Lack of CRH Affects the Behavior but Does Not Affect the Formation of Short-Term Memory.

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Varejkova, Eva; Plananska, Eva; Myslivecek, Jaromir

2018-01-01

Corticotropin-releasing hormone (CRH) is involved in modification of synaptic transmission and affects spatial discrimination learning, i.e., affects the formation of memory in long-term aspect. Therefore, we have focused on CRH effect on short-term memory. We have used stress task avoidance (maze containing three zones: entrance, aversive, and neutral) and compared the behavior and short-term memory in wild-type mice and mice lacking CRH (CRH KO) experiencing one 120-min session of restraint stress. As control, non-stressed animals were used. As expected, the animals that experienced the stress situation tend to spend less time in the zone in which the restraint chamber was present. The animals spent more time in the neutral zone. There were significant differences in number of freezing bouts in the aversive and entrance zones in CRH KO animals. CRH KO control animals entered the neutral zone much more faster than WT control and spent more time immobile in the neutral zone than WT control. These data give evidence that lacking of CRH itself improves the ability of mice to escape away from potentially dangerous area (i.e., those in which the scent of stressed animal is present).

Elevated corticotropin releasing hormone (CRH) during pregnancy and risk of postpartum depression (PPD).

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Meltzer-Brody, Samantha; Stuebe, Alison; Dole, Nancy; Savitz, David; Rubinow, David; Thorp, John

2011-01-01

Perinatal depression has a prevalence of 10% with devastating consequences for mother and baby. The prospective identification of those at risk for postpartum (PPD) or prenatal (PND) depression has led to biomarker searches in pregnancy. There are conflicting reports of associations between midpregnancy placental CRH (pCRH) and PPD or PND. The objective of the study was to quantify the association of maternal pCRH with PPD and PND. This was a prospective cohort study (the Pregnancy, Infection, and Nutrition Study). The study was conducted at a prenatal clinics at the University of North Carolina at Chapel Hill. Patients included 1230 pregnant women. The relationship between pCRH at less than 20 wk and 24-29 wk and maternal depression assessed in pregnancy [Center for Epidemiologic Studies Depression Scale (CES-D)] and postpartum (12 wk and 1 yr) with the Edinburgh Postnatal Depression Scale (EPDS). At 24-29 wk, 24.8% of women had CES-D score of 17 or greater, and 9.7% had a CES-D score of 25 or greater. At 12 wk postpartum, 18.2% of women had an EPDS score of 10 or greater and 7.6% had an EPDS score of 13 or greater. CRH measures at less than 20 wk and 24-29 wk were inversely correlated with a CES-D score at 24-29 wk (n = 1080, P PPD (covariate-adjusted odds ratio per sd 0.99, 95% confidence interval 0.69-1.42). Higher midpregnancy pCRH was not associated with an increased risk of PND or PPD.

Immune Aspects and Myometrial Actions of Progesterone and CRH in Labor

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Vrachnis, Nikolaos; Malamas, Fotodotis M.; Sifakis, Stavros; Tsikouras, Panayiotis; Iliodromiti, Zoe

2011-01-01

Progesterone and corticotropin-releasing hormone (CRH) have a critical role in pregnancy and labor, as changes related to these hormones are crucial for the transition from myometrial quiescence to contractility. The mechanisms related to their effect differ between humans and other species, thus, despite extensive research, many questions remain to be answered regarding their mediation in human labor. Immune responses to progesterone and CRH are important for labor. Progesterone acts as an i...

Effects of Insufficient Sleep on Pituitary-Adrenocortical Response to CRH Stimulation in Healthy Men.

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Guyon, Aurore; Morselli, Lisa L; Balbo, Marcella L; Tasali, Esra; Leproult, Rachel; L'Hermite-Balériaux, Mireille; Van Cauter, Eve; Spiegel, Karine

2017-06-01

Severe sleep restriction results in elevated evening cortisol levels. We examined whether this relative hypercortisolism is associated with alterations in the pituitary-adrenocortical response to evening corticotropin-releasing hormone (CRH) stimulation. Eleven subjects participated in 2 sessions (2 nights of 10 hours vs. 4 hours in bed) in randomized order. Sleep was polygraphically recorded. After the second night of each session, blood was sampled at 20-minute intervals from 09:00 to 24:00 for adrenocorticotropic hormone (ACTH) and cortisol measurements, and perceived stress was assessed hourly. Ovine CRH was injected at 18:00 (1 µg/kg body weight). Prior to CRH injection, baseline ACTH, but not cortisol, levels were elevated after sleep restriction. Relative to the well-rested condition, sleep restriction resulted in a 27% decrease in overall ACTH response to CRH (estimated by the incremental area under the curve from 18:00 to 24:00; p = .002) while the cortisol response was decreased by 21% (p = .083). Further, the magnitude of these decreases was correlated with the individual amount of sleep loss (ACTH: rSp = -0.65, p = .032; cortisol: rSp = -0.71, p = .015). The acute post-CRH increment of cortisol was reduced (p = .002) without changes in ACTH reactivity, suggesting decreased adrenal sensitivity. The rate of decline from peak post-injection levels was reduced for cortisol (p = .032), but not for ACTH. Scores of perceived stress were unaffected by CRH injection and were low and similar under both sleep conditions. Sleep restriction is associated with a reduction of the overall ACTH and cortisol responses to evening CRH stimulation, and a reduced reactivity and slower recovery of the cortisol response. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Effect of Childhood Trauma on Adult Depression and Neuroendocrine Function: Sex-Specific Moderation by CRH Receptor 1 Gene.

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Heim, Christine; Bradley, Bekh; Mletzko, Tanja C; Deveau, Todd C; Musselman, Dominique L; Nemeroff, Charles B; Ressler, Kerry J; Binder, Elisabeth B

2009-01-01

Variations of the corticotropin-releasing hormone receptor 1 (CRHR1) gene appear to moderate the development of depression after childhood trauma. Depression more frequently affects women than men. We examined sex differences in the effects of the CRHR1 gene on the relationship between childhood trauma and adult depression. We recruited 1,063 subjects from the waiting rooms of a public urban hospital. Childhood trauma exposure and symptoms of depression were assessed using dimensional rating scales. Subjects were genotyped for rs110402 within the CRHR1 gene. An independent sample of 78 subjects underwent clinical assessment, genotyping, and a dexamethasone/CRH test. The age range at recruitment was 18-77 years and 18-45, for the two studies respectively. In the hospital sample, the protective effect of the rs110402 A-allele against developing depression after childhood trauma was observed in men (N = 424), but not in women (N = 635). In the second sample, the rs110402 A-allele was associated with decreased cortisol response in the dexamethasone/CRH test only in men. In A-allele carriers with childhood trauma exposure women exhibited increased cortisol response compared men; there were no sex differences in A-allele carriers without trauma exposure. This effect may, however, not be related to gender differences per se, but to differences in the type of experienced abuse between men and women. CRHR x environment interactions in the hospital sample were observed with exposure to physical, but not sexual or emotional abuse. Physical abuse was the most common type of abuse in men in this cohort, while sexual abuse was most commonly suffered by women. Our results suggest that the CRHR1 gene may only moderate the effects of specific types of childhood trauma on depression. Gender differences in environmental exposures could thus be reflected in sex-specific CRHR1 x child abuse interactions.

Corticotropin-Releasing Hormone (CRH Promotes Macrophage Foam Cell Formation via Reduced Expression of ATP Binding Cassette Transporter-1 (ABCA1.

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Wonkyoung Cho

Full Text Available Atherosclerosis, the major pathology of cardiovascular disease, is caused by multiple factors involving psychological stress. Corticotropin-releasing hormone (CRH, which is released by neurosecretory cells in the hypothalamus, peripheral nerve terminals and epithelial cells, regulates various stress-related responses. Our current study aimed to verify the role of CRH in macrophage foam cell formation, the initial critical stage of atherosclerosis. Our quantitative real-time reverse transcriptase PCR (qRT-PCR, semi-quantitative reverse transcriptase PCR, and Western blot results indicate that CRH down-regulates ATP-binding cassette transporter-1 (ABCA1 and liver X receptor (LXR-α, a transcription factor for ABCA1, in murine peritoneal macrophages and human monocyte-derived macrophages. Oil-red O (ORO staining and intracellular cholesterol measurement of macrophages treated with or without oxidized LDL (oxLDL and with or without CRH (10 nM in the presence of apolipoprotein A1 (apoA1 revealed that CRH treatment promotes macrophage foam cell formation. The boron-dipyrromethene (BODIPY-conjugated cholesterol efflux assay showed that CRH treatment reduces macrophage cholesterol efflux. Western blot analysis showed that CRH-induced down-regulation of ABCA1 is dependent on phosphorylation of Akt (Ser473 induced by interaction between CRH and CRH receptor 1(CRHR1. We conclude that activation of this pathway by CRH accelerates macrophage foam cell formation and may promote stress-related atherosclerosis.

Alcohol dysregulates corticotropin-releasing-hormone (CRH promoter activity by interfering with the negative glucocorticoid response element (nGRE.

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Magdalena M Przybycien-Szymanska

Full Text Available EtOH exposure in male rats increases corticotropin-releasing hormone (CRH mRNA in the paraventricular nucleus of the hypothalamus (PVN, a brain region responsible for coordinating stress and anxiety responses. In this study we identified the molecular mechanisms involved in mediating these effects by examining the direct effects of EtOH on CRH promoter activity in a neuronal cell line derived from the PVN (IVB. In addition, we investigated the potential interactions of EtOH and glucocorticoids on the CRH promoter by concomitantly treating cells with EtOH and the glucocorticoid receptor (GR antagonist RU486, and by sequentially deleting GR binding sites within glucocorticoid response element (GRE on the CRH promoter. Cells were transiently transfected with a firefly luciferase reporter construct containing 2.5 kb of the rat wild type (WT or mutated CRH promoter. Our results showed that EtOH treatment induced a biphasic response in CRH promoter activity. EtOH exposure for 0.5 h significantly decreased promoter activity compared to vehicle treated controls, whereas promoter activity was significantly increased after 2.0 h of EtOH exposure. Treatment with RU486, or deletion of the GR binding sites 1 and 2 within the GRE, abolished the EtOH-induced increase in the promoter activity, however did not affect EtOH-induced decrease in CRH promoter activity at an earlier time point. Overall, our data suggest that alcohol exposure directly regulates CRH promoter activity by interfering with the normal feedback mechanisms of glucocorticoids mediated by GR signaling at the GRE site of the CRH promoter.

BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus

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Jeanneteau, Freddy D.; Lambert, W. Marcus; Ismaili, Naima; Bath, Kevin G.; Lee, Francis S.; Garabedian, Michael J.; Chao, Moses V.

2012-01-01

Regulation of the hypothalamic–pituitary–adrenal (HPA) axis is critical for adaptation to environmental changes. The principle regulator of the HPA axis is corticotrophin-releasing hormone (CRH), which is made in the parventricular nucleus and is an important target of negative feedback by glucocorticoids. However, the molecular mechanisms that regulate CRH are not fully understood. Disruption of normal HPA axis activity is a major risk factor of neuropsychiatric disorders in which decreased ...

Regulation of estradiol and progesterone production by CRH-R1 and -R2 is through divergent signaling pathways in cultured human placental trophoblasts.

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Gao, Lu; Tao, Yi; Hu, Tianxiao; Liu, Weina; Xu, Chen; Liu, Jie; You, Xingji; Gu, Hang; Ni, Xin

2012-10-01

CRH and its related peptides urocortins (UCN) have been identified in placenta and implicated to play pivotal roles in the regulation of pregnancy and parturition in humans. The objectives of present study were to investigate the effects of endogenous CRH and its related peptides in the regulation of steroid production in placenta. Placental trophoblasts were isolated from term placenta tissues and cultured for 72 h. Estradiol (E(2)) and progesterone (P(4)) contents in culture media were determined by radioimmunoassay. Treatment of cultured trophoblasts with CRH or UCNI antibody showed decreased E(2), whereas increased P(4) production. Treatment of cells with CRH receptor type 1 antagonist antalarmin or CRH receptor type 2 (CRH-R2) antagonist astressin-2b also decreased E(2) but increased P(4) production. Knockdown of CRH receptor type 1 or CRH-R2 cells showed a decrease in E(2) production and an increase in P(4) production. In CRH-R2 knockdown cells, CRH stimulated GTP-bound Gαs protein and phosphorylated phospholipase C-β3. Adenylyl cyclase and protein kinase A inhibitors blocked CRH-induced increased E(2) production but not decreased P(4) production. PLC inhibitor U73122 and protein kinase C inhibitor chelerythrine blocked the effects of CRH on E(2) and P(4) production in CRH-R2 knockdown cells. UCNIII, the specific CRH-R2 agonist, stimulated GTP-bound Gαi protein and phosphorylated phospholipase C-β3 expression. Both U73122 and chelerythrine blocked UCNIII-induced increased E(2) production and decreased P(4) production. We suggest that CRH and its related peptides might be involved in changes in the progesterone to estrogen ratio during human pregnancy.

Diagnostic accuracy and comparison of BIPSS in response to lysine vasopressin and hCRH

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Kush Dev Singh Jarial

2018-03-01

Full Text Available Context: Bilateral inferior petrosal sinus sampling (BIPSS using hCRH is currently considered the ‘gold standard’ test for the differential diagnosis of ACTH-dependent Cushing’s syndrome (CS. Vasopressin is more potent than CRH to stimulate ACTH secretion as shown in animal studies; however, no comparative data of its use are available during BIPSS. Objective: To study the diagnostic accuracy and comparison of hCRH and lysine vasopressin (LVP stimulation during BIPSS. Patients and methods: 29 patients (27-Cushing’s disease, 2-ectopic CS; confirmed on histopathology underwent BIPSS and were included for the study. Patients were randomized to receive hCRH, 5 U LVP or 10 U LVP during BIPSS for ACTH stimulation. BIPSS and contrast-enhanced magnetic resonance imaging (CEMRI were compared with intra-operative findings of trans-sphenoidal surgery (TSS for localization and lateralization of the ACTH source. Results: BIPSS correctly localized the source of ACTH excess in 29/29 of the patients with accuracy of 26/26 patients, using any of the agent, whereas sensitivity and PPV for lateralization with hCRH, 5 U LVP and 10 U LVP was seen in 10/10, 6/10; 10/10,8/10 and 7/7,6/7 patients respectively. Concordance of BIPSS with TSS was seen in 20/27, CEMRI with BIPSS in 16/24 and CEMRI with TSS in 18/24 of patients for lateralizing the adenoma. Most of the side effects were transient and were comparable in all the three groups. Conclusion: BIPSS using either hCRH or LVP (5 U or 10 U confirmed the source of ACTH excess in all the patients, while 10 U LVP correctly lateralized the pituitary adenoma in three fourth of the patients.

CRH-stimulated cortisol release and food intake in healthy, non-obese adults.

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George, Sophie A; Khan, Samir; Briggs, Hedieh; Abelson, James L

2010-05-01

There is considerable anecdotal and some scientific evidence that stress triggers eating behavior, but underlying physiological mechanisms remain uncertain. The hypothalamic-pituitary-adrenal (HPA) axis is a key mediator of physiological stress responses and may play a role in the link between stress and food intake. Cortisol responses to laboratory stressors predict consumption but it is unclear whether such responses mark a vulnerability to stress-related eating or whether cortisol directly stimulates eating in humans. We infused healthy adults with corticotropin-releasing hormone (CRH) at a dose that is subjectively undetectable but elicits a robust endogenous cortisol response, and measured subsequent intake of snack foods, allowing analysis of HPA reactivity effects on food intake without the complex psychological effects of a stress paradigm. CRH elevated cortisol levels relative to placebo but did not impact subjective anxious distress. Subjects ate more following CRH than following placebo and peak cortisol response to CRH was strongly related to both caloric intake and total consumption. These data show that HPA axis reactivity to pharmacological stimulation predicts subsequent food intake and suggest that cortisol itself may directly stimulate food consumption in humans. Understanding the physiological mechanisms that underlie stress-related eating may prove useful in efforts to attack the public health crises created by obesity. Copyright 2009 Elsevier Ltd. All rights reserved.

CRH promotes human colon cancer cell proliferation via IL-6/JAK2/STAT3 signaling pathway and VEGF-induced tumor angiogenesis.

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Fang, Xianjun; Hong, Yali; Dai, Li; Qian, Yuanyuan; Zhu, Chao; Wu, Biao; Li, Shengnan

2017-11-01

Corticotrophin-releasing hormone (CRH) has been demonstrated to participate in various diseases. Our previous study showed that its receptor CRHR1 mediated the development of colitis-associated cancer in mouse model. However, the detailed mechanisms remain unclear. In this study, we explored the oncogenetic role of CRH/CRHR1 signaling in colon cancer cells. Cell proliferation and colony formation assays revealed that CRH contributed to cell proliferation. Moreover, tube formation assay showed that CRH-treated colon cancer cell supernatant significantly promoted tube formation of human umbilical vein endothelial cells (HUVECs). And these effects could be reversed by the CRHR1 specific antagonist Antalarmin. Further investigation showed that CRH significantly upregulated the expressions of interlukin-6 (IL-6) and vascular endothelial growth factor (VEGF) through activating nuclear factor-kappa B (NF-κB). The CRH-induced IL-6 promoted phosphorylation of janus kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3). STAT3 inhibition by Stattic significantly inhibited the CRH-induced cell proliferation. In addition, silence of VEGF resulted in declined tube formation induced by CRH. Taken together, CRH/CRHR1 signaling promoted human colon cancer cell proliferation via NF-κB/IL-6/JAK2/STAT3 signaling pathway and tumor angiogenesis via NF-κB/VEGF signaling pathway. Our results provide evidence to support a critical role for the CRH/CRHR1 signaling in colon cancer progression and suggest its potential utility as a new therapeutic target for colon cancer. © 2017 Wiley Periodicals, Inc.

Addison's disease concomitant with corticotropin deficiency and pituitary CRH resistance - a case report.

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Lewandowski, Krzysztof C; Malicka, Katarzyna; Dąbrowska, Katarzyna; Lewiński, Andrzej

2017-01-01

A 36-year-old woman was found to have a low morning ACTH concentration despite a history of Addison's disease. Past medical history: At the age of 23 years the subject developed Graves's disease, which was treated with radioiodine. At about the same time, she claimed to have two episodes of pancreatitis treated with cholecystectomy. About seven months later she was euthyroid on L-thyroxine (TSH 1.51 mIU/mL) but was admitted with hypotension, hyponatraemia (sodium 109 mmol/L), and low morning cortisol (119 nmol/L). Further investigations confirmed primary adrenal failure with ACTH concentration of 779 pg/mL (ref. range 0-60) prior to the dose of hydrocortisone. About nine years later she complained about tiredness. Clinically she was normotensive and not pigmented. BMI 22.3 kg/m². Periods were regular. ACTH concentration was surprisingly low (ACTH 8.53 pg/mL, ref. range 0-46), despite very low cortisol (3.37 nmol/L). She was admitted for further assessment. Pituitary MRI scan was unremarkable. An insulin tolerance test was performed and showed a clear increase of ACTH (from 15.2 to 165 pg/mL). There was, however, hardly any increase of ACTH after CRH stimulation (from 6.05 pg/mL to 10.2 pg/mL), thus demonstrating central CRH resistance. In summary, this patient developed secondary adrenal failure in the setting of previous Addison's disease. Interestingly, hypoglycaemia (but not CRH) provided a stimulus for ACTH release, thus demonstrating CRH resistance. The case confirms that besides CRH, other factors are responsible for stimulation of the ACTH-cortisol axis during insulin tolerance test.

Effect of childhood trauma on adult depression and neuroendocrine function: sex-specific moderation by CRH receptor 1 gene

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Christine Heim

2009-11-01

Full Text Available Variations of the corticotropin-releasing hormone receptor 1 (CRHR1 gene appear to moderate the development of depression after childhood trauma. Depression more frequently affects women than men. We examined sex differences in the effects of the CRHR1 gene on the relationship between childhood trauma and adult depression. Methods: We recruited 1,063 subjects from the waiting rooms of a public urban hospital. Childhood trauma exposure and symptoms of depression were assessed using dimensional rating scales. Subjects were genotyped for rs110402 within the CRHR1 gene. An independent sample of 78 subjects underwent clinical assessment, genotyping, and a dexamethasone/CRH test. The age range at recruitment was 18-77 years and 18-45, for the two studies respectively. Results: In the hospital sample, the protective effect of the rs110402 A-allele against developing depression after childhood trauma was observed in men (N=424, but not in women (N=635. In the second sample, the rs110402 A-allele was associated with decreased cortisol response in the dexamethasone/CRH test only in men. In A-allele carriers with childhood trauma exposure women exhibited increased cortisol response compared men; there were no sex differences in A-allele carriers without trauma exposure. This effect may, however, not be related to gender-differences per se, but to differences in the type of experienced abuse between men and women. CRHR x environment interactions in the hospital sample were observed with exposure to physical, but not sexual or emotional abuse. Physical abuse was the most common type of abuse in men in this cohort, while sexual abuse was most commonly suffered by women. Conclusion: Our results suggest that the CRHR1 gene may only moderate the effects of specific types of childhood trauma on depression. Gender differences in environmental exposures could thus be reflected in sex-specific CRHR1 x child abuse interactions.

Ectopic ACTH and CRH co-secreting tumor localized by 68Ga-DOTA-TATE PET/CT

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Papadakis, Georgios Z.; Bagci, Ulas; Sadowski, Samira M.; Patronas, Nicholas J.; Stratakis, Constantine A.

2015-01-01

Diagnosis of ectopic adrenocorticotropic hormone (ACTH) and corticotropin releasing hormone (CRH) co-secreting tumors causing Cushing syndrome (CS) is challenging, since these tumors are rare and their diagnosis is frequently confused with Cushing disease (CD), due to the effect of CRH on the pituitary. We report a case of a 21-year-old male who was referred to our institution with persistent hypercortisolemia and CS after undergoing unnecessary transsphenoidal surgery (TSS). 68Ga-DOTA-TATE PET/CT revealed increased tracer uptake in the thymus which was histologically proved to be neuroendocrine tumor (NET) staining positive for ACTH and CRH. Imaging with 18F-FDG PET/CT was not diagnostic. PMID:26018709

Timing is critical for effective glucocorticoid receptor mediated repression of the cAMP-induced CRH gene.

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Siem van der Laan

Full Text Available Glucocorticoid negative feedback of the hypothalamus-pituitary-adrenal axis is mediated in part by direct repression of gene transcription in glucocorticoid receptor (GR expressing cells. We have investigated the cross talk between the two main signaling pathways involved in activation and repression of corticotrophin releasing hormone (CRH mRNA expression: cyclic AMP (cAMP and GR. We report that in the At-T20 cell-line the glucocorticoid-mediated repression of the cAMP-induced human CRH proximal promoter activity depends on the relative timing of activation of both signaling pathways. Activation of the GR prior to or in conjunction with cAMP signaling results in an effective repression of the cAMP-induced transcription of the CRH gene. In contrast, activation of the GR 10 minutes after onset of cAMP treatment, results in a significant loss of GR-mediated repression. In addition, translocation of ligand-activated GR to the nucleus was found as early as 10 minutes after glucocorticoid treatment. Interestingly, while both signaling cascades counteract each other on the CRH proximal promoter, they synergize on a synthetic promoter containing 'positive' response elements. Since the order of activation of both signaling pathways may vary considerably in vivo, we conclude that a critical time-window exists for effective repression of the CRH gene by glucocorticoids.

Treatment with CRH-1 antagonist antalarmin reduces behavioral and endocrine responses to social stressors in marmosets (Callithrix kuhlii).

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French, Jeffrey A; Fite, Jeffrey E; Jensen, Heather; Oparowski, Katie; Rukstalis, Michael R; Fix, Holly; Jones, Brenda; Maxwell, Heather; Pacer, Molly; Power, Michael L; Schulkin, Jay

2007-08-01

Corticotropin-releasing hormone (CRH) has multiple roles in coordinating the behavioral and endocrine responses to a host of environmental challenges, including social stressors. In the present study we evaluated the role of CRH in mediating responses to a moderate social stressor in Wied's black tufted-eared marmosets (Callithrix kuhlii). Male and female marmosets (n=14) were administered antalarmin (a selective CRH-1 receptor antagonist; 50 microg/kg, p.o.) or vehicle in a blind, counterbalanced, crossover design. One hr after treatment, marmosets were separated from long-term pairmates and then housed alone in a novel enclosure for 7 hr. Behavior was recorded during separation and upon reunion with the partner, and urine samples for cortisol assay collected before, during, and after the intervention. Separation from partners elevated urinary cortisol concentrations over baseline for both conditions, but antalarmin treatment reduced the magnitude of the elevation. Antalarmin also lowered rates of behavioral patterns associated with arousal (alarm and "e-e" vocalizations, object manipulate/chew), but had no effect on contact calls, locomotory activity or alertness. Although most patterns of social behavior upon reunion with the partner were not affected by antalarmin, antalarmin-treated marmosets displayed more sexual behavior (mounts and copulations) upon reunion. These data indicate that antagonism of the CRH-1 receptor acts to reduce the magnitude of both endocrine and behavioral responses to a moderate social stressor without causing any overall reduction in alertness or general activity. This supports the hypothesis that CRH, acting through its type 1 receptor, is involved in coordinating the responses to anxiety-producing events. These results further suggest that the marmoset is a useful model for exploration of the role of CRH in mediating the behavioral and neuroendocrine responses to psychosocial stressors, particularly in the context of heterosexual

Cryogenic buffer-gas loading and magnetic trapping of CrH and MnH molecules

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Stoll, M.; Bakker, J.; Steimle, T.; Meijer, G.; Peters, A.

2008-01-01

We report on the buffer-gas cooling and trapping of CrH and MnH molecules in a magnetic quadrupole trap with densities on the order of 106 cm−3 at a temperature of 650 mK. Storage times of up to 180 ms have been observed, corresponding to a 20-fold lifetime enhancement with respect to the field-free diffusion through the 3He buffer-gas. Using Monte Carlo trajectory simulations, inelastic molecule-3He collision cross sections of 1.6×10−18 and 3.1×10−17 cm2 are extracted for CrH and MnH, respec...

Brain-derived neurotrophic factor Val66Met polymorphism and dexamethasone/CRH test results in depressed patients.

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Schüle, Cornelius; Zill, Peter; Baghai, Thomas C; Eser, Daniela; Zwanzger, Peter; Wenig, Nadine; Rupprecht, Rainer; Bondy, Brigitta

2006-09-01

Data suggest that both neurotrophic and hypothalamic-pituitary-adrenocortical (HPA) systems are involved in the pathophysiology of depression. The aim of the present study was to investigate whether the non-conservative brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has an impact on HPA axis activity in depressed patients. At admission, the dexamethasone/CRH (DEX/CRH) test was performed in 187 drug-free in-patients suffering from major depression or depressed state of bipolar disorder (DSM-IV criteria). Moreover, genotyping of BDNF Val66Met polymorphism was carried out using the fluorescence resonance energy transfer method (FRET). Homozygous carriers of the Met/Met genotype showed a significantly higher HPA axis activity during the DEX/CRH test than patients carrying the Val/Val or Val/Met genotype (ACTH, cortisol). Our results further contribute to the hypothesized association between HPA axis dysregulation and reduced neuroplasticity in depression and are consistent with the assumption that BDNF is a stress-responsive intercellular messenger modifying HPA axis activity.

Activation of CRH receptor type 1 expressed on glutamatergic neurons increases excitability of CA1 pyramidal neurons by the modulation of voltage-gated ion channels

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Stephan eKratzer

2013-07-01

Full Text Available Corticotropin-releasing hormone (CRH plays an important role in a substantial number of patients with stress-related mental disorders, such as anxiety disorders and depression. CRH has been shown to increase neuronal excitability in the hippocampus, but the underlying mechanisms are poorly understood. The effects of CRH on neuronal excitability were investigated in acute hippocampal brain slices. Population spikes (PS and field excitatory postsynaptic potentials (fEPSP were evoked by stimulating Schaffer-collaterals and recorded simultaneously from the somatic and dendritic region of CA1 pyramidal neurons. CRH was found to increase PS amplitudes (mean  Standard error of the mean; 231.8  31.2% of control; n=10 while neither affecting fEPSPs (104.3 ± 4.2%; n=10 nor long-term potentiation (LTP. However, when Schaffer-collaterals were excited via action potentials (APs generated by stimulation of CA3 pyramidal neurons, CRH increased fEPSP amplitudes (119.8 ± 3.6%; n=8 and the magnitude of LTP in the CA1 region. Experiments in slices from transgenic mice revealed that the effect on PS amplitude is mediated exclusively by CRH receptor 1 (CRHR1 expressed on glutamatergic neurons. The effects of CRH on PS were dependent on phosphatase-2B, L- and T-type calcium channels and voltage-gated potassium channels but independent on intracellular Ca2+-elevation. In patch-clamp experiments, CRH increased the frequency and decay times of APs and decreased currents through A-type and delayed-rectifier potassium channels. These results suggest that CRH does not affect synaptic transmission per se, but modulates voltage-gated ion currents important for the generation of APs and hence elevates by this route overall neuronal activity.

Expression of stress hormones AVP and CRH in the hypothalamus of Mus musculus following water and food deprivation.

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Yadawa, Arun Kumar; Chaturvedi, Chandra Mohini

2016-12-01

Neurohypophyseal hormone, arginine vasopressin (AVP), in addition to acting as antidiuretic hormone is also considered to be stress hormone like hypothalamic corticotropin-releasing hormone (CRH). Present study was designed to investigate the relative response of these stress hormones during water and food deprivation. In this study, male laboratory mice of Swiss strain were divided in 5 groups, control - provided water and food ad libitum, two experimental groups water deprived for 2 and 4days respectively (WD2 and WD4) and another two groups food deprived for 2 and 4days respectively (FD2 and FD4). Results indicate an increased expression of AVP mRNA as well as peptide in the hypothalamus of WD2 mice and the expression was further upregulated after 4days of water deprivation but the expression of CRH remained unchanged compare to their respective controls. On the other hand no change was observed in the expression of hypothalamic AVP mRNA while AVP peptide increased significantly in FD2 and FD4 mice compare to control. Further, the expression of CRH mRNA although increased in hypothalamus of both FD2 and FD4 mice, the immunofluorescent staining shows decreased expression of CRH in PVN of food deprived mice. Based on these findings it is concluded that since during osmotic stress only AVP expression is upregulated but during metabolic stress i.e. food deprivation transcription and translation of both the stress hormones are differentially regulated. Further, it is suggested that role of AVP and CRH may be stress specific. Copyright © 2016 Elsevier Inc. All rights reserved.

Ectopic corticotropin-releasing hormone (CRH syndrome from metastatic small cell carcinoma: a case report and review of the literature

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Shahani Sadeka

2010-08-01

Full Text Available Abstract Background Cushing's Syndrome (CS which is caused by isolated Corticotropin-releasing hormone (CRH production, rather than adrenocorticotropin (ACTH production, is extremely rare. Methods We describe the clinical presentation, course, laboratory values and pathologic findings of a patient with isolated ectopic CRH causing CS. We review the literature of the types of tumors associated with this unusual syndrome and the behavior of these tumors by endocrine testing. Results A 56 year old woman presented with clinical and laboratory features consistent with ACTH-dependent CS. Pituitary imaging was normal and cortisol did not suppress with a high dose dexamethasone test, consistent with a diagnosis of ectopic ACTH. CT imaging did not reveal any discrete lung lesions but there were mediastinal and abdominal lymphadenopathy and multiple liver lesions suspicious for metastatic disease. Laboratory testing was positive for elevated serum carcinoembryonic antigen and the neuroendocrine marker chromogranin A. Serum markers of carcinoid, medullary thyroid carcinoma, and pheochromocytoma were in the normal range. Because the primary tumor could not be identified by imaging, biopsy of the presumed metastatic liver lesions was performed. Immunohistochemistry was consistent with a neuroendocrine tumor, specifically small cell carcinoma. Immunostaining for ACTH was negative but was strongly positive for CRH and laboratory testing revealed a plasma CRH of 10 pg/ml (normal 0 to 10 pg/ml which should have been suppressed in the presence of high cortisol. Conclusions This case illustrates the importance of considering the ectopic production of CRH in the differential diagnosis for presentations of ACTH-dependent Cushing's Syndrome.

Effects of Qiangji Jianli Yin on the hypothalamus CRH contents and plasma ACTH, cortisol levels in rat models of kidney-yang deficiency syndrome

International Nuclear Information System (INIS)

Zhao Hui; Chen Zhixi; Chen Jinyan; Li Zhiqiang; He Zanhou

2007-01-01

Objective: To investigate the effects of qiangji jianli yin on hypothalamus CRH contents and plasma ACTH, Cortisol levels in rat models with kidney-yang deficiency syndrome. Methods: Rat models of kidney-yang deficiency syndrome were prepared with intramuscular injuection of hydroeortisone and divided into 5 groups: (1) no further treatment, n=13 (2) treated with high dosage d qiangji jiandi yin, n=12 (3) treated with medium dosage of qiangji jianli yin, n=12 (4) treated with low dosage of qiangji jianli yin n=12, (5) treated with yougui wan, n=12. Ten rats injuected with intramuscular distilled water only served as controls. The animals were sacrificied 14 days later and the hypothalamus CRH contents as well as plasma AOM and cortisol levels were measured with RIA. The thymus gland weight index and the adrenal gland index were calculated. Results: (1) The hypothalamus CRH contents and plasma ACTH, cortisol levels were significantly lower (P<0.01) in the rat models of kidney-yang deficiency syndrome without any treatment thas those in controls rats; the thymus and adrenal gland weight index were significantly decreased too (P <0.01). The CRH conteats and ACTH, cortisol levels in all the three group of rat model treated with different dosage of qiangji jianli yin were significantly higher than those in the models without any treatment (P<0.05-0.01). Conclusion: In rat models of kidney-yang deficiency syndrome, dysfunction of the hypothalamus-pituitary-adrenal axis (HPAA) led to decreased secretion of related hormones. The HPAA function might be partially restored with administation of qiangji jianli yin. (authors)

Acute stress-induced sensitization of the pituitary-adrenal response to heterotypic stressors: independence of glucocorticoid release and activation of CRH1 receptors.

Science.gov (United States)

Belda, Xavier; Daviu, Núria; Nadal, Roser; Armario, Antonio

2012-09-01

A single exposure to some severe stressors causes sensitization of the hypothalamic-pituitary-adrenal (HPA) response to novel stressors. However, the putative factors involved in stress-induced sensitization are not known. In the present work we studied in adult male rats the possible role of glucocorticoids and CRH type 1 receptor (CRH-R1), using an inhibitor of glucocorticoid synthesis (metyrapone, MET), the glucocorticoid receptor (GR) antagonist RU38486 (mifepristone) and the non-peptide CRH-R1 antagonist R121919. In a first experiment we demonstrated with different doses of MET (40-150 mg/kg) that the highest dose acted as a pharmacological stressor greatly increasing ACTH release and altering the normal circadian pattern of HPA hormones, but no dose affected ACTH responsiveness to a novel environment as assessed 3 days after drug administration. In a second experiment, we found that MET, at a dose (75 mg/kg) that blocked the corticosterone response to immobilization (IMO), did not alter IMO-induced ACTH sensitization. Finally, neither the GR nor the CRH-R1 antagonists blocked IMO-induced ACTH sensitization on the day after IMO. Thus, a high dose of MET, in contrast to IMO, was unable to sensitize the HPA response to a novel environment despite the huge activation of the HPA axis caused by the drug. Neither a moderate dose of MET that markedly reduced corticosterone response to IMO, nor the blockade of GR or CRH-R1 receptors was able to alter stress-induced HPA sensitization. Therefore, stress-induced sensitization is not the mere consequence of a marked HPA activation and does not involve activation of glucocorticoid or CRH-R1 receptors. Copyright © 2012 Elsevier Inc. All rights reserved.

Epigenetic variation during the adult lifespan

DEFF Research Database (Denmark)

Talens, Rudolf P; Christensen, Kaare; Putter, Hein

2012-01-01

The accumulation of epigenetic changes was proposed to contribute to the age-related increase in the risk of most common diseases. In this study on 230 monozygotic twin pairs (MZ pairs), aged 18-89 years, we investigated the occurrence of epigenetic changes over the adult lifespan. Using mass...... individuals, ranging from 1.2-fold larger at ABCA1 (P = 0.010) to 1.6-fold larger at INS (P = 3.7 × 10(-07) ). Similarly, there was more within-MZ-pair discordance in old as compared with young MZ pairs, except for GNASAS, ranging from an 8% increase in discordance each decade at CRH (P = 8.9 × 10...... spectrometry, we investigated variation in global (LINE1) DNA methylation and in DNA methylation at INS, KCNQ1OT1, IGF2, GNASAS, ABCA1, LEP, and CRH, candidate loci for common diseases. Except for KCNQ1OT1, interindividual variation in locus-specific DNA methylation was larger in old individuals than in young...

Water-Protein Hydrogen Exchange in the Micro-Crystalline Protein Crh as Observed by Solid State NMR Spectroscopy

International Nuclear Information System (INIS)

Boeckmann, Anja; Juy, Michel; Bettler, Emmanuel; Emsley, Lyndon; Galinier, Anne; Penin, Francois; Lesage, Anne

2005-01-01

We report site-resolved observation of hydrogen exchange in the micro-crystalline protein Crh. Our approach is based on the use of proton T 2 ' -selective 1 H- 13 C- 13 C correlation spectra for site-specific assignments of carbons nearby labile protein protons. We compare the proton T 2 ' selective scheme to frequency selective water observation in deuterated proteins, and discuss the impacts of deuteration on 13 C linewidths in Crh. We observe that in micro-crystalline proteins, solvent accessible hydroxyl and amino protons show comparable exchange rates with water protons as for proteins in solution, and that structural constraints, such as hydrogen bonding or solvent accessibility, more significantly reduce exchange rates

Note introductive : les anciennes enquêtes du CRH

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2011-03-01

Full Text Available ParticipantsBéatrice Marin, co-responsableMathieu Marraud, co-responsableMichel DemonetLes données rendues disponibles ici en ligne proviennent des enquêtes anciennes menées au sein du Centre de Recherches Historiques, lesquelles ont déjà fait l'objet de publications et sont désormais librement offertes à la communauté scientifique comme aux particuliers. Converties au format Excel, elles sont la trace du rôle initial joué par le CRH dans la confection des premières bases de données sérielles...

Cryogenic buffer-gas loading and magnetic trapping of CrH and MnH molecules

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Stoll, Michael; Bakker, Joost M.; Steimle, Timothy C.; Meijer, Gerard; Peters, Achim

2008-09-01

We report on the buffer-gas cooling and trapping of CrH and MnH molecules in a magnetic quadrupole trap with densities on the order of 106cm-3 at a temperature of 650mK . Storage times of up to 180ms have been observed, corresponding to a 20-fold lifetime enhancement with respect to the field-free diffusion through the He3 buffer-gas. Using Monte Carlo trajectory simulations, inelastic molecule- He3 collision cross sections of 1.6×10-18 and 3.1×10-17cm2 are extracted for CrH and MnH, respectively. Furthermore, elastic molecule- He3 collision cross sections of 1.4(±0.5)×10-14cm2 are determined for both species. We conclude that the confinement time of these molecules in a magnetic trapping field is limited by inelastic collisions with the helium atoms leading to Zeeman relaxation.

Crh and Oprm1 mediate anxiety-related behavior and social approach in a mouse model of MECP2 duplication syndrome.

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Samaco, Rodney C; Mandel-Brehm, Caleigh; McGraw, Christopher M; Shaw, Chad A; McGill, Bryan E; Zoghbi, Huda Y

2012-01-08

Genomic duplications spanning Xq28 are associated with a spectrum of phenotypes, including anxiety and autism. The minimal region shared among affected individuals includes MECP2 and IRAK1, although it is unclear which gene when overexpressed causes anxiety and social behavior deficits. We report that doubling MECP2 levels causes heightened anxiety and autism-like features in mice and alters the expression of genes that influence anxiety and social behavior, such as Crh and Oprm1. To test the hypothesis that alterations in these two genes contribute to heightened anxiety and social behavior deficits, we analyzed MECP2 duplication mice (MECP2-TG1) that have reduced Crh and Oprm1 expression. In MECP2-TG1 animals, reducing the levels of Crh or its receptor, Crhr1, suppressed anxiety-like behavior; in contrast, reducing Oprm1 expression improved abnormal social behavior. These data indicate that increased MeCP2 levels affect molecular pathways underlying anxiety and social behavior and provide new insight into potential therapies for MECP2-related disorders.

No association of CRH1 receptor polymorphism haplotypes, harm avoidance and other personality dimensions in alcohol dependence: results from the Munich gene bank project for alcoholism.

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Soyka, M; Preuss, U W; Koller, G; Zill, P; Hesselbrock, V; Bondy, B

2004-03-01

Because corticotrophin-releasing hormone (CRH) plays a central role in stress regulation, the possible role of CRH1 polymorphism for anxiety-related personality variables such as harm avoidance possibly associated with alcoholism was studied. The research instruments used to phenotype patients were adopted partly from the US collaborative study of the genetics of alcoholism and include a number of personality inventories such as the temperament and character inventory (TCI). Based on the examination of 170 alcoholic subjects no association was found between CRH1 receptor haplotypes of four single nuclotid polymorphisms (SNPs) and low and high temperament traits of harm avoidance, novelty seeking and reward dependence. The possible implications of these findings are discussed.

Cryogenic buffer-gas loading and magnetic trapping of CrH and MnH molecules

NARCIS (Netherlands)

Stoll, M.; Bakker, J. M.; Steimle, T. C.; Meijer, G.; Peters, A.

2008-01-01

We report on the buffer- gas cooling and trapping of CrH and MnH molecules in a magnetic quadrupole trap with densities on the order of 10(6) cm(-3) at a temperature of 650 mK. Storage times of up to 180 ms have been observed, corresponding to a 20- fold lifetime enhancement with respect to the

Enhanced upregulation of CRH mRNA expression in the nucleus accumbens of male rats after a second injection of methamphetamine given thirty days later.

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Jean Lud Cadet

Full Text Available Methamphetamine (METH is a widely abused amphetamine analog. Few studies have investigated the molecular effects of METH exposure in adult animals. Herein, we determined the consequences of an injection of METH (10 mg/kg on transcriptional effects of a second METH (2.5 mg/kg injection given one month later. We thus measured gene expression by microarray analyses in the nucleus accumbens (NAc of 4 groups of rats euthanized 2 hours after the second injection: saline-pretreated followed by saline-challenged (SS or METH-challenged (SM; and METH-pretreated followed by saline-challenged (MS or METH-challenged (MM. Microarray analyses revealed that METH (2.5 mg/kg produced acute changes (1.8-fold; P<0.01 in the expression of 412 (352 upregulated, 60 down-regulated transcripts including cocaine and amphetamine regulated transcript, corticotropin-releasing hormone (Crh, oxytocin (Oxt, and vasopressin (Avp that were upregulated. Injection of METH (10 mg/kg altered the expression of 503 (338 upregulated, 165 down-regulated transcripts measured one month later (MS group. These genes also included Cart and Crh. The MM group showed altered expression of 766 (565 upregulated, 201 down-regulated transcripts including Avp, Cart, and Crh. The METH-induced increased Crh expression was enhanced in the MM group in comparison to SM and MS groups. Quantitative PCR confirmed the METH-induced changes in mRNA levels. Therefore, a single injection of METH produced long-lasting changes in gene expression in the rodent NAc. The long-term increases in Crh, Cart, and Avp mRNA expression suggest that METH exposure produced prolonged activation of the endogenous stress system. The METH-induced changes in oxytocin expression also suggest the possibility that this neuropeptide might play a significant role in the neuroplastic and affiliative effects of this drug.

The non-peptide CRH1-antagonist CP-154,526 elicits a paradoxical route-dependent activation of the HPA axis.

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Zaretsky, Dmitry V; Zaretskaia, Maria V; Sarkar, Sumit; Rusyniak, Daniel E; DiMicco, Joseph A

2017-07-13

The corticotropin-releasing hormone (CRH) plays an important role in mediating physiological response to stress and is thought to be involved in the development of various psychiatric disorders. In this paper, we compare the differences between the effect of intraperitoneal (i.p.) and intraarterial (i.a.) administration of the non-peptide CRH 1 antagonist CP-154,526 (CP) (10 and 20mg/kg) on plasma adrenocorticotropic hormone levels (ACTH), heart rate, MAP, and c-Fos expression in the paraventricular nucleus of the hypothalamus. Intraperitoneal, but not i.a., injection of CP resulted in an increase in plasma ACTH (from 105±13 to 278±51pg/ml after 20mg/kg). This effect was accompanied by a dramatic increase in c-Fos expression in cells immunoreactive for CRH in the paraventricular nucleus of the hypothalamus. When the drug was administered i.p., CP-induced activation of the HPA appears to mask the inhibitory effect of CP on stress-induced ACTH secretion, an effect which was readily apparent when the drug was given i.a. Intraperitoneal administration of CP also increased the baseline MAP which may account for previous reports that treatment with this drug attenuated the increases associated with stress. CP given by either route had no effect on baseline heart rate or stress-induced tachycardia. Thus, in all studies in which CP 154,526 is given, the route of delivery must be given careful consideration. Copyright © 2017 Elsevier B.V. All rights reserved.

Variational functionals which admit discontinuous trial functions

International Nuclear Information System (INIS)

Nelson, P. Jr.

1975-01-01

It is argued that variational synthesis with discontinuous trial functions requires variational principles applicable to equations involving operators acting between distinct Hilbert spaces. A description is given of a Roussopoulos-type variational principle generalized to cover this situation. This principle is suggested as the basis for a unified approach to the derivation of variational functionals. In addition to esthetics, this approach has the advantage that the mathematical details increase the understanding of the derived functional, particularly the sense in which a synthesized solution should be regarded as an approximation to the true solution. By way of illustration, the generalized Roussopoulos principle is applied to derive a class of first-order diffusion functionals which admit trial functions containing approximations at an interface. These ''asymptotic'' interface quantities are independent of the limiting approximations from either side and permit use of different trial spectra at and on either side of an interface. The class of functionals derived contains as special cases both the Lagrange multiplier method of Buslik and two functionals of Lambropoulos and Luco. Some numerical results for a simple two-group model confirm that the ''multipliers'' can closely approximate the appropriate quantity in the region near an interface. (U.S.)

Solid state NMR sequential resonance assignments and conformational analysis of the 2x10.4 kDa dimeric form of the Bacillus subtilis protein Crh

Energy Technology Data Exchange (ETDEWEB)

Boeckmann, Anja [Institut de Biologie et Chimie des Proteines, C.N.R.S UMR 5086 (France)], E-mail: a.bockmann@ibcp.fr; Lange, Adam [Max-Planck-Institute for Biophysical Chemistry, Solid-state NMR (Germany); Galinier, Anne [Institut de Biologie Structurale et Microbiologie, C.N.R.S UPR 9043 (France); Luca, Sorin [Max-Planck-Institute for Biophysical Chemistry, Solid-state NMR (Germany); Giraud, Nicolas; Juy, Michel [Institut de Biologie et Chimie des Proteines, C.N.R.S UMR 5086 (France); Heise, Henrike [Max-Planck-Institute for Biophysical Chemistry, Solid-state NMR (Germany); Montserret, Roland; Penin, Francois [Institut de Biologie et Chimie des Proteines, C.N.R.S UMR 5086 (France); Baldus, Marc [Max-Planck-Institute for Biophysical Chemistry, Solid-state NMR (Germany)], E-mail: maba@mpibpc.mpg.de

2003-12-15

Solid state NMR sample preparation and resonance assignments of the U-[{sup 13}C,{sup 15}N] 2x10.4 kDa dimeric form of the regulatory protein Crh in microcrystalline, PEG precipitated form are presented. Intra- and interresidue correlations using dipolar polarization transfer methods led to nearly complete sequential assignments of the protein, and to 88% of all {sup 15}N, {sup 13}C chemical shifts. For several residues, the resonance assignments differ significantly from those reported for the monomeric form analyzed by solution state NMR. Dihedral angles obtained from a TALOS-based statistical analysis suggest that the microcrystalline arrangement of Crh must be similar to the domain-swapped dimeric structure of a single crystal form recently solved using X-ray crystallography. For a limited number of protein residues, a remarkable doubling of the observed NMR resonances is observed indicative of local static or dynamic conformational disorder. Our study reports resonance assignments for the largest protein investigated by solid state NMR so far and describes the conformational dimeric variant of Crh with previously unknown chemical shifts.

On Gap Functions for Quasi-Variational Inequalities

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Kouichi Taji

2008-01-01

Full Text Available For variational inequalities, various merit functions, such as the gap function, the regularized gap function, the D-gap function and so on, have been proposed. These functions lead to equivalent optimization formulations and are used to optimization-based methods for solving variational inequalities. In this paper, we extend the regularized gap function and the D-gap functions for a quasi-variational inequality, which is a generalization of the variational inequality and is used to formulate generalized equilibrium problems. These extensions are shown to formulate equivalent optimization problems for quasi-variational inequalities and are shown to be continuous and directionally differentiable.

Research and Application of FTA and Petri Nets in Fault Diagnosis in the Pantograph-Type Current Collector on CRH EMU Trains

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Long-long Song

2015-01-01

Full Text Available A fault tree is established based on structural analysis, working principle analysis, and failure mode and effects analysis (FMEA of the pantograph-type current collector on the Chinese Rail High-Speed Electric Multiple Unit (CRH EMU train. To avoid the deficiencies of fault tree analysis (FTA, Petri nets modelling is used to address the problem of data explosion and carry out dynamic diagnosis. Relational matrix analysis is used to solve the minimal cut set equation of the fault tree. Based on the established state equation of the Petri nets, initial tokens and enable-transfer algorithms are used to express the fault transfer process mathematically and improve the efficiency of fault diagnosis inferences. Finally, using a practical fault diagnosis example for the pantographs on CRH EMU trains, the proposed method is proved to be reasonable and effective.

CRH Affects the Phenotypic Expression of Sepsis-Associated Virulence Factors by Streptococcus pneumoniae Serotype 1 In vitro

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Colette G. Ngo Ndjom

2017-06-01

Full Text Available Sepsis is a life-threatening health condition caused by infectious pathogens of the respiratory tract, and accounts for 28–50% of annual deaths in the US alone. Current treatment regimen advocates the use of corticosteroids as adjunct treatment with antibiotics, for their broad inhibitory effect on the activity and production of pro-inflammatory mediators. However, despite their use, corticosteroids have not proven to be able to reverse the death incidence among septic patients. We have previously demonstrated the potential for neuroendocrine factors to directly influence Streptococcus pneumoniae virulence, which may in turn mediate disease outcome leading to sepsis and septic shock. The current study investigated the role of Corticotropin-releasing hormone (CRH in mediating key markers of pneumococcal virulence as important phenotypic determinants of sepsis and septic shock risks. In vitro cultures of serotype 1 pneumococcal strain with CRH promoted growth rate, increased capsule thickness and penicillin resistance, as well as induced pneumolysin gene expression. These results thus provide significant insights of CRH–pathogen interactions useful in understanding the underlying mechanisms of neuroendocrine factor's role in the onset of community acquired pneumonias (CAP, sepsis and septic shock.

Associations between Single-Nucleotide Polymorphisms in Corticotropin-Releasing Hormone-Related Genes and Irritable Bowel Syndrome.

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Ayaka Sasaki

Full Text Available Irritable bowel syndrome (IBS is a common functional disorder with distinct features of stress-related pathophysiology. A key mediator of the stress response is corticotropin-releasing hormone (CRH. Although some candidate genes have been identified in stress-related disorders, few studies have examined CRH-related gene polymorphisms. Therefore, we tested our hypothesis that single-nucleotide polymorphisms (SNPs in CRH-related genes influence the features of IBS.In total, 253 individuals (123 men and 130 women participated in this study. They comprised 111 IBS individuals and 142 healthy controls. The SNP genotypes in CRH (rs28364015 and rs6472258 and CRH-binding protein (CRH-BP (rs10474485 were determined by direct sequencing and real-time polymerase chain reaction. The emotional states of the subjects were evaluated using the State-Trait Anxiety Inventory, Perceived Stress Scale, and the Self-rating Depression Scale.Direct sequencing of the rs28364015 SNP of CRH revealed no genetic variation among the study subjects. There was no difference in the genotype distributions and allele frequencies of rs6472258 and rs10474485 between IBS individuals and controls. However, IBS subjects with diarrhea symptoms without the rs10474485 A allele showed a significantly higher emotional state score than carriers.These results suggest that the CRH and CRH-BP genes have no direct effect on IBS status. However, the CRH-BP SNP rs10474485 has some effect on IBS-related emotional abnormalities and resistance to psychosocial stress.

Stress-induced and cue-induced craving for alcohol in heavy drinkers: Preliminary evidence of genetic moderation by the OPRM1 and CRH-BP genes.

Science.gov (United States)

Ray, Lara A

2011-01-01

Neurobiological theories of addiction have highlighted disruption in stress pathways as a central feature of addictive disorders, and pharmacological treatments targeting stress mechanisms hold great promise. This study examines genetic determinants of stress-induced and cue-induced craving in heavy drinkers by testing single-nucleotide polymorphisms (SNPs) of the corticotrophin-releasing hormone binding protein (CRH-BP) gene and the mu-opioid receptor (OPRM1) gene. This study combines guided imagery stress exposure and in vivo alcohol cue exposure in a sample of 64 (23 women) non-treatment-seeking heavy drinkers. Analyses, uncorrected for multiple comparisons, revealed that a tag SNP of the CRH-BP gene (rs10055255) moderated stress-induced craving in this sample. The same SNP predicted greater affective responses to the stress manipulation, including greater levels of subjective tension and negative mood. The Asp40 allele of the OPRM1 was associated with greater cue-induced alcohol craving following the neutral imagery condition. These initial results extend recent preclinical and clinical findings implicating the CRH-BP in stress-related alcoholism and confirm the role of the Asp40 allele of the OPRM1 gene in reward-driven alcohol phenotypes. Human laboratory models of stress and cue-induced craving may be useful in pharmacotherapy development targeting dysregulation of stress systems. Larger studies are needed to validate these preliminary findings, which should also be extended to clinical samples. Copyright © 2010 by the Research Society on Alcoholism.

In situ health monitoring for bogie systems of CRH380 train on Beijing-Shanghai high-speed railway

Science.gov (United States)

Hong, Ming; Wang, Qiang; Su, Zhongqing; Cheng, Li

2014-04-01

Based on the authors' research efforts over the years, an in situ structural health monitoring (SHM) technique taking advantage of guided elastic waves has been developed and deployed via an online diagnosis system. The technique and the system were recently implemented on China's latest high-speed train (CRH380CL) operated on Beijing-Shanghai High-Speed Railway. The system incorporated modularized components including active sensor network, active wave generation, multi-channel data acquisition, signal processing, data fusion, and results presentation. The sensor network, inspired by a new concept—"decentralized standard sensing", was integrated into the bogie frames during the final assembly of CRH380CL, to generate and acquire bogie-guided ultrasonic waves, from which a wide array of signal features were extracted. Fusion of signal features through a diagnostic imaging algorithm led to a graphic illustration of the overall health state of the bogie in a real-time and intuitive manner. The in situ experimentation covered a variety of high-speed train operation events including startup, acceleration/deceleration, full-speed operation (300 km/h), emergency braking, track change, as well as full stop. Mock-up damage affixed to the bogie was identified quantitatively and visualized in images. This in situ testing has demonstrated the feasibility, effectiveness, sensitivity, and reliability of the developed SHM technique and the system towards real-world applications.

Emotional exhaustion and overcommitment to work are differentially associated with hypothalamus-pituitary-adrenal (HPA) axis responses to a low-dose ACTH1-24 (Synacthen) and dexamethasone-CRH test in healthy school teachers.

Science.gov (United States)

Wolfram, Maren; Bellingrath, Silja; Feuerhahn, Nicolas; Kudielka, Brigitte M

2013-01-01

Evidence for a detrimental impact of chronic work stress on health has accumulated in epidemiological research. Recent studies indicate altered hypothalamus-pituitary-adrenal (HPA) axis regulation as a possible biological pathway underlying the link between stress and disease. However, the direction of dysregulation remains unclear, with reported HPA hyper- or hyporeactivity. To disentangle potential effects on different functional levels in the HPA axis, we examined responses using two pharmacological stimulation tests in 53 healthy teachers (31 females, 22 males; mean age: 49.3 years; age range: 30-64 years): a low-dose adrenocorticotrophic hormone (ACTH(1-24), Synacthen) test was used to assess adrenal cortex sensitivity and the combined dexamethasone-corticotropin releasing hormone (DEX-CRH) test to examine pituitary and adrenal cortex reactivity. Blood and saliva samples were collected at - 1,+15,+30,+45,+60,+90,+120 min. Emotional exhaustion (EE), the core dimension of burnout, was measured with the Maslach Burnout Inventory. Overcommitment (OC) was assessed according to Siegrist's effort-reward-imbalance model. We found a significant association between EE and higher plasma cortisol profiles after Synacthen (p = 0.045). By contrast, OC was significantly associated with attenuated ACTH (p = 0.045), plasma cortisol (p = 0.005), and salivary cortisol (p = 0.023) concentrations following DEX-CRH. Results support the notion of altered HPA axis regulation in chronically work-stressed teachers, with differential patterns of hyper- and hyporeactivity depending on individual stress condition and the tested functional level of the HPA axis.

Childhood Parental Loss and Adult Hypothalamic-Pituitary-Adrenal Function

Science.gov (United States)

Tyrka, Audrey R.; Wier, Lauren; Price, Lawrence H.; Ross, Nicole; Anderson, George M.; Wilkinson, Charles W.; Carpenter, Linda L.

2009-01-01

Background Several decades of research link childhood parental loss with risk for major depression and other forms of psychopathology. A large body of preclinical work on maternal separation and some recent studies of humans with childhood parental loss have demonstrated alterations of hypothalamic-pituitary-adrenal (HPA) axis function which could predispose to the development of psychiatric disorders. Methods Eighty-eight healthy adults with no current Axis I psychiatric disorder participated in this study. Forty-four participants experienced parental loss during childhood, including 19 with a history of parental death and 25 with a history of prolonged parental separation. The loss group was compared to a matched group of individuals who reported no history of childhood parental separation or childhood maltreatment. Participants completed diagnostic interviews and questionnaires and the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Repeated measures general linear models were used to test the effects of parental loss, a measure of parental care, sex, and age on the hormone responses to the Dex/CRH test. Results Parental loss was associated with increased cortisol responses to the test, particularly in males. The effect of loss was moderated by levels of parental care; participants with parental desertion and very low levels of care had attenuated cortisol responses. ACTH responses to the Dex/CRH test did not differ significantly as a function of parental loss. Conclusions These findings are consistent with the hypothesis that early parental loss induces enduring changes in neuroendocrine function. PMID:18339361

Total Variation Depth for Functional Data

KAUST Repository

Huang, Huang

2016-11-15

There has been extensive work on data depth-based methods for robust multivariate data analysis. Recent developments have moved to infinite-dimensional objects such as functional data. In this work, we propose a new notion of depth, the total variation depth, for functional data. As a measure of depth, its properties are studied theoretically, and the associated outlier detection performance is investigated through simulations. Compared to magnitude outliers, shape outliers are often masked among the rest of samples and harder to identify. We show that the proposed total variation depth has many desirable features and is well suited for outlier detection. In particular, we propose to decompose the total variation depth into two components that are associated with shape and magnitude outlyingness, respectively. This decomposition allows us to develop an effective procedure for outlier detection and useful visualization tools, while naturally accounting for the correlation in functional data. Finally, the proposed methodology is demonstrated using real datasets of curves, images, and video frames.

First experience with a new biomedical engineering program in Slovenia established following the TEMPUS IV CRH-BME joint project guidelines.

Science.gov (United States)

Jarm, Tomaz; Miklavcic, Damijan

2014-01-01

A new study program of biomedical engineering was recently established at Faculty of Electrical Engineering, University of Ljubljana, Slovenia. It is based on the long-lasting tradition of education in the field of BME at the host institution and is built on the BME areas in which the research groups of the Faculty of Electrical Engineering have been traditionally successful. The program was prepared in accordance with the recommendations of the TEMPUS IV CRH-BME Project consortium.

Smart variations: Functional substructures for part compatibility

KAUST Repository

Zheng, Youyi

2013-05-01

As collections of 3D models continue to grow, reusing model parts allows generation of novel model variations. Naïvely swapping parts across models, however, leads to implausible results, especially when mixing parts across different model families. Hence, the user has to manually ensure that the final model remains functionally valid. We claim that certain symmetric functional arrangements (sFarr-s), which are special arrangements among symmetrically related substructures, bear close relation to object functions. Hence, we propose a purely geometric approach based on such substructures to match, replace, and position triplets of parts to create non-trivial, yet functionally plausible, model variations. We demonstrate that starting even from a small set of models such a simple geometric approach can produce a diverse set of non-trivial and plausible model variations. © 2013 The Author(s) Computer Graphics Forum © 2013 The Eurographics Association and Blackwell Publishing Ltd.

PENINGKATAN AKTIVITAS DAN HASIL BELAJAR BENTUK PASAR DENGAN METODE COURSE REVIEW HORAY (CRH BERBANTUAN MEDIA GAMBAR KELAS VIII SMP N 1 BULU KABUPATEN SUKOHARJO

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Setyaningsih Setyaningsih

2013-11-01

Full Text Available Penelitian ini bertujuan untuk meningkatkan aktivitas dan hasil belajar siswa pada materi bentuk pasar dengan metode Course Review Horay (CRH berbantuan media gambar kelas VIII SMP N 1 Bulu Kabupaten Sukoharjo. Jenis penelitian ini adalah penelitian tindakan kelas yang terdiri dari dua siklus. Setiap siklus memiliki empat tahap yaitu perencanaan, pelaksanaan, pengamatan, dan refleksi. Subjek penelitian ini adalah siswa kelas VIIIA SMP N 1 Bulu. Data aktivitas siswa dan guru diperoleh dari lembar observasi. Data hasil belajar diperoleh dari soal evaluasi siklus I dan siklus II. Berdasarkan hasil penelitian diperoleh aktivitas siswa siklus I sebesar 70,83% meningkat menjadi 87,50% pada siklus II. Sedangkan aktivitas guru dalam siklus I sebesar 71,86% meningkat menjadi 90,6% pada siklus II. Rata-rata hasil belajar kognitif menunjukkan pada siklus I sebesar 72,67 meningkat menjadi 83,20 pada siklus II. Sedangkan ketuntasan klasikal pada siklus I sebesar 70% meningkat menjadi 83,33% pada siklus II. Dari hasil penelitian tersebut dapat disimpulkan bahwa terjadi peningkatan aktivitas dan hasil belajar siswa pada materi bentuk pasar dengan metode Course Review Horay (CRH berbantuan media gambar siswa kelas VIIIA SMP N 1 Bulu Kabupaten Sukoharjo. This research is aimed to increasing activity and student learning results in the subject matter of market forms material by using Course Review Horay (CRH method and image as media in VIIIA class of SMP N 1 Bulu. The design is Classroom Action Research (CAR consisting of two cycles, each cycle including planning, action, observation and reflection. The subjects of research were 30 students of the VIIIA class of SMP N 1 Bulu. Student and teacher activity data were obtained from observation sheet. Results learning data were obtained from test evaluation of the first cycle and second cycle. Based on the results research was obtained in the first cycle of student activities at 70,83% increased to 87,50 in the

S6K1 in the central nervous system regulates energy expenditure via MC4R/CRH pathways in response to deprivation of an essential amino acid.

