The N-terminal neurotensin fragment, NT1-11, inhibits cortisol secretion by human adrenocortical cells.

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Sicard, Flavie; Contesse, Vincent; Lefebvre, Hervé; Ait-Ali, Djida; Gras, Marjorie; Cartier, Dorthe; Decker, Annick; Chartrel, Nicolas; Anouar, Youssef; Vaudry, Hubert; Delarue, Catherine

2006-08-01

Neurotensin (NT) modulates corticosteroid secretion from the mammalian adrenal gland. The objective of this study was to investigate the possible involvement of NT in the control of cortisol secretion in the human adrenal gland. In vitro studies were conducted on cultured human adrenocortical cells. This study was conducted in a university research laboratory. Adrenal explants from patients undergoing expanded nephrectomy for kidney cancer were studied. Cortisol secretion from cultured adrenocortical cells was measured. NT1-11, the N-terminal fragment of NT, dose-dependently inhibited basal and ACTH-stimulated cortisol production by human adrenocortical cells in primary culture. In contrast, NT had no influence on cortisol output at concentrations up to 10(-6) m. HPLC and RT-PCR analyses failed to detect any significant amounts of NT and NT mRNA, respectively, in adrenal extracts. Molecular and pharmacological studies were performed to determine the type of NT receptor involved in the corticostatic effect of NT1-11. RT-PCR analysis revealed the expression of NT receptor type (NTR) 3 mRNA but not NTR1 and NTR2 mRNAs in the human adrenal tissue. However, the pharmacological profile of the adrenal NT1-11 receptor was different from that of NTR3, indicating that this receptor type is not involved in the action of NT1-11 on corticosteroidogenesis. Our results indicate that NT1-11 may act as an endocrine factor to inhibit cortisol secretion through activation of a receptor distinct from the classical NTR1, NTR2, and NTR3.

Troponin T and NT ProBNP Levels in Gestational, Type 1 and Type 2 Diabetic Mothers and Macrosomic Infants.

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Mert, Mustafa Kurthan; Satar, Mehmet; Özbarlas, Nazan; Yaman, Akgün; Özgünen, Fatma Tuncay; Asker, Hüseyin Selim; Çekinmez, Eren Kale; Tetiker, Tamer

2016-01-01

This study compares NT proBNP and troponin T levels in umbilical cord arterial blood and postnatal echocardiographic findings for infants of gestational and pregestational diabetic mothers and macrosomic infants. Twenty-seven infants of pregestational diabetic mothers, 61 infants of gestational diabetic mothers and 37 macrosomic infants of nondiabetic mothers were prospectively enrolled in this study along with a control group of 58 healthy infants of mothers without any pregestational or gestational disorders as the control group. All enrollees were born after 34 weeks of gestation. For this study, umbilical cord blood was drawn during delivery to determine NT proBNP and troponin T levels. Echocardiography was performed 24-72 h after the delivery. Umbilical cord troponin T and NT proBNP levels were found to be higher in the diabetic and macrosomic groups than in the control group (all of them p gestational infants of diabetic mothers groups (r = 0.564 and r = 0.560, respectively, p gestational diabetic mothers were divided into two groups according to HbA1c levels in the third trimester as good (6.1 %) metabolic control. In the good and suboptimal metabolic control diabetic groups, NT proBNP levels were also positively correlated with interventricular septum thickness (r = 0.536 and r = 0.576, respectively, p mothers and the control group, the myocardial performance index of macrosomic infants was lower than that of the control group (p = 0.017). Cardiac biomarkers (NT proBNP and troponin T) were elevated in infants of diabetic mothers and macrosomic infants. While there was a positive correlation between NT proBNP levels and cardiac structure in infants of pregestational and gestational diabetic mothers, there was no relationship between NT proBNP levels and cardiac function.

Níveis NT-Pro-BNP e resposta ao exercício em pacientes com fluxo lento coronariano NT-Pro-BNP levels and their response to exercise in patients with slow coronary flow

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Mustafa Yurtdaş

2012-12-01

patients with angina was higher than those without angina (76.8 ± 17.8 pg/mL vs. 63.8±17.5 pg/mL p=0.041. NT-Pro-BNP concentration in 11 patients with ST depression was also higher than those without ST depression (82.4 ± 17.3 pg/mL vs. 63.3 ± 16.1 pg/mL p=0.004. Median post-exercise increases in NT-Pro-BNP (Δ NT-Pro-BNP were higher in the SCF group than in the control group (Δ NT-Pro-BNP: 19.8±7.7 pg/mL vs. 5.7±4.5 pg/mL p<0.0001. CONCLUSION: The results of this study suggest that there may be an important pathophysiologic link between the severity of SCF (microvascular or epicardial coronary artery dysfunction and the level of circulating NT-Pro-BNP in SCF patients.

Níveis NT-Pro-BNP e resposta ao exercício em pacientes com fluxo lento coronariano NT-Pro-BNP levels and their response to exercise in patients with slow coronary flow

Directory of Open Access Journals (Sweden)

Mustafa Yurtdaş

2012-01-01

patients with angina was higher than those without angina (76.8 ± 17.8 pg/mL vs. 63.8±17.5 pg/mL p=0.041. NT-Pro-BNP concentration in 11 patients with ST depression was also higher than those without ST depression (82.4 ± 17.3 pg/mL vs. 63.3 ± 16.1 pg/mL p=0.004. Median post-exercise increases in NT-Pro-BNP (Δ NT-Pro-BNP were higher in the SCF group than in the control group (Δ NT-Pro-BNP: 19.8±7.7 pg/mL vs. 5.7±4.5 pg/mL p<0.0001. CONCLUSION: The results of this study suggest that there may be an important pathophysiologic link between the severity of SCF (microvascular or epicardial coronary artery dysfunction and the level of circulating NT-Pro-BNP in SCF patients.

Clinical Significance of Determination of the Serum Levels of NT-proBNP and hs-CRP in Patients with Acute Coronary Syndrome

International Nuclear Information System (INIS)

Zheng Zhaojun; Zheng Jing; Sun Weili; Yuan Yuan; Tao Jian; Li Weipeng

2010-01-01

To explore the clinical significance the serum levels of N-Terminal proB-Type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) in patients with acute coronary syndrome,the serum levels of NT-proBNP and hs-CRP in patients and normal controls were determined by ECi Immunity Analyzer and radioimmunoassay respectively. The results showed that the serum levels of NT-proBNP and hs-CRP in patients with acute coronary syndrome were significantly higher than that of controls (P<0.05). The diagnostic specificity for acute coronary syndrome was 100% by combined detection of NT-proBNP and hs-CRP. The results suggest that the combined detection of serum NT-proBNP and hs-CRP levels are very important to evaluate heart function in patients with acute coronary syndrome. (authors)

Elevated neurotrophin-3 and neurotrophin 4/5 levels in unmedicated bipolar depression and the effects of lithium.

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Loch, Alexandre A; Zanetti, Marcus V; de Sousa, Rafael T; Chaim, Tiffany M; Serpa, Mauricio H; Gattaz, Wagner F; Teixeira, Antonio L; Machado-Vieira, Rodrigo

2015-01-02

Bipolar disorder (BD) has been associated with diverse abnormalities in neural plasticity and cellular resilience. Neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) support synaptic neuronal survival and differentiation. NT-3 and NT-4/5 levels were found to be altered in BD, potentially representing a physiological response against cellular stress. However, the use of psychopharmacological agents and heterogeneous mood states may constitute important biases in such studies. Thus, we aimed to assess NT-3 and NT-4/5 levels in medication-free BD type I or II individuals in a current depressive episode, before and after 6 weeks of lithium monotherapy and matched with healthy controls. Twenty-three patients with BD type I or II during a depressive episode and 28 healthy controls were studied. Patients were required to have a 21-item Hamilton Depression Rating Scale score ≥18 and had not undergone any psychopharmacological treatment for at least 6 weeks prior to study entry. Patients were treated with lithium for 6 weeks and plasma NT-3 and NT-4/5 levels were determined at baseline and endpoint using ELISA method. Baseline plasma levels of both NT-3 and NT-4/5 were significantly increased in acutely depressed BD subjects in comparison to healthy controls (p=0.040 and 0.039, respectively). The NT-3 and NT-4/5 levels did not significantly change after lithium treatment. NT-3 and NT-4/5 levels were positively correlated to illness duration in BD (p=0.032 and 0.034, respectively). Our findings suggest that NT-3 and NT-4/5 levels are increased in the depressive phase of BD, which seems directly associated with illness duration. The increased levels of NT-3 and NT-4/5 may underlie a biological response to cellular stress associated with the course of BD. Copyright © 2014 Elsevier Inc. All rights reserved.

NT2 derived neuronal and astrocytic network signalling.

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Eric J Hill

Full Text Available A major focus of stem cell research is the generation of neurons that may then be implanted to treat neurodegenerative diseases. However, a picture is emerging where astrocytes are partners to neurons in sustaining and modulating brain function. We therefore investigated the functional properties of NT2 derived astrocytes and neurons using electrophysiological and calcium imaging approaches. NT2 neurons (NT2Ns expressed sodium dependent action potentials, as well as responses to depolarisation and the neurotransmitter glutamate. NT2Ns exhibited spontaneous and coordinated calcium elevations in clusters and in extended processes, indicating local and long distance signalling. Tetrodotoxin sensitive network activity could also be evoked by electrical stimulation. Similarly, NT2 astrocytes (NT2As exhibited morphology and functional properties consistent with this glial cell type. NT2As responded to neuronal activity and to exogenously applied neurotransmitters with calcium elevations, and in contrast to neurons, also exhibited spontaneous rhythmic calcium oscillations. NT2As also generated propagating calcium waves that were gap junction and purinergic signalling dependent. Our results show that NT2 derived astrocytes exhibit appropriate functionality and that NT2N networks interact with NT2A networks in co-culture. These findings underline the utility of such cultures to investigate human brain cell type signalling under controlled conditions. Furthermore, since stem cell derived neuron function and survival is of great importance therapeutically, our findings suggest that the presence of complementary astrocytes may be valuable in supporting stem cell derived neuronal networks. Indeed, this also supports the intriguing possibility of selective therapeutic replacement of astrocytes in diseases where these cells are either lost or lose functionality.

Best management practices and work plan for installation of and monitoring at temporary weirs and flumes at NT-3, NT-4, and NT-5 Oak Ridge Y-12 Plant, Oak Ridge, Tennessee

International Nuclear Information System (INIS)

1998-02-01

This Best Management Practices (BMP) and Work Plan has been developed in order to maintain compliance with applicable regulatory requirements by documenting the practices that are required during the installation and maintenance of temporary weirs and flumes at the NT-3, NT-4, and NT-5 tributaries, subsequent collection of water discharge data, and removal of the weirs and flumes. The practices included in this BMP comply with the Clean Water Act and the intent of Sect. 70-8-104(b) of the Tennessee Code Annotated: Tennessee Wildlife Resources Commission Proclamation 94-16 to prevent the destruction of the habitat of state-listed wildlife species that are designated as open-quotes in need of management.close quotes

Rise and fall of NT-proBNP in aortic valve intervention.

Science.gov (United States)

Hultkvist, Henrik; Holm, Jonas; Svedjeholm, Rolf; Vánky, Farkas

2018-01-01

To describe the dynamics of N-terminal pro-B-type natriuretic peptide (NT-proBNP) from preoperative evaluation to 6-month follow-up in patients undergoing aortic valve intervention, and to evaluate NT-proBNP with regard to 1-year mortality. At preoperative evaluation, we prospectively included 462 patients accepted for aortic valve intervention. The median time to surgical aortic valve replacement (SAVR; n=336) or transcatheter aortic valve implantation (TAVI; n=126) was 4 months. NT-proBNP was measured at enrolment for preoperative evaluation, on the day of surgery, postoperatively on day 1, day 3 and at the 6-month follow-up. Subgroups of patients undergoing SAVR with aortic regurgitation and aortic stenosis with and without coronary artery bypass were also analysed. NT-proBNP remained stable in all subgroups during the preoperative waiting period, but displayed a substantial transient early postoperative increase with a peak on day 3 except in the TAVI group, which peaked on day 1. At the 6-month follow-up, NT-proBNP had decreased to or below the preoperative level in all groups. In the SAVR group, NT-proBNP preoperatively and on postoperative days 1 and 3 revealed significant discriminatory power with regard to 1-year mortality (area under the curve (AUC)=0.79, P=0.0001; AUC=0.71, P=0.03; and AUC=0.79, P=0.002, respectively). This was not found in the TAVI group, which had higher levels of NT-proBNP both preoperatively and at the 6-month follow-up compared with the SAVR group. The dynamic profile of NT-proBNP differed between patients undergoing TAVI and SAVR. NT-proBNP in the perioperative course was associated with increased risk of 1-year mortality in SAVR but not in TAVI.

NT-proBNP, Cardiometabolic Risk Factors, and Nutritional Status in Hemodialysis Patients

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Jacques Ducros

2017-01-01

Full Text Available Background. We aimed to evaluate the association between NT-proBNP and malnutrition in HD patients while taking into account the four established categories of parameters for diagnosis of protein energy wasting (PEW. Methods. A cross-sectional study was performed in Afro-Caribbean dialysis patients. One component in each of the 4 categories for the wasting syndrome was retained: serum albumin ≤ 38 g/L, BMI ≤ 23 Kg/m2, serum creatinine ≤ 818 µmol/L, and normalized protein catabolic rate (nPCR ≤ 0.8 g/kg/day. NT-proBNP was assessed using a chemiluminescence immunoassay. Two multivariate logistic regression models were performed to determine the parameters associated with high NT-proBNP concentrations. Results. In 207 HD patients, 16.9% had PEW (at least three components. LVEF lower than 60% was found in 13.8% of patients. NT-proBNP levels ranged from 125 to 33144 pg/mL. In model 1, high levels of NT-proBNP (≥6243 pg/mL were independently associated with PEW OR 14.2 (3.25–62.4, male gender 2.80 (1.22–6.57, hsCRP > 5 mg/L 3.90 (1.77–8.57, and dialysis vintage > 3 years 3.84 (1.35–10.8. In model 2, LVEF OR was 0.93 (0.88–0.98. NT-proBNP concentrations were significantly higher when the PEW component number was higher. Conclusion. In dialysis patients, high NT-proBNP levels must draw attention to cardiac function but also to nutritional status.

Identification of fibroblast growth factor receptor 3 (FGFR3 as a protein receptor for botulinum neurotoxin serotype A (BoNT/A.

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Birgitte P S Jacky

Full Text Available Botulinum neurotoxin serotype A (BoNT/A causes transient muscle paralysis by entering motor nerve terminals (MNTs where it cleaves the SNARE protein Synaptosomal-associated protein 25 (SNAP25206 to yield SNAP25197. Cleavage of SNAP25 results in blockage of synaptic vesicle fusion and inhibition of the release of acetylcholine. The specific uptake of BoNT/A into pre-synaptic nerve terminals is a tightly controlled multistep process, involving a combination of high and low affinity receptors. Interestingly, the C-terminal binding domain region of BoNT/A, HC/A, is homologous to fibroblast growth factors (FGFs, making it a possible ligand for Fibroblast Growth Factor Receptors (FGFRs. Here we present data supporting the identification of Fibroblast Growth Factor Receptor 3 (FGFR3 as a high affinity receptor for BoNT/A in neuronal cells. HC/A binds with high affinity to the two extra-cellular loops of FGFR3 and acts similar to an agonist ligand for FGFR3, resulting in phosphorylation of the receptor. Native ligands for FGFR3; FGF1, FGF2, and FGF9 compete for binding to FGFR3 and block BoNT/A cellular uptake. These findings show that FGFR3 plays a pivotal role in the specific uptake of BoNT/A across the cell membrane being part of a larger receptor complex involving ganglioside- and protein-protein interactions.

Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) levels in post-mortem brain tissue from patients with depression compared to healthy individuals 

DEFF Research Database (Denmark)

Sheldrick, A; Camara, S; Ilieva, M

2017-01-01

The neurotrophic factors (NTF) hypothesis of depression was postulated nearly a decade ago and is nowadays widely acknowledged. Previous reports suggest that cerebral concentrations of NTF may be reduced in suicide victims who received minimal or no antidepressant pharmacotherapy. Recent evidence...... and nucleus caudatus) of 21 individuals - 7 patients of which 4 patients with major depressive disorder (MDD) and overall age 86.8±5 years who received antidepressant pharmacotherapy (selective serotonin re-uptake inhibitors [SSRI]; tricyclic antidepressants [TCA]), 3 patients with MDD without antidepressant...... medication compared to MDD untreated patients and controls. Moreover, we detected a significant decrease of NT3 levels in the parietal cortex of patients suffering from MDD non-treated patients without treatment compared to healthy individuals. Although the limited statistical power due to the small sample...

Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) levels in post-mortem brain tissue from patients with depression compared to healthy individuals - a proof of concept study.

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Sheldrick, A; Camara, S; Ilieva, M; Riederer, P; Michel, T M

2017-10-01

The neurotrophic factors (NTF) hypothesis of depression was postulated nearly a decade ago and is nowadays widely acknowledged. Previous reports suggest that cerebral concentrations of NTF may be reduced in suicide victims who received minimal or no antidepressant pharmacotherapy. Recent evidence suggests that antidepressant treatment may improve or normalise cerebral concentrations of neurotrophic factors. Therefore, we examined the concentration of brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) in different brain regions (cortex, cingulate gyrus, thalamus, hippocampus, putamen and nucleus caudatus) of 21 individuals - 7 patients of which 4 patients with major depressive disorder (MDD) and overall age 86.8±5 years who received antidepressant pharmacotherapy (selective serotonin re-uptake inhibitors [SSRI]; tricyclic antidepressants [TCA]), 3 patients with MDD without antidepressant treatment and overall age 84.3±5 years versus 14 unaffected subjects at age 70.3±13.8. We detected significant elevation of BDNF (parietal cortex) and NT3 (parietal, temporal and occipital cortex, cingulate gyrus, thalamus, putamen and nucleus caudatus regions) in MDD patients who received antidepressant medication compared to MDD untreated patients and controls. Moreover, we detected a significant decrease of NT3 levels in the parietal cortex of patients suffering from MDD non-treated patients without treatment compared to healthy individuals. Although the limited statistical power due to the small sample size in this proof of concept study corroborates data from previous studies, which show that treatment with antidepressants mediates alterations in neuroplasticity via the action of NTF. However, more research using post-mortem brain tissue with larger samples needs to be carried out as well as longitudinal studies to further verify these results. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

NT-proBNP and troponin T levels differ after haemodialysis with a low versus high flux membrane

OpenAIRE

Laveborn, Emilie; Lindmark, Krister; Skagerlind, Malin; Stegmayr, Bernd

2015-01-01

BACKGROUND: Brain natriuretic peptide (BNP), N-terminal-proBNP (NT-proBNP), and high sensitive cardiac troponin T (TnT) are markers that are elevated in chronic kidney disease and correlate with increased risk of mortality. Data are conflicting on the effect of biomarker levels by hemodialysis (HD).Our aim was to clarify to what extent HD with low-flux (LF) versus high-flux (HF) membranes affects the plasma levels of BNP, NT-proBNP, and TnT. METHODS AND MATERIALS: 31 HD patients were included...

Comparing 2-nt 3' overhangs against blunt-ended siRNAs: a systems biology based study.

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Ghosh, Preetam; Dullea, Robert; Fischer, James E; Turi, Tom G; Sarver, Ronald W; Zhang, Chaoyang; Basu, Kalyan; Das, Sajal K; Poland, Bradley W

2009-07-07

In this study, we formulate a computational reaction model following a chemical kinetic theory approach to predict the binding rate constant for the siRNA-RISC complex formation reaction. The model allowed us to study the potency difference between 2-nt 3' overhangs against blunt-ended siRNA molecules in an RNA interference (RNAi) system. The rate constant predicted by this model was fed into a stochastic simulation of the RNAi system (using the Gillespie stochastic simulator) to study the overall potency effect. We observed that the stochasticity in the transcription/translation machinery has no observable effects in the RNAi pathway. Sustained gene silencing using siRNAs can be achieved only if there is a way to replenish the dsRNA molecules in the cell. Initial findings show about 1.5 times more blunt-ended molecules will be required to keep the mRNA at the same reduced level compared to the 2-nt overhang siRNAs. However, the mRNA levels jump back to saturation after a longer time when blunt-ended siRNAs are used. We found that the siRNA-RISC complex formation reaction rate was 2 times slower when blunt-ended molecules were used pointing to the fact that the presence of the 2-nt overhangs has a greater effect on the reaction in which the bound RISC complex cleaves the mRNA.

NT-pro-BNP is an independent predictor of mortality in patients with end-stage renal disease.

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Svensson, M; Gorst-Rasmussen, A; Schmidt, E B; Jorgensen, K A; Christensen, J H

2009-04-01

Patients with end-stage renal disease (ESRD) have an increased mortality from cardiovascular disease (CVD). N-terminal pro-brain natriuretic peptide (NT-pro-BNP) is an independent predictor of mortality in patients with ischemic heart disease and congestive heart failure. Previous data have shown markedly elevated levels of NT-pro-BNP in patients with ESRD, while the prognostic value of elevated levels of NT-pro-BNP in patients with ESRD is largely unknown. The aim of the present study was to examine if the level of NT-pro-BNP predicts mortality in patients with ERSD and CVD. We prospectively followed 206 patients with ESRD and documented CVD. Levels of NT-pro-BNP were measured at baseline, and patients were followed for 2 years or until they reached the predefined endpoint of all-cause mortality. During follow-up, the total mortality was 44% (90/206). Patients who died were followed for a median of 314 days (interquartile range 179 - 530). Using Cox regression analysis, age, female sex, systolic blood pressure, dialysis efficiency and plasma levels of NT-pro-BNP were independent prognostic risk factors of mortality. In receiver operating characteristic curve analysis a cut off value for NT-pro-BNP was determined. Patients with values of NT-pro-BNP above 12.200 pg/ml had a 3 times higher risk of death than patients below the cut-off value (HR 3.05 95% CI 1.96 - 4.77, p pro-BNP, NT-pro-BNP is still an independent predictor of mortality and might add prognostic information in patients with ESRD and documented CVD.

Nuclear waste for NT

International Nuclear Information System (INIS)

Nelson, Brendan

2005-01-01

The Northern Territory may be powerless to block the dumping of low-level nuclear waste in the Territory under legislation introduced into Parliament by Minister for Education Science and Training, Dr Brendan Nelson, in October. Despite strong opposition to the dumping of nuclear waste in the NT, the Australian Government will be able to send waste to one of the three nominated Commonwealth-owned Defence sites within the NT under the Commonwealth Radioactive Waste Management Bill 2005 and the Commonwealth Radioactive Waste Management (Related Amendment) Bill 2005. The Bills veto recently drafted NT legislation designed to scuttle the plans. Low-level nuclear waste is stored at more than 100 sites around Australia, including hospitals, factories, universities and defence facilities. Medical isotopes produced at Lucas Heights and provided for medical procedures are the source of much of this waste, including some 16 cubic metres currently held at Darwin Hospital. Dr Nelson stressed that the Government would take all die necessary steps to comply with safety and regulatory precautions, including handling waste in line with relevant environmental, nuclear safety and proliferation safeguards

Purine restriction induces pronounced translational upregulation of the NT1 adenosine/pyrimidine nucleoside transporter in Leishmania major.

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Ortiz, Diana; Valdés, Raquel; Sanchez, Marco A; Hayenga, Johanna; Elya, Carolyn; Detke, Siegfried; Landfear, Scott M

2010-10-01

Leishmania and other parasitic protozoa are unable to synthesize purines de novo and are reliant upon purine nucleoside and nucleobase transporters to import preformed purines from their hosts. To study the roles of the four purine permeases NT1-NT4 in Leishmania major, null mutants in each transporter gene were prepared and the effect of each gene deletion on purine uptake was monitored. Deletion of the NT3 purine nucleobase transporter gene or both NT3 and the NT2 nucleoside transporter gene resulted in pronounced upregulation of adenosine and uridine uptake mediated by the NT1 permease and also induced up to a 200-fold enhancement in the level of the NT1 protein but not mRNA. A similar level of upregulation of NT1 was achieved in wild-type promastigotes that were transferred to medium deficient in purines. Pulse labelling and treatment of cells with the translation inhibitor cycloheximide revealed that control of NT1 expression occurs primarily at the level of translation and not protein turnover. These observations imply the existence of a translational control mechanism that enhances the ability of Leishmania parasites to import essential purines when they are present at limiting concentrations. © 2010 Blackwell Publishing Ltd.

Dicer-like 3 produces transposable element-associated 24-nt siRNAs that control agricultural traits in rice

Science.gov (United States)

Wei, Liya; Gu, Lianfeng; Song, Xianwei; Cui, Xiekui; Lu, Zhike; Zhou, Ming; Wang, Lulu; Hu, Fengyi; Zhai, Jixian; Meyers, Blake C.; Cao, Xiaofeng

2014-01-01

Transposable elements (TEs) and repetitive sequences make up over 35% of the rice (Oryza sativa) genome. The host regulates the activity of different TEs by different epigenetic mechanisms, including DNA methylation, histone H3K9 methylation, and histone H3K4 demethylation. TEs can also affect the expression of host genes. For example, miniature inverted repeat TEs (MITEs), dispersed high copy-number DNA TEs, can influence the expression of nearby genes. In plants, 24-nt small interfering RNAs (siRNAs) are mainly derived from repeats and TEs. However, the extent to which TEs, particularly MITEs associated with 24-nt siRNAs, affect gene expression remains elusive. Here, we show that the rice Dicer-like 3 homolog OsDCL3a is primarily responsible for 24-nt siRNA processing. Impairing OsDCL3a expression by RNA interference caused phenotypes affecting important agricultural traits; these phenotypes include dwarfism, larger flag leaf angle, and fewer secondary branches. We used small RNA deep sequencing to identify 535,054 24-nt siRNA clusters. Of these clusters, ∼82% were OsDCL3a-dependent and showed significant enrichment of MITEs. Reduction of OsDCL3a function reduced the 24-nt siRNAs predominantly from MITEs and elevated expression of nearby genes. OsDCL3a directly targets genes involved in gibberellin and brassinosteroid homeostasis; OsDCL3a deficiency may affect these genes, thus causing the phenotypes of dwarfism and enlarged flag leaf angle. Our work identifies OsDCL3a-dependent 24-nt siRNAs derived from MITEs as broadly functioning regulators for fine-tuning gene expression, which may reflect a conserved epigenetic mechanism in higher plants with genomes rich in dispersed repeats or TEs. PMID:24554078

NT-pro-BNP levels in patients with acute pulmonary embolism are correlated to right but not left ventricular volume and function.

Science.gov (United States)

Pasha, Sharif M; Klok, Frederikus A; van der Bijl, Noortje; de Roos, Albert; Kroft, Lucia J M; Huisman, Menno V

2012-08-01

N-terminal pro-Brain Natriuretic Peptide (NT-pro-BNP) is primarily secreted by left ventricular (LV) stretch and wall tension. Notably, NT-pro-BNP is a prognostic marker in acute pulmonary embolism (PE), which primarily stresses the right ventricle (RV). We sought to evaluate the relative contribution of the RV to NT-pro-BNP levels during PE. A post-hoc analysis of an observational prospective outcome study in 113 consecutive patients with computed tomography (CT)-proven PE and 226 patients in whom PE was clinically suspected but ruled out by CT. In all patients RV and LV function was established by assessing ECG-triggered-CT measured ventricular end-diastolic-volumes and ejection fraction (EF). NT-pro-BNP was assessed in all patients. The correlation between RV and LV end-diastolic-volumes and systolic function was evaluated by multiple linear regression corrected for known confounders. In the PE cohort increased RVEF (β-coefficient (95% confidence interval [CI]) -0.044 (± -0.011); p<0.001) and higher RV end-diastolic-volume (β-coefficient 0.005 (± 0.001); p<0.001) were significantly correlated to NT-pro-BNP, while no correlation was found with LVEF (β-coefficient 0.005 (± 0.010); p=0.587) and LV end-diastolic-volume (β-coefficient -0.003 (± 0.002); p=0.074). In control patients without PE we found a strong correlation between NT-pro-BNP levels and LVEF (β-coefficient -0.027 (± -0.006); p<0.001) although not LV end-diastolic-volume (β-coefficient 0.001 (± 0.001); p=0.418). RVEF (β-coefficient -0.002 (± -0.006); p=0.802) and RV end-diastolic-volume (β-coefficient <0.001 (± 0.001); p=0.730) were not correlated in patients without PE. In PE patients, lower RVEF and higher RV end-diastolic-volume were significantly correlated to NT-pro-BNP levels as compared to control patients without PE. These observations provide pathophysiological ground for the well-known prognostic value of NT-pro-BNP in acute PE.

Overexpression of NtWRKY50 Increases Resistance to Ralstonia solanacearum and Alters Salicylic Acid and Jasmonic Acid Production in Tobacco.

Science.gov (United States)

Liu, Qiuping; Liu, Ying; Tang, Yuanman; Chen, Juanni; Ding, Wei

2017-01-01

WRKY transcription factors (TFs) modulate plant responses to biotic and abiotic stresses. Here, we characterized a WRKY IIc TF, NtWRKY50, isolated from tobacco ( Nicotiana tabacum ) plants. The results showed that NtWRKY50 is a nuclear-localized protein and that its gene transcript is induced in tobacco when inoculated with the pathogenic bacterium Ralstonia solanacearum . Overexpression of NtWRKY50 enhanced bacterial resistance, which correlated with enhanced SA and JA/ET signaling genes. However, silencing of the NtWRKY50 gene had no obvious effects on plant disease resistance, implying functional redundancy of NtWRKY50 with other TFs. In addition, it was found that NtWRKY50 can be induced by various biotic or abiotic stresses, such as Potato virus Y, Rhizoctonia solani, Phytophthora parasitica , hydrogen peroxide, heat, cold, and wounding as well as the hormones salicylic acid (SA), jasmonic acid (JA), and ethylene (ET). Importantly, additional analysis suggests that NtWRKY50 overexpression markedly promotes SA levels but prevents pathogen-induced JA production. These data indicate that NtWRKY50 overexpression leads to altered SA and JA content, increased expression of defense-related genes and enhanced plant resistance to R. solanacearum. These probably due to increased activity of endogenous NtWRKY50 gene or could be gain-of-function phenotypes by altering the profile of genes affected by NtWRKY50 .

NT-proBNP in cardiac surgery: a new tool for the management of our patients?

Science.gov (United States)

Reyes, Guillermo; Forés, Gloria; Rodríguez-Abella, R Hugo; Cuerpo, Gregorio; Vallejo, José Luis; Romero, Carlos; Pinto, Angel

2005-06-01

Our aim was to determine NT-proBNP levels in patients undergoing cardiac surgery and if those levels are related to any of the baseline clinical characteristics of patients before surgery or any of the outcomes or events after surgery. Prospective, analytic study including 83 consecutive patients undergoing cardiac surgery. Preoperatory and postoperatory data were collected. NT-proBNP levels were measured before surgery, the day of surgery, twice the following day and every 24 h until a total of nine determinations. Venous blood was obtained by direct venipuncture and collected into serum separator tubes. Samples were centrifuged within 20 min from sampling and stored for a maximum of 12 h at 2-8 degrees C before the separation of serum. Serum was stored frozen at -40 degrees C and thawed only once at the time of analysis. Mean age was 65+/-11.8 years. An Euroscore 6 was found in 30% of patients. NYHA classification was as follows: I:27.7%; II:47%; III:25.3%. Preoperative atrial fibrilation occurred in 20.5% of patients. After surgery 18.1% of patients required inotropes. Only one death was recorded. A great variability was found in preoperative NT-proBNP levels; 759.9 (S.D.:1371.1); CI 95%: 464.9 to 1054.9 pg/ml, with a wide range (6.39-8854). Median was 366.5 pg/ml. Preoperative NT-proBNP levels were unrelated to the type of surgery (CABG vs. others), sex, age and any of the cardiovascular risk factors. NT-proBNP levels were higher in high risk patients (Euroscore 6); (P=0.021), worse NYHA class (P=0.020) and patients with preoperative atrial fibrilation (m 1767 (2205) vs m 621 (1017); P=0.001). After surgery NT-proBNP levels started increasing the following day until the fourth day (P=0.03), decreasing afterwards (P=0.019). These levels were significantly higher in patients requiring inotropes after surgery (P<0.001). We did not find any relationship between NT-proBNP levels and complications rate (P=0.59). Preoperative NT-proBNP levels depend on preoperative

Hormone therapy with tamoxifen reduces plasma levels of NT-B-type natriuretic peptide but does not change ventricular ejection fraction after chemotherapy in women with breast cancer

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F.B. Silva

2015-02-01

Full Text Available The objective of this study was to evaluate the effect of tamoxifen on the plasma concentration of NT-pro-B-type natriuretic peptide (NT-proBNP in women undergoing chemotherapy for breast cancer and to correlate changes in NT-proBNP with the left ventricular ejection fraction (LVEF. Over a period of 12 months, we followed 60 women with a diagnosis of breast cancer. The patients were separated into a group that received only chemotherapy (n=23, a group that received chemotherapy + tamoxifen (n=21, and a group that received only tamoxifen (n=16. Plasma levels of NT-proBNP were assessed at 0 (T0, 6 (T6, and 12 (T12 months of treatment, and echocardiography data were assessed at T0 and T12. Plasma NT-proBNP levels were increased in the chemotherapy-only group at T6 and T12, whereas elevated NT-proBNP levels were only found at T6 in the chemotherapy + tamoxifen group. At T12, the chemotherapy + tamoxifen group exhibited a significant reduction in the peptide to levels similar to the group that received tamoxifen alone. The chemotherapy-only group exhibited a significant decrease in LVEF at T12, whereas the chemotherapy + tamoxifen and tamoxifen-only groups maintained levels similar to those at the beginning of treatment. Treatment with tamoxifen for 6 months after chemotherapy significantly reduced the plasma levels of NT-proBNP and did not change LVEF in women with breast cancer.

Information decision making support system RECASS-NT

International Nuclear Information System (INIS)

Shershakov, V.; Kosykh, V.; Borodin, R.

2003-01-01

Full text: The primary purpose of the DSS RECASS-NT is analysis and prediction of the situation in case of emergency at nuclear facilities (in early phases of an accident) including dose estimation and working out recommendations with regard to countermeasures to protect the public affected by the accident. The system was created to satisfy the following requirements: the system should be ale to operate in two modes: automatic and interactive; the system is based an the 'client-server' principle. Clients can interact with the system both locally and remotely; all calculations in the system are carried out on the server. The client part is responsible for interaction with the system user (including data presentation). Results of model calculations can be displayed during modeling (dynamically) and on completion of calculations; the information base of the system is the operational database, the systemic database and the database with calculation results; the system should enable parallel calculations, among them calculations by different scenarios for the same accident. The automatic mode involves running a specified chain of modules using appropriate scenarios, with a final result generated. The primary purpose of the automatic mode is conducting express-calculations when detailed information about emergency is unavailable. In the interactive mode selection and start-up of a chain of calculation modules, setting parameters for used models, their correction and other actions key for the system operations are performed by a system user (expert). There are no differences between the automatic and interactive modes in terms of storage of calculation results in the system and method of data transmission between the modules within the chain. The telecommunication subsystem (TCS) is designed to provide linkage between programs occurring an different computers and connected both in the local network and the telecommunication system EGASKRO and, possibly, commercial

Brain natriuretic peptide precursor (NT-pro-BNP) levels predict for clinical benefit to sunitinib treatment in patients with metastatic renal cell carcinoma

International Nuclear Information System (INIS)

Papazisis, Konstantinos T; Kortsaris, Alexandros H; Kontovinis, Lukas F; Papandreou, Christos N; Kouvatseas, George; Lafaras, Christos; Antonakis, Evangelos; Christopoulou, Maria; Andreadis, Charalambos; Mouratidou, Despoina

2010-01-01

Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that has been approved for the treatment of metastatic renal cell carcinoma. Although the majority of sunitinib-treated patients receive a clinical benefit, almost a third of the patients will not respond. Currently there is no available marker that can predict for response in these patients. We estimated the plasma levels of NT-pro-BNP (the N-terminal precursor of brain natriuretic peptide) in 36 patients that were treated with sunitinib for metastatic clear-cell renal carcinoma. From the 36 patients, 9 had progressive disease and 27 obtained a clinical benefit (objective response or disease stabilization). Increases in plasma NT-pro-BNP were strongly correlated to clinical outcome. Patients with disease progression increased plasma BNP at statistically significant higher levels than patients that obtained a clinical benefit, and this was evident from the first 15 days of treatment (a three-fold increase in patients with progressive disease compared to stable NT-pro-BNP levels in patients with clinical benefit, p < 0.0001). Median progression-free survival was 12.0 months in patients with less than 1.5 fold increases (n = 22) and 3.9 months in patients with more than 1.5 fold increases in plasma NT-pro-BNP (n = 13) (log-rank test, p = 0.001). This is the first time that a potential 'surrogate marker' has been reported with such a clear correlation to clinical benefit at an early time of treatment. Due to the relative small number of accessed patients, this observation needs to be further addressed on larger cohorts. More analyses, including multivariate analyses are needed before such an observation can be used in clinical practice

Changes in Serum NT-Pro BNP and Left Atrial BNP Levels after Percutaneous Transvenous Mitral Commissurotomy in Sinus Rhythm Versus Atrial Firilation

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Leili Pourafkari

2014-10-01

Full Text Available Introduction: Natriuretic peptides are secreted from the heart in response to increased wall stress. Their levels are expected to be increased in patients with mitral stenosis (MS due tohigh left atrium (LA pressure and pulmonary artery pressure (PAP. Percutaneous transvenousmitral commissurotomy (PTMC if successful is pursued by a rapid decrease in LA pressure andsubsequent decrease in pulmonary artery pressure. The concurrent changes in natriuretic peptidelevels could be affected with heart rhythm.Methods: Forty five patients with severe rheumatic MS undergoing PTMC were enrolled. Weevaluated the serum NT-Pro BNP levels before and 24 hours after PTMC. BNP levels were alsomeasured from the blood samples obtained from LA before and 20 minutes after the procedure.Changes in biomarkers were assessed based on heart rhythm and success of the procedure.Results: While serum NT-Pro BNP levels showed significant decrease 24 hours after theprocedure (P= 0.04, BNP levels taken 20 minutes after PTMC from LA were similar to theirbaseline concentrations (P= 0.26. NT-Pro BNP levels decreased 51.7±182.86 pg/ml for SR and123.4±520 pg/ml for AF (P= 0.68.Conclusion: Immediate changes in BNP levels did not predict the success of procedure probablydue to the additional balloon inflation attempts in LA in several patients and half-life of BNP. BNPlevels obtained later may be of more value considering the half-life of this marker. Heart rhythmwas not found to influence the changes in biomarker levels. BNP and NT-pro BNP changes werenot found to predict success of the procedure.

