurring simultaneously with the creation of contact between the workpieces. The values of contact resistance and power changes have been determined on the basis of preliminary experimental and theoretical investigations. The obtained results present the electric and temperature field distributions in the system. Special attention has been paid to the temperature evolution at specified observation points and lines in the contact area. The obtained information could be useful for clarification of the complicated nature of interrelated electric, thermal, mechanical, and physicochemical welding processes. Adequate modeling is also an opportunity for proper control and improvement of the system.

  12. Lipid metabolism disturbances contribute to insulin resistance and decrease insulin sensitivity by malathion exposure in Wistar rat.

    Science.gov (United States)

    Lasram, Mohamed Montassar; Bouzid, Kahena; Douib, Ines Bini; Annabi, Alya; El Elj, Naziha; El Fazaa, Saloua; Abdelmoula, Jaouida; Gharbi, Najoua

    2015-04-01

    Several studies showed that organophosphorus pesticides disturb glucose homeostasis and can increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on glucose metabolism regulation, in vivo, during subchronic exposure. Malathion was administered orally (200 mg/kg), once a day for 28 consecutive days. Plasma glucose, insulin and Glycated hemoglobin levels were significantly increased while hepatic glycogen content was decreased in intoxicated animals compared with the control group. Furthermore, there was a significant disturbance of lipid content in subchronic treated and post-treated rats deprived of malathion for one month. In addition, we used the homeostasis model assessment (HOMA) to assess insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-β). Our results show that malathion increases insulin resistance biomarkers and decreases insulin sensitivity indices. Statistical analysis demonstrates that there was a positive and strong significant correlation between insulin level and insulin resistance indices, HOMA-IR, HOMA-β. Similarly, a negative and significant correlation was also found between insulin level and insulin sensitivity indices. For the first time, we demonstrate that malathion induces insulin resistance in vivo using homeostasis model assessment and these changes were detectable one month after the end of exposure. To explain insulin resistance induced by malathion we focus on lipid metabolism disturbances and their interaction with many proteins involved in insulin signaling pathways.

  13. Association of arsenobetaine with beta-cell function assessed by homeostasis model assessment (HOMA) in nondiabetic Koreans: data from the fourth Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2009.

    Science.gov (United States)

    Baek, Kiook; Lee, Namhoon; Chung, Insung

    2017-01-01

    Arsenic is known as an endocrine disruptor that people are exposed to through various sources such as drinking water and indigestion of marine products. Although some epidemiological and animal studies have reported a correlation between arsenic exposure and diabetes development, there are limited studies regarding the toxic effects of organic arsenic including arsenobetaine on the human body. Here, we analyzed the association between urine arsenobetaine and the homeostasis model assessment of β-cell function (HOMA-β), which is an index for predicting diabetes development and reflecting the function of pancreatic β-cells. In the fourth Korea National Health and Nutrition Examination Survey (KNHANES), health and nutrition surveys and screening tests were performed. Of the total survey population, people with confirmed values for urine total arsenic and arsenobetaine were included, and known diabetic patients were excluded. A total 369 participants were finally included in the study. We collected surveys on health, height, body weight, body mass index, blood mercury level, fasting glucose level, and serum insulin level and calculated HOMA index. Owing to sexual discrepancy, we performed sexually stratified analysis. Urine total arsenic and total arsenic minus arsenobetaine was not associated with HOMA-IR and HOMA-β in univariate analysis or in sexually stratified analysis. However, urine arsenobetaine showed a statistically significant relationship with HOMA-β in univariate analysis, and only male participants showed a significant correlation in sexually stratified analysis. In the analysis adjusted for age, BMI, smoking, alcohol drinking, physical activity and blood mercury, the HOMA-β value in the group below the 25th percentile of arsenobetaine was significantly higher than the group between 50 and 75th percentile, while no difference was shown for HOMA-IR. In sexually stratified analysis, The value of HOMA-β was significantly higher in male participants

  14. Iron Homeostasis in Peripheral Nervous System, Still a Black Box?

    Science.gov (United States)

    Taveggia, Carla

    2014-01-01

    Abstract Significance: Iron is the most abundant transition metal in biology and an essential cofactor for many cellular enzymes. Iron homeostasis impairment is also a component of peripheral neuropathies. Recent Advances: During the past years, much effort has been paid to understand the molecular mechanism involved in maintaining systemic iron homeostasis in mammals. This has been stimulated by the evidence that iron dyshomeostasis is an initial cause of several disorders, including genetic and sporadic neurodegenerative disorders. Critical Issues: However, very little has been done to investigate the physiological role of iron in peripheral nervous system (PNS), despite the development of suitable cellular and animal models. Future Directions: To stimulate research on iron metabolism and peripheral neuropathy, we provide a summary of the knowledge on iron homeostasis in the PNS, on its transport across the blood–nerve barrier, its involvement in myelination, and we identify unresolved questions. Furthermore, we comment on the role of iron in iron-related disorder with peripheral component, in demyelinating and metabolic peripheral neuropathies. Antioxid. Redox Signal. 21, 634–648. PMID:24409826

  15. Identifying co-targets to fight drug resistance based on a random walk model

    Directory of Open Access Journals (Sweden)

    Chen Liang-Chun

    2012-01-01

    Full Text Available Abstract Background Drug resistance has now posed more severe and emergent threats to human health and infectious disease treatment. However, wet-lab approaches alone to counter drug resistance have so far still achieved limited success due to less knowledge about the underlying mechanisms of drug resistance. Our approach apply a heuristic search algorithm in order to extract active network under drug treatment and use a random walk model to identify potential co-targets for effective antibacterial drugs. Results We use interactome network of Mycobacterium tuberculosis and gene expression data which are treated with two kinds of antibiotic, Isoniazid and Ethionamide as our test data. Our analysis shows that the active drug-treated networks are associated with the trigger of fatty acid metabolism and synthesis and nicotinamide adenine dinucleotide (NADH-related processes and those results are consistent with the recent experimental findings. Efflux pumps processes appear to be the major mechanisms of resistance but SOS response is significantly up-regulation under Isoniazid treatment. We also successfully identify the potential co-targets with literature confirmed evidences which are related to the glycine-rich membrane, adenosine triphosphate energy and cell wall processes. Conclusions With gene expression and interactome data supported, our study points out possible pathways leading to the emergence of drug resistance under drug treatment. We develop a computational workflow for giving new insights to bacterial drug resistance which can be gained by a systematic and global analysis of the bacterial regulation network. Our study also discovers the potential co-targets with good properties in biological and graph theory aspects to overcome the problem of drug resistance.

  16. Multivariate analysis and extraction of parameters in resistive RAMs using the Quantum Point Contact model

    Science.gov (United States)

    Roldán, J. B.; Miranda, E.; González-Cordero, G.; García-Fernández, P.; Romero-Zaliz, R.; González-Rodelas, P.; Aguilera, A. M.; González, M. B.; Jiménez-Molinos, F.

    2018-01-01

    A multivariate analysis of the parameters that characterize the reset process in Resistive Random Access Memory (RRAM) has been performed. The different correlations obtained can help to shed light on the current components that contribute in the Low Resistance State (LRS) of the technology considered. In addition, a screening method for the Quantum Point Contact (QPC) current component is presented. For this purpose, the second derivative of the current has been obtained using a novel numerical method which allows determining the QPC model parameters. Once the procedure is completed, a whole Resistive Switching (RS) series of thousands of curves is studied by means of a genetic algorithm. The extracted QPC parameter distributions are characterized in depth to get information about the filamentary pathways associated with LRS in the low voltage conduction regime.

  17. Leveraging Resistance to Change and the Skunk Works Model of Innovation

    DEFF Research Database (Denmark)

    Fosfuri, Andrea; Rønde, Thomas

    We study a situation in which an R&D department promotes the introduction of an innovation that results in costly re-adjustments for a production department. In response, the production department tries to resist change by improving the existing technology. We show that firms balancing...... the strengths of the two departments perform better. As a negative effect, resistance to change might distort the R&D department's effort away from radical innovations. The firm can solve this problem by implementing the so-called skunk works model of innovation where the R&D department is isolated from...... the rest of the organization. Several implications for managing resistance to change and for the optimal design of R&D activities are derived...

  18. Why Did the Bear Cross the Road? Comparing the Performance of Multiple Resistance Surfaces and Connectivity Modeling Methods

    Directory of Open Access Journals (Sweden)

    Samuel A. Cushman

    2014-12-01

    Full Text Available There have been few assessments of the performance of alternative resistance surfaces, and little is known about how connectivity modeling approaches differ in their ability to predict organism movements. In this paper, we evaluate the performance of four connectivity modeling approaches applied to two resistance surfaces in predicting the locations of highway crossings by American black bears in the northern Rocky Mountains, USA. We found that a resistance surface derived directly from movement data greatly outperformed a resistance surface produced from analysis of genetic differentiation, despite their heuristic similarities. Our analysis also suggested differences in the performance of different connectivity modeling approaches. Factorial least cost paths appeared to slightly outperform other methods on the movement-derived resistance surface, but had very poor performance on the resistance surface obtained from multi-model landscape genetic analysis. Cumulative resistant kernels appeared to offer the best combination of high predictive performance and sensitivity to differences in resistance surface parameterization. Our analysis highlights that even when two resistance surfaces include the same variables and have a high spatial correlation of resistance values, they may perform very differently in predicting animal movement and population connectivity.

  19. Sleep duration and sleep quality are associated differently with alterations of glucose homeostasis

    DEFF Research Database (Denmark)

    Byberg, Stine; Hansen, Anne-Louise Smidt; Christensen, Dirk Lund

    2012-01-01

    Abstract Aims  Studies suggest that inadequate sleep duration and poor sleep quality increase the risk of impaired glucose regulation and diabetes. However, associations with specific markers of glucose homeostasis are less well explained. The objective of this study was to explore possible...... associations of sleep duration and sleep quality with markers of glucose homeostasis and glucose tolerance status in a healthy population-based study sample. Methods  The study comprised 771 participants from the Danish, population-based cross-sectional ‘Health2008’ study. Sleep duration and sleep quality were...... measured by self-report. Markers of glucose homeostasis were derived from a 3-point oral glucose tolerance test and included fasting plasma glucose, 2-h plasma glucose, HbA1c, two measures of insulin sensitivity (the insulin sensitivity index0,120 and homeostasis model assessment of insulin sensitivity...

  20. The membrane stress response buffers lethal effects of lipid disequilibrium by reprogramming the protein homeostasis network.

    Science.gov (United States)

    Thibault, Guillaume; Shui, Guanghou; Kim, Woong; McAlister, Graeme C; Ismail, Nurzian; Gygi, Steven P; Wenk, Markus R; Ng, Davis T W

    2012-10-12

    Lipid composition can differ widely among organelles and even between leaflets of a membrane. Lipid homeostasis is critical because disequilibrium can have disease outcomes. Despite their importance, mechanisms maintaining lipid homeostasis remain poorly understood. Here, we establish a model system to study the global effects of lipid imbalance. Quantitative lipid profiling was integral to monitor changes to lipid composition and for system validation. Applying global transcriptional and proteomic analyses, a dramatically altered biochemical landscape was revealed from adaptive cells. The resulting composite regulation we term the "membrane stress response" (MSR) confers compensation, not through restoration of lipid composition, but by remodeling the protein homeostasis network. To validate its physiological significance, we analyzed the unfolded protein response (UPR), one facet of the MSR and a key regulator of protein homeostasis. We demonstrate that the UPR maintains protein biogenesis, quality control, and membrane integrity-functions otherwise lethally compromised in lipid dysregulated cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Why did the bear cross the road? Comparing the performance of multiple resistance surfaces and connectivity modeling methods

    Science.gov (United States)

    Samuel A. Cushman; Jesse S. Lewis; Erin L. Landguth

    2014-01-01

    There have been few assessments of the performance of alternative resistance surfaces, and little is known about how connectivity modeling approaches differ in their ability to predict organism movements. In this paper, we evaluate the performance of four connectivity modeling approaches applied to two resistance surfaces in predicting the locations of highway...

  2. Beverton-Holt discrete pest management models with pulsed chemical control and evolution of pesticide resistance

    Science.gov (United States)

    Liang, Juhua; Tang, Sanyi; Cheke, Robert A.

    2016-07-01

    Pest resistance to pesticides is usually managed by switching between different types of pesticides. The optimal switching time, which depends on the dynamics of the pest population and on the evolution of the pesticide resistance, is critical. Here we address how the dynamic complexity of the pest population, the development of resistance and the spraying frequency of pulsed chemical control affect optimal switching strategies given different control aims. To do this, we developed novel discrete pest population growth models with both impulsive chemical control and the evolution of pesticide resistance. Strong and weak threshold conditions which guarantee the extinction of the pest population, based on the threshold values of the analytical formula for the optimal switching time, were derived. Further, we addressed switching strategies in the light of chosen economic injury levels. Moreover, the effects of the complex dynamical behaviour of the pest population on the pesticide switching times were also studied. The pesticide application period, the evolution of pesticide resistance and the dynamic complexity of the pest population may result in complex outbreak patterns, with consequent effects on the pesticide switching strategies.

  3. [Identification of cutoff points for Homeostatic Model Assessment for Insulin Resistance index in adolescents: systematic review].

    Science.gov (United States)

    Andrade, Maria Izabel Siqueira de; Oliveira, Juliana Souza; Leal, Vanessa Sá; Lima, Niedja Maria da Silva; Costa, Emília Chagas; Aquino, Nathalia Barbosa de; Lira, Pedro Israel Cabral de

    2016-06-01

    To identify cutoff points of the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index established for adolescents and discuss their applicability for the diagnosis of insulin resistance in Brazilian adolescents. A systematic review was performed in the PubMed, Lilacs and SciELO databases, using the following descriptors: "Adolescents", "insulin resistance" and "ROC curve". Original articles carried out with adolescents published between 2005 and 2015 in Portuguese, English or Spanish languages, which included the statistical analysis using ROC curve to determine the index cutoff (HOMA-IR) were included. A total of 184 articles were identified and after the study phases were applied, seven articles were selected for the review. All selected studies established their cutoffs using a ROC curve, with the lowest observed cutoff of 1.65 for girls and 1.95 for boys and the highest of 3.82 for girls and 5.22 for boys. Of the studies analyzed, one proposed external validity, recommending the use of the HOMA-IR cutoff >2.5 for both genders. The HOMA-IR index constitutes a reliable method for the detection of insulin resistance in adolescents, as long as it uses cutoffs that are more adequate for the reality of the study population, allowing early diagnosis of insulin resistance and enabling multidisciplinary interventions aiming at health promotion of this population. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  4. Uncertainty Analysis of Resistance Tests in Ata Nutku Ship Model Testing Laboratory of Istanbul Technical University

    Directory of Open Access Journals (Sweden)

    Cihad DELEN

    2015-12-01

    Full Text Available In this study, some systematical resistance tests, where were performed in Ata Nutku Ship Model Testing Laboratory of Istanbul Technical University (ITU, have been included in order to determine the uncertainties. Experiments which are conducted in the framework of mathematical and physical rules for the solution of engineering problems, measurements, calculations include uncertainty. To question the reliability of the obtained values, the existing uncertainties should be expressed as quantities. The uncertainty of a measurement system is not known if the results do not carry a universal value. On the other hand, resistance is one of the most important parameters that should be considered in the process of ship design. Ship resistance during the design phase of a ship cannot be determined precisely and reliably due to the uncertainty resources in determining the resistance value that are taken into account. This case may cause negative effects to provide the required specifications in the latter design steps. The uncertainty arising from the resistance test has been estimated and compared for a displacement type ship and high speed marine vehicles according to ITTC 2002 and ITTC 2014 regulations which are related to the uncertainty analysis methods. Also, the advantages and disadvantages of both ITTC uncertainty analysis methods have been discussed.

  5. Thermus Thermophilus as a Model System for the Study of Ribosomal Antibiotic Resistance

    Science.gov (United States)

    Gregory, Steven T.

    2018-03-01

    Ribosomes are the intracellular ribonucleoprotein machines responsible for the translation of mRNA sequence into protein sequence. As an essential cell component, the ribosome is the target of numerous antibiotics that bind to critical functional sites to impair protein synthesis. Mutations causing resistance to antibiotics arise in antibiotic binding sites, and an understanding of the basis of resistance will be an essential component of efforts to develop new antibiotics by rational drug design. We have identified a number of antibiotic-resistance mutations in ribosomal genes of the thermophilic bacterium Thermus thermophilus. This species offers two primary advantages for examining the structural basis of antibiotic-resistance, in particular, its potential for genetic manipulation and the suitability of its ribosomes for analysis by X-ray crystallography. Mutations we have identified in this organism are in many instances identical to those found in other bacterial species, including important pathogens, a result of the extreme conservation of ribosome functional sites. Here I summarize the advantages of this organism as a model system to study antibiotic-resistance mechanisms at the molecular level.