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Xia, Tingting; Cheng, Ying; Zhang, Qian; Xiao, Fei; Liu, Bin; Chen, Shanghai; Guo, Feifan

2012-10-01

It is well established that the central nervous system (CNS), especially the hypothalamus, plays an important role in regulating energy homeostasis and lipid metabolism. We have previously shown that hypothalamic corticotropin-releasing hormone (CRH) is critical for stimulating fat loss in response to dietary leucine deprivation. The molecular mechanisms underlying the CNS regulation of leucine deprivation-stimulated fat loss are, however, still largely unknown. Here, we used intracerebroventricular injection of adenoviral vectors to identify a novel role for hypothalamic p70 S6 kinase 1 (S6K1), a major downstream effector of the kinase mammalian target of rapamycin, in leucine deprivation stimulation of energy expenditure. Furthermore, we show that the effect of hypothalamic S6K1 is mediated by modulation of Crh expression in a melanocortin-4 receptor-dependent manner. Taken together, our studies provide a new perspective for understanding the regulation of energy expenditure by the CNS and the importance of cross-talk between nutritional control and regulation of endocrine signals.

Functional characterization of genetic enzyme variations in human lipoxygenases

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Thomas Horn

2013-01-01

Full Text Available Mammalian lipoxygenases play a role in normal cell development and differentiation but they have also been implicated in the pathogenesis of cardiovascular, hyperproliferative and neurodegenerative diseases. As lipid peroxidizing enzymes they are involved in the regulation of cellular redox homeostasis since they produce lipid hydroperoxides, which serve as an efficient source for free radicals. There are various epidemiological correlation studies relating naturally occurring variations in the six human lipoxygenase genes (SNPs or rare mutations to the frequency for various diseases in these individuals, but for most of the described variations no functional data are available. Employing a combined bioinformatical and enzymological strategy, which included structural modeling and experimental site-directed mutagenesis, we systematically explored the structural and functional consequences of non-synonymous genetic variations in four different human lipoxygenase genes (ALOX5, ALOX12, ALOX15, and ALOX15B that have been identified in the human 1000 genome project. Due to a lack of a functional expression system we resigned to analyze the functionality of genetic variations in the hALOX12B and hALOXE3 gene. We found that most of the frequent non-synonymous coding SNPs are located at the enzyme surface and hardly alter the enzyme functionality. In contrast, genetic variations which affect functional important amino acid residues or lead to truncated enzyme variations (nonsense mutations are usually rare with a global allele frequency<0.1%. This data suggest that there appears to be an evolutionary pressure on the coding regions of the lipoxygenase genes preventing the accumulation of loss-of-function variations in the human population.

Stress-related neuropeptides and alcoholism: CRH, NPY and beyond

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Ciccocioppo, Roberto; Gehlert, Donald R.; Ryabinin, Andrey; Kaur, Simranjit; Cippitelli, Andrea; Thorsell, Annika; Lê, Anh D.; Hipskind, Philip A.; Hamdouchi, Chafiq; Lu, Jianliang; Hembre, Erik J.; Cramer, Jeffrey; Song, Min; McKinzie, David; Morin, Michelle; Economidou, Daina; Stopponi, Serena; Cannella, Nazzareno; Braconi, Simone; Kallupi, Marsida; de Guglielmo, Giordano; Massi, Maurizio; George, David T.; Gilman, Jody; Hersh, Jacqueline; Tauscher, Johannes T.; Hunt, Stephen P.; Hommer, Daniel; Heilig, Markus

2009-01-01

This article summarizes the proceedings of a symposium held at the conference on “Alcoholism and Stress: A Framework for Future Treatment Strategies” in Volterra, Italy, May 6–9, 2008. Chaired by Markus Heilig and Roberto Ciccocioppo, this symposium offered a forum for the presentation of recent data linking neuropetidergic neurotransmission to the regulation of different alcohol related behaviours in animals and in humans. Dr. Donald Gehlert described the development of a new corticotrophin releasing factor (CRH) receptor 1 antagonist and showed its efficacy in reducing alcohol consumption and stress-induced relapse in different animal models of alcohol abuse. Dr. Andrey Ryabinin reviewed recent findings in his laboratory indicating a role of the urocortin 1 (Ucn) receptor system in the regulation of alcohol intake. Dr. Annika Thorsell showed data supporting the significance of the neuropetide Y (NPY) receptor system in the modulation of behaviours associated with a history of ethanol intoxication. Dr. Roberto Ciccocioppo focused his presentation on the nociceptin/orphanin FQ (N/OFQ) receptors as treatment targets for alcoholism. Finally, Dr. Markus Heilig showed recent preclinical and clinical evidence suggesting that neurokinin 1 (NK1) antagonism may represent a promising new treatment for alcoholism. Collectively, these investigators highlighted the significance of neuropeptidergic neurotransmission in the regulation of neurobiological mechanisms of alcohol addiction. Data also revealed the importance of these systems as treatment targets for the development of new medication for alcoholism. PMID:19913192

Do key dimensions of seed and seedling functional trait variation capture variation in recruitment probability?

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1. Plant functional traits provide a mechanistic basis for understanding ecological variation among plant species and the implications of this variation for species distribution, community assembly and restoration. 2. The bulk of our functional trait understanding, however, is centered on traits rel...

Functional variation in the gut microbiome of wild Drosophila populations.

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Bost, Alyssa; Martinson, Vincent G; Franzenburg, Soeren; Adair, Karen L; Albasi, Alice; Wells, Martin T; Douglas, Angela E

2018-05-26

Most of the evidence that the gut microbiome of animals is functionally variable, with consequences for the health and fitness of the animal host, is based on laboratory studies, often using inbred animals under tightly controlled conditions. It is largely unknown whether these microbiome effects would be evident in outbred animal populations under natural conditions. In this study, we quantified the functional traits of the gut microbiota (metagenome) and host (gut transcriptome) and the taxonomic composition of the gut microorganisms (16S rRNA gene sequence) in natural populations of three mycophagous Drosophila species. Variation in microbiome function and composition was driven principally by the period of sample collection, while host function varied mostly with Drosophila species, indicating that variation in microbiome traits is determined largely by environmental factors, and not host taxonomy. Despite this, significant correlations between microbiome and host functional traits were obtained. In particular, microbiome functions dominated by metabolism were positively associated with host functions relating to gut epithelial turnover. Much of the functional variation in the microbiome could be attributed to variation in abundance of Bacteroidetes, rather than the two other abundant groups, the γ-Proteobacteria or Lactobacillales. We conclude that functional variation in the interactions between animals and their gut microbiome can be detectable in natural populations and, in mycophagous Drosophila, this variation relates primarily to metabolism and homeostasis of the gut epithelium. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Robust design principles for reducing variation in functional performance

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Christensen, Martin Ebro; Howard, Thomas J.

2016-01-01

This paper identifies, describes and classifies a comprehensive collection of variation reduction principles (VRP) that can be used to increase the robustness of a product and reduce its variation in functional performance. Performance variation has a negative effect on the reliability and percei......This paper identifies, describes and classifies a comprehensive collection of variation reduction principles (VRP) that can be used to increase the robustness of a product and reduce its variation in functional performance. Performance variation has a negative effect on the reliability...... and perceived quality of a product and efforts should be made to minimise it. The design principles are identified by a systematic decomposition of the Taguchi Transfer Function in combination with the use of existing literature and the authors’ experience. The paper presents 15 principles and describes...... their advantages and disadvantages along with example cases. Subsequently, the principles are classified based on their applicability in the various development and production stages. The VRP are to be added to existing robust design methodologies, helping the designer to think beyond robust design tool and method...

Association of HPA axis-related genetic variation with stress reactivity and aggressive behaviour in pigs

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Muráni Eduard

2010-08-01

Full Text Available Abstract Background Stress, elicited for example by aggressive interactions, has negative effects on various biological functions including immune defence, reproduction, growth, and, in livestock, on product quality. Stress response and aggressiveness are mutually interrelated and show large interindividual variation, partly attributable to genetic factors. In the pig little is known about the molecular-genetic background of the variation in stress responsiveness and aggressiveness. To identify candidate genes we analyzed association of DNA markers in each of ten genes (CRH g.233C>T, CRHR1 c.*866_867insA, CRHBP c.51G>A, POMC c.293_298del, MC2R c.306T>G, NR3C1 c.*2122A>G, AVP c.207A>G, AVPR1B c.1084A>G, UCN g.1329T>C, CRHR2 c.*13T>C related to the hypothalamic-pituitary-adrenocortical (HPA axis, one of the main stress-response systems, with various stress- and aggression-related parameters at slaughter. These parameters were: physiological measures of the stress response (plasma concentrations of cortisol, creatine kinase, glucose, and lactate, adrenal weight (which is a parameter reflecting activity of the central branch of the HPA axis over time and aggressive behaviour (measured by means of lesion scoring in the context of psychosocial stress of mixing individuals with different aggressive temperament. Results The SNP NR3C1 c.*2122A>G showed association with cortisol concentration (p = 0.024, adrenal weight (p = 0.003 and aggressive behaviour (front lesion score, p = 0.012; total lesion score p = 0.045. The SNP AVPR1B c.1084A>G showed a highly significant association with aggressive behaviour (middle lesion score, p = 0.007; total lesion score p = 0.003. The SNP UCN g.1329T>C showed association with adrenal weight (p = 0.019 and aggressive behaviour (front lesion score, p = 0.029. The SNP CRH g.233C>T showed a significant association with glucose concentration (p = 0.002, and the polymorphisms POMC c.293_298del and MC2R c.306T>G with adrenal

Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome.

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Sagami, Y; Shimada, Y; Tayama, J; Nomura, T; Satake, M; Endo, Y; Shoji, T; Karahashi, K; Hongo, M; Fukudo, S

2004-07-01

Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of alpha-helical CRH (alphahCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients. Ten normal healthy subjects and 10 IBS patients, diagnosed according to the Rome II criteria, were studied. The tone of the descending colon and intraluminal pressure of the sigmoid colon were measured at baseline, during rectal electrical stimulation (ES), and at recovery after administration of saline. Visceral perception after colonic distension or rectal ES was evaluated as threshold values on an ordinate scale. The same measurements were repeated after administration of alphahCRH (10 micro g/kg). ES induced significantly higher motility indices of the colon in IBS patients compared with controls. This response was significantly suppressed in IBS patients but not in controls after administration of alphahCRH. Administration of alphahCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. alphahCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by ES in IBS patients. Plasma adrenocorticotropic hormone and serum cortisol levels were generally not suppressed by alphahCRH. Peripheral administration of alphahCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.

Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome

OpenAIRE

Sagami, Y; Shimada, Y; Tayama, J; Nomura, T; Satake, M; Endo, Y; Shoji, T; Karahashi, K; Hongo, M; Fukudo, S

2004-01-01

Background and aims: Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of α-helical CRH (αhCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patient...

Use of the Dexamethasone-Corticotrophin Releasing Hormone Test to Assess Hypothalamic-Pituitary-Adrenal Axis Function in Rheumatoid Arthritis

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Eman A. Hasan

2009-01-01

Full Text Available Objectives. Hypothalamic-Pituitary-Adrenal axis function may be abnormal in rheumatoid arthritis (RA. A pilot study in 7 patients suggested impaired glucocorticoid feedback in some patients after the dexamethasone-corticotrophin releasing hormone (CRH test. This study aimed to investigate the dexamethasone-corticotrophin releasing factor test in a larger group of patients and relate the results to characteristics of the disease. Methods. Outpatients with active RA (≥3 swollen and tender joints and C-reactive protein > 10 mg/L took dexamethasone (1.5 mg at 23:00 hour in the evening. Next day, baseline saliva and plasma samples were collected, CRH was infused at 11:00 hour, and 4 serial blood and saliva samples were collected. Plasma samples were stored at −80∘C and a radioimmunoassay performed for saliva and plasma cortisol. Results. All 20 participants showed normal dexamethasone suppression and mounted no response to the CRH challenge. In samples with measurable cortisol, there was a strong correlation between saliva and plasma values (r = 0.876, n = 26, P<.01. Conclusion. No abnormalities were found in the Dexamethasone-CRH test in RA patients in contrast to a previous pilot study. Salivary cortisol measurement may offer an alternative noninvasive technique to plasma cortisol in RA patients in future studies.

Corticotropin-releasing hormone and mast cells in the regulation of mucosal barrier function in the human colon.

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Wallon, Conny; Söderholm, Johan D

2009-05-01

Corticotropin-releasing hormone (CRH) is an important neuro-endocrine mediator of the stress response. Local effects of CRH in the intestinal mucosa have become evident in recent years. We showed that CRH activates CRH receptor subtypes R1 and R2 on subepithelial mast cells, thereby inducing increased transcellular uptake of protein antigens in human colonic biopsies in Ussing chambers. Ongoing studies also implicate local cholinergic signaling in regulation of macromolecular permeability in the human colon. Since increased uptake of antigenic molecules is associated with mucosal inflammation, our findings may have implications for understanding stress-related intestinal disorders.

Variation of functional clonal traits along elevation in two fern species

International Nuclear Information System (INIS)

Song, Y.B.; Chen, L.Y.; Xiong, W.

2015-01-01

Phenotypical plasticity is generally considered among adaptive strategies by which plants can cope with environmental variation in space and time. Although much is known about plasticity in seed plants in terms of functional clonal traits while little is known about ferns. Variation of functional clonal traits of two ferns Dicranopteris dichotoma and Diplopterygium glaucum among plots differing in elevation in a subtropical evergreen broad-leaved forest in southern China was investigated. Along with elevation increasing the two fern species showed similar variation pattern of functional clonal traits: stable spacer length, increasing specific spacer length and decreasing spacer weight per ramet and specific spacer weight. The two ferns species had similar variation pattern of ramet performance traits but different variation pattern of ramet population properties. These results suggest an evolutionary trade-off between functions of foraging for and storing of resources in the two ferns, with a functional preference for the foraging in response to environmental change. (author)

Modelling the Probability Density Function of IPTV Traffic Packet Delay Variation

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Michal Halas

2012-01-01

Full Text Available This article deals with modelling the Probability density function of IPTV traffic packet delay variation. The use of this modelling is in an efficient de-jitter buffer estimation. When an IP packet travels across a network, it experiences delay and its variation. This variation is caused by routing, queueing systems and other influences like the processing delay of the network nodes. When we try to separate these at least three types of delay variation, we need a way to measure these types separately. This work is aimed to the delay variation caused by queueing systems which has the main implications to the form of the Probability density function.

Construction of A Trial Function In The Variational Procedure of ...

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A form of variational method for calculating the ground state energy of a quantum mechanical system is considered. The method is based on a systematic construction of a trial variational function at each step of the calculation of the ground state energy. The construction involves introducing more variational parameters to ...

Individual diet variation in a marine fish assemblage: Optimal Foraging Theory, Niche Variation Hypothesis and functional identity

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Cachera, M.; Ernande, B.; Villanueva, M. C.; Lefebvre, S.

2017-02-01

Individual diet variation (i.e. diet variation among individuals) impacts intra- and inter-specific interactions. Investigating its sources and relationship with species trophic niche organization is important for understanding community structure and dynamics. Individual diet variation may increase with intra-specific phenotypic (or "individual state") variation and habitat variability, according to Optimal Foraging Theory (OFT), and with species trophic niche width, according to the Niche Variation Hypothesis (NVH). OFT proposes "proximate sources" of individual diet variation such as variations in habitat or size whereas NVH relies on "ultimate sources" related to the competitive balance between intra- and inter-specific competitions. The latter implies as a corollary that species trophic niche overlap, taken as inter-specific competition measure, decreases as species niche width and individual niche variation increase. We tested the complementary predictions of OFT and NVH in a marine fish assemblage using stomach content data and associated trophic niche metrics. The NVH predictions were tested between species of the assemblage and decomposed into a between- and a within-functional group component to assess the potential influence of species' ecological function. For most species, individual diet variation and niche overlap were consistently larger than expected. Individual diet variation increased with intra-specific variability in individual state and habitat, as expected from OFT. It also increased with species niche width but in compliance with the null expectation, thus not supporting the NVH. In contrast, species niche overlap increased significantly less than null expectation with both species niche width and individual diet variation, supporting NVH corollary. The between- and within-functional group components of the NVH relationships were consistent with those between species at the assemblage level. Changing the number of prey categories used to

Genic intolerance to functional variation and the interpretation of personal genomes.

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Slavé Petrovski

Full Text Available A central challenge in interpreting personal genomes is determining which mutations most likely influence disease. Although progress has been made in scoring the functional impact of individual mutations, the characteristics of the genes in which those mutations are found remain largely unexplored. For example, genes known to carry few common functional variants in healthy individuals may be judged more likely to cause certain kinds of disease than genes known to carry many such variants. Until now, however, it has not been possible to develop a quantitative assessment of how well genes tolerate functional genetic variation on a genome-wide scale. Here we describe an effort that uses sequence data from 6503 whole exome sequences made available by the NHLBI Exome Sequencing Project (ESP. Specifically, we develop an intolerance scoring system that assesses whether genes have relatively more or less functional genetic variation than expected based on the apparently neutral variation found in the gene. To illustrate the utility of this intolerance score, we show that genes responsible for Mendelian diseases are significantly more intolerant to functional genetic variation than genes that do not cause any known disease, but with striking variation in intolerance among genes causing different classes of genetic disease. We conclude by showing that use of an intolerance ranking system can aid in interpreting personal genomes and identifying pathogenic mutations.

Regularization by Functions of Bounded Variation and Applications to Image Enhancement

International Nuclear Information System (INIS)

Casas, E.; Kunisch, K.; Pola, C.

1999-01-01

Optimization problems regularized by bounded variation seminorms are analyzed. The optimality system is obtained and finite-dimensional approximations of bounded variation function spaces as well as of the optimization problems are studied. It is demonstrated that the choice of the vector norm in the definition of the bounded variation seminorm is of special importance for approximating subspaces consisting of piecewise constant functions. Algorithms based on a primal-dual framework that exploit the structure of these nondifferentiable optimization problems are proposed. Numerical examples are given for denoising of blocky images with very high noise

Loss of hypothalamic corticotropin-releasing hormone markedly reduces anxiety behaviors in mice

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Zhang, Rong; Asai, Masato; Mahoney, Carrie E; Joachim, Maria; Shen, Yuan; Gunner, Georgia; Majzoub, Joseph A

2016-01-01

A long-standing paradigm posits that hypothalamic corticotropin-releasing hormone (CRH) regulates neuroendocrine functions such as adrenal glucocorticoid release, while extra-hypothalamic CRH plays a key role in stressor-triggered behaviors. Here we report that hypothalamus-specific Crh knockout mice (Sim1CrhKO mice, created by crossing Crhflox with Sim1Cre mice) have absent Crh mRNA and peptide mainly in the paraventricular nucleus of the hypothalamus (PVH) but preserved Crh expression in other brain regions including amygdala and cerebral cortex. As expected, Sim1CrhKO mice exhibit adrenal atrophy as well as decreased basal, diurnal and stressor-stimulated plasma corticosterone secretion and basal plasma ACTH, but surprisingly, have a profound anxiolytic phenotype when evaluated using multiple stressors including open field, elevated plus maze, holeboard, light-dark box, and novel object recognition task. Restoring plasma corticosterone did not reverse the anxiolytic phenotype of Sim1CrhKO mice. Crh-Cre driver mice revealed that PVHCrh fibers project abundantly to cingulate cortex and the nucleus accumbens shell, and moderately to medial amygdala, locus coeruleus, and solitary tract, consistent with the existence of PVHCrh-dependent behavioral pathways. Although previous, nonselective attenuation of CRH production or action, genetically in mice and pharmacologically in humans, respectively, has not produced the anticipated anxiolytic effects, our data show that targeted interference specifically with hypothalamic Crh expression results in anxiolysis. Our data identify neurons that express both Sim1 and Crh as a cellular entry point into the study of CRH-mediated, anxiety-like behaviors and their therapeutic attenuation. PMID:27595593

Ground-state densities from the Rayleigh-Ritz variation principle and from density-functional theory.

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Kvaal, Simen; Helgaker, Trygve

2015-11-14

The relationship between the densities of ground-state wave functions (i.e., the minimizers of the Rayleigh-Ritz variation principle) and the ground-state densities in density-functional theory (i.e., the minimizers of the Hohenberg-Kohn variation principle) is studied within the framework of convex conjugation, in a generic setting covering molecular systems, solid-state systems, and more. Having introduced admissible density functionals as functionals that produce the exact ground-state energy for a given external potential by minimizing over densities in the Hohenberg-Kohn variation principle, necessary and sufficient conditions on such functionals are established to ensure that the Rayleigh-Ritz ground-state densities and the Hohenberg-Kohn ground-state densities are identical. We apply the results to molecular systems in the Born-Oppenheimer approximation. For any given potential v ∈ L(3/2)(ℝ(3)) + L(∞)(ℝ(3)), we establish a one-to-one correspondence between the mixed ground-state densities of the Rayleigh-Ritz variation principle and the mixed ground-state densities of the Hohenberg-Kohn variation principle when the Lieb density-matrix constrained-search universal density functional is taken as the admissible functional. A similar one-to-one correspondence is established between the pure ground-state densities of the Rayleigh-Ritz variation principle and the pure ground-state densities obtained using the Hohenberg-Kohn variation principle with the Levy-Lieb pure-state constrained-search functional. In other words, all physical ground-state densities (pure or mixed) are recovered with these functionals and no false densities (i.e., minimizing densities that are not physical) exist. The importance of topology (i.e., choice of Banach space of densities and potentials) is emphasized and illustrated. The relevance of these results for current-density-functional theory is examined.

Endocrinology and the brain: corticotropin-releasing hormone signaling.

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Inda, Carolina; Armando, Natalia G; Dos Santos Claro, Paula A; Silberstein, Susana

2017-08-01

Corticotropin-releasing hormone (CRH) is a key player of basal and stress-activated responses in the hypothalamic-pituitary-adrenal axis (HPA) and in extrahypothalamic circuits, where it functions as a neuromodulator to orchestrate humoral and behavioral adaptive responses to stress. This review describes molecular components and cellular mechanisms involved in CRH signaling downstream of its G protein-coupled receptors (GPCRs) CRHR1 and CRHR2 and summarizes recent findings that challenge the classical view of GPCR signaling and impact on our understanding of CRHRs function. Special emphasis is placed on recent studies of CRH signaling that revealed new mechanistic aspects of cAMP generation and ERK1/2 activation in physiologically relevant contexts of the neurohormone action. In addition, we present an overview of the pathophysiological role of the CRH system, which highlights the need for a precise definition of CRHRs signaling at molecular level to identify novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders. © 2017 The authors.

A Novel Family of Cell Wall-Related Proteins Regulated Differently during the Yeast Life Cycle

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Rodríguez-Peña, José Manuel; Cid, Víctor J.; Arroyo, Javier; Nombela, César

2000-01-01

The Saccharomyces cerevisiae Ygr189c, Yel040w, and Ylr213c gene products show significant homologies among themselves and with various bacterial β-glucanases and eukaryotic endotransglycosidases. Deletion of the corresponding genes, either individually or in combination, did not produce a lethal phenotype. However, the removal of YGR189c and YEL040w, but not YLR213c, caused additive sensitivity to compounds that interfere with cell wall construction, such as Congo red and Calcofluor White, and overexpression of YEL040w led to resistance to these compounds. These genes were renamed CRH1 and CRH2, respectively, for Congo red hypersensitive. By site-directed mutagenesis we found that the putative glycosidase domain of CRH1 was critical for its function in complementing hypersensitivity to the inhibitors. The involvement of CRH1 and CRH2 in the development of cell wall architecture was clearly shown, since the alkali-soluble glucan fraction in the crh1Δ crh2Δ strain was almost twice the level in the wild-type. Interestingly, the three genes were subject to different patterns of transcriptional regulation. CRH1 and YLR213c (renamed CRR1, for CRH related) were found to be cell cycle regulated and also expressed under sporulation conditions, whereas CRH2 expression did not vary during the mitotic cycle. Crh1 and Crh2 are localized at the cell surface, particularly in chitin-rich areas. Consistent with the observed expression patterns, Crh1–green fluorescent protein was found at the incipient bud site, around the septum area in later stages of budding, and in ascospore envelopes. Crh2 was found to localize mainly at the bud neck throughout the whole budding cycle, in mating projections and zygotes, but not in ascospores. These data suggest that the members of this family of putative glycosidases might exert a common role in cell wall organization at different stages of the yeast life cycle. PMID:10757808

Humeral torsion revisited: a functional and ontogenetic model for populational variation.

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Cowgill, Libby W

2007-12-01

Anthropological interest in humeral torsion has a long history, and several functional explanations for observed variation in the orientation of the humeral head have been proposed. Recent clinical studies have revived this topic by linking patterns of humeral torsion to habitual activities such as overhand throwing. However, the precise functional implications and ontogenetic history of humeral torsion remain unclear. This study examines the ontogeny of humeral torsion in a large sample of primarily immature remains from six different skeletal collections (n = 407). The results of this research confirm that humeral torsion displays consistent developmental variation within all populations of growing children; neonates display relatively posteriorly oriented humeral heads, and the level of torsion declines steadily into adulthood. As in adults, variation in the angle of humeral torsion in immature individuals varies by population, and these differences arise early in development. However, when examined in the context of the developing muscles of the shoulder complex, it becomes apparent that variation in the angle of humeral torsion is not necessarily related to specific habitual activities. Variability in this feature is more likely caused by a generalized functional imbalance between muscles of medial and lateral rotation that can be produced by a wide variety of upper limb activity patterns during growth. (c) 2007 Wiley-Liss, Inc.

How do the many etiologies of West syndrome lead to excitability and seizures? The corticotropin releasing hormone excess hypothesis.

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Brunson, K L; Eghbal-Ahmadi, M; Baram, T Z

2001-11-01

West syndrome (WS) is associated with diverse etiological factors. This fact has suggested that there must be a 'final common pathway' for these etiologies, which operates on the immature brain to result in WS only at the maturational state present during infancy. Any theory for the pathogenesis of WS has to account for the unique features of this disorder. For example, how can a single entity have so many etiologies? Why does WS arise only in infancy, even when a known insult had occurred prenatally, and why does it disappear? Why is WS associated with lasting cognitive dysfunction? And, importantly, why do these seizures--unlike most others--respond to treatment by a hormone, ACTH? The established hormonal role of ACTH in human physiology is to function in the neuroendocrine cascade of the responses to all stressful stimuli, including insults to the brain. As part of this function, ACTH is known to suppress the production of corticotropin releasing hormone (CRH), a peptide that is produced in response to diverse insults and stressors.The many etiologies of WS all lead to activation of the stress response, including increased production and secretion of the stress-neurohormone CRH. CRH has been shown, in infant animal models, to cause severe seizures and death of neurons in areas involved with learning and memory. These effects of CRH are restricted to the infancy period because the receptors for CRH, which mediate its action on neurons, are most abundant during this developmental period. ACTH administration is known to inhibit production and release of CRH via a negative feedback mechanism. Therefore, the efficacy of ACTH for WS may depend on its ability to decrease the levels of the seizure-promoting stress-neurohormone CRH.This CRH-excess theory for the pathophysiology of WS is consistent not only with the profile of ACTH effects, but also with the many different 'causes' of WS, with the abnormal ACTH levels in the cerebrospinal fluid of affected infants and

Variational principles for the spectral radius of functional operators

International Nuclear Information System (INIS)

Antonevich, A B; Zajkowski, K

2006-01-01

The spectral radius of a functional operator with positive coefficients generated by a set of maps (a dynamical system) is shown to be a logarithmically convex functional of the logarithms of the coefficients. This yields the following variational principle: the logarithm of the spectral radius is the Legendre transform of a convex functional T defined on a set of vector-valued probability measures and depending only on the original dynamical system. A combinatorial construction of the functional T by means of the random walk process corresponding to the dynamical system is presented in the subexponential case. Examples of the explicit calculation of the functional T and the spectral radius are presented.

Evaluation of adrenal function in patients with hypothalamic and pituitary disorders : comparison of serum cortisol, urinary free cortisol and the human-corticotrophin releasing hormone test with the insulin tolerance test

NARCIS (Netherlands)

Dullaart, RPF; Pasterkamp, SH; Beentjes, JAM; Sluiter, WJ

OBJECTIVE This study aimed to evaluate the performance of screening tests (serum cortisol and 24-h urinary free cortisol) and the human-corticotrophin releasing hormone (h-CRH) test in the assessment of adrenal function in patients with hypothalamic-pituitary disorders. DESIGN Summary receiver

Iterative method of the parameter variation for solution of nonlinear functional equations

International Nuclear Information System (INIS)

Davidenko, D.F.

1975-01-01

The iteration method of parameter variation is used for solving nonlinear functional equations in Banach spaces. The authors consider some methods for numerical integration of ordinary first-order differential equations and construct the relevant iteration methods of parameter variation, both one- and multifactor. They also discuss problems of mathematical substantiation of the method, study the conditions and rate of convergence, estimate the error. The paper considers the application of the method to specific functional equations

Continuity in Λ-variation of functions of several variables and convergence of multiple Fourier series

International Nuclear Information System (INIS)

Bakhvalov, A N

2002-01-01

The behaviour of rectangular partial sums of the Fourier series of functions of several variables having bounded Λ-variation is considered. It is proved that if a continuous function is also continuous in harmonic variation, then its Fourier series uniformly converges in the sense of Pringsheim. On the other hand, it is demonstrated that in dimensions greater than 2 there always exists a continuous function of bounded harmonic variation with Fourier series divergent over cubes at the origin

Total Variation Regularization for Functions with Values in a Manifold

KAUST Repository

Lellmann, Jan

2013-12-01

While total variation is among the most popular regularizers for variational problems, its extension to functions with values in a manifold is an open problem. In this paper, we propose the first algorithm to solve such problems which applies to arbitrary Riemannian manifolds. The key idea is to reformulate the variational problem as a multilabel optimization problem with an infinite number of labels. This leads to a hard optimization problem which can be approximately solved using convex relaxation techniques. The framework can be easily adapted to different manifolds including spheres and three-dimensional rotations, and allows to obtain accurate solutions even with a relatively coarse discretization. With numerous examples we demonstrate that the proposed framework can be applied to variational models that incorporate chromaticity values, normal fields, or camera trajectories. © 2013 IEEE.

Total Variation Regularization for Functions with Values in a Manifold

KAUST Repository

Lellmann, Jan; Strekalovskiy, Evgeny; Koetter, Sabrina; Cremers, Daniel

2013-01-01

While total variation is among the most popular regularizers for variational problems, its extension to functions with values in a manifold is an open problem. In this paper, we propose the first algorithm to solve such problems which applies to arbitrary Riemannian manifolds. The key idea is to reformulate the variational problem as a multilabel optimization problem with an infinite number of labels. This leads to a hard optimization problem which can be approximately solved using convex relaxation techniques. The framework can be easily adapted to different manifolds including spheres and three-dimensional rotations, and allows to obtain accurate solutions even with a relatively coarse discretization. With numerous examples we demonstrate that the proposed framework can be applied to variational models that incorporate chromaticity values, normal fields, or camera trajectories. © 2013 IEEE.

Role of stress peptides during human pregnancy and labour.

Science.gov (United States)

Hillhouse, Edward W; Grammatopoulos, Dimitris K

2002-09-01

Premature birth is the major source of perinatal death and disability. Furthermore, the intrauterine health of the baby is important for preventing certain adult diseases. However, the molecular mechanisms driving the onset of human labour remain uncertain, although several key players have been identified. It is becoming clear that there are many pathways to parturition in humans. Stress peptides, in particular placental corticotrophin releasing hormone (CRH) and possibly the related peptide urocortin, appear to play important roles throughout pregnancy. Plasma CRH is a predictor of the duration of human gestation. During most of pregnancy, CRH, acting via specific CRH receptor subtypes, plays a 'protective' role by promoting myometrial quiescence via the generation of cAMP and cGMP, and upregulation of nitric oxide synthase expression. At term, myometrial contractility is enhanced by a complex series of molecular switches, involving the upregulation of oxytocin receptor expression and crosstalk between the oxytocin and CRH receptors. This results in protein kinase C-induced phosphorylation of specific CRH receptor subtypes, with subsequent desensitization and a shift in the intracellular microenvironment to enhance contractility. CRH/urocortin, via specific receptor isoforms, is now able to activate Gq and potentially enhance the oxytocin-driven generation of inositol triphosphate. In addition, CRH/urocortin, via specific CRH receptor subtypes, may generate prostaglandins from the fetal membranes and decidua, play a role in placental vasodilatation and participate in fetal adrenal function and organ maturation. These peptides and receptors are phylogenetically ancient and well preserved across species. They may have evolved as a mechanism to protect against the 'stress' of premature birth.

Differential Activation in Amygdala and Plasma Noradrenaline during Colorectal Distention by Administration of Corticotropin-Releasing Hormone between Healthy Individuals and Patients with Irritable Bowel Syndrome.

Directory of Open Access Journals (Sweden)

Yukari Tanaka

Full Text Available Irritable bowel syndrome (IBS often comorbids mood and anxiety disorders. Corticotropin-releasing hormone (CRH is a major mediator of the stress response in the brain-gut axis, but it is not clear how CRH agonists change human brain responses to interoceptive stimuli. We tested the hypothesis that brain activation in response to colorectal distention is enhanced after CRH injection in IBS patients compared to healthy controls. Brain H215O- positron emission tomography (PET was performed in 16 male IBS patients and 16 age-matched male controls during baseline, no distention, mild and intense distention of the colorectum using barostat bag inflation. Either CRH (2 μg/kg or saline (1:1 was then injected intravenously and the same distention protocol was repeated. Plasma adrenocorticotropic hormone (ACTH, serum cortisol and plasma noradrenaline levels were measured at each stimulation. At baseline, CRH without colorectal distention induced more activation in the right amygdala in IBS patients than in controls. During intense distention after CRH injection, controls showed significantly greater activation than IBS patients in the right amygdala. Plasma ACTH and serum cortisol secretion showed a significant interaction between drug (CRH, saline and distention. Plasma noradrenaline at baseline significantly increased after CRH injection compared to before injection in IBS. Further, plasma noradrenaline showed a significant group (IBS, controls by drug by distention interaction. Exogenous CRH differentially sensitizes brain regions of the emotional-arousal circuitry within the visceral pain matrix to colorectal distention and synergetic activation of noradrenergic function in IBS patients and healthy individuals.

A conformal gauge invariant functional for Weyl structures and the first variation formula

OpenAIRE

Ichiyama, Toshiyuki; Furuhata, Hitoshi; Urakawa, Hajime

1999-01-01

We consider a new conformal gauge invariant functional which is a natural curvature functional on the space of Weyl structures. We derive the first variation formula of its functional and characterize its critical points.

Epigenetic variation predicts regional and local intraspecific functional diversity in a perennial herb.

Science.gov (United States)

Medrano, Mónica; Herrera, Carlos M; Bazaga, Pilar

2014-10-01

The ecological significance of epigenetic variation has been generally inferred from studies on model plants under artificial conditions, but the importance of epigenetic differences between individuals as a source of intraspecific diversity in natural plant populations remains essentially unknown. This study investigates the relationship between epigenetic variation and functional plant diversity by conducting epigenetic (methylation-sensitive amplified fragment length polymorphisms, MSAP) and genetic (amplified fragment length polymorphisms, AFLP) marker-trait association analyses for 20 whole-plant, leaf and regenerative functional traits in a large sample of wild-growing plants of the perennial herb Helleborus foetidus from ten sampling sites in south-eastern Spain. Plants differed widely in functional characteristics, and exhibited greater epigenetic than genetic diversity, as shown by per cent polymorphism of MSAP fragments (92%) or markers (69%) greatly exceeding that for AFLP ones (41%). After controlling for genetic structuring and possible cryptic relatedness, every functional trait considered exhibited a significant association with at least one AFLP or MSAP marker. A total of 27 MSAP (13.0% of total) and 12 AFLP (4.4%) markers were involved in significant associations, which explained on average 8.2% and 8.0% of trait variance, respectively. Individual MSAP markers were more likely to be associated with functional traits than AFLP markers. Between-site differences in multivariate functional diversity were directly related to variation in multilocus epigenetic diversity after multilocus genetic diversity was statistically accounted for. Results suggest that epigenetic variation can be an important source of intraspecific functional diversity in H. foetidus, possibly endowing this species with the capacity to exploit a broad range of ecological conditions despite its modest genetic diversity. © 2014 John Wiley & Sons Ltd.

Maternal stress and diet may influence affective behavior and stress-response in offspring via epigenetic regulation of central peptidergic function.

Science.gov (United States)

Thorsell, Annika; Nätt, Daniel

2016-08-01

It has been shown that maternal stress and malnutrition, or experience of other adverse events, during the perinatal period may alter susceptibility in the adult offspring in a time-of-exposure dependent manner. The mechanism underlying this may be epigenetic in nature. Here, we summarize some recent findings on the effects on gene-regulation following maternal malnutrition, focusing on epigenetic regulation of peptidergic activity. Numerous neuropeptides within the central nervous system are crucial components in regulation of homeostatic energy-balance, as well as affective health (i.e. health events related to affective disorders, psychiatric disorders also referred to as mood disorders). It is becoming evident that expression, and function, of these neuropeptides can be regulated via epigenetic mechanisms during fetal development, thereby contributing to the development of the adult phenotype and, possibly, modulating disease susceptibility. Here, we focus on two such neuropeptides, neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH), both involved in regulation of endocrine function, energy homeostasis, as well as affective health. While a number of published studies indicate the involvement of epigenetic mechanisms in CRH-dependent regulation of the offspring adult phenotype, NPY has been much less studied in this context and needs further work.

Activation of AMPK-Regulated CRH Neurons in the PVH is Sufficient and Necessary to Induce Dietary Preference for Carbohydrate over Fat

Directory of Open Access Journals (Sweden)

Shiki Okamoto

2018-01-01

Full Text Available Food selection is essential for metabolic homeostasis and is influenced by nutritional state, food palatability, and social factors such as stress. However, the mechanism responsible for selection between a high-carbohydrate diet (HCD and a high-fat diet (HFD remains unknown. Here, we show that activation of a subset of corticotropin-releasing hormone (CRH-positive neurons in the rostral region of the paraventricular hypothalamus (PVH induces selection of an HCD over an HFD in mice during refeeding after fasting, resulting in a rapid recovery from the change in ketone metabolism. These neurons manifest activation of AMP-activated protein kinase (AMPK during food deprivation, and this activation is necessary and sufficient for selection of an HCD over an HFD. Furthermore, this effect is mediated by carnitine palmitoyltransferase 1c (CPT1c. Thus, our results identify the specific neurons and intracellular signaling pathway responsible for regulation of the complex behavior of selection between an HCD and an HFD.

The interpolation method of stochastic functions and the stochastic variational principle

International Nuclear Information System (INIS)

Liu Xianbin; Chen Qiu

1993-01-01

Uncertainties have been attaching more importance to increasingly in modern engineering structural design. Viewed on an appropriate scale, the inherent physical attributes (material properties) of many structural systems always exhibit some patterns of random variation in space and time, generally the random variation shows a small parameter fluctuation. For a linear mechanical system, the random variation is modeled as a random one of a linear partial differential operator and, in stochastic finite element method, a random variation of a stiffness matrix. Besides the stochasticity of the structural physical properties, the influences of random loads which always represent themselves as the random boundary conditions bring about much more complexities in structural analysis. Now the stochastic finite element method or the probabilistic finite element method is used to study the structural systems with random physical parameters, whether or not the loads are random. Differing from the general finite element theory, the main difficulty which the stochastic finite element method faces is the inverse operation of stochastic operators and stochastic matrices, since the inverse operators and the inverse matrices are statistically correlated to the random parameters and random loads. So far, many efforts have been made to obtain the reasonably approximate expressions of the inverse operators and inverse matrices, such as Perturbation Method, Neumann Expansion Method, Galerkin Method (in appropriate Hilbert Spaces defined for random functions), Orthogonal Expansion Method. Among these methods, Perturbation Method appear to be the most available. The advantage of these methods is that the fairly accurate response statistics can be obtained under the condition of the finite information of the input. However, the second-order statistics obtained by use of Perturbation Method and Neumann Expansion Method are not always the appropriate ones, because the relevant second

Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function.

Science.gov (United States)

Di Iorio, Christina R; Carey, Caitlin E; Michalski, Lindsay J; Corral-Frias, Nadia S; Conley, Emily Drabant; Hariri, Ahmad R; Bogdan, Ryan

2017-06-01

Early life stress may precipitate psychopathology, at least in part, by influencing amygdala function. Converging evidence across species suggests that links between childhood stress and amygdala function may be dependent upon hypothalamic-pituitary-adrenal (HPA) axis function. Using data from college-attending non-Hispanic European-Americans (n=308) who completed the Duke Neurogenetics Study, we examined whether early life stress (ELS) and HPA axis genetic variation interact to predict threat-related amygdala function as well as psychopathology symptoms. A biologically-informed multilocus profile score (BIMPS) captured HPA axis genetic variation (FKBP5 rs1360780, CRHR1 rs110402; NR3C2 rs5522/rs4635799) previously associated with its function (higher BIMPS are reflective of higher HPA axis activity). BOLD fMRI data were acquired while participants completed an emotional face matching task. ELS and depression and anxiety symptoms were measured using the childhood trauma questionnaire and the mood and anxiety symptom questionnaire, respectively. The interaction between HPA axis BIMPS and ELS was associated with right amygdala reactivity to threat-related stimuli, after accounting for multiple testing (empirical-p=0.016). Among individuals with higher BIMPS (i.e., the upper 21.4%), ELS was positively coupled with threat-related amygdala reactivity, which was absent among those with average or low BIMPS. Further, higher BIMPS were associated with greater self-reported anxious arousal, though there was no evidence that amygdala function mediated this relationship. Polygenic variation linked to HPA axis function may moderate the effects of early life stress on threat-related amygdala function and confer risk for anxiety symptomatology. However, what, if any, neural mechanisms may mediate the relationship between HPA axis BIMPS and anxiety symptomatology remains unclear. Copyright © 2017 Elsevier Ltd. All rights reserved.

The interaction of corticotropin-releasing hormone receptor gene and early life stress on emotional empathy.

Science.gov (United States)

Grimm, Simone; Wirth, Katharina; Fan, Yan; Weigand, Anne; Gärtner, Matti; Feeser, Melanie; Dziobek, Isabel; Bajbouj, Malek; Aust, Sabine

2017-06-30

Early life stress (ELS) is associated with increased vulnerability for depression, changes to the corticotropin-releasing hormone (CRH) system and structural and functional changes in hippocampus. Single nucleotide polymorphisms in the CRH receptor 1 (CRHR1) gene interact with ELS to predict depression, cognitive functions and hippocampal activity. Social cognition has been related to hippocampal function and might be crucial for maintaining mental health. However, the interaction of CRHR1 gene variation and ELS on social cognition has not been investigated yet. We assessed social cognition in 502 healthy subjects to test effects of ELS and the CRHR1 gene. Participants were genotyped for rs110402 and rs242924. ELS was assessed by Childhood Trauma Questionnaire, social cognition was measured via Multifaceted Empathy Test and Empathy Quotient. Severity of ELS was associated with decreased emotional, but not cognitive empathy. Subjects with the common homozygous GG GG genotype showed decreased implicit emotional empathy after ELS exposure regardless of its severity. The results reveal that specific CRHR1 polymorphisms moderate the effect of ELS on emotional empathy. Exposure to ELS in combination with a vulnerable genotype results in impaired emotional empathy in adulthood, which might represent an early marker of increased vulnerability after ELS. Copyright © 2017 Elsevier B.V. All rights reserved.

Inter-doctor variations in the assessment of functional incapacities by insurance physicians

Directory of Open Access Journals (Sweden)

Schellart Antonius JM

2011-11-01

Full Text Available Abstract Background The aim of this study was to determine the - largely unexplored - extent of systematic variation in the work disability assessment by Dutch insurance physicians (IPs of employees on long-term sick leave, and to ascertain whether this variation was associated with the individual characteristics and opinions of IPs. Methods In March 2008 we conducted a survey among IPs on the basis of the 'Attitude - Social norm - self-Efficacy' (ASE model. We used the ensuing data to form latent variables for the ASE constructs. We then linked the background variables and the measured constructs for IPs (n = 199 working at regional offices (n = 27 to the work disability assessments of clients (n = 83,755 and their characteristics. These assessments were carried out between July 2003 and April 2008. We performed multilevel regression analysis on three important assessment outcomes: No Sustainable Capacity or Restrictions for Working Hours (binominal, Functional Incapacity Score (scale 0-6 and Maximum Work Disability Class (binominal. We calculated Intra Class Correlations (ICCs at IP level and office level and explained variances (R2 for the three outcomes. A higher ICC reflects stronger systematic variation. Results The ICCs at IP level were approximately 6% for No Sustainable Capacity or Restrictions for Working Hours and Maximum Work Disability Class and 12% for Functional Incapacity Score. Background IP variables and the measured ASE constructs for physicians contributed very little to the variation - at most 1%. The ICCs at office level ranged from 0% to around 1%. The R2 was 11% for No Sustainable Capacity or Restrictions for Working Hours, 19% for Functional Incapacity Score and 37% for Maximum Work Disability Class. Conclusion Our study uncovered small to moderate systematic variations in the outcome of disability assessments in the Netherlands. However, the individual characteristics and opinions of insurance physicians have very

Thyroid Function Variations Within the Reference Range Do Not Affect Quality of Life, Mood, or Cognitive Function in Community-Dwelling Older Men.

Science.gov (United States)

Samuels, Mary H; Kaimal, Rajani; Waring, Avantika; Fink, Howard A; Yaffe, Kristine; Hoffman, Andrew R; Orwoll, Eric; Bauer, Douglas

2016-09-01

Variations in thyroid function within the laboratory reference range have been associated with a number of clinical outcomes. However, quality of life, mood, and cognitive function have not been extensively studied, and it is not clear whether mild variations in thyroid function have major effects on these neurocognitive outcomes. Data were analyzed from the Osteoporotic Fractures in Men (MrOS) Study, a cohort of community-dwelling men aged 65 years and older in the United States. A total of 539 participants who were not taking thyroid medications and had age-adjusted TSH levels within the reference range underwent detailed testing of quality of life, mood, and cognitive function at baseline. The same quality of life, mood, and cognitive outcomes were measured again in 193 of the men after a mean follow-up of 6 years. Outcomes were analyzed using thyrotropin (TSH) and free thyroxine (FT4) levels as continuous independent variables, adjusting for relevant covariates. At baseline, there were no associations between TSH or FT4 levels and measures of quality of life, mood, or cognition in the 539 euthyroid men. Baseline thyroid function did not predict changes in these outcomes over a mean of 6 years in the 193 men in the longitudinal analysis. Variations in thyroid function within the age-adjusted laboratory reference range are not associated with variations in quality of life, mood, or cognitive function in community-dwelling older men.

Rapid adjustment of bird community compositions to local climatic variations and its functional consequences.

Science.gov (United States)

Gaüzère, Pierre; Jiguet, Frédéric; Devictor, Vincent

2015-09-01

The local spatial congruence between climate changes and community changes has rarely been studied over large areas. We proposed one of the first comprehensive frameworks tracking local changes in community composition related to climate changes. First, we investigated whether and how 12 years of changes in the local composition of bird communities were related to local climate variations. Then, we tested the consequences of this climate-induced adjustment of communities on Grinnellian (habitat-related) and Eltonian (function-related) homogenization. A standardized protocol monitoring spatial and temporal trends of birds over France from 2001 to 2012 was used. For each plot and each year, we used the spring temperature and the spring precipitations and calculated three indices reflecting the thermal niche, the habitat specialization, and the functional originality of the species within a community. We then used a moving-window approach to estimate the spatial distribution of the temporal trends in each of these indices and their congruency with local climatic variations. Temperature fluctuations and community dynamics were found to be highly variable in space, but their variations were finely congruent. More interestingly, the community adjustment to temperature variations was nonmonotonous. Instead, unexplained fluctuations in community composition were observed up to a certain threshold of climate change intensity, above which a change in community composition was observed. This shift corresponded to a significant decrease in the relative abundance of habitat specialists and functionally original species within communities, regardless of the direction of temperature change. The investigation of variations in climate and community responses appears to be a central step toward a better understanding of climate change effects on biodiversity. Our results suggest a fine-scale and short-term adjustment of community composition to temperature changes. Moreover

Dynamics of Gaussian Wigner functions derived from a time-dependent variational principle

Directory of Open Access Journals (Sweden)

Jens Aage Poulsen

2017-11-01

Full Text Available By using a time-dependent variational principle formulated for Wigner phase-space functions, we obtain the optimal time-evolution for two classes of Gaussian Wigner functions, namely those of either thawed real-valued or frozen but complex Gaussians. It is shown that tunneling effects are approximately included in both schemes.

Hedgehog signaling mediates adaptive variation in a dynamic functional system in the cichlid feeding apparatus.

Science.gov (United States)

Hu, Yinan; Albertson, R Craig

2014-06-10

Adaptive variation in the craniofacial skeleton is a key component of resource specialization and habitat divergence in vertebrates, but the proximate genetic mechanisms that underlie complex patterns of craniofacial variation are largely unknown. Here we demonstrate that the Hedgehog (Hh) signaling pathway mediates widespread variation across a complex functional system that affects the kinematics of lower jaw depression--the opercular four-bar linkage apparatus--among Lake Malawi cichlids. By using a combined quantitative trait locus mapping and population genetics approach, we show that allelic variation in the Hh receptor, ptch1, affects the development of distinct bony elements in the head that represent two of three movable links in this functional system. The evolutionarily derived allele is found in species that feed from the water column, and is associated with shifts in anatomy that translate to a four-bar system capable of faster jaw rotation. Alternatively, the ancestral allele is found in species that feed on attached algae, and is associated with the development of a four-bar system that predicts slower jaw movement. Experimental manipulation of the Hh pathway during cichlid development recapitulates functionally salient natural variation in craniofacial geometry. In all, these results significantly extend our understanding of the mechanisms that fine-tune the craniofacial skeletal complex during adaptation to new foraging niches.

Regional variation in the structure and function of parrotfishes on Arabian reefs

KAUST Repository

Hoey, Andrew; Feary, David A.; Burt, John A.; Vaughan, Grace; Pratchett, Morgan S.; Berumen, Michael L.

2015-01-01

the southern Arabian Gulf, and as such rates of grazing and erosion were negligible. This regional variation in abundance and functional composition of parrotfishes appears to be related to local environmental conditions.

Spectral and geometrical variation of the bidirectional reflectance distribution function of diffuse reflectance standards.

Science.gov (United States)

Ferrero, Alejandro; Rabal, Ana María; Campos, Joaquín; Pons, Alicia; Hernanz, María Luisa

2012-12-20

A study on the variation of the spectral bidirectional reflectance distribution function (BRDF) of four diffuse reflectance standards (matte ceramic, BaSO(4), Spectralon, and white Russian opal glass) is accomplished through this work. Spectral BRDF measurements were carried out and, using principal components analysis, its spectral and geometrical variation respect to a reference geometry was assessed from the experimental data. Several descriptors were defined in order to compare the spectral BRDF variation of the four materials.

Direct measurement of human plasma corticotropin-releasing hormone by two-site immunoradiometric assay

International Nuclear Information System (INIS)

Linton, E.A.; McLean, C.; Nieuwenhuyzen Kruseman, A.C.; Tilders, F.J.; Van der Veen, E.A.; Lowry, P.J.

1987-01-01

A ''two-site'' immunoradiometric assay (IRMA) which allows the direct estimation of human CRH (hCRH) in plasma is described. Using this IRMA, basal levels of CRH in normal subjects ranged from 2-28 pg/mL [mean, 15 +/- 7 (+/- SD) pg/mL; n = 58]. Values in men and women were similar. Plasma CRH values within this range were also found in patients with Cushing's syndrome, Addison's disease, and Nelson's syndrome, with no correlation between plasma CRH and ACTH levels in these patients. Elevated plasma CRH levels were found in pregnant women near term [1462 +/- 752 (+/- SD) pg/mL; n = 55], and the dilution curve of this CRH-like immunoreactivity paralleled the IRMA standard curve. After its immunoadsorption from maternal plasma, this CRH-like material eluted on reverse phase high performance liquid chromatography with a retention time identical to that of synthetic CRH and had equipotent bioactivity with the synthetic peptide in the perfused anterior pituitary cell bioassay. Circulating CRH was not detected in Wistar rats, even after adrenalectomy and subsequent ether stress. Synthetic hCRH was degraded by fresh human plasma relatively slowly; 65% of added CRH remained after 1 h of incubation at 37 C. Degradation was inhibited by heat treatment (54 C; 1 h), cold treatment (4 C; 4 h), or freezing and thawing. Loss of synthetic rat CRH occurred more rapidly when fresh rat plasma was used; only 20% of added CRH remained under the same conditions. The inability to measure CRH in peripheral rat plasma may be due to the presence of active CRH-degrading enzymes which fragment the CRH molecule into forms not recognized by the CRH IRMA

A transcriptome-wide screen for mRNAs enriched in fetal Leydig cells: CRHR1 agonism stimulates rat and mouse fetal testis steroidogenesis.

Directory of Open Access Journals (Sweden)

Erin N McDowell

Full Text Available Fetal testis steroidogenesis plays an important role in the reproductive development of the male fetus. While regulators of certain aspects of steroidogenesis are known, the initial driver of steroidogenesis in the human and rodent fetal testis is unclear. Through comparative analysis of rodent fetal testis microarray datasets, 54 candidate fetal Leydig cell-specific genes were identified. Fetal mouse testis interstitial expression of a subset of these genes with unknown expression (Crhr1, Gramd1b, Itih5, Vgll3, and Vsnl1 was verified by whole-mount in situ hybridization. Among the candidate fetal Leydig cell-specific factors, three receptors (CRHR1, PRLR, and PROKR2 were tested for a steroidogenic function using ex vivo fetal testes treated with receptor agonists (CRH, PRL, and PROK2. While PRL and PROK2 had no effect, CRH, at low (approximately 1 to 10 nM concentration, increased expression of the steroidogenic genes Cyp11a1, Cyp17a1, Scarb1, and Star in GD15 mouse and GD17 rat testes, and in conjunction, testosterone production was increased. Exposure of GD15 fetal mouse testis to a specific CRHR1 antagonist blunted the CRH-induced steroidogenic gene expression and testosterone responses. Similar to ex vivo rodent fetal testes, ≥ 10 nM CRH exposure of MA-10 Leydig cells increased steroidogenic pathway mRNA and progesterone levels, showing CRH can enhance steroidogenesis by directly targeting Leydig cells. Crh mRNA expression was observed in rodent fetal hypothalamus, and CRH peptide was detected in rodent amniotic fluid. Together, these data provide a resource for discovering factors controlling fetal Leydig cell biology and suggest that CRHR1 activation by CRH stimulates rat and mouse fetal Leydig cell steroidogenesis in vivo.

Functional limit theorems for generalized variations of the fractional Brownian sheet

DEFF Research Database (Denmark)

Pakkanen, Mikko; Réveillac, Anthony

and on the smallest component of the Hurst parameter vector of the fBs. The limiting process in the former result is another fBs, independent of the original fBs, whereas the limit given by the latter result is an Hermite sheet, which is driven by the same white noise as the original fBs. As an application, we derive...... functional limit theorems for power variations of the fBs and discuss what is a proper way to interpolate them to ensure functional convergence....

Functional limit theorems for generalized variations of the fractional Brownian sheet

DEFF Research Database (Denmark)

Pakkanen, Mikko; Réveillac, Anthony

2016-01-01

and on the smallest component of the Hurst parameter vector of the fBs. The limiting process in the former result is another fBs, independent of the original fBs, whereas the limit given by the latter result is an Hermite sheet, which is driven by the same white noise as the original fBs. As an application, we derive...... functional limit theorems for power variations of the fBs and discuss what is a proper way to interpolate them to ensure functional convergence....

Study of gain variation as a function of physical parameters of GEM foil

CERN Document Server

Das, Supriya

2015-01-01

The ALICE experiment at LHC has planned to upgrade the TPC by replacing the MWPC with GEM based detecting elements to restrict the IBF to a tolerable value. However the variation of the gain as a function of physical parameters of industrially produced large size GEM foils is needed to be studied as a part of the QA procedure for the detector. The size of the electron avalanche and consequently the gain for GEM based detectors depend on the electric field distribution inside the holes. Geometry of a hole plays an important role in defining the electric field inside it. In this work we have studied the variation of the gain as a function of the hole diameters using Garfield++ simulation package.

Functional programming of the autonomic nervous system by early life immune exposure: implications for anxiety.

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Luba Sominsky

Full Text Available Neonatal exposure of rodents to an immune challenge alters a variety of behavioural and physiological parameters in adulthood. In particular, neonatal lipopolysaccharide (LPS; 0.05 mg/kg, i.p. exposure produces robust increases in anxiety-like behaviour, accompanied by persistent changes in hypothalamic-pituitary-adrenal (HPA axis functioning. Altered autonomic nervous system (ANS activity is an important physiological contributor to the generation of anxiety. Here we examined the long term effects of neonatal LPS exposure on ANS function and the associated changes in neuroendocrine and behavioural indices. ANS function in Wistar rats, neonatally treated with LPS, was assessed via analysis of tyrosine hydroxylase (TH in the adrenal glands on postnatal days (PNDs 50 and 85, and via plethysmographic assessment of adult respiratory rate in response to mild stress (acoustic and light stimuli. Expression of genes implicated in regulation of autonomic and endocrine activity in the relevant brain areas was also examined. Neonatal LPS exposure produced an increase in TH phosphorylation and activity at both PNDs 50 and 85. In adulthood, LPS-treated rats responded with increased respiratory rates to the lower intensities of stimuli, indicative of increased autonomic arousal. These changes were associated with increases in anxiety-like behaviours and HPA axis activity, alongside altered expression of the GABA-A receptor α2 subunit, CRH receptor type 1, CRH binding protein, and glucocorticoid receptor mRNA levels in the prefrontal cortex, hippocampus and hypothalamus. The current findings suggest that in addition to the commonly reported alterations in HPA axis functioning, neonatal LPS challenge is associated with a persistent change in ANS activity, associated with, and potentially contributing to, the anxiety-like phenotype. The findings of this study reflect the importance of changes in the perinatal microbial environment on the ontogeny of

Functional programming of the autonomic nervous system by early life immune exposure: implications for anxiety.

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Sominsky, Luba; Fuller, Erin A; Bondarenko, Evgeny; Ong, Lin Kooi; Averell, Lee; Nalivaiko, Eugene; Dunkley, Peter R; Dickson, Phillip W; Hodgson, Deborah M

2013-01-01

Neonatal exposure of rodents to an immune challenge alters a variety of behavioural and physiological parameters in adulthood. In particular, neonatal lipopolysaccharide (LPS; 0.05 mg/kg, i.p.) exposure produces robust increases in anxiety-like behaviour, accompanied by persistent changes in hypothalamic-pituitary-adrenal (HPA) axis functioning. Altered autonomic nervous system (ANS) activity is an important physiological contributor to the generation of anxiety. Here we examined the long term effects of neonatal LPS exposure on ANS function and the associated changes in neuroendocrine and behavioural indices. ANS function in Wistar rats, neonatally treated with LPS, was assessed via analysis of tyrosine hydroxylase (TH) in the adrenal glands on postnatal days (PNDs) 50 and 85, and via plethysmographic assessment of adult respiratory rate in response to mild stress (acoustic and light stimuli). Expression of genes implicated in regulation of autonomic and endocrine activity in the relevant brain areas was also examined. Neonatal LPS exposure produced an increase in TH phosphorylation and activity at both PNDs 50 and 85. In adulthood, LPS-treated rats responded with increased respiratory rates to the lower intensities of stimuli, indicative of increased autonomic arousal. These changes were associated with increases in anxiety-like behaviours and HPA axis activity, alongside altered expression of the GABA-A receptor α2 subunit, CRH receptor type 1, CRH binding protein, and glucocorticoid receptor mRNA levels in the prefrontal cortex, hippocampus and hypothalamus. The current findings suggest that in addition to the commonly reported alterations in HPA axis functioning, neonatal LPS challenge is associated with a persistent change in ANS activity, associated with, and potentially contributing to, the anxiety-like phenotype. The findings of this study reflect the importance of changes in the perinatal microbial environment on the ontogeny of physiological processes.

On Ostrowski Type Inequalities for Functions of Two Variables with Bounded Variation

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Hüseyin Budak

2016-10-01

Full Text Available In this paper, we establish a new generalization of Ostrowski type inequalities for functions of two independent variables with bounded variation and apply it for qubature formulae. Some connections with the rectangle, the midpoint and Simpson's rule are also given.

Effects of denial of reward through maternal contact in the neonatal period on adult hypothalamic-pituitary-adrenal axis function in the rat.

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Diamantopoulou, Anastasia; Raftogianni, Androniki; Stamatakis, Antonios; Oitzl, Melly S; Stylianopoulou, Fotini

2013-06-01

Emotional behavioral traits associated with stress response are well documented to be affected by early life events. In the present work, we used a novel paradigm of neonatal experience, in which pups were trained in a T-maze and either received (RER rats) or were denied (DER) the reward of maternal contact, during postnatal days 10-13. We then evaluated stress coping and key factors controlling the function of the hypothalamic-pituitary-adrenal axis in adulthood. Adult male DER rats exposed to a single session of forced swim stress (FSS) showed increased immobility, while RER rats exhibited increased escape attempts. The corticosterone response following this stressor was higher although not prolonged in the DER rats. Their CRH mRNA levels in the PVN were increased up to 2h after the forced swim. However, basal levels of these hormones did not differ among groups. In addition, the DER neonatal experience induced an increase in hippocampal GR but a decrease in CRH-R1 immunopositive cells in the CA1 area of the hippocampus and the central amygdala. Overall, these data show a distinct stress response profile in the DER male rats, characterized by passive coping during the forced swim, increased hormonal response following stress, increased inhibitory control through GR and an indirect contribution of CRH-R1, the latter two factors resulting in a modified regulation of the response termination. It thus appears that DER rats have an enhanced potential for appropriate reactivity upon an incoming challenge, while maintaining in parallel an adequate control of the duration of their stress responses. Copyright © 2012 Elsevier Ltd. All rights reserved.

On choice of trial functions in integro-differential variational principles of transport theory

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Loyalka, S.K.; Cipolla, J.W. Jr.