State-dependent increase in the levels of neurotrophin-3 and neurotrophin-4/5 in patients with bipolar disorder: A meta-analysis.

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Tseng, Ping-Tao; Chen, Yen-Wen; Tu, Kun-Yu; Wang, Hung-Yu; Chung, Weilun; Wu, Ching-Kuan; Hsu, Shih-Pin; Kuo, Hung-Chang; Lin, Pao-Yen

2016-08-01

Bipolar disorder (BD) is one of the most serious psychiatric disorders in the world, but its pathophysiology is still unclear. Regulation of neurotrophic factors have been thought to play a role in this process. There have been inconsistent findings regarding the differences in blood neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) between patients with BD and healthy controls (HCs). The aim of the current meta-analysis is to examine the changes in the levels of NT-3 and NT-4/5 in BD patients at different affective states. Eight articles (including 465 BD patients and 353 HCs) were included in the analysis, and their results were pooled by using a random effects model. We found the levels of both NT-3 (p = 0.0046) and NT-4/5 (p = 0.0003) were significantly increased in BD patients, compared to HCs. Through subgroup analysis, this increase persisted only in patients in depressed state (p = 0.0038 for NT-3 and p = 0.0001 for NT-4/5), but not in manic or euthymic state. In addition, we found the differences in NT-3 and NT-4/5 were significantly associated with the duration of illness, but not by the mean age or female proportion. Our results suggest a state-dependent increase in NT-3 and NT-4/5 levels in patients with BD. Further studies are needed to examine dynamic changes of these neurotrophins in BD patients along the disease course. Copyright © 2016 Elsevier Ltd. All rights reserved.

Görüntü Eşleme ve Genetik Algoritmalar Kullanarak Görüntü içinde Görüntü Arama

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Mehmet Karakoc

2015-10-01

Full Text Available Bu çalışmada esas alınan problem, görüntü içinde görüntü aramayı etkin bir şekilde gerçekleştirebilmektir. Bu amaçla görüntü işleme kapsamında yer alan görüntü eşleme teknikleri ile arama algoritmaları birlikte kullanılmıştır. Görüntü eşleme için Yapay Sinir Ağları ile görüntünün ortalama renk değeri, görüntüdeki renk değerlerinin standart sapması, korelasyon ve görüntü kenar parametreleri gibi özellikler; görüntü arama için Genetik Algoritmalar kullanılmıştır. Bu çalışmada, akıllı arama algoritmaları, hızlı görüntü eşleme yöntemleri ve paralel programlama tekniklerine dayanan bütünleşik bir yöntem önerilmiş ve kullanılmıştır. Önerilen yöntem çok sayıda düşük ve yüksek çözünürlüklü referans ve şablon görüntü üzerinde test edilmiştir. Elde edilen sonuçlar önerilen yöntemin eşleşen görüntüleri elde etmede başarılı olduğunu ve toplam arama süresini azalttığını göstermiştir.

The NtAMI1 gene functions in cell division of tobacco BY-2 cells in the presence of indole-3-acetamide.

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Nemoto, Keiichirou; Hara, Masamitsu; Suzuki, Masashi; Seki, Hikaru; Muranaka, Toshiya; Mano, Yoshihiro

2009-01-22

Tobacco (Nicotiana tabacum) Bright Yellow-2 (BY-2) cells can be grown in medium containing indole-3-acetamide (IAM). Based on this finding, the NtAMI1 gene, whose product is functionally equivalent to the AtAMI1 gene of Arabidopsis thaliana and the aux2 gene of Agrobacterium rhizogenes, was isolated from BY-2 cells. Overexpression of the NtAMI1 gene allowed BY-2 cells to proliferate at lower concentrations of IAM, whereas suppression of the NtAMI1 gene by RNA interference (RNAi) caused severe growth inhibition in the medium containing IAM. These results suggest that IAM is incorporated into plant cells and converted to the auxin, indole-3-acetic acid, by NtAMI1.

Probing dark matter streams with CoGeNT

International Nuclear Information System (INIS)

Natarajan, Aravind; Savage, Christopher; Freese, Katherine

2011-01-01

We examine the future sensitivity of CoGeNT to the presence of dark matter streams and find that consideration of streams in the data may lead to differences in the interpretation of the results. We show the allowed particle mass and cross section for different halo parameters, assuming spin-independent elastic scattering. As an example, we choose a stream with the same velocity profile as that of the Sagittarius stream (and in the Solar neighborhood) and find that, with an exposure of ∼10 kg yr, the CoGeNT results can be expected to exclude the standard-halo-model-only halo in favor of a standard halo model+stream halo at the 95% (99.7%) confidence level, provided the stream contributes 3% (5%) of the local dark matter density. The presence of a significant stream component may result in incorrect estimates of the particle mass and cross section unless the presence of the stream is taken into account. We conclude that the CoGeNT experiment is sensitive to streams and care should be taken to include the possibility of streams when analyzing experimental results.

Clostridium botulinum strains producing BoNT/F4 or BoNT/F5.

Science.gov (United States)

Raphael, Brian H; Bradshaw, Marite; Kalb, Suzanne R; Joseph, Lavin A; Lúquez, Carolina; Barr, John R; Johnson, Eric A; Maslanka, Susan E

2014-05-01

Botulinum neurotoxin type F (BoNT/F) may be produced by Clostridium botulinum alone or in combination with another toxin type such as BoNT/A or BoNT/B. Type F neurotoxin gene sequences have been further classified into seven toxin subtypes. Recently, the genome sequence of one strain of C. botulinum (Af84) was shown to contain three neurotoxin genes (bont/F4, bont/F5, and bont/A2). In this study, eight strains containing bont/F4 and seven strains containing bont/F5 were examined. Culture supernatants produced by these strains were incubated with BoNT/F-specific peptide substrates. Cleavage products of these peptides were subjected to mass spectral analysis, allowing detection of the BoNT/F subtypes present in the culture supernatants. PCR analysis demonstrated that a plasmid-specific marker (PL-6) was observed only among strains containing bont/F5. Among these strains, Southern hybridization revealed the presence of an approximately 242-kb plasmid harboring bont/F5. Genome sequencing of four of these strains revealed that the genomic backgrounds of strains harboring either bont/F4 or bont/F5 are diverse. None of the strains analyzed in this study were shown to produce BoNT/F4 and BoNT/F5 simultaneously, suggesting that strain Af84 is unusual. Finally, these data support a role for the mobility of a bont/F5-carrying plasmid among strains of diverse genomic backgrounds.

Ultra-Sensitive NT-proBNP Quantification for Early Detection of Risk Factors Leading to Heart Failure

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Keum-Soo Song

2017-09-01

Full Text Available Cardiovascular diseases such as acute myocardial infarction and heart failure accounted for the death of 17.5 million people (31% of all global deaths in 2015. Monitoring the level of circulating N-terminal proBNP (NT-proBNP is crucial for the detection of people at risk of heart failure. In this article, we describe a novel ultra-sensitive NT-proBNP test (us-NT-proBNP that allows the quantification of circulating NT-proBNP in 30 min at 25 °C in the linear detection range of 7.0–600 pg/mL. It is a first report on the application of a fluorescence bead labeled detection antibody, DNA-guided detection method, and glass fiber membrane platform for the quantification of NT-proBNP in clinical samples. Limit of blank, limit of detection, and limit of quantification were 2.0 pg/mL, 3.7 pg/mL, and 7 pg/mL, respectively. The coefficient of variation was found to be less than 10% in the entire detection range of 7–600 pg/mL. The test demonstrated specificity for NT-proBNP without interferences from bilirubin, intra-lipid, biotin, and hemoglobin. The serial dilution test for plasma samples containing various NT-proBNP levels showed the linear decrement in concentration with the regression coefficient of 0.980–0.998. These results indicate that us-NT-proBNP test does not suffer from the interference of the plasma components for the measurement of NT-proBNP in clinical samples.

NT-proBNP concentrations in mountain marathoners.

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Banfi, Giuseppe; Lippi, Giuseppe; Susta, Daniele; Barassi, Alessandra; D'Eril, Gianvico Melzi; Dogliotti, Giada; Corsi, Massimiliano M

2010-05-01

The 76 amino acid N-terminal proB-type natriuretic peptide (NT-proBNP) is proposed for evaluating and monitoring heart pathologies characterized by myocardial wall stress. Strenuous exercise might generate transitory ischemia, myocardial stress, and diastolic left ventricular dysfunction, possibly inducing an increase of some biochemical parameter concentrations. An alert has been claimed owing to biochemical and instrumental signs of heart dysfunction in recreational athletes during marathon races. We studied the behaviour of NT-proBNP in 15 mountain marathoners before and after a race. The concentrations of the parameter were lower than that observed in controls at rest and were similar to that observed in professional soccer and rugby players. The concentrations significantly increased after the race. NT-proBNP is low at rest in professional athletes, and the increase after physical exercise is physiological. The marathoners, even when performing races in a high-altitude environment, show NT-proBNP concentrations similar to those of athletes from other sports disciplines, characterized by low levels of effort and by a mix of aerobic and anaerobic metabolism. The increase of NT-proBNP is linked to strenuous physical exercise and to heavy heart effort, testified also by an increase of troponin I. However, the role of the NT-proBNP could be important to screen recreational and professional marathoners to avoid possible heart problems and sudden cardiac death in subjects with occult heart disease. The results of the present study are relevant to the design and evaluation of training programs for improving strength and function of professional marathoners.

Relationship between CCR and NT-proBNP in Chinese HF patients, and their correlations with severity of HF.

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Lu, Zhigang; Wang, Bo; Wang, Yunliang; Qian, Xueqing; Zheng, Wei; Wei, Meng

2014-01-01

To evaluate the relationship between creatinine clearance rate (CCR) and the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) patients and their correlations with HF severity. Two hundred and one Chinese patients were grouped according to the New York Heart Association (NYHA) classification as NYHA 1-2 and 3-4 groups and 135 cases out of heart failure patients as control group. The following variables were compared among these three groups: age, sex, body mass index (BMI), smoking status, hypertension, diabetes, NT-proBNP, creatinine (Cr), uric acid (UA), left ventricular end-diastolic diameter (LVEDD), and CCR. The biomarkers of NT-proBNP, Cr, UA, LVEDD, and CCR varied significantly in the three groups, and these variables were positively correlated with the NHYA classification. The levels of NT-proBNP and CCR were closely related to the occurrence of HF and were independent risk factors for HF. At the same time, there was a significant negative correlation between the levels of NT-proBNP and CCR. The area under the receiver operating characteristic curve suggested that the NT-proBNP and CCR have high accuracy for diagnosis of HF and have clinical diagnostic value. NT-proBNP and CCR may be important biomarkers in evaluating the severity of HF.

Differential effects of BDNF and neurotrophin 4 (NT4) on endocytic sorting of TrkB receptors.

Science.gov (United States)

Proenca, Catia C; Song, Minseok; Lee, Francis S

2016-08-01

Neurotrophins are a family of growth factors playing key roles in the survival, development, and function of neurons. The neurotrophins brain-derived neurotrophic factor (BDNF) and NT4 both bind to and activate TrkB receptors, however, they mediate distinct neuronal functions. The molecular mechanism of how TrkB activation by BDNF and NT4 leads to diverse outcomes is unknown. Here, we report that BDNF and NT4 lead to differential endocytic sorting of TrkB receptors resulting in diverse biological functions in cultured cortical neurons. Fluorescent microscopy and surface biotinylation experiments showed that both neurotrophins stimulate internalization of TrkB with similar kinetics. Exposure to BDNF for 2-3 h reduced the surface pool of TrkB receptors to half, whereas a longer treatment (4-5 h) with NT4 was necessary to achieve a similar level of down-regulation. Although BDNF and NT4 induced TrkB phosphorylation with similar intensities, BDNF induced more rapid ubiquitination and degradation of TrkB than NT4. Interestingly, TrkB receptor ubiquitination by these ligands have substantially different pH sensitivities, resulting in varying degrees of receptor ubiquitination at lower pH levels. Consequently, NT4 was capable of maintaining longer sustained downstream signaling activation that correlated with reduced TrkB ubiquitination at endosomal pH. Thus, by leading to altered endocytic trafficking itineraries for TrkB receptors, BDNF and NT4 elicit differential TrkB signaling in terms of duration, intensity, and specificity, which may contribute to their functional differences in vivo. The neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4), both bind to and activate TrkB receptors, however, they mediate distinct neuronal functions. Here, we propose that BDNF and NT4 lead to differential endocytic sorting of TrkB receptors resulting in diverse biological functions. BDNF induces more rapid ubiquitination and degradation of TrkB than NT4

Expression of brain-derived neurotrophic factors, neurotrophin-3, and neurotrophin-4 in the nucleus accumbens during heroin dependency and withdrawal.

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Li, Yixin; Xia, Baijuan; Li, Rongrong; Yin, Dan; Wang, Yanlin; Liang, Wenmei

2017-08-02

Neurotrophins, brain-derived neurotrophic factors (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), have been implicated in the modulation of heroin dependency. This study was designed to explore the expression alterations of BDNF, NT-3, and NT-4 in the context of heroin dependence and withdrawal in the rat nucleus accumbens (NAc). Heroin dependence was induced by a progressive intraperitoneal treatment of heroin. The results showed that the expression levels of BDNF and NT-4 were significantly decreased in the NAc of rats with heroin addiction in comparison with the control group, whereas there was a significant increase in BDNF and NT-4 expressions in the groups of rats with both naloxone-induced and spontaneous withdrawal. Moreover, NT-3 expression was markedly increased in the NAc of rats with heroin addiction and spontaneous withdrawal in comparison with the control group, but decreased in the NAc of rats with naloxone-induced withdrawal. These results indicated that chronic administration of heroin results in the alterations of BDNF, NT-3, and NT-4 expressions in the rat NAc. BDNF, NT-3, and NT-4 may play a critical role in the development of heroin dependency and withdrawal.

Relationship of plasma level of NT- ProBNP with development of AF in CABG patients

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Tanaray B

2010-10-01

Full Text Available "nBackground: Studies of the association between post operative AF and Plasma level of NT- Pro BNP have reported conflicting findings. The aim of the present study was evaluation of the association between post coronary bypass graft- Atrial Fibrillation (AF and Plasma level of NT- ProBNP as an independent risk factor of AF development in patients undergoing coronary artery bypass graft."n "nMethods: In a cohort study, 79 patients with sinus rhythm who admitted in Imam Khomeini Hospital in Tehran, Iran, during February 2009 and February 2010 for CABG are included the study and followed for developing post operative AF rhythm."n "nResults: Post operative AF was found in 17.7% of patients. The peak time from the operation to the first AF episode was in second post op day in ten patients (71.4%. The serum level of ProBNP in patients with AF was significantly higher (1624± 647 versus 221± 238 pg/ml, p< 0/0001. Increased age, Increased LA size and high plasma level of ProBNP were associated with increased risk for post op AF. After adjustment of risk factors, plasma level of ProBNP was the most important risk factor with odds ratio of 15.34 with CI 95% 1.77-132.95 and then LA diameter with odds ratio of 6.11 with CI 95% 0.99-37.42 was independently correlated with post op AF. Correlation between plasma level of ProBNP with age and LA size was seen too (LA size r = 0.0281, p= 0.012. Between age and ProBNP (r= 0.337, p= 0.002. The best cut off point for plasma ProBNP as a predictor of post op AF was 854 pg/ml."n "nConclusion: Increased level of preoperative ProBNP levels could be an independent predictor of post operative Atrial Fibrillation.

Elevated NT-pro-brain natriuretic peptide level is independently associated with all-cause mortality in HIV-infected women in the early and recent HAART eras in the Women's Interagency HIV Study cohort.

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Matthew R Gingo

Full Text Available HIV-infected individuals are at increased risk of right and left heart dysfunction. N-terminal-pro-brain natriuretic peptide (NT-proBNP, a marker of cardiac ventricular strain and systolic dysfunction, may be associated with all-cause mortality in HIV-infected women. The aim of this study was to determine if elevated levels of NT-proBNP is associated with increased mortality in HIV-infected women.Prospective cohort study.We measured NT-proBNP in 936 HIV-infected and 387 age-matched HIV-uninfected women early (10/11/94 to 7/17/97 and 1082 HIV-infected and 448 HIV-uninfected women late (4/1/08 to 10/7/08 in the highly active antiretroviral therapy (HAART periods in the Women's Interagency HIV Study. An NT-proBNP >75th percentile was more likely in HIV-infected persons, but only statistically significant in the late period (27% vs. 21%, unadjusted p = 0.03. In HIV-infected participants, NT-proBNP>75th percentile was independently associated with worse 5-year survival in the early HAART period (HR 1.8, 95% CI 1.3-2.4, p<0.001 and remained a predictor of mortality in the late HAART period (HR 2.8, 95% CI 1.4-5.5, p = 0.002 independent of other established risk covariates (age, race/ethnicity, body mass index, smoking, hepatitis C serostatus, hypertension, renal function, and hemoglobin. NT-proBNP level was not associated with mortality in HIV-uninfected women.NT-proBNP is a novel independent marker of mortality in HIV-infected women both when HAART was first introduced and currently. As NT-proBNP is often associated with both pulmonary hypertension and left ventricular dysfunction, these findings suggest that these conditions may contribute significantly to adverse outcomes in this population, requiring further definition of causes and treatments of elevated NT-proBNP in HIV-infected women.

NT-proBNP in unstable coronary artery disease--experiences from the FAST, GUSTO IV and FRISC II trials.

Science.gov (United States)

Jernberg, Tomas; James, Stefan; Lindahl, Bertil; Stridsberg, Mats; Venge, Per; Wallentin, Lars

2004-03-15

Risk stratification is important in patients with unstable coronary artery disease (CAD), i.e. unstable angina or non-ST-elevation myocardial infarction. This article focuses on the emerging role of N-terminal pro brain natriuretic peptide (NT-proBNP) and the results from the FAST, GUSTO IV and FRISC II trials. In the FAST study, NT-proBNP was measured on admission in 755 patients admitted because of symptoms suggestive of unstable CAD. Follow up was performed after 40 months. The GUSTO IV and the FRISC II-trials included patients with unstable CAD and NT-proBNP was analyzed in 6806 and 2019 patients, with follow up after 1 and 2 years, respectively. In the FAST study, patients in the 2nd, 3rd, and 4th NT-proBNP quartile had a relative risk of subsequent death of 4.2 (1.6-11.1), 10.7 (4.2-26.8) and 26.6 (10.8-65.5), respectively. In the GUSTO IV trial, increasing quartiles of NT-proBNP were related to short and long term mortality which at 1 year was; 1.8%, 3.9%, 7.7% and 19.2% (P<0.001), respectively. In multivariable analyses including well-known predictors of outcome, NT-proBNP level was independently associated to mortality in all three studies. In the FRISC II trial, the NT-proBNP level, especially if combined with a marker of inflammation, identified those with the greatest benefit from an early invasive strategy. NT-proBNP is strongly associated with mortality in patients with suspected or confirmed unstable CAD and, combined with a marker of inflammation, seems helpful in identifying those with greatest benefit from an early invasive strategy.

Differential ontogenetic patterns of levocabastine-sensitive neurotensin NT2 receptors and of NT1 receptors in the rat brain revealed by in situ hybridization.

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Lépée-Lorgeoux, I; Betancur, C; Rostène, W; Pélaprat, D

1999-03-12

The postnatal ontogeny of the levocabastine-sensitive neurotensin receptor (NT2) mRNA was studied by in situ hybridization in the rat brain and compared with the distribution of the levocabastine-insensitive NT1 receptor. NT2 receptor mRNA was absent at birth from all brain structures except the ependymal cell layer lining the ventricles. The development of NT2 receptor mRNA followed three ontogenetic patterns. The first pattern, involving the majority of the cerebral gray matter, was characterized by a continuous increase from postnatal day 5 (P5) to P30. The second one, involving regions rich in myelinated fibers such as the corpus callosum and lacunosum moleculare layer of the hippocampus, exhibited a pronounced increase between P5 and P10, peaked at P15 and was followed by a plateau or a slight decrease. The third pattern was observed in the ependymal cell layer lining the olfactory and lateral ventricles, where the high labeling already present at birth continued to increase during development. These different developmental patterns could reflect the variety of cells expressing NT2 receptor mRNA, including neurons, protoplasmic astrocytes in gray matter, fibrous astrocytes present in myelinated fibers tracts, and ependymal cells. In contrast, NT1 receptor mRNA, which seems to be associated only with neurons, was highly and transiently expressed during the perinatal period in the cerebral cortex, hippocampus and striatal neuroepithelium. Other regions, notably the ventral tegmental area and substantia nigra compacta, exhibited a gradual increase in NT1 receptor signal, reaching adult levels by P21. Both the differential localization and ontogenetic profiles of NT1 and NT2 receptor mRNAs suggest different involvement of these two receptors in brain functions and development. Copyright 1999 Elsevier Science B.V.

The predictive value of plasma biomarkers in discharged heart failure patients: role of plasma NT-proBNP.

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Leto, Laura; Testa, Marzia; Feola, Mauro

2016-04-01

Natriuretic peptides (NPs) have demonstrated their value to support clinical diagnosis of heart failure (HF); furthermore they are also studied for their prognostic role using them to guide appropriate management strategies. The present review gathers available evidence on prognostic role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients hospitalized for acute decompensated heart failure (ADHF). We searched Medline for English-language studies with the sequent key-words: "acute heart failure/acute decompensated heart failure", "NT-proBNP/N-terminal pro-B type natriuretic peptide" and "prognosis/mortality/readmission". Almost 30 studies were included. NT-proBNP plasma levels at admission are strongly associated with all-cause short-term mortality (2-3 months), mid-term (6-11 months) or long- term mortality (more than one year) of follow-up. Regarding the prognostic power on cardiac death fewer data are available with uncertain results. NT-proBNP at discharge demonstrated its prognostic role for all-cause mortality at mid and long-term follow-up. The relation between NT-proBNP at discharge and cardiovascular mortality or composite end-point is under investigation. A decrease in NT-proBNP values during hospitalization provided prognostic prospects mainly for cardiovascular mortality and HF readmission. A 30% variation in NT-proBNP levels during in-hospital stay seemed to be an optimal cut-off for prognostic role. SNT-proBNP plasma levels proved to have a strong correlation with all-cause mortality, cardiovascular mortality, morbidity and composite outcomes in patients discharged after an ADHF. A better definition of the correct time of serial measurements and the cut-off values might be the challenge for the future investigations.

NT-proBNP and diastolic left ventricular function in patients with Marfan syndrome

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Petra Gehle

2016-09-01

Conclusions: MFS patients presenting with normal ejection fraction show disturbed diastolic function and higher NT-proBNP levels, which is partly explained by aortic Z-score. Assessment of diastolic function and NT-proBNP levels may therefore detect early abnormalities and guide surveillance and prevention management of patients with MFS.

Permeability of the blood-brain barrier to the neurotensin8-13 analog NT1.

Science.gov (United States)

Banks, W A; Wustrow, D J; Cody, W L; Davis, M D; Kastin, A J

1995-10-09

Neurotensin (NT) has been suggested to be a neuropeptide with therapeutic potential. We used multiple-time regression analysis to measure the unidirectional influx constant (Ki) of a tritiated analog of NT8-13, NT1, with improved metabolic stability. The Ki of [3H]NT1 across the blood-brain barrier (BBB) was 5.12(10(-4)) ml/g-min and was decreased 66% by unlabeled NT1 system. The amount of NT1 crossing the BBB, 0.087% of the injected dose per gram of brain, is consistent with its exerting central effects after peripheral administration. The stable [3H]NT1 crossed the BBB in intact form as assessed by HPLC and completely crossed the endothelial cells that comprise the BBB as assessed by the capillary depletion method. The presence of a transport system could be important for the development of NT analogs.

Tobacco Transcription Factor NtWRKY12 Interacts With TGA2.2 in vitro and in vivo

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Marcel evan Verk

2011-07-01

Full Text Available The promoter of the salicylic acid-inducible PR-1a gene of Nicotiana tabacum contains binding sites for transcription factor NtWRKY12 (WK-box at position -564 and TGA factors (as-1-like element at position -592. Transactivation experiments in Arabidopsis protoplasts derived from wild type, npr1-1, tga256 and tga2356 mutant plants revealed that NtWRKY12 alone was able to induce a PR-1a::β-glucuronidase (GUS reporter gene to high levels, independent of co-expressed tobacco NtNPR1, TGA2.1, TGA2.2 or endogenous Arabidopsis NPR1, TGA2/3/5/6. By in vitro pull-down assays with GST and Strep fusion proteins and by Fluorescence Resonance Energy Transfer assays with protein-CFP and protein-YFP fusions in transfected protoplasts, it was shown that NtWRKY12 and TGA2.2 could interact in vitro and in vivo. Interaction of NtWRKY12 with TGA1a or TGA2.1 was not detectable by these techniques. A possible mechanism for the role of NtWRKY12 and TGA2.2 in PR-1a gene expression is discussed.

Widespread expression of BDNF but not NT3 by target areas of basal forebrain cholinergic neurons

Energy Technology Data Exchange (ETDEWEB)

Phillips, H.S.; Hains, J.M.; Laramee, G.R.; Rosenthal, A.; Winslow, J.W. (Genentech, San Francisco, CA (USA))

1990-10-12

Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) are homologs of the well-known neurotrophic factor nerve growth factor. The three members of this family display distinct patterns of target specificity. To examine the distribution in brain of messenger RNA for these molecules, in situ hybridization was performed. Cells hybridizing intensely to antisense BDNF probe were located throughout the major targets of the rat basal forebrain cholinergic system, that is, the hippocampus, amygdala, and neocortex. Strongly hybridizing cells were also observed in structures associated with the olfactory system. The distribution of NT3 mRNA in forebrain was much more limited. Within the hippocampus, labeled cells were restricted to CA2, the most medial portion of CA1, and the dentate gyrus. In human hippocampus, cells expressing BDNF and mRNA are distributed in a fashion similar to that observed in the rat. These findings point to both basal forebrain cholinergic cells and olfactory pathways as potential central targets for BDNF.

Widespread expression of BDNF but not NT3 by target areas of basal forebrain cholinergic neurons

International Nuclear Information System (INIS)

Phillips, H.S.; Hains, J.M.; Laramee, G.R.; Rosenthal, A.; Winslow, J.W.

1990-01-01

Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) are homologs of the well-known neurotrophic factor nerve growth factor. The three members of this family display distinct patterns of target specificity. To examine the distribution in brain of messenger RNA for these molecules, in situ hybridization was performed. Cells hybridizing intensely to antisense BDNF probe were located throughout the major targets of the rat basal forebrain cholinergic system, that is, the hippocampus, amygdala, and neocortex. Strongly hybridizing cells were also observed in structures associated with the olfactory system. The distribution of NT3 mRNA in forebrain was much more limited. Within the hippocampus, labeled cells were restricted to CA2, the most medial portion of CA1, and the dentate gyrus. In human hippocampus, cells expressing BDNF and mRNA are distributed in a fashion similar to that observed in the rat. These findings point to both basal forebrain cholinergic cells and olfactory pathways as potential central targets for BDNF

Neurotrophin-4 couples to locally modulated ACh release at the end of neuromuscular synapse maturation.

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Garcia, N; Santafe, M M; Tomas, M; Lanuza, M A; Besalduch, N; Tomas, J

2010-01-01

We use immunocytochemistry to show that neurotrophin-4 (NT-4) and its receptor proteins (p75(NTR) and tropomyosin-related tyrosine kinase B) are present in neonatal neuromuscular junctions (NMJ) colocalized with several synaptic markers. NT-4 incubation (1h, in the range 2-12 nM) does not change the size of the endplate potential between P6 and P45. However, extended exposure (3h) to a relatively low dose of NT-4 (2 nM) potentiates ACh release (approx. 70%) in adult but not in neonatal muscles. The present results suggest that the developmental mechanism of axonal competition and neonatal elimination of redundant synapses cannot be modulated by added NT-4. However, this neurotrophin was able to modulate synaptic transmission locally in the adult NMJ.

Introduction of an NT-proBNP assay to an acute admission unit--a 2-year audit.

LENUS (Irish Health Repository)

Murtagh, Gillian

2012-02-01

BACKGROUND: The differential diagnosis of dyspnoea is difficult due to the low predictive value of clinical and laboratory parameters. The elevated levels of NT-proBNP in congestive heart failure may improve diagnostic accuracy. We have evaluated the effect of the introduction of an NT-proBNP assay on hospital length of stay (LOS) and mortality. METHODS: There were 11,853 AMAU patient episodes in the 22 months study period (March 2005-Dec 2006). An NT-proBNP assay was requested in 657 (5.5%) of these. Comparison between categorical variables such as diagnosis, NT-proBNP testing, LOS, and in-hospital mortality was made using Chi-square tests. Literature review suggested that an NT-proBNP cut-off >or=5000 ng\\/L should predict acute in-patient mortality. Logistic regression analysis was used to examine the association between such an elevated NT-proBNP level and outcomes. RESULTS: Of the 396 patients with NT-proBNP <5000 ng\\/L, 8.1% died compared with 22.5% of the 178 patients dying with values >or=5000 ng\\/L (p<0.0001). An NT-proBNP >or=5000 ng\\/L was predictive of both LOS >or=9 days (odds ratios (OR) 1.54 (95% CI 1.06, 2.24: p=0.02) and LOS >or=14 days (OR=1.87 (95% CI 1.29, 2.71: p=0.0009). NT-proBNP requests increased over time, from 2.6% to 8.2% of all patients; the result fell in the diagnostic range for CHF in 60% of requests. CONCLUSION: The introduction of an NT-proBNP was reflected in an appropriate but rapidly increasing pattern of requests from clinicians. High NT-proBNP levels predicted in-hospital mortality and longer LOS in an acute medical population.

Extraction and inhibition of enzymatic activity of botulinum neurotoxins/A1, /A2, and /A3 by a panel of monoclonal anti-BoNT/A antibodies.

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Suzanne R Kalb

Full Text Available Botulinum neurotoxins (BoNTs are extremely potent toxins that are capable of causing death or respiratory failure leading to long-term intensive care. Treatment includes serotype-specific antitoxins, which must be administered early in the course of the intoxication. Rapidly determining human exposure to BoNT is an important public health goal. In previous work, our laboratory focused on developing Endopep-MS, a mass spectrometry-based endopeptidase method for detecting and differentiating BoNT/A-G serotypes in buffer and BoNT/A, /B, /E, and /F in clinical samples. We have previously reported the effectiveness of antibody-capture to purify and concentrate BoNTs from complex matrices, such as clinical samples. Because some antibodies inhibit or neutralize the activity of BoNT, the choice of antibody with which to extract the toxin is critical. In this work, we evaluated a panel of 16 anti-BoNT/A monoclonal antibodies (mAbs for their ability to inhibit the in vitro activity of BoNT/A1, /A2, and /A3 complex as well as the recombinant LC of A1. We also evaluated the same antibody panel for the ability to extract BoNT/A1, /A2, and /A3. Among the mAbs, there were significant differences in extraction efficiency, ability to extract BoNT/A subtypes, and inhibitory effect on BoNT catalytic activity. The mAbs binding the C-terminal portion of the BoNT/A heavy chain had optimal properties for use in the Endopep-MS assay.

Evaluation of NT-proBNP concentrations during exercise in asymptomatic patients with severe high-gradient aortic stenosis.

Science.gov (United States)

Dobrowolski, Piotr; Lech, Agnieszka; Klisiewicz, Anna; Hoffman, Piotr

2016-08-11

INTRODUCTION The effect of asymptomatic severe aortic stenosis (ASAS) on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels ar rest and during exercise, as well as their relevance for clinical practice remain controversial.  OBJECTIVES The aim of this study was to test the hypothesis of whether the evaluation of NT-proBNP concentrations during exercise provides additional information about the severity of aortic stenosis and left ventricular remodeling in patients with ASAS. PATIENTS AND METHODS A total of 50 patients with ASAS (mean age, 38.4 ±18.1 years) and 21 healthy subjects (mean age, 43.4 ±10.6 years) were enrolled. Rest and exercise echocardiography was performed to evaluate maximum velocity (Vmax), mean aortic gradient (AG), and aortic valve area (AVA). The left ventricular mass index (LVMI) was calculated. NT-proBNP concentrations at rest and during exercise were assessed, and the difference between the 2 values was calculated (ΔNT-proBNP). RESULTS NT-proBNP and ΔNT-proBNP levels at rest and during exercise were significantly higher in the ASAS group compared with the control group. In the ASAS group, NT-proBNP levels at rest significantly correlated with LVMI (r = 0.432; P <0.0001), AVA (r = -0.408; P <0.0001), Vmax (r = 0.375; P = 0.002), and mean AG (r = 0.257; P = 0.03). NT-proBNP levels during exercise significantly correlated with LVMI (r = 0.432; P <0.0001), mean AG (r = 0.401; P = 0.001), and AVA (r = -0.375; P = 0.001). In the multivariate logistic regression model, the factors independently associated with NT-proBNP both at rest and during exercise were age, AVA, and LVMI. CONCLUSIONS NT-proBNP levels at rest provide valuable information for identifying patients with more advanced left ventricular hypertrophy secondary to severe aortic stenosis. NT-proBNP levels during exercise do not provide new information on the severity of AS.

Polymorphisms in the B-type natriuretic peptide (BNP) gene are associated with NT-proBNP levels but not with diabetic nephropathy or mortality in type 1 diabetic patients

DEFF Research Database (Denmark)

Lajer, Maria Stenkil; Tarnow, Lise; Jorsal, Anders

2007-01-01

BACKGROUND: Circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are elevated in patients with diabetic nephropathy and independently predict excess cardiovascular morbidity and mortality. Therefore, we investigated the association between two polymorphisms -381T/C and 1551G....../A of the BNP gene, plasma NT-proBNP levels and mortality prognosis in 380 type 1 diabetic patients with and without diabetic nephropathy. METHODS: In a prospective observational follow-up study, 197 type 1 diabetic patients with diabetic nephropathy {121 men, age [mean (SD)] 41 +/- 9.5 years, duration...... of diabetes 28 +/- 8.0 years, glomerular filtration rate 67 +/- 28 ml/min/1.73 m2}, and a matched control group of 183 patients with longstanding type 1 diabetes and persistent normoalbuminuria (111 men, age 43 +/- 10.0 years, duration of diabetes 27 +/- 8.3 years) were followed for 12.6 (0.0-12.9) years...

Spectrotemporal processing in spectral tuning modules of cat primary auditory cortex.

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Craig A Atencio

Full Text Available Spectral integration properties show topographical order in cat primary auditory cortex (AI. Along the iso-frequency domain, regions with predominantly narrowly tuned (NT neurons are segregated from regions with more broadly tuned (BT neurons, forming distinct processing modules. Despite their prominent spatial segregation, spectrotemporal processing has not been compared for these regions. We identified these NT and BT regions with broad-band ripple stimuli and characterized processing differences between them using both spectrotemporal receptive fields (STRFs and nonlinear stimulus/firing rate transformations. The durations of STRF excitatory and inhibitory subfields were shorter and the best temporal modulation frequencies were higher for BT neurons than for NT neurons. For NT neurons, the bandwidth of excitatory and inhibitory subfields was matched, whereas for BT neurons it was not. Phase locking and feature selectivity were higher for NT neurons. Properties of the nonlinearities showed only slight differences across the bandwidth modules. These results indicate fundamental differences in spectrotemporal preferences--and thus distinct physiological functions--for neurons in BT and NT spectral integration modules. However, some global processing aspects, such as spectrotemporal interactions and nonlinear input/output behavior, appear to be similar for both neuronal subgroups. The findings suggest that spectral integration modules in AI differ in what specific stimulus aspects are processed, but they are similar in the manner in which stimulus information is processed.

Neurotrophin-3 and FLT3 Tyrosine Kinase Receptor in Perinatal Life

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Ariadne Malamitsi-Puchner

2005-01-01

Full Text Available Our aim is to determine—in 30 healthy full-term infants and their mothers—circulating levels of neurotrophin-3 (NT-3 (important for antenatal and postnatal brain development and implicated in the immune response and FLT3 tyrosine kinase receptor (FLT3 (controlling hematopoiesis and found in the nervous tissue, in the fetal and neonatal life. NT-3 levels, in contrast to FLT3 ones, increased significantly on the fourth postnatal day in relation to the low levels found in the mother, fetus, and day 1 neonate (P=.03, respectively. Maternal and umbilical NT3 levels positively correlated with respective FLT3 levels (P=.003 and P=.03. Circulating NT-3 levels increased in early neonatal life, possibly due to exposure to various stimuli soon after birth. FLT3 levels do not seem to behave accordingly, although these two substances probably synergize.

Investigation into Regeneration Mechanism of Hydroalcoholic Lavender (Lavandula officianalis Extract through the Evaluation of NT3 Gene Expression after Sciatic Nerve Compression in Rats

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Fereshteh Naderi Allaf

2017-05-01

Full Text Available Abstract Background: Retrograde transport to the alpha motoneurons causes spinal degeneration. The neurotrophic factor (NT3 increases the number of myelinated axons in the dorsal root, leads to differentiation and survival of sensory neurons, parasympathetic motoneurons and prevents cell death. Lavender is a plant in the family Lamiaceae which is reported to have antioxidant, antispasmodic, diuretic, anti-asthmatic, refrigerant, and antipyretic effects. This study examined NT3 gene expression changes after sciatic nerve compression in rats, in the presence of Lavandula officinalis extract. Materials and Methods: Lavender Soxhlet hydroalcoholic extraction was prepared. 36 male Wistar rats were randomly divided into 3 groups including control, compression and treatment (compression group + hydroalcoholic extract of Lavender injections 75mg/kg groups. In controls the muscle was opened without damage to gain access to the sciatic nerve. In compression and treatment groups, the sciatic nerve (right leg was compressed. The extract was injected intraperitoneally in two occasions. A biopsy was taken from the spinal cord segments L4-L6 on day 28, total RNA was extracted and cDNA was synthesized and NT3 gene expression changes were analyzed by ANOVA test by using SPSS software. Results: The results showed that NT3 gene expression had a significant reduction in compression group compared to the control group (p<0.001 and it had a significant increase in treatment group compared with the compression group (p<0.001. Conclusion: A significant increase in gene expression shows that Lavandula officinalis hydroalcoholic extract improves nerve regeneration via NT3 gene expression.

ORF Alignment: NT_033779 [GENIUS II[Archive

Lifescience Database Archive (English)

Full Text Available n-like protein CL3 [Periplaneta americana] ... Length = 128 ... Query: 1 ... MVLDNQEDKLLTTTFLKSMGLSFTQSWHH... NT_033779 gi|21357645 >1qddA 26 143 127 254 1e-07 ... dbj|BAA82266.1| Cockroach lecti

Botulinum toxin (BoNT) and back pain.