  6. Association Between Insulin Resistance and Bone Structure in Nondiabetic Postmenopausal Women

    DEFF Research Database (Denmark)

    Shanbhogue, Vikram V; Finkelstein, Joel S; Bouxsein, Mary L

    2016-01-01

    computed tomography was used to assess bone density and microstructure at the distal radius and tibia. Fasting insulin and glucose was measured and insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR) with higher values indicating greater insulin resistance....... RESULTS: There was a negative association between HOMA-IR and bone size and a positive association between HOMA-IR and total vBMD, trabecular vBMD, trabecular thickness and cortical thickness at the radius and tibia. These relationships remained even after adjusting for body weight and other potential...

  7. Insulin Resistance Predicts Mortality in Nondiabetic Individuals in the U.S.

    OpenAIRE

    Ausk, Karlee J.; Boyko, Edward J.; Ioannou, George N.

    2010-01-01

    OBJECTIVE Insulin resistance is a suspected causative factor in a wide variety of diseases. We aimed to determine whether insulin resistance, estimated by the homeostasis model assessment for insulin resistance (HOMA-IR), is associated with all-cause or disease-specific mortality among nondiabetic persons in the U.S. RESEARCH DESIGN AND METHODS We determined the association between HOMA-IR and death certificate–based mortality among 5,511 nondiabetic, adult participants of the third U.S. Nati...

  8. A multimode analytic cylindrical model for the stabilization of the resistive wall modes

    International Nuclear Information System (INIS)

    Miron, I G

    2008-01-01

    A dispersion relation concerning the stability of the resistive wall modes within a multimode cylindrical analytical model is presented. This paper generalizes the Fitzpatrick-Aydemir model (Fitzpatrick R and Aydemir A Y 1996 Nucl. Fusion 1 11) in the presence of an unlimited number of neighboring modes for a tokamak plasma column surrounded by a resistive shell and a feedback system consisting of a number of detector and active feedback coils. The model is applied to the HBT-EP tokamak (Cates C et al 2000 Phys. Plasmas 7 3133) with its peculiar feedback system disposal. Finally, an analytical dispersion relation is obtained that can be solved by using a simple MATLAB code

  9. Multi-channel conduction in redox-based resistive switch modelled using quantum point contact theory

    Energy Technology Data Exchange (ETDEWEB)

    Miranda, E., E-mail: enrique.miranda@uab.cat; Suñé, J. [Departament d' Enginyeria Electrònica, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallés, Barcelona (Spain); Mehonic, A.; Kenyon, A. J. [Department of Electronic and Electrical Engineering, University College London, Torrington Place, London WC1E 7JE (United Kingdom)

    2013-11-25

    A simple analytic model for the electron transport through filamentary-type structures in Si-rich silica (SiO{sub x})-based resistive switches is proposed. The model is based on a mesoscopic description and is able to account for the linear and nonlinear components of conductance that arise from both fully and partially formed conductive channels spanning the dielectric film. Channels are represented by arrays of identical scatterers whose number and quantum transmission properties determine the current magnitude in the low and high resistance states. We show that the proposed model not only reproduces the experimental current-voltage (I-V) characteristics but also the normalized differential conductance (dln(I)/dln(V)-V) curves of devices under test.

  10. Modeling and inversion Matlab algorithms for resistivity, induced polarization and seismic data

    Science.gov (United States)

    Karaoulis, M.; Revil, A.; Minsley, B. J.; Werkema, D. D.

    2011-12-01

    M. Karaoulis (1), D.D. Werkema (3), A. Revil (1,2), A., B. Minsley (4), (1) Colorado School of Mines, Dept. of Geophysics, Golden, CO, USA. (2) ISTerre, CNRS, UMR 5559, Université de Savoie, Equipe Volcan, Le Bourget du Lac, France. (3) U.S. EPA, ORD, NERL, ESD, CMB, Las Vegas, Nevada, USA . (4) USGS, Federal Center, Lakewood, 10, 80225-0046, CO. Abstract We propose 2D and 3D forward modeling and inversion package for DC resistivity, time domain induced polarization (IP), frequency-domain IP, and seismic refraction data. For the resistivity and IP case, discretization is based on rectangular cells, where each cell has as unknown resistivity in the case of DC modelling, resistivity and chargeability in the time domain IP modelling, and complex resistivity in the spectral IP modelling. The governing partial-differential equations are solved with the finite element method, which can be applied to both real and complex variables that are solved for. For the seismic case, forward modeling is based on solving the eikonal equation using a second-order fast marching method. The wavepaths are materialized by Fresnel volumes rather than by conventional rays. This approach accounts for complicated velocity models and is advantageous because it considers frequency effects on the velocity resolution. The inversion can accommodate data at a single time step, or as a time-lapse dataset if the geophysical data are gathered for monitoring purposes. The aim of time-lapse inversion is to find the change in the velocities or resistivities of each model cell as a function of time. Different time-lapse algorithms can be applied such as independent inversion, difference inversion, 4D inversion, and 4D active time constraint inversion. The forward algorithms are benchmarked against analytical solutions and inversion results are compared with existing ones. The algorithms are packaged as Matlab codes with a simple Graphical User Interface. Although the code is parallelized for multi

  11. Models for ductile crack initiation and tearing resistance under mode 1 loading in pressure vessel steels

    International Nuclear Information System (INIS)

    Jones, M.R.

    1988-06-01

    Micromechanistic models are presented which aim to predict plane strain ductile initiation toughness, tearing resistance and notched bar fracture strains in pressure vessel steels under monotonically increasing tensile (mode 1) loading. The models for initiation toughness and tearing resistance recognize that ductile fracture proceeds by the growth and linkage of voids with the crack-tip. The models are shown to predict the trend of initiation toughness with inclusion spacing/size ratio and can bound the available experimental data. The model for crack growth can reproduce the tearing resistance of a pressure vessel steel up to and just beyond crack growth initiation. The fracture strains of notched bars pulled in tension are shown to correspond to the achievement of a critical volume fraction of voids. This criterion is combined with the true stress - true strain history of a material point ahead of a blunting crack-tip to predict the initiation toughness. An attempt was made to predict the fracture strains of notched tensile bars by adopting a model which predicts the onset of a shear localization phenomenon. Fracture strains of the correct order are computed only if a ''secondary'' void nucleation event at carbide precipitates is taken into account. (author)

  12. A mathematical model relating response durations to amount of subclinical resistant disease.

    Science.gov (United States)

    Gregory, W M; Richards, M A; Slevin, M L; Souhami, R L

    1991-02-15

    A mathematical model is presented which seeks to determine, from examination of the response durations of a group of patients with malignant disease, the mean and distribution of the resistant tumor volume. The mean tumor-doubling time and distribution of doubling times are also estimated. The model assumes that in a group of patients there is a log-normal distribution both of resistant disease and of tumor-doubling times and implies that the shapes of certain parts of an actuarial response-duration curve are related to these two factors. The model has been applied to data from two reported acute leukemia trials: (a) a recent acute myelogenous leukemia trial was examined. Close fits were obtained for both the first and second remission-duration curves. The model results suggested that patients with long first remissions had less resistant disease and had tumors with slower growth rates following second line treatment; (b) an historical study of maintenance therapy for acute lymphoblastic leukemia was used to estimate the mean cell-kill (approximately 10(4) cells) achieved with single agent, 6-mercaptopurine. Application of the model may have clinical relevance, for example, in identifying groups of patients likely to benefit from further intensification of treatment.

  13. An individual-based model of transmission of resistant bacteria in a veterinary teaching hospital.

    Directory of Open Access Journals (Sweden)

    Neeraj Suthar

    Full Text Available Veterinary nosocomial infections caused by antibiotic resistant bacteria cause increased morbidity, higher cost and length of treatment and increased zoonotic risk because of the difficulty in treating them. In this study, an individual-based model was developed to investigate the effects of movements of canine patients among ten areas (transmission points within a veterinary teaching hospital, and the effects of these movements on transmission of antibiotic susceptible and resistant pathogens. The model simulates contamination of transmission points, healthcare workers, and patients as well as the effects of decontamination of transmission points, disinfection of healthcare workers, and antibiotic treatments of canine patients. The model was parameterized using data obtained from hospital records, information obtained by interviews with hospital staff, and the published literature. The model suggested that transmission resulting from contact with healthcare workers was common, and that certain transmission points (housing wards, diagnostics room, and the intensive care unit presented higher risk for transmission than others (lobby and surgery. Sensitivity analyses using a range of parameter values demonstrated that the risk of acquisition of colonization by resistant pathogens decreased with shorter patient hospital stays (P<0.0001, more frequent decontamination of transmission points and disinfection of healthcare workers (P<0.0001 and better compliance of healthcare workers with hygiene practices (P<0.0001. More frequent decontamination of heavily trafficked transmission points was especially effective at reducing transmission of the model pathogen.

  14. Insulin resistance and glucose levels in subjects with subclinical hypothyroidism

    International Nuclear Information System (INIS)

    Kahn, S.H.; Fazal, N.; Yasir, M.; Asif, N.; Rafi, T.

    2017-01-01

    To compare insulin resistance and glycemic indicators among subjects with euthyroidism and subclinical hypothyroidism. Study Design: Comparative cross-sectional study. Place and Duration of Study: Department of Pathology and Medicine, PNS Hafeez, Islamabad, in collaboration with the Department of Chemical Pathology and Endocrinology at the Armed Forces Institute of Pathology (AFIP), Rawalpindi, from December 2015 to September 2016. Methodology: Subjects referred for executive screening of apparently healthy population (without any known history of diabetes, hypertension, heart disease or other chronic ailments), were included. Subjects were grouped as euthyroidism and subclinical hypothyroidism. Results: Median (IQR) insulin resistance indices including fasting insulin and Homeostasis Model Assessment for Insulin Resistance in subjects with group-1 (n=176, 87%, Thyroid Stimulating Hormone: 0.5 - 3.5 mIU/L) and group-2 (n=26, 13%, Thyroid Stimulating Hormone: 3.51 - 15 mIU/L) were 7.6 (6.70) vs. 11.4 (13.72, p=0.040) and 1.77 (1.79) vs. 2.8 (3.07, p=0.071). The median differences for fasting plasma glucose were 5.0 (1.0) in group-1 vs. 5.0 (1.47) for Group-2 [p=0.618], and glycated hemoglobin was 5.60 (1.1) vs. 5.60 (1.7, p=0.824). Homeostasis Model Assessment for beta sensitivity index in paradox showed slightly higher values for group-2 [median (IQR) 86.67 (92.94)] than group-1 [111.6 (189.64, p= 0.040)]. Conclusion: Measures of insulin resistance including Homeostasis Model Assessment for Insulin Resistance and fasting insulin levels were significantly different between subjects with euthyroidism and having subclinical hypothyroidism. (author)

  15. Peripheral effects of FAAH deficiency on fuel and energy homeostasis: role of dysregulated lysine acetylation.

    Directory of Open Access Journals (Sweden)

    Bhavapriya Vaitheesvaran

    Full Text Available FAAH (fatty acid amide hydrolase, primarily expressed in the liver, hydrolyzes the endocannabinoids fatty acid ethanolamides (FAA. Human FAAH gene mutations are associated with increased body weight and obesity. In our present study, using targeted metabolite and lipid profiling, and new global acetylome profiling methodologies, we examined the role of the liver on fuel and energy homeostasis in whole body FAAH(-/- mice.FAAH(-/- mice exhibit altered energy homeostasis demonstrated by decreased oxygen consumption (Indirect calorimetry. FAAH(-/- mice are hyperinsulinemic and have adipose, skeletal and hepatic insulin resistance as indicated by stable isotope phenotyping (SIPHEN. Fed state skeletal muscle and liver triglyceride levels was increased 2-3 fold, while glycogen was decreased 42% and 57% respectively. Hepatic cholesterol synthesis was decreased 22% in FAAH(-/- mice. Dysregulated hepatic FAAH(-/- lysine acetylation was consistent with their metabolite profiling. Fasted to fed increases in hepatic FAAH(-/- acetyl-CoA (85%, p<0.01 corresponded to similar increases in citrate levels (45%. Altered FAAH(-/- mitochondrial malate dehydrogenase (MDH2 acetylation, which can affect the malate aspartate shuttle, was consistent with our observation of a 25% decrease in fed malate and aspartate levels. Decreased fasted but not fed dihydroxyacetone-P and glycerol-3-P levels in FAAH(-/- mice was consistent with a compensating contribution from decreased acetylation of fed FAAH(-/- aldolase B. Fed FAAH(-/- alcohol dehydrogenase (ADH acetylation was also decreased.Whole body FAAH deletion contributes to a pre-diabetic phenotype by mechanisms resulting in impairment of hepatic glucose and lipid metabolism. FAAH(-/- mice had altered hepatic lysine acetylation, the pattern sharing similarities with acetylation changes reported with chronic alcohol treatment. Dysregulated hepatic lysine acetylation seen with impaired FAA hydrolysis could support the liver

  16. Identification of canine coronary resistance and intramyocardial compliance on the basis of the waterfall model.

    Science.gov (United States)

    Burattini, R; Sipkema, P; van Huis, G A; Westerhof, N

    1985-01-01

    This study was performed to elucidate the effects of cardiac contraction on coronary pressure-flow relations. On the basis of the waterfall mechanism, a lumped model of the coronary arterial system is presented consisting of a proximal (epicardial) compliance, a coronary resistance, and an intramyocardial compliance. A "back"-pressure, assumed to be proportional (constant k) to left ventricular pressure, impedes flow. From steady-state measurements of circumflex coronary artery flow and inflow pressure, together with left ventricular pressure, the values of the three model parameters and the constant k have been estimated. In the control condition proximal compliance is found to be 1.7 X 10(-12) m4s2kg-1, intramyocardial compliance 110 X 10(-12)m4s2kg-1, and resistance 7.5 X 10(9) kgm-4s-1. The proportionality constant k is close to unity. Effects of changes in left ventricular pressure and inflow pressure and the effect of vasoactive drugs on the parameters are also investigated. Changes in coronary resistance are always opposite to changes in intramyocardial compliance. Sensitivity analysis showed that epicardial compliance plays its major role during isovolumic contraction and relaxation; resistance plays a role throughout the cardiac cycle but is more important in diastole than in systole, whereas intramyocardial compliance plays a role in systole and in early diastole.

  17. An analytic solution for numerical modeling validation in electromagnetics: the resistive sphere

    Science.gov (United States)

    Swidinsky, Andrei; Liu, Lifei

    2017-11-01

    We derive the electromagnetic response of a resistive sphere to an electric dipole source buried in a conductive whole space. The solution consists of an infinite series of spherical Bessel functions and associated Legendre polynomials, and follows the well-studied problem of a conductive sphere buried in a resistive whole space in the presence of a magnetic dipole. Our result is particularly useful for controlled-source electromagnetic problems using a grounded electric dipole transmitter and can be used to check numerical methods of calculating the response of resistive targets (such as finite difference, finite volume, finite element and integral equation). While we elect to focus on the resistive sphere in our examples, the expressions in this paper are completely general and allow for arbitrary source frequency, sphere radius, transmitter position, receiver position and sphere/host conductivity contrast so that conductive target responses can also be checked. Commonly used mesh validation techniques consist of comparisons against other numerical codes, but such solutions may not always be reliable or readily available. Alternatively, the response of simple 1-D models can be tested against well-known whole space, half-space and layered earth solutions, but such an approach is inadequate for validating models with curved surfaces. We demonstrate that our theoretical results can be used as a complementary validation tool by comparing analytic electric fields to those calculated through a finite-element analysis; the software implementation of this infinite series solution is made available for direct and immediate application.