1988-01-01

In several problems of particle transport, quantities of macroscopic interest can be related to stationary values of variational functionals based on general integro-differential equations and boundary conditions. Within the context of the jump (Milne's) problem, it is shown how highly accurate results can be obtained by using trial functions based on the eigenfunctions of the relevant integrodifferential equations. Such choices of trial functions should apply equally effectively to problems in curved geometries, both internal and external

Environmental Drivers of Benthic Flux Variation and Ecosystem Functioning in Salish Sea and Northeast Pacific Sediments.

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Rénald Belley

Full Text Available The upwelling of deep waters from the oxygen minimum zone in the Northeast Pacific from the continental slope to the shelf and into the Salish Sea during spring and summer offers a unique opportunity to study ecosystem functioning in the form of benthic fluxes along natural gradients. Using the ROV ROPOS we collected sediment cores from 10 sites in May and July 2011, and September 2013 to perform shipboard incubations and flux measurements. Specifically, we measured benthic fluxes of oxygen and nutrients to evaluate potential environmental drivers of benthic flux variation and ecosystem functioning along natural gradients of temperature and bottom water dissolved oxygen concentrations. The range of temperature and dissolved oxygen encountered across our study sites allowed us to apply a suite of multivariate analyses rarely used in flux studies to identify bottom water temperature as the primary environmental driver of benthic flux variation and organic matter remineralization. Redundancy analysis revealed that bottom water characteristics (temperature and dissolved oxygen, quality of organic matter (chl a:phaeo and C:N ratios and sediment characteristics (mean grain size and porosity explained 51.5% of benthic flux variation. Multivariate analyses identified significant spatial and temporal variation in benthic fluxes, demonstrating key differences between the Northeast Pacific and Salish Sea. Moreover, Northeast Pacific slope fluxes were generally lower than shelf fluxes. Spatial and temporal variation in benthic fluxes in the Salish Sea were driven primarily by differences in temperature and quality of organic matter on the seafloor following phytoplankton blooms. These results demonstrate the utility of multivariate approaches in differentiating among potential drivers of seafloor ecosystem functioning, and indicate that current and future predictive models of organic matter remineralization and ecosystem functioning of soft-muddy shelf and

Community functional responses to soil and climate at multiple spatial scales: when does intraspecific variation matter?

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Andrew Siefert

Full Text Available Despite increasing evidence of the importance of intraspecific trait variation in plant communities, its role in community trait responses to environmental variation, particularly along broad-scale climatic gradients, is poorly understood. We analyzed functional trait variation among early-successional herbaceous plant communities (old fields across a 1200-km latitudinal extent in eastern North America, focusing on four traits: vegetative height, leaf area, specific leaf area (SLA, and leaf dry matter content (LDMC. We determined the contributions of species turnover and intraspecific variation to between-site functional dissimilarity at multiple spatial scales and community trait responses to edaphic and climatic factors. Among-site variation in community mean trait values and community trait responses to the environment were generated by a combination of species turnover and intraspecific variation, with species turnover making a greater contribution for all traits. The relative importance of intraspecific variation decreased with increasing geographic and environmental distance between sites for SLA and leaf area. Intraspecific variation was most important for responses of vegetative height and responses to edaphic compared to climatic factors. Individual species displayed strong trait responses to environmental factors in many cases, but these responses were highly variable among species and did not usually scale up to the community level. These findings provide new insights into the role of intraspecific trait variation in plant communities and the factors controlling its relative importance. The contribution of intraspecific variation to community trait responses was greatest at fine spatial scales and along edaphic gradients, while species turnover dominated at broad spatial scales and along climatic gradients.

Analysis of substructural variation in families of enzymatic proteins with applications to protein function prediction

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Fofanov Viacheslav Y

2010-05-01

Full Text Available Abstract Background Structural variations caused by a wide range of physico-chemical and biological sources directly influence the function of a protein. For enzymatic proteins, the structure and chemistry of the catalytic binding site residues can be loosely defined as a substructure of the protein. Comparative analysis of drug-receptor substructures across and within species has been used for lead evaluation. Substructure-level similarity between the binding sites of functionally similar proteins has also been used to identify instances of convergent evolution among proteins. In functionally homologous protein families, shared chemistry and geometry at catalytic sites provide a common, local point of comparison among proteins that may differ significantly at the sequence, fold, or domain topology levels. Results This paper describes two key results that can be used separately or in combination for protein function analysis. The Family-wise Analysis of SubStructural Templates (FASST method uses all-against-all substructure comparison to determine Substructural Clusters (SCs. SCs characterize the binding site substructural variation within a protein family. In this paper we focus on examples of automatically determined SCs that can be linked to phylogenetic distance between family members, segregation by conformation, and organization by homology among convergent protein lineages. The Motif Ensemble Statistical Hypothesis (MESH framework constructs a representative motif for each protein cluster among the SCs determined by FASST to build motif ensembles that are shown through a series of function prediction experiments to improve the function prediction power of existing motifs. Conclusions FASST contributes a critical feedback and assessment step to existing binding site substructure identification methods and can be used for the thorough investigation of structure-function relationships. The application of MESH allows for an automated

The corticotropin-releasing hormone network and the hypothalamic-pituitary-adrenal axis: molecular and cellular mechanisms involved.

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Bonfiglio, Juan José; Inda, Carolina; Refojo, Damián; Holsboer, Florian; Arzt, Eduardo; Silberstein, Susana

2011-01-01

Corticotropin-releasing hormone (CRH) plays a key role in adjusting the basal and stress-activated hypothalamic-pituitary-adrenal axis (HPA). CRH is also widely distributed in extrahypothalamic circuits, where it acts as a neuroregulator to integrate the complex neuroendocrine, autonomic, and behavioral adaptive response to stress. Hyperactive and/or dysregulated CRH circuits are involved in neuroendocrinological disturbances and stress-related mood disorders such as anxiety and depression. This review describes the main physiological features of the CRH network and summarizes recent relevant information concerning the molecular mechanism of CRH action obtained from signal transduction studies using cells and wild-type and transgenic mice lines. Special focus is placed on the MAPK signaling pathways triggered by CRH through the CRH receptor 1 that plays an essential role in CRH action in pituitary corticotrophs and in specific brain structures. Recent findings underpin the concept of specific CRH-signaling pathways restricted to specific anatomical areas. Understanding CRH action at molecular levels will not only provide insight into the precise CRH mechanism of action, but will also be instrumental in identifying novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders. Copyright © 2011 S. Karger AG, Basel.

Effects of functionally asexual reproduction on quantitative genetic variation in the evening primroses (Oenothera, Onagraceae).

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Godfrey, Ryan M; Johnson, Marc T J

2014-11-01

It has long been predicted that a loss of sexual reproduction leads to decreased heritable variation within populations and increased differentiation between populations. Despite an abundance of theory, there are few empirical tests of how sex affects genetic variation in phenotypic traits, especially for plants. Here we test whether repeated losses of two critical components of sex (recombination and segregation) in the evening primroses (Oenothera L., Onagraceae) affect quantitative genetic variation within and between populations. We sampled multiple genetic families from 3-5 populations from each of eight Oenothera species, which represented four independent transitions between sexual reproduction and a functionally asexual genetic system called "permanent translocation heterozygosity." We used quantitative genetics methods to partition genetic variation within and between populations for eight plant traits related to growth, leaf physiology, flowering, and resistance to herbivores. Heritability was, on average, 74% higher in sexual Oenothera populations than in functionally asexual populations, with plant growth rate, specific leaf area, and the percentage of leaf water content showing the strongest differences. By contrast, genetic differentiation among populations was 2.8× higher in functionally asexual vs. sexual Oenothera species. This difference was particularly strong for specific leaf area. Sexual populations tended to exhibit higher genetic correlations among traits, but this difference was weakly supported. These results support the prediction that sexual reproduction maintains higher genetic variation within populations, which may facilitate adaptive evolution. We also found partial support for the prediction that a loss of sex leads to greater population differentiation, which may elevate speciation rates. © 2014 Botanical Society of America, Inc.

Variation in Differential and Total Cross Sections Due to Different Radial Wave Functions

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Williamson, W., Jr.; Greene, T.

1976-01-01

Three sets of analytical wave functions are used to calculate the Na (3s---3p) transition differential and total electron excitation cross sections by Born approximations. Results show expected large variations in values. (Author/CP)

Variational second-order Moller-Plesset theory based on the Luttinger-Ward functional

NARCIS (Netherlands)

Dahlen, NE; von Barth, U

2004-01-01

In recent years there have been some rather successful applications of a new variational technique for calculating the total energies of electronic systems. The new method is based on many-body perturbation theory and uses the one-electron Green function as the basic "variable" rather than the wave

Genetic Variation in Functional Traits Influences Arthropod Community Composition in Aspen (Populus tremula L.)

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Robinson, Kathryn M.; Ingvarsson, Pär K.; Jansson, Stefan; Albrectsen, Benedicte R.

2012-01-01

We conducted a study of natural variation in functional leaf traits and herbivory in 116 clones of European aspen, Populus tremula L., the Swedish Aspen (SwAsp) collection, originating from ten degrees of latitude across Sweden and grown in a common garden. In surveys of phytophagous arthropods over two years, we found the aspen canopy supports nearly 100 morphospecies. We identified significant broad-sense heritability of plant functional traits, basic plant defence chemistry, and arthropod community traits. The majority of arthropods were specialists, those coevolved with P. tremula to tolerate and even utilize leaf defence compounds. Arthropod abundance and richness were more closely related to plant growth rates than general chemical defences and relationships were identified between the arthropod community and stem growth, leaf and petiole morphology, anthocyanins, and condensed tannins. Heritable genetic variation in plant traits in young aspen was found to structure arthropod community; however no single trait drives the preferences of arthropod folivores among young aspen genotypes. The influence of natural variation in plant traits on the arthropod community indicates the importance of maintaining genetic variation in wild trees as keystone species for biodiversity. It further suggests that aspen can be a resource for the study of mechanisms of natural resistance to herbivores. PMID:22662190

Genetic variation in functional traits influences arthropod community composition in aspen (Populus tremula L..

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Kathryn M Robinson

Full Text Available We conducted a study of natural variation in functional leaf traits and herbivory in 116 clones of European aspen, Populus tremula L., the Swedish Aspen (SwAsp collection, originating from ten degrees of latitude across Sweden and grown in a common garden. In surveys of phytophagous arthropods over two years, we found the aspen canopy supports nearly 100 morphospecies. We identified significant broad-sense heritability of plant functional traits, basic plant defence chemistry, and arthropod community traits. The majority of arthropods were specialists, those coevolved with P. tremula to tolerate and even utilize leaf defence compounds. Arthropod abundance and richness were more closely related to plant growth rates than general chemical defences and relationships were identified between the arthropod community and stem growth, leaf and petiole morphology, anthocyanins, and condensed tannins. Heritable genetic variation in plant traits in young aspen was found to structure arthropod community; however no single trait drives the preferences of arthropod folivores among young aspen genotypes. The influence of natural variation in plant traits on the arthropod community indicates the importance of maintaining genetic variation in wild trees as keystone species for biodiversity. It further suggests that aspen can be a resource for the study of mechanisms of natural resistance to herbivores.

Disrupted-in-Schizophrenia-1 is essential for normal hypothalamic-pituitary-interrenal (HPI) axis function.

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Eachus, Helen; Bright, Charlotte; Cunliffe, Vincent T; Placzek, Marysia; Wood, Jonathan D; Watt, Penelope J

2017-06-01

Psychiatric disorders arise due to an interplay of genetic and environmental factors, including stress. Studies in rodents have shown that mutants for Disrupted-In-Schizophrenia-1 (DISC1), a well-accepted genetic risk factor for mental illness, display abnormal behaviours in response to stress, but the mechanisms through which DISC1 affects stress responses remain poorly understood. Using two lines of zebrafish homozygous mutant for disc1, we investigated behaviour and functioning of the hypothalamic-pituitary-interrenal (HPI) axis, the fish equivalent of the hypothalamic-pituitary-adrenal (HPA) axis. Here, we show that the role of DISC1 in stress responses is evolutionarily conserved and that DISC1 is essential for normal functioning of the HPI axis. Adult zebrafish homozygous mutant for disc1 show aberrant behavioural responses to stress. Our studies reveal that in the embryo, disc1 is expressed in neural progenitor cells of the hypothalamus, a conserved region of the vertebrate brain that centrally controls responses to environmental stressors. In disc1 mutant embryos, proliferating rx3+ hypothalamic progenitors are not maintained normally and neuronal differentiation is compromised: rx3-derived ff1b+ neurons, implicated in anxiety-related behaviours, and corticotrophin releasing hormone (crh) neurons, key regulators of the stress axis, develop abnormally, and rx3-derived pomc+ neurons are disorganised. Abnormal hypothalamic development is associated with dysfunctional behavioural and neuroendocrine stress responses. In contrast to wild type siblings, disc1 mutant larvae show altered crh levels, fail to upregulate cortisol levels when under stress and do not modulate shoal cohesion, indicative of abnormal social behaviour. These data indicate that disc1 is essential for normal development of the hypothalamus and for the correct functioning of the HPA/HPI axis. © The Author 2017. Published by Oxford University Press.

Antidepressant-Like Effects of Shuyusan in Rats Exposed to Chronic Stress: Effects on Hypothalamic-Pituitary-Adrenal Function

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Liping Chen

2012-01-01

Full Text Available This study was to investigate antidepressant activities of Shuyusan (a Chinese herb, using a rats model of depression induced by unpredictable chronic mild stress (UCMS. The administration groups were treated with Shuyusan decoction for 3 weeks and compared with fluoxetine treatment. In order to understand the potential antidepressant-like activities of Shuyusan, tail suspension test (TST and forced swimming test (FST were used as behavioral despair study. The level of corticotropin-releasing factor (CRH, adrenocorticotropic hormone (ACTH, corticosterone (CORT and hippocampus glucocorticoid receptor expression were examined. After modeling, there was a significant prolongation of immobility time in administration groups with the TST and FST. High-dose Shuyusan could reduce the immobility time measured with the TST and FST. The immobility time in high-dose herbs group and fluoxetine group was increased significantly compared with the model group. After 3 weeks herbs fed, the serum contents level of CRH, ACTH, and CORT in high-dose herb group was significantly decreased compared to the model group. The result indicated that Shuyusan had antidepressant activity effects on UCMS model rats. The potential antidepressant effect may be related to decreasing glucocorticoid levels activity, regulating the function of HPA axis, and inhibiting glucocorticoid receptor expression in hippocampus.

Mapping the human corticotropin releasing hormone binding protein gene (CRHBP) to the long arm of chromosome 5 (5q11.2-q13.3)

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Vamvakopoulos, N.C. [Univ. of Thessaly School of Medicine, Larisa (Greece); Sioutopoulou, T.O. [Univ. of Athens Medical School (Greece); Durkin, S.A. [American Type Culture Collection, Rockville, MD (United States)

1995-01-01

Unexpected stimulation or stress activates the heat shock protein (hsp) system at the cellular level and the hypothalamic-pituitary-adrenal (HPA) axis at the level of the whole organism. At the molecular level, these two systems communicate through the functional interaction between hsp90 and glucocorticoid receptor (GR). The corticotropin releasing hormone (CRH) system regulates the mammalian stress response by coordinating the activity of the HPA axis. It consists of the 41-amino-acid-long principal hypothalamic secretagogue for pituitary adrenocorticotropic hormone (ACTH), CRH, its receptor (CRHR), and its binding protein (CRHBP). Because of its central role in the coordination of stress response and whole body homeostasis, the CRH system has been implicated in the pathogenesis of neuroendocrine and psychiatric disease. 19 refs., 1 fig.

Electronic structure of homoleptic transition metal hydrides: TiH4, VH4, CrH4, MnH4, FeH4, CoH4, and NiH4

International Nuclear Information System (INIS)

Hood, D.M.; Pitzer, R.M.; Schaefer III, H.F.

1979-01-01

Ab initio molecular electronic structure theory has been applied to the family of transition metal tetrahydrides TiH 4 through NiH 4 . For the TiH 4 molecule a wide range of contracted Gaussian basis sets has been tested at the self-consistent-field (SCF) level of theory. The largest basis, labeled M(14s 11p 6d/10s 8p 3d), H(5s 1p/3s 1p), was used for all members of the series and should yield wave functions approaching true Hartree-Fock quality. Predicted SCF dissociation energies (relative to M+4H) and M--H bond distances are TiH 4 132 kcal, 1.70 A; VH 4 86 kcal, 1.64 A; CrH 4 65 kcal, 1.59 A; MnH 4 -- 36 kcal, 1.58 A; FeH 4 0 kcal, 1.58 A; CoH 4 27 kcal, 1.61 A; and NiH 4 18 kcal, 1.75 A. It should be noted immediately that each of these SCF dissociation energies will be increased by electron correlation effects by perhaps as much as 90 kcal. For all of these molecules except TiH 4 excited states have also been studied. One of the most interesting trends seen for these excited states is the shortening of the M--H bond as electrons are transferred from the antibonding 4t 2 orbital to the nonbonding 1e orbitals

Worldwide variation in within-canopy photosynthetic acclimation: differences in temporal and environmental controls among plant functional types

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Niinemets, Ülo; Keenan, Trevor

2017-04-01

Major light gradients, characteristically 10- to 50-fold, constitute the most prominent feature of plant canopies. These gradients drive within-canopy variation in foliage structural, chemical and physiological traits. As a key acclimation response to variation in light availability, foliage photosynthetic capacity per area (Aarea) increases with increasing light availability within the canopy, maximizing whole canopy photosynthesis. Recently, a worldwide database including 831 within-canopy gradients with standardized light estimates for 304 species belonging to major vascular plant functional types was constructed and within-canopy variation in photosynthetic acclimation was characterized (Niinemets Ü, Keenan TF, Hallik L (2015) Tansley review. A worldwide analysis of within-canopy variations in leaf structural, chemical and physiological traits across plant functional types. The New Phytologist 205: 973-993). However, the understanding of how within-canopy photosynthetic gradients vary during the growing season and in response to site and stand characteristics is still limited. Here we analyzed temporal, environmental and site (nutrient availability, stand density, ambient CO2 concentration, water availability) sources of variation in within-canopy photosynthetic acclimation in different plant functional types. Variation in key structural (leaf dry mass per unit area, MA), chemical (nitrogen content per dry mass, NM, and area, NA) and physiological (photosynthetic nitrogen use efficiency, EN) photosynthetic capacity per dry mass, Amass and area, Aarea) was examined. The analysis demonstrates major, typically 1.5-2-fold, time-, environment and site-dependent modifications in within-canopy variation in foliage photosynthetic capacity. However, the magnitude and direction of temporal and environmental variations in plasticity significantly varied among functional types. Species with longer leaf life span and low rates of canopy expansion or flush-type canopy

Variational Iteration Method for Volterra Functional Integrodifferential Equations with Vanishing Linear Delays

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Ali Konuralp

2014-01-01

Full Text Available Application process of variational iteration method is presented in order to solve the Volterra functional integrodifferential equations which have multi terms and vanishing delays where the delay function θ(t vanishes inside the integral limits such that θ(t=qt for 0

Coherent molecular transistor: control through variation of the gate wave function.

Science.gov (United States)

Ernzerhof, Matthias

2014-03-21

In quantum interference transistors (QUITs), the current through the device is controlled by variation of the gate component of the wave function that interferes with the wave function component joining the source and the sink. Initially, mesoscopic QUITs have been studied and more recently, QUITs at the molecular scale have been proposed and implemented. Typically, in these devices the gate lead is subjected to externally adjustable physical parameters that permit interference control through modifications of the gate wave function. Here, we present an alternative model of a molecular QUIT in which the gate wave function is directly considered as a variable and the transistor operation is discussed in terms of this variable. This implies that we specify the gate current as well as the phase of the gate wave function component and calculate the resulting current through the source-sink channel. Thus, we extend on prior works that focus on the phase of the gate wave function component as a control parameter while having zero or certain discrete values of the current. We address a large class of systems, including finite graphene flakes, and obtain analytic solutions for how the gate wave function controls the transistor.

Coherent molecular transistor: Control through variation of the gate wave function

International Nuclear Information System (INIS)

Ernzerhof, Matthias

2014-01-01

In quantum interference transistors (QUITs), the current through the device is controlled by variation of the gate component of the wave function that interferes with the wave function component joining the source and the sink. Initially, mesoscopic QUITs have been studied and more recently, QUITs at the molecular scale have been proposed and implemented. Typically, in these devices the gate lead is subjected to externally adjustable physical parameters that permit interference control through modifications of the gate wave function. Here, we present an alternative model of a molecular QUIT in which the gate wave function is directly considered as a variable and the transistor operation is discussed in terms of this variable. This implies that we specify the gate current as well as the phase of the gate wave function component and calculate the resulting current through the source-sink channel. Thus, we extend on prior works that focus on the phase of the gate wave function component as a control parameter while having zero or certain discrete values of the current. We address a large class of systems, including finite graphene flakes, and obtain analytic solutions for how the gate wave function controls the transistor

Neurogenetics of aggressive behavior: studies in primates.

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Barr, Christina S; Driscoll, Carlos

2014-01-01

Aggressive behavior can have adaptive value in certain environmental contexts, but when extreme or executed inappropriately, can also lead to maladaptive outcomes. Neurogenetic studies performed in nonhuman primates have shown that genetic variation that impacts reward sensitivity, impulsivity, and anxiety can contribute to individual differences in aggressive behavior. Genetic polymorphisms in the coding or promoter regions of the Mu-Opioid Receptor (OPRM1), Corticotropin Releasing Hormone (CRH), Monoamine Oxidase A (MAOA), Dopamine D4 Receptor (DRD4), and Serotonin Transporter (SLC6A4) genes have been shown to be functionally similar in humans and rhesus macaques and have been demonstrated to contribute to individual differences in aggression. This body of literature suggests mechanisms by which genetic variation that promotes aggressivity could simultaneously increase evolutionary success while making modern humans more vulnerable to psychopathology.

A longitudinal study of disturbances of the hypothalamic-pituitary-adrenal axis in women with progestin-negative functional hypothalamic amenorrhea.

Science.gov (United States)

Kondoh, Y; Uemura, T; Murase, M; Yokoi, N; Ishikawa, M; Hirahara, F

2001-10-01

To longitudinally evaluate disturbances of the hypothalamic-pituitary-adrenal (HPA) axis in women with secondary progestin-negative hypothalamic amenorrhea. Retrospective cohort study. Yokohama City University, Yokohama, Japan. Twenty-four women with progestin-negative hypothalamic amenorrhea. Administration of human corticotropin-releasing hormone (hCRH) and treatment with a combination of estrogen and progesterone. Plasma cortisol and ACTH concentrations and period required for recovery from amenorrhea. Plasma ACTH concentrations 30 and 60 minutes after injection of hCRH and the percent maximum increment (%Cmax) of ACTH were significantly lower in the amenorrheic patients compared with the control group patients. The basal cortisol was significantly higher, and the %Cmax of cortisol was significantly lower. In the 16 patients who recovered from amenorrhea, there was a significant positive correlation (Y = 1.93X-10.8, r = 0.629) between the basal cortisol concentrations (X) and the period for recovery (Y). The serum E2 gradually increased before recovery, and this E2 increase was preceded by changes in the plasma cortisol concentration and the %Cmax values of cortisol and ACTH. The CRH test might be useful for evaluating the roles of stress and for estimating the period required for recovery in hypothalamic amenorrhea.

Experimental hyperthyroidism and central mediators of stress axis and thyroid axis activity in common carp (Cyprinus carpio L.).

Science.gov (United States)

Geven, Edwin J W; Verkaar, Folkert; Flik, Gert; Klaren, Peter H M

2006-12-01

The effect of experimental hyperthyroidism, realized by T(4) injection, on central mediators of the hypothalamo-pituitary-interrenal axis (HPI-axis) in common carp (Cyprinus carpio L.) was studied. Our results show that hyperthyroidism evokes a marked 3.2-fold reduction in basal plasma cortisol levels. Corticotropin-releasing hormone-binding protein (CRH-BP) mRNA levels in the hypothalamus, measured by real-time quantitative PCR, were significantly elevated by 40%, but CRH, urotensin-I, prepro-TRH, prohormone convertase-1 (PC1), and POMC mRNA levels were unchanged. In the pituitary pars distalis, PC1, CRH receptor-1, and POMC mRNA levels were unaffected, as was ACTH content. Plasma alpha-MSH concentrations were significantly elevated by 30% in hyperthyroid fish, and this was reflected in PC1 and POMC mRNA levels in pituitary pars intermedia that were increased 1.5- and 2.4-fold respectively. The alpha-MSH content of the pars intermedia was unchanged. Hyperthyroidism has profound effects on the basal levels of a central mediator, i.e., CRH-BP, of HPI-axis function in unstressed carp in vivo, and we conclude that HPI- and hypothalamo-pituitary-thyroid-axis functions are strongly interrelated. We suggest that the changes in plasma cortisol, thyroid hormone, and alpha-MSH levels reflect their concerted actions on energy metabolism.

Qualitative and quantitative estimations of the effect of geomagnetic field variations on human brain functional state

International Nuclear Information System (INIS)

Belisheva, N.K.; Popov, A.N.; Petukhova, N.V.; Pavlova, L.P.; Osipov, K.S.; Tkachenko, S.Eh.; Baranova, T.I.

1995-01-01

The comparison of functional dynamics of human brain with reference to qualitative and quantitative characteristics of local geomagnetic field (GMF) variations was conducted. Steady and unsteady states of human brain can be determined: by geomagnetic disturbances before the observation period; by structure and doses of GMF variations; by different combinations of qualitative and quantitative characteristics of GMF variations. Decrease of optimal GMF activity level and the appearance of aperiodic disturbances of GMF can be a reason of unsteady brain's state. 18 refs.; 3 figs

Floristic-functional variation of tree component along an altitudinal gradient in araucaria forest areas, in Southern Brazil.

Science.gov (United States)

Soboleski, Vanessa F; Higuchi, Pedro; Silva, Ana Carolina DA; Silva, Mariele A F DA; Nunes, Amanda S; Loebens, Rodineli; Souza, Karine DE; Ferrari, Jheniffer; Lima, Carla L; Kilca, Ricardo V

2017-01-01

We aimed to investigate the taxonomic and functional variations of tree component of Araucaria Forest (AF) areas located along an altitudinal gradient (700, 900 and 1,600 m asl), in the southern region of Brazil. The functional traits determined were leaf area, specific leaf area, wood density, maximum potential height and dispersal syndromes and deciduousness. The data were analyzed through a functional and taxonomic dissimilarity dendrograms, community-weighted mean trait values, parametric and nonparametric tests, and Principal Component Analysis. The largest floristic-structural similarity was observed between the lower altitude areas (700 and 900 m asl), whose Bray-Curtis distance was 0.63. The area at 700 m asl was characterized by a predominance of deciduous and semi-deciduous species, with a high number of self- and wind-dispersed species, whereas the area at 1,600 m asl exhibited a predominance of animal-dispersed and evergreen species. It was also observed that there were significant variations for leaf traits, basic wood density and maximum potential height. Over all altitudinal gradient, the ordinations indicated that there was no evidence of functional differentiation among dispersal and deciduousness groups. In conclusion, the evaluated Araucaria Forest areas presented high floristic-functional variation of the tree component along the altitudinal gradient.

Variational principles for locally variational forms

International Nuclear Information System (INIS)

Brajercik, J.; Krupka, D.

2005-01-01

We present the theory of higher order local variational principles in fibered manifolds, in which the fundamental global concept is a locally variational dynamical form. Any two Lepage forms, defining a local variational principle for this form, differ on intersection of their domains, by a variationally trivial form. In this sense, but in a different geometric setting, the local variational principles satisfy analogous properties as the variational functionals of the Chern-Simons type. The resulting theory of extremals and symmetries extends the first order theories of the Lagrange-Souriau form, presented by Grigore and Popp, and closed equivalents of the first order Euler-Lagrange forms of Hakova and Krupkova. Conceptually, our approach differs from Prieto, who uses the Poincare-Cartan forms, which do not have higher order global analogues

Estradiol-Dependent Stimulation and Suppression of Gonadotropin-Releasing Hormone Neuron Firing Activity by Corticotropin-Releasing Hormone in Female Mice.

Science.gov (United States)

Phumsatitpong, Chayarndorn; Moenter, Suzanne M

2018-01-01

Gonadotropin-releasing hormone (GnRH) neurons are the final central regulators of reproduction, integrating various inputs that modulate fertility. Stress typically inhibits reproduction but can be stimulatory; stress effects can also be modulated by steroid milieu. Corticotropin-releasing hormone (CRH) released during the stress response may suppress reproduction independent of downstream glucocorticoids. We hypothesized CRH suppresses fertility by decreasing GnRH neuron firing activity. To test this, mice were ovariectomized (OVX) and either implanted with an estradiol capsule (OVX+E) or not treated further to examine the influence of estradiol on GnRH neuron response to CRH. Targeted extracellular recordings were used to record firing activity from green fluorescent protein-identified GnRH neurons in brain slices before and during CRH treatment; recordings were done in the afternoon when estradiol has a positive feedback effect to increase GnRH neuron firing. In OVX mice, CRH did not affect the firing rate of GnRH neurons. In contrast, CRH exhibited dose-dependent stimulatory (30 nM) or inhibitory (100 nM) effects on GnRH neuron firing activity in OVX+E mice; both effects were reversible. The dose-dependent effects of CRH appear to result from activation of different receptor populations; a CRH receptor type-1 agonist increased firing activity in GnRH neurons, whereas a CRH receptor type-2 agonist decreased firing activity. CRH and specific agonists also differentially regulated short-term burst frequency and burst properties, including burst duration, spikes/burst, and/or intraburst interval. These results indicate that CRH alters GnRH neuron activity and that estradiol is required for CRH to exert both stimulatory and inhibitory effects on GnRH neurons. Copyright © 2018 Endocrine Society.

Casscf/ci Calculations for First Row Transition Metal Hydrides - the TIH(4-PHI), VH(5-DELTA), CRH(6-SIGMA-PLUS), MNH(7-SIGMA-PLUS), FEH(4,6-DELTA) and NIH(2-DELTA) States

Science.gov (United States)

Walch, S. P.; Bauschlicher, C. W., Jr.

1983-04-01

Calculations are performed for the predicted ground states of TiH(4-phi), VH(5-delta), CrH(6-sigma-plus), MnH(7-sigma-plus), Fett(4,6-delta) and NiH(2-delta). For FeH both the 6-delta and 4-delta states are studied, since both are likely candidates for the ground state. The ground state symmetries are predicted based on a combination of atomic coupling arguments and coupling of 4s(2)3d(n) and 4s(1)3d(n+1) terms in the molecular system. Electron correlation is included by a CASSCF/CI (SD) treatment. The CASSCF includes near-degeneracy effects, while correlation of the 3d electrons in included at the CI level.

Glucocorticoid stimulates expression of corticotropin-releasing hormone gene in human placenta

International Nuclear Information System (INIS)

Robinson, B.G.; Emanuel, R.L.; Frim, D.M.; Majzoub, J.A.

1988-01-01

Primary cultures of purified human cytotrophoblasts have been used to examine the expression of the corticotropin-releasing hormone (CRH) gene in placenta. The authors report here that glucocorticoids stimulate placental CRH synthesis and secretion in primary cultures of human placenta. This stimulation is in contrast to the glucocorticoid suppression of CRH expression in hypothalamus. The positive regulation of CRH by glucocorticoids suggests that the rise in CRH preceding parturition could result from the previously described rise in fetal glucocorticoids. Furthermore, this increase in placental CRH could stimulate, via adrenocorticotropic hormone, a further rise in fetal glucocorticoids, completing a positive feedback loop that would be terminated by delivery

Corticotropin-releasing hormone: Mediator of vertebrate life stage transitions?

Science.gov (United States)

Watanabe, Yugo; Grommen, Sylvia V H; De Groef, Bert

2016-03-01

Hormones, particularly thyroid hormones and corticosteroids, play critical roles in vertebrate life stage transitions such as amphibian metamorphosis, hatching in precocial birds, and smoltification in salmonids. Since they synergistically regulate several metabolic and developmental processes that accompany vertebrate life stage transitions, the existence of extensive cross-communication between the adrenal/interrenal and thyroidal axes is not surprising. Synergies of corticosteroids and thyroid hormones are based on effects at the level of tissue hormone sensitivity and gene regulation. In addition, in representative nonmammalian vertebrates, corticotropin-releasing hormone (CRH) stimulates hypophyseal thyrotropin secretion, and thus functions as a common regulator of both the adrenal/interrenal and thyroidal axes to release corticosteroids and thyroid hormones. The dual function of CRH has been speculated to control or affect the timing of vertebrate life history transitions across taxa. After a brief overview of recent insights in the molecular mechanisms behind the synergic actions of thyroid hormones and corticosteroids during life stage transitions, this review examines the evidence for a possible role of CRH in controlling vertebrate life stage transitions. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional SOCS1 polymorphisms are associated with variation in obesity in whites

DEFF Research Database (Denmark)

Gylvin, T; Ek, J; Nolsøe, R.

2009-01-01

. A total of more than 8100 individuals were genotyped. RESULTS: Eight variations were identified in the 5' untranslated region (UTR) region. Two of these had allele frequencies below 1% and were not further examined. The six other variants were analysed in groups of T1D families (n = 1461 subjects) and T2D...... of both the rs33977706 and the rs243330 (-1656G > A) variants to obesity were found (p = 0.047 and p = 0.015) respectively. The rs33977706 affected both binding of a nuclear protein to and the transcriptional activity of the SOCS1 promoter, indicating a relationship between this polymorphism and gene...... regulation. CONCLUSIONS/INTERPRETATION: This study demonstrates that functional variations in the SOCS1 promoter may associate with alterations in BMI in the general white population....

Converging, Synergistic Actions of Multiple Stress Hormones Mediate Enduring Memory Impairments after Acute Simultaneous Stresses.

Science.gov (United States)

Chen, Yuncai; Molet, Jenny; Lauterborn, Julie C; Trieu, Brian H; Bolton, Jessica L; Patterson, Katelin P; Gall, Christine M; Lynch, Gary; Baram, Tallie Z

2016-11-02

Stress influences memory, an adaptive process crucial for survival. During stress, hippocampal synapses are bathed in a mixture of stress-released molecules, yet it is unknown whether or how these interact to mediate the effects of stress on memory. Here, we demonstrate novel synergistic actions of corticosterone and corticotropin-releasing hormone (CRH) on synaptic physiology and dendritic spine structure that mediate the profound effects of acute concurrent stresses on memory. Spatial memory in mice was impaired enduringly after acute concurrent stresses resulting from loss of synaptic potentiation associated with disrupted structure of synapse-bearing dendritic spines. Combined application of the stress hormones corticosterone and CRH recapitulated the physiological and structural defects provoked by acute stresses. Mechanistically, corticosterone and CRH, via their cognate receptors, acted synergistically on the spine-actin regulator RhoA, promoting its deactivation and degradation, respectively, and destabilizing spines. Accordingly, blocking the receptors of both hormones, but not each alone, rescued memory. Therefore, the synergistic actions of corticosterone and CRH at hippocampal synapses underlie memory impairments after concurrent and perhaps also single, severe acute stresses, with potential implications to spatial memory dysfunction in, for example, posttraumatic stress disorder. Stress influences memory, an adaptive process crucial for survival. During stress, adrenal corticosterone and hippocampal corticotropin-releasing hormone (CRH) permeate memory-forming hippocampal synapses, yet it is unknown whether (and how) these hormones interact to mediate effects of stress. Here, we demonstrate novel synergistic actions of corticosterone and CRH on hippocampal synaptic plasticity and spine structure that mediate the memory-disrupting effects of stress. Combined application of both hormones provoked synaptic function collapse and spine disruption

Anxiety/aggression--driven depression. A paradigm of functionalization and verticalization of psychiatric diagnosis.

Science.gov (United States)

Van Praag, H M

2001-05-01

A new subtype of depression is proposed, named: anxiety/aggression-driven depression. The psychopathological, psychopharmacological and biochemical evidence on which this construct is based, is being discussed. Selective postsynaptic 5-HT1A agonists together with CRH and/or cortisol antagonists are hypothesized to be a specific biological treatment for this depression type, in conjunction with psychological interventions to raise the stressor-threshold and to increase coping skills. The development of this depression construct has been contingent on the introduction of two new diagnostic procedures, called functionalization and verticalization of psychiatric diagnosis. These procedures are explained and it is stressed that they are essential to psychiatric diagnosing, in order to put this process on a scientific footing.

Noise stress changes mRNA expressions of corticotropin-releasing hormone, its receptors in amygdala, and anxiety-related behaviors

Directory of Open Access Journals (Sweden)

Evren Eraslan

2015-01-01

Full Text Available Noise is a psychological, environmental stressor that activates limbic sites in the brain. Limbic sites such as the amygdala and the amygdaloid corticotropin-releasing hormone (CRH system play an important role in integrating stress response. We investigated the association between noise exposures, CRH-related molecules in the amygdala, and behavioral alterations. In total 54 Sprague-Dawley rats were divided into the following three groups: Control (CON, acute noise exposure (ANE, and chronic noise exposure (CNE. The ANE group was exposed to 100 dB white noise only once in 4 h and the CNE group was exposed to the same for 4 h per day for 30 days. Expression profiles of CRH and its receptors CRH-R1 and CRH-R2 were analyzed by quantitative real-time polymerase chain reaction (qPCR. The same stress procedure was applied to the ANE and CNE groups for behavior testing. The anxiety responses of the animals after acute and chronic stress exposure were measured in the defensive withdrawal test. CNE upregulated CRH and CRH-R1 mRNA levels but downregulated CRH-R2 mRNA levels. ANE led to a decrease in both CRH-R1 and CRH-R2 expression. In the defensive withdrawal test, while the ANE increased, CNE reduced anxiety-like behaviors. The present study shows that the exposure of rats to white noise (100 dB leads to behavioral alterations and molecule-specific changes in the CRH system. Behavioral alterations can be related to these molecular changes in the amygdala.

Noise stress changes mRNA expressions of corticotropin-releasing hormone, its receptors in amygdala, and anxiety-related behaviors.

Science.gov (United States)

Eraslan, Evren; Akyazi, Ibrahim; Erg L-Ekiz, Elif; Matur, Erdal

2015-01-01

Noise is a psychological, environmental stressor that activates limbic sites in the brain. Limbic sites such as the amygdala and the amygdaloid corticotropin-releasing hormone (CRH) system play an important role in integrating stress response. We investigated the association between noise exposures, CRH-related molecules in the amygdala, and behavioral alterations. In total 54 Sprague-Dawley rats were divided into the following three groups: Control (CON), acute noise exposure (ANE), and chronic noise exposure (CNE). The ANE group was exposed to 100 dB white noise only once in 4 h and the CNE group was exposed to the same for 4 h per day for 30 days. Expression profiles of CRH and its receptors CRH-R1 and CRH-R2 were analyzed by quantitative real-time polymerase chain reaction (qPCR). The same stress procedure was applied to the ANE and CNE groups for behavior testing. The anxiety responses of the animals after acute and chronic stress exposure were measured in the defensive withdrawal test. CNE upregulated CRH and CRH-R1 mRNA levels but downregulated CRH-R2 mRNA levels. ANE led to a decrease in both CRH-R1 and CRH-R2 expression. In the defensive withdrawal test, while the ANE increased, CNE reduced anxiety-like behaviors. The present study shows that the exposure of rats to white noise (100 dB) leads to behavioral alterations and molecule-specific changes in the CRH system. Behavioral alterations can be related to these molecular changes in the amygdala.

Stress responsiveness of the hypothalamic-pituitary-adrenal axis: age-related features of the vasopressinergic regulation

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Nadezhda Dmitrievna Goncharova

2013-03-01

Full Text Available The hypothalamic-pituitary-adrenal (HPA axis plays a key role in adaptation to environmental stresses. Parvicellular neurons of the hypothalamic paraventricular nucleus secrete corticotrophin releasing hormone (CRH and arginine vasopressin (AVP into pituitary portal system; CRH and AVP stimulate ACTH release through specific G protein-coupled membrane receptors on pituitary corticotrophs, CRH1 for CRH and V1b for AVP; the adrenal gland cortex secretes glucocorticoids in response ACTH. The glucocorticoids activate specific receptors in brain and peripheral tissues thereby triggering the necessary metabolic, immune, neuromodulatory and behavioral changes to resist stress. While importance of CRH, as a key hypothalamic factor of HPA axis regulation in basal and stress conditions in most species, is generally recognized, role of AVP remains to be clarified. This review focuses on the role of AVP in the regulation of stress responsiveness of the HPA axis with emphasis on the effects of aging on vasopressinergic regulation of HPA axis stress responsiveness. Under most of the known stressors, AVP is necessary for acute ACTH secretion but in a context-specific manner. The current data on the AVP role in regulation of HPA responsiveness to chronic stress in adulthood are rather contradictory. The importance of the vasopressinergic regulation of the HPA stress responsiveness is greatest during fetal development, in neonatal period, and in the lactating adult. Aging associated with increased variability in several parameters of HPA function including basal state, responsiveness to stressors, and special testing. Reports on the possible role of the AVP/V1b receptor system in the increase of HPA axis hyperactivity with aging are contradictory and requires further research. Many contradictory results may be due to age and species differences in the HPA function of rodents and primates.

Vascular endothelial overexpression of human CYP2J2 (Tie2-CYP2J2 Tr) modulates cardiac oxylipin profiles and enhances coronary reactive hyperemia in mice

Science.gov (United States)

Hanif, Ahmad; Edin, Matthew L.; Zeldin, Darryl C.; Morisseau, Christophe; Falck, John R.

2017-01-01

Arachidonic acid is metabolized to epoxyeicosatrienoic acids (EETs) by cytochrome (CYP) P450 epoxygenases, and to ω-terminal hydroxyeicosatetraenoic acids (HETEs) by ω-hydroxylases. EETs and HETEs often have opposite biologic effects; EETs are vasodilatory and protect against ischemia/reperfusion injury, while ω-terminal HETEs are vasoconstrictive and cause vascular dysfunction. Other oxylipins, such as epoxyoctadecaenoic acids (EpOMEs), hydroxyoctadecadienoic acids (HODEs), and prostanoids also have varied vascular effects. Post-ischemic vasodilation in the heart, known as coronary reactive hyperemia (CRH), protects against potential damage to the heart muscle caused by ischemia. The relationship among CRH response to ischemia, in mice with altered levels of CYP2J epoxygenases has not yet been investigated. Therefore, we evaluated the effect of endothelial overexpression of the human cytochrome P450 epoxygenase CYP2J2 in mice (Tie2-CYP2J2 Tr) on oxylipin profiles and CRH. Additionally, we evaluated the effect of pharmacologic inhibition of CYP-epoxygenases and inhibition of ω-hydroxylases on CRH. We hypothesized that CRH would be enhanced in isolated mouse hearts with vascular endothelial overexpression of human CYP2J2 through modulation of oxylipin profiles. Similarly, we expected that inhibition of CYP-epoxygenases would reduce CRH, whereas inhibition of ω-hydroxylases would enhance CRH. Compared to WT mice, Tie2-CYP2J2 Tr mice had enhanced CRH, including repayment volume, repayment duration, and repayment/debt ratio (P iso-PGF2α (P < 0.05). Inhibition of CYP epoxygenases with MS-PPOH attenuated CRH (P < 0.05). Ischemia caused a decrease in mid-chain HETEs (5-, 11-, 12-, 15-HETEs P < 0.05) and HODEs (P < 0.05). These data demonstrate that vascular endothelial overexpression of CYP2J2, through changing the oxylipin profiles, enhances CRH. Inhibition of CYP epoxygenases decreases CRH, whereas inhibition of ω-hydroxylases enhances CRH. PMID:28328948

Receptors for corticotropin-releasing hormone in human pituitary: Binding characteristics and autoradiographic localization to immunocytochemically defined proopiomelanocortin cells

Energy Technology Data Exchange (ETDEWEB)

Smets, G.; Vauquelin, G.; Moons, L.; Smitz, J.; Kloeppel, G. (Department of Experimental Pathology, Vrije Universiteit Brussel (Belgium))

1991-08-01

Using autoradiography combined with immunocytochemistry, the authors demonstrated that the target cells of CRH in the human pituitary were proopiomelanocortin cells. Scatchard analysis of (125I)Tyr0-oCRH saturation binding revealed the presence of one class of saturable, high affinity sites on pituitary tissue homogenate. The equilibrium dissociation constant (Kd) for (125I)Tyr0-oCRH ranged from 1.1-1.6 nM, and the receptor density was between 200-350 fmol/mg protein. Fixation of cryostat sections with 4% paraformaldehyde before tracer incubation improved both tissue preservation and localization of the CRH receptor at the cellular level. Additional postfixation with 1% glutaraldehyde inhibited tracer diffusion during subsequent immunocytochemistry and autoradiography. (125I)Tyr0-oCRH was found in cytoplasmic inclusions or at the cell periphery of ACTH/beta-endorphin cells in the anterior pituitary. Single cells of the posterior pituitary were also CRH receptor positive. Cells staining for PRL or GH were CRH receptor negative. They conclude that CRH binds only to high affinity receptors on ACTH/{beta}-endorphin cells in the human pituitary.

Vasopressin as a target for antidepressant development: an assessment of the available evidence.

LENUS (Irish Health Repository)

Scott, Lucinda V

2012-02-03

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is one of the key biological abnormalities described in major depressive disorder, occurring in 30-50% of depressed subjects. Corticotropin-releasing hormone (CRH) and vasopressin (AVP) are the main regulators of this stress system, with the two neuropeptides acting synergistically in bringing about adrenocorticotropin (ACTH) release from the anterior pituitary and cortisol from the adrenal gland. Based on the demonstration of elevated cerebrospinal fluid levels of CRH in depressives, and other evidence, it has been postulated that excess CRH and the resultant increased HPA forward drive form the basis of neuroendocrine dysregulation in depression. However, there is an accumulating body of evidence to support a significant role for AVP in the regulation of pituitary-adrenal activity in health and also in depressive disorder. This review, based on a Medline search from 1980 to 2001, focuses on the functional neuroanatomy, receptor pharmacology, VP synergism with CRH, and the data from clinical and pre-clinical studies that support an important role for AVP in the pathophysiology of major depression. We suggest that future antidepressants may target the vasopressinergic system.

Topological variation in the evolution of new reactions in functionally diverse enzyme superfamilies.

Science.gov (United States)

Meng, Elaine C; Babbitt, Patricia C

2011-06-01

In functionally diverse enzyme superfamilies (SFs), conserved structural and active site features reflect catalytic capabilities 'hard-wired' in each SF architecture. Overlaid on this foundation, evolutionary changes in active site machinery, structural topology and other aspects of structural organization and interactions support the emergence of new reactions, mechanisms, and substrate specificity. This review connects topological with functional variation in each of the haloalkanoic acid dehalogenase (HAD) and vicinal oxygen chelate fold (VOC) SFs and a set of redox-active thioredoxin (Trx)-fold SFs to illustrate a few of the varied themes nature has used to evolve new functions from a limited set of structural scaffolds. Copyright © 2011 Elsevier Ltd. All rights reserved.

Genome Wide Distributions and Functional Characterization of Copy Number Variations between Chinese and Western Pigs.

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Hongyang Wang

Full Text Available Copy number variations (CNVs refer to large insertions, deletions and duplications in the genomic structure ranging from one thousand to several million bases in size. Since the development of next generation sequencing technology, several methods have been well built for detection of copy number variations with high credibility and accuracy. Evidence has shown that CNV occurring in gene region could lead to phenotypic changes due to the alteration in gene structure and dosage. However, it still remains unexplored whether CNVs underlie the phenotypic differences between Chinese and Western domestic pigs. Based on the read-depth methods, we investigated copy number variations using 49 individuals derived from both Chinese and Western pig breeds. A total of 3,131 copy number variation regions (CNVRs were identified with an average size of 13.4 Kb in all individuals during domestication, harboring 1,363 genes. Among them, 129 and 147 CNVRs were Chinese and Western pig specific, respectively. Gene functional enrichments revealed that these CNVRs contribute to strong disease resistance and high prolificacy in Chinese domestic pigs, but strong muscle tissue development in Western domestic pigs. This finding is strongly consistent with the morphologic characteristics of Chinese and Western pigs, indicating that these group-specific CNVRs might have been preserved by artificial selection for the favored phenotypes during independent domestication of Chinese and Western pigs. In this study, we built high-resolution CNV maps in several domestic pig breeds and discovered the group specific CNVs by comparing Chinese and Western pigs, which could provide new insight into genomic variations during pigs' independent domestication, and facilitate further functional studies of CNV-associated genes.

Effect of in ovo injection of corticotropin-releasing hormone on the timing of hatching in broiler chickens.

Science.gov (United States)

Watanabe, Yugo; Grommen, Sylvia V H; De Groef, Bert

2017-09-01

In chicken embryos, intravenous injection of corticotropin-releasing hormone (CRH) causes the release of both corticosteroids and thyroid hormones. These hormones initiate and enhance the hatching process, raising the possibility that CRH treatment of the late chicken embryo could accelerate hatching and/or decrease the spread of hatching. We performed a series of exploratory tests to investigate whether in ovo delivery methods of CRH other than intravenous injection that are more practical in a commercial setting, affect hatching time in broilers. Corticotropin-releasing hormone was injected into the air cell, albumen, or amniotic fluid of broiler breeder eggs, in the last week of embryonic development. Average incubation duration was significantly decreased by 22 h when 2 μg of CRH was injected into the air cell on embryonic day 18 (E18) of Cobb eggs. Acceleration of hatching (but only by 8 h) was also seen for Ross chicks when CRH was injected daily into the albumen between E10 and E18. However, repeats of both experiments did not show consistent effects of CRH on hatching time; in most experiments performed, CRH did not affect hatching time. We speculate that the effectiveness of CRH uptake via these delivery methods and/or the duration and magnitude of the thyroxine and corticosterone response to CRH is not sufficient to have a substantial effect on hatching time. We therefore conclude that in ovo CRH treatment does not seem a feasible option as a practical tool to increase hatchery productivity or to investigate the effects of CRH agonists and antagonists on hatching. © 2017 Poultry Science Association Inc.

HPA axis reactivity to pharmacologic and psychological stressors in euthymic women with histories of postpartum versus major depression.

Science.gov (United States)

Ferguson, Elizabeth H; Di Florio, Arianna; Pearson, Brenda; Putnam, Karen T; Girdler, Susan; Rubinow, David R; Meltzer-Brody, Samantha

2017-06-01

It is unclear whether women with a history of postpartum depression (PPD) have residual, abnormal hypothalamic-pituitary-adrenal (HPA) axis reactivity, as has been reported in major depression (MDD). Further unclear is whether the abnormalities in HPA axis reactivity associated with MDD represent a stable, underlying predisposition or a state-dependent phenomenon. This study sought the following: (1) to determine if euthymic postpartum women with a history of depression have an abnormal HPA axis reactivity to pharmacologic and psychological challenges and (2) to compare HPA reactivity in women with histories of PPD versus MDD. As a secondary objective, we wanted to determine the influence of trauma history on HPA axis function. Forty-five parous (12-24 months postpartum), euthymic women with history of MDD (n = 15), PPD (n = 15), and controls (n = 15) completed pharmacologic (dexamethasone/corticotropin-releasing hormone (CRH) test [DEX/CRH]) and psychological (Trier social stress test [TSST]) challenges during the luteal phase. Outcome measures were cortisol and adrenocorticotropic hormone (ACTH) response after DEX/CRH, and blood pressure, heart rate, epinephrine, norepinephrine, and cortisol response during the TSST. All groups had robust cortisol and ACTH response to DEX/CRH and cortisol response to TSST. Groups did not differ significantly in cortisol or ACTH response to DEX/CRH or in blood pressure, heart rate, epinephrine, norepinephrine, or cortisol response to TSST. Cortisol/ACTH ratio did not differ significantly between groups. Trauma history was associated with decreased cortisol response to DEX/CRH in women with histories of MDD, which was not significant after correction (F 8,125 , p = 0.02, Greenhouse-Geisser corrected p = 0.11). Currently euthymic women with histories of MDD or PPD did not demonstrate residual abnormal stress responsivity following administration of either a pharmacologic or psychological stressor.

Collie Eye Anomaly in Switzerland.

Science.gov (United States)

Walser-Reinhardt, L; Hässig, M; Spiess, B

2009-12-01

In this retrospective study, the results of 3'527 eye examinations in 6 different breeds affected with Collie Eye Anomaly (CEA) over a period of 8 years (1999 - 2007) are described. CEA was divided into three main ophthalmoscopic features, a) choroidal hypoplasia (CRH), b) CRH and coloboma and c) coloboma alone. Of the 101 Smooth Collies 8.9 % showed signs of CRH, whereas 36.9 % of Rough Collies were affected with CRH, 2.8 % with CRH and coloboma and 0.38 % with coloboma alone. Choroidal hypoplasia was present in 13.1 %, CRH and coloboma in 1.8 % and coloboma alone in 0.2 % of the Shetland Sheepdogs. Only one Australian Shepherd dog had CRH, while 0.7 % of the Border Collies were affected with CRH. None of the Nova Scotia Duck Tolling Retrievers were affected with CEA. There were no statistically significant differences in the occurrence of CEA between males and females, nor was there any relation between coat colors. Significant differences could be shown between dogs younger or older than 8 weeks at first examination. CEA was more often diagnosed in dogs younger than 8 weeks within the Rough Collie and Shetland Sheepdog.

Local climate and cultivation, but not ploidy, predict functional trait variation in Bouteloua gracilis (Poaceae)

Science.gov (United States)

Butterfield, Bradley J.; Wood, Troy E.

2015-01-01

Efforts to improve the diversity of seed 18 resources for important restoration species has become a high priority for land managers in many parts of the world. Relationships between functional trait values and the environment from which seed sources are collected can provide important insights into patterns of local adaptation and guidelines for seed transfer. However, little is known about which functional traits exhibit genetic differentiation across populations of restoration species and thus may contribute to local adaptation. Here, we report the results of a common garden experiment aimed at assessing genetic (including ploidy level) and environmental regulation of several functional traits among populations of Bouteloua gracilis, a dominant C4 grass and the most highly utilized restoration species across much of the Colorado Plateau. We found that leaf size and specific leaf area (SLA) varied significantly among populations, and were strongly correlated with the source population environment from which seeds were collected. However, variation in ploidy level had no significant effect on functional traits. Leaves of plants grown from commercial seed releases were significantly larger and had lower SLA than those from natural populations, a result that is concordant with the overall relation between climate and these two functional traits. We suggest that the patterns of functional trait variation shown here may extend to other grass species in the western USA, and may serve as useful proxies for more extensive genecology research. Furthermore, we argue that care should be taken to develop commercial seed lines with functional trait values that match those of natural populations occupying climates similar to target restoration sites.

Effects of corticotropin-releasing hormone and its antagonist on the gene expression of gonadotrophin-releasing hormone (GnRH) and GnRH receptor in the hypothalamus and anterior pituitary gland of follicular phase ewes.

Science.gov (United States)

Ciechanowska, Magdalena; Łapot, Magdalena; Malewski, Tadeusz; Mateusiak, Krystyna; Misztal, Tomasz; Przekop, Franciszek

2011-01-01

There is no information in the literature regarding the effect of corticotropin-releasing hormone (CRH) on genes encoding gonadotrophin-releasing hormone (GnRH) and the GnRH receptor (GnRHR) in the hypothalamus or on GnRHR gene expression in the pituitary gland in vivo. Thus, the aim of the present study was to investigate, in follicular phase ewes, the effects of prolonged, intermittent infusion of small doses of CRH or its antagonist (α-helical CRH 9-41; CRH-A) into the third cerebral ventricle on GnRH mRNA and GnRHR mRNA levels in the hypothalamo-pituitary unit and on LH secretion. Stimulation or inhibition of CRH receptors significantly decreased or increased GnRH gene expression in the hypothalamus, respectively, and led to different responses in GnRHR gene expression in discrete hypothalamic areas. For example, CRH increased GnRHR gene expression in the preoptic area, but decreased it in the hypothalamus/stalk median eminence and in the anterior pituitary gland. In addition, CRH decreased LH secretion. Blockade of CRH receptors had the opposite effect on GnRHR gene expression. The results suggest that activation of CRH receptors in the hypothalamus of follicular phase ewes can modulate the biosynthesis and release of GnRH through complex changes in the expression of GnRH and GnRHR genes in the hypothalamo-anterior pituitary unit. © CSIRO 2011 Open Access

Role of the hypothalamic pituitary adrenal axis in the control of the response to stress and infection

Directory of Open Access Journals (Sweden)

McCann S.M.

2000-01-01

Full Text Available The release of adrenocorticotropin (ACTH from the corticotrophs is controlled principally by vasopressin and corticotropin-releasing hormone (CRH. Oxytocin may augment the release of ACTH under certain conditions, whereas atrial natriuretic peptide acts as a corticotropin release-inhibiting factor to inhibit ACTH release by direct action on the pituitary. Glucocorticoids act on their receptors within the hypothalamus and anterior pituitary gland to suppress the release of vasopressin and CRH and the release of ACTH in response to these neuropeptides. CRH neurons in the paraventricular nucleus also project to the cerebral cortex and subcortical regions and to the locus ceruleus (LC in the brain stem. Cortical influences via the limbic system and possibly the LC augment CRH release during emotional stress, whereas peripheral input by pain and other sensory impulses to the LC causes stimulation of the noradrenergic neurons located there that project their axons to the CRH neurons stimulating them by alpha-adrenergic receptors. A muscarinic cholinergic receptor is interposed between the alpha-receptors and nitric oxidergic interneurons which release nitric oxide that activates CRH release by activation of cyclic guanosine monophosphate, cyclooxygenase, lipoxygenase and epoxygenase. Vasopressin release during stress may be similarly mediated. Vasopressin augments the release of CRH from the hypothalamus and also augments the action of CRH on the pituitary. CRH exerts a positive ultrashort loop feedback to stimulate its own release during stress, possibly by stimulating the LC noradrenergic neurons whose axons project to the paraventricular nucleus to augment the release of CRH.

Regional variation in the structure and function of parrotfishes on Arabian reefs

KAUST Repository

Hoey, Andrew

2015-11-20

Parrotfishes (f. Labridae) are a unique and ubiquitous group of herbivorous reef fishes. We compared the distribution and ecosystem function (grazing and erosion) of parrotfishes across 75 reefs in Arabia. Our results revealed marked regional differences in the abundance, and taxonomic and functional composition of parrotfishes between the Red Sea, Arabian Sea, and Arabian Gulf. High densities and diversity of parrotfishes, and high rates of grazing (210% year) and erosion (1.57 kg m year) characterised Red Sea reefs. Despite Arabian Sea and Red Sea reefs having broadly comparable abundances of parrotfishes, estimates of grazing (150% year) and erosion (0.43 kg m year) were markedly lower in the Arabian Sea. Parrotfishes were extremely rare within the southern Arabian Gulf, and as such rates of grazing and erosion were negligible. This regional variation in abundance and functional composition of parrotfishes appears to be related to local environmental conditions.

Beyond sex differences: new approaches for thinking about variation in brain structure and function.

Science.gov (United States)

Joel, Daphna; Fausto-Sterling, Anne

2016-02-19

In the study of variation in brain structure and function that might relate to sex and gender, language matters because it frames our research questions and methods. In this article, we offer an approach to thinking about variation in brain structure and function that pulls us outside the sex differences formulation. We argue that the existence of differences between the brains of males and females does not unravel the relations between sex and the brain nor is it sufficient to characterize a population of brains. Such characterization is necessary for studying sex effects on the brain as well as for studying brain structure and function in general. Animal studies show that sex interacts with environmental, developmental and genetic factors to affect the brain. Studies of humans further suggest that human brains are better described as belonging to a single heterogeneous population rather than two distinct populations. We discuss the implications of these observations for studies of brain and behaviour in humans and in laboratory animals. We believe that studying sex effects in context and developing or adopting analytical methods that take into account the heterogeneity of the brain are crucial for the advancement of human health and well-being. © 2016 The Author(s).

Proton magnetic resonance spectroscopy: normal findings in the cerebellar hemisphere in childhood

International Nuclear Information System (INIS)

Costa, Maria Olivia R.; Lacerda, Maria Teresa C.; Garcia Otaduy, Maria C.; Cerri, Giovanni Guido; Costa Leite, Claudia de

2002-01-01

The cerebellar hemispheres (CER) are different from the supratentorial white and gray matter embryologically, in cytoarchitecture, and probably in metabolic activity. Proton magnetic resonance spectroscopy ( 1 H MRS) can provide a noninvasive biochemical analysis of this region.Objective. To study, with 1 H MRS, metabolite concentrations in CER as a function of age and compare these metabolic data with those of parietoccipital white matter (PO WM) in healthy children.Materials and methods. Using single-voxel 1 H MRS, we studied 37 volunteers (3-18 years) with normal MRI scans of the brain. 1 H MRS was performed using the PRESS technique in CER and PO WM. The NAA/Cr, Cho/Cr, NAA/H 2 O, Cr/H 2 O, and Cho/H 2 O ratios were analyzed as a function of age. Metabolic data from these regions were compared.Results. The NAA/Cr ratio tended to increase with age in CER. Mean NAA/Cr and Cho/Cr ratios were found to be lower in CER than in PO WM. Mean NAA/H 2 O, Cr/H 2 O, and Cho/H 2 O ratios in CER were higher than in the PO WM.Conclusion. Our data confirm the regional variations between CER and PO WM metabolite ratios, and demonstrate a tendency of age-dependent change of the NAA/Cr ratio in CER. The creatine concentration was significantly higher in the cerebellum than in the PO WM. (orig.)

EEG sensorimotor rhythms' variation and functional connectivity measures during motor imagery: linear relations and classification approaches.

Science.gov (United States)

Stefano Filho, Carlos A; Attux, Romis; Castellano, Gabriela

2017-01-01

Hands motor imagery (MI) has been reported to alter synchronization patterns amongst neurons, yielding variations in the mu and beta bands' power spectral density (PSD) of the electroencephalography (EEG) signal. These alterations have been used in the field of brain-computer interfaces (BCI), in an attempt to assign distinct MI tasks to commands of such a system. Recent studies have highlighted that information may be missing if knowledge about brain functional connectivity is not considered. In this work, we modeled the brain as a graph in which each EEG electrode represents a node. Our goal was to understand if there exists any linear correlation between variations in the synchronization patterns-that is, variations in the PSD of mu and beta bands-induced by MI and alterations in the corresponding functional networks. Moreover, we (1) explored the feasibility of using functional connectivity parameters as features for a classifier in the context of an MI-BCI; (2) investigated three different types of feature selection (FS) techniques; and (3) compared our approach to a more traditional method using the signal PSD as classifier inputs. Ten healthy subjects participated in this study. We observed significant correlations ( p  < 0.05) with values ranging from 0.4 to 0.9 between PSD variations and functional network alterations for some electrodes, prominently in the beta band. The PSD method performed better for data classification, with mean accuracies of (90 ± 8)% and (87 ± 7)% for the mu and beta band, respectively, versus (83 ± 8)% and (83 ± 7)% for the same bands for the graph method. Moreover, the number of features for the graph method was considerably larger. However, results for both methods were relatively close, and even overlapped when the uncertainties of the accuracy rates were considered. Further investigation regarding a careful exploration of other graph metrics may provide better alternatives.