Science.gov (United States)

Porta, Mauro; Maggioni, G

2004-02-01

Myofascial pain syndrome is defined as subacute or chronic pain with sensory, motor and autonomic symptoms referred from active trigger points with associated painful dysfunctions. Authors present the usefulness of botulinum toxin A or B (BoNT/A or BoNT/B) injected into target muscles since the toxin is capable of controlling not only the muscular spasm but mostly the pain by alternative mechanisms of action, which are discussed. Posology of BoNT, technical aspects and results are presented. BoNT represents an interesting and useful tool for an adequate management of patients with myofascial pain.

1200 nt rat liver mRNA identified by differential hybridization exhibits coordinate regulation with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase

International Nuclear Information System (INIS)

Tanaka, R.D.; Clarke, C.F.; Fogelman, A.M.; Edwards, P.A.

1986-01-01

Differential hybridization has been used to identify genes in rat liver that encode transcripts which are increased by the drugs cholestyramine and mevinolin and are decreased by dietary cholesterol. This approach should prove useful in isolating and identifying coordinately regulated genes involved in the isoprene biosynthetic pathway. Rat liver poly (A) + RNA was isolated from animals fed diets supplemented with either cholestyramine and mevinolin or with cholesterol. Radiolabeled cDNAs generated from these two RNA preparations were used to screen a rat cDNAs library. A preliminary screen of 10,000 recombinants has led to the identification of a clone with an insert of 1200 bp that hybridizes to a mRNA species of about 1200 nt. The level of this RNA species in rat liver is elevated by the drugs cholestyramine and mevinolin and is decreased by cholesterol feeding. This RNA species is also decreased by mevalonate administration to rats. The regulation of this 1200 nt mRNA species mirrors that of HMG CoA reductase and HMG CoA synthase. It seems very likely that this 1200 nt mRNA encodes a polypeptide which is involved in the isoprene biosynthetic pathway

Combining NT3-overexpressing MSCs and PLGA microcarriers for brain tissue engineering: A potential tool for treatment of Parkinson's disease.

Science.gov (United States)

Moradian, Hanieh; Keshvari, Hamid; Fasehee, Hamidreza; Dinarvand, Rassoul; Faghihi, Shahab

2017-07-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder that characterized by destruction of substantia nigrostriatal pathway due to the loss of dopaminergic (DA) neurons. Regardless of substantial efforts for treatment of PD in recent years, an effective therapeutic strategy is still missing. In a multidisciplinary approach, bone marrow derived mesenchymal stem cells (BMSCs) are genetically engineered to overexpress neurotrophin-3 (nt-3 gene) that protect central nervous system tissues and stimulates neuronal-like differentiation of BMSCs. Poly(lactic-co-glycolic acid) (PLGA) microcarriers are designed as an injectable scaffold and synthesized via double emulsion method. The surface of PLGA microcarriers are functionalized by collagen as a bioadhesive agent for improved cell attachment. The results demonstrate effective overexpression of NT-3. The expression of tyrosine hydroxylase (TH) in transfected BMSCs reveal that NT-3 promotes the intracellular signaling pathway of DA neuron differentiation. It is also shown that transfected BMSCs are successfully attached to the surface of microcarriers. The presence of dopamine in peripheral media of cell/microcarrier complex reveals that BMSCs are successfully differentiated into dopaminergic neuron. Our approach that sustains presence of growth factor can be suggested as a novel complementary therapeutic strategy for treatment of Parkinson disease. Copyright © 2017 Elsevier B.V. All rights reserved.

The association between disease activity and NT-proBNP in 238 patients with rheumatoid arthritis: a 10-year longitudinal study

Science.gov (United States)

Provan, Sella A; Angel, Kristin; Ødegård, Sigrid; Mowinckel, Petter; Atar, Dan; Kvien, Tore K

2008-01-01

Introduction Disease activity in patients with rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality, of which N-terminal pro-brain natriuretic peptide (NT-proBNP) is a predictor. Our objective was to examine the cross-sectional and longitudinal associations between markers of inflammation, measures of RA disease activity, medication used in the treatment of RA, and NT-proBNP levels (dependent variable). Methods Two hundred thirty-eight patients with RA of less than 4 years in duration were followed longitudinally with three comprehensive assessments of clinical and radiographic data over a 10-year period. Serum samples were frozen and later batch-analyzed for NT-proBNP levels and other biomarkers. Bivariate, multivariate, and repeated analyses were performed. Results C-reactive protein (CRP) levels at baseline were cross-sectionally associated with NT-proBNP levels after adjustment for age and gender (r2 adjusted = 0.23; P < 0.05). At the 10-year follow-up, risk factors for cardiovascular disease were recorded. Duration of RA and CRP levels were independently associated with NT-proBNP in the final model that was adjusted for gender, age, and creatinine levels (r2 adjusted = 0.38; P < 0.001). In the longitudinal analyses, which adjusted for age, gender, and time of follow-up, we found that repeated measures of CRP predicted NT-proBNP levels (P < 0.001). Conclusion CRP levels are linearly associated with levels of NT-proBNP in cross-sectional and longitudinal analyses of patients with RA. The independent associations of NT-proBNP levels and markers of disease activity with clinical cardiovascular endpoints need to be further investigated. PMID:18573197

Enhanced 2/3 four-ary modulation code using soft-decision Viterbi decoding for four-level holographic data storage systems

Science.gov (United States)

Kong, Gyuyeol; Choi, Sooyong

2017-09-01

An enhanced 2/3 four-ary modulation code using soft-decision Viterbi decoding is proposed for four-level holographic data storage systems. While the previous four-ary modulation codes focus on preventing maximum two-dimensional intersymbol interference patterns, the proposed four-ary modulation code aims at maximizing the coding gains for better bit error rate performances. For achieving significant coding gains from the four-ary modulation codes, we design a new 2/3 four-ary modulation code in order to enlarge the free distance on the trellis through extensive simulation. The free distance of the proposed four-ary modulation code is extended from 1.21 to 2.04 compared with that of the conventional four-ary modulation code. The simulation result shows that the proposed four-ary modulation code has more than 1 dB gains compared with the conventional four-ary modulation code.

END OF NICE 95 AND NICE NT SERVICES

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2002-01-01

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End of NICE 95 and NICE NT services

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2003-01-01

You are concerned by this article if you still use a computer running NICE 95 or NICE NT. As recommended by the Desktop Forum, NICE 95 and NT services will be stopped according to the following schedule: 31st January 2003: NICE 95/NT will be frozen. Applications will still be able to run, but the helpdesk will not address any NICE 95/NT problems anymore. It will not be possible to reinstall NICE 95/NT anymore. Disk images of the original Windows 95 and Windows NT CDs are available on the network, but it will be up to the user to create those CDs, reinstall the machine(s), as well as to locate and install: - the required applications, - the device drivers for special hardware, - the necessary security patches, - an anti-virus software (Operational Circular N 5 of CERN's Computing Rules (http://cern.ch/ComputingRules) requires that Windows PCs are regularly checked for viruses). The original Windows 95 and Windows NT CD images can be obtained from http://cern.ch/win/services/installation/CDImages (please...

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2003-01-01

You are concerned by this article if you still use a computer running NICE 95 or NICE NT. As recommended by the Desktop Forum, NICE 95 and NT services will be stopped according to the following schedule: 31st January 2003: NICE 95/NT will be frozen. Applications will still be able to run, but the helpdesk will not address any NICE 95/NT problems anymore. It will not be possible to reinstall NICE 95/NT anymore. Disk images of the original Windows 95 and Windows NT CDs are available on the network, but it will be up to the user to create those CDs, reinstall the machine(s), as well as to locate and install: - the required applications, - the device drivers for special hardware, - the necessary security patches, - an anti-virus software (Operational Circular N 5 of CERN's Computing Rules (http://cern.ch/ComputingRules) requires that Windows PCs are regularly checked for viruses). The original Windows 95 and Windows NT CD images can be obtained from http://cern.ch/win/services/installation/CDImages (please ...

Purine Restriction Induces Pronounced Translational Upregulation of the NT1 Adenosine/Pyrimidine Nucleoside Transporter in Leishmania major

OpenAIRE

Ortiz, Diana; Valdés, Raquel; Sanchez, Marco A.; Hayenga, Johanna; Elya, Carolyn; Detke, Siegfried; Landfear, Scott M.

2010-01-01

Leishmania and other parasitic protozoa are unable to synthesize purines de novo and are reliant upon purine nucleoside and nucleobase transporters to import preformed purines from their hosts. To study the roles of the four purine permeases NT1-NT4 in Leishmania major, null mutants in each transporter gene were prepared and the effect of each gene deletion on purine uptake was monitored. Deletion of the NT3 purine nucleobase transporter gene or both NT3 and the NT2 nucleoside transporter gen...

Regulation of Brown and White Adipocyte Transcriptome by the Transcriptional Coactivator NT-PGC-1α.

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Jihyun Kim

Full Text Available The β3-adrenergic receptor (AR signaling pathway is a major component of adaptive thermogenesis in brown and white adipose tissue during cold acclimation. The β3-AR signaling highly induces the expression of transcriptional coactivator PGC-1α and its splice variant N-terminal (NT-PGC-1α, which in turn activate the transcription program of adaptive thermogenesis by co-activating a number of transcription factors. We previously reported that NT-PGC-1α is able to increase mitochondrial number and activity in cultured brown adipocytes by promoting the expression of mitochondrial and thermogenic genes. In the present study, we performed genome-wide profiling of NT-PGC-1α-responsive genes in brown adipocytes to identify genes potentially regulated by NT-PGC-1α. Canonical pathway analysis revealed that a number of genes upregulated by NT-PGC-1α are highly enriched in mitochondrial pathways including fatty acid transport and β-oxidation, TCA cycle and electron transport system, thus reinforcing the crucial role of NT-PGC-1α in the enhancement of mitochondrial function. Moreover, canonical pathway analysis of NT-PGC-1α-responsive genes identified several metabolic pathways including glycolysis and fatty acid synthesis. In order to validate the identified genes in vivo, we utilized the FL-PGC-1α-/- mouse that is deficient in full-length PGC-1α (FL-PGC-1α but expresses a slightly shorter and functionally equivalent form of NT-PGC-1α (NT-PGC-1α254. The β3-AR-induced increase of NT-PGC-1α254 in FL-PGC-1α-/- brown and white adipose tissue was closely associated with elevated expression of genes involved in thermogenesis, mitochondrial oxidative metabolism, glycolysis and fatty acid synthesis. Increased adipose tissue thermogenesis by β3-AR activation resulted in attenuation of adipose tissue expansion in FL-PGC-1α-/- adipose tissue under the high-fat diet condition. Together, the data strengthen our previous findings that NT-PGC-1�

NT-pro-BNP is associated with inducible myocardial ischemia in mildly symptomatic type 2 diabetic patients.

Science.gov (United States)

Wiersma, Jacobijne J; van der Zee, P Marc; van Straalen, Jan P; Fischer, Johan C; van Eck-Smit, Berthe L F; Tijssen, Jan G P; Trip, Mieke D; Piek, Jan J; Verberne, Hein J

2010-11-19

Baseline levels of N-terminal fragment of the brain natriuretic peptide prohormone (NT-pro-BNP) are associated with myocardial ischemia in non-diabetic patients with stable angina pectoris. A total of 281 patients with diabetes mellitus type 2 and stable angina pectoris underwent myocardial perfusion scintigraphy (MPS). Myocardial ischemia on MPS was present in 140 (50%) patients. These ischemic patients had significantly higher NT-pro-BNP levels compared with patients without ischemia: 183 pg/ml (64-324 pg/ml) vs. 88 pg/ml (34-207 pg/ml), respectively (ppro-BNP ≥180 pg/ml was an independent predictor of the presence of myocardial ischemia (OR 2.36, 95%CI 1.40-3.97, p=0.001). Possible confounding factors such as age and creatinine clearance were of no influence on the predictive value in this specific patient population. These findings strengthen the idea that NT-pro-BNP may be of value in the early detection of diabetic patients with hemodynamic significant coronary artery disease. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

NT-proBNP levels, atherosclerosis and vascular function in asymptomatic type 2 diabetic patients with microalbuminuria: peripheral reactive hyperaemia index but not NT-proBNP is an independent predictor of coronary atherosclerosis

DEFF Research Database (Denmark)

Reinhard, Henrik; Wiinberg, Niels; Hansen, Peter R

2011-01-01

Intensive multifactorial treatment aimed at cardiovascular (CV) risk factor reduction in type 2 diabetic patients with microalbuminuria can diminish fatal and non-fatal CV. Plasma N-terminal (NT)-proBNP predicts CV mortality in diabetic patients but the utility of P-NT-proBNP in screening for ath......-media thickness (CIMT)>0.90 mm, ankle-brachial index...

Life prediction and mechanical reliability of NT551 silicon nitride

Science.gov (United States)

Andrews, Mark Jay

The inert strength and fatigue performance of a diesel engine exhaust valve made from silicon nitride (Si3N4) ceramic were assessed. The Si3N4 characterized in this study was manufactured by Saint Gobain/Norton Industrial Ceramics and was designated as NT551. The evaluation was made utilizing a probabilistic life prediction algorithm that combined censored test specimen strength data with a Weibull distribution function and the stress field of the ceramic valve obtained from finite element analysis. The major assumptions of the life prediction algorithm are that the bulk ceramic material is isotropic and homogeneous and that the strength-limiting flaws are uniformly distributed. The results from mechanical testing indicated that NT551 was not a homogeneous ceramic and that its strength were functions of temperature, loading rate, and machining orientation. Fractographic analysis identified four different failure modes; 2 were identified as inhomogeneities that were located throughout the bulk of NT551 and were due to processing operations. The fractographic analysis concluded that the strength degradation of NT551 observed from the temperature and loading rate test parameters was due to a change of state that occurred in its secondary phase. Pristine and engine-tested valves made from NT551 were loaded to failure and the inert strengths were obtained. Fractographic analysis of the valves identified the same four failure mechanisms as found with the test specimens. The fatigue performance and the inert strength of the Si3N 4 valves were assessed from censored and uncensored test specimen strength data, respectively. The inert strength failure probability predictions were compared to the inert strength of the Si3N4 valves. The inert strength failure probability predictions were more conservative than the strength of the valves. The lack of correlation between predicted and actual valve strength was due to the nonuniform distribution of inhomogeneities present in NT

NT-proBNP on Cobas h 232 in point-of-care testing

DEFF Research Database (Denmark)

Gils, Charlotte; Ramanathan, R.; Breindahl, T.

2015-01-01

Background. NT-proBNP may be useful for ruling out heart failure in primary health care. In this study we examined the analytical quality of NT-proBNP in primary health care on the Cobas h 232 point-of-care instrument compared with measurements performed in a hospital laboratory. Materials...... and methods. Blood samples requested for NT-proBNP were collected in primary health care (n = 95) and in a hospital laboratory (n = 107). NT-proBNP was measured on-site on Cobas h 232 instruments both in primary health care centres and at the hospital laboratory and all samples were also analyzed...... with a comparison method at the hospital. Precision, trueness, accuracy, and lot-variation were determined at different concentration levels and evaluated according to acceptance criteria. Furthermore user-friendliness was assessed by questionnaires. Results. For Cobas h 232 repeatability CV was 8...

Agonist properties of a stable hexapeptide analog of neurotensin, N alpha MeArg-Lys-Pro-Trp-tLeu-Leu (NT1).

Science.gov (United States)

Akunne, H C; Demattos, S B; Whetzel, S Z; Wustrow, D J; Davis, D M; Wise, L D; Cody, W L; Pugsley, T A; Heffner, T G

1995-04-18

The major signal transduction pathway for neurotensin (NT) receptors is the G-protein-dependent stimulation of phospholipase C, leading to the mobilization of intracellular free Ca2+ ([Ca2+]i) and the stimulation of cyclic GMP. We investigated the functional actions of an analog of NT(8-13), N alpha MeArg-Lys-Pro-Trp-tLeu-Leu (NT1), and other NT related analogs by quantitative measurement of the cytosolic free Ca2+ concentration in HT-29 (human colonic adenocarcinoma) cells using the Ca(2+)-sensitive dye fura-2/AM and by effects on cyclic GMP levels in rat cerebellar slices. The NT receptor binding affinities for these analogs to HT-29 cell membranes and newborn (10-day-old) mouse brain membranes were also investigated. Data obtained from HT-29 cell and mouse brain membrane preparations showed saturable single high-affinity sites and binding densities (Bmax) of 130.2 and 87.5 fmol/mg protein, respectively. The respective KD values were 0.47 and 0.39 nM, and the Hill coefficients were 0.99 and 0.92. The low-affinity levocabastine-sensitive site was not present (K1 > 10,000) in either membrane preparation. Although the correlation of binding between HT-29 cell membranes and mouse brain membranes was quite significant (r = 0.92), some of the reference agents had lower binding affinities in the HT-29 cell membranes. The metabolically stable compound NT1 plus other NT analogs and related peptides [NT, NT(8-13), xenopsin, neuromedin N, NT(9-13), kinetensin and (D-Trp11)-NT] increased intracellular Ca2+ levels in HT-29 cells, indicating NT receptor agonist properties. The effect of NT1 in mobilizing [Ca2+]i blocked by SR 48692, a non-peptide NT antagonist. Receptor binding affinities of NT analogs to HT-29 cell membranes were positively correlated with potencies for mobilizing intracellular calcium in the same cells. In addition, NT1 increased cyclic GMP levels in rat cerebellar slices, confirming the latter findings of its NT agonist action. These results substantiate

Ribosomal protein NtRPL17 interacts with kinesin-12 family protein NtKRP and functions in the regulation of embryo/seed size and radicle growth.

Science.gov (United States)

Tian, Shujuan; Wu, Jingjing; Liu, Yuan; Huang, Xiaorong; Li, Fen; Wang, Zhaodan; Sun, Meng-Xiang

2017-11-28

We previously reported that a novel motor protein belonging to the kinesin-12 family, NtKRP, displays critical roles in regulating embryo and seed size establishment. However, it remains unknown exactly how NtKRP contributes to this developmental process. Here, we report that a 60S ribosomal protein NtRPL17 directly interacts with NtKRP. The phenotypes of NtRPL17 RNAi lines show notable embryo and seed size reduction. Structural observations of the NtRPL17-silenced embryos/seeds reveal that the embryo size reduction is due to a decrease in cell number. In these embryos, cell division cycle progression is delayed at the G2/M transition. These phenotypes are similar to that in NtKRP-silenced embryos/seeds, indicating that NtKRP and NtRPL17 function as partners in the same regulatory pathway during seed development and specifically regulate cell cycle progression to control embryo/seed size. This work reveals that NtRPL17, as a widely distributed ribosomal protein, plays a critical role in seed development and provides a new clue in the regulation of seed size. Confirmation of the interaction between NtKRP and NtRPL17 and their co-function in the control of the cell cycle also suggests that the mechanism might be conserved in both plants and animals. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

End of NICE 95 and NICE NT services (Reminder)

CERN Multimedia

2003-01-01

You are concerned by this article if you still use a computer running NICE 95 or NICE NT. As recommended by the Desktop Forum, NICE 95 and NT services are progressively phased out according to the following schedule: Since 31st January 2003: NICE 95/NT have been frozen. Applications are still able to run, but the helpdesk does not address any NICE 95/NT problems anymore. It is not possible to reinstall NICE 95/NT anymore. Disk images of the original Windows 95 and Windows NT CDs are available on the network, but it is up to the user to create those CDs, reinstall the machine(s), as well as to locate and install: - the required applications, - the device drivers for special hardware, - the necessary security patches, - an anti-virus software (Operational Circular N 5 of CERN's Computing Rules (http://cern.ch/ComputingRules) requires that Windows PCs are regularly checked for viruses). The original Windows 95 and Windows NT CD images can be obtained from http://cern.ch/win/services/installation/CDImages (ple...

Association between neurotrophin 4 and long-chain polyunsaturated fatty acid levels in mid-trimester amniotic fluid.

Science.gov (United States)

Benn, Kiesha; Passos, Mariana; Jayaram, Aswathi; Harris, Mary; Bongiovanni, Ann Marie; Skupski, Daniel; Witkin, Steven S

2014-11-01

The omega-3 long-chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) and the omega-6 LCPUFA arachidonic acid (AA) are essential nervous system components that increase in concentration throughout gestation. The neurotrophins, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4) are small basic peptides crucial for fetal brain development. The DHA supplementation during pregnancy has been suggested to enhance neural development. We evaluated whether amniotic fluid DHA and AA concentrations correlated with intra-amniotic neurotrophin levels. Amniotic fluid, obtained at 15 to 19 weeks gestation from 62 women, was tested for BDNF, NGF, NT3, and NT4 by enzyme-linked immunosorbent assay. Concentrations of DHA and AA, and saturated and monounsaturated fatty acids, were determined by gas chromatography. Associations were analyzed by the Spearman rank correlation test. Median levels of AA and DHA were 2.3% and 1.3% of the total intra-amniotic fatty acids, respectively. Median neurotrophin levels (pg/mL) were 36.7 for NT3, 26.8 for BDNF, 5.2 for NT4, and 0.8 for NGF. Intra-amniotic NT4 and BDNF levels were correlated (P = .0016), while NT3 and NGF levels were unrelated to each other or to BDNF or NT4. Only NT4 was positively correlated with amniotic fluid DHA (P neurotrophin and maternal age, gestational age at time of amniocentesis, amniocentesis indication, parity, or gestational age at delivery. Elevations in intra-amniotic NT4 with increasing levels of DHA and AA suggest that these LCPUFAs may specifically influence the extent of NT4-mediated fetal brain neurogenesis. © The Author(s) 2014.

Phosphatidylinositol (4,5)bisphosphate inhibits K+-efflux channel activity in NT1 tobacco cultured cells.

Science.gov (United States)

Ma, Xiaohong; Shor, Oded; Diminshtein, Sofia; Yu, Ling; Im, Yang Ju; Perera, Imara; Lomax, Aaron; Boss, Wendy F; Moran, Nava

2009-02-01

In the animal world, the regulation of ion channels by phosphoinositides (PIs) has been investigated extensively, demonstrating a wide range of channels controlled by phosphatidylinositol (4,5)bisphosphate (PtdInsP2). To understand PI regulation of plant ion channels, we examined the in planta effect of PtdInsP2 on the K+-efflux channel of tobacco (Nicotiana tabacum), NtORK (outward-rectifying K channel). We applied a patch clamp in the whole-cell configuration (with fixed "cytosolic" Ca2+ concentration and pH) to protoplasts isolated from cultured tobacco cells with genetically manipulated plasma membrane levels of PtdInsP2 and cellular inositol (1,4,5)trisphosphate: "Low PIs" had depressed levels of these PIs, and "High PIs" had elevated levels relative to controls. In all of these cells, K channel activity, reflected in the net, steady-state outward K+ currents (IK), was inversely related to the plasma membrane PtdInsP2 level. Consistent with this, short-term manipulations decreasing PtdInsP2 levels in the High PIs, such as pretreatment with the phytohormone abscisic acid (25 microM) or neutralizing the bath solution from pH 5.6 to pH 7, increased IK (i.e. NtORK activity). Moreover, increasing PtdInsP2 levels in controls or in abscisic acid-treated high-PI cells, using the specific PI-phospholipase C inhibitor U73122 (2.5-4 microM), decreased NtORK activity. In all cases, IK decreases stemmed largely from decreased maximum attainable NtORK channel conductance and partly from shifted voltage dependence of channel gating to more positive potentials, making it more difficult to activate the channels. These results are consistent with NtORK inhibition by the negatively charged PtdInsP2 in the internal plasma membrane leaflet. Such effects are likely to underlie PI signaling in intact plant cells.

NT-proBNP

DEFF Research Database (Denmark)

Andersen, Charlotte; Mellemkjær, Søren; Hilberg, Ole

2016-01-01

BACKGROUND: Pulmonary hypertension (PH) is a serious complication to interstitial lung disease (ILD) and has a poor prognosis. PH is often diagnosed by screening with echocardiography followed by right heart catheterisation. A previous study has shown that a value of NT-pro-brain natriuretic...

The Study of Effects of Aqueous and Alcoholic Extracts of Portulaca oleracea Leaves on NT3 Gene Expression in Degeneration of Alpha Neurons after Sciatic Nerve Compression in Rats

Directory of Open Access Journals (Sweden)

Shokoufe Hejazi

2017-03-01

Full Text Available Abstract Background: The injuries of peripheral nervous system cause the death of a number of motor cells of the spinal cord. Neurotrophins family genes such as NT3 involve in neuronal survive after nerve injury and their expression changes after it. With due attention to the expansion of portulaca pleracea in the world study was conducted to determine the effects of alcoholic and aqueous extracts of Potulaca oleracea on the NT3 gene expression after sciatic nerve compression in rat. Materials and Methods: This study was performed on 88 male wistar rats that randomly were divided in 13 groups of 6 each. They consisted of control group, 4 compression groups (The sciatic nerve was compressed with locker pincer and 8 treatment groups: compression + treatment with dose of 75 mg/kg of alcoholic and aqueous extract of Portulaca oleracea on days 1 and 7 (never compression was done on the first day. In all groups, Total RNA was extracted from the lumbar spinal cord segment in 1, 7, 14, 28 days and cDNA was synthesized, then NT3 expression changes were compared in groups. Results: There was a significant increase in NT3 gene expression in the compression group compared to control (p<0.001. The NT3 gene expression shows significant increase (p<0.05 in the treatment groups with alcoholic extract (except 1& 28 days. Also, there was no significant difference in gene expression between treatment group with acqueous extract and compression group in 1 and 7 days. A significant decrease was seen in the treatment groups with aqueous extract of purslane compared to compression (p<0.05. The NT3 gene expression shows significant increase in the treatment groups with alcoholic extract compared to treatment groups with aqueous extract in all days (p<0.05. Conclusion: The results reveal the Portulaca oleracea leaves extracts increase the NT3 gene expression after sciatic nerve injury. This effect is more in alcoholic extract than aqueous extract.

Elevated levels of plasma brain derived neurotrophic factor in rapid cycling bipolar disorder patients

DEFF Research Database (Denmark)

Munkholm, Klaus; Pedersen, Bente Klarlund; Kessing, Lars Vedel

2014-01-01

Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder, involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is based primarily on case-control desi......Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder, involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is based primarily on case......-control designs. The aim of this study was to investigate whether BDNF and NT-3 levels differ between patients with rapid cycling bipolar disorder and healthy control subjects and whether BDNF and NT-3 levels alter with affective states in rapid cycling bipolar disorder patients. Plasma levels of BDNF and NT-3......, levels of BDNF were significantly elevated in bipolar disorder patients in euthymic- (pdifference in BDNF levels...

On decoding of multi-level MPSK modulation codes

Science.gov (United States)

Lin, Shu; Gupta, Alok Kumar

1990-01-01

The decoding problem of multi-level block modulation codes is investigated. The hardware design of soft-decision Viterbi decoder for some short length 8-PSK block modulation codes is presented. An effective way to reduce the hardware complexity of the decoder by reducing the branch metric and path metric, using a non-uniform floating-point to integer mapping scheme, is proposed and discussed. The simulation results of the design are presented. The multi-stage decoding (MSD) of multi-level modulation codes is also investigated. The cases of soft-decision and hard-decision MSD are considered and their performance are evaluated for several codes of different lengths and different minimum squared Euclidean distances. It is shown that the soft-decision MSD reduces the decoding complexity drastically and it is suboptimum. The hard-decision MSD further simplifies the decoding while still maintaining a reasonable coding gain over the uncoded system, if the component codes are chosen properly. Finally, some basic 3-level 8-PSK modulation codes using BCH codes as component codes are constructed and their coding gains are found for hard decision multistage decoding.

ORF Alignment: NT_033777 [GENIUS II[Archive

Lifescience Database Archive (English)

Full Text Available NT_033777 gi|28571958 >1bor0 1 53 282 342 4e-04 ... ref|NP_083045.3| synoviolin 1 [Mu...s musculus] gb|AAH42199.1| Synoviolin 1 [Mus ... musculus] gb|AAH80722.1| Synoviolin 1 [Mus musculus]... ... gb|AAH57917.1| Synoviolin 1 [Mus musculus] ... Length = 61 ... Query: 280 EELRQSDNICIICREDMV

Prenatal Clinical Assessment of NT-proBNP as a Diagnostic Tool for Preeclampsia, Gestational Hypertension and Gestational Diabetes Mellitus.

Directory of Open Access Journals (Sweden)

Pawel Sadlecki

Full Text Available Common complications of pregnancy include preeclampsia (PE, gestational hypertension (GH and gestational diabetes mellitus (GDM. Hypertensive disorders (PE/GH and GDM may result in greater maternal, fetal and neonatal morbidity and mortality. Women with PE/GH, one of the most common causes of heart burden in an obstetrical setting, present with elevated serum levels of BNP and NT-proBNP. The aim of this study was to shed more light on the role of NT-proBNP in pathophysiology of PE, GH and GDM. The study included 156 pregnant women with singleton pregnancies. A total of 26 women developed arterial hypertension during pregnancy, 14 were diagnosed with PE, and GDM was detected in 81 patients. The control group included 35 women with uncomplicated pregnancies, normal arterial blood pressure and normal glucose concentrations. Patients with GH presented with significantly higher serum concentrations of NT-proBNPthan normotensive women (65.5 vs. 37.4 pg/ml; p = 0.0136. Serum levels of NT-proBNP in patients with PE were the highest of all the analyzed subsets, being significantly higher than in women without this condition (89.00 vs. 37.4pg/ml,p = 0,0136. However, women with and without GDM did not differ significantly in terms of their serum NT-proBNPconcentrations. Serum NT-proBNP (pg/ml (p = 0.0001 and BMI (p<0.0001 turned out to be independent predictors of GH on multivariate logistic regression analysis.Moreover, serum NT-proBNP (pg/ml was identified as an independent indicator of PE (p = 0.0016. A significant inverse correlation was found between birth weight and maternal serum NT-proBNP concentrations. In our opinion, NT-proBNP can be a useful clinical marker of GH and PE. Determination of NT-proBNP levels may be helpful in identification of patients with PE and GH and in their qualification for intensive treatment; this in turn, may be reflected by better neonatal outcomes.

NT-proBNP levels, atherosclerosis and vascular function in asymptomatic type 2 diabetic patients with microalbuminuria: peripheral reactive hyperaemia index but not NT-proBNP is an independent predictor of coronary atherosclerosis

DEFF Research Database (Denmark)

Reinhard, Henrik; Wiinberg, Niels; Hansen, Peter R

2011-01-01

for atherosclerosis is unclear. We examined the interrelationship between P-NT-proBNP, presence of atherosclerosis and/or vascular dysfunction in the coronary, carotid and peripheral arteries in asymptomatic type 2 diabetic patients with microalbuminuria that received intensive multifactorial treatment. METHODS...... AND RESULTS: P-NT-proBNP was measured in 200 asymptomatic type 2 patients without known cardiac disease that received intensive multifactorial treatment for CV risk reduction. Patients were examined for coronary, carotid and peripheral atherosclerosis, as defined by coronary calcium score=400, carotid intima...

Sincronización de Células de Tabaco (Nicotiana tabacum) NT-1 Synchronization of tobacco cells (Nicotiana tabacum) NT-1

OpenAIRE

León F Ruiz; Ana E Higareda; Marco A Pardo

2010-01-01

Se ha evaluado la capacidad sincronizante de afidicolina e hidroxiurea en cultivos de células de tabaco (Nicotiana tabacum) NT-1. Los cultivos sincronizados son poderosas herramientas en estudios moleculares y bioquímicos relacionados al ciclo celular y comúnmente se utilizan químicos para bloquear el ciclo celular. La línea celular de tabaco (Nicotiana tabacum) NT-1 proviene de la línea celular TBY-2, caracterizándose NT-1 por su menor velocidad de crecimiento y tamaño celular heterogéneo. L...

Cerebrolysin modulates pronerve growth factor/nerve growth factor ratio and ameliorates the cholinergic deficit in a transgenic model of Alzheimer's disease.

Science.gov (United States)

Ubhi, Kiren; Rockenstein, Edward; Vazquez-Roque, Ruben; Mante, Michael; Inglis, Chandra; Patrick, Christina; Adame, Anthony; Fahnestock, Margaret; Doppler, Edith; Novak, Philip; Moessler, Herbert; Masliah, Eliezer

2013-02-01

Alzheimer's disease (AD) is characterized by degeneration of neocortex, limbic system, and basal forebrain, accompanied by accumulation of amyloid-β and tangle formation. Cerebrolysin (CBL), a peptide mixture with neurotrophic-like effects, is reported to improve cognition and activities of daily living in patients with AD. Likewise, CBL reduces synaptic and behavioral deficits in transgenic (tg) mice overexpressing the human amyloid precursor protein (hAPP). The neuroprotective effects of CBL may involve multiple mechanisms, including signaling regulation, control of APP metabolism, and expression of neurotrophic factors. We investigate the effects of CBL in the hAPP tg model of AD on levels of neurotrophic factors, including pro-nerve growth factor (NGF), NGF, brain-derived neurotrophic factor (BDNF), neurotropin (NT)-3, NT4, and ciliary neurotrophic factor (CNTF). Immunoblot analysis demonstrated that levels of pro-NGF were increased in saline-treated hAPP tg mice. In contrast, CBL-treated hAPP tg mice showed levels of pro-NGF comparable to control and increased levels of mature NGF. Consistently with these results, immunohistochemical analysis demonstrated increased NGF immunoreactivity in the hippocampus of CBL-treated hAPP tg mice. Protein levels of other neurotrophic factors, including BDNF, NT3, NT4, and CNTF, were unchanged. mRNA levels of NGF and other neurotrophins were also unchanged. Analysis of neurotrophin receptors showed preservation of the levels of TrKA and p75(NTR) immunoreactivity per cell in the nucleus basalis. Cholinergic cells in the nucleus basalis were reduced in the saline-treated hAPP tg mice, and treatment with CBL reduced these cholinergic deficits. These results suggest that the neurotrophic effects of CBL might involve modulation of the pro-NGF/NGF balance and a concomitant protection of cholinergic neurons. Copyright © 2012 Wiley Periodicals, Inc.

Involvement of the putative Ca²⁺-permeable mechanosensitive channels, NtMCA1 and NtMCA2, in Ca²⁺ uptake, Ca²⁺-dependent cell proliferation and mechanical stress-induced gene expression in tobacco (Nicotiana tabacum) BY-2 cells.

Science.gov (United States)

Kurusu, Takamitsu; Yamanaka, Takuya; Nakano, Masataka; Takiguchi, Akiko; Ogasawara, Yoko; Hayashi, Teruyuki; Iida, Kazuko; Hanamata, Shigeru; Shinozaki, Kazuo; Iida, Hidetoshi; Kuchitsu, Kazuyuki

2012-07-01

To gain insight into the cellular functions of the mid1-complementing activity (MCA) family proteins, encoding putative Ca²⁺-permeable mechanosensitive channels, we isolated two MCA homologs of tobacco (Nicotiana tabacum) BY-2 cells, named NtMCA1 and NtMCA2. NtMCA1 and NtMCA2 partially complemented the lethality and Ca²⁺ uptake defects of yeast mutants lacking mechanosensitive Ca²⁺ channel components. Furthermore, in yeast cells overexpressing NtMCA1 and NtMCA2, the hypo-osmotic shock-induced Ca²⁺ influx was enhanced. Overexpression of NtMCA1 or NtMCA2 in BY-2 cells enhanced Ca²⁺ uptake, and significantly alleviated growth inhibition under Ca²⁺ limitation. NtMCA1-overexpressing BY-2 cells showed higher sensitivity to hypo-osmotic shock than control cells, and induced the expression of the touch-inducible gene, NtERF4. We found that both NtMCA1-GFP and NtMCA2-GFP were localized at the plasma membrane and its interface with the cell wall, Hechtian strands, and at the cell plate and perinuclear vesicles of dividing cells. NtMCA2 transcript levels fluctuated during the cell cycle and were highest at the G1 phase. These results suggest that NtMCA1 and NtMCA2 play roles in Ca²⁺-dependent cell proliferation and mechanical stress-induced gene expression in BY-2 cells, by regulating the Ca²⁺ influx through the plasma membrane.

Strength and fatigue of NT551 silicon nitride and NT551 diesel exhaust valves

Energy Technology Data Exchange (ETDEWEB)

Andrews, M.J.; Werezczak, A.A.; Kirkland, T.P.; Breder, K.

2000-02-01

The content of this report is excerpted from Mark Andrew's Ph.D. Thesis (Andrews, 1999), which was funded by a DOE/OTT High Temperature Materials Laboratory Graduate Fellowship. It involves the characterization of NT551 and valves fabricated with it. The motivations behind using silicon nitride (Si{sub 3}N{sub 4}) as an exhaust valve for a diesel engine are presented in this section. There are several economic factors that have encouraged the design and implementation of ceramic components for internal combustion (IC) engines. The reasons for selecting the diesel engine valve for this are also presented.

NT-proBNP, echocardiographic abnormalities and subclinical coronary artery disease in high risk type 2 diabetic patients

DEFF Research Database (Denmark)

Reinhard, Henrik; Hansen, Peter R; Wiinberg, Niels

2012-01-01

-NT-proBNP and the putative residual abnormalities in such patients are not well described. This study examined echocardiographic measurements of LV hypertrophy, atrial dilatation and LV dysfunction and their relation to P-NT-proBNP levels or subclinical coronary artery disease (CAD) in type 2 diabetic patients......Intensive multifactorial treatment aimed at prevention of cardiovascular (CV) disease may reduce left ventricular (LV) echocardiographic abnormalities in diabetic subjects. Plasma N-terminal (NT)-proBNP predicts CV mortality in diabetic patients but the association between P...

Linear flow dynamics near a T/NT interface

Science.gov (United States)

Teixeira, Miguel; Silva, Carlos

2011-11-01

The characteristics of a suddenly-inserted T/NT interface separating a homogeneous and isotropic shear-free turbulence region from a non-turbulent flow region are investigated using rapid distortion theory (RDT), taking full account of viscous effects. Profiles of the velocity variances, TKE, viscous dissipation rate, turbulence length scales, and pressure statistics are derived, showing very good agreement with DNS. The normalized inviscid flow statistics at the T/NT interface do not depend on the form of the assumed TKE spectrum. In the non-turbulent region, where the flow is irrotational (except within a thin viscous boundary layer), the dissipation rate decays as z-6, where z is distance from the T/NT interface. The mean pressure exhibits a decrease towards the turbulence due to the associated velocity fluctuations, consistent with the generation of a mean entrainment velocity. The vorticity variance and dissipation rate display large maxima at the T/NT interface due to the existing inviscid discontinuities of the tangential velocity, and these maxima are quantitatively related to the thickness of the viscous boundary layer (VBL). At equilibrium, RDT suggests that the thickness of the T/NT interface scales on the Kolmogorov microscale. We acknowledge the financial support of FCT under Project PTDC/EME-MFE/099636/2008.