  18. Unique behavioral characteristics and microRNA signatures in a drug resistant epilepsy model.

    Directory of Open Access Journals (Sweden)

    Jangsup Moon

    Full Text Available BACKGROUND: Pharmacoresistance is a major issue in the treatment of epilepsy. However, the mechanism underlying pharmacoresistance to antiepileptic drugs (AEDs is still unclear, and few animal models have been established for studying drug resistant epilepsy (DRE. In our study, spontaneous recurrent seizures (SRSs were investigated by video-EEG monitoring during the entire procedure. METHODS/PRINCIPAL FINDINGS: In the mouse pilocarpine-induced epilepsy model, we administered levetiracetam (LEV and valproate (VPA in sequence. AED-responsive and AED-resistant mice were naturally selected after 7-day treatment of LEV and VPA. Behavioral tests (open field, object exploration, elevated plus maze, and light-dark transition test and a microRNA microarray test were performed. Among the 37 epileptic mice with SRS, 23 showed significantly fewer SRSs during administration of LEV (n = 16, LEV sensitive (LS group or VPA (n = 7, LEV resistant/VPA sensitive (LRVS group, while 7 epileptic mice did not show any amelioration with either of the AEDs (n = 7, multidrug resistant (MDR group. On the behavioral assessment, MDR mice displayed distinctive behaviors in the object exploration and elevated plus maze tests, which were not observed in the LS group. Expression of miRNA was altered in LS and MDR groups, and we identified 4 miRNAs (miR-206, miR-374, miR-468, and miR-142-5p, which were differently modulated in the MDR group versus both control and LS groups. CONCLUSION: This is the first study to identify a pharmacoresistant subgroup, resistant to 2 AEDs, in the pilocarpine-induced epilepsy model. We hypothesize that modulation of the identified miRNAs may play a key role in developing pharmacoresistance and behavioral alterations in the MDR group.

  19. Relationship of visfatin level to pancreatic endocrine hormone level, HOMA-IR index, and HOMA β-cell index in overweight women who performed hydraulic resistance exercise

    OpenAIRE

    Ha, Chang Ho; Swearingin, Brenda; Jeon, Yong Kyun

    2015-01-01

    [Purpose] This study aimed to examine the correlation of visfatin level to pancreatic endocrine hormone level, homeostasis model assessment of insulin resistance (HOMA-IR) index, and HOMA β-cell index in hydraulic resistance exercise. Furthermore, it investigated the relationship between visfatin level and other variables affected by exercise in overweight women. [Subjects and Methods] The exercise group trained for 12 weeks, 70 minutes/day, 5 days/week. Visfatin level, pancreatic endocrine h...

  20. Using an Autonomous Scale Ship Model for Resistance and Parametric Roll Tests

    Directory of Open Access Journals (Sweden)

    Fernando LOPEZ PEŇA

    2015-04-01

    Full Text Available This work presents the developing of a self-propelled scale ship model aimed to perform resistance and parametric roll tests in towing tanks. The main characteristic of the proposed system is that it doesn’t have any material link to a towing device to carry out the tests. This ship model has been fully instrumented in order to acquire all the significant raw data, process them onboard and communicate with an inshore station. This works presents a description of the proposed model as well as some results obtained by its use during a towing tank testing campaign.

  1. Three-dimensional electrical resistivity model of a nuclear waste disposal site

    International Nuclear Information System (INIS)

    Rucker, Dale F.; Levitt, Marc T.; Greenwood, William J.

    2009-01-01

    A three-dimensional (3D) modeling study was completed on a very large electrical resistivity survey conducted at a nuclear waste site in eastern Washington. The acquisition included 47 pole-pole two dimensional (2D) resistivity profiles collected along parallel and orthogonal lines over an area of 850 m-570 m. The data were geo-referenced and inverted using EarthImager3D (EI3D). EI3D runs on a Microsoft 32-bit operating system (e.g. WIN-2K, XP) with a maximum usable memory of 2 GB. The memory limits the size of the domain for the inversion model to 200 m-200 m, based on the survey electrode density. Therefore, a series of increasing overlapping models were run to evaluate the effectiveness of dividing the survey area into smaller subdomains. The results of the smaller subdomains were compared to the inversion results of a single domain over a larger area using an upgraded form of EI3D that incorporates multi-processing capabilities and 32 GB of RAM memory. The contours from the smaller subdomains showed discontinuity at the boundaries between the adjacent models, which do not match the hydrogeologic expectations given the nature of disposal at the site. At several boundaries, the contours of the low resistivity areas close, leaving the appearance of disconnected plumes or open contours at boundaries are not met with a continuance of the low resistivity plume into the adjacent subdomain. The model results of the single large domain show a continuous monolithic plume within the central and western portion of the site, directly beneath the elongated trenches. It is recommended that where possible, the domain not be subdivided, but instead include as much of the domain as possible given the memory of available computing resources.

  2. Application of PK/PD Modeling in Veterinary Field: Dose Optimization and Drug Resistance Prediction

    Directory of Open Access Journals (Sweden)

    Ijaz Ahmad

    2016-01-01

    Full Text Available Among veterinary drugs, antibiotics are frequently used. The true mean of antibiotic treatment is to administer dose of drug that will have enough high possibility of attaining the preferred curative effect, with adequately low chance of concentration associated toxicity. Rising of antibacterial resistance and lack of novel antibiotic is a global crisis; therefore there is an urgent need to overcome this problem. Inappropriate antibiotic selection, group treatment, and suboptimal dosing are mostly responsible for the mentioned problem. One approach to minimizing the antibacterial resistance is to optimize the dosage regimen. PK/PD model is important realm to be used for that purpose from several years. PK/PD model describes the relationship between drug potency, microorganism exposed to drug, and the effect observed. Proper use of the most modern PK/PD modeling approaches in veterinary medicine can optimize the dosage for patient, which in turn reduce toxicity and reduce the emergence of resistance. The aim of this review is to look at the existing state and application of PK/PD in veterinary medicine based on in vitro, in vivo, healthy, and disease model.

  3. Effect of Ethanolic Extract of Emblica officinalis (Amla on Glucose Homeostasis in Rats Fed with High Fat Diet

    Directory of Open Access Journals (Sweden)

    Pallavi S. Kanthe

    2017-07-01

    Full Text Available Background: Emblica officinalis contains many biological active components which are found to have some medicinal properties against diseases. Aim and Objectives: To assess hypolipidemic and glucose regulatory actions of Ethanolic Extract of Emblica officinalis (EEO on High Fat Diet (HFD fed experimental rats. Material and Methods: Twenty four rats were divided into four groups, having six rats in each group as following; Group I- Control (20% fat; Group II (EEO 100 mg/kg/b w; Group III (30% fat and Group IV (30% fat + EEO 100 mg/kg/b w. The treatment was continued for 21 days. Gravimetric parameters and lipid profiles of all the groups were measured. Oral Glucose Tolerance Test (OGTT, fasting and postprandial glucose and fasting insulin levels were estimated. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR was calculated. Statistical analysis was done. Results: Significant alteration in serum lipid profile, fasting and post prandial blood glucose levels and fasting insulin level were observed in rats of Group III fed with high fat diet. Supplementation of EEO improved both of glycemic and lipid profiles in rats of Group IV fed with high fat diet. Conclusion: Results from the study indicate the beneficial role of EEO on dyslipidemia and glucose homeostasis in rats treated with high fat diet.

  4. Resistivity structure of Sumatran Fault (Aceh segment) derived from 1-D magnetotelluric modeling

    Science.gov (United States)

    Nurhasan, Sutarno, D.; Bachtiar, H.; Sugiyanto, D.; Ogawa, Y.; Kimata, F.; Fitriani, D.

    2012-06-01

    Sumatran Fault Zone is the most active fault in Indonesia as a result of strike-slip component of Indo-Australian oblique convergence. With the length of 1900 km, Sumatran fault was divided into 20 segments starting from the southernmost Sumatra Island having small slip rate and increasing to the north end of Sumatra Island. There are several geophysical methods to analyze fault structure depending on physical parameter used in these methods, such as seismology, geodesy and electromagnetic. Magnetotelluric method which is one of geophysical methods has been widely used in mapping and sounding resistivity distribution because it does not only has the ability for detecting contras resistivity but also has a penetration range up to hundreds of kilometers. Magnetotelluric survey was carried out in Aceh region with the 12 total sites crossing Sumatran Fault on Aceh and Seulimeum segments. Two components of electric and magnetic fields were recorded during 10 hours in average with the frequency range from 320 Hz to 0,01 Hz. Analysis of the pseudosection of phase and apparent resistivity exhibit vertical low phase flanked on the west and east by high phase describing the existence of resistivity contras in this region. Having rotated the data to N45°E direction, interpretation of the result has been performed using three different methods of 1D MT modeling i.e. Bostick inversion, 1D MT inversion of TM data, and 1D MT inversion of the impedance determinant. By comparison, we concluded that the use of TM data only and the impedance determinant in 1D inversion yield the more reliable resistivity structure of the fault compare to other methods. Based on this result, it has been shown clearly that Sumatra Fault is characterized by vertical contras resistivity indicating the existence of Aceh and Seulimeum faults which has a good agreement with the geological data.

  5. Gut commensal flora: tolerance and homeostasis

    OpenAIRE

    Rescigno, Maria

    2009-01-01

    Commensal microorganisms are not ignored by the intestinal immune system. Recent evidence shows that commensals actively participate in maintaining intestinal immune homeostasis by interacting with intestinal epithelial cells and delivering tolerogenic signals that are transmitted to the underlying cells of the immune system.

  6. Redox Homeostasis in Pancreatic beta Cells

    Czech Academy of Sciences Publication Activity Database

    Ježek, Petr; Dlasková, Andrea; Plecitá-Hlavatá, Lydie

    2012-01-01

    Roč. 2012, č. 2012 (2012), s. 932838 ISSN 1942-0900 R&D Projects: GA ČR(CZ) GAP302/10/0346; GA ČR(CZ) GPP304/10/P204 Institutional support: RVO:67985823 Keywords : beta cells * reactive oxygen species homeostasis * mitochondria Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.393, year: 2012

  7. Calcium homeostasis in fly photoreceptor cells

    NARCIS (Netherlands)

    Oberwinkler, J

    2002-01-01

    In fly photoreceptor cells, two processes dominate the Ca2+ homeostasis: light-induced Ca2+ influx through members of the TRP family of ion channels, and Ca2+ extrusion by Na+/Ca2+ exchange.Ca2+ release from intracellular stores is quantitatively insignificant. Both, the light-activated channels and

  8. Effectiveness of carnosine on disturbed electrolytes homeostasis ...

    African Journals Online (AJOL)

    Jane

    2011-07-20

    Jul 20, 2011 ... of the cells to cisplatin may result from the interaction of specific proteins with ..... respiration, which is similar to uncoupling of oxidative phosphorylation (Binet ... cellular ion homeostasis with decreased cellular K+ content, increased ... of sodium and hydrogen ions will take place passively. Also, magnesium ...

  9. Pharmacological modulation of mitochondrial calcium homeostasis.

    Science.gov (United States)

    Arduino, Daniela M; Perocchi, Fabiana

    2018-01-10

    Mitochondria are pivotal organelles in calcium (Ca 2+ ) handling and signalling, constituting intracellular checkpoints for numerous processes that are vital for cell life. Alterations in mitochondrial Ca 2+ homeostasis have been linked to a variety of pathological conditions and are critical in the aetiology of several human diseases. Efforts have been taken to harness mitochondrial Ca 2+ transport mechanisms for therapeutic intervention, but pharmacological compounds that direct and selectively modulate mitochondrial Ca 2+ homeostasis are currently lacking. New avenues have, however, emerged with the breakthrough discoveries on the genetic identification of the main players involved in mitochondrial Ca 2+ influx and efflux pathways and with recent hints towards a deep understanding of the function of these molecular systems. Here, we review the current advances in the understanding of the mechanisms and regulation of mitochondrial Ca 2+ homeostasis and its contribution to physiology and human disease. We also introduce and comment on the recent progress towards a systems-level pharmacological targeting of mitochondrial Ca 2+ homeostasis. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

  10. Molecular monitoring of equine joint homeostasis

    NARCIS (Netherlands)

    de Grauw, J.C.

    2010-01-01

    Chronic joint disorders are a major cause of impaired mobility and loss of quality of life in both humans and horses. Regardless of the primary insult, any joint disorder is characterized by an upset in normal joint homeostasis, the balance between tissue anabolism and catabolism that is normally

  11. Brain glucose sensing, counterregulation, and energy homeostasis.

    Science.gov (United States)

    Marty, Nell; Dallaporta, Michel; Thorens, Bernard

    2007-08-01

    Neuronal circuits in the central nervous system play a critical role in orchestrating the control of glucose and energy homeostasis. Glucose, beside being a nutrient, is also a signal detected by several glucose-sensing units that are located at different anatomical sites and converge to the hypothalamus to cooperate with leptin and insulin in controlling the melanocortin pathway.

  12. Automatic generation of groundwater model hydrostratigraphy from AEM resistivity and boreholes

    DEFF Research Database (Denmark)

    Marker, Pernille Aabye; Foged, N.; Christiansen, A. V.

    2014-01-01

    distribution govern groundwater flow. The coupling between hydrological and geophysical parameters is managed using a translator function with spatially variable parameters followed by a 3D zonation. The translator function translates geophysical resistivities into clay fractions and is calibrated...... with observed lithological data. Principal components are computed for the translated clay fractions and geophysical resistivities. Zonation is carried out by k-means clustering on the principal components. The hydraulic parameters of the zones are determined in a hydrological model calibration using head...... and discharge observations. The method was applied to field data collected at a Danish field site. Our results show that a competitive hydrological model can be constructed from the AEM dataset using the automatic procedure outlined above....

  13. Predicting the Abrasion Resistance of Tool Steels by Means of Neurofuzzy Model

    Directory of Open Access Journals (Sweden)

    Dragutin Lisjak

    2013-07-01

    Full Text Available This work considers use neurofuzzy set theory for estimate abrasion wear resistance of steels based on chemical composition, heat treatment (austenitising temperature, quenchant and tempering temperature, hardness after hardening and different tempering temperature and volume loss of materials according to ASTM G 65-94. Testing of volume loss for the following group of materials as fuzzy data set was taken: carbon tool steels, cold work tool steels, hot work tools steels, high-speed steels. Modelled adaptive neuro fuzzy inference system (ANFIS is compared to statistical model of multivariable non-linear regression (MNLR. From the results it could be concluded that it is possible well estimate abrasion wear resistance for steel whose volume loss is unknown and thus eliminate unnecessary testing.

  14. Leptin rapidly improves glucose homeostasis in obese mice by increasing hypothalamic insulin sensitivity.

    Science.gov (United States)

    Koch, Christiane; Augustine, Rachael A; Steger, Juliane; Ganjam, Goutham K; Benzler, Jonas; Pracht, Corinna; Lowe, Chrishanthi; Schwartz, Michael W; Shepherd, Peter R; Anderson, Greg M; Grattan, David R; Tups, Alexander

    2010-12-01

    Obesity is associated with resistance to the actions of both leptin and insulin via mechanisms that remain incompletely understood. To investigate whether leptin resistance per se contributes to insulin resistance and impaired glucose homeostasis, we investigated the effect of acute leptin administration on glucose homeostasis in normal as well as leptin- or leptin receptor-deficient mice. In hyperglycemic, leptin-deficient Lep(ob/ob) mice, leptin acutely and potently improved glucose metabolism, before any change of body fat mass, via a mechanism involving the p110α and β isoforms of phosphatidylinositol-3-kinase (PI3K). Unlike insulin, however, the anti-diabetic effect of leptin occurred independently of phospho-AKT, a major downstream target of PI3K, and instead involved enhanced sensitivity of the hypothalamus to insulin action upstream of PI3K, through modulation of IRS1 (insulin receptor substrate 1) phosphorylation. These data suggest that leptin resistance, as occurs in obesity, reduces the hypothalamic response to insulin and thereby impairs peripheral glucose homeostasis, contributing to the development of type 2 diabetes.

  15. Long-term characterization of the diet-induced obese and diet-resistant rat model

    DEFF Research Database (Denmark)

    Madsen, Andreas Nygaard; Hansen, Gitte; Paulsen, Sarah Juel

    2010-01-01

    , namely the selectively bred diet-induced obese (DIO) and diet-resistant (DR) rat strains. We show that they constitute useful models of the human obesity syndrome. DIO and DR rats were fed either a high-energy (HE) or a standard chow (Chow) diet from weaning to 9 months of age. Metabolic characterization......, the results underscore the effectiveness of GLP-1 mimetics both as anti-diabetes and anti-obesity agents....