Functional diversity of non-lethal effects, chemical camouflage, and variation in fish avoidance in colonizing beetles.

Science.gov (United States)

Resetarits, William J; Pintar, Matthew R

2016-12-01

Predators play an extremely important role in natural communities. In freshwater systems, fish can dominate sorting both at the colonization and post-colonization stage. Specifically, for many colonizing species, fish can have non-lethal, direct effects that exceed the lethal direct effects of predation. Functionally diverse fish species with a range of predatory capabilities have previously been observed to elicit functionally equivalent responses on oviposition in tree frogs. We tested this hypothesis of functional equivalence of non-lethal effects for four predatory fish species, using naturally colonizing populations of aquatic beetles. Among taxa other than mosquitoes, and with the exception of the chemically camouflaged pirate perch, Aphredoderus sayanus, we provide the first evidence of variation in colonization or oviposition responses to different fish species. Focusing on total abundance, Fundulus chrysotus, a gape-limited, surface-feeding fish, elicited unique responses among colonizing Hydrophilidae, with the exception of the smallest and most abundant taxa, Paracymus, while Dytiscidae responded similarly to all avoided fish. Neither family responded to A. sayanus. Analysis of species richness and multivariate characterization of the beetle assemblages for the four fish species and controls revealed additional variation among the three avoided species and confirmed that chemical camouflage in A. sayanus results in assemblages essentially identical to fishless controls. The origin of this variation in beetle responses to different fish is unknown, but may involve variation in cue sensitivity, different behavioral algorithms, or differential responses to species-specific fish cues. The identity of fish species occupying aquatic habitats is crucial to understanding community structure, as varying strengths of lethal and non-lethal effects, as well as their interaction, create complex landscapes of predator effects and challenge the notion of functional

Useful variational principle for the scattering length for the target ground-state wave function imprecisely known

International Nuclear Information System (INIS)

Blau, R.; Rosenberg, L.; Spruch, L.

1977-01-01

A minimum principle for the calculation of the scattering length, applicable when the ground-state wave function of the target system is known precisely, has been available for some time. When, as is almost always the case, the target wave function is imprecisely known, a minimum principle is available but the simple minimum principle noted above is not applicable. Further, as recent calculations show, numerical instabilities usually arise which severely limit the utility of even an ordinary variational approach. The difficulty, which can be traced to the appearance of singularities in the variational construction, is here removed through the introduction of a minimum principle, not for the true scattering length, but for one associated with a closely connected problem. This guarantees that no instability difficulties can arise as the trial scattering wave function and the trial target wave function are improved. The calculations are little different from those required when the target ground-state wave function is known, and, in fact, the original version of the minimum principle is recovered as the trial target wave function becomes exact. A careful discussion is given of the types of problems to which the method can be applied. In particular, the effects of the Pauli principle, and the existence of a finite number of composite bound states, can be accounted for

Hypothalamic and pituitary clusterin modulates neurohormonal responses to stress.

Science.gov (United States)

Shin, Mi-Seon; Chang, Hyukki; Namkoong, Churl; Kang, Gil Myoung; Kim, Hyun-Kyong; Gil, So Young; Yu, Ji Hee; Park, Kyeong Han; Kim, Min-Seon

2013-01-01

Clusterin is a sulfated glycoprotein abundantly expressed in the pituitary gland and hypothalamus of mammals. However, its physiological role in neuroendocrine function is largely unknown. In the present study, we investigated the effects of intracerebroventricular (ICV) administration of clusterin on plasma pituitary hormone levels in normal rats. Single ICV injection of clusterin provoked neurohormonal changes seen under acute stress condition: increased plasma adrenocorticotropic hormone (ACTH), corticosterone, GH and prolactin levels and decreased LH and FSH levels. Consistently, hypothalamic and pituitary clusterin expression levels were upregulated following a restraint stress, suggesting an involvement of endogenous clusterin in stress-induced neurohormonal changes. In the pituitary intermediate lobe, clusterin was coexpressed with proopiomelanocortin (POMC), a precursor of ACTH. Treatment of clusterin in POMC expressing AtT-20 pituitary cells increased basal and corticotropin-releasing hormone (CRH)-stimulated POMC promoter activities and intracellular cAMP levels. Furthermore, clusterin treatment triggered ACTH secretion from AtT-20 cells in a CRH-dependent manner, indicating that increased clusterin under stressful conditions may augment CRH-stimulated ACTH production and release. In summary, hypothalamic and pituitary clusterin may function as a modulator of neurohormonal responses under stressful conditions. © 2013 S. Karger AG, Basel.

The variation of the density functions on chaotic spheres in chaotic space-like Minkowski space time

International Nuclear Information System (INIS)

El-Ahmady, A.E.

2007-01-01

In this article we introduce types of chaotic spheres in chaotic space-like Minkowski space time M n+1 . The variations of the density functions under the folding of these chaotic spheres are defined. The foldings restriction imposed on the density function are also discussed. The relations between the folding of geometry and pure chaotic manifolds are deduced. Some theorems concerning these relations are presented

Increased cortisol in the cerebrospinal fluid of women with functional hypothalamic amenorrhea.

Science.gov (United States)

Brundu, Benedetta; Loucks, Tammy L; Adler, Lauri J; Cameron, Judy L; Berga, Sarah L

2006-04-01

The proximate cause of functional hypothalamic amenorrhea (FHA) is reduced GnRH drive. The concomitant increase in circulating cortisol suggests that psychogenic stress plays an etiologic role, but others have argued for a strictly metabolic cause, such as undernutrition or excessive exercise. Indeed, our finding that the cerebrospinal fluid (CSF) concentration of CRH was not elevated in FHA cast doubt about the extent of hypothalamic-pituitary-adrenal activation in FHA and, therefore, we wondered whether central cortisol levels were elevated. We tested the null hypothesis that CSF cortisol levels would be comparable in FHA and eumenorrheic women (EW). The study is a cross-sectional comparison. The study was set in a general clinical research center at an academic medical center. Fifteen women with FHA who were of normal body weight and 14 EW participated. Blood samples were collected at 15-min intervals for 24 h, followed by procurement of 25 ml CSF. Cortisol, cortisol-binding globulin (CBG), and SHBG levels in blood and CSF were the main outcome measures. CSF cortisol concentrations were 30% greater when serum cortisol was 16% higher in FHA compared with EW. Circulating CBG, but not SHBG, was increased in FHA and, thus, the circulating free cortisol index was similar in FHA and EW. Because CBG and SHBG were nil in CSF, the increase in CSF cortisol in FHA was unbound. The hypothalamic-pituitary-adrenal axis is activated in FHA. The maintenance of CRH drive despite increased CSF cortisol indicates resistance to cortisol feedback inhibition. The mechanisms mediating feedback resistance likely involve altered hippocampal corticosteroid reception and serotonergic and GABAergic neuromodulation.

Variations in erosive wear of metallic materials with temperature via the electron work function

Energy Technology Data Exchange (ETDEWEB)

Huang, Xiaochen; Yu, Bin [Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta, T6G 2V4 (Canada); Yan, X.G. [School of Mechanical Engineering, Taiyuan University of Science and Technology, Taiyuan, Shanxi (China); Li, D.Y., E-mail: dongyang.li@ualberta.ca [Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta, T6G 2V4 (Canada); School of Mechanical Engineering, Taiyuan University of Science and Technology, Taiyuan, Shanxi (China)

2016-04-01

Mechanical properties of metals are intrinsically determined by their electron behavior, which is largely reflected by the electron work function (EWF or φ). Since the work function varies with temperature, the dependence of material properties on temperature could be predicted via variations in work function with temperature. Combining a hardness – φ relationship and the dependence of work function on temperature, a temperature-dependent model for predicting solid-particle erosion is proposed. Erosive wear losses of copper, nickel, and carbon steel as sample materials were measured at different temperatures. Results of the tests are consistent with the theoretical prediction. This study demonstrates a promising parameter, electron work function, for looking into fundamental aspects of wear phenomena, which would also help develop alternative methodologies for material design. - Highlights: • Metallic materials' wear resistance is influenced by temperature. • Electron work function (EWF) intrinsically determines materials' wear resistance. • An EWF-based temperature-dependent solid-particle erosion model is proposed.

Variations in erosive wear of metallic materials with temperature via the electron work function

International Nuclear Information System (INIS)

Huang, Xiaochen; Yu, Bin; Yan, X.G.; Li, D.Y.

2016-01-01

Mechanical properties of metals are intrinsically determined by their electron behavior, which is largely reflected by the electron work function (EWF or φ). Since the work function varies with temperature, the dependence of material properties on temperature could be predicted via variations in work function with temperature. Combining a hardness – φ relationship and the dependence of work function on temperature, a temperature-dependent model for predicting solid-particle erosion is proposed. Erosive wear losses of copper, nickel, and carbon steel as sample materials were measured at different temperatures. Results of the tests are consistent with the theoretical prediction. This study demonstrates a promising parameter, electron work function, for looking into fundamental aspects of wear phenomena, which would also help develop alternative methodologies for material design. - Highlights: • Metallic materials' wear resistance is influenced by temperature. • Electron work function (EWF) intrinsically determines materials' wear resistance. • An EWF-based temperature-dependent solid-particle erosion model is proposed.

The Spaces of Functions of Two Variables of Bounded κΦ-Variation in the Sense of Schramm-Korenblum

Directory of Open Access Journals (Sweden)

A. Azócar

2015-01-01

Full Text Available The purpose of this paper is twofold. Firstly, we introduce the concept of bounded κΦ-variation in the sense of Schramm-Korenblum for real functions with domain in a rectangle of R2. Secondly, we study some properties of these functions and we prove that the space generated by these functions has a structure of Banach algebra.

Temporal and Spatial Variation of Soil Bacteria Richness, Composition, and Function in a Neotropical Rainforest.

Science.gov (United States)

Kivlin, Stephanie N; Hawkes, Christine V

2016-01-01

The high diversity of tree species has traditionally been considered an important controller of belowground processes in tropical rainforests. However, soil water availability and resources are also primary regulators of soil bacteria in many ecosystems. Separating the effects of these biotic and abiotic factors in the tropics is challenging because of their high spatial and temporal heterogeneity. To determine the drivers of tropical soil bacteria, we examined tree species effects using experimental tree monocultures and secondary forests at La Selva Biological Station in Costa Rica. A randomized block design captured spatial variation and we sampled at four dates across two years to assess temporal variation. We measured bacteria richness, phylogenetic diversity, community composition, biomass, and functional potential. All bacteria parameters varied significantly across dates. In addition, bacteria richness and phylogenetic diversity were affected by the interaction of vegetation type and date, whereas bacteria community composition was affected by the interaction of vegetation type and block. Shifts in bacteria community richness and composition were unrelated to shifts in enzyme function, suggesting physiological overlap among taxa. Based on the observed temporal and spatial heterogeneity, our understanding of tropical soil bacteria will benefit from additional work to determine the optimal temporal and spatial scales for sampling. Understanding spatial and temporal variation will facilitate prediction of how tropical soil microbes will respond to future environmental change.

Variation in the thermionic work function of semiconductor powders exposed to electromagnetic radiation

Science.gov (United States)

Bourasseau, S.; Martin, J. R.; Juillet, F.; Teichner, S. J.

1977-01-01

The study of the variation of thermoelectronic work function potential of TiO2 in the presence of isobutane shows that this gas is not adsorbed on this solid, in either the presence or the absence of ultraviolet radiation. These results, as well as those obtained in a previous work, lead to the mechanism of the photo-oxidation of isobutane at room temperature, in which excited atomic oxygen is the active species.

Corticotropin releasing hormone and imaging, rethinking the stress axis

International Nuclear Information System (INIS)

Contoreggi, Carlo

2015-01-01

The stress system provides integration of both neurochemical and somatic physiologic functions within organisms as an adaptive mechanism to changing environmental conditions throughout evolution. In mammals and primates the complexity and sophistication of these systems have surpassed other species in triaging neurochemical and physiologic signaling to maximize chances of survival. Corticotropin releasing hormone (CRH) and its related peptides and receptors have been identified over the last three decades and are fundamental molecular initiators of the stress response. They are crucial in the top down regulatory cascade over a myriad of neurochemical, neuroendocrine and sympathetic nervous system events. From neuroscience, we've seen that stress activation impacts behavior, endocrine and somatic physiology and influences neurochemical events that one can capture in real time with current imaging technologies. To delineate these effects one can demonstrate how the CRH neuronal networks infiltrate critical cognitive, emotive and autonomic regions of the central nervous system (CNS) with somatic effects. Abundant preclinical and clinical studies show inter-regulatory actions of CRH with multiple neurotransmitters/peptides. Stress, both acute and chronic has epigenetic effects which magnify genetic susceptibilities to alter neurochemistry; stress system activation can add critical variables in design and interpretation of basic and clinical neuroscience and related research. This review will attempt to provide an overview of the spectrum of known functions and speculative actions of CRH and stress responses in light of imaging technology and its interpretation. Metabolic and neuroreceptor positron emission/single photon tomography (PET/SPECT), functional magnetic resonance imaging (fMRI), anatomic MRI, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (pMRS) are technologies that can delineate basic mechanisms of neurophysiology and

Variational principles for nonpotential operators

CERN Document Server

Filippov, V M

1989-01-01

This book develops a variational method for solving linear equations with B-symmetric and B-positive operators and generalizes the method to nonlinear equations with nonpotential operators. The author carries out a constructive extension of the variational method to "nonvariational" equations (including parabolic equations) in classes of functionals which differ from the Euler-Lagrange functionals. In this connection, some new functions spaces are considered. Intended for mathematicians working in the areas of functional analysis and differential equations, this book would also prove useful for researchers in other areas and students in advanced courses who use variational methods in solving linear and nonlinear boundary value problems in continuum mechanics and theoretical physics.

Variational estimate of the vacuum state of the SU(2) lattice gauge theory with a disordered trial wave function

International Nuclear Information System (INIS)

Heys, D.W.; Stump, D.R.

1984-01-01

The variational principle is used to estimate the ground state of the Kogut-Susskind Hamiltonian of the SU(2) lattice gauge theory, with a trial wave function for which the magnetic fields on different plaquettes are uncorrelated. This trial function describes a disordered state. The energy expectation value is evaluated by a Monte Carlo method. The variational results are compared to similar results for a related Abelian gauge theory. Also, the expectation value of the Wilson loop operator is computed for the trial state, and the resulting estimate of the string tension is compared to the prediction of asymptotic freedom

Differential contribution of CBP:CREB binding to corticotropin-releasing hormone expression in the infant and adult hypothalamus

NARCIS (Netherlands)

Cope, J.L.; Regev, L.; Chen, Y.; Korosi, A.; Rice, C.J.; Ji, S.; Rogge, G.A.; Wood, M.A.; Baram, T.Z.

2014-01-01

Corticotropin-releasing hormone (CRH) contributes crucially to the regulation of central and peripheral responses to stress. Because of the importance of a finely-tuned stress system, CRH expression is tightly regulated in an organ- and brain region-specific manner. Thus, in hypothalamus, CRH is

Genetic variation in HTR4 and lung function: GWAS follow-up in mouse.

Science.gov (United States)

House, John S; Li, Huiling; DeGraff, Laura M; Flake, Gordon; Zeldin, Darryl C; London, Stephanie J

2015-01-01

Human genome-wide association studies (GWASs) have identified numerous associations between single nucleotide polymorphisms (SNPs) and pulmonary function. Proving that there is a causal relationship between GWAS SNPs, many of which are noncoding and without known functional impact, and these traits has been elusive. Furthermore, noncoding GWAS-identified SNPs may exert trans-regulatory effects rather than impact the proximal gene. Noncoding variants in 5-hydroxytryptamine (serotonin) receptor 4 (HTR4) are associated with pulmonary function in human GWASs. To gain insight into whether this association is causal, we tested whether Htr4-null mice have altered pulmonary function. We found that HTR4-deficient mice have 12% higher baseline lung resistance and also increased methacholine-induced airway hyperresponsiveness (AHR) as measured by lung resistance (27%), tissue resistance (48%), and tissue elastance (30%). Furthermore, Htr4-null mice were more sensitive to serotonin-induced AHR. In models of exposure to bacterial lipopolysaccharide, bleomycin, and allergic airway inflammation induced by house dust mites, pulmonary function and cytokine profiles in Htr4-null mice differed little from their wild-type controls. The findings of altered baseline lung function and increased AHR in Htr4-null mice support a causal relationship between genetic variation in HTR4 and pulmonary function identified in human GWAS. © FASEB.

Introduction to global variational geometry

CERN Document Server

Krupka, Demeter

2015-01-01

The book is devoted to recent research in the global variational theory on smooth manifolds. Its main objective is an extension of the classical variational calculus on Euclidean spaces to (topologically nontrivial) finite-dimensional smooth manifolds; to this purpose the methods of global analysis of differential forms are used. Emphasis is placed on the foundations of the theory of variational functionals on fibered manifolds - relevant geometric structures for variational principles in geometry, physical field theory and higher-order fibered mechanics. The book chapters include: - foundations of jet bundles and analysis of differential forms and vector fields on jet bundles, - the theory of higher-order integral variational functionals for sections of a fibred space, the (global) first variational formula in infinitesimal and integral forms- extremal conditions and the discussion of Noether symmetries and generalizations,- the inverse problems of the calculus of variations of Helmholtz type- variational se...

239pu alpha spectrum analysis based on PIPS detector response function and variations with vacuum and distance

Institute of Scientific and Technical Information of China (English)

Rui Shi; Xian-Guo Tuo; Huai-Liang Li; Jian-Bo Yang; Yi Cheng; Hong-Long Zheng

2017-01-01

Effect factors of the absorption of the source,air,entrance window,and dead layer of a detector must be considered in the measurement of monoenergetic alpha particles,along with statsfical noise and other factors that collectively cause the alpha spectrum to exhibit a well-known low-energy tail.Therefore,the establishment of an alpha spectrum detector response function from the perspective of a signaling system must consider the various factors mentioned above.The detector response function is the convolution of an alphaparticle pulse function,two exponential functions,and a Gaussian function,followed by calculation of the parameters of the detector response function using the weighted leastsquares fitting method as proposed in this paper.In our experiment,239pu alpha spectra were measured by a highresolution,passivated implanted planar silicon (PIPS)detector at 10 levels of vacuum and 10 source-detector distances.The spectrum-fitting results were excellent as evaluated by reduced Chi-square (x2) and correlation coefficients.Finally,the variation of parameters with vacuum level and source-detector distance was studied.Results demonstrate that ο,τ1,and τ2 exhibit no obvious trend of variation with vacuum in the range 2000-20,000 mTorr,and at a confidence level of 95％,the values of τ1 and τ2 decline in a similar fashion with source-detector distance by the power exponential function,while the value of ο declines linearly.

Identifying an unknown function in a parabolic equation with overspecified data via He's variational iteration method

International Nuclear Information System (INIS)

Dehghan, Mehdi; Tatari, Mehdi

2008-01-01

In this research, the He's variational iteration technique is used for computing an unknown time-dependent parameter in an inverse quasilinear parabolic partial differential equation. Parabolic partial differential equations with overspecified data play a crucial role in applied mathematics and physics, as they appear in various engineering models. The He's variational iteration method is an analytical procedure for finding solutions of differential equations, is based on the use of Lagrange multipliers for identification of an optimal value of a parameter in a functional. To show the efficiency of the new approach, several test problems are presented for one-, two- and three-dimensional cases

Increased pituitary-adrenal activation and shortened gestation in a sample of depressed pregnant women: a pilot study.

LENUS (Irish Health Repository)

O'Keane, V

2011-04-01

Major depression (MD) is frequently accompanied by a relatively increased production of the stress hormone cortisol. During pregnancy corticotrophin releasing hormone (CRH) is secreted from the placenta and critically high levels of CRH are one of the key triggers for parturition. Maternal cortisol promotes the secretion of placental CRH. In this study, we examined the hypothesis that women suffering with MD in pregnancy would have relatively increased cortisol secretion, a time-advanced rise in placental CRH production and an earlier delivery of the baby.

Intraspecific variation in flight metabolic rate in the bumblebee Bombus impatiens: repeatability and functional determinants in workers and drones.

Science.gov (United States)

Darveau, Charles-A; Billardon, Fannie; Bélanger, Kasandra

2014-02-15

The evolution of flight energetics requires that phenotypes be variable, repeatable and heritable. We studied intraspecific variation in flight energetics in order to assess the repeatability of flight metabolic rate and wingbeat frequency, as well as the functional basis of phenotypic variation in workers and drones of the bumblebee species Bombus impatiens. We showed that flight metabolic rate and wingbeat frequency were highly repeatable in workers, even when controlling for body mass variation using residual analysis. We did not detect significant repeatability in drones, but a smaller range of variation might have prevented us from finding significant values in our sample. Based on our results and previous findings, we associated the high repeatability of flight phenotypes in workers to the functional links between body mass, thorax mass, wing size, wingbeat frequency and metabolic rate. Moreover, differences between workers and drones were as predicted from these functional associations, where drones had larger wings for their size, lower wingbeat frequency and lower flight metabolic rate. We also investigated thoracic muscle metabolic phenotypes by measuring the activity of carbohydrate metabolism enzymes, and we found positive correlations between mass-independent metabolic rate and the activity of all enzymes measured, but in workers only. When comparing workers and drones that differ in flight metabolic rate, only the activity of the enzymes hexokinase and trehalase showed the predicted differences. Overall, our study indicates that there should be correlated evolution among physiological phenotypes at multiple levels of organization and morphological traits associated with flight.

Effects of experimentally induced hyperthyroidism on central hypothalamic-pituitary-adrenal axis function in rats: in vitro and in situ studies.

Science.gov (United States)

Johnson, Elizabeth O; Calogero, Aldo E; Konstandi, Maria; Kamilaris, Themis C; La Vignera, Sandro; Vignera, Sandro La; Chrousos, George P

2013-06-01

Hyperthyroidism is associated with hypercorticosteronemia, although the locus that is principally responsible for the hypercorticosteronism remains unclear. The purpose of this study was to assess the effects of hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis, to identify the locus in the HPA axis that is principally affected, and address the time-dependent effects of alterations in thyroid status. The functional integrity of each component of the HPA axis was examined in vitro and in situ in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given pharmacological dose (50 μg) of thyroxin for 7 or 60 days. Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days. Basal plasma ACTH levels were similar to controls. Both hypothalamic CRH content and the magnitude of KCL- and arginine vasopressin (AVP)-induced CRH release from hypothalamic culture were increased in long-term hyperthyroid rats. There was a significant increase in the content of both ACTH and β-endorphin in the anterior pituitaries of both short- and long-term hyperthyroid animals. Short-term hyperthyroid rats showed a significant increase in basal POMC mRNA expression in the anterior pituitary, and chronically hyperthyroid animals showed increased stress-induced POMC mRNA expression. Adrenal cultures taken from short-term hyperthyroid rats responded to exogenous ACTH with an exaggerated corticosterone response, while those taken from 60-day hyperthyroid animals showed responses similar to controls. The findings show that hyperthyroidism is associated with hypercorticosteronemia and HPA axis dysfunction that becomes more pronounced as the duration of hyperthyroidism increases. The evidence suggests that experimentally induced hyperthyroidism is associated with central hyperactivity of the HPA axis.

A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence.

Science.gov (United States)

Spain, S L; Pedroso, I; Kadeva, N; Miller, M B; Iacono, W G; McGue, M; Stergiakouli, E; Davey Smith, G; Putallaz, M; Lubinski, D; Meaburn, E L; Plomin, R; Simpson, M A

2016-08-01

Although individual differences in intelligence (general cognitive ability) are highly heritable, molecular genetic analyses to date have had limited success in identifying specific loci responsible for its heritability. This study is the first to investigate exome variation in individuals of extremely high intelligence. Under the quantitative genetic model, sampling from the high extreme of the distribution should provide increased power to detect associations. We therefore performed a case-control association analysis with 1409 individuals drawn from the top 0.0003 (IQ >170) of the population distribution of intelligence and 3253 unselected population-based controls. Our analysis focused on putative functional exonic variants assayed on the Illumina HumanExome BeadChip. We did not observe any individual protein-altering variants that are reproducibly associated with extremely high intelligence and within the entire distribution of intelligence. Moreover, no significant associations were found for multiple rare alleles within individual genes. However, analyses using genome-wide similarity between unrelated individuals (genome-wide complex trait analysis) indicate that the genotyped functional protein-altering variation yields a heritability estimate of 17.4% (s.e. 1.7%) based on a liability model. In addition, investigation of nominally significant associations revealed fewer rare alleles associated with extremely high intelligence than would be expected under the null hypothesis. This observation is consistent with the hypothesis that rare functional alleles are more frequently detrimental than beneficial to intelligence.

Parameterization of aquatic ecosystem functioning and its natural variation: Hierarchical Bayesian modelling of plankton food web dynamics

Science.gov (United States)

Norros, Veera; Laine, Marko; Lignell, Risto; Thingstad, Frede

2017-10-01

Methods for extracting empirically and theoretically sound parameter values are urgently needed in aquatic ecosystem modelling to describe key flows and their variation in the system. Here, we compare three Bayesian formulations for mechanistic model parameterization that differ in their assumptions about the variation in parameter values between various datasets: 1) global analysis - no variation, 2) separate analysis - independent variation and 3) hierarchical analysis - variation arising from a shared distribution defined by hyperparameters. We tested these methods, using computer-generated and empirical data, coupled with simplified and reasonably realistic plankton food web models, respectively. While all methods were adequate, the simulated example demonstrated that a well-designed hierarchical analysis can result in the most accurate and precise parameter estimates and predictions, due to its ability to combine information across datasets. However, our results also highlighted sensitivity to hyperparameter prior distributions as an important caveat of hierarchical analysis. In the more complex empirical example, hierarchical analysis was able to combine precise identification of parameter values with reasonably good predictive performance, although the ranking of the methods was less straightforward. We conclude that hierarchical Bayesian analysis is a promising tool for identifying key ecosystem-functioning parameters and their variation from empirical datasets.

On Bi-Dimensional Second µ-Variation

Directory of Open Access Journals (Sweden)

Ereú Jurancy

2014-12-01

Full Text Available In this paper, we present a generalization of the notion of bounded slope variation for functions defined on a rectangle Iba in ℝ2. Given a strictly increasing function µ-defined in a closed real interval, we introduce the class BVµ,2 (Iba , of functions of bounded second µ-variation on Iba ; and show that this class can be equipped with a norm with respect to which it is a Banach space. We also deal with the important case of factorizable functions in BVµ,2 (Iba and finally we exhibit a relation between this class and the one of double Riemann-Stieltjes integrals of functions of bi-dimensional bounded variation.

Intra- and interspecific trait variations reveal functional relationships between specific leaf area and soil niche within a subtropical forest.

Science.gov (United States)

He, Dong; Chen, Yongfa; Zhao, Kangning; Cornelissen, J H C; Chu, Chengjin

2018-02-03

How functional traits vary with environmental conditions is of fundamental importance in trait-based community ecology. However, how intraspecific variability in functional traits is connected to species distribution is not well understood. This study investigated inter- and intraspecific variation of a key functional trait, i.e. specific leaf area (leaf area per unit dry mass; SLA), in relation to soil factors and tested if trait variation is more closely associated with specific environmental regimes for low-variability species than for high-variability species. In a subtropical evergreen forest plot (50 ha, southern China), 106 700 leaves from 5335 individuals of 207 woody species were intensively collected, with 30 individuals sampled for most species to ensure a sufficient sample size representative of intraspecific variability. Soil conditions for each plant were estimated by kriging from more than 1700 observational soil locations across the plot. Intra- and interspecific variation in SLA were separately related to environmental factors. Based on the species-specific variation of SLA, species were categorized into three groups: low-, intermediate- and high-intraspecific variability. Intraspecific habitat ranges and the strength of SLA-habitat relationships were compared among these three groups. Interspecific variation in SLA overrides the intraspecific variation (77 % vs. 8 %). Total soil nitrogen (TN, positively) and total organic carbon (TOC, negatively) are the most important explanatory factors for SLA variation at both intra- and interspecific levels. SLA, both within and between species, decreases with decreasing soil nitrogen availability. As predicted, species with low intraspecific variability in SLA have narrower habitat ranges with respect to soil TOC and TN and show a stronger SLA-habitat association than high-variability species. For woody plants low SLA is a phenotypic and probably adaptive response to nitrogen stress, which drives the

Functional analysis and applied optimization in Banach spaces applications to non-convex variational models

CERN Document Server

Botelho, Fabio

2014-01-01

This book introduces the basic concepts of real and functional analysis. It presents the fundamentals of the calculus of variations, convex analysis, duality, and optimization that are necessary to develop applications to physics and engineering problems. The book includes introductory and advanced concepts in measure and integration, as well as an introduction to Sobolev spaces. The problems presented are nonlinear, with non-convex variational formulation. Notably, the primal global minima may not be attained in some situations, in which cases the solution of the dual problem corresponds to an appropriate weak cluster point of minimizing sequences for the primal one. Indeed, the dual approach more readily facilitates numerical computations for some of the selected models. While intended primarily for applied mathematicians, the text will also be of interest to engineers, physicists, and other researchers in related fields.

Smart variations: Functional substructures for part compatibility

KAUST Repository

Zheng, Youyi; Cohen-Or, Daniel; Mitra, Niloy J.

2013-01-01

As collections of 3D models continue to grow, reusing model parts allows generation of novel model variations. Naïvely swapping parts across models, however, leads to implausible results, especially when mixing parts across different model families

Photographic Records Showing the Variations of the Virtual Height of Reflection as a Function of the Radio Frequency

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The standard (analog) ionosonde produces photographic records known as ionograms, which show the variations of the virtual height of reflection as a function of the...

Dynamics of neuroendocrine stress response: bistability, timing, and control of hypocortisolism

Science.gov (United States)

D'Orsogna, Maria; Chou, Tom; Kim, Lae

The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system that regulates numerous physiological processes. Disruptions in its activity are correlated with stress-related diseases such as post-traumatic stress disorder (PTSD) and major depressive disorder. We characterize ``normal'' and ``diseased'' states of the HPA axis as basins of attraction of a dynamical system describing the inhibition of peptide hormones, corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), by circulating glucocorticoids such as cortisol (CORT). Our model includes ultradian oscillations, CRH self-upregulation of CRH release, and distinguishes two components of negative feedback by cortisol on circulating CRH levels: a slow direct suppression of CRH synthesis and a fast indirect effect on CRH release. The slow regulation mechanism mediates external stress-driven transitions between the stable states in novel, intensity, duration, and timing-dependent ways. We find that the timing of traumatic events may be an important factor in determining if and how the hallmarks of depressive disorders will manifest. Our model also suggests a mechanism whereby exposure therapy of stress disorders may act to normalize downstream dysregulation of the HPA axis.

Renal ornithine decarboxylase activity, polyamines, and compensatory renal hypertrophy in the rat

International Nuclear Information System (INIS)

Humphreys, M.H.; Etheredge, S.B.; Lin, Shanyan; Ribstein, J.; Marton, L.J.

1988-01-01

The authors determined the role of ornithine decarboxylase (ODC) in compensatory renal hypertrophy (CRH) by relating renal ODC activity and polyamine content to kidney size, expressed as a percent of body weight, 1 wk after unilateral nephrectomy (UN). In normal rats, renal ODC activity increased after UN; 1 wk later the remaining kidney weight had increased. Renal concentration of putrescine, the product of ODC's decarboxylation of ornithine, was increased 3, 8, and 48 h after UN, but concentrations of polyamines synthesized later in the pathway, spermidine and spermine, were not appreciably affected. Pretreatment with difluoromethylornithine (DFMO), an irreversible inhibitor of ODC inhibited both base-line renal ODC activity and putrescine concentration as well as increases stimulated by UN, although concentrations of spermidine and spermine were not decreased. In hypophysectomized rats, both increased renal ODC activity and CRH occurred as well, indicating that these two consequences of UN do not require intact pituitary function. Thus stimulation of renal ODC activity and putrescine content do not appear critical to the process of CRH after UN

The role of urocortins in the cardiovascular system.

Science.gov (United States)

Walczewska, J; Dzieza-Grudnik, A; Siga, O; Grodzicki, T

2014-12-01

Urocortins (Ucn) 1, 2 and 3 are a group of endogenous peptide hormones belonging to the corticotropin-releasing hormone (CRH) family of peptides. The presence of urocortins has been detected in the central nervous system as well as in peripheral tissues. They play an important role in a stress response (with respect to its duration, intensity and restoration of homeostasis). They also act as regulatory factors of the cardiovascular, gastrointestinal, reproductive and immune systems. Urocortins act by binding to G-protein-coupled receptors (GPCR). The "central" effects of urocortins are mediated mainly by activation of CRH receptor 1 (CRH-R1), and the "peripheral" effects by activation of CRH-R2. Ucn2 and Ucn3 are selective CRH-R2 agonists and have much higher binding affinity to this receptor than CRH and Ucn1. Recent studies have shown that urocortins exert various biological effects in the cardiovascular system, such as vasodilation, positive inotropic and lusitropic effects, as well as cardioprotection against ischemia-reperfusion injury. They also suppress the renin-angiotensin system and may have an impact on the sympathetic nervous system. Urocortins and CRH-R2 may be a potential therapeutic target in coronary heart disease, congestive heart failure and hypertension. This review summarizes the data published to date on the role of urocortins in the cardiovascular system.

Plasma adiponectin levels are increased despite insulin resistance in corticotropin-releasing hormone transgenic mice, an animal model of Cushing syndrome.

Science.gov (United States)

Shinahara, Masayuki; Nishiyama, Mitsuru; Iwasaki, Yasumasa; Nakayama, Shuichi; Noguchi, Toru; Kambayashi, Machiko; Okada, Yasushi; Tsuda, Masayuki; Stenzel-Poore, Mary P; Hashimoto, Kozo; Terada, Yoshio

2009-01-01

Adiponectin (AdN), an adipokine derived from the adipose tissue, has an insulin-sensitizing effect, and plasma AdN is shown to be decreased in obesity and/or insulin resistant state. To clarify whether changes in AdN are also responsible for the development of glucocorticoid-induced insulin resistance, we examined AdN concentration in plasma and AdN expression in the adipose tissue, using corticotropin-releasing hormone (CRH) transgenic mouse (CRH-Tg), an animal model of Cushing syndrome. We found, unexpectedly, that plasma AdN levels in CRHTg were significantly higher than those in wild-type littermates (wild-type: 19.7+/-2.5, CRH-Tg: 32.4+/-3.1 microg/mL, pAdN mRNA and protein levels were significantly decreased in the adipose tissue of CRH-Tg. Bilateral adrenalectomy in CRH-Tg eliminated both their Cushing's phenotype and their increase in plasma AdN levels (wild-type/sham: 9.4+/-0.5, CRH-Tg/sham: 15.7+/-2.0, CRH-Tg/ADX: 8.5+/-0.4 microg/mL). These results strongly suggest that AdN is not a major factor responsible for the development of insulin resistance in Cushing syndrome. Our data also suggest that glucocorticoid increases plasma AdN levels but decreases AdN expression in adipocytes, the latter being explained possibly by the decrease in AdN metabolism in the Cushing state.

Hypothalamic amenorrhea with normal body weight: ACTH, allopregnanolone and cortisol responses to corticotropin-releasing hormone test.

Science.gov (United States)

Meczekalski, B; Tonetti, A; Monteleone, P; Bernardi, F; Luisi, S; Stomati, M; Luisi, M; Petraglia, F; Genazzani, A R

2000-03-01

Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic-pituitary-adrenal axis in HA. We included 8 patients (aged 23.16+/-1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. Serum basal levels of FSH, LH, and estradiol as well as basal levels of allopregnanolone were significantly lower in HA patients than in controls (P<0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P<0.001). The response (area under the curve) of ACTH, allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P<0.001, P<0.05, P<0.05 respectively). In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus-pituitary-adrenal axis hyperactivity, are characterized by low allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.

Stress and visceral pain: focusing on irritable bowel syndrome.

Science.gov (United States)

Fukudo, Shin

2013-12-01

Recent advances in brain science have shown that the brain function encoding emotion depends on interoceptive signals such as visceral pain. Visceral pain arose early in our evolutionary history. Bottom-up processing from gut-to-brain and top-down autonomic/neuroendocrine mechanisms in brain-to-gut signaling constitute a circuit. Brain imaging techniques have enabled us to depict the visceral pain pathway as well as the related emotional circuit. Irritable bowel syndrome (IBS) is characterized by chronic recurrent abdominal pain or abdominal discomfort associated with bowel dysfunction. It is also thought to be a disorder of the brain-gut link associated with an exaggerated response to stress. Corticotropin-releasing hormone (CRH), a major mediator of the stress response in the brain-gut axis, is an obvious candidate in the pathophysiology of IBS. Indeed, administration of CRH has been shown to aggravate the visceral sensorimotor response in IBS patients, and the administration of peptidergic CRH antagonists seems to alleviate IBS pathophysiology. Serotonin (5-HT) is another likely candidate associated with brain-gut function in IBS, as 5-HT3 antagonists, 5-HT4 agonists, and antidepressants were demonstrated to regulate 5-HT neurotransmission in IBS patients. Autonomic nervous system function, the neuroimmune axis, and the brain-gut-microbiota axis show specific profiles in IBS patients. Further studies on stress and visceral pain neuropathways in IBS patients are warranted. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Variation in Functional Independence among Stroke Survivors Having Fatigue and Depression.

Science.gov (United States)

Badaru, Umaru Muhammad; Ogwumike, Omoyemi Olubunmi; Adeniyi, Ade Fatai; Olowe, Olajide Olubanji

2013-01-01

Objective. This study evaluated variation in functional independence in activities of daily living (ADL) and instrumental activities of daily living (IADL) among individuals with poststroke fatigue (PSF) and poststroke depression (PSD). Methods. A cross-sectional survey involved 65 consenting poststroke survivors who were purposively recruited from physiotherapy clinics of the University College Hospital, Ibadan, Adeoyo Maternity Teaching Hospital, Ibadan, and Federal Medical Center, Gusau. Participants were assessed for symptoms of PSD with short geriatric depression scale-15, PSF with fatigue severity scale, ADL with Barthel Index and IADL with Nottingham extended ADL scale. Data analysis was done using Chi-square and unpaired t-test with significance level being 0.05. Results. Participants' age ranged from 58 to 80 years. PSD alone (P = 0.002) and both PSF and PSD (P = 0.02) were significantly associated with ADL, while PSF alone was not (P = 0.233). PSD alone (P = 0.001) and both PSF and PSD (P = 0.001) significantly negatively affected IADL, while PSF alone had no significant effect (P = 0.2). Conclusions. Participants with PSD alone and those with both PSF and PSD had lower functional independence in ADL and IADL.

Variation in Functional Independence among Stroke Survivors Having Fatigue and Depression

Directory of Open Access Journals (Sweden)

Umaru Muhammad Badaru

2013-01-01

Full Text Available Objective. This study evaluated variation in functional independence in activities of daily living (ADL and instrumental activities of daily living (IADL among individuals with poststroke fatigue (PSF and poststroke depression (PSD. Methods. A cross-sectional survey involved 65 consenting poststroke survivors who were purposively recruited from physiotherapy clinics of the University College Hospital, Ibadan, Adeoyo Maternity Teaching Hospital, Ibadan, and Federal Medical Center, Gusau. Participants were assessed for symptoms of PSD with short geriatric depression scale-15, PSF with fatigue severity scale, ADL with Barthel Index and IADL with Nottingham extended ADL scale. Data analysis was done using Chi-square and unpaired t-test with significance level being 0.05. Results. Participants’ age ranged from 58 to 80 years. PSD alone (P=0.002 and both PSF and PSD (P=0.02 were significantly associated with ADL, while PSF alone was not (P=0.233. PSD alone (P=0.001 and both PSF and PSD (P=0.001 significantly negatively affected IADL, while PSF alone had no significant effect (P=0.2. Conclusions. Participants with PSD alone and those with both PSF and PSD had lower functional independence in ADL and IADL.

A function space framework for structural total variation regularization with applications in inverse problems

Science.gov (United States)

Hintermüller, Michael; Holler, Martin; Papafitsoros, Kostas

2018-06-01

In this work, we introduce a function space setting for a wide class of structural/weighted total variation (TV) regularization methods motivated by their applications in inverse problems. In particular, we consider a regularizer that is the appropriate lower semi-continuous envelope (relaxation) of a suitable TV type functional initially defined for sufficiently smooth functions. We study examples where this relaxation can be expressed explicitly, and we also provide refinements for weighted TV for a wide range of weights. Since an integral characterization of the relaxation in function space is, in general, not always available, we show that, for a rather general linear inverse problems setting, instead of the classical Tikhonov regularization problem, one can equivalently solve a saddle-point problem where no a priori knowledge of an explicit formulation of the structural TV functional is needed. In particular, motivated by concrete applications, we deduce corresponding results for linear inverse problems with norm and Poisson log-likelihood data discrepancy terms. Finally, we provide proof-of-concept numerical examples where we solve the saddle-point problem for weighted TV denoising as well as for MR guided PET image reconstruction.

Radial variation in sap velocity as a function of stem diameter and sapwood thickness in yellow-poplar trees.

Science.gov (United States)

Wullschleger, Stan D.; King, Anthony W.

2000-04-01

Canopy transpiration and forest water use are frequently estimated as the product of sap velocity and cross-sectional sapwood area. Few studies, however, have considered whether radial variation in sap velocity and the proportion of sapwood active in water transport are significant sources of uncertainty in the extrapolation process. Therefore, radial profiles of sap velocity were examined as a function of stem diameter and sapwood thickness for yellow-poplar (Liriodendron tulipifera L.) trees growing on two adjacent watersheds in eastern Tennessee. The compensation heat pulse velocity technique was used to quantify sap velocity at four equal-area depths in 20 trees that ranged in stem diameter from 15 to 69 cm, and in sapwood thickness from 2.1 to 14.8 cm. Sap velocity was highly dependent on the depth of probe insertion into the sapwood. Rates of sap velocity were greatest for probes located in the two outer sapwood annuli (P1 and P2) and lowest for probes in closest proximity to the heartwood (P3 and P4). Relative sap velocities averaged 0.98 at P1, 0.66 at P2, 0.41 at P3 and 0.35 at P4. Tree-specific sap velocities measured at each of the four probe positions, divided by the maximum sap velocity measured (usually at P1 or P2), indicated that the fraction of sapwood functional in water transport (f(S)) varied between 0.49 and 0.96. There was no relationship between f(S) and sapwood thickness, or between f(S) and stem diameter. The fraction of functional sapwood averaged 0.66 +/- 0.13 for trees on which radial profiles were determined. No significant depth-related differences were observed for sapwood density, which averaged 469 kg m(-3) across all four probe positions. There was, however, a significant decline in sapwood water content between the two outer probe positions (1.04 versus 0.89 kg kg(-1)). This difference was not sufficient to account for the observed radial variation in sap velocity. A Monte-Carlo analysis indicated that the standard error in

Opposite variations in maternal and neonatal thyroid function induced by iodine supplementation during pregnancy

DEFF Research Database (Denmark)

Nøhr, S B; Laurberg, P

2000-01-01

pregnancy, and 95 took no artificial iodine supplementation. Iodine supplementation (+I) induced opposite variations in thyroid function in the mother and the fetus. In +I mothers, TSH was 7.6% lower than in mothers with no supplementation (P ... in the +I group (P caused by opposite shifts in TSH frequency distribution in mothers and neonates. The association between iodine supplementation and high serum TSH in the neonates was further substantiated by an inverse correlation between thyroglobulin and TSH in cord blood...

Corticotropin-releasing hormone expression in patients with intrahepatic cholestasis of pregnancy after ursodeoxycholic acid treatment: an initial experience.

Science.gov (United States)

Zhou, Fan; Zhang, Li; He, Mao Mao; Liu, Zheng Fei; Gao, Bing Xin; Wang, Xiao Dong

2014-08-01

Corticotropin-releasing hormone (CRH) is one of the most potent vasodilatory factors in the human feto-placental circulation. The expression of CRH was significantly down-regulated in patients with intrahepatic cholestasis of pregnancy (ICP). One hundred pregnant women diagnosed with ICP at 34-34(+6) weeks of gestation agreed to participate in this prospective nested case-control study. Thirty ICP patients were finally recruited in this study, with 16 cases in the ursodeoxycholic acid (UDCA) group (UDCA 750 mg/d) and 14 cases in the control group (Transmetil 1000 mg/d or Essentiale 1368 mg/d). Maternal serum samples were obtained in diagnosis and at 37-37(+6) weeks of gestation. Placental tissues were obtained from participants after delivery. ELISA, enzymatic colorimetric and Western blotting were used to evaluate the concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA) and CRH in maternal serum and expression of CRH in placenta tissues. The UDCA group had greater reduction in maternal serum ALT, AST and TBA levels in ICP patients (all p < 0.01). Maternal serum CRH concentrations in the UDCA group after treatment (122.10 ± 44.20) pg/ml was significantly higher than pretreatment (95.45 ± 26.47) pg/ml (p < 0.01). After treatment, maternal serum CRH concentrations of the UDCA group (122.10 ± 44.20) pg/ml was significantly higher than in the control group (80.71 ± 41.10) pg/ml (p < 0.01). Placental CRH expression in the UDCA group (2.79 ± 1.72) was significantly higher than in the control group (0.69 ± 0.36) (p < 0.01). Maternal serum and placental CRH expression in ICP patients were up-regulated after treatment of UDCA. The up-regulation of CRH expression after UDCA treatment may play an important role in the therapeutic mechanism of ICP. All patients recruited in this study had severe cholestasis (TBA ≥ 40 µmol/L). Further studies are warranted in

Modulation of Sleep Homeostasis by Corticotropin Releasing Hormone in REM Sleep-Deprived Rats

Directory of Open Access Journals (Sweden)

Ricardo Borges Machado

2010-01-01

Full Text Available Studies have shown that sleep recovery following different protocols of forced waking varies according to the level of stress inherent to each method. Sleep deprivation activates the hypothalamic-pituitary-adrenal axis and increased corticotropin-releasing hormone (CRH impairs sleep. The purpose of the present study was to evaluate how manipulations of the CRH system during the sleep deprivation period interferes with subsequent sleep rebound. Throughout 96 hours of sleep deprivation, separate groups of rats were treated i.c.v. with vehicle, CRH or with alphahelical CRH9−41, a CRH receptor blocker, twice/day, at 07:00 h and 19:00 h. Both treatments impaired sleep homeostasis, especially in regards to length of rapid eye movement sleep (REM and theta/delta ratio and induced a later decrease in NREM and REM sleep and increased waking bouts. These changes suggest that activation of the CRH system impact negatively on the homeostatic sleep response to prolonged forced waking. These results indicate that indeed, activation of the HPA axis—at least at the hypothalamic level—is capable to reduce the sleep rebound induced by sleep deprivation.

Environmental assessment of indoor radon gas exposure health hazards and some of its public risks

International Nuclear Information System (INIS)

Hussein, Abd El-Razik. Z.; Ibrahim, M.Se.; Ragab, M.H.; El-Bukhari, M.S.

2005-01-01

This study examine the relationship between indoor radon gas exposure and the cancer risk and housing characteristics in lung cancer risk houses (CRH) compared to non lung cancer risk houses (NCRH). Mean radon concentrations measured by active method were significantly higher among CRH compared to NCRH, 9:93 pCi/L versus 4.56 pCi/L, respectively. There was no statistically significant diurnal variation as regards radon levels in all examined houses. Indoor radon concentrations show statistically significance in houses with bad ventilation (low air change rate) compared to houses with good ventilation (high air change rate). Houses with floor material of tiles, had statistically significant higher radon concentrations. Neither finishing wall material nor indoor gas source shows statistically significance as regard radon levels. Radon levels > 4 pCi/L (US EPA action level) were statistically significance higher in bed rooms compared levels in living rooms. High radon concentrations were reported in lung cane risk houses and in houses with bad ventilation

On the existence and uniqueness of minima and maxima on spheres of the integral functional of the calculus of variations

OpenAIRE

Ricceri, Biagio

2005-01-01

We deal with the integral functional of the calculus of variations assuming that the gradient of the integrand is Lipschitzian. We then prove that if this gradient does not vanish at zero, then the functional has a unique minimum and a unique maximum on each sphere, centered at zero, with radius small enough.

Sexual dimorphism of stress response and immune/ inflammatory reaction: the corticotropin releasing hormone perspective

Directory of Open Access Journals (Sweden)

Nicholas V. Vamvakopoulos

1995-01-01

Full Text Available This review higlghts key aspects of corticotropin releasing hormone (CRH biology of potential relevance to the sexual dimorphism of the stress response and immune/inflammatory reaction, and introduces two important new concepts based on the regulatory potential of the human (h CRH gene: (1 a proposed mechanism to account for the tissue-specific antithetical responses of hCRH gene expression to glucocorticolds, that may also explain the frequently observed antithetical effects of chronic glucocorticoid administration in clinical practice and (2 a heuristic diagram to illustrate the proposed modulation of the stress response and immune/ inflammatory reaction by steroid hormones, from the perspective of the CRH system.

On the co-variation between form and function of adnominal possessive modifiers in Dutch and English

DEFF Research Database (Denmark)

Rijkhoff, Jan

2009-01-01

in the noun phrase (section 3); a tentative explanation is given in section 4. The more general point this paper wants to make is that functional modifier categories like CLASSIFYING MODIFIER or QUALIFYING MODIFIER can be characterized in grammatical terms and, furthermore, that important grammatical...... that the remarkable variation in the grammatical properties of this possessive construction directly correlates with the kind of modifier function it has in the noun phrase. It is first shown that lexical possessive modifiers with van ‘of’ (“adnominal possessives” for short) are used to express most of the modifier...... functions recognized in a semantic, five-layered model of the noun phrase (section 2). I will then argue that the values for certain grammatical parameters (here subsumed under the labels MODIFICATION, PREDICATION, REFERENCE) correlate with the kind of modifier function the adnominal possessive has...

Variational theory of nuclear and neutron matter

International Nuclear Information System (INIS)

Pandharipande, V.R.; Wiringa, R.B.

1989-06-01

In these lectures we will discuss attempts to solve the A = 3 to ∞ nuclear many-body problems with the variational method. We choose the form of a variational wave function Χ v (1, 2 hor-ellipsis A) to describe the ground state. The Χ v and the ground-state energy E v are obtained by minimizing E v = left-angle Χ v |H|Χ v right-angle/left-angle Χ v |Χ v right-angle with respect to variations in Χ v . If the form of the variational wave function is chosen properly we can expect Χ v ∼ Χ 0 and E v ∼ E 0 where Χ 0 and E 0 are the exact ground-state wave function and energy. In general E v ≥ E 0 in variational calculations. 63 refs., 11 figs

Nonequilibrium thermodynamics of interacting tunneling transport: variational grand potential, density functional formulation and nature of steady-state forces

International Nuclear Information System (INIS)

Hyldgaard, P

2012-01-01

The standard formulation of tunneling transport rests on an open-boundary modeling. There, conserving approximations to nonequilibrium Green function or quantum statistical mechanics provide consistent but computational costly approaches; alternatively, the use of density-dependent ballistic-transport calculations (e.g., Lang 1995 Phys. Rev. B 52 5335), here denoted ‘DBT’, provides computationally efficient (approximate) atomistic characterizations of the electron behavior but has until now lacked a formal justification. This paper presents an exact, variational nonequilibrium thermodynamic theory for fully interacting tunneling and provides a rigorous foundation for frozen-nuclei DBT calculations as a lowest-order approximation to an exact nonequilibrium thermodynamic density functional evaluation. The theory starts from the complete electron nonequilibrium quantum statistical mechanics and I identify the operator for the nonequilibrium Gibbs free energy which, generally, must be treated as an implicit solution of the fully interacting many-body dynamics. I demonstrate a minimal property of a functional for the nonequilibrium thermodynamic grand potential which thus uniquely identifies the solution as the exact nonequilibrium density matrix. I also show that the uniqueness-of-density proof from a closely related Lippmann-Schwinger collision density functional theory (Hyldgaard 2008 Phys. Rev. B 78 165109) makes it possible to express the variational nonequilibrium thermodynamic description as a single-particle formulation based on universal electron-density functionals; the full nonequilibrium single-particle formulation improves the DBT method, for example, by a more refined account of Gibbs free energy effects. I illustrate a formal evaluation of the zero-temperature thermodynamic grand potential value which I find is closely related to the variation in the scattering phase shifts and hence to Friedel density oscillations. This paper also discusses the

Opposite variations in maternal and neonatal thyroid function induced by iodine supplementation during pregnancy

DEFF Research Database (Denmark)

Nøhr, S B; Laurberg, P

2000-01-01

Whereas the consequences of extremes in iodine intake are well described, much less is known about the effect of more moderate variations in maternal iodine intake on fetal thyroid function. The present study performed in Denmark with mild to moderate iodine deficiency dealt with the effect...... (P iodine intake in both mothers and neonates. The results suggest that the fetal thyroid, at least in areas of mild iodine deficiency, is more sensitive to the inhibitory effect of iodine...... of maternal iodine supplementation on thyroid function in the mother at term and in the fetus/neonate. Serum was collected consecutively from pregnant women at term (n = 144) and from cord blood (n = 139). Forty-nine women had a regular intake of vitamin and mineral tablets with iodine (150 microg/day) during...

Variational divergence in wave scattering theory with Kirchhoffean trial functions

Science.gov (United States)

Bird, J. F.

1986-01-01

In a recent study of variational improvement of the Kirchhoff approximation for electromagnetic scattering by rough surfaces, a key ingredient in the variational principle was found to diverge for important configurations (e.g., backscatter) if the polarization had any vertical component. The cause and a cure of this divergence are discussed here. The divergence is demonstrated to occur for arbitrary perfectly conducting scatterers and its universal characterstics are determined, by means of a general divergence criterion that is derived. A variational cure for the divergence is prescribed, and it is tested successfully on a standard scattering model.

The stress system in depression and neurodegeneration: focus on the human hypothalamus.

Science.gov (United States)

Bao, A-M; Meynen, G; Swaab, D F

2008-03-01

The stress response is mediated by the hypothalamo-pituitary-adrenal (HPA) system. Activity of the corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) forms the basis of the activity of the HPA-axis. The CRH neurons induce adrenocorticotropin (ACTH) release from the pituitary, which subsequently causes cortisol release from the adrenal cortex. The CRH neurons co-express vasopressin (AVP) which potentiates the CRH effects. CRH neurons project not only to the median eminence but also into brain areas where they, e.g., regulate the adrenal innervation of the autonomic system and affect mood. The hypothalamo-neurohypophysial system is also involved in stress response. It releases AVP from the PVN and the supraoptic nucleus (SON) and oxytocin (OXT) from the PVN via the neurohypophysis into the bloodstream. The suprachiasmatic nucleus (SCN), the hypothalamic clock, is responsible for the rhythmic changes of the stress system. Both centrally released CRH and increased levels of cortisol contribute to the signs and symptoms of depression. Symptoms of depression can be induced in experimental animals by intracerebroventricular injection of CRH. Depression is also a frequent side effect of glucocorticoid treatment and of the symptoms of Cushing's syndrome. The AVP neurons in the hypothalamic PVN and SON are also activated in depression, which contributes to the increased release of ACTH from the pituitary. Increased levels of circulating AVP are also associated with the risk for suicide. The prevalence, incidence and morbidity risk for depression are higher in females than in males and fluctuations in sex hormone levels are considered to be involved in the etiology. About 40% of the activated CRH neurons in mood disorders co-express nuclear estrogen receptor (ER)-alpha in the PVN, while estrogen-responsive elements have been found in the CRH gene promoter region, and estrogens stimulate CRH production. An androgen

Time evolution of coupled-bunch modes from beta function variation in storage rings

Directory of Open Access Journals (Sweden)

Kai Meng Hock

2007-08-01

Full Text Available We present an analytical and numerical study of the equations of motion for bunches coupled by transverse wakefields. We base our study on a recent lattice design for the damping rings in the baseline configuration of the International Linear Collider. Using the macroparticle model, and assuming resistive wall wakefield coupling, we present numerical results on the time evolution of the multibunch modes. Decay modes display growth after initial decay, and mode amplitudes exhibit high-frequency oscillations. These phenomena are not expected if the beta function is assumed to have a constant, averaged value. We show analytically that they can come from coupling between modes caused by variation of the beta function in a real lattice. The effect is shown to be comparable to the effect of a nonuniform fill pattern and significantly larger than that of the higher-order mode wakefield localized in the rf cavities. Turning to the case of constant beta function, we develop a more complete treatment of the equations of motion. We derive general formulas for the bunch trajectories, and show that such formulas can only be valid in the limit of small wakefield coupling.

Variational model for one-dimensional quantum magnets

Science.gov (United States)

Kudasov, Yu. B.; Kozabaranov, R. V.

2018-04-01

A new variational technique for investigation of the ground state and correlation functions in 1D quantum magnets is proposed. A spin Hamiltonian is reduced to a fermionic representation by the Jordan-Wigner transformation. The ground state is described by a new non-local trial wave function, and the total energy is calculated in an analytic form as a function of two variational parameters. This approach is demonstrated with an example of the XXZ-chain of spin-1/2 under a staggered magnetic field. Generalizations and applications of the variational technique for low-dimensional magnetic systems are discussed.

In vivo correlation between c-Fos expression and corticotroph stimulation by adrenocorticotrophic hormone secretagogues in rat anterior pituitary gland.

Science.gov (United States)

Takigami, Shu; Fujiwara, Ken; Kikuchi, Motoshi; Yashiro, Takashi

2008-03-01

In the anterior pituitary gland, c-Fos expression is evoked by various stimuli. However, whether c-Fos expression is directly related to the stimulation of anterior pituitary cells by hypothalamic secretagogues is unclear. To confirm whether the reception of hormone-releasing stimuli evokes c-Fos expression in anterior pituitary cells, we have examined c-Fos expression of anterior pituitary glands in rats administered with synthetic corticotrophin-releasing hormone (CRH) intravenously or subjected to restraint stress. Single intravenous administration of CRH increases the number of c-Fos-expressing cells, and this number does not change even if the dose is increased. Double-immunostaining has revealed that most of the c-Fos-expressing cells contain adrenocorticotrophic hormone (ACTH); corticotrophs that do not express c-Fos in response to CRH have also been found. However, restraint stress evokes c-Fos expression in most of the corticotrophs and in a partial population of lactotrophs. These results suggest that c-Fos expression increases in corticotrophs stimulated by ACTH secretagogues, including CRH. Furthermore, we have found restricted numbers of corticotrophs expressing c-Fos in response to CRH. Although the mechanism underlying the different responses to CRH is not apparent, c-Fos is probably a useful immunohistochemical marker for corticotrophs stimulated by ACTH secretagogues.

Sound velocity variation as function of polarization state in Lead Zirconate Titanate (PZT) Ceramics

International Nuclear Information System (INIS)

Essolaani, W; Farhat, N

2012-01-01

There are several ultrasonic techniques to measure the sound velocity, for example, the pulse-echo method. In such method, the size of transducer used to measure the sound velocity must be in the same order of the sample size. If not, the incompatibility of sizes becomes an error source of the sound velocity measurement. In this work, the Laser Induced Pressure Pulse (LIPP) method is used as ultrasonic method. This method has been very useful for studying the spatial distribution of charges and polarization in dielectrics. We take advantage of the fact that the method allows the sound velocity measurement, to study its variation as function of polarization state in (PZT) ceramics. In a sample with a known thickness e, the sound velocity ν is deduced from the measurement of the transit time T. The sound velocity depends on the elastic constants which in turn they depend on poling conditions. Thus, the variation of the sound velocity is related to the direction and the amplitude of the polarization.

Variational theory of nuclear and neutron matter

Energy Technology Data Exchange (ETDEWEB)

Pandharipande, V.R.; Wiringa, R.B. (Illinois Univ., Urbana, IL (USA). Dept. of Physics; Argonne National Lab., IL (USA))

1989-06-01

In these lectures we will discuss attempts to solve the A = 3 to {infinity} nuclear many-body problems with the variational method. We choose the form of a variational wave function {Chi}{sub v}(1, 2{hor ellipsis}A) to describe the ground state. The {Chi}{sub v} and the ground-state energy E{sub v} are obtained by minimizing E{sub v} = {l angle}{Chi}{sub v}{vert bar}H{vert bar}{Chi}{sub v}{r angle}/{l angle}{Chi}{sub v}{vert bar}{Chi}{sub v}{r angle} with respect to variations in {Chi}{sub v}. If the form of the variational wave function is chosen properly we can expect {Chi}{sub v} {approx} {Chi}{sub 0} and E{sub v} {approx} E{sub 0} where {Chi}{sub 0} and E{sub 0} are the exact ground-state wave function and energy. In general E{sub v} {ge} E{sub 0} in variational calculations. 63 refs., 11 figs.

Sexual dimorphism of stress response and immune/ inflammatory reaction: the corticotropin releasing hormone perspective

OpenAIRE

Vamvakopoulos, Nicholas V.

1995-01-01

This review higlghts key aspects of corticotropin releasing hormone (CRH) biology of potential relevance to the sexual dimorphism of the stress response and immune/inflammatory reaction, and introduces two important new concepts based on the regulatory potential of the human (h) CRH gene: (1) a proposed mechanism to account for the tissue-specific antithetical responses of hCRH gene expression to glucocorticolds, that may also explain the frequently observed antithetical effects of chronic gl...

Temporal and spatial variations in fly ash quality

Science.gov (United States)

Hower, J.C.; Trimble, A.S.; Eble, C.F.

2001-01-01

Fly ash quality, both as the amount of petrographically distinguishable carbons and in chemistry, varies in both time and space. Temporal variations are a function of a number of variables. Variables can include variations in the coal blend organic petrography, mineralogy, and chemistry; variations in the pulverization of the coal, both as a function of the coal's Hardgrove grindability index and as a function of the maintenance and settings of the pulverizers; and variations in the operating conditions of the boiler, including changes in the pollution control system. Spatial variation, as an instantaneous measure of fly ash characteristics, should not involve changes in the first two sets of variables listed above. Spatial variations are a function of the gas flow within the boiler and ducts, certain flow conditions leading to a tendency for segregation of the less-dense carbons in one portion of the gas stream. Caution must be applied in sampling fly ash. Samples from a single bin, or series of bins, m ay not be representative of the whole fly ash, providing a biased view of the nature of the material. Further, it is generally not possible to be certain about variation until the analysis of the ash is complete. ?? 2001 Elsevier Science B.V. All rights reserved.

The stress response and the hypothalamic-pituitary-adrenal axis: from molecule to melancholia.