Decreased plasma neurotrophin-4/5 levels in bipolar disorder patients in mania.

Science.gov (United States)

Barbosa, Izabela G; Morato, Isabela B; Huguet, Rodrigo B; Rocha, Fabio L; Machado-Vieira, Rodrigo; Teixeira, Antônio L

2014-01-01

To evaluate two poorly explored neurotrophins (NT), NT-3 and NT-4/5, in bipolar disorder (BD). Forty patients with type I BD (18 in remission and 22 in mania) and 25 healthy controls matched for age, gender, and educational attainment were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatric Interview; the Young Mania Rating Scale and the Hamilton Depression Rating Scale were used to evaluate severity of symptoms in BD patients. Plasma levels of NT-3 and NT-4/5 were measured by enzyme-linked immunosorbent assay (ELISA). BD patients in mania presented decreased NT-4/5 plasma levels in comparison with controls (p neurotrophin dysfunction is associated with mood states in patients with BD.

SU-E-T-417: The Impact of Normal Tissue Constraints On PTV Dose Homogeneity for Intensity Modulated Radiotherapy (IMRT), Volume Modulated Arc Therapy (VMAT) and Tomotherapy

Energy Technology Data Exchange (ETDEWEB)

Peng, J; McDonald, D; Ashenafi, M; Ellis, A; Vanek, K [Medical University of South Carolina, Charleston, SC (United States)

2014-06-01

Purpose: Complex intensity modulated arc therapy tends to spread low dose to normal tissue(NT)regions to obtain improved target conformity and homogeneity and OAR sparing.This work evaluates the trade-offs between PTV homogeneity and reduction of the maximum dose(Dmax)spread to NT while planning of IMRT,VMAT and Tomotherapy. Methods: Ten prostate patients,previously planned with step-and-shoot IMRT,were selected.To fairly evaluate how PTV homogeneity was affected by NT Dmax constraints,original IMRT DVH objectives for PTV and OARs(femoral heads,and rectal and bladder wall)applied to 2 VMAT plans in Pinnacle(V9.0), and Tomotherapy(V4.2).The only constraint difference was the NT which was defined as body contours excluding targets,OARs and dose rings.NT Dmax constraint for 1st VMAT was set to the prescription dose(Dp).For 2nd VMAT(VMAT-NT)and Tomotherapy,it was set to the Dmax achieved in IMRT(~70-80% of Dp).All NT constraints were set to the lowest priority.Three common homogeneity indices(HI),RTOG-HI=Dmax/Dp,moderated-HI=D95%/D5% and complex-HI=(D2%-D98%)/Dp*100 were calculated. Results: All modalities with similar dosimetric endpoints for PTV and OARs.The complex-HI shows the most variability of indices,with average values of 5.9,4.9,9.3 and 6.1 for IMRT,VMAT,VMAT-NT and Tomotherapy,respectively.VMAT provided the best PTV homogeneity without compromising any OAR/NT sparing.Both VMAT-NT and Tomotherapy,planned with more restrictive NT constraints,showed reduced homogeneity,with VMAT-NT showing the worst homogeneity(P<0.0001)for all HI.Tomotherapy gave the lowest NT Dmax,with slightly decreased homogeneity compared to VMAT. Finally, there was no significant difference in NT Dmax or Dmean between VMAT and VMAT-NT. Conclusion: PTV HI is highly dependent on permitted NT constraints. Results demonstrated that VMAT-NT with more restrictive NT constraints does not reduce Dmax NT,but significantly receives higher Dmax and worse target homogeneity.Therefore, it is critical

Evidence for a role of NTS2 receptors in the modulation of tonic pain sensitivity

Directory of Open Access Journals (Sweden)

Martinez Jean

2009-07-01

Full Text Available Abstract Background Central neurotensin (NT administration results in a naloxone-insensitive antinociceptive response in animal models of acute and persistent pain. Both NTS1 and NTS2 receptors were shown to be required for different aspects of NT-induced analgesia. We recently demonstrated that NTS2 receptors were extensively associated with ascending nociceptive pathways, both at the level of the dorsal root ganglia and of the spinal dorsal horn. Then, we found that spinally administered NTS2-selective agonists induced dose-dependent antinociceptive responses in the acute tail-flick test. In the present study, we therefore investigated whether activation of spinal NTS2 receptors suppressed the persistent inflammatory pain symptoms observed after intraplantar injection of formalin. Results We first demonstrated that spinally administered NT and NT69L agonists, which bind to both NTS1 and NTS2 receptors, significantly reduced pain-evoked responses during the inflammatory phase of the formalin test. Accordingly, pretreatment with the NTS2-selective analogs JMV-431 and levocabastine was effective in inhibiting the aversive behaviors induced by formalin. With resolution at the single-cell level, we also found that activation of spinal NTS2 receptors reduced formalin-induced c-fos expression in dorsal horn neurons. However, our results also suggest that NTS2-selective agonists and NTS1/NTS2 mixed compounds differently modulated the early (21–39 min and late (40–60 min tonic phase 2 and recruited endogenous pain inhibitory mechanisms integrated at different levels of the central nervous system. Indeed, while non-selective drugs suppressed pain-related behaviors activity in both part of phase 2, intrathecal injection of NTS2-selective agonists was only efficient in reducing pain during the late phase 2. Furthermore, assessment of the stereotypic pain behaviors of lifting, shaking, licking and biting to formalin also revealed that unlike non

NT-proBNP as Marker of Ventricular Dilatation and Pulmonary Regurgitation After Surgical Correction of Tetralogy of Fallot: A MRI Validation Study.

Science.gov (United States)

Paolino, Annalisa; Hussain, Tarique; Pavon, Antonio; Velasco, Maria Nieves; Uribe, Sergio; Ordoñez, Antonio; Valverde, Israel

2017-02-01

The goal of this study is to evaluate whether NT-proBNP plasma levels may help as a screening biomarker for monitoring right ventricular dilatation, pulmonary regurgitation and the onset of heart failure in patients with repaired Tetralogy of Fallot. Our single-centre observational prospective study involved 43 patients (15.1 years, SD = 8) with corrected Tetralogy of Fallot. Data collection included: clinical parameters (electrocardiogram, chest X-ray, NYHA scale, time since last surgery), biochemistry (NT-proBNP levels) and MRI values (ventricular volumetry, pulmonary flow assessment). Mean time since last surgery was 13.5 years (SD = 7.8). There was a statistically significant correlation between the NT-proBNP levels (187.4 pg/ml, SD = 154.9) and right ventricular dilatation for both the right ventricular end-diastolic volume (124.9 ml/m 2 , SD = 31.2) (Pearson = 0.19, p Tetralogy of Fallot, NT-proBNP levels correlate with right ventricular dilatation and the degree of pulmonary regurgitation. Ambulatory determination of NT-proBNP might be an easy, readily available and cost-effective alternative for MRI follow-up evaluation of these patients.

Particulated articular cartilage: CAIS and DeNovo NT.

Science.gov (United States)

Farr, Jack; Cole, Brian J; Sherman, Seth; Karas, Vasili

2012-03-01

Cartilage Autograft Implantation System (CAIS; DePuy/Mitek, Raynham, MA) and DeNovo Natural Tissue (NT; ISTO, St. Louis, MO) are novel treatment options for focal articular cartilage defects in the knee. These methods involve the implantation of particulated articular cartilage from either autograft or juvenile allograft donor, respectively. In the laboratory and in animal models, both CAIS and DeNovo NT have demonstrated the ability of the transplanted cartilage cells to "escape" from the extracellular matrix, migrate, multiply, and form a new hyaline-like cartilage tissue matrix that integrates with the surrounding host tissue. In clinical practice, the technique for both CAIS and DeNovo NT is straightforward, requiring only a single surgery to affect cartilage repair. Clinical experience is limited, with short-term studies demonstrating both procedures to be safe, feasible, and effective, with improvements in subjective patient scores, and with magnetic resonance imaging evidence of good defect fill. While these treatment options appear promising, prospective randomized controlled studies are necessary to refine the indications and contraindications for both CAIS and DeNovo NT.

Tobacco arabinogalactan protein NtEPc can promote banana (Musa AAA) somatic embryogenesis.

Science.gov (United States)

Shu, H; Xu, L; Li, Z; Li, J; Jin, Z; Chang, S

2014-12-01

Banana is an important tropical fruit worldwide. Parthenocarpy and female sterility made it impossible to improve banana varieties through common hybridization. Genetic transformation for banana improvement is imperative. But the low rate that banana embryogenic callus was induced made the transformation cannot be performed in many laboratories. Finding ways to promote banana somatic embryogenesis is critical for banana genetic transformation. After tobacco arabinogalactan protein gene NtEPc was transformed into Escherichia coli (DE3), the recombinant protein was purified and filter-sterilized. A series of the sterilized protein was added into tissue culture medium. It was found that the number of banana immature male flowers developing embryogenic calli increased significantly in the presence of NtEPc protein compared with the effect of the control medium. Among the treatments, explants cultured on medium containing 10 mg/l of NtEPc protein had the highest chance to develop embryogenic calli. The percentage of lines that developed embryogenic calli on this medium was about 12.5 %. These demonstrated that NtEPc protein can be used to promote banana embryogenesis. This is the first paper that reported that foreign arabinogalactan protein (AGP) could be used to improve banana somatic embryogenesis.

Polymer-based 2D/3D wafer level heterogeneous integration for SSL module

NARCIS (Netherlands)

Yuan, C.; Wei, J.; Ye, H.; Koh, S.; Harianto, S.; Nieuwenhof, M.A. van den; Zhang, G.Q.

2012-01-01

This paper demonstrates a heterogeneous integration of solid state lighting (SSL) module, including light source (LED) and driver/control components. Such integration has been realized by the polymer-based reconfigured wafer level package technologies and such structure has been prototyped and

Neurotensin Phosphorylates GSK-3α/β through the Activation of PKC in Human Colon Cancer Cells

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Qingding Wang

2006-09-01

Full Text Available Neurotensin (NT, a gastrointestinal hormone, binds its receptor [neurotensin receptor (NTR] to regulate the growth of normal and neoplastic intestinal cells; molecular mechanisms remain largely undefined. Glycogen synthase kinase-3 (GSK-3 regulates diverse cellular processes, including cell growth and apoptosis. Here, we show that NT induces the phosphorylation of GSK-3α/β in the human colon cancer cell line HT29, HCT116, or SW480, which possesses high-affinity NTR. The effect of NT was blocked by inhibitors of protein kinase C (PKC, but not by inhibitors of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK1 or phosphatidylinositol-3 kinase, suggesting a predominant role for PKC in GSK-3β phosphorylation by NT. Pretreatment with Gö6976 (which inhibits PKCα and PKCβ1 or downregulation of endogenous PKCα or PKCβ1 blocked NT-mediated GSK-3β (but not GSK-3α phosphorylation. Moreover, a selective PKCβ inhibitor, LY379196, reduced NT-mediated GSK-3β (but not GSK-3α phosphorylation, suggesting a role for PKCbβ in the NT-mediated phosphorylation of GSK-3β and an undefined kinase in the NT-mediated phosphorylation of GSK-3α. Treatment with NT or the GSK-3 inhibitor SB216763 increased the expression of cyclin D1, a downstream effector protein of GSK-3 and a critical protein for the proliferation of various cells. Our results indicate that NT uses PKC-dependent pathways to modulate GSK-3, which may play a role in the NT regulation of intestinal cell growth.

Mortality and preoperative cardiac function in vascular amputees: an N-terminal pro-brain natriuretic peptide (NT-proBNP) pilot study

OpenAIRE

Riemersma, Marcel; Dijkstra, Pieter U.; van Veldhuisen, Dirk Jan; Muskiet, Frits A. J.; van den Dungen, Jan A. M. M.; Geertzen, Jan H. B.

2008-01-01

Objective: To determine preoperative ventricular function in vascular amputees by measuring N-terminal pro-brain natriuretic peptide (NT-proBNP) and to analyse the relationship between NT-proBNP levels and 30-day postoperative mortality. Design: Prospective pilot study. Subjects and methods: In 19 patients planned for a lower limb amputation for nonreconstructable peripheral arterial disease NT-proBNP was measured the day before amputation. Results: Four amputees died within 30 days after the...

NT-proBNP (N-Terminal pro-B-Type Natriuretic Peptide)-Guided Therapy in Acute Decompensated Heart Failure: PRIMA II Randomized Controlled Trial (Can NT-ProBNP-Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure Reduce Mortality and Readmissions?).

Science.gov (United States)

Stienen, Susan; Salah, Khibar; Moons, Arno H; Bakx, Adrianus L; van Pol, Petra; Kortz, R A Mikael; Ferreira, João Pedro; Marques, Irene; Schroeder-Tanka, Jutta M; Keijer, Jan T; Bayés-Genis, Antoni; Tijssen, Jan G P; Pinto, Yigal M; Kok, Wouter E

2018-04-17

The concept of natriuretic peptide guidance has been extensively studied in patients with chronic heart failure (HF), with only limited success. The effect of NT-proBNP (N-terminal probrain natriuretic peptide)-guided therapy in patients with acute decompensated HF using a relative NT-proBNP target has not been investigated. This study aimed to assess whether NT-proBNP-guided therapy of patients with acute decompensated HF using a relative NT-proBNP target would lead to improved outcomes compared with conventional therapy. We conducted a prospective randomized controlled trial to study the impact of in-hospital guidance for acute decompensated HF treatment by a predefined NT-proBNP target (>30% reduction from admission to discharge) versus conventional treatment. Patients with acute decompensated HF with NT-proBNP levels >1700 ng/L were eligible. After achieving clinical stability, 405 patients were randomized to either NT-proBNP-guided or conventional treatment (1:1). The primary end point was dual: a composite of all-cause mortality and HF readmissions in 180 days and the number of days alive out of the hospital in 180 days. Secondary end points were all-cause mortality within 180 days, HF readmissions within 180 days, and a composite of all-cause mortality and HF readmissions within 90 days. Significantly more patients in the NT-proBNP-guided therapy group were discharged with an NT-proBNP reduction of >30% (80% versus 64%, P =0.001). Nonetheless, NT-proBNP-guided therapy did not significantly improve the combined event rate for all-cause mortality and HF readmissions (hazard ratio, 0.96; 95% confidence interval, 0.72-1.37; P =0.99) or the median number of days alive outside of the hospital (178 versus 179 days for NT-proBNP versus conventional patients, P =0.39). Guided therapy also did not significantly improve any of the secondary end points. The PRIMA II trial (Can NT-ProBNP-Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure

Overexpression of NtPR-Q Up-Regulates Multiple Defense-Related Genes in Nicotiana tabacum and Enhances Plant Resistance to Ralstonia solanacearum

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Yuanman Tang

2017-11-01

Full Text Available Various classes of plant pathogenesis-related proteins have been identified in the past several decades. PR-Q, a member of the PR3 family encoding chitinases, has played an important role in regulating plant resistance and preventing pathogen infection. In this paper, we functionally characterized NtPR-Q in tobacco plants and found that the overexpression of NtPR-Q in tobacco Yunyan87 resulted in higher resistance to Ralstonia solanacearum inoculation. Surprisingly, overexpression of NtPR-Q led to the activation of many defense-related genes, such as salicylic acid (SA-responsive genes NtPR1a/c, NtPR2 and NtCHN50, JA-responsive gene NtPR1b and ET production-associated genes NtACC Oxidase and NtEFE26. Consistent with the role of NtPR-Q in multiple stress responses, NtPR-Q transcripts were induced by the exogenous hormones SA, ethylene and methyl jasmonate, which could enhance the resistance of tobacco to R. solanacearum. Collectively, our results suggested that NtPR-Q overexpression led to the up-regulation of defense-related genes and enhanced plant resistance to R. solanacearum infection.

A study of radiation parameters at Nabarlek uranium mine, N.T

International Nuclear Information System (INIS)

Leach, V.A.; Lokan, K.H.; Martin, L.J.

1980-09-01

Radiation parameters associated with the open pit mining of a small (10,000 tonnes), but high grade (2 per cent) uranium deposit at Nabarlek, N.T., have been investigated. External radiation levels, radon emanation rates and radon daughter levels were measured systematically during the development of the mine, and are correlated with ore grade, properties of the host rock and atmospheric conditions. Significant radon daughter concentrations were observed only under stable atmospheric conditions, usually during the night and were invariably associated with thermal inversions. The mean cumulative exposure to radon daughters was estimated from the measured levels to be 0.065 Working Level Months for exployees working in the pit for the entire four and a half months of mining. The mean cumulative external gamma ray exposure for the same employee group was measured using thermoluminescent dosimeters to be 2.3 mSv (230 millirem). Data on long lived radionuclides in dust and on particle size distribution are also presented

Dosimetric analysis of testicular doses in prostate intensity-modulated and volumetric-modulated arc radiation therapy at different energy levels

Energy Technology Data Exchange (ETDEWEB)

Onal, Cem, E-mail: hcemonal@hotmail.com; Arslan, Gungor; Dolek, Yemliha; Efe, Esma

2016-01-01

The aim of this study is to evaluate the incidental testicular doses during prostate radiation therapy with intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc radiotherapy (VMAT) at different energies. Dosimetric data of 15 patients with intermediate-risk prostate cancer who were treated with radiotherapy were analyzed. The prescribed dose was 78 Gy in 39 fractions. Dosimetric analysis compared testicular doses generated by 7-field intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy with a single arc at 6, 10, and 15 MV energy levels. Testicular doses calculated from the treatment planning system and doses measured from the detectors were analyzed. Mean testicular doses from the intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy per fraction calculated in the treatment planning system were 16.3 ± 10.3 cGy vs 21.5 ± 11.2 cGy (p = 0.03) at 6 MV, 13.4 ± 10.4 cGy vs 17.8 ± 10.7 cGy (p = 0.04) at 10 MV, and 10.6 ± 8.5 cGy vs 14.5 ± 8.6 cGy (p = 0.03) at 15 MV, respectively. Mean scattered testicular doses in the phantom measurements were 99.5 ± 17.2 cGy, 118.7 ± 16.4 cGy, and 193.9 ± 14.5 cGy at 6, 10, and 15 MV, respectively, in the intensity-modulated radiotherapy plans. In the volumetric-modulated arc radiotherapy plans, corresponding testicular doses per course were 90.4 ± 16.3 cGy, 103.6 ± 16.4 cGy, and 139.3 ± 14.6 cGy at 6, 10, and 15 MV, respectively. In conclusions, this study was the first to measure the incidental testicular doses by intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy plans at different energy levels during prostate-only irradiation. Higher photon energy and volumetric-modulated arc radiotherapy plans resulted in higher incidental testicular doses compared with lower photon energy and intensity-modulated radiotherapy plans.

MRI-Monitored Intra-Tumoral Injection of Iron-Oxide Labeled Clostridium novyi-NT Anaerobes in Pancreatic Carcinoma Mouse Model

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Zheng, Linfeng; Zhang, Zhuoli; Khazaie, Khashayarsha; Saha, Saurabh; Lewandowski, Robert J.; Zhang, Guixiang; Larson, Andrew C.

2014-01-01

Objectives To validate the feasibility of labeling Clostridium novyi-NT (C.novyi-NT) anaerobes with iron-oxide nanoparticles for magnetic resonance imaging (MRI) and demonstrate the potential to use MRI to visualize intra-tumoral delivery of these iron-oxide labeled C.novyi-NT during percutaneous injection procedures. Materials and Methods All studies were approved by IACUC. C.novyi-NT were labeled with hybrid iron-oxide Texas red nanoparticles. Growth of labeled and control samples were evaluated with optical density. Labeling was confirmed with confocal fluorescence and transmission electron microscopy (TEM). MRI were performed using a 7 Tesla scanner with T2*-weighted (T2*W) sequence. Contrast-to-noise ratio (CNR) measurements were performed for phantoms and signal-to-noise ratio (SNR) measurements performed in C57BL/6 mice (n = 12) with Panc02 xenografts before and after percutaneous injection of iron-oxide labeled C.novyi-NT. MRI was repeated 3 and 7 days post-injection. Hematoxylin-eosin (HE), Prussian blue and Gram staining of tumor specimens were performed for confirmation of intra-tumoral delivery. Results Iron-oxide labeling had no influence upon C.novyi-NT growth. The signal intensity (SI) within T2*W images was significantly decreased for iron-oxide labeled C.novyi-NT phantoms compared to unlabeled controls. Under confocal fluorescence microscopy, the iron-oxide labeled C.novyi-NT exhibited a uniform red fluorescence consistent with observed regions of DAPI staining and overall labeling efficiency was 100% (all DAPI stained C.novyi-NT exhibited red fluorescence). Within TEM images, a large number iron granules were observed within the iron-oxide labeled C.novyi-NT; these were not observed within unlabeled controls. Intra-procedural MRI measurements permitted in vivo visualization of the intra-tumoral distribution of iron-oxide labeled C.novyi-NT following percutaneous injection (depicted as punctate regions of SI reductions within T2*-weighted

Mortality and preoperative cardiac function in vascular amputees : an N-terminal pro-brain natriuretic peptide (NT-proBNP) pilot study

NARCIS (Netherlands)

Riemersma, Marcel; Dijkstra, Pieter U.; van Veldhuisen, Dirk Jan; Muskiet, Frits A. J.; van den Dungen, Jan A. M. M.; Geertzen, Jan H. B.

Objective: To determine preoperative ventricular function in vascular amputees by measuring N-terminal pro-brain natriuretic peptide (NT-proBNP) and to analyse the relationship between NT-proBNP levels and 30-day postoperative mortality. Design: Prospective pilot study. Subjects and methods: In 19

Phosphatidylinositol (4,5)Bisphosphate Inhibits K+-Efflux Channel Activity in NT1 Tobacco Cultured Cells1[W][OA

Science.gov (United States)

Ma, Xiaohong; Shor, Oded; Diminshtein, Sofia; Yu, Ling; Im, Yang Ju; Perera, Imara; Lomax, Aaron; Boss, Wendy F.; Moran, Nava

2009-01-01

In the animal world, the regulation of ion channels by phosphoinositides (PIs) has been investigated extensively, demonstrating a wide range of channels controlled by phosphatidylinositol (4,5)bisphosphate (PtdInsP2). To understand PI regulation of plant ion channels, we examined the in planta effect of PtdInsP2 on the K+-efflux channel of tobacco (Nicotiana tabacum), NtORK (outward-rectifying K channel). We applied a patch clamp in the whole-cell configuration (with fixed “cytosolic” Ca2+ concentration and pH) to protoplasts isolated from cultured tobacco cells with genetically manipulated plasma membrane levels of PtdInsP2 and cellular inositol (1,4,5)trisphosphate: “Low PIs” had depressed levels of these PIs, and “High PIs” had elevated levels relative to controls. In all of these cells, K channel activity, reflected in the net, steady-state outward K+ currents (IK), was inversely related to the plasma membrane PtdInsP2 level. Consistent with this, short-term manipulations decreasing PtdInsP2 levels in the High PIs, such as pretreatment with the phytohormone abscisic acid (25 μm) or neutralizing the bath solution from pH 5.6 to pH 7, increased IK (i.e. NtORK activity). Moreover, increasing PtdInsP2 levels in controls or in abscisic acid-treated high-PI cells, using the specific PI-phospholipase C inhibitor U73122 (2.5–4 μm), decreased NtORK activity. In all cases, IK decreases stemmed largely from decreased maximum attainable NtORK channel conductance and partly from shifted voltage dependence of channel gating to more positive potentials, making it more difficult to activate the channels. These results are consistent with NtORK inhibition by the negatively charged PtdInsP2 in the internal plasma membrane leaflet. Such effects are likely to underlie PI signaling in intact plant cells. PMID:19052153

Neurotrophin-3 Enhances the Synaptic Organizing Function of TrkC-Protein Tyrosine Phosphatase σ in Rat Hippocampal Neurons.

Science.gov (United States)

Ammendrup-Johnsen, Ina; Naito, Yusuke; Craig, Ann Marie; Takahashi, Hideto

2015-09-09

Neurotrophin-3 (NT-3) and its high-affinity receptor TrkC play crucial trophic roles in neuronal differentiation, axon outgrowth, and synapse development and plasticity in the nervous system. We demonstrated previously that postsynaptic TrkC functions as a glutamatergic synapse-inducing (synaptogenic) cell adhesion molecule trans-interacting with presynaptic protein tyrosine phosphatase σ (PTPσ). Given that NT-3 and PTPσ bind distinct domains of the TrkC extracellular region, here we tested the hypothesis that NT-3 modulates TrkC/PTPσ binding and synaptogenic activity. NT-3 enhanced PTPσ binding to cell surface-expressed TrkC and facilitated the presynapse-inducing activity of TrkC in rat hippocampal neurons. Imaging of recycling presynaptic vesicles combined with TrkC knockdown and rescue approaches demonstrated that NT-3 rapidly potentiates presynaptic function via binding endogenous postsynaptic TrkC in a tyrosine kinase-independent manner. Thus, NT-3 positively modulates the TrkC-PTPσ complex for glutamatergic presynaptic assembly and function independently from TrkC kinase activation. Our findings provide new insight into synaptic roles of neurotrophin signaling and mechanisms controlling synaptic organizing complexes. Significance statement: Although many synaptogenic adhesion complexes have been identified in recent years, little is known about modulatory mechanisms. Here, we demonstrate a novel role of neurotrophin-3 in synaptic assembly and function as a positive modulator of the TrkC-protein tyrosine phosphatase σ complex. This study provides new insight into the involvement of neurotrophin signaling in synapse development and plasticity, presenting a molecular mechanism that may underlie previous observations of short- and long-term enhancement of presynaptic function by neurotrophin. Given the links of synaptogenic adhesion molecules to autism and schizophrenia, this study might also contribute to a better understanding of the pathogenesis of

Sandwich-Type Electrochemiluminescence Sensor for Detection of NT-proBNP by Using High Efficiency Quench Strategy of Fe3O4@PDA toward Ru(bpy)32+ Coordinated with Silver Oxalate.

Science.gov (United States)

Shi, Li; Li, Xiaojian; Zhu, Wenjuan; Wang, Yaoguang; Du, Bin; Cao, Wei; Wei, Qin; Pang, Xuehui

2017-12-22

Heart failure (HF) is a burgeoning public health problem trigged by a heart circulation disorder. N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been acknowledged as a prognostic biomarker for cardiac disease. Herein, a sandwich-type electrochemiluminescence (ECL) immunosensor was introduced for sensitive detection of NT-proBNP. Gold nanoparticle modified graphene oxide-Ru(bpy) 3 2+ /Ag 2 C 2 O 4 was used as a luminophore and a desirable platform for immobilization of the captured antibodies. The more stable immobilization of plentiful Ru(bpy) 3 2+ could be implemented by direct covalent bonding chelation with Ag 2 C 2 O 4 . More importantly, significant quenching can be achieved by introducing polydopamine (PDA) coated Fe 3 O 4 onto the electrode via sandwich immunoreactions. The quenching mechanism mainly showed that the excited states of Ru(bpy) 3 2+ could be annihilated by quinone units in PDA via energy transfer. The ECL quenching efficiency was logarithmically related to the concentration of the NT-proBNP in the range from 0.0005 ng/mL to 100.0 ng/mL with a detection limit of 0.28 pg/mL. Furthermore, this specific immunosensor presented good stability and repeatability as well as selectivity, which offers a guiding significance in both fundamental and clinical diagnosis of NT-proBNP.

Pharmacogenetic characterization of naturally occurring germline NT5C1A variants to chemotherapeutic nucleoside analogs

Science.gov (United States)

Saliba, Jason; Zabriskie, Ryan; Ghosh, Rajarshi; Powell, Bradford C; Hicks, Stephanie; Kimmel, Marek; Meng, Qingchang; Ritter, Deborah I; Wheeler, David A; Gibbs, Richard A; Tsai, Francis T F; Plon, Sharon E

2016-01-01

Background Mutations or alteration in expression of the 5’ nucleotidase gene family can confer altered responses to treatment with nucleoside analogs. While investigating leukemia susceptibility genes, we discovered a very rare p.L254P NT5C1A missense variant in the substrate recognition motif. Given the paucity of cellular drug response data from NT5C1A germline variation, we characterized p.L254P and eight rare variants of NT5C1A from genomic databases. Methods Through lentiviral infection, we created HEK293 cell lines that stably overexpress wildtype NT5C1A, p.L254P, or eight NT5C1A variants reported in the NHLBI Exome Variant server (one truncating and seven missense). IC50 values were determined by cytotoxicity assays after exposure to chemotherapeutic nucleoside analogs (Cladribine, Gemcitabine, 5-Fluorouracil). In addition, we used structure-based homology modeling to generate a 3D model for the C-terminal region of NT5C1A. Results The p.R180X (truncating), p.A214T, and p.L254P missense changes were the only variants that significantly impaired protein function across all nucleotide analogs tested (>5-fold difference versus WT; p<.05). Several of the remaining variants individually displayed differential effects (both more and less resistant) across the analogs tested. The homology model provided a structural framework to understand the impact of NT5C1A mutants on catalysis and drug processing. The model predicted active site residues within NT5C1A motif III and we experimentally confirmed that p.K314 (not p.K320) is required for NT5C1A activity. Conclusion We characterized germline variation and predicted protein structures of NT5C1A. Individual missense changes showed substantial variation in response to the different nucleoside analogs tested, which may impact patients’ responses to treatment. PMID:26906009

Hypersensitive detection and quantitation of BoNT/A by IgY antibody against substrate linear-peptide.

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Tao Li

Full Text Available Botulinum neurotoxin A (BoNT/A, the most acutely poisonous substance to humans known, cleave its SNAP-25 substrate with high specificity. Based on the endopeptidase activity, different methods have been developed to detect BoNT/A, but most lack ideal reproducibility or sensitivity, or suffer from long-term or unwanted interferences. In this study, we developed a simple method to detect and quantitate trace amounts of botulinum neurotoxin A using the IgY antibody against a linear-peptide substrate. The effects of reaction buffer, time, and temperature were analyzed and optimized. When the optimized assay was used to detect BoNT/A, the limit of detection of the assay was 0.01 mouse LD50 (0.04 pg, and the limit of quantitation was 0.12 mouse LD50/ml (0.48 pg. The findings also showed favorable specificity of detecting BoNT/A. When used to detect BoNT/A in milk or human serum, the proposed assay exhibited good quantitative accuracy (88% < recovery < 111%; inter- and intra-assay CVs < 18%. This method of detection took less than 3 h to complete, indicating that it can be a valuable method of detecting BoNT/A in food or clinical diagnosis.

Learning from Clostridium novyi-NT: How to defeat cancer

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Li Wang

2018-01-01

Full Text Available Side effects associated with conventional anticancer therapies have prompted the new idea of solid tumor treatment strategy. One of them is using bacteria explored as potential antitumor agents over more than one century. Notably, the ideal therapy is a specifical target to tumors with limited toxicity. Here, we take “Clostridium novyi” for the search keyword in the PubMed from 2000 to 2015 and describe that C. novyi-NT spores act as “Trojan horse” for bacteriolytic therapy. This therapy is based on the fact that the live and attenuated obligate anaerobic bacteria are capable of binary fission selectively in anoxic areas of solid tumors and direct tumoricidal effects. Our succinct review mainly concentrates on the potential mechanisms of combination bacteriolytic therapy, an effective and safe tumor therapy with the help of C. novyi-NT. Importantly, C. novyi-NT spores were shown to induce solid tumor regression and exhibit the property to initiate an immune response. Therefore, C. novyi-NT spores should be an effective and safe tumor therapy.

Comparative Study on Atmospheric Dispersion Module of Level 3 PSA

Energy Technology Data Exchange (ETDEWEB)

Kwon, Dahye; Jang, Misuk; Kang, Hyun Sik; Kim, Seoung Rae [NESS, Daejeon (Korea, Republic of)

2016-10-15

Some regulation documents such as Regulatory Guides and NUREG publications from the U.S. Nuclear Regulatory Commission (NRC) have influences on domestic radiation environmental analyses. As renewal versions of NUREG-0800 and NUREG-1555 have issued lately, the assessment for Severe Accident (SA) with Probabilistic Safety Assessment (PSA) should be added to Safety Analysis Report (SAR) and Radiation Environmental Report (RER). Because these reports are the required documents for obtaining the construction permit and operating license, it is important to understand the PSA methodology and it needs to improve the site-specific input data of L3PSA codes for SA. First, our review focuses on the atmospheric dispersion and deposition related input data of L3PSA code in this paper. Then we will continue to review the improvements of other input data. Two atmospheric dispersion models, which are PAVAN developed for design basis accident and ATMOS of MACCS2 code developed for SA, were reviewed in this paper. L3PSA deals with the effects of severe accidents and basically includes the evaluation of both short- and long-term effects. Therefore, both the deposition effects and nuclide information(type, amount, and chemical characteristics of released radionuclide) would be considered as the input parameters of atmospheric dispersion model for L3PSA. Additionally, the meteorological data would be sampled randomly to meet the purpose of probabilistic method. However, the sampling method would be selected according to analysis purpose. After review, ATMOS module and its input data are suitably developed for the atmospheric dispersion analysis of L3PSA. However, ATMOS module was developed using the site-specific terrain and environment characteristics. For the domestic application, it needs to study the input data reflecting the Korean terrain and environment characteristics. It would be also continuously improved in response to the time- and site-specific changes of weather

Effect of carvedilol treatment on plasma neuropeptides levels in patients with essential hypertension

International Nuclear Information System (INIS)

Li Qian; Cheng Guanghua; Yang Jian

2008-01-01

Objective: To study the changes of plasma neuropeptide Y(NPY) and neurotension (NT) levels in patients with essential hypertension after treatment with carvedilol. Methods: Blood pressure and plasma NPY and NT concentrations (with RIA) were measured in 56 patients with essential hypertension both before and after carvedilol therapy (5-10 mg bid) for 3 months as well as 30 controls. Results: Before treatment plasma NPY levels were significantly higher in hypertensive patients than those in controls (P<0.01), but plasma NT levels were significantly lower (P also <0.01). After carvedilol treatment, blood pressure and plasma NPY levels were reduced significantly and plasma NT levels were increased significantly. Conclusion: Treatment with carvedilol results in the correction of plasma concentrations of NPY and NT in patients with essential hypertension, the effect may be related to blood pressure decrease. (authors)

HYDRAULICS AND MIXING EVALUATIONS FOR NT-21/41 TANKS

Energy Technology Data Exchange (ETDEWEB)

Lee, S.; Barnes, O.

2014-11-17

The hydraulic results demonstrate that pump head pressure of 20 psi recirculates about 5.6 liters/min flowrate through the existing 0.131-inch orifice when a valve connected to NT-41 is closed. In case of the valve open to NT-41, the solution flowrates to HB-Line tanks, NT-21 and NT-41, are found to be about 0.5 lpm and 5.2 lpm, respectively. The modeling calculations for the mixing operations of miscible fluids contained in the HB-Line tank NT-21 were performed by taking a three-dimensional Computational Fluid Dynamics (CFD) approach. The CFD modeling results were benchmarked against the literature results and the previous SRNL test results to validate the model. Final performance calculations were performed for the nominal case by using the validated model to quantify the mixing time for the HB-Line tank. The results demonstrate that when a pump recirculates a solution volume of 5.7 liters every minute out of the 72-liter tank contents containing two acid solutions of 2.7 M and 0 M concentrations (i.e., water), a minimum mixing time of 1.5 hours is adequate for the tank contents to get the tank contents adequately mixed. In addition, the sensitivity results for the tank contents of 8 M existing solution and 1.5 M incoming species show that the mixing time takes about 2 hours to get the solutions mixed.

The Significance of the Cardiac Peptide NT-proBNP in the Assessment of Risk for Myocardial Revascularization in Patients with Decreased Left Ventricular Ejection Fraction

Directory of Open Access Journals (Sweden)

V. V. Moroz

2010-01-01

Full Text Available Objective: to substantiate a procedure for predicting the severity of postperfusion acute heart failure (AHF from the baseline level of NT-proBNP during myocardial revascularization in patients with a left ventricular ejection fraction (LVEF of less than 35%. Subjects and materials. Fifty-six patients with a LVEF of less than 35% were examined. A total of 3.5±0.1 (range 2—4 coronary arteries were shunted under cardio-pulmonary bypass (CPB (71.0±5.5 min. The concentration of NT-proBNP was measured before surgery (Cardiac Reader®, Roche. Mortality rates, sympathomimetic agents’ dosages required after EC, and the frequency of use of intraaortic balloon pumping (IABP were analyzed. Results. A good clinical course was observed in 47 cases (Group 1. AHF was recorded in 9 patients (Group 2. Comparative analysis demonstrated that the preoperative concentration of NT-proBNP (871±111 pg/ml in Group 1 and 1946±236 pg/ml in Group 2 was of the highest prognostic value as compared with the traditional indicators (p=0.0015. Patients with a NT-proBNP concentration of less than 600 pg/ml did not virtually need inotropic therapy after EC. In a group with a biomarker level of 600—1200 mg/ml, the infusion of dopamine and dobutamine achieved the traditional cardiotonic dosages and every three patients needed epinephrine. With NT-proBNP of 1200-2000 pg/ml, mortality from AHF was 15.4%; a need for epinephrine and IABC was 46.4 and 7.7%, respectively. The peptide concentration of more than 2000 pg/ml indicated the extremely high risk of severe AHF. In the postperfusion period, each patient was given epinephrine and an IABC system was installed in half of them. In this group mortality achieved 50%. Conclusion. It is expedient to determine a preoperative NT-proBNP concentration in a LVEF of less than 35% to predict AHF to be occurred after myocardial revascularization. The concentration of less than 1200 pg/ml may be considered to be a safe level of the

NT-proBNP and Circulating Inflammation Markers in Prediction of a Normal Myocardial Scintigraphy in Patients with Symptoms of Coronary Artery Disease

DEFF Research Database (Denmark)

Rathcke, C.N.; Kjøller, Erik; Fogh-Andersen, N.

2010-01-01

with an intermediate risk of CAD or with known CAD with renewed suspicion of ischemia were referred to MPI. Blood samples were analyzed for N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP), YKL-40, IL-6, matrix metalloproteinase 9 (MMP-9) and high sensitive C-reactive protein (hs......CRP). Patients with myocardial perfusion defects had elevated levels of NT-proBNP (p95% regardless of existing CAD. Conclusions: 20-25% of patients suspected of CAD could have been spared a MPI by using a NT-proBNP cut-off concentration at 25 ng/l with a negative predictive value >95%. NT-proBNP has...