  16. Low-dimensional model of resistive interchange convection in magnetized plasma

    International Nuclear Information System (INIS)

    Bazdenkov, S.; Sato, Tetsuya

    1997-09-01

    Self-organization and generation of large shear flow component in turbulent resistive interchange convection in magnetized plasma is considered. The effect of plasma density-electrostatic potential coupling via the inertialess electron dynamics along the magnetic field is shown to play significant role in the onset of shear component. The results of large-scale numerical simulation and low-dimensional (reduced) model are presented and compared. (author)

  17. Modeling of the bacterial mechanism of methicillin-resistance by a systems biology approach.

    Directory of Open Access Journals (Sweden)

    Ida Autiero

    Full Text Available BACKGROUND: A microorganism is a complex biological system able to preserve its functional features against external perturbations and the ability of the living systems to oppose to these external perturbations is defined "robustness". The antibiotic resistance, developed by different bacteria strains, is a clear example of robustness and of ability of the bacterial system to acquire a particular functional behaviour in response to environmental changes. In this work we have modeled the whole mechanism essential to the methicillin-resistance through a systems biology approach. The methicillin is a beta-lactamic antibiotic that act by inhibiting the penicillin-binding proteins (PBPs. These PBPs are involved in the synthesis of peptidoglycans, essential mesh-like polymers that surround cellular enzymes and are crucial for the bacterium survival. METHODOLOGY: The network of genes, mRNA, proteins and metabolites was created using CellDesigner program and the data of molecular interactions are stored in Systems Biology Markup Language (SBML. To simulate the dynamic behaviour of this biochemical network, the kinetic equations were associated with each reaction. CONCLUSIONS: Our model simulates the mechanism of the inactivation of the PBP by methicillin, as well as the expression of PBP2a isoform, the regulation of the SCCmec elements (SCC: staphylococcal cassette chromosome and the synthesis of peptidoglycan by PBP2a. The obtained results by our integrated approach show that the model describes correctly the whole phenomenon of the methicillin resistance and is able to respond to the external perturbations in the same way of the real cell. Therefore, this model can be useful to develop new therapeutic approaches for the methicillin control and to understand the general mechanism regarding the cellular resistance to some antibiotics.

  18. Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study.

    Science.gov (United States)

    Sharma, Aditya; Hill, Andrew; Kurbatova, Ekaterina; van der Walt, Martie; Kvasnovsky, Charlotte; Tupasi, Thelma E; Caoili, Janice C; Gler, Maria Tarcela; Volchenkov, Grigory V; Kazennyy, Boris Y; Demikhova, Olga V; Bayona, Jaime; Contreras, Carmen; Yagui, Martin; Leimane, Vaira; Cho, Sang Nae; Kim, Hee Jin; Kliiman, Kai; Akksilp, Somsak; Jou, Ruwen; Ershova, Julia; Dalton, Tracy; Cegielski, Peter

    2017-07-01

    Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa. We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa. The model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12·4% (95% prediction interval 9·4-16·2) in India, 8·9% (4·5-11·7) in the Philippines, 32·5% (27·0-35·8) in Russia, and 5·7% (3·0-7·6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8·9% (95% prediction interval 5·1-12·9) in India, 9·0% (4·0-14·7) in the Philippines, 9·0% (4·8-14·2) in Russia, and 8·5% (2·5-14·7) in South Africa in 2040. Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040. MDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR

  19. A Collective Study on Modeling and Simulation of Resistive Random Access Memory

    Science.gov (United States)

    Panda, Debashis; Sahu, Paritosh Piyush; Tseng, Tseung Yuen

    2018-01-01

    In this work, we provide a comprehensive discussion on the various models proposed for the design and description of resistive random access memory (RRAM), being a nascent technology is heavily reliant on accurate models to develop efficient working designs and standardize its implementation across devices. This review provides detailed information regarding the various physical methodologies considered for developing models for RRAM devices. It covers all the important models reported till now and elucidates their features and limitations. Various additional effects and anomalies arising from memristive system have been addressed, and the solutions provided by the models to these problems have been shown as well. All the fundamental concepts of RRAM model development such as device operation, switching dynamics, and current-voltage relationships are covered in detail in this work. Popular models proposed by Chua, HP Labs, Yakopcic, TEAM, Stanford/ASU, Ielmini, Berco-Tseng, and many others have been compared and analyzed extensively on various parameters. The working and implementations of the window functions like Joglekar, Biolek, Prodromakis, etc. has been presented and compared as well. New well-defined modeling concepts have been discussed which increase the applicability and accuracy of the models. The use of these concepts brings forth several improvements in the existing models, which have been enumerated in this work. Following the template presented, highly accurate models would be developed which will vastly help future model developers and the modeling community.

  20. Calculating electron cyclotron current drive stabilization of resistive tearing modes in a nonlinear magnetohydrodynamic model

    International Nuclear Information System (INIS)

    Jenkins, Thomas G.; Schnack, Dalton D.; Kruger, Scott E.; Hegna, C. C.; Sovinec, Carl R.

    2010-01-01

    A model which incorporates the effects of electron cyclotron current drive (ECCD) into the magnetohydrodynamic equations is implemented in the NIMROD code [C. R. Sovinec et al., J. Comput. Phys. 195, 355 (2004)] and used to investigate the effect of ECCD injection on the stability, growth, and dynamical behavior of magnetic islands associated with resistive tearing modes. In addition to qualitatively and quantitatively agreeing with numerical results obtained from the inclusion of localized ECCD deposition in static equilibrium solvers [A. Pletzer and F. W. Perkins, Phys. Plasmas 6, 1589 (1999)], predictions from the model further elaborate the role which rational surface motion plays in these results. The complete suppression of the (2,1) resistive tearing mode by ECCD is demonstrated and the relevant stabilization mechanism is determined. Consequences of the shifting of the mode rational surface in response to the injected current are explored, and the characteristic short-time responses of resistive tearing modes to spatial ECCD alignments which are stabilizing are also noted. We discuss the relevance of this work to the development of more comprehensive predictive models for ECCD-based mitigation and control of neoclassical tearing modes.

  1. A constriction resistance model of conjugated polymer based piezoresistive sensors for electronic skin applications.

    Science.gov (United States)

    Khalili, N; Naguib, H E; Kwon, R H

    2016-05-14

    Human intervention can be replaced through the development of tools resulting from utilization of sensing devices possessing a wide range of applications including humanoid robots or remote and minimally invasive surgeries. Similar to the five human senses, sensors interface with their surroundings to stimulate a suitable response or action. The sense of touch which arises in human skin is among the most challenging senses to emulate due to its ultra high sensitivity. This has brought forth novel challenging issues to consider in the field of biomimetic robotics. In this work, using a multiphase reaction, a polypyrrole (PPy) based hydrogel is developed as a resistive type pressure sensor with an intrinsically elastic microstructure stemming from three dimensional hollow spheres. It is shown that the electrical conductivity of the fabricated PPy based piezoresistive sensors is enhanced as a result of adding conductive fillers and therefore, endowing the sensors with a higher sensitivity. A semi-analytical constriction resistance based model accounting for the real contact area between the PPy hydrogel sensors and the electrode along with the dependency of the contact resistance change on the applied load is developed. The model is then solved using a Monte Carlo technique and its corresponding sensitivity is obtained. Comparing the results with their experimental counterparts, the proposed modeling methodology offers a good tracking ability.

  2. An analytical model and parametric study of electrical contact resistance in proton exchange membrane fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zhiliang; Wang, Shuxin; Zhang, Lianhong [School of Mechanical Engineering, Tianjin University, Tianjin 300072 (China); Hu, S. Jack [Department of Mechanical Engineering, The University of Michigan, Ann Arbor, MI 48109-2125 (United States)

    2009-04-15

    This paper presents an analytical model of the electrical contact resistance between the carbon paper gas diffusion layers (GDLs) and the graphite bipolar plates (BPPs) in a proton exchange membrane (PEM) fuel cell. The model is developed based on the classical statistical contact theory for a PEM fuel cell, using the same probability distributions of the GDL structure and BPP surface profile as previously described in Wu et al. [Z. Wu, Y. Zhou, G. Lin, S. Wang, S.J. Hu, J. Power Sources 182 (2008) 265-269] and Zhou et al. [Y. Zhou, G. Lin, A.J. Shih, S.J. Hu, J. Power Sources 163 (2007) 777-783]. Results show that estimates of the contact resistance compare favorably with experimental data by Zhou et al. [Y. Zhou, G. Lin, A.J. Shih, S.J. Hu, J. Power Sources 163 (2007) 777-783]. Factors affecting the contact behavior are systematically studied using the analytical model, including the material properties of the two contact bodies and factors arising from the manufacturing processes. The transverse Young's modulus of chopped carbon fibers in the GDL and the surface profile of the BPP are found to be significant to the contact resistance. The factor study also sheds light on the manufacturing requirements of carbon fiber GDLs for a better contact performance in PEM fuel cells. (author)

  3. Joint inversion of seismic refraction and resistivity data using layered models - applications to hydrogeology

    Science.gov (United States)

    Juhojuntti, N. G.; Kamm, J.

    2010-12-01

    We present a layered-model approach to joint inversion of shallow seismic refraction and resistivity (DC) data, which we believe is a seldom tested method of addressing the problem. This method has been developed as we believe that for shallow sedimentary environments (roughly fairly simple 2D geometries, mainly for checking the validity of the calculations. The inversion generally converges towards the correct solution, although there could be stability problems if the starting model is too erroneous. We have also applied the code to field data from seismic refraction and multi-electrode resistivity measurements at typical sand-gravel groundwater reservoirs. The tests are promising, as the calculated depths agree fairly well with information from drilling and the velocity and resistivity values appear reasonable. Current work includes better regularization of the inversion as well as defining individual weight factors for the different datasets, as the present algorithm tends to constrain the depths mainly by using the seismic data. More complex synthetic examples will also be tested, including models addressing the seismic hidden-layer problem.

  4. The `L' Array, a method to model 3D Electrical Resistivity Tomography (ERT) data

    Science.gov (United States)

    Chavez Segura, R. E.; Chavez-Hernandez, G.; Delgado, C.; Tejero-Andrade, A.

    2010-12-01

    The electrical resistivity tomography (ERT) is a method designed to calculate the distribution of apparent electrical resistivities in the subsoil by means of a great number of observations with the aim of determining an electrical image displaying the distribution of true resistivities in the subsoil. Such process can be carried out to define 2D or 3D models of the subsurface. For a 3D ERT, usually, the electrodes are placed in a squared grid keeping the distance between adjacent electrodes constant in the x and y directions. Another design employed, consists of a series of parallel lines whose space inter-lines must be smaller or equal to four times the electrode separation. The most common electrode arrays frequently employed for this type of studies are the pole-pole, pole-dipole and dipole-dipole. Unfortunately, ERT surface sampling schemes are limited by physical conditions or obstacles, like buildings, highly populated urban zones, and geologic/topographic features, where the lines of electrodes cannot be set. However, it is always necessary to characterize the subsoil beneath such anthropogenic or natural features. The ‘L’ shaped array has the main purpose to overcome such difficulties by surrounding the study area with a square of electrode lines. The measurements are obtained by switching automatically current and potential electrodes from one line to the other. Each observation adds a level of information, from one profile to the other. Once the total levels of data are completed, the opposite ‘L’ array can be measured following the same process. The complete square is computed after the parallel profiles are observed as well. At the end, the computed resistivities are combined to form a 3D matrix of observations. Such set of data can be inverted to obtain the true resistivity distribution at depth in the form of a working cube, which can be interpreted. The method was tested with theoretical models, which included a set of two resistive cubes

  5. Association of glucose homeostasis measures with heart rate variability among Hispanic/Latino adults without diabetes: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

    Science.gov (United States)

    Meyer, Michelle L; Gotman, Nathan M; Soliman, Elsayed Z; Whitsel, Eric A; Arens, Raanan; Cai, Jianwen; Daviglus, Martha L; Denes, Pablo; González, Hector M; Moreiras, Juan; Talavera, Gregory A; Heiss, Gerardo

    2016-03-16

    Reduced heart rate variability (HRV), a measure of cardiac autonomic function, is associated with an increased risk of cardiovascular disease (CVD) and mortality. Glucose homeostasis measures are associated with reduced cardiac autonomic function among those with diabetes, but inconsistent associations have been reported among those without diabetes. This study aimed to examine the association of glucose homeostasis measures with cardiac autonomic function among diverse Hispanic/Latino adults without diabetes. The Hispanic community Health Study/Study of Latinos (HCHS/SOL; 2008-2011) used two-stage area probability sampling of households to enroll 16,415 self-identified Hispanics/Latinos aged 18-74 years from four USA communities. Resting, standard 12-lead electrocardiogram recordings were used to estimate the following ultrashort-term measures of HRV: RR interval (RR), standard deviation of all normal to normal RR (SDNN) and root mean square of successive differences in RR intervals (RMSSD). Multivariable regression analysis was used to estimate associations between glucose homeostasis measures with HRV using data from 11,994 adults without diabetes (mean age 39 years; 52 % women). Higher fasting glucose was associated with lower RR, SDNN, and RMSSD. Fasting insulin and the homeostasis model assessment of insulin resistance was negatively associated with RR, SDNN, and RMSSD, and the association was stronger among men compared with women. RMSSD was, on average, 26 % lower in men with higher fasting insulin and 29 % lower in men with lower insulin resistance; for women, the corresponding estimates were smaller at 4 and 9 %, respectively. Higher glycated hemoglobin was associated with lower RR, SDNN, and RMSSD in those with abdominal adiposity, defined by sex-specific cut-points for waist circumference, after adjusting for demographics and medication use. There were no associations between glycated hemoglobin and HRV measures among those without abdominal adiposity

  6. Sedentary lifestyle and its relation to cardiovascular risk factors, insulin resistance and inflammatory profile.

    Science.gov (United States)

    León-Latre, Montserrat; Moreno-Franco, Belén; Andrés-Esteban, Eva M; Ledesma, Marta; Laclaustra, Martín; Alcalde, Víctor; Peñalvo, José L; Ordovás, José M; Casasnovas, José A

    2014-06-01

    To analyze the association between sitting time and biomarkers of insulin resistance and inflammation in a sample of healthy male workers. Cross-sectional study carried out in a sample of 929 volunteers belonging to the Aragon Workers' Health Study cohort. Sociodemographic, anthropometric, pharmacological and laboratory data were collected: lipids-total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoproteins A-1 and B-100, lipoprotein (a)-, insulin resistance-glucose, glycated hemoglobin, homeostasis model assessment of insulin resistance, insulin, and triglyceride/high-density lipoprotein cholesterol ratio-, and inflammatory profile-C-reactive protein and leukocytes. Information on sitting time and physical activity was assessed using a questionnaire. Sedentary behavior was analyzed in terms of prevalences and medians, according to tertiles, using a multivariate model (crude and adjusted linear regression) with biomarkers of inflammation and insulin resistance. The most sedentary individuals had higher body mass index, greater waist circumference, and higher systolic blood pressure, with a significant upward trend in each tertile. Likewise, they had a worse lipid profile with a higher C-reactive protein level, homeostasis model assessment of insulin resistance index, triglyceride/high-density lipoprotein cholesterol ratio, and insulin concentration. In the multivariate analysis, we observed a significant association between the latter parameters and sitting time in hours (log C-reactive protein [β = 0.07], log homeostasis model assessment of insulin resistance index [β = 0.05], triglyceride/high-density lipoprotein cholesterol ratio [β = 0.23], and insulin [β = 0.44]), which remained after adjustment for metabolic equivalents-h/week. Workers who spend more time sitting show a worse inflammatory and insulin resistance profile independently of the physical activity performed. Copyright © 2013

  7. A multistate model of cognitive dynamics in relation to resistance training: the contribution of baseline function.

    Science.gov (United States)

    Fallah, Nader; Hsu, Chun L; Bolandzadeh, Niousha; Davis, Jennifer; Beattie, B Lynn; Graf, Peter; Liu-Ambrose, Teresa

    2013-08-01

    We investigated: (1) the effect of different targeted exercise training on an individual's overall probability for cognitive improvement, maintenance, or decline; and (2) the simultaneous effect of targeted exercise training and baseline function on the dynamics of executive functions when a multistate transition model is used. Analyses are based on a 12-month randomized clinical trial including 155 community-dwelling women 65-75 years of age who were randomly allocated to once-weekly resistance training (1x RT; n = 54), twice-weekly resistance training (2x RT; n = 52), or twice-weekly balance and tone training (BAT; n = 49). The primary outcome measure was performance on the Stroop test, an executive cognitive test of selective attention and conflict resolution. Secondary outcomes of executive functions were set shifting and working memory. Individuals in the 1x RT or 2x RT group demonstrated a significantly greater probability for improved performance on the Stroop Test (0.49; 95% confidence interval, 0.41-0.57) compared with those in the BAT group (0.25; 95% confidence interval, 0.25-0.40). Resistance training had significant effects on transitions in selective attention and conflict resolution. Resistance training is efficacious in improving a measure of selective attention and conflict resolution in older women, probably more so among those with greater baseline cognitive function. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Priming of plant resistance by natural compounds. Hexanoic acid as a model

    Directory of Open Access Journals (Sweden)

    Paz eAranega Bou

    2014-10-01

    Full Text Available Some alternative control strategies of currently emerging plant diseases are based on the use of resistance inducers. This review highlights the recent advances made in the characterization of natural compounds that induce resistance by a priming mechanism. These include vitamins, chitosans, oligogalacturonides, volatile organic compounds, azelaic and pipecolic acid, among others. Overall, other than providing novel disease control strategies that meet environmental regulations, natural priming agents are valuable tools to help unravel the complex mechanisms underlying the induced resistance phenomenon. The data presented in this review reflect the novel contributions made from studying these natural plant inducers, with special emphasis placed on hexanoic acid (Hx, proposed herein as a model tool for this research field. Hx is a potent natural priming agent of proven efficiency in a wide range of host plants and pathogens. It can early activate broad-spectrum defenses by inducing callose deposition and the SA and JA pathways. Later it can prime pathogen-specific responses according to the pathogen’s lifestyle. Interestingly, Hx primes redox-related genes to produce an anti-oxidant protective effect, which might be critical for limiting the infection of necrotrophs. Our Hx-induced resistance (Hx-IR findings also strongly suggest that it is an attractive tool for the molecular characterization of the plant alarmed state, with the added advantage of it being a natural compound.