LENUS (Irish Health Repository)

O'Connor, T M

2012-02-03

Organisms survive by maintaining equilibrium with their environment. The stress system is critical to this homeostasis. Glucocorticoids modulate the stress response at a molecular level by altering gene expression, transcription, and translation, among other pathways. The effect is the inhibition of the functions of inflammatory cells, predominantly mediated through inhibition of cytokines, such as IL-1, IL-6, and TNF-alpha. The central effectors of the stress response are the corticotrophin-releasing hormone (CRH) and locus coeruleus-norepinephrine (LC-NE)\\/sympathetic systems. The CRH system activates the stress response and is subject to modulation by cytokines, hormones, and neurotransmitters. Glucocorticoids also modulate the growth, reproductive and thyroid axes. Abnormalities of stress system activation have been shown in inflammatory diseases such as rheumatoid arthritis, as well as behavioural syndromes such as melancholic depression. These disorders are comparable to those seen in rats whose CRH system is genetically abnormal. Thus, the stress response is central to resistance to inflammatory and behavioural syndromes. In this review, we describe the response to stress at molecular, cellular, neuroendocrine and behavioural levels, and discuss the disease processes that result from a dysregulation of this response, as well as recent developments in their treatment.

The two-hole ground state of the Hubbard-Anderson model, approximated by a variational RVB-type wave function

NARCIS (Netherlands)

Traa, M.R.M.J.; Traa, M.R.M.J.; Caspers, W.J.; Caspers, W.J.; Banning, E.J.; Banning, E.J.

1994-01-01

In this paper the Hubbard-Anderson model on a square lattice with two holes is studied. The ground state (GS) is approximated by a variational RVB-type wave function. The holes interact by exchange of a localized spin excitation (SE), which is created or absorbed if a hole moves to a

Elevated Midpregnancy Corticotropin-Releasing Hormone Is Associated with Prenatal, But Not Postpartum, Maternal Depression

OpenAIRE

Rich-Edwards, J. W.; Mohllajee, A. P.; Kleinman, K.; Hacker, M. R.; Majzoub, J.; Wright, R. J.; Gillman, M. W.

2008-01-01

Context: Elevated hypothalamic CRH has been implicated in melancholic major depression in nonpregnant individuals, but the role of placental CRH in maternal prenatal and postpartum depression is largely unexplored.

Variational principles for the projected breakup amplitude

International Nuclear Information System (INIS)

Hahn, Y.

1976-01-01

Two alternate forms of variational principles for the breakup amplitude describing the two- to three-cluster transition are derived such that all the integrals involved in the intermediate stages are well defined. The first form contains a trial Green's function with which both the initial and final state trial wave functions are constructed. The earlier form of the Kohn-type variational principle derived by Lieber, Rosenberg, and Spruch is recovered, however, when this connection between the trial functions is removed. The second form of the variational principle is derived by projecting out from the trial functions all the open channel components which correspond to the two-cluster structures including the rearrangement channels. The remaining part of the wave functions describes the channels with three-cluster structures, and the integrals involving this part are then mathematically well defined

Characterization and potential functional significance of human-chimpanzee large INDEL variation

Directory of Open Access Journals (Sweden)

Polavarapu Nalini

2011-10-01

Full Text Available Abstract Background Although humans and chimpanzees have accumulated significant differences in a number of phenotypic traits since diverging from a common ancestor about six million years ago, their genomes are more than 98.5% identical at protein-coding loci. This modest degree of nucleotide divergence is not sufficient to explain the extensive phenotypic differences between the two species. It has been hypothesized that the genetic basis of the phenotypic differences lies at the level of gene regulation and is associated with the extensive insertion and deletion (INDEL variation between the two species. To test the hypothesis that large INDELs (80 to 12,000 bp may have contributed significantly to differences in gene regulation between the two species, we categorized human-chimpanzee INDEL variation mapping in or around genes and determined whether this variation is significantly correlated with previously determined differences in gene expression. Results Extensive, large INDEL variation exists between the human and chimpanzee genomes. This variation is primarily attributable to retrotransposon insertions within the human lineage. There is a significant correlation between differences in gene expression and large human-chimpanzee INDEL variation mapping in genes or in proximity to them. Conclusions The results presented herein are consistent with the hypothesis that large INDELs, particularly those associated with retrotransposons, have played a significant role in human-chimpanzee regulatory evolution.

Unambiguous results from variational matrix Pade approximants

International Nuclear Information System (INIS)

Pindor, Maciej.

1979-10-01

Variational Matrix Pade Approximants are studied as a nonlinear variational problem. It is shown that although a stationary value of the Schwinger functional is a stationary value of VMPA, the latter has also another stationary value. It is therefore proposed that instead of looking for a stationary point of VMPA, one minimizes some non-negative functional and then one calculates VMPA at the point where the former has the absolute minimum. This approach, which we call the Method of the Variational Gradient (MVG) gives unambiguous results and is also shown to minimize a distance between the approximate and the exact stationary values of the Schwinger functional

Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels

DEFF Research Database (Denmark)

Nossent, Anne Yaël; Robben, J H; Deen, P M T

2010-01-01

SUMMARY OBJECTIVES: Stimulation of arginine vasopressin 2 receptor (V2R) with arginine vasopressin (AVP) results in a rise in von Willebrand factor (VWF) and factor VIII plasma levels. We hypothesized that gain-of-function variations in the V2R gene (AVPR2) would lead to higher plasma levels of V...

Gauging Variational Inference

Energy Technology Data Exchange (ETDEWEB)

Chertkov, Michael [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Ahn, Sungsoo [Korea Advanced Inst. Science and Technology (KAIST), Daejeon (Korea, Republic of); Shin, Jinwoo [Korea Advanced Inst. Science and Technology (KAIST), Daejeon (Korea, Republic of)

2017-05-25

Computing partition function is the most important statistical inference task arising in applications of Graphical Models (GM). Since it is computationally intractable, approximate methods have been used to resolve the issue in practice, where meanfield (MF) and belief propagation (BP) are arguably the most popular and successful approaches of a variational type. In this paper, we propose two new variational schemes, coined Gauged-MF (G-MF) and Gauged-BP (G-BP), improving MF and BP, respectively. Both provide lower bounds for the partition function by utilizing the so-called gauge transformation which modifies factors of GM while keeping the partition function invariant. Moreover, we prove that both G-MF and G-BP are exact for GMs with a single loop of a special structure, even though the bare MF and BP perform badly in this case. Our extensive experiments, on complete GMs of relatively small size and on large GM (up-to 300 variables) confirm that the newly proposed algorithms outperform and generalize MF and BP.

Symmetry-Adapted Ro-vibrational Basis Functions for Variational Nuclear Motion Calculations: TROVE Approach.

Science.gov (United States)

Yurchenko, Sergei N; Yachmenev, Andrey; Ovsyannikov, Roman I

2017-09-12

We present a general, numerically motivated approach to the construction of symmetry-adapted basis functions for solving ro-vibrational Schrödinger equations. The approach is based on the property of the Hamiltonian operator to commute with the complete set of symmetry operators and, hence, to reflect the symmetry of the system. The symmetry-adapted ro-vibrational basis set is constructed numerically by solving a set of reduced vibrational eigenvalue problems. In order to assign the irreducible representations associated with these eigenfunctions, their symmetry properties are probed on a grid of molecular geometries with the corresponding symmetry operations. The transformation matrices are reconstructed by solving overdetermined systems of linear equations related to the transformation properties of the corresponding wave functions on the grid. Our method is implemented in the variational approach TROVE and has been successfully applied to many problems covering the most important molecular symmetry groups. Several examples are used to illustrate the procedure, which can be easily applied to different types of coordinates, basis sets, and molecular systems.

Re-examining the Non-Linear Moisture-Precipitation Relationship over the Tropical Oceans.

Science.gov (United States)

Rushley, S S; Kim, D; Bretherton, C S; Ahn, M-S

2018-01-28

Bretherton et al. (2004) used the Special Sensor Microwave Imager (SSM/I) version 5 product to derive an exponential curve that describes the relationship between precipitation and column relative humidity (CRH) over the tropical oceans. The curve, which features a precipitation pickup at a CRH of about 0.75 and a rapid increase of precipitation with CRH after the pickup, has been widely used in the studies of the tropical atmosphere. This study re-examines the moisture-precipitation relationship by using the version 7 SSM/I data, in which several biases in the previous version are corrected, and evaluates the relationship in the Coupled Model Intercomparison Project phase 5 (CMIP5) models. In the revised exponential curve derived using the updated satellite data, the precipitation pick-up occurs at a higher CRH (~0.8), and precipitation increases more slowly with CRH than in the previous curve. In most CMIP5 models, the precipitation pickup is too early due to the common model bias of overestimated (underestimated) precipitation in the dry (wet) regime.

Variational Optimization of the Second-Order Density Matrix Corresponding to a Seniority-Zero Configuration Interaction Wave Function.

Science.gov (United States)

Poelmans, Ward; Van Raemdonck, Mario; Verstichel, Brecht; De Baerdemacker, Stijn; Torre, Alicia; Lain, Luis; Massaccesi, Gustavo E; Alcoba, Diego R; Bultinck, Patrick; Van Neck, Dimitri

2015-09-08

We perform a direct variational determination of the second-order (two-particle) density matrix corresponding to a many-electron system, under a restricted set of the two-index N-representability P-, Q-, and G-conditions. In addition, we impose a set of necessary constraints that the two-particle density matrix must be derivable from a doubly occupied many-electron wave function, i.e., a singlet wave function for which the Slater determinant decomposition only contains determinants in which spatial orbitals are doubly occupied. We rederive the two-index N-representability conditions first found by Weinhold and Wilson and apply them to various benchmark systems (linear hydrogen chains, He, N2, and CN(-)). This work is motivated by the fact that a doubly occupied many-electron wave function captures in many cases the bulk of the static correlation. Compared to the general case, the structure of doubly occupied two-particle density matrices causes the associate semidefinite program to have a very favorable scaling as L(3), where L is the number of spatial orbitals. Since the doubly occupied Hilbert space depends on the choice of the orbitals, variational calculation steps of the two-particle density matrix are interspersed with orbital-optimization steps (based on Jacobi rotations in the space of the spatial orbitals). We also point to the importance of symmetry breaking of the orbitals when performing calculations in a doubly occupied framework.

Quantum statistical field theory an introduction to Schwinger's variational method with Green's function nanoapplications, graphene and superconductivity

CERN Document Server

Morgenstern Horing, Norman J

2017-01-01

This book provides an introduction to the methods of coupled quantum statistical field theory and Green's functions. The methods of coupled quantum field theory have played a major role in the extensive development of nonrelativistic quantum many-particle theory and condensed matter physics. This introduction to the subject is intended to facilitate delivery of the material in an easily digestible form to advanced undergraduate physics majors at a relatively early stage of their scientific development. The main mechanism to accomplish this is the early introduction of variational calculus and the Schwinger Action Principle, accompanied by Green's functions. Important achievements of the theory in condensed matter and quantum statistical physics are reviewed in detail to help develop research capability. These include the derivation of coupled field Green's function equations-of-motion for a model electron-hole-phonon system, extensive discussions of retarded, thermodynamic and nonequilibrium Green's functions...

Antidepressant effects of abscisic acid mediated by the downregulation of corticotrophin-releasing hormone gene expression in rats.

Science.gov (United States)

Qi, Cong-Cong; Zhang, Zhi; Fang, Hui; Liu, Ji; Zhou, Nan; Ge, Jin-Fang; Chen, Fang-Han; Xiang, Cheng-Bin; Zhou, Jiang-Ning

2014-10-31

Corticotrophin-releasing hormone (CRH) is considered to be the central driving force of the hypothalamic-pituitary-adrenal axis, which plays a key role in the stress response and depression. Clinical reports have suggested that excess retinoic acid (RA) is associated with depression. Abscisic acid (ABA) and RA are direct derivatives of carotenoids and share a similar molecular structure. Here, we proposed that ABA also plays a role in the regulation of CRH activity sharing with the RA signaling pathway. [3H]-ABA radioimmunoassay demonstrated that the hypothalamus of rats shows the highest concentration of ABA compared with the cortex and the hippocampus under basal conditions. Under acute stress, ABA concentrations increased in the serum, but decreased in the hypothalamus and were accompanied by increased corticosterone in the serum and c-fos expression in the hypothalamus. Moreover, chronic ABA administration increased sucrose intake and decreased the mRNA expression of CRH and retinoic acid receptor alpha (RARα) in the hypothalamus of rats. Furthermore, ABA improved the symptom of chronic unpredictable mild stress in model rats, as indicated by increased sucrose intake, increased swimming in the forced swim test, and reduced mRNA expression of CRH and RARα in the rat hypothalamus. In vitro, CRH expression decreased after ABA treatment across different neural cells. In BE(2)-C cells, ABA inhibited a series of retinoid receptor expression, including RARα, a receptor that could facilitate CRH expression directly. These results suggest that ABA may play a role in the pathogenesis of depression by downregulating CRH mRNA expression shared with the RA signaling pathway. © The Author 2014. Published by Oxford University Press on behalf of CINP.

Nonpeptide corticotropin-releasing hormone receptor type 1 antagonists and their applications in psychosomatic disorders.

Science.gov (United States)

Contoreggi, Carlo; Rice, Kenner C; Chrousos, George

2004-01-01

Overproduction of corticotropin-releasing hormone (CRH) and stress system abnormalities are seen in psychiatric diseases such as depression, anxiety, eating disorders, and addiction. Investigations of CRH type 1 receptor (CRHR1) nonpeptide antagonists suggest therapeutic potential for treatment of these and other neuropsychiatric diseases. However, overproduction of CRH in the brain and on its periphery and disruption of the hypothalamic-pituitary-adrenal axis are also found in 'somatic' disorders. Some rare forms of Cushing's disease and related pituitary/adrenal disorders are obvious applications for CRHR1 antagonists. In addition, however, these antagonists may also be effective in treating more common somatic diseases. Patients with obesity and metabolic syndrome who often have subtle, but chronic hypothalamic-pituitary-adrenal hyperactivity, which may reflect central dysregulation of CRH and consequently glucocorticoid hypersecretion, could possibly be treated by administration of CRHR1 antagonists. Hormonal, autonomic, and immune aberrations are also present in chronic inflammatory, autoimmune, and allergic diseases, with considerable evidence linking CRH with the observed abnormalities. Furthermore, autonomic dysregulation is a prominent feature of common gastrointestinal disorders, such as irritable bowel syndrome and peptic ulcer disease. Patients with irritable bowel syndrome and other gastrointestinal disorders frequently develop altered pain perception and affective symptoms. CRH acts peripherally to modulate bowel activity both directly through the autonomic system and centrally by processing viscerosensory and visceromotor neural signals. This review presents clinical and preclinical evidence for the role of CRH in the pathophysiology of these disorders and for potential diagnostic and therapeutic applications of CRHR1 antagonists. Recognition of a dysfunctional stress system in these and other diseases will alter the understanding and treatment of

A Systematic Approach for Computing Zero-Point Energy, Quantum Partition Function, and Tunneling Effect Based on Kleinert's Variational Perturbation Theory.

Science.gov (United States)

Wong, Kin-Yiu; Gao, Jiali

2008-09-09

In this paper, we describe an automated integration-free path-integral (AIF-PI) method, based on Kleinert's variational perturbation (KP) theory, to treat internuclear quantum-statistical effects in molecular systems. We have developed an analytical method to obtain the centroid potential as a function of the variational parameter in the KP theory, which avoids numerical difficulties in path-integral Monte Carlo or molecular dynamics simulations, especially at the limit of zero-temperature. Consequently, the variational calculations using the KP theory can be efficiently carried out beyond the first order, i.e., the Giachetti-Tognetti-Feynman-Kleinert variational approach, for realistic chemical applications. By making use of the approximation of independent instantaneous normal modes (INM), the AIF-PI method can readily be applied to many-body systems. Previously, we have shown that in the INM approximation, the AIF-PI method is accurate for computing the quantum partition function of a water molecule (3 degrees of freedom) and the quantum correction factor for the collinear H(3) reaction rate (2 degrees of freedom). In this work, the accuracy and properties of the KP theory are further investigated by using the first three order perturbations on an asymmetric double-well potential, the bond vibrations of H(2), HF, and HCl represented by the Morse potential, and a proton-transfer barrier modeled by the Eckart potential. The zero-point energy, quantum partition function, and tunneling factor for these systems have been determined and are found to be in excellent agreement with the exact quantum results. Using our new analytical results at the zero-temperature limit, we show that the minimum value of the computed centroid potential in the KP theory is in excellent agreement with the ground state energy (zero-point energy) and the position of the centroid potential minimum is the expectation value of particle position in wave mechanics. The fast convergent property

Variational methods in molecular modeling

CERN Document Server

2017-01-01

This book presents tutorial overviews for many applications of variational methods to molecular modeling. Topics discussed include the Gibbs-Bogoliubov-Feynman variational principle, square-gradient models, classical density functional theories, self-consistent-field theories, phase-field methods, Ginzburg-Landau and Helfrich-type phenomenological models, dynamical density functional theory, and variational Monte Carlo methods. Illustrative examples are given to facilitate understanding of the basic concepts and quantitative prediction of the properties and rich behavior of diverse many-body systems ranging from inhomogeneous fluids, electrolytes and ionic liquids in micropores, colloidal dispersions, liquid crystals, polymer blends, lipid membranes, microemulsions, magnetic materials and high-temperature superconductors. All chapters are written by leading experts in the field and illustrated with tutorial examples for their practical applications to specific subjects. With emphasis placed on physical unders...

Quantum variational calculus

CERN Document Server

Malinowska, Agnieszka B

2014-01-01

This Brief puts together two subjects, quantum and variational calculi by considering variational problems involving Hahn quantum operators. The main advantage of its results is that they are able to deal with nondifferentiable (even discontinuous) functions, which are important in applications. Possible applications in economics are discussed. Economists model time as continuous or discrete. Although individual economic decisions are generally made at discrete time intervals, they may well be less than perfectly synchronized in ways discrete models postulate. On the other hand, the usual assumption that economic activity takes place continuously, is nothing else than a convenient abstraction that in many applications is far from reality. The Hahn quantum calculus helps to bridge the gap between the two families of models: continuous and discrete. Quantum Variational Calculus is self-contained and unified in presentation. It provides an opportunity for an introduction to the quantum calculus of variations fo...

Inclusion of ecologically based trait variation in plant functional types reduces the projected land carbon sink in an earth system model.

Science.gov (United States)

Verheijen, Lieneke M; Aerts, Rien; Brovkin, Victor; Cavender-Bares, Jeannine; Cornelissen, Johannes H C; Kattge, Jens; van Bodegom, Peter M

2015-08-01

Earth system models demonstrate large uncertainty in projected changes in terrestrial carbon budgets. The lack of inclusion of adaptive responses of vegetation communities to the environment has been suggested to hamper the ability of modeled vegetation to adequately respond to environmental change. In this study, variation in functional responses of vegetation has been added to an earth system model (ESM) based on ecological principles. The restriction of viable mean trait values of vegetation communities by the environment, called 'habitat filtering', is an important ecological assembly rule and allows for determination of global scale trait-environment relationships. These relationships were applied to model trait variation for different plant functional types (PFTs). For three leaf traits (specific leaf area, maximum carboxylation rate at 25 °C, and maximum electron transport rate at 25 °C), relationships with multiple environmental drivers, such as precipitation, temperature, radiation, and CO2 , were determined for the PFTs within the Max Planck Institute ESM. With these relationships, spatiotemporal variation in these formerly fixed traits in PFTs was modeled in global change projections (IPCC RCP8.5 scenario). Inclusion of this environment-driven trait variation resulted in a strong reduction of the global carbon sink by at least 33% (2.1 Pg C yr(-1) ) from the 2nd quarter of the 21st century onward compared to the default model with fixed traits. In addition, the mid- and high latitudes became a stronger carbon sink and the tropics a stronger carbon source, caused by trait-induced differences in productivity and relative respirational costs. These results point toward a reduction of the global carbon sink when including a more realistic representation of functional vegetation responses, implying more carbon will stay airborne, which could fuel further climate change. © 2015 John Wiley & Sons Ltd.

Using the Screened Coulomb Potential to Illustrate the Variational Method

Science.gov (United States)

Zuniga, Jose; Bastida, Adolfo; Requena, Alberto

2012-01-01

The screened Coulomb potential, or Yukawa potential, is used to illustrate the application of the single and linear variational methods. The trial variational functions are expressed in terms of Slater-type functions, for which the integrals needed to carry out the variational calculations are easily evaluated in closed form. The variational…

Derivation of the RPA (Random Phase Approximation) Equation of ATDDFT (Adiabatic Time Dependent Density Functional Ground State Response Theory) from an Excited State Variational Approach Based on the Ground State Functional.

Science.gov (United States)

Ziegler, Tom; Krykunov, Mykhaylo; Autschbach, Jochen

2014-09-09

The random phase approximation (RPA) equation of adiabatic time dependent density functional ground state response theory (ATDDFT) has been used extensively in studies of excited states. It extracts information about excited states from frequency dependent ground state response properties and avoids, thus, in an elegant way, direct Kohn-Sham calculations on excited states in accordance with the status of DFT as a ground state theory. Thus, excitation energies can be found as resonance poles of frequency dependent ground state polarizability from the eigenvalues of the RPA equation. ATDDFT is approximate in that it makes use of a frequency independent energy kernel derived from the ground state functional. It is shown in this study that one can derive the RPA equation of ATDDFT from a purely variational approach in which stationary states above the ground state are located using our constricted variational DFT (CV-DFT) method and the ground state functional. Thus, locating stationary states above the ground state due to one-electron excitations with a ground state functional is completely equivalent to solving the RPA equation of TDDFT employing the same functional. The present study is an extension of a previous work in which we demonstrated the equivalence between ATDDFT and CV-DFT within the Tamm-Dancoff approximation.

Geometrical treatment of non-potential interactions: the exterior variational calculus, dynamical systems, physical 1-forms and variational selfadjointness

International Nuclear Information System (INIS)

Trostel, R.

1982-01-01

A mathematical objective of this paper is to provide geometrical formulation of the integrability conditions for the existence of an action functional, that is, to provide a geometrical counterpart (similar to that by Abraham, Marsden, and Hughes) of the variational and functional approach to self-adjointness. This objective is achieved via the exterior variational calculus, an exterior differential calculus on the vector space of functions depending on time or space time, using from the outset extensively the concept of functional differentiation as its foundation. Variational self-adjointness equals the variational closure of the physical 1-form, the vanishing of a generalized curl-operation applied to the equations of motion. The convenience of this more formal approach is demonstrated, not only when deriving the conditions of variational self-adjointness for materials of differential type of arbitrary order (particles or fields), using roughly no more than Dirac's delta-distributions, but also when treating materials of a broader class (including causal and acausal constitutive functionals, materials of rate type, integral type, etc.). A physical objective of this paper is achieved by pointing out that, as physics is primarily concerned with the solutions of the evolution equations, i.e., with the set of the zero points of the physical 1-form, an equivalence relation among the physical 1-forms on the infinite dimensional vector space of functions is constructed by leaving the set of their zero points unchanged. Using this result, a direct Lagrangian universality is indicated and an almost one presented. Moreover, all physical 1-forms connected by invertible supermatrices (thus mixing the evolution law of different times or space-time) are equivalent. Choosing these supermatrices to be diagonal in time or space-time yields the indirect analytical representation factors

A min-max variational principle

International Nuclear Information System (INIS)

Georgiev, P.G.

1995-11-01

In this paper a variational principle for min-max problems is proved that is of the same spirit as Deville-Godefroy-Zizler's variational principle for minimization problems. A localization theorem in which the mini-max points for the perturbed function with respect top a given ε-min-max point are localized is presented. 3 refs

Human feeding biomechanics: performance, variation, and functional constraints

Science.gov (United States)

Dechow, Paul C.; Wang, Qian; Gharpure, Poorva H.; Baab, Karen L.; Smith, Amanda L.; Weber, Gerhard W.; Grosse, Ian R.; Ross, Callum F.; Richmond, Brian G.; Wright, Barth W.; Byron, Craig; Wroe, Stephen; Strait, David S.

2016-01-01

The evolution of the modern human (Homo sapiens) cranium is characterized by a reduction in the size of the feeding system, including reductions in the size of the facial skeleton, postcanine teeth, and the muscles involved in biting and chewing. The conventional view hypothesizes that gracilization of the human feeding system is related to a shift toward eating foods that were less mechanically challenging to consume and/or foods that were processed using tools before being ingested. This hypothesis predicts that human feeding systems should not be well-configured to produce forceful bites and that the cranium should be structurally weak. An alternate hypothesis, based on the observation that humans have mechanically efficient jaw adductors, states that the modern human face is adapted to generate and withstand high biting forces. We used finite element analysis (FEA) to test two opposing mechanical hypotheses: that compared to our closest living relative, chimpanzees (Pan troglodytes), the modern human craniofacial skeleton is (1) less well configured, or (2) better configured to generate and withstand high magnitude bite forces. We considered intraspecific variation in our examination of human feeding biomechanics by examining a sample of geographically diverse crania that differed notably in shape. We found that our biomechanical models of human crania had broadly similar mechanical behavior despite their shape variation and were, on average, less structurally stiff than the crania of chimpanzees during unilateral biting when loaded with physiologically-scaled muscle loads. Our results also show that modern humans are efficient producers of bite force, consistent with previous analyses. However, highly tensile reaction forces were generated at the working (biting) side jaw joint during unilateral molar bites in which the chewing muscles were recruited with bilateral symmetry. In life, such a configuration would have increased the risk of joint dislocation and

Human feeding biomechanics: performance, variation, and functional constraints

Directory of Open Access Journals (Sweden)

Justin A. Ledogar

2016-07-01

Full Text Available The evolution of the modern human (Homo sapiens cranium is characterized by a reduction in the size of the feeding system, including reductions in the size of the facial skeleton, postcanine teeth, and the muscles involved in biting and chewing. The conventional view hypothesizes that gracilization of the human feeding system is related to a shift toward eating foods that were less mechanically challenging to consume and/or foods that were processed using tools before being ingested. This hypothesis predicts that human feeding systems should not be well-configured to produce forceful bites and that the cranium should be structurally weak. An alternate hypothesis, based on the observation that humans have mechanically efficient jaw adductors, states that the modern human face is adapted to generate and withstand high biting forces. We used finite element analysis (FEA to test two opposing mechanical hypotheses: that compared to our closest living relative, chimpanzees (Pan troglodytes, the modern human craniofacial skeleton is (1 less well configured, or (2 better configured to generate and withstand high magnitude bite forces. We considered intraspecific variation in our examination of human feeding biomechanics by examining a sample of geographically diverse crania that differed notably in shape. We found that our biomechanical models of human crania had broadly similar mechanical behavior despite their shape variation and were, on average, less structurally stiff than the crania of chimpanzees during unilateral biting when loaded with physiologically-scaled muscle loads. Our results also show that modern humans are efficient producers of bite force, consistent with previous analyses. However, highly tensile reaction forces were generated at the working (biting side jaw joint during unilateral molar bites in which the chewing muscles were recruited with bilateral symmetry. In life, such a configuration would have increased the risk of joint

Age-Related Decline in the Variation of Dynamic Functional Connectivity: A Resting State Analysis

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Yuanyuan Chen

2017-06-01

Full Text Available Normal aging is typically characterized by abnormal resting-state functional connectivity (FC, including decreasing connectivity within networks and increasing connectivity between networks, under the assumption that the FC over the scan time was stationary. In fact, the resting-state FC has been shown in recent years to vary over time even within minutes, thus showing the great potential of intrinsic interactions and organization of the brain. In this article, we assumed that the dynamic FC consisted of an intrinsic dynamic balance in the resting brain and was altered with increasing age. Two groups of individuals (N = 36, ages 20–25 for the young group; N = 32, ages 60–85 for the senior group were recruited from the public data of the Nathan Kline Institute. Phase randomization was first used to examine the reliability of the dynamic FC. Next, the variation in the dynamic FC and the energy ratio of the dynamic FC fluctuations within a higher frequency band were calculated and further checked for differences between groups by non-parametric permutation tests. The results robustly showed modularization of the dynamic FC variation, which declined with aging; moreover, the FC variation of the inter-network connections, which mainly consisted of the frontal-parietal network-associated and occipital-associated connections, decreased. In addition, a higher energy ratio in the higher FC fluctuation frequency band was observed in the senior group, which indicated the frequency interactions in the FC fluctuations. These results highly supported the basis of abnormality and compensation in the aging brain and might provide new insights into both aging and relevant compensatory mechanisms.

The NOS1 variant rs6490121 is associated with variation in prefrontal function and grey matter density in healthy individuals.

LENUS (Irish Health Repository)

Rose, Emma J

2012-03-01

A common polymorphism within the nitric oxide sythanse-1 (NOS1) gene (rs6490121), initially identified as risk variant for schizophrenia, has been associated with variation in working memory and IQ. Here we investigated how this variation might be mediated at the level of brain structure and function. In healthy individuals (N=157), voxel based morphometry was used to compare grey matter (GM) volume between homozygous and heterozygous carriers of the \\'G\\' allele (i.e. the allele associated with impaired cognition and schizophrenia risk) and homozygous carriers of the non-risk \\'A\\' allele. Functional brain imaging data were also acquired from 48 participants during performance of a spatial working memory (SWM) task, and analysed to determine any effect of NOS1 risk status. An a priori region-of-interest analysis identified a significant reduction in ventromedial prefrontal GM volume in \\'G\\' allele carriers. Risk carriers also exhibited altered patterns of activation in the prefrontal cortex, caudate, and superior parietal lobe, which were characteristic of abnormal increases in activation in frontoparietal working memory networks and a failure to disengage regions of the default mode network. These functional changes suggest a NOS1-mediated processing inefficiency, which may contribute to cognitive dysfunction in schizophrenia. While the mechanisms by which NOS1 may influence brain structure and\\/or function have not yet been well delineated, these data provide further evidence for a role of NOS1 in risk for schizophrenia via an impact upon cognitive function.

Reduced vasopressin receptors activation mediates the anti-depressant effects of fluoxetine and venlafaxine in bulbectomy model of depression.

Science.gov (United States)

Poretti, María Belén; Sawant, Rahul S; Rask-Andersen, Mathias; de Cuneo, Marta Fiol; Schiöth, Helgi B; Perez, Mariela F; Carlini, Valeria Paola

2016-03-01

In response to stress, corticotropin releasing hormone (CRH) and vasopressin (AVP) are released from the hypothalamus, activate their receptors (CRHR1, CRHR2 or AVPr1b), and synergistically act to induce adrenocorticotropic hormone (ACTH) release from the anterior pituitary. Overstimulation of this system has been frequently associated with major depression states. The objective of the study is to assess the role of AVP and CRH receptors in fluoxetine and venlafaxine effects on the expression of depression-related behavior. In an animal model of depression (olfactory bulbectomy in mice, OB), we evaluated the effects of fluoxetine or venlafaxine (both 10 mg/kg/day) chronic administration on depression-related behavior in the tail suspension test. Plasma levels of AVP, CRH, and ACTH were determined as well as participation of their receptors in the expression of depression related-behavior and gene expression of AVP and CRH receptors (AVPr1b, CRHR1, and CRHR2) in the pituitary gland. The expression of depressive-like behavior in OB animals was reversed by treatment with both antidepressants. Surprisingly, OB-saline mice exhibited increased AVP and ACTH plasma levels, with no alterations in CRH levels when compared to sham mice. Chronic fluoxetine or venlafaxine reversed these effects. In addition, a significant increase only in AVPr1b gene expression was found in OB-saline. The antidepressant therapy used seems to be more likely related to a reduced activation of AVP rather than CRH receptors, since a positive correlation between AVP levels and depressive-like behavior was observed in OB animals. Furthermore, a full restoration of depressive behavior was observed in OB-fluoxetine- or venlafaxine-treated mice only when AVP was centrally administered but not CRH.

Genetic influences on variation in female orgasmic function: a twin study

Science.gov (United States)

Dunn, Kate M; Cherkas, Lynn F; Spector, Tim D

2005-01-01

Orgasmic dysfunction in females is commonly reported in the general population with little consensus on its aetiology. We performed a classical twin study to explore whether there were observable genetic influences on female orgasmic dysfunction. Adult females from the TwinsUK register were sent a confidential survey including questions on sexual problems. Complete responses to the questions on orgasmic dysfunction were obtained from 4037 women consisting of 683 monozygotic and 714 dizygotic pairs of female twins aged between 19 and 83 years. One in three women (32%) reported never or infrequently achieving orgasm during intercourse, with a corresponding figure of 21% during masturbation. A significant genetic influence was seen with an estimated heritability for difficulty reaching orgasm during intercourse of 34% (95% confidence interval 27–40%) and 45% (95% confidence interval 38–52%) for orgasm during masturbation. These results show that the wide variation in orgasmic dysfunction in females has a genetic basis and cannot be attributed solely to cultural influences. These results should stimulate further research into the biological and perhaps evolutionary processes governing female sexual function. PMID:17148182

Investigation of the spatial generalization of Kato's theorem by a variational density-functional approach

International Nuclear Information System (INIS)

Csavinszky, P.

1990-01-01

In a recent work, March has considered the quantum-mechanical system of an arbitrary number of closed electronic shells around an atomic nucleus of charge Z a e. March has assumed that the shells are filled by noninteracting electrons, moving in the bare Coulomb potential energy of V(r) = -Z a e 2 /r. In this framework, the basic quantity is the total electron (number) density ρ(r), built by summing the (number) density ρ n (r) of the nth closed electronic shell over the principal quantum number n. March has shown that Kato's theorem, (∂ρ(r)/∂r) r=0 = -(2Z a /a 0 )ρ (r = 0), with a 0 = ℎ 2 /me 2 , is amenable to a spatially dependent generalization that can be expressed by ∂ρ(r)/∂r = -(2Z a /a 0 )ρ s (r), where ρ s (r) is the s-state contribution from the n closed electronic shells to ρ(r). The present work investigates the spatially dependent generalization of Kato's theorem for the Ne atom by making use of a variational density-functional approach and adopting several expressions for the kinetic-energy functional of the electrons. The intriguing question of identifying the best kinetic-energy functional is raised and discussed

Nonlinear variational inequalities of semilinear parabolic type

Directory of Open Access Journals (Sweden)

Park Jong-Yeoul

2001-01-01

Full Text Available The existence of solutions for the nonlinear functional differential equation governed by the variational inequality is studied. The regularity and a variation of solutions of the equation are also given.

Variation of Parameters in Differential Equations (A Variation in Making Sense of Variation of Parameters)

Science.gov (United States)

Quinn, Terry; Rai, Sanjay

2012-01-01

The method of variation of parameters can be found in most undergraduate textbooks on differential equations. The method leads to solutions of the non-homogeneous equation of the form y = u[subscript 1]y[subscript 1] + u[subscript 2]y[subscript 2], a sum of function products using solutions to the homogeneous equation y[subscript 1] and…

Functional impact of global rare copy number variation in autism spectrum disorders.

Science.gov (United States)

Pinto, Dalila; Pagnamenta, Alistair T; Klei, Lambertus; Anney, Richard; Merico, Daniele; Regan, Regina; Conroy, Judith; Magalhaes, Tiago R; Correia, Catarina; Abrahams, Brett S; Almeida, Joana; Bacchelli, Elena; Bader, Gary D; Bailey, Anthony J; Baird, Gillian; Battaglia, Agatino; Berney, Tom; Bolshakova, Nadia; Bölte, Sven; Bolton, Patrick F; Bourgeron, Thomas; Brennan, Sean; Brian, Jessica; Bryson, Susan E; Carson, Andrew R; Casallo, Guillermo; Casey, Jillian; Chung, Brian H Y; Cochrane, Lynne; Corsello, Christina; Crawford, Emily L; Crossett, Andrew; Cytrynbaum, Cheryl; Dawson, Geraldine; de Jonge, Maretha; Delorme, Richard; Drmic, Irene; Duketis, Eftichia; Duque, Frederico; Estes, Annette; Farrar, Penny; Fernandez, Bridget A; Folstein, Susan E; Fombonne, Eric; Freitag, Christine M; Gilbert, John; Gillberg, Christopher; Glessner, Joseph T; Goldberg, Jeremy; Green, Andrew; Green, Jonathan; Guter, Stephen J; Hakonarson, Hakon; Heron, Elizabeth A; Hill, Matthew; Holt, Richard; Howe, Jennifer L; Hughes, Gillian; Hus, Vanessa; Igliozzi, Roberta; Kim, Cecilia; Klauck, Sabine M; Kolevzon, Alexander; Korvatska, Olena; Kustanovich, Vlad; Lajonchere, Clara M; Lamb, Janine A; Laskawiec, Magdalena; Leboyer, Marion; Le Couteur, Ann; Leventhal, Bennett L; Lionel, Anath C; Liu, Xiao-Qing; Lord, Catherine; Lotspeich, Linda; Lund, Sabata C; Maestrini, Elena; Mahoney, William; Mantoulan, Carine; Marshall, Christian R; McConachie, Helen; McDougle, Christopher J; McGrath, Jane; McMahon, William M; Merikangas, Alison; Migita, Ohsuke; Minshew, Nancy J; Mirza, Ghazala K; Munson, Jeff; Nelson, Stanley F; Noakes, Carolyn; Noor, Abdul; Nygren, Gudrun; Oliveira, Guiomar; Papanikolaou, Katerina; Parr, Jeremy R; Parrini, Barbara; Paton, Tara; Pickles, Andrew; Pilorge, Marion; Piven, Joseph; Ponting, Chris P; Posey, David J; Poustka, Annemarie; Poustka, Fritz; Prasad, Aparna; Ragoussis, Jiannis; Renshaw, Katy; Rickaby, Jessica; Roberts, Wendy; Roeder, Kathryn; Roge, Bernadette; Rutter, Michael L; Bierut, Laura J; Rice, John P; Salt, Jeff; Sansom, Katherine; Sato, Daisuke; Segurado, Ricardo; Sequeira, Ana F; Senman, Lili; Shah, Naisha; Sheffield, Val C; Soorya, Latha; Sousa, Inês; Stein, Olaf; Sykes, Nuala; Stoppioni, Vera; Strawbridge, Christina; Tancredi, Raffaella; Tansey, Katherine; Thiruvahindrapduram, Bhooma; Thompson, Ann P; Thomson, Susanne; Tryfon, Ana; Tsiantis, John; Van Engeland, Herman; Vincent, John B; Volkmar, Fred; Wallace, Simon; Wang, Kai; Wang, Zhouzhi; Wassink, Thomas H; Webber, Caleb; Weksberg, Rosanna; Wing, Kirsty; Wittemeyer, Kerstin; Wood, Shawn; Wu, Jing; Yaspan, Brian L; Zurawiecki, Danielle; Zwaigenbaum, Lonnie; Buxbaum, Joseph D; Cantor, Rita M; Cook, Edwin H; Coon, Hilary; Cuccaro, Michael L; Devlin, Bernie; Ennis, Sean; Gallagher, Louise; Geschwind, Daniel H; Gill, Michael; Haines, Jonathan L; Hallmayer, Joachim; Miller, Judith; Monaco, Anthony P; Nurnberger, John I; Paterson, Andrew D; Pericak-Vance, Margaret A; Schellenberg, Gerard D; Szatmari, Peter; Vicente, Astrid M; Vieland, Veronica J; Wijsman, Ellen M; Scherer, Stephen W; Sutcliffe, James S; Betancur, Catalina

2010-07-15

The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.

Narrow intra-individual variation of maternal thyroid function in pregnancy based on a longitudinal study on 132 women

DEFF Research Database (Denmark)

Boas, M.; Forman, Julie Lyng; Juul, A.

2009-01-01

BACKGROUND: Adaptive alterations in maternal physiology cause changes in thyroid hormone levels throughout pregnancy, and precise biochemical evaluation is thus highly dependent on gestation-specific reference intervals and expected intra-individual variation. OBJECTIVE: The aim of the study...... was the assessment of the intra-individual variation as well as the longitudinal course of thyroid hormones during normal pregnancy and factors that influence the normal reference range for thyroid function. For this purpose, a longitudinal statistical model was applied. DESIGN: In a cohort of 132 pregnant women......, serial blood samples were obtained and ultrasound scans were performed throughout pregnancy. METHODS: Serum levels of TSH, free and total thyroxine (T(4)), free and total triiodothyronine (T(3)) as well as autoantibodies against thyroid peroxidase and thyroglobulin were measured in 979 serum samples...

Exploring Duopoly Markets with Conjectural Variations

Science.gov (United States)

Julien, Ludovic A.; Musy, Olivier; Saïdi, Aurélien W.

2014-01-01

In this article, the authors investigate competitive firm behaviors in a two-firm environment assuming linear cost and demand functions. By introducing conjectural variations, they capture the different market structures as specific configurations of a more general model. Conjectural variations are based on the assumption that each firm believes…

Anomalous singularities in the complex Kohn variational principle of quantum scattering theory

International Nuclear Information System (INIS)

Lucchese, R.R.

1989-01-01

Variational principles for symmetric complex scattering matrices (e.g., the S matrix or the T matrix) based on the Kohn variational principle have been thought to be free from anomalous singularities. We demonstrate that singularities do exist for these variational principles by considering single and multichannel model problems based on exponential interaction potentials. The singularities are found by considering simultaneous variations in two nonlinear parameters in the variational calculation (e.g., the energy and the cutoff function for the irregular continuum functions). The singularities are found when the cutoff function for the irregular continuum functions extends over a range of the radial coordinate where the square-integrable basis set does not have sufficient flexibility. Effects of these singularities generally should not appear in applications of the complex Kohn method where a fixed variational basis set is considered and only the energy is varied

The stress system in depression and neurodegeneration: Focus on the human hypothalamus

NARCIS (Netherlands)

Bao, A.-M.; Meynen, G.; Swaab, D.F.

2008-01-01

The stress response is mediated by the hypothalamo-pituitary-adrenal (HPA) system. Activity of the corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) forms the basis of the activity of the HPA-axis. The CRH neurons induce adrenocorticotropin (ACTH)

Biomechanics on the half shell: functional performance influences patterns of morphological variation in the emydid turtle carapace.

Science.gov (United States)

Stayton, C Tristan

2011-09-01

This study uses the carapace of emydid turtles to address hypothesized differences between terrestrial and aquatic species. Geometric morphometrics are used to quantify shell shape, and performance is estimated for two shell functions: shell strength and hydrodynamics. Aquatic turtle shells differ in shape from terrestrial turtle shells and are characterized by lower frontal areas and presumably lower drag. Terrestrial turtle shells are stronger than those of aquatic turtles; many-to-one mapping of morphology to function does not entirely mitigate a functional trade-off between mechanical strength and hydrodynamic performance. Furthermore, areas of morphospace characterized by exceptionally poor performance in either of the functions are not occupied by any emydid species. Though aquatic and terrestrial species show no significant differences in the rate of morphological evolution, aquatic species show a higher lineage density, indicative of a greater amount of convergence in their evolutionary history. The techniques employed in this study, including the modeling of theoretical shapes to assess performance in unoccupied areas of morphospace, suggest a framework for future studies of morphological variation. Copyright © 2011 Elsevier GmbH. All rights reserved.

An Integrative Review on Role and Mechanisms of Ghrelin in Stress, Anxiety and Depression.

Science.gov (United States)

Bali, Anjana; Jaggi, Amteshwar Singh

2016-01-01

Ghrelin is orexigenic hormone primarily synthesized by endocrine X/A-like cells of gastric oxyntic mucosa to stimulate appetite and food intake along with regulation of growth hormone and insulin secretion; glucose and lipid metabolism; gastrointestinal motility; blood pressure, heart rate and neurogenesis. Furthermore, peripherally (after crossing the blood brain barrier) as well as centrally synthesized ghrelin (in the hypothalamus) regulates diverse functions of central nervous system including stress-associated behavioral functions. Exposure to stress alters the ghrelin levels and alteration in ghrelin levels significantly affects neuro-endocrinological parameters; metabolism-related physiology, behavior and mood. Studies have shown both anxiolytic and anxiogenic role of ghrelin suggesting its dual role in modulating anxiety-related behavior. However, it is proposed that increase in ghrelin levels during stress condition is an endogenous stress coping behavior and increased ghrelin levels may be required to prevent excessive anxiety. In preclinical and clinical studies, an elevation in ghrelin levels during depression has been correlated with their antidepressant activities. Ghrelin-induced modulation of stress and associated conditions has been linked to alteration in hypothalamic-pituitary-adrenal (HPA) axis; autonomic nervous system (mainly sympathetic nervous system and serotonergic neurotransmission. A reciprocal relationship has been reported between corticotropin-releasing hormone (CRH) and ghrelin as ghrelin increases the release of CRH, ACTH and corticosteroids; while CRH decreases the expression of ghrelin. Similarly, ghrelin increases the serotonin turnover and in turn, serotonin controls ghrelin signaling to modulate anxiety-related behavior. The present review discusses the dual role of ghrelin in stress and related behavioral disorders along with possible mechanisms.

Neocortical concentrations of neuropeptides in senile dementia of the Alzheimer and Lewy body type: comparison with Parkinson's disease and severity correlations.

Science.gov (United States)

Leake, A; Perry, E K; Perry, R H; Jabeen, S; Fairbairn, A F; McKeith, I G; Ferrier, I N

1991-02-15

Corticotropin releasing hormone (CRH), somatostatin (SRIF), and arginine vasopressin (AVP) concentrations were estimated using radioimmunoassay in the temporal and occipital cortices in postmortem brain from patients clinically and neuropathologically diagnosed as senile dementia of the Lewy body type (SDLT), senile dementia of the Alzheimer type (SDAT), and Parkinson's disease (PD) and from neurologically normal controls. The concentration of temporal and occipital neocortical CRH was diminished in both SDAT and SDLT compared to control values, whereas SRIF was reduced only in temporal cortex in both these conditions. In contrast, the concentrations of both CRH and SRIF were unaltered in PD. The concentrations of AVP in SDLT, SDAT, and PD were similar to those found in the control groups. The decrement in SRIF, but not CRH, was found to be correlated with some indices of severity of illness in SDAT; a similar but nonsignificant trend for SRIF was observed in SDLT.

Brain-specific inactivation of the Crhr1 gene inhibits post-dependent and stress-induced alcohol intake, but does not affect relapse-like drinking

DEFF Research Database (Denmark)

Molander, Anna; Vengeliene, Valentina; Heilig, Markus

2012-01-01

, a conditional brain-specific Crhr1-knockout (Crhr1(NestinCre)) and a global knockout mouse line were studied for basal alcohol drinking, stress-induced alcohol consumption, deprivation-induced intake, and escalated alcohol consumption in the post-dependent state. In a second set of experiments, we tested CRHR1...... not affect relapse-like drinking after a deprivation period in rats. We conclude that CRH/CRHR1 extra-HPA and HPA signaling may have opposing effects on stress-related alcohol consumption. CRHR1 does not have a role in basal alcohol intake or relapse-like drinking situations with a low stress load.......Corticotropin-releasing hormone (CRH) and its receptor, CRH receptor-1 (CRHR1), have a key role in alcoholism. Especially, post-dependent and stress-induced alcohol intake involve CRH/CRHR1 signaling within extra-hypothalamic structures, but a contribution of the hypothalamic-pituitary-adrenal (HPA...

Overlapping constraint for variational surface reconstruction

DEFF Research Database (Denmark)

Aanæs, Henrik; Solem, J.E.

2005-01-01

In this paper a counter example, illustrating a shortcoming in most variational formulations for 3D surface estimation, is presented. The nature of this shortcoming is a lack of an overlapping constraint. A remedy for this shortcoming is presented in the form of a penalty function with an analysi...... of the effects of this function on surface motion. For practical purposes, this will only have minor influence on current methods. However, the insight provided in the analysis is likely to influence future developments in the field of variational surface reconstruction....

Variations in body morphology explain sex differences in thermoeffector function during compensable heat stress.

Science.gov (United States)

Notley, Sean R; Park, Joonhee; Tagami, Kyoko; Ohnishi, Norikazu; Taylor, Nigel A S

2017-05-01

What is the central question of this study? Can sex-related differences in cutaneous vascular and sudomotor responses be explained primarily by variations in the ratio between body surface area and mass during compensable exercise that elicits equivalent heat-loss requirements and mean body temperature changes across participants? What is the main finding and its importance? Mass-specific surface area was a significant determinant of vasomotor and sudomotor responses in men and women, explaining 10-48% of the individual thermoeffector variance. Nonetheless, after accounting for changes in mean body temperature and morphological differences, sex explained only 5% of that inter-individual variability. It was concluded that sex differences in thermoeffector function are morphologically dependent, but not sex dependent. Sex is sometimes thought to be an independent modulator of cutaneous vasomotor and sudomotor function during heat exposure. Nevertheless, it was hypothesized that, when assessed during compensable exercise that evoked equal heat-loss requirements across participants, sex differences in those thermoeffectors would be explained by variations in the ratio between body surface area and mass (specific surface area). To evaluate that possibility, vasomotor and sudomotor functions were assessed in 60 individuals (36 men and 24 women) with widely varying (overlapping) specific surface areas (range, 232.3-292.7 and 241.2-303.1 cm 2  kg -1 , respectively). Subjects completed two trials in compensable conditions (28°C, 36% relative humidity) involving rest (20 min) and steady-state cycling (45 min) at fixed, area-specific metabolic heat-production rates (light, ∼135 W m -2 ; moderate, ∼200 W m -2 ). Equivalent heat-loss requirements and mean body temperature changes were evoked across participants. Forearm blood flow and vascular conductance were positively related to specific surface area during light work in men (r = 0.67 and r = 0

High-confidence assessment of functional impact of human mitochondrial non-synonymous genome variations by APOGEE.

Directory of Open Access Journals (Sweden)

Stefano Castellana

2017-06-01

Full Text Available 24,189 are all the possible non-synonymous amino acid changes potentially affecting the human mitochondrial DNA. Only a tiny subset was functionally evaluated with certainty so far, while the pathogenicity of the vast majority was only assessed in-silico by software predictors. Since these tools proved to be rather incongruent, we have designed and implemented APOGEE, a machine-learning algorithm that outperforms all existing prediction methods in estimating the harmfulness of mitochondrial non-synonymous genome variations. We provide a detailed description of the underlying algorithm, of the selected and manually curated training and test sets of variants, as well as of its classification ability.

Existence of evolutionary variational solutions via the calculus of variations

Science.gov (United States)

Bögelein, Verena; Duzaar, Frank; Marcellini, Paolo

In this paper we introduce a purely variational approach to time dependent problems, yielding the existence of global parabolic minimizers, that is ∫0T ∫Ω [uṡ∂tφ+f(x,Du)] dx dt⩽∫0T ∫Ω f(x,Du+Dφ) dx dt, whenever T>0 and φ∈C0∞(Ω×(0,T),RN). For the integrand f:Ω×R→[0,∞] we merely assume convexity with respect to the gradient variable and coercivity. These evolutionary variational solutions are obtained as limits of maps depending on space and time minimizing certain convex variational functionals. In the simplest situation, with some growth conditions on f, the method provides the existence of global weak solutions to Cauchy-Dirichlet problems of parabolic systems of the type ∂tu-divDξf(x,Du)=0 in Ω×(0,∞).

Inter-doctor variations in the assessment of functional incapacities by insurance physicians

NARCIS (Netherlands)

Schellart, A.J.; Mulders, H.; Steenbeek, R.; Anema, J.R.; Kroneman, H.; Besseling, J.

2011-01-01

Background. The aim of this study was to determine the - largely unexplored - extent of systematic variation in the work disability assessment by Dutch insurance physicians (IPs) of employees on long-term sick leave, and to ascertain whether this variation was associated with the individual

Calculation of the exchange coupling constants of copper binuclear systems based on spin-flip constricted variational density functional theory.

Science.gov (United States)

Zhekova, Hristina R; Seth, Michael; Ziegler, Tom

2011-11-14

We have recently developed a methodology for the calculation of exchange coupling constants J in weakly interacting polynuclear metal clusters. The method is based on unrestricted and restricted second order spin-flip constricted variational density functional theory (SF-CV(2)-DFT) and is here applied to eight binuclear copper systems. Comparison of the SF-CV(2)-DFT results with experiment and with results obtained from other DFT and wave function based methods has been made. Restricted SF-CV(2)-DFT with the BH&HLYP functional yields consistently J values in excellent agreement with experiment. The results acquired from this scheme are comparable in quality to those obtained by accurate multi-reference wave function methodologies such as difference dedicated configuration interaction and the complete active space with second-order perturbation theory. © 2011 American Institute of Physics

Functional-analytic and numerical issues in splitting methods for total variation-based image reconstruction

International Nuclear Information System (INIS)

Hintermüller, Michael; Rautenberg, Carlos N; Hahn, Jooyoung

2014-01-01

Variable splitting schemes for the function space version of the image reconstruction problem with total variation regularization (TV-problem) in its primal and pre-dual formulations are considered. For the primal splitting formulation, while existence of a solution cannot be guaranteed, it is shown that quasi-minimizers of the penalized problem are asymptotically related to the solution of the original TV-problem. On the other hand, for the pre-dual formulation, a family of parametrized problems is introduced and a parameter dependent contraction of an associated fixed point iteration is established. Moreover, the theory is validated by numerical tests. Additionally, the augmented Lagrangian approach is studied, details on an implementation on a staggered grid are provided and numerical tests are shown. (paper)

The genetic variation in Monocarboxylic acid transporter 2 (MCT2 has functional and clinical relevance with male infertility

Directory of Open Access Journals (Sweden)

Jinu Lee

2014-10-01

Full Text Available Monocarboxylic acid transporter 2 (MCT2 transports pyruvate and lactate outside and inside of sperms, mainly as energy sources and plays roles in the regulation of spermatogenesis. We investigated the association among genetic variations in the MCT2 gene, male infertility and MCT2 expression levels in sperm. The functional and genetic significance of the intron 2 (+28201A > G, rs10506398 and 3' untranslated region (UTR single nucleotide polymorphism (SNP (+2626G > A, rs10506399 of MCT2 variants were investigated. Two MCT2 polymorphisms were associated with male infertility (n = 471, P A had a strong association with the oligoasthenoteratozoospermia (OAT group. The +2626GG type had an almost 2.4-fold higher sperm count than that of the +2626AA type (+2626GG; 66 × 10 6 vs +2626AA; 27 × 10 6 , P < 0.0001. The MCT2-3' UTR SNP may be important for expression, as it is located at the MCT2 3' UTR. The average MCT2 protein amount in sperm of the +2626GG type was about two times higher than that of the +2626AA type. The results suggest that genetic variation in MCT2 has functional and clinical relevance with male infertility.

SDSS-IV MaNGA: Variation of the Stellar Initial Mass Function in Spiral and Early-type Galaxies

Science.gov (United States)

Li, Hongyu; Ge, Junqiang; Mao, Shude; Cappellari, Michele; Long, R. J.; Li, Ran; Emsellem, Eric; Dutton, Aaron A.; Li, Cheng; Bundy, Kevin; Thomas, Daniel; Drory, Niv; Lopes, Alexandre Roman

2017-04-01

We perform Jeans anisotropic modeling (JAM) on elliptical and spiral galaxies from the MaNGA DR13 sample. By comparing the stellar mass-to-light ratios estimated from stellar population synthesis and from JAM, we find a systematic variation of the initial mass function (IMF) similar to that in the earlier {{ATLAS}}3{{D}} results. Early-type galaxies (elliptical and lenticular) with lower velocity dispersions within one effective radius are consistent with a Chabrier-like IMF, while galaxies with higher velocity dispersions are consistent with a more bottom-heavy IMF such as the Salpeter IMF. Spiral galaxies have similar systematic IMF variations, but with slightly different slopes and larger scatters, due to the uncertainties caused by the higher gas fractions and extinctions for these galaxies. Furthermore, we examine the effects of stellar mass-to-light ratio gradients on our JAM modeling, and we find that the trends become stronger after considering the gradients.

Homogenization of variational inequalities for obstacle problems

International Nuclear Information System (INIS)

Sandrakov, G V

2005-01-01

Results on the convergence of solutions of variational inequalities for obstacle problems are proved. The variational inequalities are defined by a non-linear monotone operator of the second order with periodic rapidly oscillating coefficients and a sequence of functions characterizing the obstacles. Two-scale and macroscale (homogenized) limiting variational inequalities are obtained. Derivation methods for such inequalities are presented. Connections between the limiting variational inequalities and two-scale and macroscale minimization problems are established in the case of potential operators.

Ensembl variation resources

Directory of Open Access Journals (Sweden)

Marin-Garcia Pablo

2010-05-01

Full Text Available Abstract Background The maturing field of genomics is rapidly increasing the number of sequenced genomes and producing more information from those previously sequenced. Much of this additional information is variation data derived from sampling multiple individuals of a given species with the goal of discovering new variants and characterising the population frequencies of the variants that are already known. These data have immense value for many studies, including those designed to understand evolution and connect genotype to phenotype. Maximising the utility of the data requires that it be stored in an accessible manner that facilitates the integration of variation data with other genome resources such as gene annotation and comparative genomics. Description The Ensembl project provides comprehensive and integrated variation resources for a wide variety of chordate genomes. This paper provides a detailed description of the sources of data and the methods for creating the Ensembl variation databases. It also explores the utility of the information by explaining the range of query options available, from using interactive web displays, to online data mining tools and connecting directly to the data servers programmatically. It gives a good overview of the variation resources and future plans for expanding the variation data within Ensembl. Conclusions Variation data is an important key to understanding the functional and phenotypic differences between individuals. The development of new sequencing and genotyping technologies is greatly increasing the amount of variation data known for almost all genomes. The Ensembl variation resources are integrated into the Ensembl genome browser and provide a comprehensive way to access this data in the context of a widely used genome bioinformatics system. All Ensembl data is freely available at http://www.ensembl.org and from the public MySQL database server at ensembldb.ensembl.org.

Corticotropin-releasing hormone-mediated metamorphosis in the neotenic axolotl Ambystoma mexicanum: synergistic involvement of thyroxine and corticoids on brain type II deiodinase.

Science.gov (United States)

Kühn, Eduard R; De Groef, Bert; Van der Geyten, Serge; Darras, Veerle M

2005-08-01

In the present study, morphological changes leading to complete metamorphosis have been induced in the neotenic axolotl Ambystoma mexicanum using a submetamorphic dose of T(4) together with an injection of corticotropin-releasing hormone (CRH). An injection of CRH alone is ineffective in this regard presumably due to a lack of thyrotropic stimulation. Using this low hormone profile for induction of metamorphosis, the deiodinating enzymes D2 and D3 known to be present in amphibians were measured in liver and brain 24h following an intraperitoneal injection. An injection of T(4) alone did not influence liver nor brain D2 and D3, but dexamethasone (DEX) or CRH alone or in combination with T(4) decreased liver D2 and D3. Brain D2 activity was slightly increased with a higher dose of DEX, though CRH did not have this effect. A profound synergistic effect occurred when T(4) and DEX or CRH were injected together, in the dose range leading to metamorphosis, increasing brain D2 activity more than fivefold. This synergistic effect was not found in the liver. It is concluded that brain T(3) availability may play an important role for the onset of metamorphosis in the neotenic axolotl.

A functionally gradient variational porosity architecture for hollowed scaffolds fabrication

Energy Technology Data Exchange (ETDEWEB)

Khoda, A K M [Department of Industrial Engineering, University at Buffalo, Buffalo, NY 14260 (United States); Ozbolat, Ibrahim T [Department of Mechanical and Industrial Engineering, Center for Computer Aided Design, University of Iowa, Iowa City, IA 52242-1527 (United States); Koc, Bahattin, E-mail: bahattinkoc@sabanciuniv.edu [Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul 34956 (Turkey)

2011-09-15

This paper presents a novel continuous tool-path planning methodology for hollowed scaffold fabrication in tissue engineering. A new functionally gradient porous architecture is proposed with a continuous material deposition planning scheme. A controllable variational pore size and hence the porosity have been achieved with a combination of two geometrically oriented consecutive layers. The desired porosity has been achieved with consecutive layers by geometrically partitioning each layer into sub-regions based on the area and the tissue scaffold design constraints. A continuous, interconnected and optimized tool-path for layers has been generated for a three-dimensional biomaterial deposition/printing process. A zigzag pattern tool-path has been proposed for an accumulated sub-region layer, and a concentric spiral-like optimal tool-path pattern has been generated for the successive layer to ensure continuity along the structure. Three-dimensional layers, formed by the proposed tool-path plan, vary the pore size and the porosity based on the biological and mechanical requirements. Several examples demonstrate the proposed methodology along with illustrative results. Also a comparative study between the proposed design and conventional Cartesian coordinate scaffolds has been performed. The results demonstrate a significant reduction in design error with the proposed method. Moreover, sample examples have been fabricated using a micro-nozzle biomaterial deposition system, and characterized for validation.

A functionally gradient variational porosity architecture for hollowed scaffolds fabrication

International Nuclear Information System (INIS)

Khoda, A K M; Ozbolat, Ibrahim T; Koc, Bahattin

2011-01-01

This paper presents a novel continuous tool-path planning methodology for hollowed scaffold fabrication in tissue engineering. A new functionally gradient porous architecture is proposed with a continuous material deposition planning scheme. A controllable variational pore size and hence the porosity have been achieved with a combination of two geometrically oriented consecutive layers. The desired porosity has been achieved with consecutive layers by geometrically partitioning each layer into sub-regions based on the area and the tissue scaffold design constraints. A continuous, interconnected and optimized tool-path for layers has been generated for a three-dimensional biomaterial deposition/printing process. A zigzag pattern tool-path has been proposed for an accumulated sub-region layer, and a concentric spiral-like optimal tool-path pattern has been generated for the successive layer to ensure continuity along the structure. Three-dimensional layers, formed by the proposed tool-path plan, vary the pore size and the porosity based on the biological and mechanical requirements. Several examples demonstrate the proposed methodology along with illustrative results. Also a comparative study between the proposed design and conventional Cartesian coordinate scaffolds has been performed. The results demonstrate a significant reduction in design error with the proposed method. Moreover, sample examples have been fabricated using a micro-nozzle biomaterial deposition system, and characterized for validation.

A functionally gradient variational porosity architecture for hollowed scaffolds fabrication.

Science.gov (United States)

Khoda, A K M; Ozbolat, Ibrahim T; Koc, Bahattin

2011-09-01

This paper presents a novel continuous tool-path planning methodology for hollowed scaffold fabrication in tissue engineering. A new functionally gradient porous architecture is proposed with a continuous material deposition planning scheme. A controllable variational pore size and hence the porosity have been achieved with a combination of two geometrically oriented consecutive layers. The desired porosity has been achieved with consecutive layers by geometrically partitioning each layer into sub-regions based on the area and the tissue scaffold design constraints. A continuous, interconnected and optimized tool-path for layers has been generated for a three-dimensional biomaterial deposition/printing process. A zigzag pattern tool-path has been proposed for an accumulated sub-region layer, and a concentric spiral-like optimal tool-path pattern has been generated for the successive layer to ensure continuity along the structure. Three-dimensional layers, formed by the proposed tool-path plan, vary the pore size and the porosity based on the biological and mechanical requirements. Several examples demonstrate the proposed methodology along with illustrative results. Also a comparative study between the proposed design and conventional Cartesian coordinate scaffolds has been performed. The results demonstrate a significant reduction in design error with the proposed method. Moreover, sample examples have been fabricated using a micro-nozzle biomaterial deposition system, and characterized for validation.