Strength and Fatigue of NT551 Silicon Nitride and NT551 Diesel Exhaust Valves

Energy Technology Data Exchange (ETDEWEB)

Andrews, M.J.; Wereszczak, A.A.; Kirkland, T.P.; Breder, K.

2000-02-01

The content of this report is excerpted from Mark Andrew's Ph.D. Thesis (Andrews, 1999), which was funded by a DOEYOTT High Temperature Materials Laboratory Graduate Fellowship. It involves the characterization of NT551 and valves fabricated with it. Greater detail of the described issues may be found in that reference or through communications with Andrew Wereszczak.

Extremely intense (SML ≤–2500 nT substorms: isolated events that are externally triggered?

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B. T. Tsurutani

2015-05-01

Full Text Available We examine particularly intense substorms (SML ≤–2500 nT, hereafter called "supersubstorms" or SSS events, to identify their nature and their magnetic storm dependences. It is found that these intense substorms are typically isolated events and are only loosely related to magnetic storms. SSS events can occur during super (Dst ≤–250 nT and intense (−100 nT ≥ Dst >–250 magnetic storms. SSS events can also occur during nonstorm (Dst ≥–50 nT intervals. SSSs are important because the strongest ionospheric currents will flow during these events, potentially causing power outages on Earth. Several SSS examples are shown. SSS events appear to be externally triggered by small regions of very high density (~30 to 50 cm−3 solar wind plasma parcels (PPs impinging upon the magnetosphere. Precursor southward interplanetary magnetic fields are detected prior to the PPs hitting the magnetosphere. Our hypothesis is that these southward fields input energy into the magnetosphere/magnetotail and the PPs trigger the release of the stored energy.

Modulation of phosducin-like protein 3 (PhLP3 levels promotes cytoskeletal remodelling in a MAPK and RhoA-dependent manner.

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Nandini V L Hayes

Full Text Available Phosducin-like protein 3 (PhLP3 forms a ternary complex with the ATP-dependent molecular chaperone CCT and its folding client tubulin. In vitro studies suggest PhLP3 plays an inhibitory role in β-tubulin folding while conversely in vivo genetic studies suggest PhLP3 is required for the correct folding of β-tubulin. We have a particular interest in the cytoskeleton, its chaperones and their role in determining cellular phenotypes associated with high level recombinant protein expression from mammalian cell expression systems.As studies into PhLP3 function have been largely carried out in non mammalian systems, we examined the effect of human PhLP3 over-expression and siRNA silencing using a single murine siRNA on both tubulin and actin systems in mammalian Chinese hamster ovary (CHO cell lines. We show that over-expression of PhLP3 promotes an imbalance of α and β tubulin subunits, microtubule disassembly and cell death. In contrast, β-actin levels are not obviously perturbed. On-the-other-hand, RNA silencing of PhLP3 increases RhoA-dependent actin filament formation and focal adhesion formation and promotes a dramatic elongated fibroblast-like change in morphology. This was accompanied by an increase in phosphorylated MAPK which has been associated with promoting focal adhesion assembly and maturation. Transient overexpression of PhLP3 in knockdown experiments rescues cells from the morphological change observed during PhLP3 silencing but mitosis is perturbed, probably reflecting a tipping back of the balance of PhLP3 levels towards the overexpression state.Our results support the hypothesis that PhLP3 is important for the maintenance of β-tubulin levels in mammalian cells but also that its modulation can promote actin-based cytoskeletal remodelling by a mechanism linked with MAPK phosphorylation and RhoA-dependent changes. PhLP3 levels in mammalian cells are thus finely poised and represents a novel target for engineering industrially

Modulation Methods for Three-level Neutral-Point-Clamped Inverter Achieving Stress Redistribution under Moderate Modulation Index

DEFF Research Database (Denmark)

Ma, Ke; Blaabjerg, Frede

2016-01-01

This letter investigates the loss and thermal behaviors of a three-level neutral-point-clamped (3L-NPC) inverter undergoing moderate modulation index, which is typically presented during minor voltage sags of the power grid or speed changes of the electric machines. A series of new space vector m...

Synaptosomal ecto-5'-nucleotidases activity modulation after ionizing irradiation

International Nuclear Information System (INIS)

Drakulic, D.; Stanojevic, I.; Petrovic, S.; Velickovic, N.; Horvat, A.

2009-01-01

Adenine nucleotides, such as ATP and adenosine are involved in the regulation of variety of physiological processes in the central nervous system (CNS), including development and tissue remodeling following trauma, stroke, ischemia or neurodegenerative disorders. Ecto-5'- nucleotidase (ecto-5'-NT), membrane enzyme, catalyzes the last step of extracellular nucleotide degradation and it is responsible for purinergic signaling modulation and termination. In order to investigate if ionizing irradiation could modulate CNS purinergic signalization in synaptic plasma membranes (SPM) the activity of ecto-5'-NT was monitored after whole-body acute irradiation with low (0,5 Gy) or therapeutic (2 Gy) doses, 1h, 24h and 72h after irradiating juvenile (15-day old), prepubertal (30 days), pubertal (60 days) and adult (90-day old) female rats. Results suggest that acute irradiation could modulate activity of the enzymes that are necessary for purinergic signal termination depended of dose and time after irradiation, as well as brain development stage. (author) [sr

Modulation Strategy of a 3 × 5 Modular Multilevel Matrix Converter

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Rutian Wang

2018-02-01

Full Text Available In this paper, a modulation strategy of a 3 × 5 modular multilevel matrix converter (M3C is proposed. The circuit of 3 × 5 M3C is firstly introduced. Then, operation rules of 3 × 5 M3C are illustrated, and a connection pattern of branches is determined based on these rules. Different voltage states in the input and output side can be achieved by different connection patterns. These voltage states are represented in the form of vector. It is hard to synthesize five-phase output with the three-level synthesis method. Therefore, the five-level synthesis method is adopted in this paper; i.e., is the branch states have been increased. Ten effective vectors and a zero vector are selected based on the five-level synthesis method. With this modulation strategy, we achieve output line-to-line voltages that are in line with the trend of a sine wave. The segment division and duty cycle calculation are very simple, and the modulation strategy can be implemented easily. The simulation model of 3 × 5 M3C is constructed based on Matlab/Simulink, and the corresponding experimental platform is set up. The results of simulation and experiment show that the proposed method is reasonable and correct.

Transcriptional coactivator NT-PGC-1α promotes gluconeogenic gene expression and enhances hepatic gluconeogenesis.

Science.gov (United States)

Chang, Ji Suk; Jun, Hee-Jin; Park, Minsung

2016-10-01

The transcriptional coactivator PGC-1α plays a central role in hepatic gluconeogenesis. We previously reported that alternative splicing of the PGC-1α gene produces an additional transcript encoding the truncated protein NT-PGC-1α NT-PGC-1α is co-expressed with PGC-1α and highly induced by fasting in the liver. NT-PGC-1α regulates tissue-specific metabolism, but its role in the liver has not been investigated. Thus, the objective of this study was to determine the role of hepatic NT-PGC-1α in the regulation of gluconeogenesis. Adenovirus-mediated expression of NT-PGC-1α in primary hepatocytes strongly stimulated the expression of key gluconeogenic enzyme genes (PEPCK and G6Pase), leading to increased glucose production. To further understand NT-PGC-1α function in hepatic gluconeogenesis in vivo, we took advantage of a previously reported FL-PGC-1α -/- mouse line that lacks full-length PGC-1α (FL-PGC-1α) but retains a slightly shorter and functionally equivalent form of NT-PGC-1α (NT-PGC-1α 254 ). In FL-PGC-1α -/- mice, NT-PGC-1α 254 was induced by fasting in the liver and recruited to the promoters of PEPCK and G6Pase genes. The enrichment of NT-PGC-1α 254 at the promoters was closely associated with fasting-induced increase in PEPCK and G6Pase gene expression and efficient production of glucose from pyruvate during a pyruvate tolerance test in FL-PGC-1α -/- mice. Moreover, FL-PGC-1α -/- primary hepatocytes showed a significant increase in gluconeogenic gene expression and glucose production after treatment with dexamethasone and forskolin, suggesting that NT-PGC-1α 254 is sufficient to stimulate the gluconeogenic program in the absence of FL-PGC-1α Collectively, our findings highlight the role of hepatic NT-PGC-1α in stimulating gluconeogenic gene expression and glucose production. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Distinct functional characteristics of levocabastine sensitive rat neurotensin NT2 receptor expressed in Chinese hamster ovary cells.

Science.gov (United States)

Yamada, M; Yamada, M; Lombet, A; Forgez, P; Rostène, W

1998-01-01

Neurotensin has been shown to produce pharmacological effects both in brain and periphery. Several of these effects are mediated by a high-affinity neurotensin NT1 receptor. On the other hand, a low-affinity levocabastine-sensitive neurotensin NT2 receptor was molecularly cloned from rodent brain recently. In this study, in contrast to NT1 receptor, levocabastine (a histamine H1 receptor antagonist) and SR48692 (an antagonist for NT1 receptor) strongly stimulated intracellular Ca2+ mobilization in transfected Chinese hamster ovary cells expressing rat NT2 receptor, thus acting as potent NT2 receptor. Furthermore, despite of their affinities for NT2 receptor, the Ca2+ responses to potent NT1 agonists, neurotensin or JMV449 ([Lys8-(CH2NH)-Lys9]Pro-Tyr-Ile-Leu, a peptidase resistant analogue of neurotensin) were much smaller than that observed with SR48692. These findings suggest that NT1 and NT2 receptors present distinct functional characteristics and that SR48692 may act as a potent agonist for NT2 receptor.

Ruling out cardiac failure: Cost-benefit analysis of a sequential testing strategy with NT-proBNP before echocardiography

Science.gov (United States)

Ferrandis, Maria-José; Ryden, Ingvar; Lindahl, Tomas L.

2013-01-01

Objectives To estimate the possible economic benefit of a sequential testing strategy with NT-proBNP to reduce the number of echocardiographies. Methods Retrospective study in a third-party payer perspective. The costs were calculated from three Swedish counties: Blekinge, Östergötland, and Uppland. Two cut-off levels of NT-proBNP were used: 400 and 300 pg/mL. The cost-effectiveness of the testing strategy was estimated through the short-term cost avoidance and reduction in demand for echocardiographies. Results The estimated costs for NT-proBNP tests and echocardiographies per county were reduced by 33%–36% with the 400 pg/mL cut-off and by 28%–29% with the 300 pg/mL cut-off. This corresponded to a yearly cost reduction of approximately €2–5 million per million inhabitants in these counties. Conclusion The use of NT-proBNP as a screening test could substantially reduce the number of echocardiographies in the diagnostic work-up of patients with suspected cardiac failure, as well as the associated costs. PMID:23230860

Impact of underlying heart disease per se on the utility of preoperative NT-proBNP in adult cardiac surgery.

Directory of Open Access Journals (Sweden)

Huiqi Jiang

Full Text Available The primary aim was to investigate the role of underlying heart disease on preoperative NT-proBNP levels in patients admitted for adult cardiac surgery, after adjusting for the known confounders age, gender, obesity and renal function. The second aim was to investigate the predictive value of preoperative NT-proBNP with regard to severe postoperative heart failure (SPHF and postoperative mortality.A retrospective cohort study based on preoperative NT-proBNP measurements in an unselected cohort including all patients undergoing first time surgery for coronary artery disease (CAD; n = 2226, aortic stenosis (AS; n = 406 or mitral regurgitation (MR; n = 346 from April 2010 to August 2016 in the southeast region of Sweden (n = 2978. Concomitant procedures were not included, with the exception of Maze or tricuspid valve procedures.Preoperative NT-proBNP was 1.67 times (p<0.0001 and 1.41 times (p<0.0001 higher in patients with AS or MR respectively, than in patients with CAD after adjusting for confounders. NT-proBNP demonstrated significant discrimination with regard to SPHF in CAD (AUC = 0.79, 95%CI 0.73-0.85, p<0.0001, MR (AUC = 0.80, 95%CI 0.72-0.87, p<0.0001 and AS (AUC = 0.66, 95%CI 0.51-0.81, p = 0.047. In CAD patients NT-proBNP demonstrated significant discrimination with regard to postoperative 30-day or in-hospital mortality (AUC = 0.78; 95%CI 0.71-0.85, p<0.0001. The number of deaths was too few in the AS and MR group to permit analysis. Elevated NT-proBNP emerged as an independent risk factor for SPHF, and postoperative mortality in CAD.Patients with AS or MR have higher preoperative NT-proBNP than CAD patients even after adjusting for confounders. The predictive value of NT-proBNP with regard to SPHF was confirmed in CAD and MR patients but was less convincing in AS patients.

A Virtual Astronomical Research Machine in No Time (VARMiNT)

Science.gov (United States)

Beaver, John

2012-05-01

We present early results of using virtual machine software to help make astronomical research computing accessible to a wider range of individuals. Our Virtual Astronomical Research Machine in No Time (VARMiNT) is an Ubuntu Linux virtual machine with free, open-source software already installed and configured (and in many cases documented). The purpose of VARMiNT is to provide a ready-to-go astronomical research computing environment that can be freely shared between researchers, or between amateur and professional, teacher and student, etc., and to circumvent the often-difficult task of configuring a suitable computing environment from scratch. Thus we hope that VARMiNT will make it easier for individuals to engage in research computing even if they have no ready access to the facilities of a research institution. We describe our current version of VARMiNT and some of the ways it is being used at the University of Wisconsin - Fox Valley, a two-year teaching campus of the University of Wisconsin System, as a means to enhance student independent study research projects and to facilitate collaborations with researchers at other locations. We also outline some future plans and prospects.

Spinal electro-magnetic stimulation combined with transgene delivery of neurotrophin NT-3 and exercise: novel combination therapy for spinal contusion injury.

Science.gov (United States)

Petrosyan, Hayk A; Alessi, Valentina; Hunanyan, Arsen S; Sisto, Sue A; Arvanian, Victor L

2015-11-01

Our recent terminal experiments revealed that administration of a single train of repetitive spinal electromagnetic stimulation (sEMS; 35 min) enhanced synaptic plasticity in spinal circuitry following lateral hemisection spinal cord injury. In the current study, we have examined effects of repetitive sEMS applied as a single train and chronically (5 wk, every other day) following thoracic T10 contusion. Chronic studies involved examination of systematic sEMS administration alone and combined with exercise training and transgene delivery of neurotrophin [adeno-associated virus 10-neurotrophin 3 (AAV10-NT3)]. Electrophysiological intracellular/extracellular recordings, immunohistochemistry, behavioral testing, and anatomical tracing were performed to assess effects of treatments. We found that administration of a single sEMS train induced transient facilitation of transmission through preserved lateral white matter to motoneurons and hindlimb muscles in chronically contused rats with effects lasting for at least 2 h. These physiological changes associated with increased immunoreactivity of GluR1 and GluR2/3 glutamate receptors in lumbar neurons. Systematic administration of sEMS alone for 5 wk, however, was unable to induce cumulative improvements of transmission in spinomuscular circuitry or improve impaired motor function following thoracic contusion. Encouragingly, chronic administration of sEMS, followed by exercise training (running in an exercise ball and swimming), induced the following: 1) sustained strengthening of transmission to lumbar motoneurons and hindlimb muscles, 2) better retrograde transport of anatomical tracer, and 3) improved locomotor function. Greatest improvements were seen in the group that received exercise combined with sEMS and AAV-NT3.

Modulating the level of components within plants

Science.gov (United States)

Bobzin, Steven Craig; Apuya, Nestor; Chiang, Karen; Doukhanina, Elena; Feldmann, Kenneth; Jankowski, Boris; Margolles-Clark, Emilio; Mumenthaler, Daniel; Okamuro, Jack; Park, Joon-Hyun; Van Fleet, Jennifer E.; Zhang, Ke

2017-09-12

Materials and Methods for identifying lignin regulatory region-regulatory protein associations are disclosed. Materials and methods for modulating lignin accumulation are also disclosed. In addition, methods and materials for modulating (e.g., increasing or decreasing) the level of a component (e.g., protein, oil, lignin, carbon, a carotenoid, or a triterpenoid) in plants are disclosed.

A design of optical modulation system with pixel-level modulation accuracy

Science.gov (United States)

Zheng, Shiwei; Qu, Xinghua; Feng, Wei; Liang, Baoqiu

2018-01-01

Vision measurement has been widely used in the field of dimensional measurement and surface metrology. However, traditional methods of vision measurement have many limits such as low dynamic range and poor reconfigurability. The optical modulation system before image formation has the advantage of high dynamic range, high accuracy and more flexibility, and the modulation accuracy is the key parameter which determines the accuracy and effectiveness of optical modulation system. In this paper, an optical modulation system with pixel level accuracy is designed and built based on multi-points reflective imaging theory and digital micromirror device (DMD). The system consisted of digital micromirror device, CCD camera and lens. Firstly we achieved accurate pixel-to-pixel correspondence between the DMD mirrors and the CCD pixels by moire fringe and an image processing of sampling and interpolation. Then we built three coordinate systems and calculated the mathematic relationship between the coordinate of digital micro-mirror and CCD pixels using a checkerboard pattern. A verification experiment proves that the correspondence error is less than 0.5 pixel. The results show that the modulation accuracy of system meets the requirements of modulation. Furthermore, the high reflecting edge of a metal circular piece can be detected using the system, which proves the effectiveness of the optical modulation system.

The Circuit-Level Decoupling Modulation Strategy for Three-Level Neutral-Point-Clamped (TL-NPC) Inverter

DEFF Research Database (Denmark)

Zhang, Zhe; Thomsen, Ole Cornelius; Andersen, Michael A. E.

2011-01-01

In this paper, a circuit-level decoupling modulation strategy is proposed for the three-level (TL) neutral-point-clamped (NPC) inverters. With the proposed modulation scheme, the TL-NPC inverter can be decoupled into two three-level Buck converters in each defined operating section, which makes...

Ectopic Expression of the Coleus R2R3 MYB-Type Proanthocyanidin Regulator Gene SsMYB3 Alters the Flower Color in Transgenic Tobacco.

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Qinlong Zhu

Full Text Available Proanthocyanidins (PAs play an important role in plant disease defense and have beneficial effects on human health. We isolated and characterized a novel R2R3 MYB-type PA-regulator SsMYB3 from a well-known ornamental plant, coleus (Solenostemon scutellarioides, to study the molecular regulation of PAs and to engineer PAs biosynthesis. The expression level of SsMYB3 was correlated with condensed tannins contents in various coleus tissues and was induced by wounding and light. A complementation test in the Arabidopsis tt2 mutant showed that SsMYB3 could restore the PA-deficient seed coat phenotype and activated expression of the PA-specific gene ANR and two related genes, DFR and ANS. In yeast two-hybrid assays, SsMYB3 interacted with the Arabidopsis AtTT8 and AtTTG1 to reform the ternary transcriptional complex, and also interacted with two tobacco bHLH proteins (NtAn1a and NtJAF13-1 and a WD40 protein, NtAn11-1. Ectopic overexpression of SsMYB3 in transgenic tobacco led to almost-white flowers by greatly reducing anthocyanin levels and enhancing accumulation of condensed tannins. This overexpression of SsMYB3 upregulated the key PA genes (NtLAR and NtANR and late anthocyanin structural genes (NtDFR and NtANS, but downregulated the expression of the final anthocyanin gene NtUFGT. The formative SsMYB3-complex represses anthocyanin accumulation by directly suppressing the expression of the final anthocyanin structural gene NtUFGT, through competitive inhibition or destabilization of the endogenous NtAn2-complex formation. These results suggested that SsMYB3 may form a transcription activation complex to regulate PA biosynthesis in the Arabidopsis tt2 mutant and transgenic tobacco. Our findings suggest that SsMYB3 is involved in the regulation of PA biosynthesis in coleus and has the potential as a molecular tool for manipulating biosynthesis of PAs in fruits and other crops using metabolic engineering.

Is N.D. and N.T. v. Spain the new Hirsi?

NARCIS (Netherlands)

Pijnenburg, Annick

2017-01-01

On 3 October the Third Chamber of the European Court of Human Rights published its judgment N.D. and N.T. v. Spain, which concerns Spain’s pushback policy in Melilla. It found a violation of Article 4 of Protocol 4 (prohibition of collective expulsions of aliens) and of Article 13 (right to an

Comparison of Abbott AxSYM and Roche Elecsys 2010 for measurement of BNP and NT-proBNP.

Science.gov (United States)

Chien, Tzu-I; Chen, Hui-Hou; Kao, Jau-Tsuen

2006-07-15

B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are small cardiac hormones released from the heart. They can be used as an important aid to diagnose congestive heart failure (CHF). We compared the performances of the Abbott AxSYM and Roche Elecsys 2010 for the measurement of BNP and NT-proBNP. The first method uses a microparticle enzyme-linked immunoassay, whereas the other uses chemiluminescent immunometric assay. The CVs using pooled sera ranged from 3.7% to 12.7% for the AxSYM and 0.9% to 2.2% for the Elecsys 2010. The Passing and Bablok regression was Elecsys 2010 NT-proBNP=7.23xAxSYM BNP+2.53. The BNP in EDTA plasma was more stable than in serum. The immunoreactivity difference of NT-proBNP in serum or EDTA plasma was within 10% when stored at 4 degrees Celsius or 25 degrees Celsius for 72 h. Receiver operating characteristic (ROC) curves were different for both assays, and the areas under the curves were 0.704 and 0.841 for the AxSYM and Elecsys 2010 method, respectively. Both assays were not entirely specific for heart failure. The precision and stability for NT-proBNP was better than for BNP in serum. It is important to use method-appropriate reference ranges (or cutoff) for the BNP and NT-proBNP, respectively, in the assessment of CHF.

[Inhibitory effect of RNA interference targeting GFI-1 on the proliferation of atypical chronic myelogenous leukemia NT1 cells].

Science.gov (United States)

Yang, X; Liu, H; Lin, Z H; Qian, J; Xu, X R

2016-08-01

To investigate the inhibitory effects of RNA interference targeting GFI-1 on growth and proliferation of atypical chronic myelogenous leukemia (aCML) NT1 cells. NT1 cells were transfected with PBS and liposome complex (vehicle group), scrambled siRNA and liposome complex (negative control, NC group), and GFI-1 siRNA and liposome complex (GFI-1 siRNA group), respectively. Real-time quantitative RT-PCR (qRT-PCR) and Western blot were performed to examine the expression levels of GFI-1 mRNA and protein, respectively. The proliferation abilities of NT1 cells of the three groups were evaluated by MTT assay. The cell cycle in cells of the three groups was analyzed by flow cytometry. Moreover, nude mouse xenograft model was used to detect the tumor formation ability in the three group cells. Quantitative real-time PCR data showed that the expression level of GFI-1 mRNA in GFI-1 siRNA group was significantly lower than those of NC group and vehicle group [(0.367±0.017) vs. (0.918±0.006) and (1.010±0.005), respectively, (PNT1 cells in the GFI-1 siRNA group (0.667±0.059) was significantly lower than those of the NC group (1.096±0.049) and vehicle group (1.193±0.064, P=0.023). Flow cytometry data showed that sub-G1 and G0/G1 phase proportions of the GFI-1 siRNA group were significantly higher than those of the NC and vehicle groups [sub-G1: (8.2±2.5)% vs. (1.9±1.3)% and (2.0±3.6)%, respectively, (PNT1 cells, which may provide a new therapeutic target for atypical chronic myelogenous leukemia.

Multi-stage decoding of multi-level modulation codes

Science.gov (United States)

Lin, Shu; Kasami, Tadao; Costello, Daniel J., Jr.

1991-01-01

Various types of multi-stage decoding for multi-level modulation codes are investigated. It is shown that if the component codes of a multi-level modulation code and types of decoding at various stages are chosen properly, high spectral efficiency and large coding gain can be achieved with reduced decoding complexity. Particularly, it is shown that the difference in performance between the suboptimum multi-stage soft-decision maximum likelihood decoding of a modulation code and the single-stage optimum soft-decision decoding of the code is very small, only a fraction of dB loss in signal to noise ratio at a bit error rate (BER) of 10(exp -6).

ORF Alignment: NT_033778 [GENIUS II[Archive

Lifescience Database Archive (English)

Full Text Available de-binding protein [Periplaneta americana] ... pir||JQ0708 lipopolysaccharide-binding protein precurs... NT_033778 gi|24762680 >1qddA 8 141 113 253 1e-15 ... dbj|BAA00616.1| lipopolysacchari

Reliability of the Nidek NT-1000 non contact tonometer.

Science.gov (United States)

Van de Velde, T; Zeyen, T

1995-01-01

In this prospective study, we compared the intraocular pressure (IOP) readings of 100 patients measured with the Goldmann applanation tonometer and the Nidek NT-1000 pneumotonometer. The correlation coefficient between the Goldmann and Nidek readings was 0.86. On the average the pneumotonometer overestimated the intraocular pressure with 0.43 mm Hg. The Nidek NT-1000 non contact tonometer can be used for screening purposes provided an appropriately low IOP value is used to indicate the need for further assessment with the Goldman applanation tonometer.

The NT-ProBNP Test in Subjects with End-Stage Renal Disease on Hemodialysis Presenting with Acute Dyspnea: Is Knowing Worth the Cost?

Directory of Open Access Journals (Sweden)

Shaffer R. S. Mok

2013-01-01

Full Text Available Background. The NT-ProBNP/BNP test has been validated as a marker for determining the etiology of acute dyspnea. In the setting of end-stage renal disease on hemodialysis (ESRD on HD, the utility of the NT-ProBNP/BNP test has not been validated. This study examines the clinical utility of the NT-ProBNP test in the setting of ESRD on HD patients presenting with acute dyspnea. Methods. A retrospective case series of 250 subjects were admitted to Cooper University Hospital, 07/2010-03/2011, with ESRD and HD presenting with dyspnea. The incidences of echocardiography, cardiology consultation, and NT-ProBNP elevated and normal were examined. Correlation coefficients were calculated for NT-ProBNP with age (years, estimated dry weight (kg, amount of fluid removed (L, and ejection fraction (EF in % among other echocardiography parameters. Results. Of the total sample 235 patients had NT-ProBNP levels performed. Cardiology consults were placed in 68.8% and 58% who underwent echocardiography. Of those for whom an echocardiography was performed estimated mean EFs of 54.6%, 50.8%, and 61.7% were observed among the NT-ProBNP elevated group, normal group, and no NT-ProBNP group, respectively. No differences were detected in all other echocardiography measurements. No correlation was observed between NT-ProBNP and age (, baseline EDW (, amount of fluid removed (, or EF (. Conclusion. In the setting of ESRD on HD, the NT-ProBNP test has no clinical utility in determining the etiology of acute dyspnea. This can be demonstrated through echocardiographic and therapeutic parameters measured in this study.

Sincronización de Células de Tabaco (Nicotiana tabacum) NT-1

OpenAIRE

Ruiz, León F; Higareda, Ana E; Pardo, Marco A

2010-01-01

Se ha evaluado la capacidad sincronizante de afidicolina e hidroxiurea en cultivos de células de tabaco (Nicotiana tabacum) NT-1. Los cultivos sincronizados son poderosas herramientas en estudios moleculares y bioquímicos relacionados al ciclo celular y comúnmente se utilizan químicos para bloquear el ciclo celular. La línea celular de tabaco (Nicotiana tabacum) NT-1 proviene de la línea celular TBY-2, caracterizándose NT-1 por su menor velocidad de crecimiento y tamaño celular heterogéneo. L...

Serum Pentraxin 3 and hs-CRP Levels in Children with Severe Pulmonary Hypertension

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Cemşit Karakurt

2014-09-01

Full Text Available Background: Pulmonary arterial hypertension secondary to untreated left-to-right shunt defects leads to increased pulmonary blood flow, endothelial dysfunction, increased pulmonary vascular resistance, vascular remodelling, neointimal and plexiform lesions. Some recent studies have shown that inflammation has an important role in the pathophysiology of pulmonary arterial hypertension. Aims: The aim of this study is to evaluate serum pentraxin 3 and high sensitive (hs-C reactive protein (hs-CRP levels in children with severe pulmonary arterial hypertension (PAH secondary to untreated congenital heart defects and evaluate the role of inflammation in pulmonary hypertension. Study Design: Cross sectional study. Methods: After ethics committee approval and receiving consent from parents, there were 31 children were selected for the study with severe PAH, mostly with a left-to-right shunt, who had been assessed by cardiac catheterisation and were taking specific pulmonary vasodilators. The control group consisted of 39 age and gender matched healthy children. After recording data about all the patients including age, gender, weight, haemodynamic studies and vasodilator testing, a physical examination was done for all subjects. Blood was taken from patients and the control group using peripheral veins to analyse serum Pentraxin 3, N-terminal pro-Brain Natriuretic Peptide (NT-ProBNP and hs-CRP levels. Serum Pentraxin-3 levels were measured by enzyme linked immunosorbent assay (ELISA and expressed as ng/mL. Serum hs-CRP levels were measured with an immunonephelometric method and expressed as mg/dL. The serum concentration of NT-proBNP was determined by a chemiluminescent immunumetric assay and expressed as pg/mL. Results: Serum Pentraxin- 3 levels were determined to be 1.28±2.12 (0.12-11.43 in the PAH group (group 1 and 0.40±0.72 (0.07-3.45 in group 2. There was a statistically significant difference between the two groups (p<0.01. Serum hs-CRP levels

ORF Alignment: NT_033777 [GENIUS II[Archive

Lifescience Database Archive (English)

Full Text Available NT_033777 gi|24648160 >1mc2A 1 134 1 122 2e-29 ... gb|AAB20876.1| ammodytin L=myotoxi...c phospholipase A2 homologue [Vipera ... ammodytes=European viper, Peptide, 123 aa] ... Length

Purification and characterization of a novel subtype a3 botulinum neurotoxin.

Science.gov (United States)

Tepp, William H; Lin, Guangyun; Johnson, Eric A

2012-05-01

Botulinum neurotoxins (BoNTs) produced by Clostridium botulinum are of considerable importance due to their being the cause of human and animal botulism, their potential as bioterrorism agents, and their utility as important pharmaceuticals. Type A is prominent due to its high toxicity and long duration of action. Five subtypes of type A BoNT are currently recognized; BoNT/A1, -/A2, and -/A5 have been purified, and their properties have been studied. BoNT/A3 is intriguing because it is not effectively neutralized by polyclonal anti-BoNT/A1 antibodies, and thus, it may potentially replace BoNT/A1 for patients who have become refractive to treatment with BoNT/A1 due to antibody formation or other modes of resistance. Purification of BoNT/A3 has been challenging because of its low levels of production in culture and the need for innovative purification procedures. In this study, modified Mueller-Miller medium was used in place of traditional toxin production medium (TPM) to culture C. botulinum A3 (CDC strain) and boost toxin production. BoNT/A3 titers were at least 10-fold higher than those produced in TPM. A purification method was developed to obtain greater than 95% pure BoNT/A3. The specific toxicity of BoNT/A3 as determined by mouse bioassay was 5.8 × 10(7) 50% lethal doses (LD(50))/mg. Neutralization of BoNT/A3 toxicity by a polyclonal anti-BoNT/A1 antibody was approximately 10-fold less than the neutralization of BoNT/A1 toxicity. In addition, differences in symptoms were observed between mice that were injected with BoNT/A3 and those that were injected with BoNT/A1. These results indicate that BoNT/A3 has novel biochemical and pharmacological properties compared to those of other subtype A toxins.

Plasma NT-proBNP mirrors the deleterious cardiovascular and renal continuum in hypertension.

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Courand, Pierre-Yves; Harbaoui, Brahim; Bècle, Clément; Mouly-Bertin, Carine; Lantelme, Pierre

2017-03-01

Background The aims of this study were (a) to test the ability of N-terminal pro-brain natriuretic peptide (NT-proBNP) to detect subclinical target organ damage (TOD) denoted by left ventricular hypertrophy (LVH), aortic stiffness or renal damage and (b) to test its reproducibility in two different conditions in an ancillary study. Methods The study included 837 patients (50.9% men) with hypertension aged 50 ± 24 years with a median 24-h ambulatory blood pressure (BP) of 148/90 mmHg. LVH was assessed by transthoracic echocardiography and echocardiography, aortic stiffness was assessed by carotid-femoral pulse wave (PWV) measurements and renal dysfunction by measurements of the estimated glomerular filtration rate (eGFR) and microalbuminuria. Results After the exclusion of patients with a history of heart failure, NT-proBNP was independently correlated with sex, systolic BP, primary hypertension, PWV, LVH and eGFR, but not with microalbuminuria. The median (interquartile range) NT-proBNP increased gradually according to the number of target organs damaged: 42 (24-70), 77 (39-151), 141 (81-250) and 334 (177-556) pg/mL, for damage to 0, 1, 2 and 3 target organs, respectively ( p secondary hypertension. A threshold at 90 pg/mL for men and 142 pg/mL in women had a specificity of 95% to detect at least one TOD (areas under ROC curve 0.790 and 0.783, respectively). The reproducibility of NT-proBNP was fairly good in this setting ( r = 0.952, p hypertension.

Sequence variations and protein expression levels of the two immune evasion proteins Gpm1 and Pra1 influence virulence of clinical Candida albicans isolates.

Science.gov (United States)

Luo, Shanshan; Hipler, Uta-Christina; Münzberg, Christin; Skerka, Christine; Zipfel, Peter F

2015-01-01

Candida albicans, the important human fungal pathogen uses multiple evasion strategies to control, modulate and inhibit host complement and innate immune attack. Clinical C. albicans strains vary in pathogenicity and in serum resistance, in this work we analyzed sequence polymorphisms and variations in the expression levels of two central fungal complement evasion proteins, Gpm1 (phosphoglycerate mutase 1) and Pra1 (pH-regulated antigen 1) in thirteen clinical C. albicans isolates. Four nucleotide (nt) exchanges, all representing synonymous exchanges, were identified within the 747-nt long GPM1 gene. For the 900-nt long PRA1 gene, sixteen nucleotide exchanges were identified, which represented synonymous, as well as non-synonymous exchanges. All thirteen clinical isolates had a homozygous exchange (A to G) at position 73 of the PRA1 gene. Surface levels of Gpm1 varied by 8.2, and Pra1 levels by 3.3 fold in thirteen tested isolates and these differences influenced fungal immune fitness. The high Gpm1/Pra1 expressing candida strains bound the three human immune regulators more efficiently, than the low expression strains. The difference was 44% for Factor H binding, 51% for C4BP binding and 23% for plasminogen binding. This higher Gpm1/Pra1 expressing strains result in enhanced survival upon challenge with complement active, Factor H depleted human serum (difference 40%). In addition adhesion to and infection of human endothelial cells was increased (difference 60%), and C3b surface deposition was less effective (difference 27%). Thus, variable expression levels of central immune evasion protein influences immune fitness of the human fungal pathogen C. albicans and thus contribute to fungal virulence.

Genetic transformation of tobacco NT1 cells with Agrobacterium tumefaciens.

Science.gov (United States)

Mayo, Kristin J; Gonzales, Barbara J; Mason, Hugh S

2006-01-01

This protocol is used to produce stably transformed tobacco (Nicotiana tabacum) NT1 cell lines, using Agrobacterium tumefaciens-mediated DNA delivery of a binary vector containing a gene encoding hepatitis B surface antigen and a gene encoding the kanamycin selection marker. The NT1 cultures, at the appropriate stage of growth, are inoculated with A. tumefaciens containing the binary vector. A 3-day cocultivation period follows, after which the cultures are rinsed and placed on solid selective medium. Transformed colonies ('calli') appear in approximately 4 weeks; they are subcultured until adequate material is obtained for analysis of antigen production. 'Elite' lines are selected based on antigen expression and growth characteristics. The time required for the procedure from preparation of the plant cell materials to callus development is approximately 5 weeks. Growth of selected calli to sufficient quantities for antigen screening may require 4-6 weeks beyond the initial selection. Creation of the plasmid constructs, transformation of the A. tumefaciens line, and ELISA and Bradford assays to assess protein production require additional time.

NEU3 sialidase strictly modulates GM3 levels in skeletal myoblasts C2C12 thus favoring their differentiation and protecting them from apoptosis.

Science.gov (United States)

Anastasia, Luigi; Papini, Nadia; Colazzo, Francesca; Palazzolo, Giacomo; Tringali, Cristina; Dileo, Loredana; Piccoli, Marco; Conforti, Erika; Sitzia, Clementina; Monti, Eugenio; Sampaolesi, Maurilio; Tettamanti, Guido; Venerando, Bruno

2008-12-26

Membrane-bound sialidase NEU3, often referred to as the "ganglioside sialidase," has a critical regulatory function on the sialoglycosphingolipid pattern of the cell membrane, with an anti-apoptotic function, especially in cancer cells. Although other sialidases have been shown to be involved in skeletal muscle differentiation, the role of NEU3 had yet to be disclosed. Herein we report that NEU3 plays a key role in skeletal muscle differentiation by strictly modulating the ganglioside content of adjacent cells, with special regard to GM3. Induced down-regulation of NEU3 in murine C2C12 myoblasts, even when partial, totally inhibits their capability to differentiate by increasing the GM3 level above a critical point, which causes epidermal growth factor receptor inhibition (and ultimately its down-regulation) and an higher responsiveness of myoblasts to the apoptotic stimuli.

Analysis of Harmonic Injection to the Modulation of Multi-Level ...

African Journals Online (AJOL)

This paper explores the analysis of third and ninth harmonic injection to the modulation of a multilevel diode clamped converter (DCC) at a varying modulation index. The spectral distributions of the various multi-level waveforms obtained under normal modulation index of 0.8 and over modulation index of 1.15 were ...

NT-pro-BNP is associated with inducible myocardial ischemia in mildly symptomatic type 2 diabetic patients

NARCIS (Netherlands)

Wiersma, Jacobijne J.; van der Zee, P. Marc; van Straalen, Jan P.; Fischer, Johan C.; van Eck-Smit, Berthe L. F.; Tijssen, Jan G. P.; Trip, Mieke D.; Piek, Jan J.; Verberne, Hein J.

2010-01-01

Baseline levels of N-terminal fragment of the brain natriuretic peptide prohormone (NT-pro-BNP) are associated with myocardial ischemia in non-diabetic patients with stable angina pectoris. A total of 281 patients with diabetes mellitus type 2 and stable angina pectoris underwent myocardial

Binaural processing of modulated interaural level differences

DEFF Research Database (Denmark)

Thompson, Eric Robert; Dau, Torsten

2008-01-01

Two experiments are presented that measure the acuity of binaural processing of modulated interaural level differences ILDs using psychoacoustic methods. In both experiments, dynamic ILDs were created by imposing an interaurally antiphasic sinusoidal amplitude modulation AM signal on high...... frequency, broadly tuned, bandpass-shaped patterns were obtained. Simulations with an existing binaural model show that a low-pass filter to limit the binaural temporal resolution is not sufficient to predict the results of the experiments....