  9. Genetic Mapping of a Major Resistance Gene to Pea Aphid (Acyrthosipon pisum in the Model Legume Medicago truncatula

    Directory of Open Access Journals (Sweden)

    Lars G. Kamphuis

    2016-07-01

    Full Text Available Resistance to the Australian pea aphid (PA; Acyrthosiphon pisum biotype in cultivar Jester of the model legume Medicago truncatula is mediated by a single dominant gene and is phloem-mediated. The genetic map position for this resistance gene, APR (Acyrthosiphon pisum resistance, is provided and shows that APR maps 39 centiMorgans (cM distal of the A. kondoi resistance (AKR locus, which mediates resistance to a closely related species of the same genus bluegreen aphid (A. kondoi. The APR region on chromosome 3 is dense in classical nucleotide binding site leucine-rich repeats (NLRs and overlaps with the region harbouring the RAP1 gene which confers resistance to a European PA biotype in the accession Jemalong A17. Further screening of a core collection of M. truncatula accessions identified seven lines with strong resistance to PA. Allelism experiments showed that the single dominant resistance to PA in M. truncatula accessions SA10481 and SA1516 are allelic to SA10733, the donor of the APR locus in cultivar Jester. While it remains unclear whether there are multiple PA resistance genes in an R-gene cluster or the resistance loci identified in the other M. truncatula accessions are allelic to APR, the introgression of APR into current M. truncatula cultivars will provide more durable resistance to PA.

  10. Compartmental modelling of the pharmacokinetics of a breast cancer resistance protein.

    Science.gov (United States)

    Grandjean, Thomas R B; Chappell, Mike J; Yates, James T W; Jones, Kevin; Wood, Gemma; Coleman, Tanya

    2011-11-01

    A mathematical model for the pharmacokinetics of Hoechst 33342 following administration into a culture medium containing a population of transfected cells (HEK293 hBCRP) with a potent breast cancer resistance protein inhibitor, Fumitremorgin C (FTC), present is described. FTC is reported to almost completely annul resistance mediated by BCRP in vitro. This non-linear compartmental model has seven macroscopic sub-units, with 14 rate parameters. It describes the relationship between the concentration of Hoechst 33342 and FTC, initially spiked in the medium, and the observed change in fluorescence due to Hoechst 33342 binding to DNA. Structural identifiability analysis has been performed using two methods, one based on the similarity transformation/exhaustive modelling approach and the other based on the differential algebra approach. The analyses demonstrated that all models derived are uniquely identifiable for the experiments/observations available. A kinetic modelling software package, namely FACSIMILE (MPCA Software, UK), was used for parameter fitting and to obtain numerical solutions for the system equations. Model fits gave very good agreement with in vitro data provided by AstraZeneca across a variety of experimental scenarios. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Modeling and evaluating proliferation resistance of nuclear energy systems for strategy switching proliferation

    International Nuclear Information System (INIS)

    Yue, M.; Cheng, L.-Y.; Bari, R.A.

    2013-01-01

    Highlights: ► Sensitivity analysis is carried out for the model and physical input parameters. ► Interphase drag has minor effect on the dryout heat flux (DHF) in 1D configuration. ► Model calibration on pressure drop experiments fails to improve prediction of DHF. ► Calibrated classical model provides the best agreement with DHF data from 1D tests. ► Further validation of drag models requires data from 2D and 3D experiments on DHF. - Abstract: This paper reports a Markov model based approach to systematically evaluating the proliferation resistance (PR) of nuclear energy systems (NESs). The focus of the study is on the development of the Markov models for a class of complex PR scenarios, i.e., mixed covert/overt strategy switching proliferation, for NESs with two modes of material flow, batch and continuous. In particular, a set of diversion and/or breakout scenarios and covert/overt misuse scenarios are studied in detail for an Example Sodium Fast Reactor (ESFR) system. Both probabilistic and deterministic PR measures are calculated using a software tool that implements the proposed approach and can be used to quantitatively compare proliferation resistant characteristics of different scenarios for a given NES, according to the computed PR measures

  12. The homeostasis of Plasmodium falciparum-infected red blood cells.

    Directory of Open Access Journals (Sweden)

    Jakob M A Mauritz

    2009-04-01

    Full Text Available The asexual reproduction cycle of Plasmodium falciparum, the parasite responsible for severe malaria, occurs within red blood cells. A merozoite invades a red cell in the circulation, develops and multiplies, and after about 48 hours ruptures the host cell, releasing 15-32 merozoites ready to invade new red blood cells. During this cycle, the parasite increases the host cell permeability so much that when similar permeabilization was simulated on uninfected red cells, lysis occurred before approximately 48 h. So how could infected cells, with a growing parasite inside, prevent lysis before the parasite has completed its developmental cycle? A mathematical model of the homeostasis of infected red cells suggested that it is the wasteful consumption of host cell hemoglobin that prevents early lysis by the progressive reduction in the colloid-osmotic pressure within the host (the colloid-osmotic hypothesis. However, two critical model predictions, that infected cells would swell to near prelytic sphericity and that the hemoglobin concentration would become progressively reduced, remained controversial. In this paper, we are able for the first time to correlate model predictions with recent experimental data in the literature and explore the fine details of the homeostasis of infected red blood cells during five model-defined periods of parasite development. The conclusions suggest that infected red cells do reach proximity to lytic rupture regardless of their actual volume, thus requiring a progressive reduction in their hemoglobin concentration to prevent premature lysis.

  13. Dynamic Inversion for Hydrological Process Monitoring with Electrical Resistance Tomography Under Model Uncertainty

    Energy Technology Data Exchange (ETDEWEB)

    Lehikoinen, A.; Huttunen, J.M.J.; Finsterle, S.; Kowalsky, M.B.; Kaipio, J.P.

    2009-08-01

    We propose an approach for imaging the dynamics of complex hydrological processes. The evolution of electrically conductive fluids in porous media is imaged using time-lapse electrical resistance tomography. The related dynamic inversion problem is solved using Bayesian filtering techniques, that is, it is formulated as a sequential state estimation problem in which the target is an evolving posterior probability density of the system state. The dynamical inversion framework is based on the state space representation of the system, which involves the construction of a stochastic evolution model and an observation model. The observation model used in this paper consists of the complete electrode model for ERT, with Archie's law relating saturations to electrical conductivity. The evolution model is an approximate model for simulating flow through partially saturated porous media. Unavoidable modeling and approximation errors in both the observation and evolution models are considered by computing approximate statistics for these errors. These models are then included in the construction of the posterior probability density of the estimated system state. This approximation error method allows the use of approximate - and therefore computationally efficient - observation and evolution models in the Bayesian filtering. We consider a synthetic example and show that the incorporation of an explicit model for the model uncertainties in the state space representation can yield better estimates than a frame-by-frame imaging approach.

  14. Sleep homeostasis, habits and habituation.

    Science.gov (United States)

    Vyazovskiy, Vladyslav V; Walton, Mark E; Peirson, Stuart N; Bannerman, David M

    2017-06-01

    The importance of sleep for behavioural performance during waking is long-established, but the underlying reasons and mechanisms remain elusive. Waking and sleep are associated with changes in the levels of GluA1 AMPAR subunit in synaptic membranes, while studies using genetically-modified mice have identified an important role for GluA1-dependent synaptic plasticity in a non-associative form of memory that underlies short-term habituation to recently experienced stimuli. Here we posit that sleep may play a role in dishabituation, which restores attentional capacity and maximises the readiness of the animal for learning and goal-directed behaviour during subsequent wakefulness. Furthermore we suggest that sleep disturbance may fundamentally change the nature of behaviour, making it more model-free and habitual as a result of reduced attentional capacity. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Research and development of earthquake-resistant structure model for nuclear fuel facility

    Energy Technology Data Exchange (ETDEWEB)

    Uryu, Mitsuru; Terada, S.; Shioya, I. [and others

    1999-05-01

    It is important for a nuclear fuel facility to reduce an input intensity of earthquake on the upper part of the building. To study of a response of the building caused by earthquake, an earthquake-resistant structure model is constructed. The weight of the structure model is 90 ton, and is supported by multiple layers of natural ruber and steel. And a weight support device which is called 'softlanding' is also installed to prevent the structure model from loosing the function at excess deformation. The softlanding device consists of Teflon. Dynamic response characteristics of the structure model caused by sine wave and simulated seismic waves are measured and analyzed. Soil tests of the fourth geologic stratum on which the structure model is sited are made to confirm the safety of soil-structure interactions caused by earthquake. (M. Suetake)

  16. Correlation models between environmental factors and bacterial resistance to antimony and copper.

    Directory of Open Access Journals (Sweden)

    Zunji Shi

    Full Text Available Antimony (Sb and copper (Cu are toxic heavy metals that are associated with a wide variety of minerals. Sb(III-oxidizing bacteria that convert the toxic Sb(III to the less toxic Sb(V are potentially useful for environmental Sb bioremediation. A total of 125 culturable Sb(III/Cu(II-resistant bacteria from 11 different types of mining soils were isolated. Four strains identified as Arthrobacter, Acinetobacter and Janibacter exhibited notably high minimum inhibitory concentrations (MICs for Sb(III (>10 mM,making them the most highly Sb(III-resistant bacteria to date. Thirty-six strains were able to oxidize Sb(III, including Pseudomonas-, Comamonas-, Acinetobacter-, Sphingopyxis-, Paracoccus- Aminobacter-, Arthrobacter-, Bacillus-, Janibacter- and Variovorax-like isolates. Canonical correspondence analysis (CCA revealed that the soil concentrations of Sb and Cu were the most obvious environmental factors affecting the culturable bacterial population structures. Stepwise linear regression was used to create two predictive models for the correlation between soil characteristics and the bacterial Sb(III or Cu(II resistance. The concentrations of Sb and Cu in the soil was the significant factors affecting the bacterial Sb(III resistance, whereas the concentrations of S and P in the soil greatly affected the bacterial Cu(II resistance. The two stepwise linear regression models that we derived are as follows: MIC(Sb(III=606.605+0.14533 x C(Sb+0.4128 x C(Cu and MIC((Cu(II=58.3844+0.02119 x C(S+0.00199 x CP [where the MIC(Sb(III and MIC(Cu(II represent the average bacterial MIC for the metal of each soil (μM, and the C(Sb, C(Cu, C(S and C(P represent concentrations for Sb, Cu, S and P (mg/kg in soil, respectively, p<0.01]. The stepwise linear regression models we developed suggest that metals as well as other soil physicochemical parameters can contribute to bacterial resistance to metals.

  17. Network analysis of an in vitro model of androgen-resistance in prostate cancer

    International Nuclear Information System (INIS)

    Detchokul, Sujitra; Elangovan, Aparna; Crampin, Edmund J.; Davis, Melissa J.; Frauman, Albert G.

    2015-01-01

    The development of androgen resistance is a major limitation to androgen deprivation treatment in prostate cancer. We have developed an in vitro model of androgen-resistance to characterise molecular changes occurring as androgen resistance evolves over time. Our aim is to understand biological network profiles of transcriptomic changes occurring during the transition to androgen-resistance and to validate these changes between our in vitro model and clinical datasets (paired samples before and after androgen-deprivation therapy of patients with advanced prostate cancer). We established an androgen-independent subline from LNCaP cells by prolonged exposure to androgen-deprivation. We examined phenotypic profiles and performed RNA-sequencing. The reads generated were compared to human clinical samples and were analysed using differential expression, pathway analysis and protein-protein interaction networks. After 24 weeks of androgen-deprivation, LNCaP cells had increased proliferative and invasive behaviour compared to parental LNCaP, and its growth was no longer responsive to androgen. We identified key genes and pathways that overlap between our cell line and clinical RNA sequencing datasets and analysed the overlapping protein-protein interaction network that shared the same pattern of behaviour in both datasets. Mechanisms bypassing androgen receptor signalling pathways are significantly enriched. Several steroid hormone receptors are differentially expressed in both datasets. In particular, the progesterone receptor is significantly differentially expressed and is part of the interaction network disrupted in both datasets. Other signalling pathways commonly altered in prostate cancer, MAPK and PI3K-Akt pathways, are significantly enriched in both datasets. The overlap between the human and cell-line differential expression profiles and protein networks was statistically significant showing that the cell-line model reproduces molecular patterns observed in

  18. Pharmacodynamic Model To Describe the Concentration-Dependent Selection of Cefotaxime-Resistant Escherichia coli

    Science.gov (United States)

    Olofsson, Sara K.; Geli, Patricia; Andersson, Dan I.; Cars, Otto

    2005-01-01

    Antibiotic dosing regimens may vary in their capacity to select mutants. Our hypothesis was that selection of a more resistant bacterial subpopulation would increase with the time within a selective window (SW), i.e., when drug concentrations fall between the MICs of two strains. An in vitro kinetic model was used to study the selection of two Escherichia coli strains with different susceptibilities to cefotaxime. The bacterial mixtures were exposed to cefotaxime for 24 h and SWs of 1, 2, 4, 8, and 12 h. A mathematical model was developed that described the selection of preexisting and newborn mutants and the post-MIC effect (PME) as functions of pharmacokinetic parameters. Our main conclusions were as follows: (i) the selection between preexisting mutants increased with the time within the SW; (ii) the emergence and selection of newborn mutants increased with the time within the SW (with a short time, only 4% of the preexisting mutants were replaced by newborn mutants, compared to the longest times, where 100% were replaced); and (iii) PME increased with the area under the concentration-time curve (AUC) and was slightly more pronounced with a long elimination half-life (T1/2) than with a short T1/2 situation, when AUC is fixed. We showed that, in a dynamic competition between strains with different levels of resistance, the appearance of newborn high-level resistant mutants from the parental strains and the PME can strongly affect the outcome of the selection and that pharmacodynamic models can be used to predict the outcome of resistance development. PMID:16304176

  19. Selection of resistant Streptococcus pneumoniae during penicillin treatment in vitro and in three animal models

    DEFF Research Database (Denmark)

    Knudsen, Jenny Dahl; Odenholt, Inga; Erlendsdottir, Helga

    2003-01-01

    Pharmacokinetic (PK) and pharmacodynamic (PD) properties for the selection of resistant pneumococci were studied by using three strains of the same serotype (6B) for mixed-culture infection in time-kill experiments in vitro and in three different animal models, the mouse peritonitis, the mouse....../ml was used in the rabbit tissue cage model. During the different treatment regimens, the differences in numbers of CFU between treated and control animals were calculated to measure the efficacies of the regimens. Selective media with erythromycin or different penicillin concentrations were used to quantify...

  20. Resilience and resistance of sagebrush ecosystems: implications for state and transition models and management treatments

    Science.gov (United States)

    Chambers, Jeanne C.; Miller, Richard F.; Board, David I.; Pyke, David A.; Roundy, Bruce A.; Grace, James B.; Schupp, Eugene W.; Tausch, Robin J.