Up-regulation of corticotropin releasing hormone is associated with ...

African Journals Online (AJOL)

established in literature that stress signals such as psoriasis prompts the release of CRH from the hypothalamus paraventricular nucleus (PVN). CRH in turn triggers ACTH release from anterior pituitary [8] which ultimately controls the glucocorticoid discharge from adrenal cortex. Several of the glucocorticoids, which include ...

The stress system in the human brain in depression and neurodegeneration

NARCIS (Netherlands)

Swaab, Dick F.; Bao, Ai-Min; Lucassen, Paul J.

2005-01-01

Corticotropin-releasing hormone (CRH) plays a central role in the regulation of the hypothalamicpituitary-adrenal (HPA)-axis, i.e., the final common pathway in the stress response. The action of CRH on ACTH release is strongly potentiated by vasopressin, that is co-produced in increasing amounts

The stress system in the human brain in depression and neurodegeneration.

NARCIS (Netherlands)

Swaab, D.F.; Bao, A.-M.; Lucassen, P.J.

2005-01-01

Corticotropin-releasing hormone (CRH) plays a central role in the regulation of the hypothalamic-pituitary-adrenal (HPA)-axis, i.e., the final common pathway in the stress response. The action of CRH on ACTH release is strongly potentiated by vasopressin, that is co-produced in increasing amounts

The stress system in the human brain in depression and neurodegeneration

NARCIS (Netherlands)

Swaab, D.F.; Bao, A.M; Lucassen, P.J.

2005-01-01

Corticotropin-releasing hormone (CRH) plays a central role in the regulation of the hypothalamic-pituitary-adrenal (HPA)-axis, i.e., the final common pathway in the stress response. The action of CRH on ACTH release is strongly potentiated by vasopressin, that is co-produced in increasing amounts

Splines and variational methods

CERN Document Server

Prenter, P M

2008-01-01

One of the clearest available introductions to variational methods, this text requires only a minimal background in calculus and linear algebra. Its self-contained treatment explains the application of theoretic notions to the kinds of physical problems that engineers regularly encounter. The text's first half concerns approximation theoretic notions, exploring the theory and computation of one- and two-dimensional polynomial and other spline functions. Later chapters examine variational methods in the solution of operator equations, focusing on boundary value problems in one and two dimension

A Cortical Circuit for Sexually Dimorphic Oxytocin-Dependent Anxiety Behaviors.

Science.gov (United States)

Li, Kun; Nakajima, Miho; Ibañez-Tallon, Ines; Heintz, Nathaniel

2016-09-22

The frequency of human social and emotional disorders varies significantly between males and females. We have recently reported that oxytocin receptor interneurons (OxtrINs) modulate female sociosexual behavior. Here, we show that, in male mice, OxtrINs regulate anxiety-related behaviors. We demonstrate that corticotropin-releasing-hormone-binding protein (CRHBP), an antagonist of the stress hormone CRH, is specifically expressed in OxtrINs. Production of CRHBP blocks the CRH-induced potentiation of postsynaptic layer 2/3 pyramidal cell activity of male, but not female, mice, thus producing an anxiolytic effect. Our data identify OxtrINs as critical for modulation of social and emotional behaviors in both females and males and reveal a molecular mechanism that acts on local medial prefrontal cortex (mPFC) circuits to coordinate responses to OXT and CRH. They suggest that additional studies of the impact of the OXT/OXTR and CRHBP/CRH pathways in males and females will be important in development of gender-specific therapies. Published by Elsevier Inc.

Neuroanatomical pathways underlying the effects of hypothalamo-hypophysial-adrenal hormones on exploratory activity.

Science.gov (United States)

Lalonde, Robert; Strazielle, Catherine

2017-07-26

When injected via the intracerebroventricular route, corticosterone-releasing hormone (CRH) reduced exploration in the elevated plus-maze, the center region of the open-field, and the large chamber in the defensive withdrawal test. The anxiogenic action of CRH in the elevated plus-maze also occurred when infused in the basolateral amygdala, ventral hippocampus, lateral septum, bed nucleus of the stria terminalis, nucleus accumbens, periaqueductal grey, and medial frontal cortex. The anxiogenic action of CRH in the defensive withdrawal test was reproduced when injected in the locus coeruleus, while the amygdala, hippocampus, lateral septum, nucleus accumbens, and lateral globus pallidus contribute to center zone exploration in the open-field. In addition to elevated plus-maze and open-field tests, the amygdala appears as a target region for CRH-mediated anxiety in the elevated T-maze. Thus, the amygdala is the principal brain region identified with these three tests, and further research must identify the neural circuits underlying this form of anxiety.

Solution of problems in calculus of variations via He's variational iteration method

International Nuclear Information System (INIS)

Tatari, Mehdi; Dehghan, Mehdi

2007-01-01

In the modeling of a large class of problems in science and engineering, the minimization of a functional is appeared. Finding the solution of these problems needs to solve the corresponding ordinary differential equations which are generally nonlinear. In recent years He's variational iteration method has been attracted a lot of attention of the researchers for solving nonlinear problems. This method finds the solution of the problem without any discretization of the equation. Since this method gives a closed form solution of the problem and avoids the round off errors, it can be considered as an efficient method for solving various kinds of problems. In this research He's variational iteration method will be employed for solving some problems in calculus of variations. Some examples are presented to show the efficiency of the proposed technique

Up-regulation of corticotropin releasing hormone is associated with ...

African Journals Online (AJOL)

Purpose: To determine the expression of corticotropin-releasing hormone (CRH) in psoriasis and normal skin biopsy samples, and to correlate the expression of CRH with the expression of CRHBP and inflammatory cytokines IL-8 and IL-33. Methods: Psoriasis and normal skin biopsy samples were obtained from three ...

Influence of trichloroacetic acid peeling on the skin stress response system.

Science.gov (United States)

Kimura, Ayako; Kanazawa, Nobuo; Li, Hong-Jin; Yonei, Nozomi; Yamamoto, Yuki; Furukawa, Fukumi

2011-08-01

Although trichloroacetic acid (TCA) peeling is widely applied for cosmetic treatment of photodamaged skin, the entire biological mechanisms have yet to be determined. The skin stress response system (SSRS) involves corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) products that are locally-generated in response to locally-provided stressors or pro-inflammatory cytokines. This system would restrict tissue damage and restore local homeostasis. To determine the influence of TCA peeling on the SSRS in vitro and in vivo, expressions of POMC, melanocortin receptor 1 (MC1R), CRH and CRH receptor 1 (CRHR1) mRNA were examined by reverse transcription polymerase chain reaction in Pam212 murine keratinocytes, murine plantar and healthy human abdominal skin specimens after TCA treatment. In addition, their protein expressions as well as those of POMC-derived peptides were examined immunohistochemically. After TCA treatment, transient upregulation of POMC and MC1R mRNA expressions was observed in both murine and human skin, as well as in Pam212. Enhanced POMC protein, recovery of once-impaired MC1R protein, and no enhancement of POMC-derived peptide productions were revealed immunohistochemically in both murine and human epidermis. In contrast, neither expression levels of CRH and CRHR1 mRNA nor epidermal protein were enhanced after TCA application in murine and human skin, except for induction of human CRH mRNA expression. These results suggest that TCA activates the SSRS by inducing POMC and MC1R productions of keratinocytes in the CRH-independent manner, and that the biological effects of POMC itself are responsible for the TCA-induced epidermal SSRS activation. © 2010 Japanese Dermatological Association.

Paternal responsiveness is associated with, but not mediated by reduced neophobia in male California mice (Peromyscus californicus).

Science.gov (United States)

Chauke, Miyetani; de Jong, Trynke R; Garland, Theodore; Saltzman, Wendy

2012-08-20

Hormones associated with pregnancy and parturition have been implicated in facilitating the onset of maternal behavior via reductions in neophobia, anxiety, and stress responsiveness. To determine whether the onset of paternal behavior has similar associations in biparental male California mice (Peromyscus californicus), we compared paternal responsiveness, neophobia (novel-object test), and anxiety-like behavior (elevated plus maze, EPM) in isolated virgins (housed alone), paired virgins (housed with another male), expectant fathers (housed with pregnant pairmate), and new fathers (housed with pairmate and pups). Corticotropin-releasing hormone (CRH) and Fos immunoreactivity (IR) were quantified in brain tissues following exposure to a predator-odor stressor or under baseline conditions. New fathers showed lower anxiety-like behavior than expectant fathers and isolated virgins in EPM tests. In all housing conditions, stress elevated Fos-IR in the hypothalamic paraventricular nucleus (PVN). Social isolation reduced overall (baseline and stress-induced) Fos- and colocalized Fos/CRH-IR, and increased overall CRH-IR, in the PVN. In the central nucleus of the amygdala, social isolation increased stress-induced CRH-IR and decreased stress-induced activation of CRH neurons. Across all housing conditions, paternally behaving males displayed more anxiety-related behavior than nonpaternal males in the EPM, but showed no differences in CRH- or Fos-IR. Finally, the latency to engage in paternal behavior was positively correlated with the latency to approach a novel object. These results suggest that being a new father does not reduce anxiety, neophobia, or neural stress responsiveness. Low levels of neophobia, however, were associated with, but not necessary for paternal responsiveness. Copyright © 2012 Elsevier Inc. All rights reserved.

The variation management framework (VMF): A unifying graphical representation of robust design

DEFF Research Database (Denmark)

Howard, Thomas J.; Eifler, Tobias; Pedersen, Søren Nygaard

2017-01-01

In this article a framework for robust design and variation management is proposed by combining central models to Robust Design, namely, the Quality Loss Function, the Transfer Function, and the Domains of Axiomatic Design. The Variation Management Framework (VMF) shows how variation can be mapped...... from production variation right through to the quality loss perceived by the customer for a single characteristic chain. Seven levers which can be activated to increase product quality are described and positioned on the VMF and variation metrics are proposed....

Variational principles in terms of entransy for heat transfer

International Nuclear Information System (INIS)

Xu, Mingtian

2012-01-01

A variational principle for heat conduction is formulated which results in the steady state heat conduction equation established from the Fourier law. Furthermore based on the thermodynamics in terms of entransy a more general functional is defined for incompressible fluids. We show that extremizing this functional gives rise to the state described by the Navier-Stokes-Fourier equations with vanishing substantive derivatives of the temperature and velocity field. In this sense one may conclude that this variational principle is consistent with the Navier-Stokes-Fourier equations. Therefore the variational principle developed in the present work demonstrates a great advantage over the minimum entropy production principle. -- Highlights: ► A variational principle for heat transfer of incompressible fluid is established in terms of entransy. ► For pure heat conduction the variational principle leads to the classical steady state heat conduction equation. ► For heat convection the variational principle is consistent with the Navier-Stokes-Fourier equations.

Anatomic variation and orgasm: Could variations in anatomy explain differences in orgasmic success?

Science.gov (United States)

Emhardt, E; Siegel, J; Hoffman, L

2016-07-01

Though the public consciousness is typically focused on factors such as psychology, penis size, and the presence of the "G-spot," there are other anatomical and neuro-anatomic differences that could play an equal, or more important, role in the frequency and intensity of orgasms. Discovering these variations could direct further medical or procedural management to improve sexual satisfaction. The aim of this study is to review the available literature of anatomical sexual variation and to explain why this variation may predispose some patients toward a particular sexual experience. In this review, we explored the available literature on sexual anatomy and neuro-anatomy. We used PubMed and OVID Medline for search terms, including orgasm, penile size variation, clitoral variation, Grafenberg spot, and benefits of orgasm. First we review the basic anatomy and innervation of the reproductive organs. Then we describe several anatomical variations that likely play a superior role to popular known variation (penis size, presence of g-spot, etc). For males, the delicate play between the parasympathetic and sympathetic nervous systems is vital to achieve orgasm. For females, the autonomic component is more complex. The clitoris is the primary anatomical feature for female orgasm, including its migration toward the anterior vaginal wall. In conclusions, orgasms are complex phenomena involving psychological, physiological, and anatomic variation. While these variations predispose people to certain sexual function, future research should explore how to surgically or medically alter these. Clin. Anat. 29:665-672, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Epigenetic Pathways in Human Disease: The Impact of DNA Methylation on Stress-Related Pathogenesis and Current Challenges in Biomarker Development

Directory of Open Access Journals (Sweden)

M. Austin Argentieri

2017-04-01

Full Text Available HPA axis genes implicated in glucocorticoid regulation play an important role in regulating the physiological impact of social and environmental stress, and have become a focal point for investigating the role of glucocorticoid regulation in the etiology of disease. We conducted a systematic review to critically assess the full range of clinical associations that have been reported in relation to DNA methylation of CRH, CRH-R1/2, CRH-BP, AVP, POMC, ACTH, ACTH-R, NR3C1, FKBP5, and HSD11β1/2 genes in adults. A total of 32 studies were identified. There is prospective evidence for an association between HSD11β2 methylation and hypertension, and functional evidence of an association between NR3C1 methylation and both small cell lung cancer (SCLC and breast cancer. Strong associations have been reported between FKBP5 and NR3C1 methylation and PTSD, and biologically-plausible associations have been reported between FKBP5 methylation and Alzheimer's Disease. Mixed associations between NR3C1 methylation and mental health outcomes have been reported according to different social and environmental exposures, and according to varying gene regions investigated. We conclude by highlighting key challenges and future research directions that will need to be addressed in order to develop both clinically meaningful prognostic biomarkers and an evidence base that can inform public policy practice.

Individual variation of human S1P₁ coding sequence leads to heterogeneity in receptor function and drug interactions.

Science.gov (United States)

Obinata, Hideru; Gutkind, Sarah; Stitham, Jeremiah; Okuno, Toshiaki; Yokomizo, Takehiko; Hwa, John; Hla, Timothy

2014-12-01

Sphingosine 1-phosphate receptor 1 (S1P₁), an abundantly-expressed G protein-coupled receptor which regulates key vascular and immune responses, is a therapeutic target in autoimmune diseases. Fingolimod/Gilenya (FTY720), an oral medication for relapsing-remitting multiple sclerosis, targets S1P₁ receptors on immune and neural cells to suppress neuroinflammation. However, suppression of endothelial S1P₁ receptors is associated with cardiac and vascular adverse effects. Here we report the genetic variations of the S1P₁ coding region from exon sequencing of >12,000 individuals and their functional consequences. We conducted functional analyses of 14 nonsynonymous single nucleotide polymorphisms (SNPs) of the S1PR1 gene. One SNP mutant (Arg¹²⁰ to Pro) failed to transmit sphingosine 1-phosphate (S1P)-induced intracellular signals such as calcium increase and activation of p44/42 MAPK and Akt. Two other mutants (Ile⁴⁵ to Thr and Gly³⁰⁵ to Cys) showed normal intracellular signals but impaired S1P-induced endocytosis, which made the receptor resistant to FTY720-induced degradation. Another SNP mutant (Arg¹³ to Gly) demonstrated protection from coronary artery disease in a high cardiovascular risk population. Individuals with this mutation showed a significantly lower percentage of multi-vessel coronary obstruction in a risk factor-matched case-control study. This study suggests that individual genetic variations of S1P₁ can influence receptor function and, therefore, infer differential disease risks and interaction with S1P₁-targeted therapeutics. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Anatomy of melancholia: focus on hypothalamic-pituitary-adrenal axis overactivity and the role of vasopressin.

LENUS (Irish Health Repository)

Dinan, Timothy G

2012-02-03

Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis characterized by hypercortisolism, adrenal hyperplasia and abnormalities in negative feedback is the most consistently described biological abnormality in melancholic depression. Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are the main secretagogues of the HPA\\/stress system. Produced in the parvicellular division of the hypothalamic paraventricular nucleus the release of these peptides is influenced by inputs from monoaminergic neurones. In depression, anterior pituitary CRH1 receptors are down-regulated and response to CRH infusion is blunted. By contrast, vasopressin V3 receptors on the anterior pituitary show enhanced response to AVP stimulation and this enhancement plays a key role in maintaining HPA overactivity.

Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis

Science.gov (United States)

Colizzi, Marco; Iyegbe, Conrad; Powell, John; Ursini, Gianluca; Porcelli, Annamaria; Bonvino, Aurora; Taurisano, Paolo; Romano, Raffaella; Masellis, Rita; Blasi, Giuseppe; Morgan, Craig; Aitchison, Katherine; Mondelli, Valeria; Luzi, Sonija; Kolliakou, Anna; David, Anthony; Murray, Robin M.; Bertolino, Alessandro; Forti, Marta Di

2015-01-01

Both cannabis use and the dopamine receptor (DRD2) gene have been associated with schizophrenia, psychosis-like experiences, and cognition. However, there are no published data investigating whether genetically determined variation in DRD2 dopaminergic signaling might play a role in individual susceptibility to cannabis-associated psychosis. We genotyped (1) a case-control study of 272 patients with their first episode of psychosis and 234 controls, and also from (2) a sample of 252 healthy subjects, for functional variation in DRD2, rs1076560. Data on history of cannabis use were collected on all the studied subjects by administering the Cannabis Experience Questionnaire. In the healthy subjects’ sample, we also collected data on schizotypy and cognitive performance using the Schizotypal Personality Questionnaire and the N-back working memory task. In the case-control study, we found a significant interaction between the rs1076560 DRD2 genotype and cannabis use in influencing the likelihood of a psychotic disorder. Among cannabis users, carriers of the DRD2, rs1076560, T allele showed a 3-fold increased probability to suffer a psychotic disorder compared with GG carriers (OR = 3.07; 95% confidence interval [CI]: 1.22–7.63). Among daily users, T carrying subjects showed a 5-fold increase in the odds of psychosis compared to GG carriers (OR = 4.82; 95% CI: 1.39–16.71). Among the healthy subjects, T carrying cannabis users had increased schizotypy compared with T carrying cannabis-naïve subjects, GG cannabis users, and GG cannabis-naïve subjects (all P ≤ .025). T carrying cannabis users had reduced working memory accuracy compared with the other groups (all P ≤ .008). Thus, variation of the DRD2, rs1076560, genotype may modulate the psychosis-inducing effect of cannabis use. PMID:25829376

Energies and wave functions of an off-centre donor in hemispherical quantum dot: Two-dimensional finite difference approach and ritz variational principle

Energy Technology Data Exchange (ETDEWEB)

Nakra Mohajer, Soukaina; El Harouny, El Hassan [Laboratoire de Physique de la Matière Condensée, Département de Physique, Faculté des Sciences, Université Abdelmalek Essaadi, B.P. 2121 M’Hannech II, 93030 Tétouan (Morocco); Ibral, Asmaa [Equipe d’Optique et Electronique du Solide, Département de Physique, Faculté des Sciences, Université Chouaïb Doukkali, B. P. 20 El Jadida Principale, El Jadida (Morocco); Laboratoire d’Instrumentation, Mesure et Contrôle, Département de Physique, Faculté des Sciences, Université Chouaïb Doukkali, B. P. 20 El Jadida Principale, El Jadida (Morocco); El Khamkhami, Jamal [Laboratoire de Physique de la Matière Condensée, Département de Physique, Faculté des Sciences, Université Abdelmalek Essaadi, B.P. 2121 M’Hannech II, 93030 Tétouan (Morocco); and others

2016-09-15

Eigenvalues equation solutions of a hydrogen-like donor impurity, confined in a hemispherical quantum dot deposited on a wetting layer and capped by an insulating matrix, are determined in the framework of the effective mass approximation. Conduction band alignments at interfaces between quantum dot and surrounding materials are described by infinite height barriers. Ground and excited states energies and wave functions are determined analytically and via one-dimensional finite difference approach in case of an on-center donor. Donor impurity is then moved from center to pole of hemispherical quantum dot and eigenvalues equation is solved via Ritz variational principle, using a trial wave function where Coulomb attraction between electron and ionized donor is taken into account, and by two-dimensional finite difference approach. Numerical codes developed enable access to variations of donor total energy, binding energy, Coulomb correlation parameter, spatial extension and radial probability density with respect to hemisphere radius and impurity position inside the quantum dot.

Energies and wave functions of an off-centre donor in hemispherical quantum dot: Two-dimensional finite difference approach and ritz variational principle

International Nuclear Information System (INIS)

Nakra Mohajer, Soukaina; El Harouny, El Hassan; Ibral, Asmaa; El Khamkhami, Jamal

2016-01-01

Eigenvalues equation solutions of a hydrogen-like donor impurity, confined in a hemispherical quantum dot deposited on a wetting layer and capped by an insulating matrix, are determined in the framework of the effective mass approximation. Conduction band alignments at interfaces between quantum dot and surrounding materials are described by infinite height barriers. Ground and excited states energies and wave functions are determined analytically and via one-dimensional finite difference approach in case of an on-center donor. Donor impurity is then moved from center to pole of hemispherical quantum dot and eigenvalues equation is solved via Ritz variational principle, using a trial wave function where Coulomb attraction between electron and ionized donor is taken into account, and by two-dimensional finite difference approach. Numerical codes developed enable access to variations of donor total energy, binding energy, Coulomb correlation parameter, spatial extension and radial probability density with respect to hemisphere radius and impurity position inside the quantum dot.

Variational collocation on finite intervals

International Nuclear Information System (INIS)

Amore, Paolo; Cervantes, Mayra; Fernandez, Francisco M

2007-01-01

In this paper, we study a set of functions, defined on an interval of finite width, which are orthogonal and which reduce to the sinc functions when the appropriate limit is taken. We show that these functions can be used within a variational approach to obtain accurate results for a variety of problems. We have applied them to the interpolation of functions on finite domains and to the solution of the Schroedinger equation, and we have compared the performance of the present approach with others

Introduction to the calculus of variations

CERN Document Server

Sagan, Hans

1992-01-01

Excellent text provides basis for thorough understanding of the problems, methods and techniques of the calculus of variations and prepares readers for the study of modern optimal control theory. Treatment limited to extensive coverage of single integral problems in one and more unknown functions. Carefully chosen variational problems and over 400 exercises. ""Should find wide acceptance as a text and reference.""-American Mathematical Monthly. 1969 edition. Bibliography.

Total Variation Depth for Functional Data

KAUST Repository

Huang, Huang; Sun, Ying

2016-01-01

that are associated with shape and magnitude outlyingness, respectively. This decomposition allows us to develop an effective procedure for outlier detection and useful visualization tools, while naturally accounting for the correlation in functional data. Finally

Variations in the small-scale galactic magnetic field and short time-scale intensity variations of extragalactic radio sources

International Nuclear Information System (INIS)

Simonetti, J.H.

1985-01-01

Structure functions of the Faraday rotation measures (RMs) of extragalactic radio sources are used to investigate variations in the interstellar magnetic field on length scales of approx.0.01 to 100 pc. Model structure functions derived assuming a power-law power spectrum of irregularities in n/sub e/B, are compared with those observed. The results indicate an outer angular scale for RM variations of approximately less than or equal to 5 0 and evidence for RM variations on scales as small as 1'. Differences in the variance of n/sub e/B fluctuations for various lines of sight through the Galaxy are found. Comparison of pulsar scintillations in right- and left-circular polarizations yield an upper limit to the variations in n/sub e/ on a length scale of approx.10 11 cm. RMs were determined through high-velocity molecular flows in galactic star-formation regions, with the goal of constraining magnetic fields in and near the flows. RMs of 7 extragalactic sources with a approx.20 arcmin wide area seen through Cep A, fall in two groups separated by approx.150 rad m -2 - large given our knowledge of RM variations on small angular scales and possibly a result of the anisotropy of the high-velocity material

and chebyshev functions

Directory of Open Access Journals (Sweden)

Mohsen Razzaghi

2000-01-01

Full Text Available A direct method for finding the solution of variational problems using a hybrid function is discussed. The hybrid functions which consist of block-pulse functions plus Chebyshev polynomials are introduced. An operational matrix of integration and the integration of the cross product of two hybrid function vectors are presented and are utilized to reduce a variational problem to the solution of an algebraic equation. Illustrative examples are included to demonstrate the validity and applicability of the technique.

Calculation of exchange coupling constants in triply-bridged dinuclear Cu(II) compounds based on spin-flip constricted variational density functional theory.

Science.gov (United States)

Seidu, Issaka; Zhekova, Hristina R; Seth, Michael; Ziegler, Tom

2012-03-08

The performance of the second-order spin-flip constricted variational density functional theory (SF-CV(2)-DFT) for the calculation of the exchange coupling constant (J) is assessed by application to a series of triply bridged Cu(II) dinuclear complexes. A comparison of the J values based on SF-CV(2)-DFT with those obtained by the broken symmetry (BS) DFT method and experiment is provided. It is demonstrated that our methodology constitutes a viable alternative to the BS-DFT method. The strong dependence of the calculated exchange coupling constants on the applied functionals is demonstrated. Both SF-CV(2)-DFT and BS-DFT affords the best agreement with experiment for hybrid functionals.

Diurnal Variation of Plasma Brain-Derived Neurotrophic Factor Levels in Women with Functional Hypothalamic Amenorrhea.

Science.gov (United States)

Drakopoulos, Panagiotis; Casarosa, Elena; Bucci, Fiorella; Piccinino, Manuela; Wenger, Jean-Marie; Nappi, Rossella Elena; Polyzos, Nicholas; Genazzani, Andrea Riccardo; Pluchino, Nicola

2015-01-01

Brain-derived neurotrophic factor (BDNF) is strongly related to hormonal networks and is modulated by hypothalamic activity. To evaluate plasma BDNF concentration in patients with functional hypothalamic amenorrhea (FHA), with reference to the BDNF circadian rhythm and its relation with the cortisol (F) rhythm, and to assess whether the duration of amenorrhea might influence the BDNF:F ratio in FHA. This was an observational study evaluating 36 amenorrheic and 30 eumenorrheic women. Basal values of BDNF and hormones were examined in blood samples collected from 7:00 to 9:00 h in all the women. Basal BDNF and F levels were determined in blood samples collected in 12 subjects from each group at 8:00, 12:00, 16:00, 20:00, and 24:00 h. BDNF plasma levels are significantly lower in amenorrheic women (p 0.05), sex steroids, and F in FHA. Low plasma BDNF levels in FHA are not significantly correlated with duration of amenorrhea. The 24-hour variation of BDNF in amenorrheic women is significantly lower when compared to the control group, and normal daily variations of BDNF disappeared in FHA patients. F preserved its circadian rhythm in both groups. Interactions between BDNF, the hypothalamus-pituitary-adrenal axis, and sex steroids might be critical in clinical conditions of modified homeostasis/adaptation, such as FHA. © 2015 S. Karger AG, Basel.

Different stress-related gene expression in depression and suicide.

Science.gov (United States)

Zhao, J; Qi, X-R; Gao, S-F; Lu, J; van Wamelen, D J; Kamphuis, W; Bao, A-M; Swaab, D F

2015-09-01

Suicide occurs in some, but not all depressed patients. So far, it remains unknown whether the studied stress-related candidate genes change in depression, suicide or both. The prefrontal cortex (PFC) is involved in, among other things, impulse control and inhibitory behavior and plays an important role in both suicide and depression. We have employed qPCR to study 124 anterior cingulate cortex (ACC) and dorsolateral PFC (DLPFC) brain samples, obtained from two brain banks, from: i) young depressed patients (average age 43 years) who committed suicide (MDD-S) and depressed patients who died from causes other than suicide (MDD-NS) and from ii) elderly depressed patients (average age 75 years) who did not commit suicide (DEP). Both cohorts were individually matched with non-psychiatric non-suicide control subjects. We determined the transcript levels of hypothalamic-pituitary-adrenal axis-regulating molecules (corticotropin-releasing hormone (CRH), CRH receptors, CRH binding protein, mineralocorticoid receptor/glucocorticoid receptor), transcription factors that regulate CRH expression, CRH-stimulating cytokines, chaperone proteins, retinoid signaling, brain-derived neurotrophic factor and tropomyosin-related kinase B, cytochrome proteins, nitric oxide synthase (NOS) and monoamines. In the MDD-S group, expression levels of CRH and neuronal NOS-interacting DHHC domain-containing protein with dendritic mRNA (NIDD) were increased. Other changes were only present in the DEP group, i.e. decreased NIDD, and increased and 5-hydroxytryptamine receptor 1A (5-HT1A) expression levels. Changes were found to be more pronounced in the anterior cingulate cortex than in the dorsolateral PFC. Depressed patients who committed suicide have different gene expression patterns than depressed patients who died of causes other than suicide. Copyright © 2015 Elsevier Ltd. All rights reserved.

On unravelling mechanism of interplay between cloud and large scale circulation: a grey area in climate science

Science.gov (United States)

De, S.; Agarwal, N. K.; Hazra, Anupam; Chaudhari, Hemantkumar S.; Sahai, A. K.

2018-04-01

The interaction between cloud and large scale circulation is much less explored area in climate science. Unfolding the mechanism of coupling between these two parameters is imperative for improved simulation of Indian summer monsoon (ISM) and to reduce imprecision in climate sensitivity of global climate model. This work has made an effort to explore this mechanism with CFSv2 climate model experiments whose cloud has been modified by changing the critical relative humidity (CRH) profile of model during ISM. Study reveals that the variable CRH in CFSv2 has improved the nonlinear interactions between high and low frequency oscillations in wind field (revealed as internal dynamics of monsoon) and modulates realistically the spatial distribution of interactions over Indian landmass during the contrasting monsoon season compared to the existing CRH profile of CFSv2. The lower tropospheric wind error energy in the variable CRH simulation of CFSv2 appears to be minimum due to the reduced nonlinear convergence of error to the planetary scale range from long and synoptic scales (another facet of internal dynamics) compared to as observed from other CRH experiments in normal and deficient monsoons. Hence, the interplay between cloud and large scale circulation through CRH may be manifested as a change in internal dynamics of ISM revealed from scale interactive quasi-linear and nonlinear kinetic energy exchanges in frequency as well as in wavenumber domain during the monsoon period that eventually modify the internal variance of CFSv2 model. Conversely, the reduced wind bias and proper modulation of spatial distribution of scale interaction between the synoptic and low frequency oscillations improve the eastward and northward extent of water vapour flux over Indian landmass that in turn give feedback to the realistic simulation of cloud condensates attributing improved ISM rainfall in CFSv2.

From genomic variation to personalized medicine

DEFF Research Database (Denmark)

Wesolowska, Agata; Schmiegelow, Kjeld

Genomic variation is the basis of interindividual differences in observable traits and disease susceptibility. Genetic studies are the driving force of personalized medicine, as many of the differences in treatment efficacy can be attributed to our genomic background. The rapid development...... a considerable amount of the phenotype variability, hence the major difficulty of interpretation lies in the complexity of molecular interactions. This PhD thesis describes the state-of-art of the functional human variation research (Chapter 1) and introduces childhood acute lymphoblastic leukaemia (ALL...... the thesis and includes some final remarks on the perspectives of genomic variation research and personalized medicine. In summary, this thesis demonstrates the feasibility of integrative analyses of genomic variations and introduces large-scale hypothesis-driven SNP exploration studies as an emerging...

Genetic contributions to variation in general cognitive function: A meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

NARCIS (Netherlands)

G. Davies (Gail); N.J. Armstrong (Nicola J.); J.C. Bis (Joshua); J. Bressler (Jan); V. Chouraki (Vincent); S. Giddaluru (Sudheer); E. Hofer; C.A. Ibrahim-Verbaas (Carla); M. Kirin (Mirna); J. Lahti; S.J. van der Lee (Sven); S. Le Hellard (Stephanie); T. Liu; R.E. Marioni (Riccardo); C. Oldmeadow (Christopher); D. Postmus (Douwe); G.D. Smith; J.A. Smith (Jennifer A); A. Thalamuthu (Anbupalam); R. Thomson (Russell); V. Vitart (Veronique); J. Wang; L. Yu; L. Zgaga (Lina); W. Zhao (Wei); R. Boxall (Ruth); S.E. Harris (Sarah); W.D. Hill (W. David); D.C. Liewald (David C.); M. Luciano (Michelle); H.H.H. Adams (Hieab); D. Ames (David); N. Amin (Najaf); P. Amouyel (Philippe); A.A. Assareh; R. Au; J.T. Becker (James); A. Beiser; C. Berr (Claudine); L. Bertram (Lars); E.A. Boerwinkle (Eric); B.M. Buckley (Brendan M.); H. Campbell (Harry); J. Corley; P.L. De Jager; C. Dufouil (Carole); J.G. Eriksson (Johan G.); T. Espeseth (Thomas); J.D. Faul; I. Ford; G. Scotland (Generation); R.F. Gottesman (Rebecca); M.D. Griswold (Michael); V. Gudnason (Vilmundur); T.B. Harris; G. Heiss (Gerardo); A. Hofman (Albert); E.G. Holliday (Elizabeth); J.E. Huffman (Jennifer); S.L.R. Kardia (Sharon); N.A. Kochan (Nicole A.); D.S. Knopman (David); J.B. Kwok; J.-C. Lambert; T. Lee; G. Li; S.-C. Li; M. Loitfelder (Marisa); O.L. Lopez (Oscar); A.J. Lundervold; A. Lundqvist; R. Mather; S.S. Mirza (Saira); L. Nyberg; B.A. Oostra (Ben); A. Palotie (Aarno); G. Papenberg; A. Pattie (Alison); K. Petrovic (Katja); O. Polasek (Ozren); B.M. Psaty (Bruce); P. Redmond (Paul); S. Reppermund; J.I. Rotter; R. Schmidt (Reinhold); M. Schuur (Maaike); P.W. Schofield; R.J. Scott; V.M. Steen (Vidar); D.J. Stott (David J.); J.C. van Swieten (John); K.D. Taylor (Kent); J. Trollor; S. Trompet (Stella); A.G. Uitterlinden (André); G. Weinstein; E. Widen (Elisabeth); B.G. Windham (B Gwen); J.W. Jukema (Jan Wouter); A. Wright (Alan); M.J. Wright (Margaret); Q. Yang (Qiong Fang); H. Amieva (Hélène); J. Attia (John); D.A. Bennett (David); H. Brodaty (Henry); A.J. de Craen (Anton); C. Hayward; M.A. Ikram (Arfan); U. Lindenberger; L.-G. Nilsson; D.J. Porteous (David J.); K. Räikkönen (Katri); I. Reinvang (Ivar); I. Rudan (Igor); P.S. Sachdev (Perminder); R. Schmidt; P. Schofield (Peter); V. Srikanth; J.M. Starr (John); S.T. Turner (Stephen); D.R. Weir (David R.); J.F. Wilson (James F); C.M. van Duijn (Cornelia); L.J. Launer (Lenore); A.L. Fitzpatrick (Annette); S. Seshadri (Sudha); T.H. Mosley (Thomas H.); I.J. Deary (Ian J.)

2015-01-01

textabstractGeneral cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of

Preventive effects of ginsenoside Rg1 on post-traumatic stress disorder (PTSD)-like behavior in male C57/B6 mice.

Science.gov (United States)

Wang, Zhongli; Zhu, Kexuan; Chen, Lin; Ou Yang, Liufeng; Huang, Yufang; Zhao, Yunan

2015-09-25

We investigated the preventive effects of Rg1 on a model of mouse post-traumatic stress disorder (PTSD) induced by electric shock combined with situation reminder and explored the underlying mechanism. In the experiment, before the PTSD animal model was developed, Rg1 (10, 5, and 2.5mg/kg) was orally administered for one week. After the animal model was established, PTSD-like behavior was observed using elevated plus maze, black and light box, and open field tests. One hour after the behavior test, all mice were sacrificed, and then serum corticosterone (CORT) and hypothalamus corticotrophin-releasing hormone (CRH) assays were performed. Results showed that Rg1 (5mg/kg) treatments relieved PTSD-like behavior by altering elevated serum corticosterone and hypothalamus CRH levels. By contrast, fluoxetine (3mg/kg) treatment reversed the behavior changes and had no effect on increased CORT and CRH levels. These findings confirmed the preventive effect of Rg1 in PTSD model. Decreasing CORT and CRH levels may be one of the underlying mechanisms. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Mono-(2-Ethylhexyl Phthalate Promotes Pro-Labor Gene Expression in the Human Placenta.

Directory of Open Access Journals (Sweden)

Ximi K Wang

Full Text Available Women exposed to phthalates during pregnancy are at increased risk for delivering preterm, but the mechanism behind this relationship is unknown. Placental corticotropin-releasing hormone (CRH and cyclooxygenase-2 (COX-2 are key mediators of parturition and are regulated by the non-canonical NF-kB (RelB/p52 signaling pathway. In this study, we demonstrate that one of the major phthalate metabolites, mono-(2-ethylhexyl-phthalate (MEHP, increased CRH and COX-2 mRNA and protein abundance in a dose-dependent manner in primary cultures of cytotrophoblast. This was coupled with an increase in nuclear import of RelB/p52 and its association with the CRH and COX-2 promoters. Silencing of NF-kB inducing kinase, a central signaling component of the non-canonical NF-kB pathway, blocked MEHP-induced upregulation of CRH and COX-2. These results suggest a potential mechanism mediated by RelB/p52 by which phthalates could prematurely induce pro-labor gene activity and lead to preterm birth.

Non-codingRNA sequence variations in human chronic lymphocytic leukemia and colorectal cancer.

Science.gov (United States)

Wojcik, Sylwia E; Rossi, Simona; Shimizu, Masayoshi; Nicoloso, Milena S; Cimmino, Amelia; Alder, Hansjuerg; Herlea, Vlad; Rassenti, Laura Z; Rai, Kanti R; Kipps, Thomas J; Keating, Michael J; Croce, Carlo M; Calin, George A

2010-02-01

Cancer is a genetic disease in which the interplay between alterations in protein-coding genes and non-coding RNAs (ncRNAs) plays a fundamental role. In recent years, the full coding component of the human genome was sequenced in various cancers, whereas such attempts related to ncRNAs are still fragmentary. We screened genomic DNAs for sequence variations in 148 microRNAs (miRNAs) and ultraconserved regions (UCRs) loci in patients with chronic lymphocytic leukemia (CLL) or colorectal cancer (CRC) by Sanger technique and further tried to elucidate the functional consequences of some of these variations. We found sequence variations in miRNAs in both sporadic and familial CLL cases, mutations of UCRs in CLLs and CRCs and, in certain instances, detected functional effects of these variations. Furthermore, by integrating our data with previously published data on miRNA sequence variations, we have created a catalog of DNA sequence variations in miRNAs/ultraconserved genes in human cancers. These findings argue that ncRNAs are targeted by both germ line and somatic mutations as well as by single-nucleotide polymorphisms with functional significance for human tumorigenesis. Sequence variations in ncRNA loci are frequent and some have functional and biological significance. Such information can be exploited to further investigate on a genome-wide scale the frequency of genetic variations in ncRNAs and their functional meaning, as well as for the development of new diagnostic and prognostic markers for leukemias and carcinomas.

Functional Coding Variation in Recombinant Inbred Mouse Lines Reveals Novel Serotonin Transporter-Associated Phenotypes

Energy Technology Data Exchange (ETDEWEB)

Carneiro, Ana [Vanderbilt University; Airey, David [University of Tennessee Health Science Center, Memphis; Thompson, Brent [Vanderbilt University; Zhu, C [Vanderbilt University; Rinchik, Eugene M [ORNL; Lu, Lu [University of Tennessee Health Science Center, Memphis; Chesler, Elissa J [ORNL; Erikson, Keith [University of North Carolina; Blakely, Randy [Vanderbilt University

2009-01-01

The human serotonin (5-hydroxytryptamine, 5-HT) transporter (hSERT, SLC6A4) figures prominently in the etiology or treatment of many prevalent neurobehavioral disorders including anxiety, alcoholism, depression, autism and obsessive-compulsive disorder (OCD). Here we utilize naturally occurring polymorphisms in recombinant inbred (RI) lines to identify novel phenotypes associated with altered SERT function. The widely used mouse strain C57BL/6J, harbors a SERT haplotype defined by two nonsynonymous coding variants (Gly39 and Lys152 (GK)). At these positions, many other mouse lines, including DBA/2J, encode Glu39 and Arg152 (ER haplotype), assignments found also in hSERT. Synaptosomal 5-HT transport studies revealed reduced uptake associated with the GK variant. Heterologous expression studies confirmed a reduced SERT turnover rate for the GK variant. Experimental and in silico approaches using RI lines (C57Bl/6J X DBA/2J=BXD) identifies multiple anatomical, biochemical and behavioral phenotypes specifically impacted by GK/ER variation. Among our findings are multiple traits associated with anxiety and alcohol consumption, as well as of the control of dopamine (DA) signaling. Further bioinformatic analysis of BXD phenotypes, combined with biochemical evaluation of SERT knockout mice, nominates SERT-dependent 5-HT signaling as a major determinant of midbrain iron homeostasis that, in turn, dictates ironregulated DA phenotypes. Our studies provide a novel example of the power of coordinated in vitro, in vivo and in silico approaches using murine RI lines to elucidate and quantify the system-level impact of gene variation.

TU-F-17A-09: Four-Dimensional Cone Beam CT Ventilation Imaging Can Detect Interfraction Lung Function Variations for Locally Advanced Lung Cancer Patients

Energy Technology Data Exchange (ETDEWEB)

Kipritidis, J; Keall, P [Radiation Physics Laboratory, University of Sydney, Sydney NSW 2006 Australia (Australia); Hugo, G; Weiss, E; Williamson, J [Department of Radiation Oncology, Virginia Commonwealth University, Richmond VA (United States)

2014-06-15

Purpose: Four-dimensional cone beam CT ventilation imaging (4D-CBCT VI) is a novel functional lung imaging modality requiring validation. We hypothesize that 4D-CBCT VI satisfies a necessary condition for validity: that intrafraction variations (e.g. due to poor 4D-CBCT image quality) are substantially different to interfraction variations (e.g. due to changes in underlying function). We perform the first comparison of intrafraction (pre/post fraction) and interfraction (week-to-week) 4D-CBCT VIs for locally advanced non small cell lung cancer (LA NSCLC) patients undergoing radiation therapy. Methods: A total of 215 4D-CBCT scans were acquired for 19 LA NSCLC patients over 4-6 weeks of radiation therapy, including 75 pairs of pre-/post-fraction scans on the same day. 4D-CBCT VIs were obtained by applying state-of-the-art, B-spline deformable image registration to obtain the Jacobian determinant of deformation between the end-exhale and end-inhale phases. All VIs were deformably registered to the corresponding first day scan, normalized between the 10th and 90th percentile values and cropped to the ipsilateral lung only. Intrafraction variations were assessed by computing the mean and standard deviation of voxel-wise differences between all same-day pairs of pre-/post-fraction VIs. Interfraction differences were computed between first-day VIs and treatment weeks 2, 4 and 6 for all 19 patients. We tested the hypothesis by comparing cumulative distribution functions (CDFs) of intrafraction and interfraction ventilation differences using two-sided Kolmogorov-Smirnov goodness-of-fit tests. Results: The (mean ± std. dev.) of intrafraction differences was (−0.007 ± 0.079). Interfraction differences for weeks 2, 4 and 6 were (−0.035 ± 0.103), (−0.006 ± 0.094) and (−0.019 ± 0.127) respectively. For week 2, the changes in CDFs for intrafraction and interfraction differences approached statistical significance (p=0.099). Conclusion: We have shown that 4D-CBCT VI

Genetic variation in an individual human exome.

Directory of Open Access Journals (Sweden)

Pauline C Ng

2008-08-01

Full Text Available There is much interest in characterizing the variation in a human individual, because this may elucidate what contributes significantly to a person's phenotype, thereby enabling personalized genomics. We focus here on the variants in a person's 'exome,' which is the set of exons in a genome, because the exome is believed to harbor much of the functional variation. We provide an analysis of the approximately 12,500 variants that affect the protein coding portion of an individual's genome. We identified approximately 10,400 nonsynonymous single nucleotide polymorphisms (nsSNPs in this individual, of which approximately 15-20% are rare in the human population. We predict approximately 1,500 nsSNPs affect protein function and these tend be heterozygous, rare, or novel. Of the approximately 700 coding indels, approximately half tend to have lengths that are a multiple of three, which causes insertions/deletions of amino acids in the corresponding protein, rather than introducing frameshifts. Coding indels also occur frequently at the termini of genes, so even if an indel causes a frameshift, an alternative start or stop site in the gene can still be used to make a functional protein. In summary, we reduced the set of approximately 12,500 nonsilent coding variants by approximately 8-fold to a set of variants that are most likely to have major effects on their proteins' functions. This is our first glimpse of an individual's exome and a snapshot of the current state of personalized genomics. The majority of coding variants in this individual are common and appear to be functionally neutral. Our results also indicate that some variants can be used to improve the current NCBI human reference genome. As more genomes are sequenced, many rare variants and non-SNP variants will be discovered. We present an approach to analyze the coding variation in humans by proposing multiple bioinformatic methods to hone in on possible functional variation.

The variational spiked oscillator

International Nuclear Information System (INIS)

Aguilera-Navarro, V.C.; Ullah, N.

1992-08-01

A variational analysis of the spiked harmonic oscillator Hamiltonian -d 2 / d x 2 + x 2 + δ/ x 5/2 , δ > 0, is reported in this work. A trial function satisfying Dirichlet boundary conditions is suggested. The results are excellent for a large range of values of the coupling parameter. (author)

Variational approach to nuclear fluid dynamics

International Nuclear Information System (INIS)

Da Providencia, J.P.; Holzwarth, G.

1983-01-01

A variational derivation of a fluid-dynamical formalism for finite Fermi systems is presented which is based on a single determinant as variational function and does not exclude the possibility of transverse flow. Therefore the explicit specification of the time-odd part has to go beyond the local chi-approximation, while the time-even part is taken in the generalized scaling form. The necessary boundary conditions are derived from the variation of the lagrangian. The results confirm previous simplified approaches to a remarkable degree for quadrupole modes; for other multipolarities the deviations are much less than might be expected according to a sizeable change in the transverse sound speed. (orig.)

Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis.

Science.gov (United States)

Colizzi, Marco; Iyegbe, Conrad; Powell, John; Ursini, Gianluca; Porcelli, Annamaria; Bonvino, Aurora; Taurisano, Paolo; Romano, Raffaella; Masellis, Rita; Blasi, Giuseppe; Morgan, Craig; Aitchison, Katherine; Mondelli, Valeria; Luzi, Sonija; Kolliakou, Anna; David, Anthony; Murray, Robin M; Bertolino, Alessandro; Di Forti, Marta

2015-09-01

Both cannabis use and the dopamine receptor (DRD2) gene have been associated with schizophrenia, psychosis-like experiences, and cognition. However, there are no published data investigating whether genetically determined variation in DRD2 dopaminergic signaling might play a role in individual susceptibility to cannabis-associated psychosis. We genotyped (1) a case-control study of 272 patients with their first episode of psychosis and 234 controls, and also from (2) a sample of 252 healthy subjects, for functional variation in DRD2, rs1076560. Data on history of cannabis use were collected on all the studied subjects by administering the Cannabis Experience Questionnaire. In the healthy subjects' sample, we also collected data on schizotypy and cognitive performance using the Schizotypal Personality Questionnaire and the N-back working memory task. In the case-control study, we found a significant interaction between the rs1076560 DRD2 genotype and cannabis use in influencing the likelihood of a psychotic disorder. Among cannabis users, carriers of the DRD2, rs1076560, T allele showed a 3-fold increased probability to suffer a psychotic disorder compared with GG carriers (OR = 3.07; 95% confidence interval [CI]: 1.22-7.63). Among daily users, T carrying subjects showed a 5-fold increase in the odds of psychosis compared to GG carriers (OR = 4.82; 95% CI: 1.39-16.71). Among the healthy subjects, T carrying cannabis users had increased schizotypy compared with T carrying cannabis-naïve subjects, GG cannabis users, and GG cannabis-naïve subjects (all P ≤ .025). T carrying cannabis users had reduced working memory accuracy compared with the other groups (all P ≤ .008). Thus, variation of the DRD2, rs1076560, genotype may modulate the psychosis-inducing effect of cannabis use. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Summertime Spatial Variations in Atmospheric Particulate Matter and Its Chemical Components in Different Functional Areas of Xiamen, China

Directory of Open Access Journals (Sweden)

Shuhui Zhao

2015-02-01

Full Text Available Due to the highly heterogeneous and dynamic nature of urban areas in Chinese cities, air pollution exhibits well-defined spatial variations. Rapid urbanization in China has heightened the importance of understanding and characterizing atmospheric particulate matter (PM concentrations and their spatiotemporal variations. To investigate the small-scale spatial variations in PM in Xiamen, total suspended particulate (TSP, PM10, PM5 and PM2.5 measurements were collected between August and September in 2012. Their average mass concentrations were 102.50 μg∙m−3, 82.79 μg∙m−3, 55.67 μg∙m−3 and 43.70 μg∙m−3, respectively. Organic carbon (OC and elemental carbon (EC in PM2.5 were measured using thermal optical transmission. Based on the PM concentrations for all size categories, the following order for the different functional areas studied was identified: hospital > park > commercial area > residential area > industrial area. OC contributed approximately 5%–23% to the PM2.5 mass, whereas EC accounted for 0.8%–6.95%. Secondary organic carbon constituted most of the carbonaceous particles found in the park, commercial, industrial and residential areas, with the exception of hospitals. The high PM and EC concentrations in hospitals were primarily caused by vehicle emissions. Thus, the results suggest that long-term plans should be to limit the number of vehicles entering hospital campuses, construct large-capacity underground parking structures, and choose hospital locations far from major roads.

Activation of the hypothalamic-pituitary-adrenal axis by addictive drugs: different pathways, common outcome.

Science.gov (United States)

Armario, Antonio

2010-07-01

Addictive drugs (opiates, ethanol, cannabinoids (CBs), nicotine, cocaine, amphetamines) induce activation of the hypothalamic-pituitary-adrenal (HPA) axis, with the subsequent release of adrenocorticotropic hormone and glucocorticoids. The sequence of events leading to HPA activation appears to start within the brain, suggesting that activation is not secondary to peripheral homeostatic alterations. The precise neurochemical mechanisms and brain pathways involved are markedly dependent on the particular drug, although it is assumed that information eventually converges into the hypothalamic paraventricular nucleus (PVN). Whereas some drugs may act on the hypothalamus or directly within PVN neurons (i.e. ethanol), others exert their primary action outside the PVN (i.e. CBs, nicotine, cocaine). Corticotropin-releasing hormone (CRH) has a critical role in most cases, but the changes in c-fos and CRH gene expression in the PVN also reveal differences among drugs. More studies are needed to understand how addictive drugs act on this important neuroendocrine system and their functional consequences. Copyright 2010 Elsevier Ltd. All rights reserved.

Variational lower bound on the scattering length

International Nuclear Information System (INIS)

Rosenberg, L.; Spruch, L.

1975-01-01

The scattering length A characterizes the zero-energy scattering of one system by another. It was shown some time ago that a variational upper bound on A could be obtained using methods, of the Rayleigh-Ritz type, which are commonly employed to obtain upper bounds on energy eigenvalues. Here we formulate a method for obtaining a variational lower bound on A. Once again the essential idea is to express the scattering length as a variational estimate plus an error term and then to reduce the problem of bounding the error term to one involving bounds on energy eigenvalues. In particular, the variational lower bound on A is rigorously established provided a certin modified Hamiltonian can be shown to have no discrete states lying below the level of the continuum threshold. It is unfortunately true that necessary conditions for the existence of bound states are not available for multiparticle systems in general. However, in the case of positron-atom scattering the adiabatic approximation can be introduced as an (essentially) solvable comparison problem to rigorously establish the nonexistence of bound states of the modified Hamiltonian. It has recently been shown how the validity of the variational upper bound on A can be maintained when the target ground-state wave function is imprecisely known. Similar methods can be used to maintain the variational lower bound on A. Since the bound is variational, the error in the calculated scattering length will be of second order in the error in the wave function. The use of the adiabatic approximation in the present context places no limitation in principle on the accuracy achievable

[The hypothalamic-pituitary-adrenal axis and depressive disorder: recent progress].

Science.gov (United States)

Kunugi, Hiroshi; Hori, Hiroaki; Numakawa, Tadahiro; Ota, Miho

2012-08-01

Depression is a stress-induced disorder and there is compelling evidence for the involvement of hypothalamic-pituitary-adrenal (HPA) axis abnormalities in the disease. Chronic hyperactivity of the HPA axis and resultant excessive glucocorticoid (hypercortisolism) may be causal to depression. We demonstrated that the dexamethasone (DEX)/CRH test is a sensitive state-dependent marker to monitor HPA axis abnormalities. Restoration from HPA axis abnormalities occurs with clinical responses to treatment. Brain-derived neurotrophic factor (BDNF) has also been implicated in depression. We found that glucocorticoid (DEX) suppresses BDNF-induced dendrite outgrowth and synaptic formation via blocking the MAPK pathway in early-developing cultured hippocampal neurons. Furthermore, we demonstrated that glucocorticoid receptor (GR) and TrkB (a specific receptor of BDNF) interact and that DEX acutely suppresses BDNF-induced glutamate release by affecting the PLC-gamma pathway in cultured cortical neurons, indicating a mechanism underlying the effect of excessive glucocorticoid on BDNF function and resultant damage in cortical neurons. In a macroscopic view using magnetic resonance imaging (MRI), we found that individuals with hypercortisolism detected by the DEX/CRH test demonstrated volume loss in gray matter and reduced neural network assessed with diffusion tensor imaging in several brain regions. Finally, we observed that individuals with hypocortisolism detected by the DEX/CRH test tend to present more distress symptoms, maladaptive coping styles, and schizotypal personality traits than their counterparts, which points to the important role of hypocortisolism as well as hypercortisolism in depression spectrum disorders.

The difficulties of pseudo-Cushing's syndrome (or "non-neoplastic hypercortisolism").

Science.gov (United States)

Chabre, Olivier

2018-06-01

Pseudo-Cushing's syndrome covers different pathological conditions responsible for mild-to-moderate ACTH-dependent hypercortisolism, related not to an ACTH-secreting tumor but rather to CRH and/or AVP hypothalamic secretion through activation of various neural pathways, in patients generally displaying excess central adiposity. It is better termed "non-neoplastic hypercortisolism" (NNH). The main conditions implicated in NNH comprise: neuropsychiatric disorder, alcohol abuse, insulin-resistant obesity, polycystic ovary syndrome, and end-stage kidney disease. Glucocorticoid resistance is one differential diagnosis, as are some cases of primary adrenal disease with incompletely suppressed ACTH. Differentiating between NNH and mild-to-moderate Cushing's disease can be a real challenge. Clinical analysis, based on thorough history taking and screening for catabolic signs is essential; useful explorations include midnight serum or salivary cortisol and Dex/CRH and ddAVP stimulation response. Pituitary MRI suffers from limitations regarding both sensitivity and specificity, while bilateral inferior petrosal sinus sampling cannot distinguish between pituitary ACTH secretion by a tumor or by normal cells stimulated by endogenous CRH. Definitive diagnosis of functional etiology requires demonstrating that treatment of the underlying condition restores normal secretion of ACTH and cortisol, but this is not always possible. Lingering diagnostic uncertainty has to be accepted in certain patients, who will have to be followed up for some time before diagnosis can be considered more or less definitive. Copyright © 2018. Published by Elsevier Masson SAS.

Circadian variations of thyrotropin (TSH), triiodothyronine (T3) and thyroxine (T4) in surgical and functional pinealectomy in rats

International Nuclear Information System (INIS)

Ostrowska, Z.; Zwirska-Korczala, K.; Buntner, B.; Jarzab, B.; Kucharzewski, M.

1994-01-01

The aim of the present study was to determine the regulatory influence of surgical and functional pinealectomy on circadian variations of thyrotropin (TSH), triiodothyronine (T 3 ) and thyroxine (T 4 ) in male Wistar rats. The serum hormone levels were estimated with RIA method, and the circadian rhythm secretion was analyzed by means of cosinor method. Our study shows that there are marked differences in circadian fluctuations of T 3 and T 4 between the two generally used models of pinealectomy. (author). 55 refs, 4 figs

Evolutionary significance of epigenetic variation

NARCIS (Netherlands)

Richards, C.L.; Verhoeven, K.J.F.; Bossdorf, O.; Wendel, J.F.; Greilhuber, J.; Dolezel, J.; Leitch, I.J.

2012-01-01

Several chapters in this volume demonstrate how epigenetic work at the molecular level over the last few decades has revolutionized our understanding of genome function and developmental biology. However, epigenetic processes not only further our understanding of variation and regulation at the

Desempenho de cordeiros Santa Inês alimentados com dietas completas contendo feno de maniçoba Performance of Santa Inês lambs fed total mixed rations containing different ratios of concentrate to ceara rubbertree hay

Directory of Open Access Journals (Sweden)

Jacilene Maria da Cunha Castro

2007-06-01

Full Text Available Avaliou-se o desempenho de cordeiros alimentados com dieta completa formulada com diferentes proporções de feno de maniçoba. Foram utilizados 32 animais Santa Inês machos, não-castrados (idade inicial de 70 dias e peso vivo de 16,02±2,37 kg, distribuídos em delineamento inteiramente casualizado, com quatro tratamentos e oito repetições. As dietas foram constituídas de concentrado e feno de maniçoba (FM nas proporções de 20, 40, 60 e 80%. As proporções de feno na dieta não influenciaram os consumos de MS, PB e CT, cujas médias diárias foram 1,214; 0,201 e 0,816 kg, respectivamente. Os níveis de feno tiveram efeito linear positivo sobre o consumo de FDN e efeito linear negativo sobre o consumo de EM e CNF. O ganho de peso diário foi afetado pelos níveis de feno na dieta, apresentando médias de 290,84; 293,62; 253,35 e 208,48 g, respectivamente, para as dietas com 20, 40, 60 e 80% de feno de maniçoba. As dietas influenciaram a conversão (Y = 3,332+0,028x e a eficiência alimentar (Y = 0,280,0013x. Pela análise econômica, observaram-se relações custo:benefício de 1,49; 1,57; 1,69 e 1,84 para os níveis de 20, 40, 60 e 80% de feno de maniçoba na dieta. O custo operacional efetivo por quilograma de carcaça produzida foi de R$ 3,68; R$ 3,49; R$ 3,23 e R$ 2,98, respectivamente, para as dietas com 20, 40, 60 e 80% de feno. A inclusão de 80% de feno de maniçoba em dietas completas possibilitou a obtenção de desempenho satisfatório dos cordeiros e melhor retorno financeiro.The objective of this trial was to investigate the effect of different dietary ratios of concentrate (C to ceara rubbertree hay (CRH; Manihot Glaziovii Muell. Arg. on performance of lambs. Thirty two intact Santa Inês lambs averaging 70 days of age and 16.02±2.371 kg of body weight were fed one of the following four treatments as total mixed rations: 80C:20CRH (diet A, 60C:40CRH (diet B, 40C:60CRH (diet C, or 20C:80CRH (diet D in a completely

Role of brain-derived neurotrophic factor and nerve growth factor in the regulation of Neuropeptide W in vitro and in vivo.

Science.gov (United States)

Wang, Rikang; Yan, Fengxia; Liao, Rifang; Wan, Pei; Little, Peter J; Zheng, Wenhua

2017-05-15

Nerve growth factor (NGF) and Brain-derived neurotrophic factor (BDNF) are neurotrophic factors involved in the growth, survival and functioning of neurons. In addition, a possible role of neurotrophins, particularly BDNF, in HPA axis hyperactivation has recently been proposed. Neuropeptide W (NPW) is an endogenous peptide ligand for the GPR7 and GPR8 and a stress mediator in the hypothalamus. It activates the HPA axis by working on hypothalamic corticotrophin-releasing hormone (CRH). No information is available about the interrelationships between neurotrophines like NGF/BDNF and NPW. We studied the effect and underlying mechanisms of NGF/BDNF on the production of NPW in PC12 cells and hypothalamus. NGF time- and concentration-dependently stimulated the expression of NPW in PC12 cells. The effect of NGF was blocked by the inhibition of PI3K/Akt signal pathway with specific inhibitors for PI3K or AktsiRNA for Akt while inhibition of ERK pathway had no effect. Moreover, BDNF concentration-dependently induced the expression of NPW mRNA and decreased the expression of NPY mRNA in primary cultured hypothalamic neurons which was also blocked by a PI3K kinase inhibitor. Finally, in vivo study showed that exogenous BDNF injected icv increased NPW production in the hypothalamus and this effect was reversed by a PI3 kinase inhibitor. These results and the fact that BDNF was able to stimulate the expression of CRH demonstrated that neurotrophines can modulate the expression of NPW in neuronal cells via the PI3K/Akt pathway and suggest that BDNF might be involved in functions of the HPA axis, at least in part by modulating the expression of NPW/NPY and CRH. Copyright © 2017 Elsevier B.V. All rights reserved.

On the foundation of a variational principle for decaying systems

International Nuclear Information System (INIS)

Szasz, G.I.

1976-01-01

Taking into account the circumstances that the decay of an unstable microscopic system into two fragments is established by the counting of one of the decay products in a detector, the observed exponential decay law then asserts only knowledge of the spatiotemporal behaviour of the probability density (and therewith knowledge of the decaying state) at a large finite distance from the site of decay. We therefore formulate a variational principle, of which stationary functions show this decay behaviour. In addition to the resonant wave functions there are also solutions of the variational principle, which decrease exponentially with increasing distance, i.e., functions which could be used to describe the bound states. As the time-dependent treatment shows, the decaying states cannot occur in isolation in a scattering process. The mathematical characterisation of the decaying states via a variational principle is incorporated in a theory of open physical systems. In contradiction to the variational principle of Schroedinger our principle does not provide complete knowledge of the quantum states, but this is not needed in order to describe the decay. (orig.) [de

The variational method in the atomic structure calcularion

International Nuclear Information System (INIS)

Tomimura, A.

1970-01-01

The importance and limitations of variational methods on the atomic structure calculations is set into relevance. Comparisons are made to the Perturbation Theory. Ilustrating it, the method is applied to the H - , H + and H + 2 simple atomic structure systems, and the results are analysed with basis on the study of the associated essential eigenvalue spectrum. Hydrogenic functions (where the screening constants are replaced by variational parameters) are combined to construct the wave function with proper symmetry for each one of the systems. This shows the existence of a bound state for H - , but no conclusions can be made for the others, where it may or may not be necessary to use more flexible wave functions, i.e., with greater number of terms and parameters. (author) [pt

Variational Approach to Enhanced Sampling and Free Energy Calculations

Science.gov (United States)

Valsson, Omar; Parrinello, Michele

2014-08-01

The ability of widely used sampling methods, such as molecular dynamics or Monte Carlo simulations, to explore complex free energy landscapes is severely hampered by the presence of kinetic bottlenecks. A large number of solutions have been proposed to alleviate this problem. Many are based on the introduction of a bias potential which is a function of a small number of collective variables. However constructing such a bias is not simple. Here we introduce a functional of the bias potential and an associated variational principle. The bias that minimizes the functional relates in a simple way to the free energy surface. This variational principle can be turned into a practical, efficient, and flexible sampling method. A number of numerical examples are presented which include the determination of a three-dimensional free energy surface. We argue that, beside being numerically advantageous, our variational approach provides a convenient and novel standpoint for looking at the sampling problem.