Multi-level trellis coded modulation and multi-stage decoding

Science.gov (United States)

Costello, Daniel J., Jr.; Wu, Jiantian; Lin, Shu

1990-01-01

Several constructions for multi-level trellis codes are presented and many codes with better performance than previously known codes are found. These codes provide a flexible trade-off between coding gain, decoding complexity, and decoding delay. New multi-level trellis coded modulation schemes using generalized set partitioning methods are developed for Quadrature Amplitude Modulation (QAM) and Phase Shift Keying (PSK) signal sets. New rotationally invariant multi-level trellis codes which can be combined with differential encoding to resolve phase ambiguity are presented.

Biochemical properties of the matrix metalloproteinase NtMMP1 from Nicotiana tabacum cv. BY-2 suspension cells.

Science.gov (United States)

Mandal, Manoj K; Fischer, Rainer; Schillberg, Stefan; Schiermeyer, Andreas

2010-09-01

A zinc-dependent matrix metalloproteinase (NtMMP1) found in the plasma membrane of Nicotiana tabacum cv. Bright Yellow 2 (BY-2) suspension cells is thought to be responsible for the degradation of recombinant proteins secreted into the culture supernatant. We have characterized the proteolytic activity of NtMMP1 by expressing a recombinant derivative lacking the C-terminal transmembrane domain in yeast. After purifying the protein by affinity chromatography, its autocatalytic activity was analyzed using monoclonal antibodies raised against its N-terminal and C-terminal portions. Both the unprocessed and processed forms of NtMMP1 displayed caseinolytic activity and N-terminal sequencing identified an autocatalytic cleavage site within the sequence motif HFSFFP, which is similar to the corresponding sequences of the human matrix metalloproteinases stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10). Unlike all other matrix metalloproteinases investigated so far, NtMMP1 contains a disulfide bond within its propeptide thus rendering the proenzyme catalytically active. Kinetic analysis of NtMMP1 with a synthetic substrate revealed a K(m) of 10.55 +/- 0.9 microM, a k(cat) of 0.6 +/- 0.01 s(-1) and maximum activity at pH 7.5. We found that NtMMP1 degrades Desmodus rotundus salivary plasminogen activator alpha 1 (DSPAalpha1), a biopharmaceutical protein, that has proven difficult to produce in tobacco BY-2 cells. This provides a likely explanation for the frequent instability of secreted recombinant biopharmaceuticals produced in plant suspension cell cultures. Our data suggest new avenues that can be explored to improve the production of pharmaceutical proteins in plants and plant cells.

Expression of mRNAs for PPT, CGRP, NF-200, and MAP-2 in cocultures of dissociated DRG neurons and skeletal muscle cells in administration of NGF or NT-3

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Weiwei Zhang

2012-07-01

Full Text Available Both neurotrophins (NTs and target skeletal muscle (SKM cells are essential for the maintenance of the function of neurons and nerve-muscle communication. However, much less is known about the association of target SKM cells with distinct NTs on the expression of mRNAs for preprotachykinin (PPT, calcitonin-gene related peptide (CGRP, neurofilament 200 (NF-200, and microtubule associated protein 2 (MAP-2 in dorsal root ganglion (DRG sensory neurons. In the present study, a neuromuscular coculture model of dissociated dorsal root ganglion (DRG neurons and SKM cells was established. The morphology of DRG neurons and SKM cells in coculture was observed with an inverted phase contrast microscope. The effects of nerve growth factor (NGF or neurotrophin-3 (NT-3 on the expression of mRNAs for PPT, CGRP, NF-200, and MAP-2 was analyzed by real time-PCR assay. The morphology of DRG neuronal cell bodies and SKM cells in neuromuscular coculture at different conditions was similar. The neurons presented evidence of dense neurite outgrowth in the presence of distinct NTs in neuromuscular cocultures. NGF and NT-3 increased mRNA levels of PPT, CGRP, and NF-200, but not MAP-2, in neuromuscular cocultures. These results offer new clues towards a better understanding of the association of target SKM cells with distinct NTs on the expression of mRNAs for PPT, CGRP, NF-200 and MAP-2, and implicate the association of target SKM cells and NTs with DRG sensory neuronal phenotypes.

Neurotensin is an antagonist of the human neurotensin NT2 receptor expressed in Chinese hamster ovary cells.

Science.gov (United States)

Vita, N; Oury-Donat, F; Chalon, P; Guillemot, M; Kaghad, M; Bachy, A; Thurneyssen, O; Garcia, S; Poinot-Chazel, C; Casellas, P; Keane, P; Le Fur, G; Maffrand, J P; Soubrie, P; Caput, D; Ferrara, P

1998-11-06

The human levocabastine-sensitive neurotensin NT2 receptor was cloned from a cortex cDNA library and stably expressed in Chinese hamster ovary (CHO) cells in order to study its binding and signalling characteristics. The receptor binds neurotensin as well as several other ligands already described for neurotensin NT1 receptor. It also binds levocabastine, a histamine H1 receptor antagonist that is not recognised by neurotensin NT1 receptor. Neurotensin binding to recombinant neurotensin NT2 receptor expressed in CHO cells does not elicit a biological response as determined by second messenger measurements. Levocabastine, and the peptides neuromedin N and xenin were also ineffective on neurotensin NT2 receptor activation. Experiments with the neurotensin NT1 receptor antagonists SR48692 and SR142948A, resulted in the unanticipated discovery that both molecules are potent agonists on neurotensin NT2 receptor. Both compounds, following binding to neurotensin NT2 receptor, enhance inositol phosphates (IP) formation with a subsequent [Ca2+]i mobilisation; induce arachidonic acid release; and stimulate mitogen-activated protein kinase (MAPK) activity. Interestingly, these activities are antagonised by neurotensin and levocabastine in a concentration-dependent manner. These activities suggest that the human neurotensin NT2 receptor may be of physiological importance and that a natural agonist for the receptor may exist.

The Fifteenth International Conference on the Science and Application of Nanotubes (NT14)

Energy Technology Data Exchange (ETDEWEB)

cronin, stephen

2015-01-06

The Fifteenth International Conference on the Science and Application of Nanotubes (NT14) was held at the University of Southern California in Los Angeles, California on June 2-6, 2014. NT14 upheld the NT tradition of presenting the latest results in the science and applications of nanotubes and related materials in plenary sessions. Emphasis was given to convivial poster sessions and student participation. Over 225 participants attended the conference, including students, post-docs, faculty, and members from industry. A total of 45 talks were presented, as well as 157 posters.

Hypertension-Related Gene Polymorphisms of G-Protein-Coupled Receptor Kinase 4 Are Associated with NT-proBNP Concentration in Normotensive Healthy Adults

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Junichi Yatabe

2012-01-01

Full Text Available G protein-coupled receptor kinase 4 (GRK4 with activating polymorphisms desensitize the natriuric renal tubular D1 dopamine receptor, and these GRK4 polymorphisms are strongly associated with salt sensitivity and hypertension. Meanwhile, N-terminal pro-B-type natriuretic peptide (NT-proBNP may be useful in detecting slight volume expansion. However, relations between hypertension-related gene polymorphisms including GRK4 and cardiovascular indices such as NT-proBNP are not clear, especially in healthy subjects. Therefore, various hypertension-related polymorphisms and cardiovascular indices were analyzed in 97 normotensive, healthy Japanese adults. NT-proBNP levels were significantly higher in subjects with two or more GRK4 polymorphic alleles. Other hypertension-related gene polymorphisms, such as those of renin-angiotensin-aldosterone system genes, did not correlate with NT-proBNP. There was no significant association between any of the hypertension-related gene polymorphisms and central systolic blood pressure, cardioankle vascular index, augmentation index, plasma aldosterone concentration, or an oxidative stress marker, urinary 8-OHdG. Normotensive individuals with GRK4 polymorphisms show increased serum NT-proBNP concentration and may be at a greater risk of developing hypertension and cardiovascular disease.

Receptor-mediated internalization of [3H]-neurotensin in synaptosomal preparations from rat neostriatum.

Science.gov (United States)

Nguyen, Ha Minh Ky; Cahill, Catherine M; McPherson, Peter S; Beaudet, Alain

2002-06-01

Following its binding to somatodendritic receptors, the neuropeptide neurotensin (NT) internalizes via a clathrin-mediated process. In the present study, we investigated whether NT also internalizes presynaptically using synaptosomes from rat neostriatum, a region in which NT1 receptors are virtually all presynaptic. Binding of [(3)H]-NT to striatal synaptosomes in the presence of levocabastine to block NT2 receptors is specific, saturable, and has NT1 binding properties. A significant fraction of the bound radioactivity is resistant to hypertonic acid wash indicating that it is internalized. Internalization of [(3)H]-NT, like that of [(125)I]-transferrin, is blocked by sucrose and low temperature, consistent with endocytosis occurring via a clathrin-dependent pathway. However, contrary to what was reported at the somatodendritic level, neither [(3)H]-NT nor [(125)I]-transferrin internalization in synaptosomes is sensitive to the endocytosis inhibitor phenylarsine oxide. Moreover, treatment of synaptosomes with monensin, which prevents internalized receptors from recycling to the plasma membrane, reduces [(3)H]-NT binding and internalization, suggesting that presynaptic NT1 receptors, in contrast to somatodendritic ones, are recycled back to the plasma membrane. Taken together, these results suggest that NT internalizes in nerve terminals via an endocytic pathway that is related to, but is mechanistically distinct from that responsible for NT internalization in nerve cell bodies.

Swapping the N- and C-terminal domains of human apolipoprotein E3 and AI reveals insights into their structure/activity relationship.

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Mark T Lek

Full Text Available Apolipoprotein (apo E3 and apoAI are exchangeable apolipoproteins that play a dominant role in regulating plasma lipoprotein metabolism. ApoE3 (299 residues is composed of an N-terminal (NT domain bearing a 4-helix bundle and a C-terminal (CT domain bearing a series of amphipathic α-helices. ApoAI (243 residues also comprises a highly helical NT domain and a less structured CT tail. The objective of this study was to understand their structural and functional role by generating domain swapped chimeras: apoE3-NT/apoAI-CT and apoAI-NT/apoE-CT. The bacterially overexpressed chimeras were purified by affinity chromatography and their identity confirmed by immunoblotting and mass spectrometry. Their α-helical content was comparable to that of the parent proteins. ApoE3-NT/apoAI-CT retained the denaturation profile of apoE3 NT domain, with apoAI CT tail eliciting a relatively unstructured state; its lipid binding ability improved dramatically compared to apoE3 indicative of a significant role of apoAI CT tail in lipid binding interaction. The LDL receptor interaction and ability to promote ABCA1-mediated cholesterol efflux of apoE3-NT/apoAI-CT was comparable to that of apoE3. In contrast, apoAI-NT/apoE-CT elicited an unfolding pattern and lipid binding ability that were similar to that of apoAI. As expected, DMPC/apoAI-NT/apoE-CT discoidal particles did not elicit LDLr binding ability, and promoted SR-B1 mediated cellular uptake of lipids to a limited extent. However, apoAI-NT/apoE-CT displayed an enhanced ability to promote cholesterol efflux compared to apoAI, indicative of a significant role for apoE CT domain in mediating this function. Together, these results indicate that the functional attributes of apoAI and apoE3 can be conferred on each other and that NT-CT domain interactions significantly modulate their structure and function.

2.3-MW Medium-Voltage, Three-Level Wind Energy Inverter Applying a Unique Bus Structure and 4.5-kV Si/SiC Hybrid Isolated Power Modules: Preprint

Energy Technology Data Exchange (ETDEWEB)

Erdman, W.; Keller, J.; Grider, D.; VanBrunt, E.

2014-11-01

A high-efficiency, 2.3-MW, medium-voltage, three-level inverter utilizing 4.5-kV Si/SiC (silicon carbide) hybrid modules for wind energy applications is discussed. The inverter addresses recent trends in siting the inverter within the base of multimegawatt turbine towers. A simplified split, three-layer laminated bus structure that maintains low parasitic inductances is introduced along with a low-voltage, high-current test method for determining these inductances. Feed-thru bushings, edge fill methods, and other design features of the laminated bus structure provide voltage isolation that is consistent with the 10.4-kV module isolation levels. Inverter efficiency improvement is a result of the (essential) elimination of the reverse recovery charge present in 4.5-kV Si PIN diodes, which can produce a significant reduction in diode turn-off losses as well as insulated-gate bipolar transistor (IGBT) turn-on losses. The hybrid modules are supplied in industry-standard 140 mm x 130 mm and 190 mm x 130 mm packages to demonstrate direct module substitution into existing inverter designs. A focus on laminated bus/capacitor-bank/module subassembly level switching performance is presented.

Free triiodothyronine levels and short-term prognosis in chronic heart failure patients with type 2 diabetes.

Science.gov (United States)

Chen, Pingan; Li, Shaonan; Lei, Xiaoming; Liu, Zhen; Wu, Daihong; Luo, Yi; Xu, Dingli

2015-08-01

In chronic heart failure (CHF) patients with type 2 diabetes mellitus (T2DM), the role of thyroid hormone (TH) in predicting CHF severity and prognosis is unclear. The authors therefore investigated the role of TH in predicting CHF severity and prognosis in these specific patients. A total of 224 CHF patients (114 with T2DM) over a mean follow-up time of 6.56 ± 0.18 months were studied. TH, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and other parameters were measured. Free triiodothyronine (FT3) levels were lower in the T2DM group compared with the nondiabetes group (P = 0.026) and higher in the New York Heart Association (NYHA) I group than in the NYHA III and IV groups (both P < 0.05). Compared with the low NT-proBNP group, the high NT-proBNP group had lower FT3 levels (P < 0.01). NT-proBNP correlated with NYHA classes (r = 0.541, P < 0.001), and inversely correlated with left ventricular ejection fraction (r = -0.431, P < 0.001) and FT3 levels (r = -0.335, P < 0.001). In multiple linear regression analysis, NT-proBNP was significantly correlated with NYHA classes (P < 0.001), left ventricular ejection fraction (P < 0.001) and FT3 (P = 0.004). Kaplan-Meier curves showed that the low FT3 group had an increased rate of short-term adverse outcomes of CHF (log rank, χ = 9.794, P = 0.002). FT3 levels are associated with the severity of CHF and seem to reflect short-term outcomes in CHF patients with T2DM.

Elevated NT-proBNP is associated with unfavorably altered plasma fibrin clot properties in atrial fibrillation.

Science.gov (United States)

Matusik, Paweł T; Matusik, Patrycja S; Kornacewicz-Jach, Zdzisława; Małecka, Barbara; Ząbek, Andrzej; Undas, Anetta

2017-09-15

Dense fibrin clot formation and hypofibrinolysis have been reported in atrial fibrillation (AF). It is unclear which factors affect fibrin clot properties in AF. We investigated plasma fibrin clot permeability (K s ), clot lysis time (CLT), endogenous thrombin potential (ETP) as well as other coagulation and fibrinolysis parameters along with N-terminal pro-B-type natriuretic peptide (NT-proBNP) in 160 AF patients (median age, 70.5years). Previous stroke (n=15; 9.4%) was associated with decreased K s (P=0.04) and longer CLT (P=0.005), together with higher antiplasmin (P=0.03) and lower tissue-type plasminogen activator (P=0.01). Lower K s (P=0.04) and tendency towards longer CLT (P=0.10) were observed in patients with a left atrium diameter>40mm. Patients with a CHA 2 DS 2 -VASc score of 3 or more (82.5%) were characterized by higher thrombin-activatable fibrinolysis inhibitor antigen (P=0.009). K s was inversely correlated with log NT-proBNP (r=-0.34, PCLT was positively correlated with log NT-proBNP (R=0.61, PCLT (the top quartile,≥109min). In AF patients prothrombotic fibrin clot properties assessed ex vivo are determined by PAI-1 and NT-proBNP and this phenotype is associated with prior ischemic stroke. Copyright © 2017 Elsevier B.V. All rights reserved.

Mechanism of Activating the Proprioceptive NT-3/TrkC Signalling Pathway by Reverse Intervention for the Anterior Cruciate Ligament–Hamstring Reflex Arc with Electroacupuncture

Directory of Open Access Journals (Sweden)

Lei Zhang

2018-01-01

Full Text Available The anterior cruciate ligament (ACL is an important structure maintaining stability of the knee joints. Deficits in physical stability and the proprioceptive capabilities of the knee joints are observed, when the ACL is damaged. Additionally, a unilateral ACL injury can affect bilateral knee proprioception; therefore, proprioception of the ACL may play a key role in stability. Electroacupuncture therapy has a definite effect nerve regeneration. In this study, cynomolgus monkeys were randomly divided into 4 groups: the model control group, intervention of the injured knee with electroacupuncture (IIKE group, intervention of the bilateral knees with electroacupuncture (IBKE group, and the blank control group. The unilateral ACL injury model was developed in IIKE and IBKE groups; acupuncture points around the knees underwent intervention similarly in the IIKE and IBKE groups. Then, mRNA and protein expressions of NT-3 and TrkC in the dorsal root ganglion and of growth-associated protein-43 in the ACL increased according to reverse-transcription quantitative polymerase chain reaction and Western blotting results. Decreased incubations and increased amplitudes were found for somatosensory-evoked potentials and motor nerve conduction velocity. The finding indicates that electroacupuncture may play an important role in the recovery of proprioception in the ACL by activating the NT-3/TrkC signalling pathway.

Increased NT-proANP predicts risk of congestive heart failure in Cavalier King Charles spaniels with mitral regurgitation caused by myxomatous valve disease.

Science.gov (United States)

Eriksson, Anders S; Häggström, Jens; Pedersen, Henrik Duelund; Hansson, Kerstin; Järvinen, Anna-Kaisa; Haukka, Jari; Kvart, Clarence

2014-09-01

To evaluate the predictive value of plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and nitric oxide end-products (NOx) as markers for progression of mitral regurgitation caused by myxomatous mitral valve disease. Seventy-eight privately owned Cavalier King Charles spaniels with naturally occurring myxomatous mitral valve disease. Prospective longitudinal study comprising 312 measurements over a 4.5 year period. Clinical values were recorded, NT-proANP concentrations were measured by radioimmunoassay, and NOx were analyzed colorimetrically. To predict congestive heart failure (CHF), Cox proportional hazards models with time-varying covariates were constructed. The hazard ratio for NT-proANP (per 1000 pmol/l increase) to predict future CHF was 6.7 (95% confidence interval, 3.6-12.5; p 1000 pmol/l was 11 months (95% confidence interval, 5.6-12.6 months), compared to 54 months (46 - infinity) for dogs with concentrations ≤ 1000 pmol/l (p 130 beats per minute) and grade of murmur (≥ 3/6). The risk of CHF due to mitral regurgitation is increased in dogs with blood NT-proANP concentrations above 1000 pmol/l. Measurement of NT-proANP can be a valuable tool to identify dogs that may develop CHF within months. Copyright © 2014 Elsevier B.V. All rights reserved.

Relation of left ventricular function, mass, and volume to NT-proBNP in type 1 diabetic patients

DEFF Research Database (Denmark)

Astrup, A.S.; Kim, W.Y.; Tarnow, L.

2008-01-01

OBJECTIVES: To measure left ventricular mass (LVM), left ventricular volumes, and left ventricular function (LVF) in a cohort of type 1 diabetic patients and to correlate measures of imaging to NH(2)-terminal pro-brain natriuretic peptide (NT-proBNP). RESEARCH DESIGN AND METHODS: In a cross......-sectional study, all patients with type 1 diabetes underwent cardiovascular magnetic resonance imaging. We included 63 patients with diabetic nephropathy and 73 patients with normoalbuminuria. RESULTS: All patients had normal global LVF. LVM was increased in patients with diabetic nephropathy compared...... is identified in asymptomatic type 1 diabetic patients with nephropathy compared with normoalbuminuric patients. Elevated levels of NT-proBNP were associated with increased LVM, which are both markers of increased cardiovascular risk Udgivelsesdato: 2008/5...

Multi-stage decoding for multi-level block modulation codes

Science.gov (United States)

Lin, Shu

1991-01-01

In this paper, we investigate various types of multi-stage decoding for multi-level block modulation codes, in which the decoding of a component code at each stage can be either soft-decision or hard-decision, maximum likelihood or bounded-distance. Error performance of codes is analyzed for a memoryless additive channel based on various types of multi-stage decoding, and upper bounds on the probability of an incorrect decoding are derived. Based on our study and computation results, we find that, if component codes of a multi-level modulation code and types of decoding at various stages are chosen properly, high spectral efficiency and large coding gain can be achieved with reduced decoding complexity. In particular, we find that the difference in performance between the suboptimum multi-stage soft-decision maximum likelihood decoding of a modulation code and the single-stage optimum decoding of the overall code is very small: only a fraction of dB loss in SNR at the probability of an incorrect decoding for a block of 10(exp -6). Multi-stage decoding of multi-level modulation codes really offers a way to achieve the best of three worlds, bandwidth efficiency, coding gain, and decoding complexity.

Search for an Annual Modulation in a p-Type Point Contact Germanium Dark Matter Detector

Energy Technology Data Exchange (ETDEWEB)

Aalseth, Craig E.; Barbeau, Phil; Colaresi, J.; Collar, J. I.; Diaz Leon, J.; Fast, James E.; Fields, N.; Hossbach, Todd W.; Keillor, Martin E.; Kephart, Jeremy D.; Knecht, A.; Marino, Michael G.; Miley, Harry S.; Miller, M. L.; Orrell, John L.; Radford, D. C.; Wilkerson, J.; Yocum, K. M.

2011-09-01

Fifteen months of cumulative CoGeNT data are examined for indications of an annual modulation, a predicted signature of Weakly Interacting Massive Particle (WIMP) interactions. Presently available data support the presence of a modulated component of unknown origin, with parameters prima facie compatible with a galactic halo composed of light-mass WIMPs.

Plasma N-terminal pro-brain natriuretic peptide levels in patients with acute myocardial infarction, unstable angina pectoris and non-insulin-dependent diabetes

International Nuclear Information System (INIS)

Zhang Yonggang; Li Yuguang

2004-01-01

Objective: Determination of plasma N-terminal pro-brain natriuretic peptide [NT-proBNP (1-76)] levels is useful for the diagnosis of heart failure. Present study was to investigate the significance of changes of plasma NT-proBNP (1-76) levels in patients with acute myocardial infarction (AMI), unstable angina pectoris (UAP) and non-insulin-dependent diabetes (NIDD). Methods: Plasma NT-proBNP (1-76) levels were determined with RIA in 32 patients with AMI, 27 patients with UAP, 12 patients with NIDD and 20 controls. Moreover, 16 of the 32 AMI patients underwent percutaneous transluminal coronary angioplasty (PTCA) and plasma (1-76) levels were again determined 12hr before and 12hr after the procedure. Results: The plasma NT-proBNP (1-76) levels in controls were 360.8 ± 57.3 pg/ ml with no significant difference between the sexes. In patients with AMI, UAP and NIDD, NT-proBNP (1-76) levels were 554.1 ± 195.9 pg/ml, 525.7 ± 199.1 pg/ml and 552.6 ± 141.9 pg/ml respectively; all of them were significantly higher than those in controls (P 0.05). Conclusion: The plasma NT-proBNP (1-76) levels in patients with AMI, UAP and NIDD were increased significantly and the result suggested that NT-proBNP (1-76) might be a useful risk marker for these diseases. (authors)

Dynamic modeling of the manipulator RD5NT

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Eduardo Monteiro Aguiar

2015-05-01

Full Text Available This article presents the development of a dynamicmathematical model for the DIDACTA ITALIARD5NT manipulator. The model is intendedto be used in the development of strategies ofposition-trajectory control. The choice modelingtype aims at identifying the physical parametersof the manipulator.

The value of T/NT in FDG imaging with a coincidence camera for diagnosis of pulmonary nodules and mass lesions

International Nuclear Information System (INIS)

Sun Da; Zhan Hongwei; Xu Wei; Ye Xiaojuan; Liu Qichang

2004-01-01

Objectives: To assess the value of T/NT in FDG imaging with a coincidence camera for diagnosis of pulmonary nodules and mass lesions. Methods: 18F-FDG imaging were performed in 57 patients with a mean age of 62.18 (range from 33 83 years old) for diagnosis of pulmonary nodules and mass lesions using a gamma camera with 1 inch crystal in coincidence mode (Siemens E.comduet). 175 296 MBq (5 8 mci) of 18F-FDG was given by iv on an empty stomach at least for 6 hours, and a whole body imaging without brain and legs was performed after 40 60 minutes. The count rate of target ROI and no-target ROI (T/NT) were calculated as a semiquantative analysis to differentiate malignant from inflammatory lesions. The result was compared with CT, MRI, and/or pathology. Results: The mean value of T/NT in malignant lesions (N=45) in lungs is 4.32 (range 1.61 10.62). But it is 1.52 (range 1.37 1.95) in inflammatory lesions (N=17) in lungs, and 4.09 (range 2.2 7.01) in lung tuberculosis lesions (N=5). In 45 malignant, the value of T/NT is less than 2.0 in only 3 lesions. So the overlapping of T/NT value is very little between malignant and inflammatory lesions. But there is full overlapping of T/NT value between malignant and tuberculosis lesions. Conclusions: Focal pulmonary nodules and mass lesions are commonly encountered in clinical practice, and PET with 18F-FDG has proved to be an accurate noninvasive test for identifying pulmonary malignant lesions. The technique of semiquantity with T/NT is useful to differentiate malignant from inflammatory lesions. But it is invalidate for distinguishing malignant from tuberculosis lesions. (authors)

BAG3 down-modulation reduces anaplastic thyroid tumor growth by enhancing proteasome-mediated degradation of BRAF protein.

Science.gov (United States)

Chiappetta, Gennaro; Basile, Anna; Arra, Claudio; Califano, Daniela; Pasquinelli, Rosa; Barbieri, Antonio; De Simone, Veronica; Rea, Domenica; Giudice, Aldo; Pezzullo, Luciano; De Laurenzi, Vincenzo; Botti, Gerardo; Losito, Simona; Conforti, Daniela; Turco, Maria Caterina

2012-01-01

Anaplastic thyroid tumors (ATC) express high levels of BAG3, a member of the BAG family of cochaperone proteins that is involved in regulating cell apoptosis through multiple mechanisms. The objective of the study was the investigation of the influence of B-cell lymphoma-2-associated athanogene 3 (BAG3) on ATC growth. We investigated the effects of BAG3 down-modulation, obtained by using a specific small interfering RNA, on in vitro and in vivo growth of the human ATC cell line 8505C. Because BRAF protein plays an important role in ATC cell growth, we analyzed the effects of BAG3 down-modulation on BRAF protein levels. Furthermore, by using a proteasome inhibitor, we verified whether BAG3-mediated regulation of BRAF levels involved a proteasome-dependent mechanism. BAG3 down-modulation significantly inhibits ATC growth in vitro and in vivo. BAG3 coimmunoprecipitates with BRAF protein, and its down-modulation results in a significant reduction of BRAF protein levels, which can be reverted by incubation with the proteasome inhibitor MG132. BAG3 protein sustains ATC growth in vitro and in vivo. The underlying molecular mechanism appears to rely on BAG3 binding to BRAF, thus protecting it from proteasome-dependent degradation. These results are in line with the reported ability of BAG3 to interfere with the proteasomal delivery of a number of other client proteins.

Space Vector Pulse Width Modulation of a Multi-Level Diode ...

African Journals Online (AJOL)

Space Vector Pulse Width Modulation of a Multi-Level Diode Clamped ... of MATLAB /SIMULINK modeling of the space vector pulse-width modulation and the ... two adjacent active vectors in determining the switching process of the multilevel ...

Study of plasma neuropeptide levels in patients with acute cardiovascular and cerebrovascular disease

International Nuclear Information System (INIS)

Xu Youfen; Lan Suixin; Chen Yu; He Ling; Huang Yuan; Ma Yaling

2003-01-01

Objective: To explore the relationship between the dynamic changes of plasma neuropeptide (β-EP, NT, NPY) levels and the pathogenesis as well as clinical outcomes of acute cardiovascular and cerebrovascular diseases. Methods: The concentrations of serum neuropeptides (β-EP, NT, NPY) were measured on the 1 st, 3 rd, 7 th, 14 th day after the onset of disease with RIA in 103 patients with acute cardiovascular and cerebrovascular diseases (38 cases of acute cerebral infarction, 32 cases of cerebral hemorrhage, 33 cases of acute myocardial infarction and acute heart failure) and 66 controls. Results: 1. NPY, NT and β-EP levels in patients with acute cardiovascular and cerebrovascular disease were significantly higher than those in controls (p<0.01). (F=39.54, p<0.01; F=33.38, p<0.01; F=8.38, p<0.01 For β-EP, NPY and NT respectively). 2. The plasma neuropeptide levels were highest at onset and gradually lowered till to normal levels on the 14 th day. Conclusion: Plasma neuropeptide levels were closely related to the pathogenesis and clinical outcome of acute cardiovascular and cerebrovascular diseases, study of which might be useful in the clinical management of the diseases

The influence of BANXIAXIEXIN decoction and its analogous preparations on neurotensin (NT) in rat models with reflux esophagitis

International Nuclear Information System (INIS)

Liu Xiaoni; Gao Yanqing; Si Yinchu; Niu Xin

2003-01-01

Objective: To investigate the mechanism of BANXIAXIEXIN TANG Decoction and its analogous preparations in treatment of reflux esophagitis. Methods: 60 rat models with duodenogastroesophageal reflux were divided into 4 equal numbered groups; control group, BANXIAXIEXIN TANG group, SHENGJIANGXIEXIN TANG group, GANCAOXIEXIN TANG group. The contents of NT in hypothalamus, ileum and plasma were measured by radioimmunoassay in all these models and the relationship between NT concentration and degree of esophageal mucosa injury in the control group was analysed. Results: BANXIAXIEXIN Decoction and its analogous preparations could reduce the degree of the esophageal mucosa injury significantly (p<0.01). Compared with the control group: the hypothalamus content of NT in SHENGJIANGXIEXIN TANG group was significantly lowered (p<0.05), the ileum content of NT in BANXIAXIEXIN TANG group was significantly lowered (p<0.01), the plasma contents of NT in both groups were significantly lowered (p<0.05) as well. There was positive correlation (r=0.442, p<0.01) between content of NT in ileum and degree of the esophageal mucosa injury in control group. Conclusion: NT may play an important role in the development reflux esophagitis. Regulating the synthesis and secretion of NT may be one of the mechanisms of BANXIAXIEXIN Decoction and its analogus preparations in treatment of reflux esophagitis

3D Pattern Synthesis of Time-Modulated Conformal Arrays with a Multiobjective Optimization Approach

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Wentao Li

2014-01-01

Full Text Available This paper addresses the synthesis of the three-dimensional (3D radiation patterns of the time-modulated conformal arrays. Due to the nature of periodic time modulation, harmonic radiation patterns are generated at the multiples of the modulation frequency in time-modulated arrays. Thus, the optimization goal of the time-modulated conformal array includes the optimization of the sidelobe level at the operating frequency and the sideband levels (SBLs at the harmonic frequency, and the design can be regarded as a multiobjective problem. The multiobjective particle swarm optimization (MOPSO is applied to optimize the switch-on instants and pulse durations of the time-modulated conformal array. To significantly reduce the optimization variables, the modified Bernstein polynomial is employed in the synthesis process. Furthermore, dual polarized patch antenna is designed as radiator to achieve low cross-polarization level during the beam scanning. A 12 × 13 (156-element conical conformal microstrip array is simulated to demonstrate the proposed synthesis mechanism, and good results reveal the promising ability of the proposed algorithm in solving the synthesis of the time-modulated conformal arrays problem.

Spectroscopic Classification of SN 2018nt as a Reddened Type Ia Supernova

Science.gov (United States)

Vinko, J.; Szeged, U.; Wheeler, J. C.

2018-02-01

An optical spectrum (range 360-700 nm) of SN 2018nt (K2 C16-0043), was obtained with the "Low Resolution Spectrograph-2" (LRS2) on the 10m Hobby-Eberly Telescope at McDonald Observatory by S. Odewahn on 2018 Feb 05.20 UT. The spectrum is consistent with that of a heavily reddened Type Ia supernova (with Av > 2 mag) about 3 weeks after maximum light.

Predictive value of NT-proBNP for 30-day mortality in patients with non-ST-elevation acute coronary syndromes: a comparison with the GRACE and TIMI risk scores.

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Schellings, Dirk Aam; Adiyaman, Ahmet; Dambrink, Jan-Henk E; Gosselink, At Marcel; Kedhi, Elvin; Roolvink, Vincent; Ottervanger, Jan Paul; Van't Hof, Arnoud Wj

2016-01-01

The biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts outcome in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). Whether NT-proBNP has incremental prognostic value beyond established risk strategies is still questionable. To evaluate the predictive value of NT-proBNP for 30-day mortality over and beyond the Global Registry of Acute Coronary Events (GRACE) and Thrombolysis In Myocardial Infarction (TIMI) risk scores in patients with NSTE-ACS. Patients included in our ACS registry were candidates. NT-proBNP levels on admission were measured and the GRACE and TIMI risk scores were assessed. We compared the predictive value of NT-proBNP to both risk scores and evaluated whether NT-proBNP improves prognostication by using receiver operator curves and measures of discrimination improvement. A total of 1324 patients were included and 50 patients died during follow-up. On logistic regression analysis NT-proBNP and the GRACE risk score (but not the TIMI risk score) both independently predicted mortality at 30 days. The predictive value of NT-proBNP did not differ significantly compared to the GRACE risk score (area under the curve [AUC]) 0.85 vs 0.87 p =0.67) but was considerably higher in comparison to the TIMI risk score (AUC 0.60 p risk score by adding NT-proBNP did not improve prognostication: AUC 0.86 ( p =0.57), integrated discrimination improvement 0.04 ( p =0.003), net reclassification improvement 0.12 ( p =0.21). In patients with NSTE-ACS, NT-proBNP and the GRACE risk score (but not the TIMI risk score) both have good and comparable predictive value for 30-day mortality. However, incremental prognostic value of NT-proBNP beyond the GRACE risk score could not be demonstrated.

Expression of neurotensin and NT1 receptor in human breast cancer: a potential role in tumor progression.

Science.gov (United States)

Souazé, Frédérique; Dupouy, Sandra; Viardot-Foucault, Véronique; Bruyneel, Erik; Attoub, Samir; Gespach, Christian; Gompel, Anne; Forgez, Patricia

2006-06-15

Emerging evidence supports neurotensin as a trophic and antiapoptotic factor, mediating its control via the high-affinity neurotensin receptor (NT1 receptor) in several human solid tumors. In a series of 51 patients with invasive ductal breast cancers, 34% of all tumors were positive for neurotensin and 91% positive for NT1 receptor. We found a coexpression of neurotensin and NT1 receptor in a large proportion (30%) of ductal breast tumors, suggesting a contribution of the neurotensinergic signaling cascade within breast cancer progression. Functionally expressed NT1 receptor, in the highly malignant MDA-MB-231 human breast cancer cell line, coordinated a series of transforming functions, including cellular migration, invasion, induction of the matrix metalloproteinase (MMP)-9 transcripts, and MMP-9 gelatinase activity. Disruption of NT1 receptor signaling by silencing RNA or use of a specific NT1 receptor antagonist, SR48692, caused the reversion of these transforming functions and tumor growth of MDA-MB-231 cells xenografted in nude mice. Our findings support the contribution of neurotensin in human breast cancer progression and point out the utility to develop therapeutic molecules targeting neurotensin or NT1 receptor signaling cascade. These strategies would increase the range of therapeutic approaches and be beneficial for specific patients.

Spore Coat Architecture of Clostridium novyi-NT spores

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Plomp, M; McCafferey, J; Cheong, I; Huang, X; Bettegowda, C; Kinzler, K; Zhou, S; Vogelstein, B; Malkin, A

2007-05-07

Spores of the anaerobic bacterium Clostridium novyi-NT are able to germinate in and destroy hypoxic regions of tumors in experimental animals. Future progress in this area will benefit from a better understanding of the germination and outgrowth processes that are essential for the tumorilytic properties of these spores. Towards this end, we have used both transmission electron microscopy and atomic force microscopy to determine the structure of dormant as well as germinating spores. We found that the spores are surrounded by an amorphous layer intertwined with honeycomb parasporal layers. Moreover, the spore coat layers had apparently self-assembled and this assembly was likely to be governed by crystal growth principles. During germination and outgrowth, the honeycomb layers as well as the underlying spore coat and undercoat layers sequentially dissolved until the vegetative cell was released. In addition to their implications for understanding the biology of C. novyi-NT, these studies document the presence of proteinaceous growth spirals in a biological organism.

Relation of Renal Function with Left Ventricular Systolic Function and NT-proBNP Level and Its Prognostic Implication in Heart Failure with Preserved versus Reduced Ejection Fraction: an analysis from the Korean Heart Failure (KorHF) Registry.

Science.gov (United States)

Park, Chan Soon; Park, Jin Joo; Oh, Il-Young; Yoon, Chang-Hwan; Choi, Dong-Ju; Park, Hyun-Ah; Kang, Seok-Min; Yoo, Byung-Su; Jeon, Eun-Seok; Kim, Jae-Joong; Cho, Myeong-Chan; Chae, Shung Chull; Ryu, Kyu-Hyung; Oh, Byung-Hee

2017-09-01

The relationship between ejection fraction (EF), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and renal function is unknown as stratified by heart failure (HF) type. We investigated their relation and the prognostic value of renal function in heart failure with preserved ejection fraction (HFpEF) vs. reduced ejection fraction (HFrEF). NT-proBNP, glomerular filtration rate (GFR), and EF were obtained in 1,932 acute heart failure (AHF) patients. HFrEF was defined as EFrenal dysfunction as GFRrenal dysfunction: 30≤GFRrenal dysfunction: GFRrenal dysfunction did not differ between HFpEF and HFrEF (49% vs. 52%, p=0.210). Patients with renal dysfunction had higher 12-month mortality in both HFpEF (7.9% vs. 15.2%, log-rank p=0.008) and HFrEF (8.6% vs. 16.8%, log-rank prenal dysfunction was an independent predictor of 12-month mortality (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.40-3.11). When stratified according to EF: the prognostic value of severe renal dysfunction was attenuated in HFpEF patients (HR, 1.46; 95% CI, 0.66-3.21) contrary to HFrEF patients (HR, 2.43; 95% CI, 1.52-3.89). In AHF patients, the prevalence of renal dysfunction did not differ between HFpEF and HFrEF patients. However, the prognostic value of renal dysfunction was attenuated in HFpEF patients.