    2014-01-01

    In sagebrush ecosystems invasion of annual exotics and expansion of piñon (Pinus monophylla Torr. and Frem.) and juniper (Juniperus occidentalis Hook., J. osteosperma [Torr.] Little) are altering fire regimes and resulting in large-scale ecosystem transformations. Management treatments aim to increase resilience to disturbance and enhance resistance to invasive species by reducing woody fuels and increasing native perennial herbaceous species. We used Sagebrush Steppe Treatment Evaluation Project data to test predictions on effects of fire vs. mechanical treatments on resilience and resistance for three site types exhibiting cheatgrass (Bromus tectorum L.) invasion and/or piñon and juniper expansion: 1) warm and dry Wyoming big sagebrush (WY shrub); 2) warm and moist Wyoming big sagebrush (WY PJ); and 3) cool and moist mountain big sagebrush (Mtn PJ). Warm and dry (mesic/aridic) WY shrub sites had lower resilience to fire (less shrub recruitment and native perennial herbaceous response) than cooler and moister (frigid/xeric) WY PJ and Mtn PJ sites. Warm (mesic) WY Shrub and WY PJ sites had lower resistance to annual exotics than cool (frigid to cool frigid) Mtn PJ sites. In WY shrub, fire and sagebrush mowing had similar effects on shrub cover and, thus, on perennial native herbaceous and exotic cover. In WY PJ and Mtn PJ, effects were greater for fire than cut-and-leave treatments and with high tree cover in general because most woody vegetation was removed increasing resources for other functional groups. In WY shrub, about 20% pretreatment perennial native herb cover was necessary to prevent increases in exotics after treatment. Cooler and moister WY PJ and especially Mtn PJ were more resistant to annual exotics, but perennial native herb cover was still required for site recovery. We use our results to develop state and transition models that illustrate how resilience and resistance influence vegetation dynamics and management options.

  1. Model-based control of the resistive wall mode in DIII-D: A comparison study

    International Nuclear Information System (INIS)

    Dalessio, J.; Schuster, E.; Humphreys, D.A.; Walker, M.L.; In, Y.; Kim, J.-S.

    2009-01-01

    One of the major non-axisymmetric instabilities under study in the DIII-D tokamak is the resistive wall mode (RWM), a form of plasma kink instability whose growth rate is moderated by the influence of a resistive wall. One of the approaches for RWM stabilization, referred to as magnetic control, uses feedback control to produce magnetic fields opposing the moving field that accompanies the growth of the mode. These fields are generated by coils arranged around the tokamak. One problem with RWM control methods used in present experiments is that they predominantly use simple non-model-based proportional-derivative (PD) controllers requiring substantial derivative gain for stabilization, which implies a large response to noise and perturbations, leading to a requirement for high peak voltages and coil currents, usually leading to actuation saturation and instability. Motivated by this limitation, current efforts in DIII-D include the development of model-based RWM controllers. The General Atomics (GA)/Far-Tech DIII-D RWM model represents the plasma surface as a toroidal current sheet and characterizes the wall using an eigenmode approach. Optimal and robust controllers have been designed exploiting the availability of the RWM dynamic model. The controllers are tested through simulations, and results are compared to present non-model-based PD controllers. This comparison also makes use of the μ structured singular value as a measure of robust stability and performance of the closed-loop system.

  2. Three-dimensional forward modeling of DC resistivity using the aggregation-based algebraic multigrid method

    Science.gov (United States)

    Chen, Hui; Deng, Ju-Zhi; Yin, Min; Yin, Chang-Chun; Tang, Wen-Wu

    2017-03-01

    To speed up three-dimensional (3D) DC resistivity modeling, we present a new multigrid method, the aggregation-based algebraic multigrid method (AGMG). We first discretize the differential equation of the secondary potential field with mixed boundary conditions by using a seven-point finite-difference method to obtain a large sparse system of linear equations. Then, we introduce the theory behind the pairwise aggregation algorithms for AGMG and use the conjugate-gradient method with the V-cycle AGMG preconditioner (AGMG-CG) to solve the linear equations. We use typical geoelectrical models to test the proposed AGMG-CG method and compare the results with analytical solutions and the 3DDCXH algorithm for 3D DC modeling (3DDCXH). In addition, we apply the AGMG-CG method to different grid sizes and geoelectrical models and compare it to different iterative methods, such as ILU-BICGSTAB, ILU-GCR, and SSOR-CG. The AGMG-CG method yields nearly linearly decreasing errors, whereas the number of iterations increases slowly with increasing grid size. The AGMG-CG method is precise and converges fast, and thus can improve the computational efficiency in forward modeling of three-dimensional DC resistivity.

  3. Physical activity, fitness, glucose homeostasis, and brain morphology in twins.

    Science.gov (United States)

    Rottensteiner, Mirva; Leskinen, Tuija; Niskanen, Eini; Aaltonen, Sari; Mutikainen, Sara; Wikgren, Jan; Heikkilä, Kauko; Kovanen, Vuokko; Kainulainen, Heikki; Kaprio, Jaakko; Tarkka, Ina M; Kujala, Urho M

    2015-03-01

    The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male monozygotic twin pairs discordant for physical activity. From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32-36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage measured by dual-energy x-ray absorptiometry), glucose homeostasis including homeostatic model assessment index and insulin sensitivity index (Matsuda index, calculated from glucose and insulin values from an oral glucose tolerance test), and whole brain magnetic resonance imaging for regional volumetric analyses. According to pairwise analysis, the active twins had lower body fat percentage (P = 0.029) and homeostatic model assessment index (P = 0.031) and higher Matsuda index (P = 0.021) compared with their inactive co-twins. Striatal and prefrontal cortex (subgyral and inferior frontal gyrus) brain gray matter volumes were larger in the nondominant hemisphere in active twins compared with those in inactive co-twins, with a statistical threshold of P physical activity is associated with improved glucose homeostasis and modulation of striatum and prefrontal cortex gray matter volume, independent of genetic background. The findings may contribute to later reduced risk of type 2 diabetes and mobility limitations.

  4. Atmospheric Convective Organization: Self-Organized Criticality or Homeostasis?

    Science.gov (United States)

    Yano, Jun-Ichi

    2015-04-01

    Atmospheric convection has a tendency organized on a hierarchy of scales ranging from the mesoscale to the planetary scales, with the latter especially manifested by the Madden-Julian oscillation. The present talk examines two major possible mechanisms of self-organization identified in wider literature from a phenomenological thermodynamic point of view by analysing a planetary-scale cloud-resolving model simulation. The first mechanism is self-organized criticality. A saturation tendency of precipitation rate with the increasing column-integrated water, reminiscence of critical phenomena, indicates self-organized criticality. The second is a self-regulation mechanism that is known as homeostasis in biology. A thermodynamic argument suggests that such self-regulation maintains the column-integrated water below a threshold by increasing the precipitation rate. Previous analyses of both observational data as well as cloud-resolving model (CRM) experiments give mixed results. A satellite data analysis suggests self-organized criticality. Some observational data as well as CRM experiments support homeostasis. Other analyses point to a combination of these two interpretations. In this study, a CRM experiment over a planetary-scale domain with a constant sea-surface temperature is analyzed. This analysis shows that the relation between the column-integrated total water and precipitation suggests self-organized criticality, whereas the one between the column-integrated water vapor and precipitation suggests homeostasis. The concurrent presence of these two mechanisms are further elaborated by detailed statistical and budget analyses. These statistics are scale invariant, reflecting a spatial scaling of precipitation processes. These self-organization mechanisms are most likely be best theoretically understood by the energy cycle of the convective systems consisting of the kinetic energy and the cloud-work function. The author has already investigated the behavior of this

  5. AMP-18 Targets p21 to Maintain Epithelial Homeostasis.

    Science.gov (United States)

    Chen, Peili; Li, Yan Chun; Toback, F Gary

    2015-01-01

    Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD). We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP)-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF)-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI) mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21 WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD.

  6. AMP-18 Targets p21 to Maintain Epithelial Homeostasis.

    Directory of Open Access Journals (Sweden)

    Peili Chen

    Full Text Available Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD. We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21 WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD.

  7. A method for increase abrasive wear resistance parts by obtaining on methods casting on gasifying models

    Science.gov (United States)

    Sedukhin, V. V.; Anikeev, A. N.; Chumanov, I. V.

    2017-11-01

    Method optimizes hardening working layer parts’, working in high-abrasive conditions looks in this work: bland refractory particles WC and TiC in respect of 70/30 wt. % prepared by beforehand is applied on polystyrene model in casting’ mould. After metal poured in mould, withstand for crystallization, and then a study is carried out. Study macro- and microstructure received samples allows to say that thickness and structure received hardened layer depends on duration interactions blend harder carbides and liquid metal. Different character interactions various dispersed particles and matrix metal observed under the same conditions. Tests abrasive wear resistance received materials of method calculating residual masses was conducted in laboratory’ conditions. Results research wear resistance showed about that method obtaining harder coating of blend carbide tungsten and carbide titanium by means of drawing on surface foam polystyrene model before moulding, allows receive details with surface has wear resistance in 2.5 times higher, than details of analogy steel uncoated. Wherein energy costs necessary for transformation units mass’ substances in powder at obtained harder layer in 2.06 times higher, than materials uncoated.

  8. OpenSim Model Improvements to Support High Joint Angle Resistive Exercising

    Science.gov (United States)

    Gallo, Christopher; Thompson, William; Lewandowski, Beth; Humphreys, Brad

    2016-01-01

    Long duration space travel to Mars or to an asteroid will expose astronauts to extended periods of reduced gravity. Since gravity is not present to aid loading, astronauts will use resistive and aerobic exercise regimes for the duration of the space flight to minimize the loss of bone density, muscle mass and aerobic capacity that occurs during exposure to a reduced gravity environment. Unlike the International Space Station (ISS), the area available for an exercise device in the next generation of spacecraft is limited. Therefore, compact resistance exercise device prototypes are being developed. The Advanced Resistive Exercise Device (ARED) currently on the ISS is being used as a benchmark for the functional performance of these new devices. Rigorous testing of these proposed devices in space flight is difficult so computational modeling provides an estimation of the muscle forces and joint loads during exercise to gain insight on the efficacy to protect the musculoskeletal health of astronauts. The NASA Digital Astronaut Project (DAP) is supporting the Advanced Exercise Concepts (AEC) Project, Exercise Physiology and Countermeasures (ExPC) project and the National Space Biomedical Research Institute (NSBRI) funded researchers by developing computational models of exercising with these new advanced exercise device concepts

  9. Evolutionary stability and resistance to cheating in an indirect reciprocity model based on reputation

    Science.gov (United States)

    Martinez-Vaquero, Luis A.; Cuesta, José A.

    2013-05-01

    Indirect reciprocity is one of the main mechanisms to explain the emergence and sustainment of altruism in societies. The standard approach to indirect reciprocity is reputation models. These are games in which players base their decisions on their opponent's reputation gained in past interactions with other players (moral assessment). The combination of actions and moral assessment leads to a large diversity of strategies; thus determining the stability of any of them against invasions by all the others is a difficult task. We use a variant of a previously introduced reputation-based model that let us systematically analyze all these invasions and determine which ones are successful. Accordingly, we are able to identify the third-order strategies (those which, apart from the action, judge considering both the reputation of the donor and that of the recipient) that are evolutionarily stable. Our results reveal that if a strategy resists the invasion of any other one sharing its same moral assessment, it can resist the invasion of any other strategy. However, if actions are not always witnessed, cheaters (i.e., individuals with a probability of defecting regardless of the opponent's reputation) have a chance to defeat the stable strategies for some choices of the probabilities of cheating and of being witnessed. Remarkably, by analyzing this issue with adaptive dynamics we find that whether an honest population resists the invasion of cheaters is determined by a Hamilton-like rule, with the probability that the cheat is discovered playing the role of the relatedness parameter.

  10. Development of Conformation Independent Computational Models for the Early Recognition of Breast Cancer Resistance Protein Substrates

    Directory of Open Access Journals (Sweden)

    Melisa Edith Gantner

    2013-01-01

    Full Text Available ABC efflux transporters are polyspecific members of the ABC superfamily that, acting as drug and metabolite carriers, provide a biochemical barrier against drug penetration and contribute to detoxification. Their overexpression is linked to multidrug resistance issues in a diversity of diseases. Breast cancer resistance protein (BCRP is the most expressed ABC efflux transporter throughout the intestine and the blood-brain barrier, limiting oral absorption and brain bioavailability of its substrates. Early recognition of BCRP substrates is thus essential to optimize oral drug absorption, design of novel therapeutics for central nervous system conditions, and overcome BCRP-mediated cross-resistance issues. We present the development of an ensemble of ligand-based machine learning algorithms for the early recognition of BCRP substrates, from a database of 262 substrates and nonsubstrates compiled from the literature. Such dataset was rationally partitioned into training and test sets by application of a 2-step clustering procedure. The models were developed through application of linear discriminant analysis to random subsamples of Dragon molecular descriptors. Simple data fusion and statistical comparison of partial areas under the curve of ROC curves were applied to obtain the best 2-model combination, which presented 82% and 74.5% of overall accuracy in the training and test set, respectively.

  11. Quercetin Decreases Insulin Resistance in a Polycystic Ovary Syndrome Rat Model by Improving Inflammatory Microenvironment.

    Science.gov (United States)

    Wang, Zhenzhi; Zhai, Dongxia; Zhang, Danying; Bai, Lingling; Yao, Ruipin; Yu, Jin; Cheng, Wen; Yu, Chaoqin

    2017-05-01

    Insulin resistance (IR) is a clinical feature of polycystic ovary syndrome (PCOS). Quercetin, derived from Chinese medicinal herbs such as hawthorn, has been proven practical in the management of IR in diabetes. However, whether quercetin could decrease IR in PCOS is unknown. This study aims to observe the therapeutic effect of quercetin on IR in a PCOS rat model and explore the underlying mechanism. An IR PCOS rat model was established by subcutaneous injection with dehydroepiandrosterone. The body weight, estrous cycle, and ovary morphology of the quercetin-treated rats were observed. Serum inflammatory cytokines were analyzed using enzyme-linked immunosorbent assay. In ovarian tissues, the expression of key genes involved in the inflammatory signaling pathway was detected through Western blot, real-time polymerase chain reaction, or immunohistochemistry. The nuclear translocation of nuclear factor κB (NF-κB) was also observed by immunofluorescence. The estrous cycle recovery rate of the insulin-resistant PCOS model after quercetin treatment was 58.33%. Quercetin significantly reduced the levels of blood insulin, interleukin 1β, IL-6, and tumor necrosis factor α. Quercetin also significantly decreased the granulosa cell nuclear translocation of NF-κB in the insulin-resistant PCOS rat model. The treatment inhibited the expression of inflammation-related genes, including the nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox, oxidized low-density lipoprotein, and Toll-like receptor 4, in ovarian tissue. Quercetin improved IR and demonstrated a favorable therapeutic effect on the PCOS rats. The underlying mechanism of quercetin potentially involves the inhibition of the Toll-like receptor/NF-κB signaling pathway and the improvement in the inflammatory microenvironment of the ovarian tissue of the PCOS rat model.

  12. Dietary glycemic index, glycemic load, fiber, simple sugars, and insulin resistance - The Inter99 study

    DEFF Research Database (Denmark)

    Lau, Cathrine; Pedersen, Oluf; Færch, Kristine

    2005-01-01

    , and insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). Multiple regressions were performed with HOMA-IR as the dependent variable and carbohydrate-related factors as explanatory variables. All models were adjusted for age, sex, smoking, physical activity......, total energy intake, BMI, and waist circumference. RESULTS - intake of lactose was positively associated with HOMA-IR (P < 0.0001), whereas daily glycemic load and intake of glucose, fructose, dietary fiber, total carbohydrate, fruit, and vegetables were inversely associated with HOMA-IR (P < 0...

  13. A model for prediction of the transient rolling resistance of tyres based on inner-liner temperatures

    Science.gov (United States)

    Greiner, Matthias; Unrau, Hans-Joachim; Gauterin, Frank

    2018-01-01

    Measurements of rolling resistance in thermal equilibrium of a tyre, like measurements according to ISO 28580, do not allow statements about rolling resistances under other driving conditions. Such statements, however, are necessary to determine the energy consumption in driving cycles. Especially for the proper calculation of electric-vehicle remaining ranges and the selection of the respective driving strategies, the real amount of energy consumption is required. This paper presents a model approach, which by means of only one standardised rolling resistance measurement can be parameterised and, considering the present driving speed and tyre temperature, can predict the respective current rolling resistance.