Variation in Crustal Structure of the Lesser Caucasus Region from Teleseismic Receiver Functions

Science.gov (United States)

Lin, C. M.; Tseng, T. L.; Huang, B. S.; Legendre, C. P.; Karakhanian, A.

2016-12-01

The Caucasus, including the mountains of Greater and Lesser Caucasus, is formed by the continental collision between Arabia and Eurasia. The crustal thickness for this region was mostly constrained by joint analysis of receiver functions and surface waves. Although the thickest value of 52 km was reported under the Lesser Caucasus, the resolution of earlier studies were often limited by sparse array. Large gradient across Moho also makes the definition of Moho difficult. Moreover, higher value of the Vp/Vs ratio is commonly reported in the northeastern Turkey but no estimates had been made for the Caucasus. To further investigate the detail structure around the Lesser Caucasus, we constructed a new seismic network in Georgia and Armenia. We also include other broadband stations to enhance the coverage. The average interval in the Lesser Caucasus is roughly 30 km, much denser than any previous experiments. We selected P-waveforms from teleseismic earthquakes during the operation (January 2012 - June 2016) to calculate receiver functions and then estimate the crustal thickness (H) and Vp/Vs ratio (k) with the H-k stacking technique. Our preliminary results show that Moho depth increases from 40 km under the northeastern Turkey to 50 km beneath northern Georgia, no station with Moho deeper than 50 km under the Lesser Caucasus. The Vp/Vs ratios in the northeastern Anatolian plateau are around 1.8, which is slightly higher than the average of global continents but consistent with the previous estimates. Further to the east, some stations show anomalously higher Vp/Vs ratio in central & southern Armenia that may be associated with Holocene volcanism. In the future, we plan to join locally measured dispersion curves to invert the velocity model without velocity-depth trade-off. We expect to resolve the velocity variations of the crust beneath this region in small scale that may be tied to the continental collision and surface volcanism. Keywords: Caucasus, receiver

Power variation for Gaussian processes with stationary increments

DEFF Research Database (Denmark)

Barndorff-Nielsen, Ole Eiler; Corcuera, J.M.; Podolskij, Mark

2009-01-01

We develop the asymptotic theory for the realised power variation of the processes X=•G, where G is a Gaussian process with stationary increments. More specifically, under some mild assumptions on the variance function of the increments of G and certain regularity conditions on the path of the pr......We develop the asymptotic theory for the realised power variation of the processes X=•G, where G is a Gaussian process with stationary increments. More specifically, under some mild assumptions on the variance function of the increments of G and certain regularity conditions on the path...... a chaos representation....

Variational Variance Reduction for Monte Carlo Criticality Calculations

International Nuclear Information System (INIS)

Densmore, Jeffery D.; Larsen, Edward W.

2001-01-01

A new variational variance reduction (VVR) method for Monte Carlo criticality calculations was developed. This method employs (a) a variational functional that is more accurate than the standard direct functional, (b) a representation of the deterministically obtained adjoint flux that is especially accurate for optically thick problems with high scattering ratios, and (c) estimates of the forward flux obtained by Monte Carlo. The VVR method requires no nonanalog Monte Carlo biasing, but it may be used in conjunction with Monte Carlo biasing schemes. Some results are presented from a class of criticality calculations involving alternating arrays of fuel and moderator regions

A morphological classification capturing functional variation in phytoplankton

NARCIS (Netherlands)

Kruk, C.; Huszar, V.M.; Peeters, E.T.H.M.; Bonilla, S.; Costa, L.; Lürling, M.F.L.L.W.; Reynolds, C.S.; Scheffer, M.

2010-01-01

1. A logical way of distinguishing functional groups of phytoplankton is to cluster species according to their functional traits, such as growth rate and nutrient assimilation constants. However, data for such an approach are lacking for the vast majority of the species. 2. In this study, we show

Intraspecific diversity among partners drives functional variation in coral symbioses.

Science.gov (United States)

Parkinson, John Everett; Banaszak, Anastazia T; Altman, Naomi S; LaJeunesse, Todd C; Baums, Iliana B

2015-10-26

The capacity of coral-dinoflagellate mutualisms to adapt to a changing climate relies in part on standing variation in host and symbiont populations, but rarely have the interactions between symbiotic partners been considered at the level of individuals. Here, we tested the importance of inter-individual variation with respect to the physiology of coral holobionts. We identified six genetically distinct Acropora palmata coral colonies that all shared the same isoclonal Symbiodinium 'fitti' dinoflagellate strain. No other Symbiodinium could be detected in host tissues. We exposed fragments of each colony to extreme cold and found that the stress-induced change in symbiont photochemical efficiency varied up to 3.6-fold depending on host genetic background. The S. 'fitti' strain was least stressed when associating with hosts that significantly altered the expression of 184 genes under cold shock; it was most stressed in hosts that only adjusted 14 genes. Key expression differences among hosts were related to redox signaling and iron availability pathways. Fine-scale interactions among unique host colonies and symbiont strains provide an underappreciated source of raw material for natural selection in coral symbioses.

Prevalence of rape-related pregnancy as an indication for abortion at two urban family planning clinics.

Science.gov (United States)

Perry, Rachel; Zimmerman, Lindsay; Al-Saden, Iman; Fatima, Aisha; Cowett, Allison; Patel, Ashlesha

2015-05-01

We sought to estimate the prevalence of rape-related pregnancy as an indication for abortion at two public Chicago facilities and to describe demographic and clinical correlates of women who terminated rape-related pregnancies. We performed a cross-sectional study of women obtaining abortion at the Center for Reproductive Health (CRH) at University of Illinois Health Sciences Center and Reproductive Health Services (RHS) at John H. Stroger, Jr. Hospital between August 2009 and August 2013. Gestational age limits at CRH and RHS were 23+6 and 13+6weeks, respectively. We estimated the prevalence of rape-related pregnancy based on billing code (CRH) or data from an administrative database (RHS), and examined relationships between rape-related pregnancy and demographic and clinical variables. Included were 19,465 visits for abortion. The majority of patients were Black (85.6%). Prevalence of abortion for rape-related pregnancy was 1.9%, and was higher at CRH (6.9%) than RHS (1.5%). Later gestational age was associated with abortion for rape-related pregnancy (median 12days, prape-related pregnancy at CRH only (prape-related pregnancy than among those terminating for other indications. Rape-related pregnancy as an indication for abortion had a low, but clinically significant prevalence at two urban Chicago family planning centers. Later gestational age was associated with abortion for rape-related pregnancy. Rape-related pregnancy may occur with higher prevalence among some subgroups of women seeking abortion than others. Efforts to address rape-related pregnancy in the abortion care setting are needed. Copyright © 2015 Elsevier Inc. All rights reserved.

A Combined First and Second Order Variational Approach for Image Reconstruction

KAUST Repository

Papafitsoros, K.

2013-05-10

In this paper we study a variational problem in the space of functions of bounded Hessian. Our model constitutes a straightforward higher-order extension of the well known ROF functional (total variation minimisation) to which we add a non-smooth second order regulariser. It combines convex functions of the total variation and the total variation of the first derivatives. In what follows, we prove existence and uniqueness of minimisers of the combined model and present the numerical solution of the corresponding discretised problem by employing the split Bregman method. The paper is furnished with applications of our model to image denoising, deblurring as well as image inpainting. The obtained numerical results are compared with results obtained from total generalised variation (TGV), infimal convolution and Euler\\'s elastica, three other state of the art higher-order models. The numerical discussion confirms that the proposed higher-order model competes with models of its kind in avoiding the creation of undesirable artifacts and blocky-like structures in the reconstructed images-a known disadvantage of the ROF model-while being simple and efficiently numerically solvable. ©Springer Science+Business Media New York 2013.

Variation-aware advanced CMOS devices and SRAM

CERN Document Server

Shin, Changhwan

2016-01-01

This book provides a comprehensive overview of contemporary issues in complementary metal-oxide semiconductor (CMOS) device design, describing how to overcome process-induced random variations such as line-edge-roughness, random-dopant-fluctuation, and work-function variation, and the applications of novel CMOS devices to cache memory (or Static Random Access Memory, SRAM). The author places emphasis on the physical understanding of process-induced random variation as well as the introduction of novel CMOS device structures and their application to SRAM. The book outlines the technical predicament facing state-of-the-art CMOS technology development, due to the effect of ever-increasing process-induced random/intrinsic variation in transistor performance at the sub-30-nm technology nodes. Therefore, the physical understanding of process-induced random/intrinsic variations and the technical solutions to address these issues plays a key role in new CMOS technology development. This book aims to provide the reade...

17β-Estradiol is required for the sexually dimorphic effects of repeated binge-pattern alcohol exposure on the HPA axis during adolescence.

Directory of Open Access Journals (Sweden)

Magdalena M Przybycien-Szymanska

Full Text Available Alcohol consumption during adolescence has long-term sexually dimorphic effects on anxiety behavior and mood disorders. We have previously shown that repeated binge-pattern alcohol exposure increased the expression of two critical central regulators of stress and anxiety, corticotrophin-releasing hormone (CRH and arginine vasopressin (AVP, in adolescent male rats. By contrast, there was no effect of alcohol on these same genes in adolescent females. Therefore, we tested the hypothesis that 17β-estradiol (E(2, the predominant sex steroid hormone in females, prevents alcohol-induced changes in CRH and AVP gene expression in the paraventricular nucleus (PVN of the hypothalamus. To test this hypothesis, postnatal day (PND 26 females were ovariectomized and given E(2 replacement or cholesterol as a control. Next, they were given an alcohol exposure paradigm of 1 saline alone, 2 acute (single dose or 3 a repeated binge-pattern. Our results showed that acute and repeated binge-pattern alcohol treatment increased plasma ACTH and CORT levels in both E(2- and Ch-treated groups, however habituation to repeated binge-pattern alcohol exposure was evident only in E(2-treated animals. Further, repeated binge-pattern alcohol exposure significantly decreased CRH and AVP mRNA in Ch-, but not E(2-treated animals, which was consistent with our previous observations in gonad intact females. We further tested the effects of E(2 and alcohol treatment on the activity of the wild type CRH promoter in a PVN-derived neuronal cell line. Alcohol increased CRH promoter activity in these cells and concomitant treatment with E(2 completely abolished the effect. Together our data suggest that E(2 regulates the reactivity of the HPA axis to a repeated stressor through modulation of the habituation response and further serves to maintain normal steady state mRNA levels of CRH and AVP in the PVN in response to a repeated alcohol stressor.

Efeito da composição do substrato no enraizamento de estacas de maracujazeiro azedo Growing average moisture release curve and cutting propagation of pasion fruit

Directory of Open Access Journals (Sweden)

Paulo Vítor Dutra de Souza

2006-08-01

Full Text Available Testaram-se diferentes proporções vermiculita (V e casca de arroz carbonizada (CAC para a composição de substratos, na propagação de maracujazeiro (Passiflora edulis Sims f. flavicarpa Deg. por estaquia. As estacas apresentavam duas folhas e suas bases foram submersas por 10 segundos em uma solução hidroalcoólica de AIB (1000mg.L-1 no momento da instalação do experimento. O experimento transcorreu em casa de vegetação com microaspersão intermitente e obedeceu ao delineamento experimental de blocos casualizados, com 5 tratamentos, que compreenderam as seguintes proporções em volume (100% V ; 75% V: 25% CAC; 50% V: 50% CAC; 25% V: 75% CAC e 100% CAC. Utilizaram-se 4 repetições e 15 estacas por parcela. No substrato, foram avaliadas as seguintes características: teor total de sais solúveis, pH em água, densidade úmida, densidade seca e curva de retenção de água. Nas estacas, avaliaram-se: a porcentagem de estacas vivas, o número de raízes, de brotos e de folhas remanescentes por estaca, o comprimento e a matéria seca das raízes e dos brotos. A melhor resposta de enraizamento foi obtida pelo substrato formado pelas misturas dos dois componentes, nas proporções de 50% V: 50% CAC e 25% V: 75% CAC.The present experiment tested different vermiculite (V proportions and carbonized rice husks (CRH over passion fruit (Passiflora edulis Sims f. flavicarpa Deg. cutting propagation. The cuttings had two leaves treated with 1000 mg.L-1 of indolebutyric acid for 10 seconds. The experiment was conducted under greenhouse conditions with an intermittent micro spraying system. The experimental design was randomized in blocks with 5 different treatments (100% V ; 75% V: 25% CRH; 50% V: 50% CRH; 25% V: 75% CRH; e 100% CRH, 4 replicas and 15 cuttings per experimental unit. Salinity, pH, bulk density, and moisture release curve of growing average were evaluated. In addition, cuttings were evaluated on survival; roots number, branches and

Bounded variation and around

CERN Document Server

Appell, Jürgen; Merentes Díaz, Nelson José

2013-01-01

This monographis a self-contained exposition of the definition and properties of functionsof bounded variation and their various generalizations; the analytical properties of nonlinear composition operators in spaces of such functions; applications to Fourier analysis, nonlinear integral equations, and boundary value problems. The book is written for non-specialists. Every chapter closes with a list of exercises and open problems.

Unified Sequence-Based Association Tests Allowing for Multiple Functional Annotations and Meta-analysis of Noncoding Variation in Metabochip Data.

Science.gov (United States)

He, Zihuai; Xu, Bin; Lee, Seunggeun; Ionita-Laza, Iuliana

2017-09-07

Substantial progress has been made in the functional annotation of genetic variation in the human genome. Integrative analysis that incorporates such functional annotations into sequencing studies can aid the discovery of disease-associated genetic variants, especially those with unknown function and located outside protein-coding regions. Direct incorporation of one functional annotation as weight in existing dispersion and burden tests can suffer substantial loss of power when the functional annotation is not predictive of the risk status of a variant. Here, we have developed unified tests that can utilize multiple functional annotations simultaneously for integrative association analysis with efficient computational techniques. We show that the proposed tests significantly improve power when variant risk status can be predicted by functional annotations. Importantly, when functional annotations are not predictive of risk status, the proposed tests incur only minimal loss of power in relation to existing dispersion and burden tests, and under certain circumstances they can even have improved power by learning a weight that better approximates the underlying disease model in a data-adaptive manner. The tests can be constructed with summary statistics of existing dispersion and burden tests for sequencing data, therefore allowing meta-analysis of multiple studies without sharing individual-level data. We applied the proposed tests to a meta-analysis of noncoding rare variants in Metabochip data on 12,281 individuals from eight studies for lipid traits. By incorporating the Eigen functional score, we detected significant associations between noncoding rare variants in SLC22A3 and low-density lipoprotein and total cholesterol, associations that are missed by standard dispersion and burden tests. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Functional translation and linguistic variation: the use of didactic sequence in teaching languages

Directory of Open Access Journals (Sweden)

Valdecy Oliveira Pontes

2017-12-01

Full Text Available In the context of the approach of the linguistic variation of Spanish and the use of Functionalist Translation in Foreign Language classes, this article aims to report the results of the application of a Didactic Sequence (SD, in the style of the Geneva School, Hispanic plays for the teaching of linguistic variation in the pronominal treatment forms of the Spanish-Portuguese Brazilian language pair. SD was applied in the subject "Introduction to Translation Studies in Spanish Language" (2nd semester, offered by the course in Letters - Spanish Language and its Literatures, of the Federal University of Ceará. This article was based on the theoretical foundations of Functionalist Translation (NORD, 1994, 1996, 2009, 2012, Translation and Sociolinguistics (BOLAÑOS-CUELLAR, 2000; MAYORAL, 1998, elaboration of SD (DOLZ; NOVERRAZ; SCHNEUWLY, 2004; CRISTÓVÃO, 2010; BARROS, 2012 and research on the variation in the forms of treatment of Spanish and Portuguese (FONTANELLA DE WEINBER, 1999; SCHERRE et al, 2015.

Variation as a main feature of norm

Directory of Open Access Journals (Sweden)

S. Poladova

2017-09-01

Full Text Available The past half-century has witnessed remarkable growth in the study of language variation, and it has now become a highly productive subfield of research in sociolinguistics. Variability is everywhere in language, from the unique details in each production of a sound or sign to the auditory or visual processing of the linguistic signal. All languages that we can observe today show variation; what is more, they vary in identical ways, namely geographically and socially. It’s no secret that languages like English are full of variation. So, the aim of the article is to detect the reasons of variation and to uncover rates of usage of different free variations for a given set of lexical items. The research work is carried out by using the descriptive, comparative methods by subjecting to analysis the specific language materials. The discovery of law of variation became a starting point for the evolution of linguistics. The problem of search of variation facts and its role in the functioning of language system concerns many specialists from the outset. The scope of the investigation was to set up a system out of chaos of phenomena. Currently, the fact of conditionality of variation by system relations existing in the language is considered to be established.

In silico detection of sequence variations modifying transcriptional regulation.

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Malin C Andersen

2008-01-01

Full Text Available Identification of functional genetic variation associated with increased susceptibility to complex diseases can elucidate genes and underlying biochemical mechanisms linked to disease onset and progression. For genes linked to genetic diseases, most identified causal mutations alter an encoded protein sequence. Technological advances for measuring RNA abundance suggest that a significant number of undiscovered causal mutations may alter the regulation of gene transcription. However, it remains a challenge to separate causal genetic variations from linked neutral variations. Here we present an in silico driven approach to identify possible genetic variation in regulatory sequences. The approach combines phylogenetic footprinting and transcription factor binding site prediction to identify variation in candidate cis-regulatory elements. The bioinformatics approach has been tested on a set of SNPs that are reported to have a regulatory function, as well as background SNPs. In the absence of additional information about an analyzed gene, the poor specificity of binding site prediction is prohibitive to its application. However, when additional data is available that can give guidance on which transcription factor is involved in the regulation of the gene, the in silico binding site prediction improves the selection of candidate regulatory polymorphisms for further analyses. The bioinformatics software generated for the analysis has been implemented as a Web-based application system entitled RAVEN (regulatory analysis of variation in enhancers. The RAVEN system is available at http://www.cisreg.ca for all researchers interested in the detection and characterization of regulatory sequence variation.

In Silico Detection of Sequence Variations Modifying Transcriptional Regulation

Science.gov (United States)

Andersen, Malin C; Engström, Pär G; Lithwick, Stuart; Arenillas, David; Eriksson, Per; Lenhard, Boris; Wasserman, Wyeth W; Odeberg, Jacob

2008-01-01

Identification of functional genetic variation associated with increased susceptibility to complex diseases can elucidate genes and underlying biochemical mechanisms linked to disease onset and progression. For genes linked to genetic diseases, most identified causal mutations alter an encoded protein sequence. Technological advances for measuring RNA abundance suggest that a significant number of undiscovered causal mutations may alter the regulation of gene transcription. However, it remains a challenge to separate causal genetic variations from linked neutral variations. Here we present an in silico driven approach to identify possible genetic variation in regulatory sequences. The approach combines phylogenetic footprinting and transcription factor binding site prediction to identify variation in candidate cis-regulatory elements. The bioinformatics approach has been tested on a set of SNPs that are reported to have a regulatory function, as well as background SNPs. In the absence of additional information about an analyzed gene, the poor specificity of binding site prediction is prohibitive to its application. However, when additional data is available that can give guidance on which transcription factor is involved in the regulation of the gene, the in silico binding site prediction improves the selection of candidate regulatory polymorphisms for further analyses. The bioinformatics software generated for the analysis has been implemented as a Web-based application system entitled RAVEN (regulatory analysis of variation in enhancers). The RAVEN system is available at http://www.cisreg.ca for all researchers interested in the detection and characterization of regulatory sequence variation. PMID:18208319

On the notion of Jacobi fields in constrained calculus of variations

Directory of Open Access Journals (Sweden)

Massa Enrico

2016-12-01

Full Text Available In variational calculus, the minimality of a given functional under arbitrary deformations with fixed end-points is established through an analysis of the so called second variation. In this paper, the argument is examined in the context of constrained variational calculus, assuming piecewise differentiable extremals, commonly referred to as extremaloids. The approach relies on the existence of a fully covariant representation of the second variation of the action functional, based on a family of local gauge transformations of the original Lagrangian and on a set of scalar attributes of the extremaloid, called the corners' strengths [16]. In dis- cussing the positivity of the second variation, a relevant role is played by the Jacobi fields, defined as infinitesimal generators of 1-parameter groups of diffeomorphisms preserving the extremaloids. Along a piecewise differentiable extremal, these fields are generally discontinuous across the corners. A thorough analysis of this point is presented. An alternative characterization of the Jacobi fields as solutions of a suitable accessory variational problem is established.

Structure variations of carbonizing lignin

International Nuclear Information System (INIS)

Otani, C.; Polidoro, H.A.; Otani, S.; Craievich, A.F.

1984-01-01

The studied lignin is a by-product of the process of ethanol production from eucaliptus. It was heat-treated under inert atmosphere conditions at increasing temperatures from 300C up to 2400C. The structural variations were studied by wide-angle X-ray diffraction, small-angle X-ray scattering and infrared absorption spectroscopy. The bulk and 'real' density of the compacted materials have also been determined as functions of the final temperature. These experimental results enabled us to establish a mechanism of structure variation based on the formation of a turbostratic graphite-like and porous structure within the initially amorphous lignin matrix. (Author) [pt

Limit theorems for power variations of ambit field driven by white noise

DEFF Research Database (Denmark)

Pakkanen, Mikko S.

2014-01-01

We study the asymptotics of lattice power variations of two-parameter ambit fields driven by white noise. Our first result is a law of large numbers for power variations. Under a constraint on the memory of the ambit field, normalized power variations converge to certain integral functionals...

Pregnancy outcomes are not altered by variation in thyroid function within the normal range in women free of thyroid disease.

Science.gov (United States)

Veltri, Flora; Kleynen, Pierre; Grabczan, Lidia; Salajan, Alexandra; Rozenberg, Serge; Pepersack, Thierry; Poppe, Kris

2018-02-01

In the recently revised guidelines on the management of thyroid dysfunction during pregnancy, treatment with thyroid hormone (LT4) is not recommended in women without thyroid autoimmunity (TAI) and TSH levels in the range 2.5-4.0 mIU/L, and in a recent study in that particular group of pregnant women, more complications were observed when a treatment with LT4 was given. The objective of the study was therefore to investigate whether variation in thyroid function within the normal (non-pregnant) range in women free of thyroid disease was associated with altered pregnancy outcomes? Cross-sectional data analysis of 1321 pregnant women nested within an ongoing prospective collection of pregnant women's data in a single centre in Brussels, Belgium. Thyroid peroxidase antibodies (TPO-abs), thyroid-stimulating hormone (TSH), free T4 (FT4) and ferritin levels were measured and baseline characteristics were recorded. Women taking LT4, with TAI and thyroid function outside the normal non-pregnant range were excluded. Pregnancy outcomes and baseline characteristics were correlated with all TSH and FT4 levels within the normal range and compared between two groups (TSH cut-off 500 mL) was inversely associated with serum FT4 levels (OR: 0.35; CI 95%: 0.13-0.96); P  = 0.040. Also 10% of women free of thyroid disease had serum TSH levels ≥2.5 mIU/L. Variation in thyroid function during the first trimester within the normal (non-pregnant) range in women free of thyroid disease was not associated with altered pregnancy outcomes. These results add evidence to the recommendation against LT4 treatment in pregnant women with high normal TSH levels and without TPO antibodies. © 2018 European Society of Endocrinology.

A role for gene duplication and natural variation of gene expression in the evolution of metabolism.

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Daniel J Kliebenstein

Full Text Available BACKGROUND: Most eukaryotic genomes have undergone whole genome duplications during their evolutionary history. Recent studies have shown that the function of these duplicated genes can diverge from the ancestral gene via neo- or sub-functionalization within single genotypes. An additional possibility is that gene duplicates may also undergo partitioning of function among different genotypes of a species leading to genetic differentiation. Finally, the ability of gene duplicates to diverge may be limited by their biological function. METHODOLOGY/PRINCIPAL FINDINGS: To test these hypotheses, I estimated the impact of gene duplication and metabolic function upon intraspecific gene expression variation of segmental and tandem duplicated genes within Arabidopsis thaliana. In all instances, the younger tandem duplicated genes showed higher intraspecific gene expression variation than the average Arabidopsis gene. Surprisingly, the older segmental duplicates also showed evidence of elevated intraspecific gene expression variation albeit typically lower than for the tandem duplicates. The specific biological function of the gene as defined by metabolic pathway also modulated the level of intraspecific gene expression variation. The major energy metabolism and biosynthetic pathways showed decreased variation, suggesting that they are constrained in their ability to accumulate gene expression variation. In contrast, a major herbivory defense pathway showed significantly elevated intraspecific variation suggesting that it may be under pressure to maintain and/or generate diversity in response to fluctuating insect herbivory pressures. CONCLUSION: These data show that intraspecific variation in gene expression is facilitated by an interaction of gene duplication and biological activity. Further, this plays a role in controlling diversity of plant metabolism.

The Environmental Pollutant Tributyltin Chloride Disrupts the Hypothalamic-Pituitary-Adrenal Axis at Different Levels in Female Rats.

Science.gov (United States)

Merlo, Eduardo; Podratz, Priscila L; Sena, Gabriela C; de Araújo, Julia F P; Lima, Leandro C F; Alves, Izabela S S; Gama-de-Souza, Letícia N; Pelição, Renan; Rodrigues, Lívia C M; Brandão, Poliane A A; Carneiro, Maria T W D; Pires, Rita G W; Martins-Silva, Cristina; Alarcon, Tamara A; Miranda-Alves, Leandro; Silva, Ian V; Graceli, Jones B

2016-08-01

Tributyltin chloride (TBT) is an environmental contaminant that is used as a biocide in antifouling paints. TBT has been shown to induce endocrine-disrupting effects. However, studies evaluating the effects of TBT on the hypothalamus-pituitary-adrenal (HPA) axis are especially rare. The current study demonstrates that exposure to TBT is critically responsible for the improper function of the mammalian HPA axis as well as the development of abnormal morphophysiology in the pituitary and adrenal glands. Female rats were treated with TBT, and their HPA axis morphophysiology was assessed. High CRH and low ACTH expression and high plasma corticosterone levels were detected in TBT rats. In addition, TBT leads to an increased in the inducible nitric oxide synthase protein expression in the hypothalamus of TBT rats. Morphophysiological abnormalities, including increases in inflammation, a disrupted cellular redox balance, apoptosis, and collagen deposition in the pituitary and adrenal glands, were observed in TBT rats. Increases in adiposity and peroxisome proliferator-activated receptor-γ protein expression in the adrenal gland were observed in TBT rats. Together, these data provide in vivo evidence that TBT leads to functional dissociation between CRH, ACTH, and costicosterone, which could be associated an inflammation and increased of inducible nitric oxide synthase expression in hypothalamus. Thus, TBT exerts toxic effects at different levels on the HPA axis function.

Moments of inertia for solids of revolution and variational methods

International Nuclear Information System (INIS)

Diaz, Rodolfo A; Herrera, William J; Martinez, R

2006-01-01

We present some formulae for the moments of inertia of homogeneous solids of revolution in terms of the functions that generate the solids. The development of these expressions exploits the cylindrical symmetry of these objects and avoids the explicit use of multiple integration, providing an easy and pedagogical approach. The explicit use of the functions that generate the solid gives the possibility of writing the moment of inertia as a functional, which in turn allows us to utilize the calculus of variations to obtain new insight into some properties of this fundamental quantity. In particular, minimization of moments of inertia under certain restrictions is possible by using variational methods

On convexity and Schoenberg's variation diminishing splines

International Nuclear Information System (INIS)

Feng, Yuyu; Kozak, J.

1992-11-01

In the paper we characterize a convex function by the monotonicity of a particular variation diminishing spline sequence. The result extends the property known for the Bernstein polynomial sequence. (author). 4 refs

Quantum mechanical algebraic variational methods for inelastic and reactive molecular collisions

Science.gov (United States)

Schwenke, David W.; Haug, Kenneth; Zhao, Meishan; Truhlar, Donald G.; Sun, Yan

1988-01-01

The quantum mechanical problem of reactive or nonreactive scattering of atoms and molecules is formulated in terms of square-integrable basis sets with variational expressions for the reactance matrix. Several formulations involving expansions of the wave function (the Schwinger variational principle) or amplitude density (a generalization of the Newton variational principle), single-channel or multichannel distortion potentials, and primitive or contracted basis functions are presented and tested. The test results, for inelastic and reactive atom-diatom collisions, suggest that the methods may be useful for a variety of collision calculations and may allow the accurate quantal treatment of systems for which other available methods would be prohibitively expensive.

A formalism for the calculus of variations with spinors

Energy Technology Data Exchange (ETDEWEB)

Bäckdahl, Thomas, E-mail: thobac@chalmers.se [The School of Mathematics, University of Edinburgh, JCMB 6228, Peter Guthrie Tait Road, Edinburgh EH9 3FD, United Kingdom and Mathematical Sciences - Chalmers University of Technology and University of Gothenburg - SE-412 96 Gothenburg (Sweden); Valiente Kroon, Juan A., E-mail: j.a.valiente-kroon@qmul.ac.uk [School of Mathematical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS (United Kingdom)

2016-02-15

We develop a frame and dyad gauge-independent formalism for the calculus of variations of functionals involving spinorial objects. As a part of this formalism, we define a modified variation operator which absorbs frame and spin dyad gauge terms. This formalism is applicable to both the standard spacetime (i.e., SL(2, ℂ)) 2-spinors as well as to space (i.e., SU(2, ℂ)) 2-spinors. We compute expressions for the variations of the connection and the curvature spinors.

A formalism for the calculus of variations with spinors

International Nuclear Information System (INIS)

Bäckdahl, Thomas; Valiente Kroon, Juan A.

2016-01-01

We develop a frame and dyad gauge-independent formalism for the calculus of variations of functionals involving spinorial objects. As a part of this formalism, we define a modified variation operator which absorbs frame and spin dyad gauge terms. This formalism is applicable to both the standard spacetime (i.e., SL(2, ℂ)) 2-spinors as well as to space (i.e., SU(2, ℂ)) 2-spinors. We compute expressions for the variations of the connection and the curvature spinors

Association of functional variations in COMT and GCH1 genes with postherniotomy pain and related impairment

DEFF Research Database (Denmark)

Belfer, Inna; Dai, Feng; Kehlet, Henrik

2015-01-01

Persistent postoperative pain is a well-established clinical problem with potential severe personal and socioeconomic implications. The prevalence of persistent pain varies across surgery types. Severe persistent pain and related impairment occur in 5% to 10% of patients after groin hernia repair....... The substantial interindividual variability in pain-related phenotypes within each surgery type cannot be explained by environmental factors alone, suggesting that genetic variation may play a role. We investigated the contribution of COMT and GCH1 to persistent postherniotomy pain (PPP)-related functional...... moderate-to-severe pain-related activity impairment 6 months postoperatively as measured by Activity Assessment Scale (≥8.3). Patients with the G allele of COMT SNP rs6269 and C allele of COMT SNP rs4633 had less impairment (P = 0.03 and 0.01, respectively); in addition, the COMT haplotype GCG...

Geographic variation in nasal cavity form among three human groups from the Japanese Archipelago: Ecogeographic and functional implications.

Science.gov (United States)

Fukase, Hitoshi; Ito, Tsuyoshi; Ishida, Hajime

2016-05-01

Geographic variation in human nasal form has often been interpreted as a climatic adaptation, owing to the nasal air-conditioning function. The aim of this study was to further address morphofunctional issues of the nasal cavity, using three human groups from subarctic, temperate, and subtropical regions of the Japanese Archipelago: prehistoric Okhotsk, early-modern Honshu and Okinawa groups. Using three-dimensional coordinates of craniometric landmarks surrounding the nasal cavity, we compared linear measurements regarding nasal cavity form among the three groups and also conducted 3D geometric morphometrics. Both linear measurements and morphometric analyses corroborate the previously reported covariation pattern of nasal cavity shape with climate, where humans from a cold/dry climate tend to possess a relatively tall, narrow, and deep nasal cavity compared with those from a warm/humid environment. The northern Okhotsk group had overall larger cranial airways, which may be attributable to their large facial skeleton. However, the ratio of nasal/bimaxillary breadth was significantly lower in the Okhotsk group, indicating that maxillary size does not necessarily constrain the nasal breadth. In addition, despite the presence of obvious geographic clines in anterior nasal shape, posterior choanal shape lacked the north-south geographic cline. This suggests a certain level of morphofunctional independence between the anterior and posterior nasal openings. The observed geographic variations must, however, be partly considered as a reflection of different ancestral traits and population histories of the three groups. Nevertheless, the results indicate that intergroup variations in nasal cavity morphology can be largely explained by climatic conditions. Am. J. Hum. Biol. 28:343-351, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Geometric morphometrics of functionally distinct floral organs in Iris pumila: Analyzing patterns of symmetric and asymmetric shape variations

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Radović Sanja

2017-01-01

Full Text Available The Iris flower is a complex morphological structure composed of two trimerous whorls of functionally distinct petaloid organs (the falls and the standards, one whorl of the stamens and one tricarpellary gynoecium. The petal-like style arms of the carpels are banded over the basal part of the falls, forming three pollination tunnels, each of which is perceived by the Iris pollinators as a single bilaterally symmetrical flower. Apart from the stamens, all petaloid floral organs are preferentially involved in advertising rewards to potential pollinators. Here we used the methods of geometric morphometrics to explore the shape variation in falls, standards and style arms of the Iris pumila flowers and to disentangle the symmetric and the asymmetric component of the total shape variance. Our results show that symmetric variation contributes mostly to the total shape variance in each of the three floral organs. Fluctuating asymmetry (FA was the dominant component of the asymmetric shape variation in the falls and the standards, but appeared to be marginally significant in the style arms. The values of FA indexes for the shape of falls (insects’ landing platforms and for the shape of standards (long-distance reward signals were found to be two orders of magnitude greater compared to that of the style arms. Directional asymmetry appeared to be very low, but highly statistically significant for all analyzed floral organs. Because floral symmetry can reliably indicate the presence of floral rewards, an almost perfect symmetry recorded for the style arm shape might be the outcome of pollinator preferences for symmetrical pollination units. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 173007

Massless quantum electrodynamics: a variational study

International Nuclear Information System (INIS)

Piquini, P.C.

1990-01-01

The variational method was used to study the probable existence of a compound vacuum in quantum electrodynamics. An Ansatz containing a condensate of electron-positron pairs was investigated and an optimization equation for the condensate wave function found. (L.C.J.A.)

USE OF RENEWABLE SUBSTRATES FOR EX VITRO PRODUCTION OF Melaleuca alternifolia CHEEL CLONAL PLANTS BY MINI-CUTTINGS TECHNIQUE

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Carlos Andre Stuepp

2017-12-01

Full Text Available The Australian species Melaleuca alternifolia Cheel. has a strong commercial importance due to the extraction of essential oils from its leaves used in the cosmetic and pharmaceutical industry. In order to obtain an efficient plant production system of M. alternifolia the mini-cuttings technique and the clonal mini-garden management in the productivity and rooting of mini-cuttings and different substrate compositions were analyzed during all the seasons. Mini-stumps derived from cuttings and grown in pots (2 L, were submitted to successive harvesting of their sprouts during the four seasons (september/2013 to august/2014. From the mini-stumps sprouts mini-cuttings were produced, wich were were planted in plastic tubes and kept in a greenhouse for 45 days. Six substrates were used for planting the mini-cuttings: commercial substrate (S1; substrate composed of 100% carbonized rice husk (CRH (S2; substrate composed of 100% coconut fiber (CF (S3; substrate composed of 50% CF and 50% CRH (S4; substrate composed of 30% CF and 70% CRH (S5; substrate composed of 70% FC and 30% CRH (S6. The high survival of mini-stumps (over 90% and the mini-cuttings production (282 mini-cuttings.m-2.month-1 in the shade house demonstrate the technical feasibility for the species, being summer the most appropriate time to collect propagules. The substrate composed by 70% CF + 30% CRH (S6 shows superior results for vegetative propagation of M. alternifolia (91.7% of rooted mini-cuttings, as the single one to contemplate simultaneously all parameters. Summer is recommended as the best time for rooting of mini-cuttings.

The effect of acute moderate psychological stress on working memory-related neural activity is modulated by a genetic variation in catecholaminergic function in humans

Directory of Open Access Journals (Sweden)

Shaozheng eQin

2012-05-01

Full Text Available Acute stress has an important impact on higher-order cognitive functions supported by the prefrontal cortex (PFC such as working memory (WM. In rodents, such effects are mediated by stress-induced alterations in catecholaminergic signaling, but human data in support of this notion is lacking. A common variation in the gene encoding Catechol-O-methyltransferase (COMT is known to affect basal catecholaminergic availability and PFC functions. Here, we investigated whether this genetic variation (Val158Met modulates effects of stress on WM-related prefrontal activity in humans. In a counterbalanced crossover design, 41 healthy young men underwent functional Magnetic Resonance Imaging (fMRI while performing a numerical N-back WM task embedded in a stressful or neutral context. Moderate psychological stress was induced by a well-controlled procedure involving viewing strongly aversive (versus emotionally neutral movie material in combination with a self-referencing instruction. Acute stress resulted in genotype-dependent effects on WM performance and WM-related activation in the dorsolateral PFC, with a relatively negative impact of stress in COMT Met-homozygotes as opposed to a relatively positive effect in Val-carriers. A parallel interaction was found for WM-related deactivation in the anterior medial temporal lobe. Our findings suggest that individuals with higher baseline catecholaminergic availability (COMT Met-homozygotes appear to reach a supraoptimal state under moderate levels of stress. In contrast, individuals with lower baselines (Val-carriers may reach an optimal state. Thus, our data show that effects of acute stress on higher-order cognitive functions vary depending on catecholaminergic availability at baseline, and thereby corroborate animal models of catecholaminergic signaling that propose a non-linear relationship between catecholaminergic activity and prefrontal functions.

Exploration of Rice Husk Compost as an Alternate Organic Manure to Enhance the Productivity of Blackgram in Typic Haplustalf and Typic Rhodustalf

Directory of Open Access Journals (Sweden)

Subramanium Thiyageshwari

2018-02-01

Full Text Available The present study was aimed at using cellulolytic bacterium Enhydrobacter and fungi Aspergillus sp. for preparing compost from rice husk (RH. Further, the prepared compost was tested for their effect on blackgram growth promotion along with different levels of recommended dose of fertilizer (RDF in black soil (typic Haplustalf and red soil (typic Rhodustalf soil. The results revealed that, inoculation with lignocellulolytic fungus (LCF Aspergillus sp. @ 2% was considered as the most efficient method of composting within a short period. Characterization of composted rice husk (CRH was examined through scanning electron microscope (SEM for identifying significant structural changes. At the end of composting, N, P and K content increased with decrease in CO2 evolution, C:N and C:P ratios. In comparison to inorganic fertilization, an increase in grain yield of 16% in typic Haplustalf and 17% in typic Rhodustalf soil over 100% RDF was obtained from the integrated application of CRH@ 5 t ha−1 with 50% RDF and biofertilizers. The crude protein content was maximum with the combined application of CRH, 50% RDF and biofertilizers of 20% and 21% in typic Haplustalf and typic Rhodustalf soils, respectively. Nutrient rich CRH has proved its efficiency on crop growth and soil fertility.

DISTRIBUCIÓN Y GRADO DE ESTABLECIMIENTO DE COCHINILLA ROSADA DEL HIBISCO EN NAYARIT, MÉXICO

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Briseño Fierro P

2013-01-01

Full Text Available La cochinilla rosada del hibisco (Maconellicoccus hirsutus, Green(CRH es una plaga con rápida distribución en las áreas donde se presenta y con un amplio rango de hospederos. Se realizó el análisis de distribución de CRH en el estado de Nayarit, México a partir de los registros del Comité Estatal de Sanidad Vegetal de Nayarit en la campaña contra cochinilla rosada, la información se organizó en una base de datos por localidad, tipo de área, hospedantes y semanas de muestreo. Asimismo, se relacionaron los niveles de infestación presentados con los datos de temperatura y humedad de estaciones climáticas. CRH se hizo presente en Nayarit, México en 2004; para 2009 estaba presente en 16 de los 20 municipios del estado, con preferencia en obelisco (Hibiscus rosa-sinensis, majahua (Hibiscus pernambucensis, huinol (Acacia cymbispina y guanábano (Annona muricata como hospedantes y marginada a zonas urbanas. Las condiciones ambientales que prevalecieron cuando ocurrieron los niveles más altos de CRH fueron temperaturas entre 14.61 y 29.1°C, y humedad relativa de 72 %.

Corticotropin-releasing hormone induces depression-like changes of sleep electroencephalogram in healthy women.

Science.gov (United States)

Schüssler, P; Kluge, M; Gamringer, W; Wetter, T C; Yassouridis, A; Uhr, M; Rupprecht, R; Steiger, A

2016-12-01

We reported previously that repetitive intravenous injections of corticotropin-releasing hormone (CRH) around sleep onset prompt depression-like changes in certain sleep and endocrine activity parameters (e.g. decrease of slow-wave sleep during the second half of the night, blunted growth hormone peak, elevated cortisol concentration during the first half of the night). Furthermore a sexual dimorphism of the sleep-endocrine effects of the hormones growth hormone-releasing hormone and ghrelin was observed. In the present placebo-controlled study we investigated the effect of pulsatile administration of 4×50μg CRH on sleep electroencephalogram (EEG) and nocturnal cortisol and GH concentration in young healthy women. After CRH compared to placebo, intermittent wakefulness increased during the total night and the sleep efficiency index decreased. During the first third of the night, REM sleep and stage 2 sleep increased and sleep stage 3 decreased. Cortisol concentration was elevated throughout the night and during the first and second third of the night. GH secretion remained unchanged. Our data suggest that after CRH some sleep and endocrine activity parameters show also depression-like changes in healthy women. These changes are more distinct in women than in men. Copyright © 2016 Elsevier Ltd. All rights reserved.

Super-Planckian spatial field variations and quantum gravity

Energy Technology Data Exchange (ETDEWEB)

Klaewer, Daniel; Palti, Eran [Institut für Theoretische Physik, Ruprecht-Karls-Universität,Philosophenweg 19, 69120 Heidelberg (Germany)

2017-01-20

We study scenarios where a scalar field has a spatially varying vacuum expectation value such that the total field variation is super-Planckian. We focus on the case where the scalar field controls the coupling of a U(1) gauge field, which allows us to apply the Weak Gravity Conjecture to such configurations. We show that this leads to evidence for a conjectured property of quantum gravity that as a scalar field variation in field space asymptotes to infinity there must exist an infinite tower of states whose mass decreases as an exponential function of the scalar field variation. We determine the rate at which the mass of the states reaches this exponential behaviour showing that it occurs quickly after the field variation passes the Planck scale.

Normalization constraint for variational bounds on fluid permeability

International Nuclear Information System (INIS)

Berryman, J.G.; Milton, G.W.

1985-01-01

A careful reexamination of the formulation of Prager's original variational principle for viscous flow through porous media has uncovered a subtle error in the normalization constraint on the trial functions. Although a certain surface integral of the true pressure field over the internal surface area always vanishes for isotropic materials, the corresponding surface integral for a given trial pressure field does not necessarily vanish but has nevertheless been previously neglected in the normalization. When this error is corrected, the form of the variational estimate is actually simpler than before and furthermore the resulting bounds have been shown to improve when the constant trial functions are used in either the two-point or three-point bounds

Effects of climate variability and functional changes on the interannual variation of the carbon balance in a temperate deciduous forest

DEFF Research Database (Denmark)

Wu, Jian; van der Linden, Leon; Lasslop, G.

2012-01-01

scale, direct climatic variability and changes in ecosystem functional properties regulated the IAV of the carbon balance at this site. Correlation analysis showed that the sensitivity of carbon fluxes to climatic variability was significantly higher at shorter than at longer time scales and changed...... seasonally. Ecosystem response anomalies implied that changes in the distribution of climate anomalies during the vegetation period will have stronger impacts on future ecosystem carbon balances than changes in average climate. We improved a published modelling approach which distinguishes the direct....... At the annual time scale as much as 80% of the IAV in NEE was attributed to the variation in photosynthesis and respiration related model parameters. Our results suggest that the observed decadal NEE trend at the investigated site was dominated by changes in ecosystem functioning. In general this study showed...

Departments as teams: Functioning, variations and alternatives

NARCIS (Netherlands)

Witziers, B.; Sleegers, P.J.C.; Imants, J.G.M.

1999-01-01

Complex, multi-dimensional and often conflicting reform has led in The Netherlands to a situation in which the management of schools is no longer seen as the exclusive preserve of senior management. In order to manage changes within schools it is deemed necessary to expand the management function to

Coarse Grained Exponential Variational Autoencoders

KAUST Repository

Sun, Ke

2017-02-25

Variational autoencoders (VAE) often use Gaussian or category distribution to model the inference process. This puts a limit on variational learning because this simplified assumption does not match the true posterior distribution, which is usually much more sophisticated. To break this limitation and apply arbitrary parametric distribution during inference, this paper derives a \\\\emph{semi-continuous} latent representation, which approximates a continuous density up to a prescribed precision, and is much easier to analyze than its continuous counterpart because it is fundamentally discrete. We showcase the proposition by applying polynomial exponential family distributions as the posterior, which are universal probability density function generators. Our experimental results show consistent improvements over commonly used VAE models.

Determining Criteria to Predict Repeatability of Performance in Older Adults: Using Coefficients of Variation for Strength and Functional Measures.

Science.gov (United States)

Raj, Isaac Selva; Bird, Stephen R; Westfold, Ben A; Shield, Anthony J

2017-01-01

Reliable measures of muscle strength and functional capacity in older adults are essential. The aim of this study was to determine whether coefficients of variation (CVs) of individuals obtained at the first session can infer repeatability of performance in a subsequent session. Forty-eight healthy older adults (mean age 68.6 ± 6.1 years; age range 60-80 years) completed two assessment sessions, and on each occasion undertook: dynamometry for isometric and isokinetic quadriceps strength, 6 meter fast walk (6MFWT), timed up and go (TUG), stair climb and descent, and vertical jump. Significant linear relationships were observed between CVs in session 1 and the percentage difference between sessions 1 and 2 for torque at 60, 120, 240 and 360°/s, 6MFWT, TUG, stair climb, and stair descent. The results of this study could be used to establish criteria for determining an acceptably reliable performance in strength and functional tests.

Habitat Fragmentation Differentially Affects Genetic Variation, Phenotypic Plasticity and Survival in Populations of a Gypsum Endemic

Directory of Open Access Journals (Sweden)

Silvia Matesanz

2017-05-01

Full Text Available Habitat fragmentation, i.e., fragment size and isolation, can differentially alter patterns of neutral and quantitative genetic variation, fitness and phenotypic plasticity of plant populations, but their effects have rarely been tested simultaneously. We assessed the combined effects of size and connectivity on these aspects of genetic and phenotypic variation in populations of Centaurea hyssopifolia, a narrow endemic gypsophile that previously showed performance differences associated with fragmentation. We grew 111 maternal families sampled from 10 populations that differed in their fragment size and connectivity in a common garden, and characterized quantitative genetic variation, phenotypic plasticity to drought for key functional traits, and plant survival, as a measure of population fitness. We also assessed neutral genetic variation within and among populations using eight microsatellite markers. Although C. hyssopifolia is a narrow endemic gypsophile, we found substantial neutral genetic variation and quantitative variation for key functional traits. The partition of genetic variance indicated that a higher proportion of variation was found within populations, which is also consistent with low population differentiation in molecular markers, functional traits and their plasticity. This, combined with the generally small effect of habitat fragmentation suggests that gene flow among populations is not restricted, despite large differences in fragment size and isolation. Importantly, population’s similarities in genetic variation and plasticity did not reflect the lower survival observed in isolated populations. Overall, our results indicate that, although the species consists of genetically variable populations able to express functional plasticity, such aspects of adaptive potential may not always reflect populations’ survival. Given the differential effects of habitat connectivity on functional traits, genetic variation and fitness

Molecular photoionization using the complex Kohn variational method

International Nuclear Information System (INIS)

Lynch, D.L.; Schneider, B.I.

1992-01-01

We have applied the complex Kohn variational method to the study of molecular-photoionization processes. This requires electron-ion scattering calculations enforcing incoming boundary conditions. The sensitivity of these results to the choice of the cutoff function in the Kohn method has been studied and we have demonstrated that a simple matching of the irregular function to a linear combination of regular functions produces accurate scattering phase shifts

Forever young: Endocrinology of paedomorphosis in the Mexican axolotl (Ambystoma mexicanum).

Science.gov (United States)

De Groef, Bert; Grommen, Sylvia V H; Darras, Veerle M

2018-05-16

The Mexican axolotl (Ambystoma mexicanum) is a salamander species that does not undergo metamorphosis, resulting in the retention of juvenile characteristics in the mature breeding stage (paedomorphosis). Here we review the endocrinological studies investigating the proximate cause of axolotl paedomorphosis with a focus on the hypothalamo-pituitary-thyroid (HPT) axis. It is well established that axolotl paedomorphosis is a consequence of low activity of the HPT axis. The pituitary hormone thyrotropin (TSH) is capable of inducing metamorphosis in the axolotl, which indicates that all processes and interactions in the HPT axis below the pituitary level are functional, but that TSH release is impaired. In metamorphosing species, TSH secretion is largely controlled by the hypothalamic neuropeptide corticotropin-releasing hormone (CRH), which seems to have lost its thyrotropic activity in the axolotl. However, preliminary experiments have not yet confirmed a role for faulty CRH signalling in axolotl paedomorphosis. Other hypothalamic factors and potential pituitary inhibitors need to be investigated to identify their roles in amphibian metamorphosis and axolotl paedomorphosis. Copyright © 2018 Elsevier Inc. All rights reserved.

Error estimation for variational nodal calculations

International Nuclear Information System (INIS)

Zhang, H.; Lewis, E.E.

1998-01-01

Adaptive grid methods are widely employed in finite element solutions to both solid and fluid mechanics problems. Either the size of the element is reduced (h refinement) or the order of the trial function is increased (p refinement) locally to improve the accuracy of the solution without a commensurate increase in computational effort. Success of these methods requires effective local error estimates to determine those parts of the problem domain where the solution should be refined. Adaptive methods have recently been applied to the spatial variables of the discrete ordinates equations. As a first step in the development of adaptive methods that are compatible with the variational nodal method, the authors examine error estimates for use in conjunction with spatial variables. The variational nodal method lends itself well to p refinement because the space-angle trial functions are hierarchical. Here they examine an error estimator for use with spatial p refinement for the diffusion approximation. Eventually, angular refinement will also be considered using spherical harmonics approximations

Association of genetic variation in cannabinoid mechanisms and gastric motor functions and satiation in overweight and obesity.

Science.gov (United States)

Vazquez-Roque, M I; Camilleri, M; Vella, A; Carlson, P; Laugen, J; Zinsmeister, A R

2011-07-01

The endocannabinoid system is associated with food intake. We hypothesized that genes regulating cannabinoids are associated with obesity. Genetic variations in fatty acid amide hydroxylase (FAAH) and cannabinoid receptor 1 (CNR1) are associated with satiation and gastric motor function. In 62 overweight or obese adults of European ancestry, single nucleotide polymorphisms of rs806378 (nearest gene CNR1) and rs324420 (nearest gene FAAH) were genotyped and the associations with gastric emptying (GE) of solids and liquids, gastric volume (GV), and satiation [maximum tolerated volume (MTV) and symptoms after Ensure(®) nutrient drink test] were explored using a dominant genetic model, with gender and BMI as covariates. rs806378 CC genotype was associated with reduced fasting GV (210.2±11.0mL for CC group compared to 242.5±11.3mL for CT/TT group, P=0.031) and a modest, non-significant association with GE of solids (P=0.17). rs324420 genotype was not associated with alterations in gastric motor functions; however, there was a difference in the Ensure(®) MTV (1174.6±37.2mL for CC group compared to 1395.0±123.1mL for CA/AA group, P=0.046) suggesting higher satiation with CC genotype. Our data suggest that CNR1 and FAAH are associated with altered gastric functions or satiation that may predispose to obesity. © 2011 Blackwell Publishing Ltd.

Calculus of variations involving Caputo-Fabrizio fractional differentiation

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Nuno R. O. Bastos

2018-02-01

Full Text Available This paper is devoted to study some variational problems with functionals containing the Caputo-Fabrizio fractional derivative, that is a fractional derivative with a non-singular kernel.

Fractional variational calculus in terms of Riesz fractional derivatives

International Nuclear Information System (INIS)

Agrawal, O P

2007-01-01

This paper presents extensions of traditional calculus of variations for systems containing Riesz fractional derivatives (RFDs). Specifically, we present generalized Euler-Lagrange equations and the transversality conditions for fractional variational problems (FVPs) defined in terms of RFDs. We consider two problems, a simple FVP and an FVP of Lagrange. Results of the first problem are extended to problems containing multiple fractional derivatives, functions and parameters, and to unspecified boundary conditions. For the second problem, we present Lagrange-type multiplier rules. For both problems, we develop the Euler-Lagrange-type necessary conditions which must be satisfied for the given functional to be extremum. Problems are considered to demonstrate applications of the formulations. Explicitly, we introduce fractional momenta, fractional Hamiltonian, fractional Hamilton equations of motion, fractional field theory and fractional optimal control. The formulations presented and the resulting equations are similar to the formulations for FVPs given in Agrawal (2002 J. Math. Anal. Appl. 272 368, 2006 J. Phys. A: Math. Gen. 39 10375) and to those that appear in the field of classical calculus of variations. These formulations are simple and can be extended to other problems in the field of fractional calculus of variations

Gutzwiller variational wave function for a two-orbital Hubbard model on a square lattice

Energy Technology Data Exchange (ETDEWEB)

Muenster, Kevin Torben zu

2015-07-01

In this work, we formulated and applied the Gutzwiller variational many-body approach to multi-band Hubbard models. In chapter 1, we gave a short introduction to the problem and an outline of the scope of the work. In the chapter 2, we developed a complete, concise diagrammatic formalism for a perturbative evaluation of expectation values for Gutzwiller-correlated wave functions on finite lattices. The derivation of the diagrammatic expansion consists of three steps. In a first step, we introduced a one-to-one mapping between a sequence of fermion operators and their Hartree-Fock counterparts in order to eliminate all local contractions. We explicitly showed the consistency of the mapping. In a second step, we derived and applied the linked-cluster theorem. To this end, we expanded numerator and denominator in the Gutzwiller expectation value of one-site and two-site operators in terms of a perturbation series, and used Wick's theorem to express the coefficients in terms of diagrams. The introduction of the Hartree-Fock operators excludes all local contractions so that lines between identical lattice sites are zero by definition. The normal ordering of the operators and the sum over distinctive lattice sites permitted the introduction of Grassmann variables. For multi-band Gutzwiller wave functions, we had to introduce a formal representation of local operators in terms of an exponential series which led to a re-definition of the values of external and internal vertices. Then, the linked-cluster theorem applied, both for infinite and finite lattices, i.e., the unconnected diagrams in the numerator are canceled by the denominator. In this way, the nth-order in perturbation theory corresponds to summing all connected diagrams with n internal nodes. As a third and last step, we eliminated all internal nodes with two lines by fixing a subset of our variational parameters. We showed that, for our applications, this gauge fixing does not restrict the variational

A simple and realistic triton wave function

International Nuclear Information System (INIS)

Lomnitz-Adler, J.; Pandharipande, V.R.

1980-01-01

We propose a simple triton wave function that consists of a product of three correlation operators operating on a three-body spin-isospin state. This wave function is formally similar to that used in the recent variational theories of nuclear matter, the main difference being in the long-range behavior of the correlation operators. Variational calculations are carried out with the Reid potential, using this wave function in the so-called 'symmetrized product' and 'independent pair' forms. The triton energy and density distributions obtained with the symmetrized product wave function agree with those obtained in Faddeev and other variational calculations using harmonic oscillator states. The proposed wave function and calculational methods can be easily generalized to treat the four-nucleon α-particle. (orig.)

Expression of genes related to the hypothalamic-pituitary-adrenal axis in murine fetal lungs in late gestation

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Côté Mélissa

2010-11-01

Full Text Available Abstract Background Lung maturation is modulated by several factors, including glucocorticoids. Expression of hypothalamic-pituitary-adrenal (HPA axis-related components, with proposed or described local regulatory systems analogous to the HPA axis, was reported in peripheral tissues. Here, HPA axis-related genes were studied in the mouse developing lung during a period overlapping the surge of surfactant production. Methods Expression of genes encoding for corticotropin-releasing hormone (CRH, CRH receptors (CRHR 1 and 2beta, CRH-binding protein, proopiomelanocortin (POMC, melanocortin receptor 2 (MC2R, and glucocorticoid receptor was quantified by real-time PCR and localized by in situ hydridization in fetal lungs at gestational days (GD 15.5, 16.5, and 17.5, and was also quantified in primary mesenchymal- and epithelial cell-enriched cultures. In addition, the capability of CRH and adrenocorticotropic hormone (ACTH to stimulate pulmonary expression of enzymes involved in the adrenal pathway of glucocorticoid synthesis was addressed, as well as the glucocorticoid production by fetal lung explants. Results We report that all the studied genes are expressed in fetal lungs according to different patterns. On GD 15.5, Mc2r showed peaks in expression in samples that have previously presented high mRNA levels for glucocorticoid synthesizing enzymes, including 11beta-hydroxylase (Cyp11b1. Crhr1 mRNA co-localized with Pomc mRNA in cells surrounding the proximal epithelium on GD 15.5 and 16.5. A transition in expression sites toward distal epithelial cells was observed between GD 15.5 and 17.5 for all the studied genes. CRH or ACTH stimulation of genes involved in the adrenal pathway of glucocorticoid synthesis was not observed in lung explants on GD 15.5, whereas CRH significantly increased expression of 21-hydroxylase (Cyp21a1 on GD 17.5. A deoxycorticosterone production by fetal lung explants was observed. Conclusions Temporal and spatial

Survival-variation within and between functional categories of the African multimammate rat

DEFF Research Database (Denmark)

Julliard, Romain; Leirs, Herwig; Stenseth, Nils Chr.

1999-01-01

in the population immediately after their first capture; (iv) subadults survival in later months is, however, positively related to density; and (v) adult survival shows negative density-dependence. 3. Both density-dependent and density-independent factors simultaneously determine stage-dependent survival variation...

Duality for Multitime Multiobjective Ratio Variational Problems on First Order Jet Bundle

Directory of Open Access Journals (Sweden)

Mihai Postolache

2012-01-01

Full Text Available We consider a new class of multitime multiobjective variational problems of minimizing a vector of quotients of functionals of curvilinear integral type. Based on the efficiency conditions for multitime multiobjective ratio variational problems, we introduce a ratio dual of generalized Mond-Weir-Zalmai type, and under some assumptions of generalized convexity, duality theorems are stated. We prove our weak duality theorem for efficient solutions, showing that the value of the objective function of the primal cannot exceed the value of the dual. Direct and converse duality theorems are stated, underlying the connections between the values of the objective functions of the primal and dual programs. As special cases, duality results of Mond-Weir-Zalmai type for a multitime multiobjective variational problem are obtained. This work further develops our studies in (Pitea and Postolache (2011.

Analysis of Idiom Variation in the Framework of Linguistic Subjectivity

Science.gov (United States)

Liu, Zhengyuan

2012-01-01

Idiom variation is a ubiquitous linguistic phenomenon which has raised a lot of research questions. The past approach was either formal or functional. Both of them did not pay much attention to cognitive factors of language users. By putting idiom variation in the framework of linguistic subjectivity, we have offered a new perspective in the…

Network hubs buffer environmental variation in Saccharomyces cerevisiae.

Directory of Open Access Journals (Sweden)

Sasha F Levy

2008-11-01

Full Text Available Regulatory and developmental systems produce phenotypes that are robust to environmental and genetic variation. A gene product that normally contributes to this robustness is termed a phenotypic capacitor. When a phenotypic capacitor fails, for example when challenged by a harsh environment or mutation, the system becomes less robust and thus produces greater phenotypic variation. A functional phenotypic capacitor provides a mechanism by which hidden polymorphism can accumulate, whereas its failure provides a mechanism by which evolutionary change might be promoted. The primary example to date of a phenotypic capacitor is Hsp90, a molecular chaperone that targets a large set of signal transduction proteins. In both Drosophila and Arabidopsis, compromised Hsp90 function results in pleiotropic phenotypic effects dependent on the underlying genotype. For some traits, Hsp90 also appears to buffer stochastic variation, yet the relationship between environmental and genetic buffering remains an important unresolved question. We previously used simulations of knockout mutations in transcriptional networks to predict that many gene products would act as phenotypic capacitors. To test this prediction, we use high-throughput morphological phenotyping of individual yeast cells from single-gene deletion strains to identify gene products that buffer environmental variation in Saccharomyces cerevisiae. We find more than 300 gene products that, when absent, increase morphological variation. Overrepresented among these capacitors are gene products that control chromosome organization and DNA integrity, RNA elongation, protein modification, cell cycle, and response to stimuli such as stress. Capacitors have a high number of synthetic-lethal interactions but knockouts of these genes do not tend to cause severe decreases in growth rate. Each capacitor can be classified based on whether or not it is encoded by a gene with a paralog in the genome. Capacitors with a

Variate generation for probabilistic fracture mechanics and fitness-for-service studies

International Nuclear Information System (INIS)

Walker, J.R.

1987-01-01

Atomic Energy of Canada Limited is conducting studies in Probabilistic Fracture Mechanics. These studies are being conducted as part of a fitness-for-service programme in support of CANDU reactors. The Monte Carlo analyses, which form part of the Probabilistic Fracture Mechanics studies, require that variates can be sampled from probability density functions. Accurate pseudo-random numbers are necessary for accurate variate generation. This report details the principles of variate generation, and describes the production and testing of pseudo-random numbers. A new algorithm has been produced for the correct performance of the lattice test for the independence of pseudo-random numbers. Two new pseudo-random number generators have been produced. These generators have excellent randomness properties and can be made fully machine-independent. Versions, in FORTRAN, for VAX and CDC computers are given. Accurate and efficient algorithms for the generation of variates from the specialized probability density functions of Probabilistic Fracture Mechanics are given. 38 refs

Asymptotic Behaviour of Total Generalised Variation

KAUST Repository

Papafitsoros, Konstantinos; Valkonen, Tuomo

2015-01-01

© Springer International Publishing Switzerland 2015. The recently introduced second order total generalised variation functional TGV2 β,α has been a successful regulariser for image processing purposes. Its definition involves two positive parameters α and β whose values determine the amount and the quality of the regularisation. In this paper we report on the behaviour of TGV2 β,α in the cases where the parameters α, β as well as their ratio β/α becomes very large or very small. Among others, we prove that for sufficiently symmetric two dimensional data and large ratio β/α, TGV2 β,α regularisation coincides with total variation (TV) regularization

Population genetic variation in gene expression is associated withphenotypic variation in Saccharomyces cerevisiae

Energy Technology Data Exchange (ETDEWEB)

Fay, Justin C.; McCullough, Heather L.; Sniegowski, Paul D.; Eisen, Michael B.