A New Method for Blood NT-proBNP Determination Based on a Near-infrared Point of Care Testing Device with High Sensitivity and Wide Scope.

Science.gov (United States)

Zhang, Xiao Guang; Shu, Yao Gen; Gao, Ju; Wang, Xuan; Liu, Li Peng; Wang, Meng; Cao, Yu Xi; Zeng, Yi

2017-06-01

To develop a rapid, highly sensitive, and quantitative method for the detection of NT-proBNP levels based on a near-infrared point-of-care diagnostic (POCT) device with wide scope. The lateral flow assay (LFA) strip of NT-proBNP was first prepared to achieve rapid detection. Then, the antibody pairs for NT-proBNP were screened and labeled with the near-infrared fluorescent dye Dylight-800. The capture antibody was fixed on a nitrocellulose membrane by a scribing device. Serial dilutions of serum samples were prepared using NT-proBNP-free serum series. The prepared test strips, combined with a near-infrared POCT device, were validated by known concentrations of clinical samples. The POCT device gave the output of the ratio of the intensity of the fluorescence signal of the detection line to that of the quality control line. The relationship between the ratio value and the concentration of the specimen was plotted as a work curve. The results of 62 clinical specimens obtained from our method were compared in parallel with those obtained from the Roche E411 kit. Based on the log-log plot, the new method demonstrated that there was a good linear relationship between the ratio value and NT-proBNP concentrations ranging from 20 pg/mL to 10 ng/mL. The results of the 62 clinical specimens measured by our method showed a good linear correlation with those measured by the Roche E411 kit. The new LFA detection method of NT-proBNP levels based on the near-infrared POCT device was rapid and highly sensitive with wide scope and was thus suitable for rapid and early clinical diagnosis of cardiac impairment. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Arabidopsis ATRX Modulates H3.3 Occupancy and Fine-Tunes Gene Expression

KAUST Repository

Duc, Céline

2017-07-07

Histones are essential components of the nucleosome, the major chromatin subunit that structures linear DNA molecules and regulates access of other proteins to DNA. Specific histone chaperone complexes control the correct deposition of canonical histones and their variants to modulate nucleosome structure and stability. In this study, we characterize the Arabidopsis Alpha Thalassemia-mental Retardation X-linked (ATRX) ortholog and show that ATRX is involved in histone H3 deposition. Arabidopsis ATRX mutant alleles are viable, but show developmental defects and reduced fertility. Their combination with mutants of the histone H3.3 chaperone HIRA (Histone Regulator A) results in impaired plant survival, suggesting that HIRA and ATRX function in complementary histone deposition pathways. Indeed, ATRX loss of function alters cellular histone H3.3 pools and in consequence modulates the H3.1/H3.3 balance in the cell. H3.3 levels are affected especially at genes characterized by elevated H3.3 occupancy, including the 45S ribosomal DNA (45S rDNA) loci, where loss of ATRX results in altered expression of specific 45S rDNA sequence variants. At the genome-wide scale, our data indicate that ATRX modifies gene expression concomitantly to H3.3 deposition at a set of genes characterized both by elevated H3.3 occupancy and high expression. Altogether, our results show that ATRX is involved in H3.3 deposition and emphasize the role of histone chaperones in adjusting genome expression.

Small-molecule quinolinol inhibitor identified provides protection against BoNT/A in mice.

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Padma Singh

Full Text Available Botulinum neurotoxins (BoNTs, etiological agents of the life threatening neuroparalytic disease botulism, are the most toxic substances currently known. The potential for the use as bioweapon makes the development of small-molecule inhibitor against these deadly toxins is a top priority. Currently, there are no approved pharmacological treatments for BoNT intoxication. Although an effective vaccine/immunotherapy is available for immuno-prophylaxis but this cannot reverse the effects of toxin inside neurons. A small-molecule pharmacological intervention, especially one that would be effective against the light chain protease, would be highly desirable. Similarity search was carried out from ChemBridge and NSC libraries to the hit (7-(phenyl(8-quinolinylaminomethyl-8-quinolinol; NSC 84096 to mine its analogs. Several hits obtained were screened for in silico inhibition using AutoDock 4.1 and 19 new molecules selected based on binding energy and Ki. Among these, eleven quinolinol derivatives potently inhibited in vitro endopeptidase activity of botulinum neurotoxin type A light chain (rBoNT/A-LC on synaptosomes isolated from rat brain which simulate the in vivo system. Five of these inhibitor molecules exhibited IC(50 values ranging from 3.0 nM to 10.0 µM. NSC 84087 is the most potent inhibitor reported so far, found to be a promising lead for therapeutic development, as it exhibits no toxicity, and is able to protect animals from pre and post challenge of botulinum neurotoxin type A (BoNT/A.

Modulation of the major histocompatibility complex by neural stem cell-derived neurotrophic factors used for regenerative therapy in a rat model of stroke

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Sun Chongran

2010-08-01

Full Text Available Abstract Background The relationship between functional improvements in ischemic rats given a neural stem cell (NSC transplant and the modulation of the class I major histocompatibility complex (MHC mediated by NSC-derived neurotrophins was investigated. Methods The levels of gene expression of nerve growth factor (NGF, brain-derived neurotropic factor (BDNF and neurotrophin-3 (NT-3 were assayed from cultures of cortical NSC from Sprague-Dawley rat E16 embryos. The levels of translated NGF in spent culture media from NSC cultures and the cerebral spinal fluid (CSF of rats with and without NGF injection or NSC transplant were also measured. Results We found a significant increase of NGF, BDNF and NT-3 transcripts and NGF proteins in both the NSC cultures and the CSF of the rats. The immunochemical staining for MHC in brain sections and the enzyme-linked immunosorbent assay of CSF were carried out in sham-operated rats and rats with surgically induced focal cerebral ischemia. These groups were further divided into animals that did and did not receive NGF administration or NSC transplant into the cisterna magna. Our results show an up-regulation of class I MHC in the ischemic rats with NGF and NSC administration. The extent of caspase-III immunoreactivity was comparable among three arms in the ischemic rats. Conclusion Readouts of somatosensory evoked potential and the trap channel test illustrated improvements in the neurological function of ischemic rats treated with NGF administration and NSC transplant.

Solar Drivers of 11-yr and Long-Term Cosmic Ray Modulation

Science.gov (United States)

Cliver, E. W.; Richardson, I. G.; Ling, A. G.

2011-01-01

In the current paradigm for the modulation of galactic cosmic rays (GCRs), diffusion is taken to be the dominant process during solar maxima while drift dominates at minima. Observations during the recent solar minimum challenge the pre-eminence of drift: at such times. In 2009, the approx.2 GV GCR intensity measured by the Newark neutron monitor increased by approx.5% relative to its maximum value two cycles earlier even though the average tilt angle in 2009 was slightly larger than that in 1986 (approx.20deg vs. approx.14deg), while solar wind B was significantly lower (approx.3.9 nT vs. approx.5.4 nT). A decomposition of the solar wind into high-speed streams, slow solar wind, and coronal mass ejections (CMEs; including postshock flows) reveals that the Sun transmits its message of changing magnetic field (diffusion coefficient) to the heliosphere primarily through CMEs at solar maximum and high-speed streams at solar minimum. Long-term reconstructions of solar wind B are in general agreement for the approx. 1900-present interval and can be used to reliably estimate GCR intensity over this period. For earlier epochs, however, a recent Be-10-based reconstruction covering the past approx. 10(exp 4) years shows nine abrupt and relatively short-lived drops of B to value of approx.2.8 nT. A floor in solar wind B implies a ceiling in the GCR intensity (a permanent modulation of the local interstellar spectrum) at a given energy/rigidity. The 30-40% increase in the intensity of 2.5 GV electrons observed by Ulysses during the recent solar minimum raises an interesting paradox that will need to be resolved.

Characterization of ectonucleotidases in human medulloblastoma cell lines: ecto-5'NT/CD73 in metastasis as potential prognostic factor.

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Angélica Regina Cappellari

Full Text Available Medulloblastoma (MB is the most common malignant brain tumor in children and occurs mainly in the cerebellum. Important intracellular signaling molecules, such those present in the Sonic Hedgehog and Wnt pathways, are involved in its development and can also be employed to determine tumor grade and prognosis. Ectonucleotidases, particularly ecto-5'NT/CD73, are important enzymes in the malignant process of different tumor types regulating extracellular ATP and adenosine levels. Here, we investigated the activity of ectonucleotidases in three malignant human cell lines: Daoy and ONS76, being representative of primary MB, and the D283 cell line, derived from a metastatic MB. All cell lines secreted ATP into the extracellular medium while hydrolyze poorly this nucleotide, which is in agreement with the low expression and activity of pyrophosphate/phosphodiesterase, NTPDases and alkaline phosphatase. The analysis of AMP hydrolysis showed that Daoy and ONS76 completely hydrolyzed AMP, with parallel adenosine production (Daoy and inosine accumulation (ONS76. On the other hand, D283 cell line did not hydrolyze AMP. Moreover, primary MB tumor cells, Daoy and ONS76 express the ecto-5'NT/CD73 while D283 representative of a metastatic tumor, revealed poor expression of this enzyme, while the ecto-adenosine deaminase showed higher expression in D283 compared to Daoy and ONS76 cells. Nuclear beta-catenin has been suggested as a marker for MB prognosis. Further it can promotes expression of ecto-5'NT/CD73 and suppression of adenosine deaminase. It was observed that Daoy and ONS76 showed greater nuclear beta-catenin immunoreactivity than D283, which presented mainly cytoplasmic immunoreactivity. In summary, the absence of ecto-5'NT/CD73 in the D283 cell line, a metastatic MB phenotype, suggests that high expression levels of this ectonucleotidase could be correlated with a poor prognosis in patients with MB.

The ability of NT-proBNP to detect chronic heart failure and predict all-cause mortality is higher in elderly Chinese coronary artery disease patients with chronic kidney disease

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Fu S

2013-04-01

Full Text Available Shihui Fu, Leiming Luo, Ping Ye, Shuangyan Yi, Yuan Liu, Bing Zhu, Liang Wang, Tiehui Xiao, Yongyi Bai Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, People's Republic of China Objective: To analyze the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP and renal function, and compare the ability and cut-off thresholds of NT-proBNP to detect chronic heart failure (CHF and predict mortality in elderly Chinese coronary artery disease (CAD patients with and without chronic kidney disease (CKD. Methods: The study included 999 CAD patients older than 60 years. The endpoint was all-cause mortality over a mean follow-up period of 417 days. Results: The median age was 86 years (range: 60–104 years, and the median NT-proBNP level was 409.8 pg/mL. CKD was present in 358 patients. Three hundred and six patients were positive for CHF. One hundred and ten CKD patients and 105 non-CKD patients died. Not only CKD, but also estimated glomerular filtration rate independently affected NT-proBNP. NT-proBNP detected CHF with a cut-off value of 298.4 pg/mL in non-CKD patients and a cut-off value of 435.7 pg/mL in CKD patients. NT-proBNP predicted death with a cut-off value of 369.5 pg/mL in non-CKD patients and a cut-off value of 2584.1 pg/mL in CKD patients. The NT-proBNP level was significantly related to the prevalence of CHF and all-cause mortality in CAD patients with and without CKD; this effect persisted after adjustment. The crude and multiple adjusted hazard ratios of NT-proBNP to detect CHF and predict mortality were significantly higher in patients with CKD compared with the remainder of the population. The addition of NT-proBNP to the three-variable and six-variable models generated a significant increase in the C-statistic. Conclusion: Amongst elderly Chinese CAD patients, there was an independently inverse association between NT-proBNP and renal function. With the higher cutoff points, NT

Experimental Investigations of 3-D-/4-D-CAP Modulation With Directly Modulated VCSELs

DEFF Research Database (Denmark)

Binti Othman, Maisara; Zhang, Xu; Deng, Lei

2012-01-01

correction limit of 2.8 × 10-3 for error-free reception is achieved after 20 km of SSMF transmission. Spectral efficiencies of 2.68 and 2.08 b/s/Hz are reported for 3-D-CAP and 4-D-CAP, respectively. We believe that multidimensional modulation formats represent an attractive solution for providing more......In this letter, we present experimental investigations of multidimensional multilevel carrierless amplitude phase (CAP) modulation with directly modulated vertical cavity surface-emitting lasers. The signals are transmitted over 20 km of standard single-mode fiber (SSMF). For multilevel 3-D...

In-Vivo Neutralization of Botulinum Neurotoxin Serotype E Using Rabbit Polyclonal Antibody Developed against BoNT/E Light Chain.

Science.gov (United States)

Rani, Sarita; Ponmariappan, S; Sharma, Arti; Kamboj, D V; Jain, A K

2017-01-01

Clostridium botulinum is an obligate anaerobic, Gram positive bacterium that secretes extremely toxic substances known as botulinum neurotoxins (BoNTs) that cause serious paralytic illness called botulism. Based upon the serological properties, these neurotoxin have been classified into seven serotypes designated from A to G. Due to extreme toxicity of BoNTs, these neurotoxins have been designated as category A biowarfare agents. There is no commercial neutralizing antibody available for the treatment of botulism. Hence there is an urgent need to develop therapeutic intervention for prevention and cure of botulism within short period. BoNT antiserum injection is still the effective treatment. In the present study, the recombinant light chain of BoNT/E was successfully purified in soluble form. The purified rBoNT/E LC was used for the generation of polyclonal antibody in rabbit. In order to find out the neutralizing capacity of generated antisera, rabbit antiserum was incubated with 20 LD50 of botulinum neurotoxin type E for 1 hour at 37°C and then injected intraperitoneally (IP) into mice. Further in another set of experiments antiserum was administered in different ways that included administration of - antiserum and BoNT/E toxin simultaneously without preincubation, one after another at the same and different time points for its therapeutic ability. To find out cross neutralization capacity, rBoNT/E LC antiserum was pre-incubated with 5 LD50 of BoNT/A, BoNT/B, BoNT/F and then injected (IP) into mice. In all the cases mice were observed continuously for 96 hours. The results clearly indicate that developed polyclonal rabbit antiserum showed serotype specific neutralization of BoNT/E toxin only but not of BoNT/A, BoNT/B and BoNT/F. The developed antibodies will be used for preventive and therapeutic intervention of type 'E' botulism. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

IP3 levels and their modulation FY fusicoccin measured by a novel [3H] IP3 binding assay

International Nuclear Information System (INIS)

Aducci, P.; Marra, M.

1990-01-01

A recently developed sensitive assay based on the binding reaction of IP3 to bovine adrenal preparations has been utilized for determining the level of endogenous inositol-1,4,5 trisphosphate (IP3) in maize roots and coleoptiles. The amount of IP3 found in these tissues ranges from 0.1 to 1.0 nmol g-1 fresh weight. Reproducible results were obtained with extracts of tissues from a same harvest, while they showed a 2-3 fold variation when different batches of plantlets were compared. The fungal phytotoxin fusicoccin (FC) known to affect several physiological processes in higher plants, increases the level of IP3 in coleoptiles. This observation suggests that IP3 might be involved in the transduction of the FC encoded signal from its receptors at the plasmalemma level to the cell machinery

Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury

Science.gov (United States)

Keefe, Kathleen M.; Sheikh, Imran S.; Smith, George M.

2017-01-01

Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI). We focus on nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord. PMID:28273811

Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury.

Science.gov (United States)

Keefe, Kathleen M; Sheikh, Imran S; Smith, George M

2017-03-03

Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI). We focus on nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord.

Search for an Annual Modulation in a p-Type Point Contact Germanium Dark Matter Detector

Energy Technology Data Exchange (ETDEWEB)

Barbeau, P.S. [University of Chicago; Collar, J.I. [University of Chicago; Fields, N. [University of Chicago; Hossbach, T.W. [Pacific Northwest National Laboratory (PNNL); Aalseth, C.E. [Pacific Northwest National Laboratory (PNNL); Fast, James E. [Pacific Northwest National Laboratory (PNNL); Keillor, M. [Pacific Northwest National Laboratory (PNNL); Kephart, J.D. [Pacific Northwest National Laboratory (PNNL); Miley, H.S. [Pacific Northwest National Laboratory (PNNL); Orrell, John L. [Pacific Northwest National Laboratory (PNNL); Colaresi, James F. [Canberra Industries, Inc., Meriden, CT; Yocum, K. Michael [Canberra Industries, Inc., Meriden, CT; Leon, J. Diaz [University of Washington, Ctr Expt Nucle Phys & Astrophys; Knecht, A. [University of Washington, Ctr Expt Nucle Phys & Astrophys; Marino, M. G. [University of Washington, Ctr Expt Nucle Phys & Astrophys; Miller, M. L. [University of Washington, Ctr Expt Nucle Phys & Astrophys; Radford, David C [ORNL; Wilkerson, John F [University of North Carolina, Chapel Hill

2011-01-01

Fifteen months of cumulative CoGeNT data are examined for indications of an annual modulation, a predicted signature of weakly interacting massive particle (WIMP) interactions. Presently available data support the presence of a modulated component of unknown origin, with parameters prima facie compatible with a galactic halo composed of light-mass WIMPs. Unoptimized estimators yield a statistical significance for a modulation of {approx}2.8{sigma}, limited by the short exposure.

Random mutagenesis of BoNT/E Hc nanobody to construct a secondary phage-display library.

Science.gov (United States)

Shahi, B; Mousavi Gargari, S L; Rasooli, I; Rajabi Bazl, M; Hoseinpoor, R

2014-08-01

To construct secondary mutant phage-display library of recombinant single variable domain (VHH) against botulinum neurotoxin E by error-prone PCR. The gene coding for specific VHH derived from the camel immunized with binding domain of botulinum neurotoxin E (BoNT/E) was amplified by error-prone PCR. Several biopanning rounds were used to screen the phage-displaying BoNT/E Hc nanobodies. The final nanobody, SHMR4, with increased affinity recognized BoNT/E toxin with no cross-reactivity with other antigens especially with related BoNT toxins. The constructed nanobody could be a suitable candidate for VHH-based biosensor production to detect the Clostridium botulinum type E. Diagnosis and treatment of botulinum neurotoxins are important. Generation of high-affinity antibodies based on the construction of secondary libraries using affinity maturation step leads to the development of reagents for precise diagnosis and therapy. © 2014 The Society for Applied Microbiology.

The nT1 translocation separates vulval regulatory elements from the egl-18 and elt-6 GATA factor genes.

Science.gov (United States)

Koh, Kyunghee; Bernstein, Yelena; Sundaram, Meera V

2004-03-01

egl-18 and elt-6 are partially redundant, adjacent genes encoding GATA factors essential for viability, seam cell development, and vulval development in Caenorhabditis elegans. The nT1 reciprocal translocation causes a strong Vulvaless phenotype, and an nT1 breakpoint was previously mapped to the left arm of LGIV, where egl-18/elt-6 are located. Here we present evidence that the nT1 vulval phenotype is due to a disruption of egl-18/elt-6 function specifically in the vulva. egl-18 mutations do not complement nT1 for vulval defects, and the nT1 breakpoint on LGIV is located within approximately 800 bp upstream of a potential transcriptional start site of egl-18. In addition, we have identified a approximately 350-bp cis-regulatory region sufficient for vulval expression just upstream of the nT1 breakpoint. By examining the fusion state and division patterns of the cells in the developing vulva of nT1 mutants, we demonstrate that egl-18/elt-6 prevent fusion and promote cell proliferation at multiple steps of vulval development.

TeraTools: Multiparameter data acquisition software for the Windows 95/NT OS

International Nuclear Information System (INIS)

Piercey, R.B.

1997-01-01

TeraTools, a general purpose, multiparameter, data acquisition application for Windows 95NT is described. It is based on the Kmax architecture which has been used since 1986 on the Macintosh computer at numerous industrial, education, and research sites world-wide. TeraTools includes high-level support for industry-standard modular instrumentation; a built-in scripting language; drivers for commercially available interfaces; hooks for external code extensions; event file sorting and replay; and a full set of histogramming and display tools. The environment is scalable and may be applied to problems involving a few parameters or many parameters

Physics capabilities of the second stage Baikal detector NT-200

International Nuclear Information System (INIS)

Spiering, C.; Heller, R.; Heukenkamp, H.; Krabi, J.; Mikolajski, T.; Thon, T.; Wischnewski, R.; Alatin, S.D.; Fialkovsky, S.V.; Kulepov, V.F.; Milenin, M.B.; Belolaptikov, I.A.; Bezrukov, L.B.; Borisovets, B.A.; Bugaev, E.V.; Djilkibaev, Zh.A.M.; Domogatsky, G.V.; Donskich, L.A.; Doroshenko, A.A.; Galperin, M.D.; Gushtan, M.N.; Klabukov, A.M.; Klimushin, S.I.; Lanin, O.J.; Lubsandorzhiev, B.K.; Ogievietzky, N.V.; Panfilov, A.I.; Sokalsky, I.A.; Trofimenko, I.I.; Budnev, N.M.; Chensky, A.G.; Dobrynin, V.I.; Gress, O.A.; Koshechkin, A.P.; Lanin, J.B.; Litunenko, G.A.; Lopin, A.L.; Naumov, V.A.; Nemchenko, M.I.; Parfenov, Yu.V.; Pavlov, A.A.; Pokalev, O.P.; Primin, V.A.; Sumanov, A.A.; Tarashansky, V.A.; Zurbanov, V.L.; Dudkin, G.N.; Egorov, V.Yu.; Lukanin, A.A.; Ovcharov, A.M.; Padalko, V.M.; Padusenko, A.H.; Golikov, A.V.; Kabikov, V.B.; Kuzmichov, L.A.; Osipova, E.A.; Zaslavskaya, E.S.; Jenek, L.; Kiss, D.; Tanko, L.; Kusner, Yu.S.; Poleschuk, V.A.; Sherstyankin, P.P.; Levin, A.A.; Nikiforov, A.I.; Rosanov, M.I.

1991-12-01

We describe the lake Baikal deep underwater detector 'NT-200' and discuss its physics capabilities to investigate problems in the field of neutrino astrophysics, cosmic ray physics and particle physics. (orig.)

Biological profile of 99mTc-HYNIC-βAla-NT(8-13) in MDAMB-231 breast cancer cell line

International Nuclear Information System (INIS)

Teodoro, Rodrigo; Faintuch, Bluma L.; Wiecek, Danielle P.; Silva, Natanael G.; Vallejo, Natalia M.

2009-01-01

Introduction: Neurotensin (NT) is a tridecapeptide involved in several growth-steps of human cancers. Recent studies postulated the role of NT and NT-receptor subtype 1 in breast cancer progression. However, the main drawback of natural NT is its rapid degradation in plasma. In an effort to develop a NT peptide-based radiopharmaceutical for the detection of breast cancer, the aim of this study was the radiolabeling of the double stabilized NT(8-13) peptide using HYNIC as chelating agent. Methods: Conjugated HYNIC-βAla-NT(8-13) was labeled with 99m Tc using tricine and EDDA as coligands. Radiochemical purity was checked by TLC and confirmed by RP-HPLC. 99m Tc-HYNIC-βAla-NT(8-13) (0.1 mL/74 MBq) was administered in Nude mice bearing MDA-MB-231 breast cancer cells and biodistribution studies were carried out at 30 and 90 min postinjection (pi). Blocking evaluation was also conducted by co-injection of 115 nmol of cold NT (8-13) analog. Planar gamma-camera imaging was acquired at the earlier time point studied. Results: Radiochemical purity of the radioconjugate was higher than 99%. Biodistribution studies revealed a very fast accumulation in tumor (1.97±0.18% ID/g, 30 min pi) with a sharply decrease at the later time point studied (0.44±0.02% ID/g). The specificity of the radioconjugate was evaluated with blockade studies. A reduction of 45.94%, 27.73% and 36.39% was found for tumor, large and small intestines, respectively, at 30 min pi. Otherwise, a less impressive blockade was observed for tumor and small intestine (28.68% and 24.90%, respectively) at the later time point studied. Conclusion: The results provide encouraging evidence in the development of radiolabeled NT(8-13) analogues for breast cancer diagnosis. (author)

The prognostic value of individual NT-proBNP values in chronic heart failure does not change with advancing age.

Science.gov (United States)

Frankenstein, L; Clark, A L; Goode, K; Ingle, L; Remppis, A; Schellberg, D; Grabs, F; Nelles, M; Cleland, J G F; Katus, H A; Zugck, C

2009-05-01

It is unclear whether age-related increases in N-terminal pro-brain natriuretic peptide (NT-proBNP) represent a normal physiological process-possibly affecting the prognostic power-of NT-proBNP-or reflect age-related subclinical pathological changes. To determine the effect of age on the short-term prognostic value of NT-proBNP in patients with chronic heart failure (CHF). Prospective observational study with inclusion and matching of consecutive patients aged >65 years (mean (SD) 73.1 (6.0) years) to patients <65 years (53.7 (8.6) years) with respect to NT-proBNP, New York Heart Association stage, sex and aetiology of CHF (final n = 443). University hospital outpatient departments in the UK and Germany. Chronic stable heart failure due to systolic left ventricular dysfunction. None. All-cause mortality. In both age groups, NT-proBNP was a significant univariate predictor of mortality, and independent of age, sex and other established risk markers. The prognostic information given by NT-proBNP was comparable between the two groups, as reflected by the 1-year mortality of 9% in both groups. The prognostic accuracy of NT-proBNP as judged by the area under the receiver operating characteristics curve for the prediction of 1-year mortality was comparable for elderly and younger patients (0.67 vs 0.71; p = 0.09). NT-proBNP reflects disease severity in elderly and younger patients alike. In patients with chronic stable heart failure, the NT-proBNP value carries the same 1-year prognostic information regardless of the age of the patient.

Three enzymatically active neurotoxins of Clostridium botulinum strain Af84: BoNT/A2, /F4, and /F5.

Science.gov (United States)

Kalb, Suzanne R; Baudys, Jakub; Smith, Theresa J; Smith, Leonard A; Barr, John R

2014-04-01

Botulinum neurotoxins (BoNTs) are produced by various species of clostridia and are potent neurotoxins which cause the disease botulism, by cleaving proteins needed for successful nerve transmission. There are currently seven confirmed serotypes of BoNTs, labeled A-G, and toxin-producing clostridia typically only produce one serotype of BoNT. There are a few strains (bivalent strains) which are known to produce more than one serotype of BoNT, producing either both BoNT/A and /B, BoNT/A and /F, or BoNT/B and /F, designated as Ab, Ba, Af, or Bf. Recently, it was reported that Clostridium botulinum strain Af84 has three neurotoxin gene clusters: bont/A2, bont/F4, and bont/F5. This was the first report of a clostridial organism containing more than two neurotoxin gene clusters. Using a mass spectrometry based proteomics approach, we report here that all three neurotoxins, BoNT/A2, /F4, and /F5, are produced by C. botulinum Af84. Label free MS(E) quantification of the three toxins indicated that toxin composition is 88% BoNT/A2, 1% BoNT/F4, and 11% BoNT/F5. The enzymatic activity of all three neurotoxins was assessed by examining the enzymatic activity of the neurotoxins upon peptide substrates, which mimic the toxins' natural targets, and monitoring cleavage of the substrates by mass spectrometry. We determined that all three neurotoxins are enzymatically active. This is the first report of three enzymatically active neurotoxins produced in a single strain of Clostridium botulinum.

Sezary syndrome cells unlike normal circulating T lymphocytes fail to migrate following engagement of NT1 receptor.

Science.gov (United States)

Magazin, Marilyn; Poszepczynska-Guigné, Ewa; Bagot, Martine; Boumsell, Laurence; Pruvost, Christelle; Chalon, Pascale; Culouscou, Jean-Michel; Ferrara, Pascual; Bensussan, Armand

2004-01-01

Circulating malignant Sezary cells are a clonal proliferation of CD4+CD45RO+ T lymphocytes primarily involving the skin. To study the biology of these malignant T lymphocytes, we tested their ability to migrate in chemotaxis assays. Previously, we had shown that the neuropeptide neurotensin (NT) binds to freshly isolated Sezary malignant cells and induces through NT1 receptors the cell migration of the cutaneous T cell lymphoma cell line Cou-L. Here, we report that peripheral blood Sezary cells as well as the Sezary cell line Pno fail to migrate in response to neurotensin although they are capable of migrating to the chemokine stromal-cell-derived factor 1 alpha. This is in contrast with normal circulating CD4+ or CD8+ lymphocytes, which respond to both types of chemoattractants except after ex vivo short-time anti-CD3 monoclonal antibody activation, which abrogates the neurotensin-induced lymphocyte migration. Furthermore, we demonstrate that neurotensin-responsive T lymphocytes express the functional NT1 receptor responsible for chemotaxis. In these cells, but not in Sezary cells, neurotensin induces recruitment of phosphatidylinositol-3 kinase, and redistribution of phosphorylated cytoplasmic tyrosine kinase focal adhesion kinase and filamentous actin. Taken together, these results, which show functional distinctions between normal circulating lymphocytes and Sezary syndrome cells, contribute to further understanding of the physiopathology of these atypical cells.

Genome sequence of a microbial lipid producing fungus Cryptococcus albidus NT2002.

Science.gov (United States)

Yong, Xiaoyu; Yan, Zhiying; Xu, Lin; Zhou, Jun; Wu, Xiayuan; Wu, Yuandong; Li, Yang; Chen, Zugeng; Zhou, Hua; Wei, Ping; Jia, Honghua

2016-04-10

Cryptococcus albidus NT2002, isolated from the soil in Xinjiang, China, appeared to have the ability to accumulate microbial lipid by utilizing various carbon sources. The predominant properties make it as a potential bio-platform for biodiesel production. Here, we report the complete genome sequence of C. albidus NT2002, which might provide a basis for further elucidation of the genetic background of this promising strain for developing metabolic engineering strategies to produce biodiesel in a green and sustainable manner. Copyright © 2016 Elsevier B.V. All rights reserved.

Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury

Directory of Open Access Journals (Sweden)

Kathleen M. Keefe

2017-03-01

Full Text Available Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI. We focus on nerve growth factor (NGF, brain derived neurotrophic factor (BDNF, and neurotrophin-3 (NT-3, and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord.

Proteasome modulator 9 and macrovascular pathology of T2D

Directory of Open Access Journals (Sweden)

Gragnoli Claudia

2011-04-01

Full Text Available Abstract Aims Coronary artery disease (CAD and stroke share a major linkage at the chromosome 12q24 locus. The same chromosome region entails at least a major risk gene for type 2 diabetes (T2D within NIDDM2, the non-insulin-dependent-diabetes 2 locus. The gene of Proteasome Modulator 9 (PSMD9 lies in the NIDDM2 region and is implicated in diabetes in mice. PSMD9 mutations rarely cause T2D and common variants are linked to both late-onset T2D and maturity-onset-diabetes of the young (MODY3. In this study, we aimed at determining whether PSMD9 is linked to macrovascular pathology of T2D. Methods and Results In our 200 T2D families from Italy, we characterized the clinical phenotype of macrovascular pathology by defining the subjects for presence or absence of CAD, stroke and/or transitory ischemic attacks (TIA, plaques of the large arterial vessels (macro-vasculopathy and arterial angioplasty performance. We then screened 200 T2D siblings/families for PSMD9 +nt460A/G, +nt437C/T and exon E197G A/G single nucleotide polymorphisms (SNPs and performed a non-parametric linkage study to test for linkage for coronary artery disease, stroke/TIA, macro-vasculopathy and macrovascular pathology of T2D. We performed 1,000 replicates to test the power of our significant results. Our results show a consistent significant LOD score in linkage with all the above-mentioned phenotypes. Our 1000 simulation analyses, performed for each single test, confirm that the results are not due to random chance. Conclusions In summary, the PSMD9 IVS3+nt460A/G, +nt437C/T and exon E197G A/G SNPs are linked to CAD, stroke/TIA and macrovascular pathology of T2D in Italians.

Validation of One-Dimensional Module of MARS-KS1.2 Computer Code By Comparison with the RELAP5/MOD3.3/patch3 Developmental Assessment Results

International Nuclear Information System (INIS)

Bae, S. W.; Chung, B. D.

2010-07-01

This report records the results of the code validation for the one-dimensional module of the MARS-KS thermal hydraulics analysis code by means of result-comparison with the RELAP5/MOD3.3 computer code. For the validation calculations, simulations of the RELAP5 Code Developmental Assessment Problem, which consists of 22 simulation problems in 3 categories, have been selected. The results of the 3 categories of simulations demonstrate that the one-dimensional module of the MARS code and the RELAP5/MOD3.3 code are essentially the same code. This is expected as the two codes have basically the same set of field equations, constitutive equations and main thermal hydraulic models. The result suggests that the high level of code validity of the RELAP5/MOD3.3 can be directly applied to the MARS one-dimensional module

Levels of NT-proBNP, markers of low-grade inflammation, and endothelial dysfunction during spironolactone treatment in patients with diabetic kidney disease

DEFF Research Database (Denmark)

Nielsen, Stine; Schjoedt, Katrine J; Rossing, Kasper

2013-01-01

with spironolactone 25 mg and placebo daily for 60 days.Outcome measures:Changes in inflammatory (hsCRP, s-ICAM, TNFα, IL-6, IL-8, Serum amyloid A, IL1β), endothelial dysfunction (sE-selectin, s-ICAM1, s-VCAM1, VWF, p-selectin, s-thrombomodulin) and NT-proBNP after each treatment period. RESULTS: During...

Neurotrophin 3 upregulates proliferation and collagen production in human aortic valve interstitial cells: a potential role in aortic valve sclerosis.

Science.gov (United States)

Yao, Qingzhou; Song, Rui; Ao, Lihua; Cleveland, Joseph C; Fullerton, David A; Meng, Xianzhong

2017-06-01

Calcific aortic valve disease (CAVD) is a leading cardiovascular disorder in the elderly. Diseased aortic valves are characterized by sclerosis (fibrosis) and nodular calcification. Sclerosis, an early pathological change, is caused by aortic valve interstitial cell (AVIC) proliferation and overproduction of extracellular matrix (ECM) proteins. However, the mechanism of aortic valve sclerosis remains unclear. Recently, we observed that diseased human aortic valves overexpress growth factor neurotrophin 3 (NT3). In the present study, we tested the hypothesis that NT3 is a profibrogenic factor to human AVICs. AVICs isolated from normal human aortic valves were cultured in M199 growth medium and treated with recombinant human NT3 (0.10 µg/ml). An exposure to NT3 induced AVIC proliferation, upregulated the production of collagen and matrix metalloproteinase (MMP), and augmented collagen deposition. These changes were abolished by inhibition of the Trk receptors. NT3 induced Akt phosphorylation and increased cyclin D1 protein levels in a Trk receptor-dependent fashion. Inhibition of Akt abrogated the effect of NT3 on cyclin D1 production. Furthermore, inhibition of either Akt or cyclin D1 suppressed NT3-induced cellular proliferation and MMP-9 and collagen production, as well as collagen deposition. Thus, NT3 upregulates cellular proliferation, ECM protein production, and collagen deposition in human AVICs. It exerts these effects through the Trk-Akt-cyclin D1 cascade. NT3 is a profibrogenic mediator in human aortic valve, and overproduction of NT3 by aortic valve tissue may contribute to the mechanism of valvular sclerosis. Copyright © 2017 the American Physiological Society.

Understanding of phase modulation in two-level systems through inverse scattering

International Nuclear Information System (INIS)

Hasenfeld, A.; Hammes, S.L.; Warren, W.S.

1988-01-01

Analytical and numerical calculations describe the effects of shaped radiation pulses on two-level systems in terms of quantum-mechanical scattering. Previous results obtained in the reduced case of amplitude modulation are extended to the general case of simultaneous amplitude and phase modulation. We show that an infinite family of phase- and amplitude-modulated pulses all generate rectangular inversion profiles. Experimental measurements also verify the theoretical analysis

Extracellular Matrix Biomarker, Fibulin-1, Is Closely Related to NT-proBNP and Soluble Urokinase Plasminogen Activator Receptor in Patients with Aortic Valve Stenosis (The SEAS Study)

DEFF Research Database (Denmark)

Kruger, Ruan; Rasmussen, Lars M; Argraves, William S

2014-01-01

associated with subclinical atherosclerosis. Therefore, we aimed to explore the interplay between these biomarkers and mild to moderate aortic valve stenosis (AS). METHODS: In 374 patients with mild to moderate AS, we investigated the relationship of fibulin-1 with NT-proBNP, levels of suPAR and the degree.......01), and suPAR (βyear0 = 0.09, p = 0.26, βyear1 = 0.23, βyear4 = 0.21, both plevels of fibulin-1 were independently associated with higher levels of suPAR and NT-proBNP especially in patients with lower AVAI, suggesting...

Differentiating human NT2/D1 neurospheres as a versatile in vitro 3D model system for developmental neurotoxicity testing

International Nuclear Information System (INIS)

Hill, E.J.; Woehrling, E.K.; Prince, M.; Coleman, M.D.

2008-01-01

Developmental neurotoxicity is a major issue in human health and may have lasting neurological implications. In this preliminary study we exposed differentiating Ntera2/clone D1 (NT2/D1) cell neurospheres to known human teratogens classed as non-embryotoxic (acrylamide), weakly embryotoxic (lithium, valproic acid) and strongly embryotoxic (hydroxyurea) as listed by European Centre for the Validation of Alternative Methods (ECVAM) and examined endpoints of cell viability and neuronal protein marker expression specific to the central nervous system, to identify developmental neurotoxins. Following induction of neuronal differentiation, valproic acid had the most significant effect on neurogenesis, in terms of reduced viability and decreased neuronal markers. Lithium had least effect on viability and did not significantly alter the expression of neuronal markers. Hydroxyurea significantly reduced cell viability but did not affect neuronal protein marker expression. Acrylamide reduced neurosphere viability but did not affect neuronal protein marker expression. Overall, this NT2/D1-based neurosphere model of neurogenesis, may provide the basis for a model of developmental neurotoxicity in vitro

Increased NT-pro-B-type natriuretic peptide independently predicts outcome following catheter ablation of atrial fibrillation

DEFF Research Database (Denmark)

Nilsson, Brian; Goetze, Jens Peter; Chen, Xu

2009-01-01

AIMS: To investigate whether NT-proBNP before ablation treatment and after exercise testing has predictive information regarding the clinical outcome following pulmonary vein isolation in patients with atrial fibrillation (AF). METHODS: NT-proBNP analysis were obtained before the ablation (before...

BoNT-A related changes of cortical activity in patients suffering from severe hand paralysis with arm spasticity following ischemic stroke.