  14. Analytical Model of Thermo-electrical Behaviour in Superconducting Resistive Core Cables

    CERN Document Server

    Calvi, M; Breschi, M; Coccoli, M; Granieri, P; Iriart, G; Lecci, F; Siemko, A

    2006-01-01

    High field superconducting Nb$_{3}$Sn accelerators magnets above 14 T, for future High Energy Physics applications, call for improvements in the design of the protection system against resistive transitions. The longitudinal quench propagation velocity (vq) is one of the parameters defining the requirements of the protection. Up to now vq has been always considered as a physical parameter defined by the operating conditions (the bath temperature, cooling conditions, the magnetic field and the over all current density) and the type of superconductor and stabilizer used. It is possible to enhance the quench propagation velocity by segregating a percent of the stabilizer into the core, although keeping the total amount constant and tuning the contact resistance between the superconducting strands and the core. Analytical model and computer simulations are presented to explain the phenomenon. The consequences with respect to minimum quench energy are evidenced and the strategy to optimize the cable designed is di...

  15. Differential in vivo gene expression of major Leptospira proteins in resistant or susceptible animal models.

    Science.gov (United States)

    Matsui, Mariko; Soupé, Marie-Estelle; Becam, Jérôme; Goarant, Cyrille

    2012-09-01

    Transcripts of Leptospira 16S rRNA, FlaB, LigB, LipL21, LipL32, LipL36, LipL41, and OmpL37 were quantified in the blood of susceptible (hamsters) and resistant (mice) animal models of leptospirosis. We first validated adequate reference genes and then evaluated expression patterns in vivo compared to in vitro cultures. LipL32 expression was downregulated in vivo and differentially regulated in resistant and susceptible animals. FlaB expression was also repressed in mice but not in hamsters. In contrast, LigB and OmpL37 were upregulated in vivo. Thus, we demonstrated that a virulent strain of Leptospira differentially adapts its gene expression in the blood of infected animals.

  16. Improved External Base Resistance Extraction for Submicrometer InP/InGaAs DHBT Models

    DEFF Research Database (Denmark)

    Johansen, Tom Keinicke; Krozer, Viktor; Nodjiadjim, Virginie

    2011-01-01

    An improved direct parameter extraction method is proposed for III–V heterojunction bipolar transistor (HBT) external base resistance $R_{\\rm bx}$ extraction from forward active $S$-parameters. The method is formulated taking into account the current dependence of the intrinsic base–collector cap......An improved direct parameter extraction method is proposed for III–V heterojunction bipolar transistor (HBT) external base resistance $R_{\\rm bx}$ extraction from forward active $S$-parameters. The method is formulated taking into account the current dependence of the intrinsic base...... factor given as the ratio of the emitter to the collector area. The determination of the parameters $I_{p}$ and $X_{0}$ from experimental $S$-parameters is described. The method is applied to high-speed submicrometer InP/InGaAs DHBT devices and leads to small-signal equivalent circuit models, which...

  17. Role of perisynaptic parameters in neurotransmitter homeostasis - computational study of a general synapse

    Science.gov (United States)

    Pendyam, Sandeep; Mohan, Ashwin; Kalivas, Peter W.; Nair, Satish S.

    2015-01-01

    Extracellular neurotransmitter concentrations vary over a wide range depending on the type of neurotransmitter and location in the brain. Neurotransmitter homeostasis near a synapse is achieved by a balance of several mechanisms including vesicular release from the presynapse, diffusion, uptake by transporters, non-synaptic production, and regulation of release by autoreceptors. These mechanisms are also affected by the glia surrounding the synapse. However, the role of these mechanisms in achieving neurotransmitter homeostasis is not well understood. A biophysical modeling framework was proposed to reverse engineer glial configurations and parameters related to homeostasis for synapses that support a range of neurotransmitter gradients. Model experiments reveal that synapses with extracellular neurotransmitter concentrations in the micromolar range require non-synaptic neurotransmitter sources and tight synaptic isolation by extracellular glial formations. The model was used to identify the role of perisynaptic parameters on neurotransmitter homeostasis, and to propose glial configurations that could support different levels of extracellular neurotransmitter concentrations. Ranking the parameters based on their effect on neurotransmitter homeostasis, non-synaptic sources were found to be the most important followed by transporter concentration and diffusion coefficient. PMID:22460547

  18. Selection of drug resistant mutants from random library of Plasmodium falciparum dihydrofolate reductase in Plasmodium berghei model

    Directory of Open Access Journals (Sweden)

    Yuthavong Yongyuth

    2011-05-01

    Full Text Available Abstract Background The prevalence of drug resistance amongst the human malaria Plasmodium species has most commonly been associated with genomic mutation within the parasites. This phenomenon necessitates evolutionary predictive studies of possible resistance mutations, which may occur when a new drug is introduced. Therefore, identification of possible new Plasmodium falciparum dihydrofolate reductase (PfDHFR mutants that confer resistance to antifolate drugs is essential in the process of antifolate anti-malarial drug development. Methods A system to identify mutations in Pfdhfr gene that confer antifolate drug resistance using an animal Plasmodium parasite model was developed. By using error-prone PCR and Plasmodium transfection technologies, libraries of Pfdhfr mutant were generated and then episomally transfected to Plasmodium berghei parasites, from which pyrimethamine-resistant PfDHFR mutants were selected. Results The principal mutation found from this experiment was S108N, coincident with the first pyrimethamine-resistance mutation isolated from the field. A transgenic P. berghei, in which endogenous Pbdhfr allele was replaced with the mutant PfdhfrS108N, was generated and confirmed to have normal growth rate comparing to parental non-transgenic parasite and also confer resistance to pyrimethamine. Conclusion This study demonstrated the power of the transgenic P. berghei system to predict drug-resistant Pfdhfr mutations in an in vivo parasite/host setting. The system could be utilized for identification of possible novel drug-resistant mutants that could arise against new antifolate compounds and for prediction the evolution of resistance mutations.

  19. Implementation of model predictive control for resistive wall mode stabilization on EXTRAP T2R

    Science.gov (United States)

    Setiadi, A. C.; Brunsell, P. R.; Frassinetti, L.

    2015-10-01

    A model predictive control (MPC) method for stabilization of the resistive wall mode (RWM) in the EXTRAP T2R reversed-field pinch is presented. The system identification technique is used to obtain a linearized empirical model of EXTRAP T2R. MPC employs the model for prediction and computes optimal control inputs that satisfy performance criterion. The use of a linearized form of the model allows for compact formulation of MPC, implemented on a millisecond timescale, that can be used for real-time control. The design allows the user to arbitrarily suppress any selected Fourier mode. The experimental results from EXTRAP T2R show that the designed and implemented MPC successfully stabilizes the RWM.

  20. Implementation of model predictive control for resistive wall mode stabilization on EXTRAP T2R

    International Nuclear Information System (INIS)

    Setiadi, A C; Brunsell, P R; Frassinetti, L

    2015-01-01

    A model predictive control (MPC) method for stabilization of the resistive wall mode (RWM) in the EXTRAP T2R reversed-field pinch is presented. The system identification technique is used to obtain a linearized empirical model of EXTRAP T2R. MPC employs the model for prediction and computes optimal control inputs that satisfy performance criterion. The use of a linearized form of the model allows for compact formulation of MPC, implemented on a millisecond timescale, that can be used for real-time control. The design allows the user to arbitrarily suppress any selected Fourier mode. The experimental results from EXTRAP T2R show that the designed and implemented MPC successfully stabilizes the RWM. (paper)

  1. pyres: a Python wrapper for electrical resistivity modeling with R2

    Science.gov (United States)

    Befus, Kevin M.

    2018-04-01

    A Python package, pyres, was written to handle common as well as specialized input and output tasks for the R2 electrical resistivity (ER) modeling program. Input steps including handling field data, creating quadrilateral or triangular meshes, and data filtering allow repeatable and flexible ER modeling within a programming environment. pyres includes non-trivial routines and functions for locating and constraining specific known or separately-parameterized regions in both quadrilateral and triangular meshes. Three basic examples of how to run forward and inverse models with pyres are provided. The importance of testing mesh convergence and model sensitivity are also addressed with higher-level examples that show how pyres can facilitate future research-grade ER analyses.

  2. Neutrophils in Homeostasis, Immunity, and Cancer.

    Science.gov (United States)

    Nicolás-Ávila, José Ángel; Adrover, José M; Hidalgo, Andrés

    2017-01-17

    Neutrophils were among the first leukocytes described and visualized by early immunologists. Prominent effector functions during infection and sterile inflammation classically placed them low in the immune tree as rapid, mindless aggressors with poor regulatory functions. This view is currently under reassessment as we uncover new aspects of their life cycle and identify transcriptional and phenotypic diversity that endows them with regulatory properties that extend beyond their lifetime in the circulation. These properties are revealing unanticipated roles for neutrophils in supporting homeostasis, as well as complex disease states such as cancer. We focus this review on these emerging functions in order to define the true roles of neutrophils in homeostasis, immunity, and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Imbalanced immune homeostasis in immune thrombocytopenia.

    Science.gov (United States)

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Homeostasis as the Mechanism of Evolution

    Directory of Open Access Journals (Sweden)

    John S. Torday

    2015-09-01

    Full Text Available Homeostasis is conventionally thought of merely as a synchronic (same time servo-mechanism that maintains the status quo for organismal physiology. However, when seen from the perspective of developmental physiology, homeostasis is a robust, dynamic, intergenerational, diachronic (across-time mechanism for the maintenance, perpetuation and modification of physiologic structure and function. The integral relationships generated by cell-cell signaling for the mechanisms of embryogenesis, physiology and repair provide the needed insight to the scale-free universality of the homeostatic principle, offering a novel opportunity for a Systems approach to Biology. Starting with the inception of life itself, with the advent of reproduction during meiosis and mitosis, moving forward both ontogenetically and phylogenetically through the evolutionary steps involved in adaptation to an ever-changing environment, Biology and Evolution Theory need no longer default to teleology.

  5. The liver in regulation of iron homeostasis.

    Science.gov (United States)

    Rishi, Gautam; Subramaniam, V Nathan

    2017-09-01

    The liver is one of the largest and most functionally diverse organs in the human body. In addition to roles in detoxification of xenobiotics, digestion, synthesis of important plasma proteins, gluconeogenesis, lipid metabolism, and storage, the liver also plays a significant role in iron homeostasis. Apart from being the storage site for excess body iron, it also plays a vital role in regulating the amount of iron released into the blood by enterocytes and macrophages. Since iron is essential for many important physiological and molecular processes, it increases the importance of liver in the proper functioning of the body's metabolism. This hepatic iron-regulatory function can be attributed to the expression of many liver-specific or liver-enriched proteins, all of which play an important role in the regulation of iron homeostasis. This review focuses on these proteins and their known roles in the regulation of body iron metabolism. Copyright © 2017 the American Physiological Society.

  6. Mitochondrial Iron Transport and Homeostasis in Plants

    Directory of Open Access Journals (Sweden)

    Anshika eJain

    2013-09-01

    Full Text Available Iron (Fe is an essential nutrient for plants and although the mechanisms controlling iron uptake from the soil are relatively well understood, comparatively little is known about subcellular trafficking of iron in plant cells. Mitochondria represent a significant iron sink within cells, as iron is required for the proper functioning of respiratory chain protein complexes. Mitochondria are a site of Fe-S cluster synthesis, and possibly heme synthesis as well. Here we review recent insights into the molecular mechanisms controlling mitochondrial iron transport and homeostasis. We focus on the recent identification of a mitochondrial iron uptake transporter in rice and a possible role for metalloreductases in iron uptake by mitochondria. In addition, we highlight recent advances in mitochondrial iron homeostasis with an emphasis on the roles of frataxin and ferritin in iron trafficking and storage within mitochondria.

  7. [Infecting glial cells with antimony resistant Leishmania tropica: A new ex-vivo model].

    Science.gov (United States)

    Zorbozan, Orçun; Harman, Mehmet; Evren, Vedat; Erdoğan, Mümin Alper; Kılavuz, Aslı; Tunalı, Varol; Çavuş, İbrahim; Yılmaz, Özlem; Özbilgin, Ahmet; Turgay, Nevin

    2018-01-01

    Leishmaniasis is a vector-borne zoonotic disease that shows different clinical features like cutaneous, mucocutaneous, visceral and viscerotropic forms. The protocols used in the treatment of leishmaniasis are toxic and have many limitations during administration. One of the limitations of treatment is the resistance against the protocols in practice. There is also a need to define new treatment options especially for resistant patients. Ex-vivo models using primary cell cultures may be a good source for evaluating new drug options in patients with antimony resistance, in addition to in-vitro and in-vivo studies. In this study, it was aimed to define a new ex-vivo culture model to evaluate treatment options in patients with cutaneous leishmaniasis who did not respond to treatment. In our experimental model of ex-vivo infection, Leishmania tropica promastigotes isolated from a case previously diagnosed with cutaneous leishmaniasis were used. The primary astroglial cell culture used for the ex-vivo model was prepared from 2-3 days old neonatal Sprague Dawley rat brains under sterile conditions by the modification McCarthy's method. The astroglia cells, which reached sufficient density, were infected with antimony resistant L.tropica promastigotes. After 24 hours of incubation, the supernatant on the cells were collected, the cell culture plate was dried at room temperature, then fixed with methyl alcohol and stained with Giemsa to search for L.tropica amastigotes. Amastigotes were intensely observed in glia cells in primary cell cultures infected with L.tropica promastigotes. No promastigotes were seen on Giemsa stained preparations of the precipitates prepared from the bottom sediment after the centrifugation of the liquid medium removed from the infected plates. In this study, promastigotes from a cutaneous leishmaniasis patient unable to respond to pentavalent antimony therapy were shown to infect rat glia cells and converted to amastigote form. This amastigote

  8. MicroRNAs and Periodontal Homeostasis.

    Science.gov (United States)

    Luan, X; Zhou, X; Trombetta-eSilva, J; Francis, M; Gaharwar, A K; Atsawasuwan, P; Diekwisch, T G H

    2017-05-01

    MicroRNAs (miRNAs) are a group of small RNAs that control gene expression in all aspects of eukaryotic life, primarily through RNA silencing mechanisms. The purpose of the present review is to introduce key miRNAs involved in periodontal homeostasis, summarize the mechanisms by which they affect downstream genes and tissues, and provide an introduction into the therapeutic potential of periodontal miRNAs. In general, miRNAs function synergistically to fine-tune the regulation of biological processes and to remove expression noise rather than by causing drastic changes in expression levels. In the periodontium, miRNAs play key roles in development and periodontal homeostasis and during the loss of periodontal tissue integrity as a result of periodontal disease. As part of the anabolic phase of periodontal homeostasis and periodontal development, miRNAs direct periodontal fibroblasts toward alveolar bone lineage differentiation and new bone formation through WNT, bone morphogenetic protein, and Notch signaling pathways. miRNAs contribute equally to the catabolic aspect of periodontal homeostasis as they affect osteoclastogenesis and osteoclast function, either by directly promoting osteoclast activity or by inhibiting osteoclast signaling intermediaries or through negative feedback loops. Their small size and ability to target multiple regulatory networks of related sets of genes have predisposed miRNAs to become ideal candidates for drug delivery and tissue regeneration. To address the immense therapeutic potential of miRNAs and their antagomirs, an ever growing number of delivery approaches toward clinical applications have been developed, including nanoparticle carriers and secondary structure interference inhibitor systems. However, only a fraction of the miRNAs involved in periodontal health and disease are known today. It is anticipated that continued research will lead to a more comprehensive understanding of the periodontal miRNA world, and a systematic

  9. The Commensal Microbiota Drives Immune Homeostasis

    OpenAIRE

    Arrieta, Marie-Claire; Finlay, Barton Brett

    2012-01-01

    For millions of years, microbes have coexisted with eukaryotic cells at the mucosal surfaces of vertebrates in a complex, yet usually harmonious symbiosis. An ever-expanding number of reports describe how eliminating or shifting the intestinal microbiota has profound effects on the development and functionality of the mucosal and systemic immune systems. Here, we examine some of the mechanisms by which bacterial signals affect immune homeostasis. Focusing on the strategies that microbes use t...

  10. Molecular monitoring of equine joint homeostasis

    OpenAIRE

    de Grauw, J.C.

    2010-01-01

    Chronic joint disorders are a major cause of impaired mobility and loss of quality of life in both humans and horses. Regardless of the primary insult, any joint disorder is characterized by an upset in normal joint homeostasis, the balance between tissue anabolism and catabolism that is normally maintained by resident articular cells. This upset is often fuelled by a local inflammatory response in the synovial membrane and the articular cartilage. Our current understanding of the pathogenesi...