2004-02-25

The relationship between genetic variation in gene expression and phenotypic variation observable in nature is not well understood. Identifying how many phenotypes are associated with differences in gene expression and how many gene-expression differences are associated with a phenotype is important to understanding the molecular basis and evolution of complex traits. Results: We compared levels of gene expression among nine natural isolates of Saccharomyces cerevisiae grown either in the presence or absence of copper sulfate. Of the nine strains, two show a reduced growth rate and two others are rust colored in the presence of copper sulfate. We identified 633 genes that show significant differences in expression among strains. Of these genes,20 were correlated with resistance to copper sulfate and 24 were correlated with rust coloration. The function of these genes in combination with their expression pattern suggests the presence of both correlative and causative expression differences. But the majority of differentially expressed genes were not correlated with either phenotype and showed the same expression pattern both in the presence and absence of copper sulfate. To determine whether these expression differences may contribute to phenotypic variation under other environmental conditions, we examined one phenotype, freeze tolerance, predicted by the differential expression of the aquaporin gene AQY2. We found freeze tolerance is associated with the expression of AQY2. Conclusions: Gene expression differences provide substantial insight into the molecular basis of naturally occurring traits and can be used to predict environment dependent phenotypic variation.

Variational integrators for reduced magnetohydrodynamics

Energy Technology Data Exchange (ETDEWEB)

Kraus, Michael, E-mail: michael.kraus@ipp.mpg.de [Max-Planck-Institut für Plasmaphysik, Boltzmannstraße 2, 85748 Garching (Germany); Technische Universität München, Zentrum Mathematik, Boltzmannstraße 3, 85748 Garching (Germany); Tassi, Emanuele, E-mail: tassi@cpt.univ-mrs.fr [Aix-Marseille Université, Université de Toulon, CNRS, CPT, UMR 7332, 163 avenue de Luminy, case 907, 13288 cedex 9 Marseille (France); Grasso, Daniela, E-mail: daniela.grasso@infm.polito.it [ISC-CNR and Politecnico di Torino, Dipartimento Energia, C.so Duca degli Abruzzi 24, 10129 Torino (Italy)

2016-09-15

Reduced magnetohydrodynamics is a simplified set of magnetohydrodynamics equations with applications to both fusion and astrophysical plasmas, possessing a noncanonical Hamiltonian structure and consequently a number of conserved functionals. We propose a new discretisation strategy for these equations based on a discrete variational principle applied to a formal Lagrangian. The resulting integrator preserves important quantities like the total energy, magnetic helicity and cross helicity exactly (up to machine precision). As the integrator is free of numerical resistivity, spurious reconnection along current sheets is absent in the ideal case. If effects of electron inertia are added, reconnection of magnetic field lines is allowed, although the resulting model still possesses a noncanonical Hamiltonian structure. After reviewing the conservation laws of the model equations, the adopted variational principle with the related conservation laws is described both at the continuous and discrete level. We verify the favourable properties of the variational integrator in particular with respect to the preservation of the invariants of the models under consideration and compare with results from the literature and those of a pseudo-spectral code.

A Modified Alternating Direction Method for Variational Inequality Problems

International Nuclear Information System (INIS)

Han, D.

2002-01-01

The alternating direction method is an attractive method for solving large-scale variational inequality problems whenever the subproblems can be solved efficiently. However, the subproblems are still variational inequality problems, which are as structurally difficult to solve as the original one. To overcome this disadvantage, in this paper we propose a new alternating direction method for solving a class of nonlinear monotone variational inequality problems. In each iteration the method just makes an orthogonal projection to a simple set and some function evaluations. We report some preliminary computational results to illustrate the efficiency of the method

Non-linear variation of the beta function with momentum

International Nuclear Information System (INIS)

Parzen, G.

1983-07-01

A theory is presented for computing the non-linear dependence of the β-functions on momentum. Results are found for the quadratic term. The results of the theory are compared with computed results. A procedure is proposed for computing the strengths of the sextupole correctors to correct the dependence of the β-function on momentum

Aerodynamic design on high-speed trains

Science.gov (United States)

Ding, San-San; Li, Qiang; Tian, Ai-Qin; Du, Jian; Liu, Jia-Li

2016-04-01

Compared with the traditional train, the operational speed of the high-speed train has largely improved, and the dynamic environment of the train has changed from one of mechanical domination to one of aerodynamic domination. The aerodynamic problem has become the key technological challenge of high-speed trains and significantly affects the economy, environment, safety, and comfort. In this paper, the relationships among the aerodynamic design principle, aerodynamic performance indexes, and design variables are first studied, and the research methods of train aerodynamics are proposed, including numerical simulation, a reduced-scale test, and a full-scale test. Technological schemes of train aerodynamics involve the optimization design of the streamlined head and the smooth design of the body surface. Optimization design of the streamlined head includes conception design, project design, numerical simulation, and a reduced-scale test. Smooth design of the body surface is mainly used for the key parts, such as electric-current collecting system, wheel truck compartment, and windshield. The aerodynamic design method established in this paper has been successfully applied to various high-speed trains (CRH380A, CRH380AM, CRH6, CRH2G, and the Standard electric multiple unit (EMU)) that have met expected design objectives. The research results can provide an effective guideline for the aerodynamic design of high-speed trains.

Relevance of variations in the opposing dentition for the functionality of fixed and removable partial dentures: a systematic review.

Science.gov (United States)

Pommer, Bernhard; Krainhöfner, Martin; Watzek, Georg; Tepper, Gabor; Dintsios, Charalabos-Markos

2012-01-01

The aim of this systematic review was to evaluate the functionality of fixed and removable partial dentures as test interventions in relation to variations in the opposing dentition and their prosthetic restoration. The abstracts identified in the respective databases were screened independently by two investigators. RCTs and uncontrolled studies were considered, provided the patients were included consecutively and the confounding variables were adequately monitored. Seventeen papers were included. The study and publication quality was assessed using a "biometric quality" tool showing an overall poor quality. The reported outcomes, such as survival rates, were in each case obtained from a single study. Two possible trends could be deduced for the endpoint longevity: (a) the first trend in favor of removable partial dentures, compared to fixed partial dentures, with a fully edentulous opposing arch fitted with a removable prosthesis; (b) the second trend in favor of implant-supported partial dentures, compared to conventionally fixed partial dentures, with natural opposing dentition or with a removable partial denture in the opposing arch. No evidence could be generated as to whether, and if so how, variations in the opposing dentition have a bearing on the decision to fit a partially edentulous arch with a fixed or removable partial denture.

Relevance of Variations in the Opposing Dentition for the Functionality of Fixed and Removable Partial Dentures: A Systematic Review

Directory of Open Access Journals (Sweden)

Bernhard Pommer

2012-01-01

Full Text Available The aim of this systematic review was to evaluate the functionality of fixed and removable partial dentures as test interventions in relation to variations in the opposing dentition and their prosthetic restoration. The abstracts identified in the respective databases were screened independently by two investigators. RCTs and uncontrolled studies were considered, provided the patients were included consecutively and the confounding variables were adequately monitored. Seventeen papers were included. The study and publication quality was assessed using a “biometric quality” tool showing an overall poor quality. The reported outcomes, such as survival rates, were in each case obtained from a single study. Two possible trends could be deduced for the endpoint longevity: (a the first trend in favor of removable partial dentures, compared to fixed partial dentures, with a fully edentulous opposing arch fitted with a removable prosthesis; (b the second trend in favor of implant-supported partial dentures, compared to conventionally fixed partial dentures, with natural opposing dentition or with a removable partial denture in the opposing arch. No evidence could be generated as to whether, and if so how, variations in the opposing dentition have a bearing on the decision to fit a partially edentulous arch with a fixed or removable partial denture.

A source of parametric variation in the lexicon

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Guglielmo Cinque

2016-12-01

Full Text Available An influential conjecture concerning parameters is that they can possibly be “restricted to formal features of functional categories” (Chomsky 1995: 6. In Rizzi (2009, 2011 such features are understood as instructions triggering one of the following syntactic actions: (1 External Merge; (2 Internal Merge (Move; (3 Pronunciation/Non pronunciation (the latter arguably dependent on Internal Merge – Kayne 2005a, b. In this article I consider a particular source of parametric variation across languages in the domain of the lexicon (both functional and substantive which appears to be due to the possibility of underspecifying certain features in some languages. The paradigmatic variation can be characterized as follows: language A has two (or more lexical items which correspond to just one lexical item in language B.

THE CONTROL VARIATIONAL METHOD FOR ELASTIC CONTACT PROBLEMS

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Mircea Sofonea

2010-07-01

Full Text Available We consider a multivalued equation of the form Ay + F(y = fin a real Hilbert space, where A is a linear operator and F represents the (Clarke subdifferential of some function. We prove existence and uniqueness results of the solution by using the control variational method. The main idea in this method is to minimize the energy functional associated to the nonlinear equation by arguments of optimal control theory. Then we consider a general mathematical model describing the contact between a linearly elastic body and an obstacle which leads to a variational formulation as above, for the displacement field. We apply the abstract existence and uniqueness results to prove the unique weak solvability of the corresponding contact problem. Finally, we present examples of contact and friction laws for which our results work.

On Quadratic Variation of Martingales

Indian Academy of Sciences (India)

where D ( [ 0 , ∞ ) , R ) denotes the class of real valued r.c.l.l. functions on [ 0 , ∞ ) such that for a locally square integrable martingale ( M t ) with r.c.l.l. paths,. Ψ ( M . ( ) ) = A . ( ). gives the quadratic variation process (written usually as [ M , M ] t ) of ( M t ) . We also show that this process ( A t ) is the unique increasing ...

Structure analyses of swollen rubber-carbon black systems by contrast variation SANS

International Nuclear Information System (INIS)

Takenaka, Mikihito; Nishitsuji, Shotaro; Fujii, Sumiaki; Amino, Naoya; Ishikawa, Yasuhiro; Yamaguchi, Daisuke; Koizumi, Satoshi

2010-01-01

The polymer layers adsorbed on carbon black (CB) aggregates in rubber/CB systems have been investigated with contrast variation small-angle neutron scattering (SANS) method. Specimens were swollen by toluene/deuterated toluene solvents having various scattering length densities and their scattering intensities were measured with SANS. The contrast variation SANS for the specimens yielded partial scattering functions: the scattering function for polymer-polymer correlation S pp (q), the scattering function for CB- CB correlation S cc (q), and the scattering function for polymer- CB correlation S pc (q). The analyses of the partial scattering functions explored the existence of dense polymer layers around CB aggregates. Several characteristic parameters are estimated from the analyses, such as the size of aggregates, the thickness of layers, and the volume fractions of polymer of layers and matrix. (author)

Functional conservation of nucleosome formation selectively biases presumably neutral molecular variation in yeast genomes.

Science.gov (United States)

Babbitt, Gregory A; Cotter, C R

2011-01-01

One prominent pattern of mutational frequency, long appreciated in comparative genomics, is the bias of purine/pyrimidine conserving substitutions (transitions) over purine/pyrimidine altering substitutions (transversions). Traditionally, this transitional bias has been thought to be driven by the underlying rates of DNA mutation and/or repair. However, recent sequencing studies of mutation accumulation lines in model organisms demonstrate that substitutions generally do not accumulate at rates that would indicate a transitional bias. These observations have called into question a very basic assumption of molecular evolution; that naturally occurring patterns of molecular variation in noncoding regions accurately reflect the underlying processes of randomly accumulating neutral mutation in nuclear genomes. Here, in Saccharomyces yeasts, we report a very strong inverse association (r = -0.951, P < 0.004) between the genome-wide frequency of substitutions and their average energetic effect on nucleosome formation, as predicted by a structurally based energy model of DNA deformation around the nucleosome core. We find that transitions occurring at sites positioned nearest the nucleosome surface, which are believed to function most importantly in nucleosome formation, alter the deformation energy of DNA to the nucleosome core by only a fraction of the energy changes typical of most transversions. When we examined the same substitutions set against random background sequences as well as an existing study reporting substitutions arising in mutation accumulation lines of Saccharomyces cerevisiae, we failed to find a similar relationship. These results support the idea that natural selection acting to functionally conserve chromatin organization may contribute significantly to genome-wide transitional bias, even in noncoding regions. Because nucleosome core structure is highly conserved across eukaryotes, our observations may also help to further explain locally elevated

Measure functional differential equations in the space of functions of bounded variation

Czech Academy of Sciences Publication Activity Database

Afonso, S.; Rontó, András

2013-01-01

Roč. 2013, č. 582161 (2013), s. 582161 ISSN 1085-3375 Institutional support: RVO:67985840 Keywords : measure differential equations * functional differential equations Subject RIV: BA - General Mathematics Impact factor: 1.274, year: 2013 http://www.hindawi.com/journals/ aaa /2013/582161/

Edgeworth expansion for functionals of continuous diffusion processes

DEFF Research Database (Denmark)

Podolskij, Mark; Yoshida, Nakahiro

This paper presents new results on the Edgeworth expansion for high frequency functionals of continuous diffusion processes. We derive asymptotic expansions for weighted functionals of the Brownian motion and apply them to provide the Edgeworth expansion for power variation of diffusion processes....... Our methodology relies on martingale embedding, Malliavin calculus and stable central limit theorems for semimartingales. Finally, we demonstrate the density expansion for studentized statistics of power variations.......This paper presents new results on the Edgeworth expansion for high frequency functionals of continuous diffusion processes. We derive asymptotic expansions for weighted functionals of the Brownian motion and apply them to provide the Edgeworth expansion for power variation of diffusion processes...

Looking at the origin of phenotypic variation from pattern formation ...

Indian Academy of Sciences (India)

Prakash

evolutionary considerations, a large number of researchers, ... This article critically reviews some widespread views about the overall functioning of development. ... Thus, a great deal about the evolution and functioning of ... variants and thus take patterns of phenotypic variation as ..... Evolutionary thinking to the rescue.

Matrix-variational method: an efficient approach to bound state eigenproblems

International Nuclear Information System (INIS)

Gerck, E.; d'Oliveira, A.B.

1978-11-01

A new matrix-variational method for solving the radial Schroedinger equation is described. It consists in obtaining an adjustable matrix formulation for the boundary value differential equation, using a set of three functions that obey the boundary conditions. These functions are linearly combined at every three adjacents points to fit the true unknown eigenfunction by a variational technique. With the use of a new class of central differences, the exponential differences, tridiagonal or bidiagonal matrices are obtained. In the bidiagonal case, closed form expressions for the eigenvalues are given for the Coulomb, harmonic, linear, square-root and logarithmic potentials. The values obtained are within 0.1% of the true numerical value. The eigenfunction can be calculated using the eigenvectors to reconstruct the linear combination of the set functions [pt

Explicit formula for a fundamental class of functions

OpenAIRE

Avdispahić, Muharem; Smajlović, Lejla

2005-01-01

The purpose of this paper is to prove an analogue of A. Weil's explicit formula for a fundamental class of functions, i.e. the class of meromorphic functions that have an Euler sum representation and satisfy certain a functional equation. The advance of this explicit formula is that it enlarges the class of allowed test functions, from the class of functions with bounded Jordan variation to the class of functions of $\\phi $-bounded variation. A condition posed to the test fu...

Homogenization of variational inequalities and equations defined by pseudomonotone operators

International Nuclear Information System (INIS)

Sandrakov, G V

2008-01-01

Results on the convergence of sequences of solutions of non-linear equations and variational inequalities for obstacle problems are proved. The variational inequalities and equations are defined by a non-linear, pseudomonotone operator of the second order with periodic, rapidly oscillating coefficients and by sequences of functions characterizing the obstacles and the boundary conditions. Two-scale and macroscale (homogenized) limiting problems for such variational inequalities and equations are obtained. Results on the relationship between solutions of these limiting problems are established and sufficient conditions for the uniqueness of solutions are presented. Bibliography: 25 titles

Variational method for the derivative nonlinear Schroedinger equation with computational applications

Energy Technology Data Exchange (ETDEWEB)

Helal, M A [Mathematics Department, Faculty of Science, Cairo University (Egypt); Seadawy, A R [Mathematics Department, Faculty of Science, Beni-Suef University (Egypt)], E-mail: mahelal@yahoo.com, E-mail: aly742001@yahoo.com

2009-09-15

The derivative nonlinear Schroedinger equation (DNLSE) arises as a physical model for ultra-short pulse propagation. In this paper, the existence of a Lagrangian and the invariant variational principle (i.e. in the sense of the inverse problem of calculus of variations through deriving the functional integral corresponding to a given coupled nonlinear partial differential equations) for two-coupled equations describing the nonlinear evolution of the Alfven wave with magnetosonic waves at a much larger scale are given and the functional integral corresponding to those equations is derived. We found the solutions of DNLSE by choice of a trial function in a region of a rectangular box in two cases, and using this trial function, we find the functional integral and the Lagrangian of the system without loss. Solution of the general case for the two-box potential can be obtained on the basis of a different ansatz where we approximate the Jost function using polynomials of order n instead of the piecewise linear function. An example for the third order is given for illustrating the general case.

A CONSTRAINT ON BROWN DWARF FORMATION VIA EJECTION: RADIAL VARIATION OF THE STELLAR AND SUBSTELLAR MASS FUNCTION OF THE YOUNG OPEN CLUSTER IC 2391

International Nuclear Information System (INIS)

Boudreault, S.; Bailer-Jones, C. A. L.

2009-01-01

We present the stellar and substellar mass function (MF) of the open cluster IC 2391, plus its radial dependence, and use this to put constraints on the formation mechanism of brown dwarfs (BDs). Our multi-band optical and infrared photometric survey with spectroscopic follow-up covers 11 deg 2 , making it the largest survey of this cluster to date. We observe a radial variation in the MF over the range 0.072-0.3 M sun , but no significant variation in the MF below the substellar boundary at the three cluster radius intervals is analyzed. This lack of radial variation for low masses is what we would expect with the ejection scenario for BD formation, although considering that IC 2391 has an age about three times older than its crossing time, we expect that BDs with a velocity greater than the escape velocity have already escaped the cluster. Alternatively, the variation in the MF of the stellar objects could be an indication that they have undergone mass segregation via dynamical evolution. We also observe a significant variation across the cluster in the color of the (background) field star locus in color-magnitude diagrams and conclude that this is due to variable background extinction in the Galactic plane. From our preliminary spectroscopic follow-up, to confirm BD status and cluster membership, we find that all candidates are M dwarfs (in either the field or the cluster), demonstrating the efficiency of our photometric selection method in avoiding contaminants (e.g., red giants). About half of our photometric candidates for which we have spectra are spectroscopically confirmed as cluster members; two are new spectroscopically confirmed BD members of IC 2391.

Variational techniques in non-perturbative QCD

CERN Document Server

Kovner, Alex; Kovner, Alex

2004-01-01

We review attempts to apply the variational principle to understand the vacuum of non-abelian gauge theories. In particular, we focus on the method explored by Ian Kogan and collaborators, which imposes exact gauge invariance on the trial Gaussian wave functional prior to the minimization of energy. We describe the application of the method to a toy model -- confining compact QED in 2+1 dimensions -- where it works wonderfully and reproduces all known non-trivial results. We then follow its applications to pure Yang-Mills theory in 3+1 dimensions at zero and finite temperature. Among the results of the variational calculation are dynamical mass generation and the analytic description of the deconfinement phase transition.

Measurement of Conjectural Variations Elasticity in an Oligopoly Structure (Using Iwata Approach for Iranians Food and Beverage Industry

Directory of Open Access Journals (Sweden)

M. Nabishahyakitash

2015-05-01

Full Text Available In this paper, we investigate Conjectural Variations elasticity in Iranians Food and Beverage industry using Iwata approach, The conjectural variation function is extracted from demand and supply information also optimization process on producers’ behavior. The experimental estimates of conjectural variation elasticities were obtained based on price elasticity of demand, cost elasticity and marginal cost elasticity for the selected industries. In this research demand function AIDS was used to obtain the price elasticity. The AIDS function was estimated using SUR and the demand price elasticity is calculated by calfent. The results show that "Vegetable oils and animal" industry with 19.37 have the most conjectural variation elasticity among the selected industries (The more divergent the conjectural variation elasticity is from zero the more likely the monopoly exists. In addition, dairy, sugar and malt industries have the most conjectural variation elasticity with 18.01, 17.18, and 10.51 respectively.

Variational field theoretic approach to relativistiv meson-nucleon scattering

International Nuclear Information System (INIS)

Alexandrou, C.; Rosenfelder, R.; Schreiber, A.W.; TRIUMF, Vancouver, BC; Adelaide Univ., SA; Adelaide Univ., SA; Univ. Adelaide

1998-01-01

Non-perturbative polaron variational methods are applied, within the so-called particle or worldline representation of relativistic field theory, to study scattering in the context of the scalar Wick-Cutkosky model. Important features of the variational calculation are that it is a controlled approximation scheme valid for arbitrary coupling strengths, the Green functions have all the cuts and poles expected for the exact result at any order in perturbation theory and that the variational parameters are simultaneously sensitive to the infrared as well as the ultraviolet behaviour of the theory. We generalize the previously used quadratic trial action by allowing more freedom for off-shell propagation without a change in the on-shell variational equations and evaluate the scattering amplitude at first order in the variational scheme. Particular attention is paid to the s-channel scattering near threshold because here non-perturbative effects can be large. We check the unitarity of a our numerical calculation and find it greatly improved compared to perturbation theory and to the zeroth order variational results. (orig.)

Heterogeneous treatment in the variational nodal method

International Nuclear Information System (INIS)

Fanning, T.H.

1995-01-01

The variational nodal transport method is reduced to its diffusion form and generalized for the treatment of heterogeneous nodes while maintaining nodal balances. Adapting variational methods to heterogeneous nodes requires the ability to integrate over a node with discontinuous cross sections. In this work, integrals are evaluated using composite gaussian quadrature rules, which permit accurate integration while minimizing computing time. Allowing structure within a nodal solution scheme avoids some of the necessity of cross section homogenization, and more accurately defines the intra-nodal flux shape. Ideally, any desired heterogeneity can be constructed within the node; but in reality, the finite set of basis functions limits the practical resolution to which fine detail can be defined within the node. Preliminary comparison tests show that the heterogeneous variational nodal method provides satisfactory results even if some improvements are needed for very difficult, configurations

Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

Science.gov (United States)

Davies, G; Armstrong, N; Bis, J C; Bressler, J; Chouraki, V; Giddaluru, S; Hofer, E; Ibrahim-Verbaas, C A; Kirin, M; Lahti, J; van der Lee, S J; Le Hellard, S; Liu, T; Marioni, R E; Oldmeadow, C; Postmus, I; Smith, A V; Smith, J A; Thalamuthu, A; Thomson, R; Vitart, V; Wang, J; Yu, L; Zgaga, L; Zhao, W; Boxall, R; Harris, S E; Hill, W D; Liewald, D C; Luciano, M; Adams, H; Ames, D; Amin, N; Amouyel, P; Assareh, A A; Au, R; Becker, J T; Beiser, A; Berr, C; Bertram, L; Boerwinkle, E; Buckley, B M; Campbell, H; Corley, J; De Jager, P L; Dufouil, C; Eriksson, J G; Espeseth, T; Faul, J D; Ford, I; Scotland, Generation; Gottesman, R F; Griswold, M E; Gudnason, V; Harris, T B; Heiss, G; Hofman, A; Holliday, E G; Huffman, J; Kardia, S L R; Kochan, N; Knopman, D S; Kwok, J B; Lambert, J-C; Lee, T; Li, G; Li, S-C; Loitfelder, M; Lopez, O L; Lundervold, A J; Lundqvist, A; Mather, K A; Mirza, S S; Nyberg, L; Oostra, B A; Palotie, A; Papenberg, G; Pattie, A; Petrovic, K; Polasek, O; Psaty, B M; Redmond, P; Reppermund, S; Rotter, J I; Schmidt, H; Schuur, M; Schofield, P W; Scott, R J; Steen, V M; Stott, D J; van Swieten, J C; Taylor, K D; Trollor, J; Trompet, S; Uitterlinden, A G; Weinstein, G; Widen, E; Windham, B G; Jukema, J W; Wright, A F; Wright, M J; Yang, Q; Amieva, H; Attia, J R; Bennett, D A; Brodaty, H; de Craen, A J M; Hayward, C; Ikram, M A; Lindenberger, U; Nilsson, L-G; Porteous, D J; Räikkönen, K; Reinvang, I; Rudan, I; Sachdev, P S; Schmidt, R; Schofield, P R; Srikanth, V; Starr, J M; Turner, S T; Weir, D R; Wilson, J F; van Duijn, C; Launer, L; Fitzpatrick, A L; Seshadri, S; Mosley, T H; Deary, I J

2015-01-01

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10−9, MIR2113; rs17522122, P=2.55 × 10−8, AKAP6; rs10119, P=5.67 × 10−9, APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10−6). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10−17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C. PMID:25644384

An experimental trip to the Calculus of Variations

Science.gov (United States)

Arroyo, Josu

2008-04-01

This paper presents a collection of experiments in the Calculus of Variations. The implementation of the Gradient Descent algorithm built on cubic-splines acting as "numerically friendly" elementary functions, give us ways to solve variational problems by constructing the solution. It wins a pragmatic point of view: one gets solutions sometimes as fast as possible, sometimes as close as possible to the true solutions. The balance speed/precision is not always easy to achieve. Starting from the most well-known, classic or historical formulation of a variational problem, section 2 describes briefly the bridge between theoretical and computational formulations. The next sections show the results of several kind of experiments; from the most basics, as those about geodesics, to the most complex, as those about vesicles.

Exploration of Structural and Functional Variations Owing to Point Mutations in α-NAGA.

Science.gov (United States)

Meshach Paul, D; Rajasekaran, R

2018-03-01

Schindler disease is a lysosomal storage disorder caused due to deficiency or defective activity of alpha-N-acetylgalactosaminidase (α-NAGA). Mutations in gene encoding α-NAGA cause wide range of diseases, characterized with mild to severe clinical features. Molecular effects of these mutations are yet to be explored in detail. Therefore, this study was focused on four missense mutations of α-NAGA namely, S160C, E325K, R329Q and R329W. Native and mutant structures of α-NAGA were analysed to determine geometrical deviations such as the contours of root mean square deviation, root mean square fluctuation, percentage of residues in allowed regions of Ramachandran plot and solvent accessible surface area, using conformational sampling technique. Additionally, global energy-minimized structures of native and mutants were further analysed to compute their intra-molecular interactions, hydrogen bond dilution and distribution of secondary structure. In addition, docking studies were also performed to determine variations in binding energies between native and mutants. The deleterious effects of mutants were evident due to variations in their active site residues pertaining to spatial conformation and flexibility, comparatively. Hence, variations exhibited by mutants, namely S160C, E325K, R329Q and R329W to that of native, consequently, lead to the detrimental effects causing Schindler disease. This study computationally explains the underlying reasons for the pathogenesis of the disease, thereby aiding future researchers in drug development and disease management.

mathematical model of thermal explosion, the dual variational formulation of nonlinear problem, alternative functional

Directory of Open Access Journals (Sweden)

V. S. Zarubin

2016-01-01

in its plane, and in the circular cylinder unlimited in length.An approximate numerical solution of the differential equation that is included in a nonlinear mathematical model of the thermal explosion enables us to obtain quantitative estimates of combination of determining parameters at which the limit state occurs in areas of not only canonical form. A capability to study of the thermal explosion state can be extended in the context of development of mathematical modeling methods, including methods of model analysis to describe the thermal state of solids.To analyse a mathematical model of the thermal explosion in a homogeneous solid the paper uses a variational approach based on the dual variational formulation of the appropriate nonlinear stationary problem of heat conduction in such a body. This formulation contains two alternative functional reaching the matching values in their stationary points corresponding to the true temperature distribution. This functional feature allows you to not only get an approximate quantitative estimate of the combination of parameters that determine the thermal explosion state, but also to find the greatest possible error in such estimation.

Integrative mining of traditional Chinese medicine literature and MEDLINE for functional gene networks.

Science.gov (United States)

Zhou, Xuezhong; Liu, Baoyan; Wu, Zhaohui; Feng, Yi

2007-10-01

The amount of biomedical data in different disciplines is growing at an exponential rate. Integrating these significant knowledge sources to generate novel hypotheses for systems biology research is difficult. Traditional Chinese medicine (TCM) is a completely different discipline, and is a complementary knowledge system to modern biomedical science. This paper uses a significant TCM bibliographic literature database in China, together with MEDLINE, to help discover novel gene functional knowledge. We present an integrative mining approach to uncover the functional gene relationships from MEDLINE and TCM bibliographic literature. This paper introduces TCM literature (about 50,000 records) as one knowledge source for constructing literature-based gene networks. We use the TCM diagnosis, TCM syndrome, to automatically congregate the related genes. The syndrome-gene relationships are discovered based on the syndrome-disease relationships extracted from TCM literature and the disease-gene relationships in MEDLINE. Based on the bubble-bootstrapping and relation weight computing methods, we have developed a prototype system called MeDisco/3S, which has name entity and relation extraction, and online analytical processing (OLAP) capabilities, to perform the integrative mining process. We have got about 200,000 syndrome-gene relations, which could help generate syndrome-based gene networks, and help analyze the functional knowledge of genes from syndrome perspective. We take the gene network of Kidney-Yang Deficiency syndrome (KYD syndrome) and the functional analysis of some genes, such as CRH (corticotropin releasing hormone), PTH (parathyroid hormone), PRL (prolactin), BRCA1 (breast cancer 1, early onset) and BRCA2 (breast cancer 2, early onset), to demonstrate the preliminary results. The underlying hypothesis is that the related genes of the same syndrome will have some biological functional relationships, and will constitute a functional network. This paper presents

Green function iterative solution of ground state wave function for Yukawa potential

International Nuclear Information System (INIS)

Zhang Zhao

2003-01-01

The newly developed single trajectory quadrature method is applied to solve central potentials. First, based on the series expansion method an exact analytic solution of the ground state for Hulthen potential and an approximate solution for Yukawa potential are obtained respectively. Second, the newly developed iterative method based on Green function defined by quadratures along the single trajectory is applied to solve Yukawa potential using the Coulomb solution and Hulthen solution as the trial functions respectively. The results show that a more proper choice of the trial function will give a better convergence. To further improve the convergence the iterative method is combined with the variational method to solve the ground state wave function for Yukawa potential, using variational solutions of the Coulomb and Hulthen potentials as the trial functions. The results give much better convergence. Finally, the obtained critical screen coefficient is applied to discuss the dissociate temperature of J/ψ in high temperature QGP

Tensor-optimized antisymmetrized molecular dynamics as a successive variational method in nuclear many-body system

Energy Technology Data Exchange (ETDEWEB)

Myo, Takayuki, E-mail: takayuki.myo@oit.ac.jp [General Education, Faculty of Engineering, Osaka Institute of Technology, Osaka 535-8585 (Japan); Research Center for Nuclear Physics (RCNP), Osaka University, Ibaraki 567-0047 (Japan); Toki, Hiroshi [Research Center for Nuclear Physics (RCNP), Osaka University, Ibaraki 567-0047 (Japan); Ikeda, Kiyomi [RIKEN Nishina Center, Wako, Saitama 351-0198 (Japan); Horiuchi, Hisashi [Research Center for Nuclear Physics (RCNP), Osaka University, Ibaraki 567-0047 (Japan); Suhara, Tadahiro [Matsue College of Technology, Matsue 690-8518 (Japan)

2017-06-10

We study the tensor-optimized antisymmetrized molecular dynamics (TOAMD) as a successive variational method in many-body systems with strong interaction for nuclei. In TOAMD, the correlation functions for the tensor force and the short-range repulsion and their multiples are operated to the AMD state as the variational wave function. The total wave function is expressed as the sum of all the components and the variational space can be increased successively with the multiple correlation functions to achieve convergence. All the necessary matrix elements of many-body operators, consisting of the multiple correlation functions and the Hamiltonian, are expressed analytically using the Gaussian integral formula. In this paper we show the results of TOAMD with up to the double products of the correlation functions for the s-shell nuclei, {sup 3}H and {sup 4}He, using the nucleon–nucleon interaction AV8′. It is found that the energies and Hamiltonian components of two nuclei converge rapidly with respect to the multiple of correlation functions. This result indicates the efficiency of TOAMD for the power series expansion in terms of the tensor and short-range correlation functions.

Schwartz distributions in the Lagrange variational problem

International Nuclear Information System (INIS)

Anton, H.; Bahar, L.Y.

1978-01-01

Schwartz distributions are used to eliminate the necessity of imposing a priori conditions on the class of admissible functions in the Lagrange fixed end-point variational problem. This makes it possible to defer the imposition of conditions on the extremals until such conditions become apparent from physical considerations

From a Nonlinear, Nonconvex Variational Problem to a Linear, Convex Formulation

International Nuclear Information System (INIS)

Egozcue, J.; Meziat, R.; Pedregal, P.

2002-01-01

We propose a general approach to deal with nonlinear, nonconvex variational problems based on a reformulation of the problem resulting in an optimization problem with linear cost functional and convex constraints. As a first step we explicitly explore these ideas to some one-dimensional variational problems and obtain specific conclusions of an analytical and numerical nature

Variation of left heart function and thyroid hormone in cirrhosis

International Nuclear Information System (INIS)

Liu Junchi; Du Sujun; Mao Shaorong; Lu Jun; Tang Xiaoling

1996-01-01

The observation of 52 cases of cirrhosis left heart function indices traced with 113 In m in quiet and motion, and the combining determination of thyroid hormone serum levels with RIA are described. The cirrhosis to the function of liver damage increased, the indices of left heart function has great change. Moreover, the serum levels of T 3 , FT 3 in thyroid hormone are decreased obviously and the serum level of rT 3 is also increased significantly

Peripheral lipopolysaccharide administration transiently affects expression of brain-derived neurotrophic factor, corticotropin and proopiomelanocortin in mouse brain.

Science.gov (United States)

Schnydrig, Sabine; Korner, Lukas; Landweer, Svenja; Ernst, Beat; Walker, Gaby; Otten, Uwe; Kunz, Dieter

2007-12-11

Peripheral inflammation induced by intraperitoneal (i.p.) injection of Lipopolysaccharide (LPS) is known to cause functional impairments in the brain affecting memory and learning. One of mechanisms may be the interference with neurotrophin (NT) expression and function. In the current study we administered a single, high dose of LPS (3mg/kg, i.p.) into mice and investigated changes in brain-derived neurotrophic factor (BDNF) gene expression within 1-6 days after LPS injection. Crude synaptosomes were isolated from brain tissue and subjected to Western-blot analyses. We found transient reductions in synaptosomal proBDNF- and BDNF protein expression, with a maximal decrease at day 3 as compared to saline injected controls. The time course of reduction of BDNF mRNA in whole brain extracts parallels the decrease in protein levels in synaptosomes. LPS effects in the central nervous system (CNS) are known to crucially involve the activation of the hypothalamic-pituitary-adrenal (HPA) axis. We analysed the time course of corticotropin releasing hormone (CRH)- and proopiomelanocortin (POMC) mRNA expression. As observed for BDNF-, CRH- and POMC mRNA levels are also significantly reduced on day 3 indicating a comparable time course. These results suggest that peripheral inflammation causes a reduction of trophic supply in the brain, including BDNF at synaptic sites. The mechanisms involved could be a negative feedback of the activated HPA axis.

Dynamics of nonholonomic systems from variational principles embedded variation identity

International Nuclear Information System (INIS)

Guo Yongxin; Liu Shixing; Liu Chang; Chang Peng

2009-01-01

Nondeterminacy of dynamics, i.e., the nonholonomic or the vakonomic, fundamental variational principles, e.g., the Lagrange-d'Alembert or Hamiltonian, and variational operators, etc., of nonholonomic mechanical systems can be attributed to the non-uniqueness of ways how to realize nonholonomic constraints. Making use of a variation identity of nonholonomic constraints embedded into the Hamilton's principle with the method of Lagrange undetermined multipliers, three kinds of dynamics for the nonholonomic systems including the vakonomic and nonholonomic ones and a new one are obtained if the variation is respectively reduced to three conditional variations: vakonomic variation, Hoelder's variation and Suslov's variation, defined by the identity. Therefore, different dynamics of nonholonomic systems can be derived from an integral variational principle, utilizing one way of embedding constraints into the principle, with different variations. It is verified that the similar embedding of the identity into the Lagrange-d'Alembert principle gives rise to the nonholonomic dynamics but fails to give the vakonomic one unless the constraints are integrable.

Multiple Functional Variants in cis Modulate PDYN Expression.

Science.gov (United States)

Babbitt, Courtney C; Silverman, Jesse S; Haygood, Ralph; Reininga, Jennifer M; Rockman, Matthew V; Wray, Gregory A

2010-02-01

Understanding genetic variation and its functional consequences within cis-regulatory regions remains an important challenge in human genetics and evolution. Here, we present a fine-scale functional analysis of segregating variation within the cis-regulatory region of prodynorphin, a gene that encodes an endogenous opioid precursor with roles in cognition and disease. In order to characterize the functional consequences of segregating variation in cis in a region under balancing selection in different human populations, we examined associations between specific polymorphisms and gene expression in vivo and in vitro. We identified five polymorphisms within the 5' flanking region that affect transcript abundance: a 68-bp repeat recognized in prior studies, as well as two microsatellites and two single nucleotide polymorphisms not previously implicated as functional variants. The impact of these variants on transcription differs by brain region, sex, and cell type, implying interactions between cis genotype and the differentiated state of cells. The effects of individual variants on expression level are not additive in some combinations, implying epistatic interactions between nearby variants. These data reveal an unexpectedly complex relationship between segregating genetic variation and its expression-trait consequences and highlights the importance of close functional scrutiny of natural genetic variation within even relatively well-studied cis-regulatory regions.

A first course in the calculus of variations

CERN Document Server

Kot, Mark

2014-01-01

This book is intended for a first course in the calculus of variations, at the senior or beginning graduate level. The reader will learn methods for finding functions that maximize or minimize integrals. The text lays out important necessary and sufficient conditions for extrema in historical order, and it illustrates these conditions with numerous worked-out examples from mechanics, optics, geometry, and other fields. The exposition starts with simple integrals containing a single independent variable, a single dependent variable, and a single derivative, subject to weak variations, but stead

Three-dimensional analytical model for the spatial variation of the foreshock electron distribution function: Systematics and comparisons with ISEE observations

International Nuclear Information System (INIS)

Fitzenreiter, R.J.; Scudder, J.D.; Klimas, A.J.

1990-01-01

A model of the gyrophase-averaged electron distribution in the Earth's foreshock consistent with boundary conditions at the bow shock and in the solar wind has been constructed according to the reversible guiding center characteristics and compared with ISEE electron and wave observations. This model demonstrates (1) that the basic features and morphology of beams in the observed and reduced distributions F(υ parallel ) are determined almost exclusively by the solar wind electrons mirrored at the shock's magnetic ramp and are relatively insensitive to the leakage fluxes from the magnetosheath, (2) that the wave particle modifications have been detected by contrasting the reversible model with the direct observations, (3) that the nonmonotonic reduced distributions F(υ parallel ) are rarely the result of a nonmonotonic energy spectra but are rather the result of the transverse velocity space integration necessary to produce F(υ parallel ) from the directly observed electron distribution function f(v), (4) that the time scale for beam resupply to F(υ parallel ) from the dc spatial gradients of the self-consistent reversible distribution function can have a factor of 100 variation across the foreshock, being shortest within a few degrees of the magnetic tangent surface, (5) that the beams predicted by the model have strongly varying and correlated variations of mean energy, thermal spread, and number density with angular departure from the magnetic tangent with the coldest, most tenuous, and lowest mean energy beams suggested to be present deep behind the magnetic tangent (≅5 degree-10 degree), and (6) that the lowest-energy beams have low contrast to the background solar wind distributing and although difficult to detect have beam density and temperature parameters compatible with ω pe growth of electrostatic waves

Variational approach in transport theory

International Nuclear Information System (INIS)

Panta Pazos, R.; Tullio de Vilhena, M.

2004-01-01

In this work we present a variational approach to some methods to solve transport problems of neutral particles. We consider a convex domain X (for example the geometry of a slab, or a convex set in the plane, or a convex bounded set in the space) and we use discrete ordinates quadrature to get a system of differential equations derived from the neutron transport equation. The boundary conditions are vacuum for a subset of the boundary, and of specular reflection for the complementary subset of the boundary. Recently some different approximation methods have been presented to solve these transport problems. We introduce in this work the adjoint equations and the conjugate functions obtained by means of the variational approach. First we consider the general formulation, and then some numerical methods such as spherical harmonics and spectral collocation method. (authors)

Variational approach in transport theory

Energy Technology Data Exchange (ETDEWEB)

Panta Pazos, R. [Nucler Engineering Department, UFRGS, Porto-Alegre (Brazil); Tullio de Vilhena, M. [Institute of Mathematics, UFRGS, Porto-Alegre (Brazil)

2004-07-01

In this work we present a variational approach to some methods to solve transport problems of neutral particles. We consider a convex domain X (for example the geometry of a slab, or a convex set in the plane, or a convex bounded set in the space) and we use discrete ordinates quadrature to get a system of differential equations derived from the neutron transport equation. The boundary conditions are vacuum for a subset of the boundary, and of specular reflection for the complementary subset of the boundary. Recently some different approximation methods have been presented to solve these transport problems. We introduce in this work the adjoint equations and the conjugate functions obtained by means of the variational approach. First we consider the general formulation, and then some numerical methods such as spherical harmonics and spectral collocation method. (authors)

Variational P1 approximations of general-geometry multigroup transport problems

International Nuclear Information System (INIS)

Rulko, R.P.; Tomasevic, D.; Larsen, E.W.

1995-01-01

A variational approximation is developed for general-geometry multigroup transport problems with arbitrary anisotropic scattering. The variational principle is based on a functional that approximates a reaction rate in a subdomain of the system. In principle, approximations that result from this functional ''optimally'' determine such reaction rates. The functional contains an arbitrary parameter α and requires the approximate solutions of a forward and an adjoint transport problem. If the basis functions for the forward and adjoint solutions are chosen to be linear functions of the angular variable Ω, the functional yields the familiar multigroup P 1 equations for all values of α. However, the boundary conditions that result from the functional depend on α. In particular, for problems with vacuum boundaries, one obtains the conventional mixed boundary condition, but with an extrapolation distance that depends continuously on α. The choice α = 0 yields a generalization of boundary conditions derived earlier by Federighi and Pomraning for a more limited class of problems. The choice α = 1 yields a generalization of boundary conditions derived previously by Davis for monoenergetic problems. Other boundary conditions are obtained by choosing different values of α. The authors discuss this indeterminancy of α in conjunction with numerical experiments

Process Variations and Probabilistic Integrated Circuit Design

CERN Document Server

Haase, Joachim

2012-01-01

Uncertainty in key parameters within a chip and between different chips in the deep sub micron era plays a more and more important role. As a result, manufacturing process spreads need to be considered during the design process.  Quantitative methodology is needed to ensure faultless functionality, despite existing process variations within given bounds, during product development.   This book presents the technological, physical, and mathematical fundamentals for a design paradigm shift, from a deterministic process to a probability-orientated design process for microelectronic circuits.  Readers will learn to evaluate the different sources of variations in the design flow in order to establish different design variants, while applying appropriate methods and tools to evaluate and optimize their design.  Trains IC designers to recognize problems caused by parameter variations during manufacturing and to choose the best methods available to mitigate these issues during the design process; Offers both qual...

Flight biomechanics of developmentally-induced size variation in the solitary bee Osmia lignaria

Science.gov (United States)

Body size covaries with morphology, functional performance, and fitness. For insects, variation in adult phenotypies are derived from developmental variation in larval growth and metamorphosis. In this study, we asked how larval growth impacted adult morphology in Osmia lignaria—especially traits th...

On a variational principle for shape optimization and elliptic free boundary problems

Directory of Open Access Journals (Sweden)

Raúl B. González De Paz

2009-02-01

Full Text Available A variational principle for several free boundary value problems using a relaxation approach is presented. The relaxed Energy functional is concave and it is defined on a convex set, so that the minimizing points are characteristic functions of sets. As a consequence of the first order optimality conditions, it is shown that the corresponding sets are domains bounded by free boundaries, so that the equivalence of the solution of the relaxed problem with the solution of several free boundary value problem is proved. Keywords: Calculus of variations, optimization, free boundary problems.

Dynamics of nonholonomic systems from variational principles embedded variation identity

Energy Technology Data Exchange (ETDEWEB)

Guo Yongxin, E-mail: yxguo@lnu.edu.c [College of Physics, Liaoning University, Shenyang 110036 (China); Liu Shixing [College of Physics, Liaoning University, Shenyang 110036 (China); Liu Chang; Chang Peng [Department of Applied Mechanics, Beijing Institute of Technology, Beijing 100081 (China)

2009-10-19

Nondeterminacy of dynamics, i.e., the nonholonomic or the vakonomic, fundamental variational principles, e.g., the Lagrange-d'Alembert or Hamiltonian, and variational operators, etc., of nonholonomic mechanical systems can be attributed to the non-uniqueness of ways how to realize nonholonomic constraints. Making use of a variation identity of nonholonomic constraints embedded into the Hamilton's principle with the method of Lagrange undetermined multipliers, three kinds of dynamics for the nonholonomic systems including the vakonomic and nonholonomic ones and a new one are obtained if the variation is respectively reduced to three conditional variations: vakonomic variation, Hoelder's variation and Suslov's variation, defined by the identity. Therefore, different dynamics of nonholonomic systems can be derived from an integral variational principle, utilizing one way of embedding constraints into the principle, with different variations. It is verified that the similar embedding of the identity into the Lagrange-d'Alembert principle gives rise to the nonholonomic dynamics but fails to give the vakonomic one unless the constraints are integrable.

Methodology for dimensional variation analysis of ITER integrated systems

International Nuclear Information System (INIS)

Fuentes, F. Javier; Trouvé, Vincent; Cordier, Jean-Jacques; Reich, Jens

2016-01-01

Highlights: • Tokamak dimensional management methodology, based on 3D variation analysis, is presented. • Dimensional Variation Model implementation workflow is described. • Methodology phases are described in detail. The application of this methodology to the tolerance analysis of ITER Vacuum Vessel is presented. • Dimensional studies are a valuable tool for the assessment of Tokamak PCR (Project Change Requests), DR (Deviation Requests) and NCR (Non-Conformance Reports). - Abstract: The ITER machine consists of a large number of complex systems highly integrated, with critical functional requirements and reduced design clearances to minimize the impact in cost and performances. Tolerances and assembly accuracies in critical areas could have a serious impact in the final performances, compromising the machine assembly and plasma operation. The management of tolerances allocated to part manufacture and assembly processes, as well as the control of potential deviations and early mitigation of non-compliances with the technical requirements, is a critical activity on the project life cycle. A 3D tolerance simulation analysis of ITER Tokamak machine has been developed based on 3DCS dedicated software. This integrated dimensional variation model is representative of Tokamak manufacturing functional tolerances and assembly processes, predicting accurate values for the amount of variation on critical areas. This paper describes the detailed methodology to implement and update the Tokamak Dimensional Variation Model. The model is managed at system level. The methodology phases are illustrated by its application to the Vacuum Vessel (VV), considering the status of maturity of VV dimensional variation model. The following topics are described in this paper: • Model description and constraints. • Model implementation workflow. • Management of input and output data. • Statistical analysis and risk assessment. The management of the integration studies based on

Methodology for dimensional variation analysis of ITER integrated systems

Energy Technology Data Exchange (ETDEWEB)

Fuentes, F. Javier, E-mail: FranciscoJavier.Fuentes@iter.org [ITER Organization, Route de Vinon-sur-Verdon—CS 90046, 13067 St Paul-lez-Durance (France); Trouvé, Vincent [Assystem Engineering & Operation Services, rue J-M Jacquard CS 60117, 84120 Pertuis (France); Cordier, Jean-Jacques; Reich, Jens [ITER Organization, Route de Vinon-sur-Verdon—CS 90046, 13067 St Paul-lez-Durance (France)

2016-11-01

Highlights: • Tokamak dimensional management methodology, based on 3D variation analysis, is presented. • Dimensional Variation Model implementation workflow is described. • Methodology phases are described in detail. The application of this methodology to the tolerance analysis of ITER Vacuum Vessel is presented. • Dimensional studies are a valuable tool for the assessment of Tokamak PCR (Project Change Requests), DR (Deviation Requests) and NCR (Non-Conformance Reports). - Abstract: The ITER machine consists of a large number of complex systems highly integrated, with critical functional requirements and reduced design clearances to minimize the impact in cost and performances. Tolerances and assembly accuracies in critical areas could have a serious impact in the final performances, compromising the machine assembly and plasma operation. The management of tolerances allocated to part manufacture and assembly processes, as well as the control of potential deviations and early mitigation of non-compliances with the technical requirements, is a critical activity on the project life cycle. A 3D tolerance simulation analysis of ITER Tokamak machine has been developed based on 3DCS dedicated software. This integrated dimensional variation model is representative of Tokamak manufacturing functional tolerances and assembly processes, predicting accurate values for the amount of variation on critical areas. This paper describes the detailed methodology to implement and update the Tokamak Dimensional Variation Model. The model is managed at system level. The methodology phases are illustrated by its application to the Vacuum Vessel (VV), considering the status of maturity of VV dimensional variation model. The following topics are described in this paper: • Model description and constraints. • Model implementation workflow. • Management of input and output data. • Statistical analysis and risk assessment. The management of the integration studies based on

The uniqueness of the solution for the definite problem of a parabolic variational inequality

Directory of Open Access Journals (Sweden)

Liping Song

2016-12-01

Full Text Available Abstract The uniqueness of the solution for the definite problem of a parabolic variational inequality is proved. The problem comes from the study of the optimal exercise strategies for the perpetual executive stock options with unrestricted exercise in financial market. Because the variational inequality is degenerate and the obstacle condition contains the partial derivative of an unknown function, it makes the theoretical study of the definite problem of the variational inequality problem very difficult. Firstly, the property which the value function satisfies is derived by applying the Jensen inequality. Then the uniqueness of the solution is proved by using this property and maximum principles.

Sequence variation of functional HTLV-II tax alleles among isolates from an endemic population: lack of evidence for oncogenic determinant in tax.

Science.gov (United States)

Hjelle, B; Chaney, R

1992-02-01

Human T-cell leukemia-lymphoma virus type II (HTLV-II) has been isolated from patients with hairy cell leukemia (HCL). We previously described a population with longstanding endemic HTLV-II infection, and showed that there is no increased risk for HCL in the affected groups. We thus have direct evidence that the endemic form(s) of HTLV-II cause HCL infrequently, if at all. By comparison, there is reason to suspect that the viruses isolated from patients with HCL had an etiologic role in the disease in those patients. One way to reconcile these conflicting observations is to consider that isolates of HTLV-II might differ in oncogenic potential. To determine whether the structure of the putative oncogenic determinant of HTLV-II, tax2, might differ in the new isolates compared to the tax of the prototype HCL isolate, MO, four new functional tax cDNAs were cloned from new isolates. Sequence analysis showed only minor (0.9-2.0%) amino acid variation compared to the published sequence of MO tax2. Some codons were consistently different from published sequences of the MO virus, but in most cases, such variations were also found in each of two tax2 clones we isolated from the MO T-cell line. These variations rendered the new clones more similar to the tax1 of the pathogenic virus HTLV-I. Thus we find no evidence that pathologic determinants of HTLV-II can be assigned to the tax gene.

Patterns of variation across primates in jaw-muscle electromyography during mastication.

Science.gov (United States)

Vinyard, Christopher J; Wall, Christine E; Williams, Susan H; Hylander, William L

2008-08-01

Biologists that study mammals continue to discuss the evolution of and functional variation in jaw-muscle activity during chewing. A major barrier to addressing these issues is collecting sufficient in vivo data to adequately capture neuromuscular variation in a clade. We combine data on jaw-muscle electromyography (EMG) collected during mastication from 14 species of primates and one of treeshrews to assess patterns of neuromuscular variation in primates. All data were collected and analyzed using the same methods. We examine the variance components for EMG parameters using a nested ANOVA design across successive hierarchical factors from chewing cycle through species for eight locations in the masseter and temporalis muscles. Variation in jaw-muscle EMGs was not distributed equally across hierarchical levels. The timing of peak EMG activity showed the largest variance components among chewing cycles. Relative levels of recruitment of jaw muscles showed the largest variance components among chewing sequences and cycles. We attribute variation among chewing cycles to (1) changes in food properties throughout the chewing sequence, (2) variation in bite location, and (3) the multiple ways jaw muscles can produce submaximal bite forces. We hypothesize that variation among chewing sequences is primarily related to variation in properties of food. The significant proportion of variation in EMGs potentially linked to food properties suggests that experimental biologists must pay close attention to foods given to research subjects in laboratory-based studies of feeding. The jaw muscles exhibit markedly different variance components among species suggesting that primate jaw muscles have evolved as distinct functional units. The balancing-side deep masseter (BDM) exhibits the most variation among species. This observation supports previous hypotheses linking variation in the timing and activation of the BDM to symphyseal fusion in anthropoid primates and in strepsirrhines

A primer on the calculus of variations and optimal control theory

CERN Document Server

Mesterton-Gibbons, Mike

2009-01-01

The calculus of variations is used to find functions that optimize quantities expressed in terms of integrals. Optimal control theory seeks to find functions that minimize cost integrals for systems described by differential equations. This book is an introduction to both the classical theory of the calculus of variations and the more modern developments of optimal control theory from the perspective of an applied mathematician. It focuses on understanding concepts and how to apply them. The range of potential applications is broad: the calculus of variations and optimal control theory have been widely used in numerous ways in biology, criminology, economics, engineering, finance, management science, and physics. Applications described in this book include cancer chemotherapy, navigational control, and renewable resource harvesting. The prerequisites for the book are modest: the standard calculus sequence, a first course on ordinary differential equations, and some facility with the use of mathematical softwa...

Regularization in global sound equalization based on effort variation

DEFF Research Database (Denmark)

Stefanakis, Nick; Sarris, John; Jacobsen, Finn

2009-01-01

. Effort variation equalization involves modifying the conventional cost function in sound equalization, which is based on minimizing least-squares reproduction errors, by adding a term that is proportional to the squared deviations between complex source strengths, calculated independently for the sources......Sound equalization in closed spaces can be significantly improved by generating propagating waves that are naturally associated with the geometry, as, for example, plane waves in rectangular enclosures. This paper presents a control approach termed effort variation regularization based on this idea...

Ecological and evolutionary consequences of tri-trophic interactions: Spatial variation and effects of plant density.

Science.gov (United States)

Abdala-Roberts, Luis; Parra-Tabla, Víctor; Moreira, Xoaquín; Ramos-Zapata, José

2017-02-01

The factors driving variation in species interactions are often unknown, and few studies have made a link between changes in interactions and the strength of selection. We report on spatial variation in functional responses by a seed predator (SP) and its parasitic wasps associated with the herb Ruellia nudiflora . We assessed the influence of plant density on consumer responses and determined whether density effects and spatial variation in functional responses altered natural selection by these consumers on the plant. We established common gardens at two sites in Yucatan, Mexico, and planted R. nudiflora at two densities in each garden. We recorded fruit output and SP and parasitoid attack; calculated relative fitness (seed number) under scenarios of three trophic levels (accounting for SP and parasitoid effects), two trophic levels (accounting for SP but not parasitoid effects), and one trophic level (no consumer effects); and compared selection strength on fruit number under these scenarios across sites and densities. There was spatial variation in SP recruitment, whereby the SP functional response was negatively density-dependent at one site but density-independent at the other; parasitoid responses were density-independent and invariant across sites. Site variation in SP attack led, in turn, to differences in SP selection on fruit output, and parasitoids did not alter SP selection. There were no significant effects of density at either site. Our results provide a link between consumer functional responses and consumer selection on plants, which deepens our understanding of geographic variation in the evolutionary outcomes of multitrophic interactions. © 2017 Botanical Society of America.

Efficient algorithm for bifurcation problems of variational inequalities

International Nuclear Information System (INIS)

Mittelmann, H.D.

1983-01-01

For a class of variational inequalities on a Hilbert space H bifurcating solutions exist and may be characterized as critical points of a functional with respect to the intersection of the level surfaces of another functional and a closed convex subset K of H. In a recent paper [13] we have used a gradient-projection type algorithm to obtain the solutions for discretizations of the variational inequalities. A related but Newton-based method is given here. Global and asymptotically quadratic convergence is proved. Numerical results show that it may be used very efficiently in following the bifurcating branches and that is compares favorably with several other algorithms. The method is also attractive for a class of nonlinear eigenvalue problems (K = H) for which it reduces to a generalized Rayleigh-quotient interaction. So some results are included for the path following in turning-point problems

Convex Minimization with Constraints of Systems of Variational Inequalities, Mixed Equilibrium, Variational Inequality, and Fixed Point Problems

Directory of Open Access Journals (Sweden)

Lu-Chuan Ceng

2014-01-01

Full Text Available We introduce and analyze one iterative algorithm by hybrid shrinking projection method for finding a solution of the minimization problem for a convex and continuously Fréchet differentiable functional, with constraints of several problems: finitely many generalized mixed equilibrium problems, finitely many variational inequalities, the general system of variational inequalities and the fixed point problem of an asymptotically strict pseudocontractive mapping in the intermediate sense in a real Hilbert space. We prove strong convergence theorem for the iterative algorithm under suitable conditions. On the other hand, we also propose another iterative algorithm by hybrid shrinking projection method for finding a fixed point of infinitely many nonexpansive mappings with the same constraints, and derive its strong convergence under mild assumptions.

The effect of water vapor on the corrosion of carbon steel at 65 degree C

International Nuclear Information System (INIS)

Gdowski, G.E.; Estill, J.C.

1995-01-01

AISI 1020 carbon steel was exposed to air at various relative humidities at 65 degrees C. A ''critical relative humidity'' (CRH) of 75--85% was determined. The CRH is the transitional relative humidity where oxidation/corrosion changes from dry oxidation to aqueous film electrochemical corrosion. Short term testing suggests that aqueous film electrochemical corrosion results in the formation of an inner oxide of Fe 3 O 4 , and an outer oxide of a powdery Fe 2 O 3 and/or Fe 2 O 3 ·xH 2 O

Insulin signaling and dietary restriction differentially influence the decline of learning and memory with age.

Directory of Open Access Journals (Sweden)

Amanda L Kauffman

2010-05-01

Full Text Available Of all the age-related declines, memory loss is one of the most devastating. While conditions that increase longevity have been identified, the effects of these longevity-promoting factors on learning and memory are unknown. Here we show that the C. elegans Insulin/IGF-1 receptor mutant daf-2 improves memory performance early in adulthood and maintains learning ability better with age but, surprisingly, demonstrates no extension in long-term memory with age. By contrast, eat-2 mutants, a model of Dietary Restriction (DR, exhibit impaired long-term memory in young adulthood but maintain this level of memory longer with age. We find that crh-1, the C. elegans homolog of the CREB transcription factor, is required for long-term associative memory, but not for learning or short-term memory. The expression of crh-1 declines with age and differs in the longevity mutants, and CREB expression and activity correlate with memory performance. Our results suggest that specific longevity treatments have acute and long-term effects on cognitive functions that decline with age through their regulation of rate-limiting genes required for learning and memory.

Neofunctionalization of duplicated Tic40 genes caused a gain-of-function variation related to male fertility in Brassica oleracea lineages.

Science.gov (United States)

Dun, Xiaoling; Shen, Wenhao; Hu, Kaining; Zhou, Zhengfu; Xia, Shengqian; Wen, Jing; Yi, Bin; Shen, Jinxiong; Ma, Chaozhi; Tu, Jinxing; Fu, Tingdong; Lagercrantz, Ulf

2014-11-01

Gene duplication followed by functional divergence in the event of polyploidization is a major contributor to evolutionary novelties. The Brassica genus evolved from a common ancestor after whole-genome triplication. Here, we studied the evolutionary and functional features of Brassica spp. homologs to Tic40 (for translocon at the inner membrane of chloroplasts with 40 kDa). Four Tic40 loci were identified in allotetraploid Brassica napus and two loci in each of three basic diploid Brassica spp. Although these Tic40 homologs share high sequence identities and similar expression patterns, they exhibit altered functional features. Complementation assays conducted on Arabidopsis thaliana tic40 and the B. napus male-sterile line 7365A suggested that all Brassica spp. Tic40 homologs retain an ancestral function similar to that of AtTic40, whereas BolC9.Tic40 in Brassica oleracea and its ortholog in B. napus, BnaC9.Tic40, in addition, evolved a novel function that can rescue the fertility of 7365A. A homologous chromosomal rearrangement placed bnac9.tic40 originating from the A genome (BraA10.Tic40) as an allele of BnaC9.Tic40 in the C genome, resulting in phenotypic variation for male sterility in the B. napus near-isogenic two-type line 7365AB. Assessment of the complementation activity of chimeric B. napus Tic40 domain-swapping constructs in 7365A suggested that amino acid replacements in the carboxyl terminus of BnaC9.Tic40 cause this functional divergence. The distribution of these amino acid replacements in 59 diverse Brassica spp. accessions demonstrated that the neofunctionalization of Tic40 is restricted to B. oleracea and its derivatives and thus occurred after the divergence of the Brassica spp. A, B, and C genomes. © 2014 American Society of Plant Biologists. All Rights Reserved.

Sensitivity analysis with respect to observations in variational data assimilation for parameter estimation

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V. Shutyaev

2018-06-01

Full Text Available The problem of variational data assimilation for a nonlinear evolution model is formulated as an optimal control problem to find unknown parameters of the model. The observation data, and hence the optimal solution, may contain uncertainties. A response function is considered as a functional of the optimal solution after assimilation. Based on the second-order adjoint techniques, the sensitivity of the response function to the observation data is studied. The gradient of the response function is related to the solution of a nonstandard problem involving the coupled system of direct and adjoint equations. The nonstandard problem is studied, based on the Hessian of the original cost function. An algorithm to compute the gradient of the response function with respect to observations is presented. A numerical example is given for the variational data assimilation problem related to sea surface temperature for the Baltic Sea thermodynamics model.

Uniqueness theorems for variational problems by the method of transformation groups

CERN Document Server

Reichel, Wolfgang

2004-01-01

A classical problem in the calculus of variations is the investigation of critical points of functionals {\\cal L} on normed spaces V. The present work addresses the question: Under what conditions on the functional {\\cal L} and the underlying space V does {\\cal L} have at most one critical point? A sufficient condition for uniqueness is given: the presence of a "variational sub-symmetry", i.e., a one-parameter group G of transformations of V, which strictly reduces the values of {\\cal L}. The "method of transformation groups" is applied to second-order elliptic boundary value problems on Riemannian manifolds. Further applications include problems of geometric analysis and elasticity.

Calculus of variations

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