  11. THE WORLD VIEW, IDENTITY AND SOCIOCULTUR HOMEOSTASIS

    Directory of Open Access Journals (Sweden)

    Marina Yur’evna Neronova

    2016-02-01

    Full Text Available The paper presents the relationship between the phenomenon of world view and sociocultural identity both individuals and the community as a whole. The research is being carried out in the context of current crisis of world view accepted in so-called art Nouveau era. This paper also presents the identity crisis typical for modern civilized societies. A new notion of sociocultural homeostasis is introduced in connection with analyzable phenomena and their mutual relations.Purpose. Study of the relationship between the phenomenon of the world view and sociocultural identity as a structural and functional mechanism.Methodology. Phenomenological and systematic methods with the elements of historical method were employed. Cultural analysis is based on using both axiological and phenomenological approach, and also the elements of semiotic approach.Results. The dependence of identity on the world view is revealed (or is being revealed?, the phenomenon of sociocultural homeostasis is singled out (or is being singled out in the capacity of the mechanism setting up the correspondence in the contradictory unity between the world view as a subjective image and concrete reality as an objective part of this contradictory. The analysis of sociocultural homeostasis is carried out (or is being carried out and the conclusion is being drown that instability of the latter leads to serious problems in the identification of both individuals and communities as a whole. Besides, (moreover the relationship between the legitimacy level of the world view and stability of sociocultural homeostasis is established. (is being established.Practical implications: the system of education.

  12. Guest editor's introduction: Energy homeostasis in context.

    Science.gov (United States)

    Schneider, Jill E

    2014-06-01

    This article is part of a Special Issue "Energy Balance". Energy homeostasis is achieved through neuroendocrine and metabolic control of energy intake, storage, and expenditure. Traditionally, these controls have been studied in an unrealistic and narrow context. The appetite for food, for example, is most often assumed to be independent of other motivations, such as sexual desire, fearfulness, and competition. Furthermore, our understanding of all aspects of energy homeostasis is based on studying males of only a few species. The baseline control subjects are most often housed in enclosed spaces, with continuous, unlimited access to food. In the last century, this approach has generated useful information, but all the while, the global prevalence of obesity has increased and remains at unprecedented levels (Ogden et al., 2013, 2014). It is likely, however, that the mechanisms that control ingestive behavior were molded by evolutionary forces, and that few, if any vertebrate species evolved in the presence of a limitless food supply, in an enclosed 0.5 × 1 ft space, and exposed to a constant ambient temperature of 22+2 °C. This special issue of Hormones and Behavior therefore contains 9 review articles and 7 data articles that consider energy homeostasis within the context of other motivations and physiological processes, such as early development, sexual differentiation, sexual motivation, reproduction, seasonality, hibernation, and migration. Each article is focused on a different species or on a set of species, and most vertebrate classes are represented. Energy homeostasis is viewed in the context of the selection pressures that simultaneously molded multiple aspects of energy intake, storage, and expenditure. This approach yields surprising conclusions regarding the function of those traits and their underlying neuroendocrine mechanisms. Copyright © 2014. Published by Elsevier Inc.

  13. Orm family proteins mediate sphingolipid homeostasis

    DEFF Research Database (Denmark)

    Breslow, David K; Collins, Sean R; Bodenmiller, Bernd

    2010-01-01

    a conserved complex with serine palmitoyltransferase, the first and rate-limiting enzyme in sphingolipid production. We also define a regulatory pathway in which phosphorylation of Orm proteins relieves their inhibitory activity when sphingolipid production is disrupted. Changes in ORM gene expression...... or mutations to their phosphorylation sites cause dysregulation of sphingolipid metabolism. Our work identifies the Orm proteins as critical mediators of sphingolipid homeostasis and raises the possibility that sphingolipid misregulation contributes to the development of childhood asthma....

  14. Fabp4-Cre-mediated Sirt6 deletion impairs adipose tissue function and metabolic homeostasis in mice.

    Science.gov (United States)

    Xiong, Xiwen; Zhang, Cuicui; Zhang, Yang; Fan, Rui; Qian, Xinlai; Dong, X Charlie

    2017-06-01

    SIRT6 is a member of sirtuin family of deacetylases involved in diverse processes including genome stability, metabolic homeostasis and anti-inflammation. However, its function in the adipose tissue is not well understood. To examine the metabolic function of SIRT6 in the adipose tissue, we generated two mouse models that are deficient in Sirt6 using the Cre-lox approach. Two commonly used Cre lines that are driven by either the mouse Fabp4 or Adipoq gene promoter were chosen for this study. The Sirt6- knockout mice generated by the Fabp4-Cre line ( Sirt6 f/f : Fabp4-Cre) had a significant increase in both body weight and fat mass and exhibited glucose intolerance and insulin resistance as compared with the control wild-type mice. At the molecular levels, the Sirt6 f/f :Fabp4-Cre-knockout mice had increased expression of inflammatory genes including F4/80, TNFα, IL-6 and MCP-1 in both white and brown adipose tissues. Moreover, the knockout mice showed decreased expression of the adiponectin gene in the white adipose tissue and UCP1 in the brown adipose tissue, respectively. In contrast, the Sirt6 knockout mice generated by the Adipoq-Cre line ( Sirt6 f/f :Adipoq-Cre) only had modest insulin resistance. In conclusion, our data suggest that the function of SIRT6 in the Fabp4-Cre-expressing cells in addition to mature adipocytes plays a critical role in body weight maintenance and metabolic homeostasis. © 2017 Society for Endocrinology.

  15. The Association Between IGF-I and Insulin Resistance

    DEFF Research Database (Denmark)

    Friedrich, Nele; Thuesen, Betina; Jørgensen, Torben

    2012-01-01

    OBJECTIVEIGF-I has an almost 50% amino acid sequence homology with insulin and elicits nearly the same hypoglycemic response. Studies showed that low and high IGF-I levels are related to impaired glucose tolerance and to a higher risk of type 2 diabetes. The aim of the current study was to evaluate...... the association between IGF-I level and insulin resistance in a Danish general population.RESEARCH DESIGN AND METHODSIncluded were 3,354 adults, aged 19-72 years, from the cross-sectional Health2006 study. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as the index to estimate insulin...... with intermediate (Q3) IGF-I levels. These associations remained statistically significant after the exclusion of subjects with type 2 diabetes and by using the updated computer HOMA2-IR model.CONCLUSIONSLow- and high-normal IGF-I levels are both related to insulin resistance. The biological mechanism...

  16. Type 2 diabetes mellitus as a disorder of galanin resistance.

    Science.gov (United States)

    Fang, Penghua; Shi, Mingyi; Zhu, Yan; Bo, Ping; Zhang, Zhenwen

    2016-01-01

    The increasing prevalence of type 2 diabetes mellitus with its high morbidity and mortality becomes an important health problem. The multifactorial etiology of type 2 diabetes mellitus is relative to many gene and molecule alterations, and increased insulin resistance. Besides these, however, there are still other predisposing and risk factors accounting for type 2 diabetes mellitus not to be identified and recognized. Emerging evidence indicated that defects in galanin function played a crucial role in development of type 2 diabetes mellitus. Galanin homeostasis is tightly relative to insulin resistance and is regulated by blood glucose. Hyperglycemia, hyperinsulinism, enhanced plasma galanin levels and decreased galanin receptor activities are some of the characters of type 2 diabetes mellitus. The discrepancy between high insulin level and low glucose handling is named as insulin resistance. Similarly, the discrepancy between high galanin level and low glucose handling may be denominated as galanin resistance too. In this review, the characteristic milestones of type 2 diabetes mellitus were condensed as two analogical conceptual models, obesity-hyper-insulin-insulin resistance-type 2 diabetes mellitus and obesity-hyper-galanin-galanin resistance-type 2 diabetes mellitus. Both galanin resistance and insulin resistance are correlative with each other. Conceptualizing the etiology of type 2 diabetes mellitus as a disorder of galanin resistance may inspire a new concept to deepen our knowledge about pathogenesis of type 2 diabetes mellitus, eventually leading to novel preventive and therapeutic interventions for type 2 diabetes mellitus. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Retinol binding protein 4, obesity, and insulin resistance in adolescents

    Directory of Open Access Journals (Sweden)

    Ronaldi Noor

    2017-02-01

    Full Text Available Background Obesity is a global problem. Even in poor and developing countries, obesity has reached alarming levels. In childhood, obesity may lead to insulin resistance. Retinol binding protein (RBP4, secreted primarily by liver and adipose tissues, was recently proposed as a link between obesity and insulin resistance. The role of RBP4 in pediatric obesity and its relationship with insulin resistance have not been well elucidated. Objective To compare RBP4 levels in obese and lean adolescents and to assess for a relationship between RBP4 levels and insulin resistance. Method This cross-sectional study was conducted in three senior high schools in Padang, West Sumatera, Indonesia. Subjects were adolescents aged 14-18 years, who were obese or normal weight (n=56. We measured subjects’ body mass index (BMI and serum RBP4 concentrations. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR index. Results Similar RBP4 levels were found in the obese and normoweight groups (P>0.05. Higher RBP4 levels were found in the insulin resistant compared to the non-insulin resistant group, but the difference was not significant (P > 0.05. Conclusion There is no significant difference in mean RBP4 levels in obese adolescents compared to normoweight adolescents. Nor are mean RBP4 levels significantly different between obese adolescents with and without insulin resistance.

  18. GDSL lipases modulate immunity through lipid homeostasis in rice.

    Science.gov (United States)

    Gao, Mingjun; Yin, Xin; Yang, Weibing; Lam, Sin Man; Tong, Xiaohong; Liu, Jiyun; Wang, Xin; Li, Qun; Shui, Guanghou; He, Zuhua

    2017-11-01

    Lipids and lipid metabolites play important roles in plant-microbe interactions. Despite the extensive studies of lipases in lipid homeostasis and seed oil biosynthesis, the involvement of lipases in plant immunity remains largely unknown. In particular, GDSL esterases/lipases, characterized by the conserved GDSL motif, are a subfamily of lipolytic enzymes with broad substrate specificity. Here, we functionally identified two GDSL lipases, OsGLIP1 and OsGLIP2, in rice immune responses. Expression of OsGLIP1 and OsGLIP2 was suppressed by pathogen infection and salicylic acid (SA) treatment. OsGLIP1 was mainly expressed in leaf and leaf sheath, while OsGLIP2 showed high expression in elongating internodes. Biochemical assay demonstrated that OsGLIP1 and OsGLIP2 are functional lipases that could hydrolyze lipid substrates. Simultaneous down-regulation of OsGLIP1 and OsGLIP2 increased plant resistance to both bacterial and fungal pathogens, whereas disease resistance in OsGLIP1 and OsGLIP2 overexpression plants was significantly compromised, suggesting that both genes act as negative regulators of disease resistance. OsGLIP1 and OsGLIP2 proteins mainly localize to lipid droplets and the endoplasmic reticulum (ER) membrane. The proper cellular localization of OsGLIP proteins is indispensable for their functions in immunity. Comprehensive lipid profiling analysis indicated that the alteration of OsGLIP gene expression was associated with substantial changes of the levels of lipid species including monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG). We show that MGDG and DGDG feeding could attenuate disease resistance. Taken together, our study indicates that OsGLIP1 and OsGLIP2 negatively regulate rice defense by modulating lipid metabolism, thus providing new insights into the function of lipids in plant immunity.

  19. The inaccuracy of conventional one-dimensional parallel thermal resistance circuit model for two-dimensional composite walls

    International Nuclear Information System (INIS)

    Wong, K.-L.; Hsien, T.-L.; Hsiao, M.-C.; Chen, W.-L.; Lin, K.-C.

    2008-01-01

    This investigation is to show that two-dimensional steady state heat transfer problems of composite walls should not be solved by the conventionally one-dimensional parallel thermal resistance circuits (PTRC) model because the interface temperatures are not unique. Thus PTRC model cannot be used like its conventional recognized analogy, parallel electrical resistance circuits (PERC) model which has the unique node electric voltage. Two typical composite wall examples, solved by CFD software, are used to demonstrate the incorrectness. The numerical results are compared with those obtained by PTRC model, and very large differences are observed between their results. This proves that the application of conventional heat transfer PTRC model to two-dimensional composite walls, introduced in most heat transfer text book, is totally incorrect. An alternative one-dimensional separately series thermal resistance circuit (SSTRC) model is proposed and applied to the two-dimensional composite walls with isothermal boundaries. Results with acceptable accuracy can be obtained by the new model

  20. Incorrectness of conventional one-dimensional parallel thermal resistance circuit model for two-dimensional circular composite pipes

    International Nuclear Information System (INIS)

    Wong, K.-L.; Hsien, T.-L.; Chen, W.-L.; Yu, S.-J.

    2008-01-01

    This study is to prove that two-dimensional steady state heat transfer problems of composite circular pipes cannot be appropriately solved by the conventional one-dimensional parallel thermal resistance circuits (PTRC) model because its interface temperatures are not unique. Thus, the PTRC model is definitely different from its conventional recognized analogy, parallel electrical resistance circuits (PERC) model, which has unique node electric voltages. Two typical composite circular pipe examples are solved by CFD software, and the numerical results are compared with those obtained by the PTRC model. This shows that the PTRC model generates large error. Thus, this conventional model, introduced in most heat transfer text books, cannot be applied to two-dimensional composite circular pipes. On the contrary, an alternative one-dimensional separately series thermal resistance circuit (SSTRC) model is proposed and applied to a two-dimensional composite circular pipe with isothermal boundaries, and acceptable results are returned

  1. Hydrogeological bedrock inferred from electrical resistivity model in Taichung Basin, Taiwan

    Science.gov (United States)

    Chiang, C. W.; Chang, P. Y.; Chang, L. C.

    2015-12-01

    The four-year project of the study of groundwater hydrogeology and recharge model was indicated by Central Geological Survey, MOEA, Taiwan (R.O.C.) to evaluate recharge groundwater areas in Taiwan where included Taipei, Taichung Basins, Lanyang and Chianan Plains. The groundwater recharge models of Lanyang Plain and Taipei Basin have successfully been estimated in two years ago (2013-2014). The third year of the project integrates with geophysical, geochemistry, and hydrogeology models to estimate the groundwater recharge model in Taichung Basin region. Taichung Basin is mainly covered by Pre-Pleistocene of thick gravel, sandy and muddy sediment rocks within a joint alluvial fan, whereas the depth of the hydrological bedrock remains uncertain. Two electrical resistivity geophysical tools were carried out utilizing direct current resistivity and audio-magnetotelluric (AMT) explorations, which could ideally provide the depth resolutions from shallow to depth for evaluating the groundwater resources. The study has carried out 21 AMT stations in the southern Taichung Basin in order to delineate hydrological bedrock in the region. All the AMT stations were deployed about 24 hours and processed with remote reference technique to reduce culture noises. The quality of most stations shows acceptable in the area which two stations were excluded due to near-field source effect in the southwestern basin. The best depth resolution is identified in 500 meters for the model. The preliminary result shows that the depths of the bedrock gradually changes from southern ~20 m toward to ~400 m in central, and eastern ~20 m to 180 m in the western basin inferred from the AMT model. The investigation shows that AMT method could be a useful geophysical tool to enhance the groundwater recharge model estimation without dense loggings in the region.

  2. Improved characterisation and modelling of measurement errors in electrical resistivity tomography (ERT) surveys

    Science.gov (United States)

    Tso, Chak-Hau Michael; Kuras, Oliver; Wilkinson, Paul B.; Uhlemann, Sebastian; Chambers, Jonathan E.; Meldrum, Philip I.; Graham, James; Sherlock, Emma F.; Binley, Andrew

    2017-11-01

    Measurement errors can play a pivotal role in geophysical inversion. Most inverse models require users to prescribe or assume a statistical model of data errors before inversion. Wrongly prescribed errors can lead to over- or under-fitting of data; however, the derivation of models of data errors is often neglected. With the heightening interest in uncertainty estimation within hydrogeophysics, better characterisation and treatment of measurement errors is needed to provide improved image appraisal. Here we focus on the role of measurement errors in electrical resistivity tomography (ERT). We have analysed two time-lapse ERT datasets: one contains 96 sets of direct and reciprocal data collected from a surface ERT line within a 24 h timeframe; the other is a two-year-long cross-borehole survey at a UK nuclear site with 246 sets of over 50,000 measurements. Our study includes the characterisation of the spatial and temporal behaviour of measurement errors using autocorrelation and correlation coefficient analysis. We find that, in addition to well-known proportionality effects, ERT measurements can also be sensitive to the combination of electrodes used, i.e. errors may not be uncorrelated as often assumed. Based on these findings, we develop a new error model that allows grouping based on electrode number in addition to fitting a linear model to transfer resistance. The new model explains the observed measurement errors better and shows superior inversion results and uncertainty estimates in synthetic examples. It is robust, because it groups errors together based on the electrodes used to make the measurements. The new model can be readily applied