Science.gov (United States)

Veverka, Tomáš; Hluštík, Petr; Tomášová, Zuzana; Hok, Pavel; Otruba, Pavel; Král, Michal; Tüdös, Zbyněk; Zapletalová, Jana; Herzig, Roman; Krobot, Alois; Kaňovský, Petr

2012-08-15

Investigations were performed to localize and analyze the botulinum toxin (BoNT-A) related changes of cerebral cortex activation in chronic stroke patients suffering from severe hand paralysis with arm spasticity. Effects on task- related cerebral activation were evaluated by functional magnetic resonance imaging (fMRI). 14 patients (5 males, 9 females, mean age 55.3 years) suffering from upper limb post-stroke spasticity were investigated. The change of arm spasticity was assessed by using the modified Ashworth scale (MAS). FMRI sessions were performed before (W0), four weeks (W4) and 11 weeks (W11) after BoNT-A application. Patients were scanned while performing imaginary movement with the impaired hand. Group fMRI analysis included patient age as a covariate. BoNT-A treatment was effective in alleviation of arm spasticity. Mean MAS was at Week 0: 2.5 (SD 0.53), at Week 4: 1.45 (SD 0.38), at Week 11: 2.32 (SD 0.44). Task-related fMRI prior to the treatment showed extensive activation of bilateral frontoparietal sensorimotor cortical areas, anterior cingulate gyrus, pallidum, thalamus and cerebellum. Effective BoNT-A treatment (W4) resulted in partial reduction of active network volume in most of the observed areas, whereas BoNT-free data (W11) revealed further volume reduction in the sensorimotor network. On direct comparison, significant activation decreases associated with BoNT-A treatment were located in areas outside the classical sensorimotor system, namely, ipsilesional lateral occipital cortex, supramarginal gyrus and precuneus cortex. On comparison of W4 and W11, no activation increases were found, instead, activation further decreased in ipsilesional insular cortex, contralesional superior frontal gyrus and bilateral frontal pole. Whole brain activation patterns during BoNT-A treatment of post-stroke arm spasticity and further follow up document predominantly gradual changes both within and outside the classical sensorimotor system. Copyright © 2012

SequenceL: Automated Parallel Algorithms Derived from CSP-NT Computational Laws

Science.gov (United States)

Cooke, Daniel; Rushton, Nelson

2013-01-01

With the introduction of new parallel architectures like the cell and multicore chips from IBM, Intel, AMD, and ARM, as well as the petascale processing available for highend computing, a larger number of programmers will need to write parallel codes. Adding the parallel control structure to the sequence, selection, and iterative control constructs increases the complexity of code development, which often results in increased development costs and decreased reliability. SequenceL is a high-level programming language that is, a programming language that is closer to a human s way of thinking than to a machine s. Historically, high-level languages have resulted in decreased development costs and increased reliability, at the expense of performance. In recent applications at JSC and in industry, SequenceL has demonstrated the usual advantages of high-level programming in terms of low cost and high reliability. SequenceL programs, however, have run at speeds typically comparable with, and in many cases faster than, their counterparts written in C and C++ when run on single-core processors. Moreover, SequenceL is able to generate parallel executables automatically for multicore hardware, gaining parallel speedups without any extra effort from the programmer beyond what is required to write the sequen tial/singlecore code. A SequenceL-to-C++ translator has been developed that automatically renders readable multithreaded C++ from a combination of a SequenceL program and sample data input. The SequenceL language is based on two fundamental computational laws, Consume-Simplify- Produce (CSP) and Normalize-Trans - pose (NT), which enable it to automate the creation of parallel algorithms from high-level code that has no annotations of parallelism whatsoever. In our anecdotal experience, SequenceL development has been in every case less costly than development of the same algorithm in sequential (that is, single-core, single process) C or C++, and an order of magnitude less

Serum N-terminal-pro-brain natriuretic peptide level and its clinical implications in patients with atrial fibrillation.

Science.gov (United States)

Bai, Mei; Yang, Jiefu; Li, Yingying

2009-12-01

Brain natriuretic peptide (BNP) is increasingly being used for screening and monitoring of congestive heart failure. However, the role of BNP in patients with atrial fibrillation (AF) and normal left ventricular function has not been determined. This study investigates serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level and its clinical implications in patients with AF. Serum NT-proBNP levels were measured by enzyme-linked immunosorbent assay (ELISA) and transthoracic echocardiography was performed in 136 subjects (90 cases with AF and 46 cases with sinus rhythm [SR]). Subjects were excluded if they had a history of myocardial infarction, cardiomyopathy, rheumatic heart disease, or hyperthyroidism that preceded the onset of AF. Controls (n = 30) were from a healthy outpatient primary care population. Potential determinants of serum NT-proBNP levels were identified by univariate and multivariate analyses. Individuals with AF had higher serum NT-proBNP levels (689.56 +/- 251.87 fmol/ml) than those with SR (456.11 +/- 148.14 fmol/ml, P NT-proBNP levels (P > 0.05). The regression model of serum NT-proBNP levels and clinical predictors showed that presence of AF, older age, and larger right atrial diameter were independently predictive of higher serum NT-proBNP values. Patients with AF were associated with increased serum NT-proBNP levels. Examining the change of serum NT-proBNP levels is helpful to evaluate the cardiac function in patients with AF. Copyright 2009 Wiley Periodicals, Inc.

Diet and exercise training reduce blood pressure and improve autonomic modulation in women with prehypertension.

Science.gov (United States)

Sales, Allan R K; Silva, Bruno M; Neves, Fabricia J; Rocha, Natália G; Medeiros, Renata F; Castro, Renata R T; Nóbrega, Antonio C L

2012-09-01

Despite mortality from heart disease has been decreasing, the decline in death in women remains lower than in men. Hypertension (HT) is a major risk factor for cardiovascular disease. Therefore, approaches to prevent or delay the onset of HT would be valuable in women. Given this background, we investigated the effect of diet and exercise training on blood pressure (BP) and autonomic modulation in women with prehypertension (PHT). Ten women with PHT (39 ± 6 years, mean ± standard deviation) and ten with normotension (NT) (35 ± 11 years) underwent diet and exercise training for 12 weeks. Autonomic modulation was assessed through heart rate (HR) and systolic BP (SBP) variability, using time and frequency domain analyses. At preintervention, women with PHT had higher SBP (PHT: 128 ± 7 vs. NT: 111 ± 6 mmHg, p 0.05). Moreover, reduction in SBP was associated with augmentation in SDNN (r = -0.46, p diet and exercise training reduced SBP in women with PHT, and this was associated with augmentation in parasympathetic and probably reduction in sympathetic cardiac modulation.

Biological profile of {sup 99m}Tc-HYNIC-betaAla-NT(8-13) in MDAMB-231 breast cancer cell line

Energy Technology Data Exchange (ETDEWEB)

Teodoro, Rodrigo; Faintuch, Bluma L.; Wiecek, Danielle P.; Silva, Natanael G.; Vallejo, Natalia M., E-mail: teodoro_rodrigo@yahoo.com.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Diretoria de Radiofarmacia

2009-07-01

Introduction: Neurotensin (NT) is a tridecapeptide involved in several growth-steps of human cancers. Recent studies postulated the role of NT and NT-receptor subtype 1 in breast cancer progression. However, the main drawback of natural NT is its rapid degradation in plasma. In an effort to develop a NT peptide-based radiopharmaceutical for the detection of breast cancer, the aim of this study was the radiolabeling of the double stabilized NT(8-13) peptide using HYNIC as chelating agent. Methods: Conjugated HYNIC-betaAla-NT(8-13) was labeled with {sup 99m}Tc using tricine and EDDA as coligands. Radiochemical purity was checked by TLC and confirmed by RP-HPLC. {sup 99m}Tc-HYNIC-betaAla-NT(8-13) (0.1 mL/74 MBq) was administered in Nude mice bearing MDA-MB-231 breast cancer cells and biodistribution studies were carried out at 30 and 90 min postinjection (pi). Blocking evaluation was also conducted by co-injection of 115 nmol of cold NT (8-13) analog. Planar gamma-camera imaging was acquired at the earlier time point studied. Results: Radiochemical purity of the radioconjugate was higher than 99%. Biodistribution studies revealed a very fast accumulation in tumor (1.97+-0.18% ID/g, 30 min pi) with a sharply decrease at the later time point studied (0.44+-0.02% ID/g). The specificity of the radioconjugate was evaluated with blockade studies. A reduction of 45.94%, 27.73% and 36.39% was found for tumor, large and small intestines, respectively, at 30 min pi. Otherwise, a less impressive blockade was observed for tumor and small intestine (28.68% and 24.90%, respectively) at the later time point studied. Conclusion: The results provide encouraging evidence in the development of radiolabeled NT(8-13) analogues for breast cancer diagnosis. (author)

CLC-Nt1, a putative chloride channel protein of tobacco, co-localizes with mitochondrial membrane markers.

Science.gov (United States)

Lurin, C; Güclü, J; Cheniclet, C; Carde, J P; Barbier-Brygoo, H; Maurel, C

2000-06-01

The voltage-dependent chloride channel (CLC) family of membrane proteins has cognates in animals, yeast, bacteria and plants, and chloride-channel activity has been assigned to most of the animal homologues. Lack of evidence of CLC functions in plants prompted us to characterize the cellular localization of the tobacco CLC-Nt1 protein. Specific polyclonal antibodies were raised against an N-terminal polypeptide of CLC-Nt1. These antibodies were used to probe membrane proteins prepared by various cell-fractionation methods. These included aqueous two-phase partitioning (for plasma membranes), free-flow electrophoresis (for vacuolar and plasma membranes), intact vacuole isolation, Percoll-gradient centrifugation (for plastids and mitochondria) and stepped, linear, sucrose-density-gradient centrifugation (for mitochondria). Each purified membrane fraction was characterized with specific marker enzyme activities or antibodies. Our studies ruled out the possibility that the major cell localization of CLC-Nt1 was the vacuolar or plasma membranes, the endoplasmic reticulum, the Golgi apparatus or the plastids. In contrast, we showed that the tobacco CLC-Nt1 specifically co-localized with the markers of the mitochondrial inner membrane, cytochrome c oxidase and NAD9 protein. CLC-Nt1 may correspond to the inner membrane anion channel ('IMAC') described previously in animal and plant mitochondria.

GLI1 is involved in cell cycle regulation and proliferation of NT2 embryonal carcinoma stem cells

DEFF Research Database (Denmark)

Vestergaard, Janni; Lind-Thomsen, Allan; Pedersen, Mikkel W.

2008-01-01

of altered HH signaling are interpreted by specific cell types. We have investigated the role of the HH transcription factor glioma-associated oncogene homolog 1 (GLI1) in the human Ntera2=D1 (NT2) embryonal carcinoma stem cell line. The study revealed that expression of GLI1 and its direct transcriptional......1 phase cyclins. In conclusion, our results suggest that GLI1 is involved in cell cycle and proliferation control in the embryonal carcinoma stem cell line NT2....... target Patched (PTCH) is downregulated in the early stages of retinoic acid-induced neuronal differentiation of NT2 cells. To identify transcriptional targets of the HH transcription factor GLI1 in NT2 cells, we performed global expression profiling following GLI1 RNA interference (RNAi). Of the similar...

Use of the decision support system RECASS NT (Radio Ecological Analysis Support System) for anti terrorism actions

International Nuclear Information System (INIS)

Bulgakov, V.G.; Gariyants, A.M.; Kosykh, V.S.; Shershakov, V.M.

2006-01-01

Decision support system RECASS NT (Radio Ecological Analysis Support System) was developed and is still enhancing in Federal Service Roshydromet for providing on-line estimates and prognoses of radiation and chemical situation in the event of an emergency, including acts of terrorism, as well as to estimate transboundary pollutants transport. RECASS NT has been installed at all ten NPPs of the Russian Federation, in Crisis Centers of Roshydromet, concern Rosenergoatom and Minatom, at plants for destroying chemical weapons. The paper describes the structure of RECASS NT system and discuss its possible application in case of an emergency on examples of using the system during radiation emergency response exercises at NPPs. RECASS NT can be used for developing recommendations regarding time when anti terrorism operations are better to be started with a view to minimize damage

TF.Learn: TensorFlow's High-level Module for Distributed Machine Learning

OpenAIRE

Tang, Yuan

2016-01-01

TF.Learn is a high-level Python module for distributed machine learning inside TensorFlow. It provides an easy-to-use Scikit-learn style interface to simplify the process of creating, configuring, training, evaluating, and experimenting a machine learning model. TF.Learn integrates a wide range of state-of-art machine learning algorithms built on top of TensorFlow's low level APIs for small to large-scale supervised and unsupervised problems. This module focuses on bringing machine learning t...

The front-end (Level-0) electronics interface module for the LHCb RICH detectors

Energy Technology Data Exchange (ETDEWEB)

Adinolfi, M. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Bibby, J.H. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Brisbane, S. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Gibson, V. [Cavendish Laboratory, University of Cambridge, Madingley Road, Cambridge CB3 0HE (United Kingdom); Harnew, N. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Jones, M. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Libby, J. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom)]. E-mail: j.libby1@physics.ox.ac.uk; Powell, A. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Newby, C. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Rotolo, N. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Smale, N. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Somerville, L.; Sullivan, P.; Topp-Jorgensen, S. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Wotton, S. [Cavendish Laboratory, University of Cambridge, Madingley Road, Cambridge CB3 0HE (United Kingdom); Wyllie, K. [CERN, CH-1211, Geneva 23 (Switzerland)

2007-03-11

The front-end (Level-0) electronics interface module for the LHCb Ring Imaging Cherenkov (RICH) detectors is described. This module integrates the novel hybrid photon detectors (HPDs), which instrument the RICH detectors, to the LHCb trigger, data acquisition (DAQ) and control systems. The system operates at 40 MHz with a first-level trigger rate of 1 MHz. The module design is presented and results are given for both laboratory and beam tests.

The front-end (Level-0) electronics interface module for the LHCb RICH detectors

International Nuclear Information System (INIS)

Adinolfi, M.; Bibby, J.H.; Brisbane, S.; Gibson, V.; Harnew, N.; Jones, M.; Libby, J.; Powell, A.; Newby, C.; Rotolo, N.; Smale, N.; Somerville, L.; Sullivan, P.; Topp-Jorgensen, S.; Wotton, S.; Wyllie, K.

2007-01-01

The front-end (Level-0) electronics interface module for the LHCb Ring Imaging Cherenkov (RICH) detectors is described. This module integrates the novel hybrid photon detectors (HPDs), which instrument the RICH detectors, to the LHCb trigger, data acquisition (DAQ) and control systems. The system operates at 40 MHz with a first-level trigger rate of 1 MHz. The module design is presented and results are given for both laboratory and beam tests

A Three-level 4 x 3 Conventinal Matrix Converter

DEFF Research Database (Denmark)

Rong, Runjie; Loh, Poh Chiang; Wang, Peter

2007-01-01

This paper proposes a topology of a three-level 4 × 3 conventional matrix converter with 12 bi-directional switches. PWM control and modulation index compensation have been investigated. Operation theory has been verified by the simulation results using Matlab. The simulation results show...

Power penalties for multi-level PAM modulation formats at arbitrary bit error rates

Science.gov (United States)

Kaliteevskiy, Nikolay A.; Wood, William A.; Downie, John D.; Hurley, Jason; Sterlingov, Petr

2016-03-01

There is considerable interest in combining multi-level pulsed amplitude modulation formats (PAM-L) and forward error correction (FEC) in next-generation, short-range optical communications links for increased capacity. In this paper we derive new formulas for the optical power penalties due to modulation format complexity relative to PAM-2 and due to inter-symbol interference (ISI). We show that these penalties depend on the required system bit-error rate (BER) and that the conventional formulas overestimate link penalties. Our corrections to the standard formulas are very small at conventional BER levels (typically 1×10-12) but become significant at the higher BER levels enabled by FEC technology, especially for signal distortions due to ISI. The standard formula for format complexity, P = 10log(L-1), is shown to overestimate the actual penalty for PAM-4 and PAM-8 by approximately 0.1 and 0.25 dB respectively at 1×10-3 BER. Then we extend the well-known PAM-2 ISI penalty estimation formula from the IEEE 802.3 standard 10G link modeling spreadsheet to the large BER case and generalize it for arbitrary PAM-L formats. To demonstrate and verify the BER dependence of the ISI penalty, a set of PAM-2 experiments and Monte-Carlo modeling simulations are reported. The experimental results and simulations confirm that the conventional formulas can significantly overestimate ISI penalties at relatively high BER levels. In the experiments, overestimates up to 2 dB are observed at 1×10-3 BER.

NT Logistika kitsaskohast sai ettevõttele trump / Elo Odres

Index Scriptorium Estoniae

Odres, Elo, 1969-

2007-01-01

NT Logistika pälvis kõige pere- ja töötajasõbralikuma ettevõtte tiitli. Vt. samas: Edetabel: Töötajasõbralike TOP; Peresõbralike TOP; Massaaž tuleb firmasse kätte; Suurfirmadel raske konkureerida; Töötajate lastest võrsub järelkasv; Tasuta lõunad on olemas

Unexplained week-to-week variation in BNP and NT-proBNP is low in chronic heart failure patients during steady state

DEFF Research Database (Denmark)

Schou, Morten; Gustafsson, Finn; Nielsen, Per H

2006-01-01

BACKGROUND: The usefulness of brain-natriuretic-peptide (BNP) and N-terminal-pro-brain-natriuretic-peptide (NT-proBNP) for monitoring of chronic heart failure (CHF) patients has been questioned because of high levels of unexplained variation. AIMS: Week-to-week total variance (CV(T)), unexplained...

Pulse width modulated buck-boost five-level current source inverters

DEFF Research Database (Denmark)

Blaabjerg, Frede; Gao, F.; Loh, P.C.

2008-01-01

, resulting in the natural balance of input current. For maintaining the normalized volt-sec average unchanged, the alternative phase opposition disposition (APOD) modulation scheme with typical gating signal mapping technique from voltage source inverter (VSI) to CSI can be assumed to control the five......This paper presents new five-level current source inverters (CSIs) with voltage/current buck-boost capability. Being different from the existing multilevel CSI, the proposed CSIs were first designed to regulate the flowing path of dc input current by controlling two additional active switches......-level buck-boost CSIs. Next by observing the hidden current charging path during inductive charging interval under APOD modulation, it is noted that the buck-boost five-level CSI can then be further modified with lesser active component without degrading output performance. To verify the theoretical findings...

NT10: recent advances in carbon nanotube science and applications.

Science.gov (United States)

Dresselhaus, Mildred S

2010-08-24

A review of recent advances in carbon nanotube science and applications is presented in terms of what was learned at the NT10 11th International Conference on the Science and Application of Nanotubes held in Montreal, Canada, June 29-July 2, 2010.

Interferon-β Inhibits Neurotrophin 3 Signalling and Pro-Survival Activity by Upregulating the Expression of Truncated TrkC-T1 Receptor.

Science.gov (United States)

Dedoni, Simona; Olianas, Maria C; Ingianni, Angela; Onali, Pierluigi

2017-04-01

Although clinically useful for the treatment of various diseases, type I interferons (IFNs) have been implicated as causative factors of a number of neuroinflammatory disorders characterized by neuronal damage and altered CNS functions. As neurotrophin 3 (NT3) plays a critical role in neuroprotection, we examined the effects of IFN-β on the signalling and functional activity of the NT3/TrkC system. We found that prolonged exposure of differentiated human SH-SY5Y neuroblastoma cells to IFN-β impaired the ability of NT3 to induce transphosphorylation of the full-length TrkC receptor (TrkC-FL) and the phosphorylation of downstream signalling molecules, including PLCγ1, Akt, GSK-3β and ERK1/2. NT3 was effective in protecting the cells against apoptosis triggered by serum withdrawal or thapsigargin but not IFN-β. Prolonged exposure to the cytokine had little effects on TrkC-FL levels but markedly enhanced the messenger RNA (mRNA) and protein levels of the truncated isoform TrkC-T1, a dominant-negative receptor that inhibits TrkC-FL activity. Cell depletion of TrkC-T1 by small interfering RNA (siRNA) treatment enhanced NT3 signalling through TrkC-FL and allowed the neurotrophin to counteract IFN-β-induced apoptosis. Furthermore, the upregulation of TrkC-T1 by IFN-β was associated with the inhibition of NT3-induced recruitment of the scaffold protein tamalin to TrkC-T1 and tamalin tyrosine phosphorylation. These data indicate that IFN-β exerts a negative control on NT3 pro-survival signalling through a novel mechanism involving the upregulation of TrkC-T1.

The relation between electrocardiographic ST-T changes and NT-proBNP in patients with acute ischemic stroke

DEFF Research Database (Denmark)

Jensen, Jesper K; Korsholm, Lars; Høilund-Carlsen, Poul Flemming

2007-01-01

BACKGROUND: ST-segment depression and T-wave inversion (ST-T changes) in the electrocardiogram (ECG) and raised levels of natriuretic peptide have been observed in acute ischemic stroke patients. It is unknown whether any relation between ST-T changes and raised levels of natriuretic peptides...... in patients with an acute ischemic stroke exists. METHODS: Serial measurements of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and 12-lead ECGs were obtained in 192 consecutive patients with an acute ischemic stroke without ischemic heart disease, atrial fibrillation, heart- or renal failure...

Contribution of serum FGF21 level to the identification of left ventricular systolic dysfunction and cardiac death.

Science.gov (United States)

Shen, Yun; Zhang, Xueli; Pan, Xiaoping; Xu, Yiting; Xiong, Qin; Lu, Zhigang; Ma, Xiaojing; Bao, Yuqian; Jia, Weiping

2017-08-18

The relationship between fibroblast growth factor 21 (FGF21) and cardiovascular disease has been well established in recent studies. This study aimed to investigate the relationship between FGF21 and left ventricular systolic dysfunction and cardiac death. Two-dimensional echocardiography was used to measure the left ventricular ejection fraction (LVEF) to estimate left ventricular systolic function. The optimal cutoff of FGF21 for identifying left ventricular systolic dysfunction at baseline was analyzed via receiver operating characteristic (ROC) curves. The identification of different serum levels of FGF21 and their association with cardiac death was analyzed via Kaplan-Meier survival curves. Serum FGF21 level was measured by an enzyme-linked immunosorbent assay kit, and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level was determined by a chemiluminescent immunoassay. A total of 253 patients were recruited for this study at baseline. Patients were excluded if they lacked echocardiography or laboratory measurement data, and there were 218 patients enrolled in the final analysis. The average age was 66.32 ± 10.10 years. The optimal cutoff values of FGF21 and NT-pro-BNP for identifying left ventricular systolic dysfunction at baseline were 321.5 pg/mL and 131.3 ng/L, respectively, determined separately via ROC analysis. The areas under the curves were non-significant among FGF21, NT-pro-BNP and FGF21 + NT-pro-BNP as determined by pairwise comparisons. Both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP were independent risk factors for left ventricular systolic dysfunction at baseline (odd ratio (OR) 3.138 [1.037-9.500], P = 0.043, OR 9.207 [2.036-41.643], P = 0.004, separately). Further Kaplan-Meier survival analysis indicated an association between both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP with cardiac death in 5 years [RR 5.000 (1.326-18.861), P = 0.026; RR 9.643 (2

Brain-derived neurotrophic factor/neurotrophin 3 regulate axon initial segment location and affect neuronal excitability in cultured hippocampal neurons.

Science.gov (United States)

Guo, Yu; Su, Zi-Jun; Chen, Yi-Kun; Chai, Zhen

2017-07-01

Plasticity of the axon initial segment (AIS) has aroused great interest in recent years because it regulates action potential initiation and neuronal excitability. AIS plasticity manifests as modulation of ion channels or variation in AIS structure. However, the mechanisms underlying structural plasticity of the AIS are not well understood. Here, we combined immunofluorescence, patch-clamp recordings, and pharmacological methods in cultured hippocampal neurons to investigate the factors participating in AIS structural plasticity during development. With lowered neuronal density, the distance between the AIS and the soma increased, while neuronal excitability decreased, as shown by the increased action potential threshold and current threshold for firing an action potential. This variation in the location of the AIS was associated with cellular secretory substances, including brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3). Indeed, blocking BDNF and NT3 with TrkB-Fc eliminated the effect of conditioned medium collected from high-density cultures on AIS relocation. Elevating the extracellular concentration of BDNF or NT3 promoted movement of the AIS proximally to the soma and increased neuronal excitability. Furthermore, knockdown of neurotrophin receptors TrkB and TrkC caused distal movement of the AIS. Our results demonstrate that BDNF and NT3 regulate AIS location and neuronal excitability. These regulatory functions of neurotrophic factors provide insight into the molecular mechanisms underlying AIS biology. © 2017 International Society for Neurochemistry.

Modulation Schemes of Multi-phase Three-Level Z-Source Inverters

DEFF Research Database (Denmark)

Gao, F.; Loh, P.C.; Blaabjerg, Frede

2007-01-01

different modulation requirement and output performance. For clearly illustrating the detailed modulation process, time domain analysis instead of the traditional multi-dimensional space vector demonstration is assumed which reveals the right way to insert shoot-through durations in the switching sequence...... with minimal commutation count. Lastly, the theoretical findings are verified in Matlab/PLECS simulation and experimentally using constructed laboratory prototypes.......This paper investigates the modulation schemes of three-level multiphase Z-source inverters with either two Z-source networks or single Z-source network connected between the dc sources and inverter circuitry. With the proper offset added for achieving both desired four-leg operation and optimized...

Modulation of i-motif thermodynamic stability by the introduction of UNA (unlocked nucleic acid) monomers

DEFF Research Database (Denmark)

Pasternak, Anna; Wengel, Jesper

2011-01-01

The influence of acyclic RNA derivatives, UNA (unlocked nucleic acid) monomers, on i-DNA thermodynamic stability has been investigated. The 22 nt human telomeric fragment was chosen as the model sequence for stability studies. UNA monomers modulate i-motif stability in a position-depending manner...

[Impact of plasma pro-B-type natriuretic peptide amino-terminal and galectin-3 levels on the predictive capacity of the LIPID Clinical Risk Scale in stable coronary disease].

Science.gov (United States)

Higueras, Javier; Martín-Ventura, José Luis; Blanco-Colio, Luis; Cristóbal, Carmen; Tarín, Nieves; Huelmos, Ana; Alonso, Joaquín; Pello, Ana; Aceña, Álvaro; Carda, Rocío; Lorenzo, Óscar; Mahíllo-Fernández, Ignacio; Asensio, Dolores; Almeida, Pedro; Rodríguez-Artalejo, Fernando; Farré, Jerónimo; López Bescós, Lorenzo; Egido, Jesús; Tuñón, José

2015-01-01

At present, there is no tool validated by scientific societies for risk stratification of patients with stable coronary artery disease (SCAD). It has been shown that plasma levels of monocyte chemoattractant protein-1 (MCP-1), galectin-3 and pro-B-type natriuretic peptide amino-terminal (NT-proBNP) have prognostic value in this population. To analyze the prognostic value of a clinical risk scale published in Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study and determining its predictive capacity when combined with plasma levels of MCP-1, galectin-3 and NT-proBNP in patients with SCAD. A total of 706 patients with SCAD and a history of acute coronary syndrome (ACS) were analyzed over a follow up period of 2.2 ± 0.99 years. The primary endpoint was the occurrence of an ischemic event (any SCA, stroke or transient ischemic attack), heart failure, or death. A clinical risk scale derived from the LIPID study significantly predicted the development of the primary endpoint, with an area under the ROC curve (Receiver Operating Characteristic) of 0.642 (0.579 to 0.705); Pvalue improved with an area under the curve of 0.744 (0.684 to 0.805); P<0.001 (P=0.022 for comparison). A score greater than 21.5 had a sensitivity of 74% and a specificity of 61% for the development of the primary endpoint (P<0.001, log -rank test). Plasma levels of MCP-1, galectin -3 and NT-proBNP improve the ability of the LIPID clinical scale to predict the prognosis of patients with SCAD. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Systematics of (n,t) reactions in medium and heavy mass nuclei at 14.6 MeV

International Nuclear Information System (INIS)

Woo, T.T.

1979-01-01

The production cross sections for (n,t) reactions of 14.6-MeV neutrons with isotopes of the natural elements Ca, Ti, Cr, Fe, Ni, Y, Mo, Pd, Cd, Sn, Pb, La, and with the enriched isotopes 86 Sr, 114 Cd, 130 Te, 205 Tl were measured by the activation technique using high-energy resolution gamma-ray spectrometry. The systematics for the (n,t) reactions were investigated as a function of the relative neutron excess. The experimentally determined values of the cross sections are in good agreement with values calculated by an empirical equation. The cross section ratios (n,t) and (n,p) reactions were calculated on the basis of the statistical model

Molecular tweezers modulate 14-3-3 protein-protein interactions

Science.gov (United States)

Bier, David; Rose, Rolf; Bravo-Rodriguez, Kenny; Bartel, Maria; Ramirez-Anguita, Juan Manuel; Dutt, Som; Wilch, Constanze; Klärner, Frank-Gerrit; Sanchez-Garcia, Elsa; Schrader, Thomas; Ottmann, Christian

2013-03-01

Supramolecular chemistry has recently emerged as a promising way to modulate protein functions, but devising molecules that will interact with a protein in the desired manner is difficult as many competing interactions exist in a biological environment (with solvents, salts or different sites for the target biomolecule). We now show that lysine-specific molecular tweezers bind to a 14-3-3 adapter protein and modulate its interaction with partner proteins. The tweezers inhibit binding between the 14-3-3 protein and two partner proteins—a phosphorylated (C-Raf) protein and an unphosphorylated one (ExoS)—in a concentration-dependent manner. Protein crystallography shows that this effect arises from the binding of the tweezers to a single surface-exposed lysine (Lys214) of the 14-3-3 protein in the proximity of its central channel, which normally binds the partner proteins. A combination of structural analysis and computer simulations provides rules for the tweezers' binding preferences, thus allowing us to predict their influence on this type of protein-protein interactions.

Polybutylcyanoacrylate nanoparticles for delivering hormone response element-conjugated neurotrophin-3 to the brain of intracerebral hemorrhagic rats.

Science.gov (United States)

Chung, Chiu-Yen; Yang, Jen-Tsung; Kuo, Yung-Chih

2013-12-01

Hypertensive intracerebral hemorrhage (ICH) is a rapidly evolutional pathology, inducing necrotic cell death followed by apoptosis, and alters gene expression levels in surrounding tissue of an injured brain. For ICH therapy by controlled gene release, the development of intravenously administrable delivery vectors to promote the penetration across the blood-brain barrier (BBB) is a critical challenge. To enhance transfer efficiency of genetic materials under hypoxic conditions, polybutylcyanoacrylate (PBCA) nanoparticles (NPs) were used to mediate the intracellular transport of plasmid neurotrophin-3 (NT-3) containing hormone response element (HRE) with a cytomegalovirus (cmv) promoter and to differentiate induced pluripotent stem cells (iPSCs). The differentiation ability of iPSCs to neurons was justified by various immunological stains for protein fluorescence. The effect of PBCA NP/cmvNT-3-HRE complexes on treating ICH rats was studied by immunostaining, western blotting and Nissl staining. We found that the treatments with PBCA NP/cmvNT-3-HRE complexes increased the capability of differentiating iPSCs to express NT-3, TrkC and MAP-2. Moreover, PBCA NPs could protect cmvNT-3-HRE against degradation with EcoRI/PstI and DNase I in vitro and raise the delivery across the BBB in vivo. The administration of PBCA NP/cmvNT-3-HRE complexes increased the expression of NT-3, inhibited the expression of apoptosis-inducing factor, cleaved caspase-3 and DNA fragmentation, and reduced the cell death rate after ICH in vivo. PBCA NPs are demonstrated as an appropriate delivery system for carrying cmvNT-3-HRE to the brain for ICH therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

NT-proBNP is associated with fibulin-1 in Africans

DEFF Research Database (Denmark)

Kruger, R; Schutte, R; Huisman, H W

2012-01-01

, expressed in elastin-containing fibres of blood vessels, and also in the heart. Due to an alarming prevalence of hypertensive heart disease in black South Africans, we investigated the associations of NT-proBNP with fibulin-1 and markers of arterial stiffness in Africans and Caucasians....

Parametric resonances in the amplitude-modulated probe-field absorption spectrum of a two-level atom driven by a resonance amplitude- and phase-modulated pumping field

International Nuclear Information System (INIS)

Sushilov, N.V.; Kholodkevich, E.D.

1995-01-01

An analytical expression is derived for the polarization induced by a weak probe field with periodically modulated amplitude in a two-level medium saturated by a strong amplitude-and phase-modulated resonance field. It is shown that the absorption spectrum of the probe field includes parametric resonances, the maxima corresponding to the condition δ= 2nΓ-Ω w and the minima to that of δ= (2n + 1)Γ- w , where δ is the probe-field detuning front the resonance frequency, Ω w is the modulation frequency of the probe-field amplitude, and Γ is the transition line width, n = 1, 2, 3, hor-ellipsis. At the specific modulation parameters, a substantial region of negative values (i.e., the region of amplification without the population inversion) exists in the absorption spectrum of the probe field

47 CFR 73.1570 - Modulation levels: AM, FM, TV and Class A TV aural.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Modulation levels: AM, FM, TV and Class A TV... levels: AM, FM, TV and Class A TV aural. (a) The percentage of modulation is to be maintained at as high a level as is consistent with good quality of transmission and good broadcast service, with maximum...

HIV-1 Tat protein induces glial cell autophagy through enhancement of BAG3 protein levels.

Science.gov (United States)

Bruno, Anna Paola; De Simone, Francesca Isabella; Iorio, Vittoria; De Marco, Margot; Khalili, Kamel; Sariyer, Ilker Kudret; Capunzo, Mario; Nori, Stefania Lucia; Rosati, Alessandra

2014-01-01

BAG3 protein has been described as an anti-apoptotic and pro-autophagic factor in several neoplastic and normal cells. We previously demonstrated that BAG3 expression is elevated upon HIV-1 infection of glial and T lymphocyte cells. Among HIV-1 proteins, Tat is highly involved in regulating host cell response to viral infection. Therefore, we investigated the possible role of Tat protein in modulating BAG3 protein levels and the autophagic process itself. In this report, we show that transfection with Tat raises BAG3 levels in glioblastoma cells. Moreover, BAG3 silencing results in highly reducing Tat- induced levels of LC3-II and increasing the appearance of sub G0/G1 apoptotic cells, in keeping with the reported role of BAG3 in modulating the autophagy/apoptosis balance. These results demonstrate for the first time that Tat protein is able to stimulate autophagy through increasing BAG3 levels in human glial cells.

Delineating neurotrophin-3 dependent signaling pathways underlying sympathetic axon growth along intermediate targets.

Science.gov (United States)

Keeler, Austin B; Suo, Dong; Park, Juyeon; Deppmann, Christopher D

2017-07-01

Postganglionic sympathetic neurons detect vascular derived neurotrophin 3 (NT3) via the axonally expressed receptor tyrosine kinase, TrkA, to promote chemo-attraction along intermediate targets. Once axons arrive to their final target, a structurally related neurotrophic factor, nerve growth factor (NGF), also acts through TrkA to promote final target innervation. Does TrkA signal differently at these different locales? We previously found that Coronin-1 is upregulated in sympathetic neurons upon exposure to NGF, thereby endowing the NGF-TrkA complex with new signaling capabilities (i.e. calcium signaling), which dampens axon growth and branching. Based on the notion that axons do not express functional levels of Coronin-1 prior to final target innervation, we developed an in vitro model for axon growth and branching along intermediate targets using Coro1a -/- neurons grown in NT3. We found that, similar to NGF-TrkA, NT3-TrkA is capable of inducing MAPK and PI3K in the presence or absence of Coronin-1. However, unlike NGF, NT3 does not induce calcium release from intracellular stores. Using a combination of pharmacology, knockout neurons and in vitro functional assays, we suggest that the NT3-TrkA complex uses Ras/MAPK and/or PI3K-AKT signaling to induce axon growth and inhibit axon branching along intermediate targets. However, in the presence of Coronin-1, these signaling pathways lose their ability to impact NT3 dependent axon growth or branching. This is consistent with a role for Coronin-1 as a molecular switch for axon behavior and suggests that Coronin-1 suppresses NT3 dependent axon behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

Validation of one-dimensional module of MARS 2.1 computer code by comparison with the RELAP5/MOD3.3 developmental assessment results

International Nuclear Information System (INIS)

Lee, Y. J.; Bae, S. W.; Chung, B. D.

2003-02-01

This report records the results of the code validation for the one-dimensional module of the MARS 2.1 thermal hydraulics analysis code by means of result-comparison with the RELAP5/MOD3.3 computer code. For the validation calculations, simulations of the RELAP5 code development assessment problem, which consists of 22 simulation problems in 3 categories, have been selected. The results of the 3 categories of simulations demonstrate that the one-dimensional module of the MARS 2.1 code and the RELAP5/MOD3.3 code are essentially the same code. This is expected as the two codes have basically the same set of field equations, constitutive equations and main thermal hydraulic models. The results suggests that the high level of code validity of the RELAP5/MOD3.3 can be directly applied to the MARS one-dimensional module

Relation of N-terminal pro B-type natriuretic peptide levels after symptom-limited exercise to baseline and ischemia levels.

Science.gov (United States)

van der Zee, P Marc; Verberne, Hein J; van Spijker, Rianne C; van Straalen, Jan P; Fischer, Johan C; Sturk, Augueste; van Eck-Smit, Berthe L F; de Winter, Robbert J

2009-03-01

Circulating levels of B-type natriuretic peptide (BNP) and the amino-terminal portion of the prohormone (NT-proBNP) have been reported to increase immediately after myocardial ischemia. The association between extent of exercise-induced myocardial ischemia measured using myocardial perfusion scintigraphy and the magnitude and time course of changes in NT-proBNP was studied. One hundred one patients underwent symptom-limited exercise myocardial perfusion scintigraphy. Myocardial ischemia was assessed semiquantitatively. Serum samples were obtained before the start of exercise (baseline), at maximal exercise, and every hour up to 6 hours after maximal exercise. Myocardial ischemia was present in 37 patients (37%). NT-proBNP rapidly increased during exercise (to 113%, interquartile range 104 to 144, and 118%, interquartile range 106 to 142, of baseline, respectively), with a second peak at 4 (141%, interquartile range 119 to 169) and 5 hours (136%, interquartile range 93 to 188), respectively. Absolute changes between NT-proBNP at baseline and at maximum exercise in patients with versus without ischemia were similar (median, 30 pg/ml, interquartile range 7 to 45 vs 15, interquartile range 4 to 46, respectively, p = 0.230), but absolute change between baseline and the secondary peak was higher in patients with ischemia than in patients without ischemia (median 64 pg/ml, interquartile range 32 to 172 vs 34, interquartile range 19 to 85, respectively, p = 0.024). In multivariate linear stepwise regression analysis of determinants of changes in NT-proBNP after exercise, baseline NT-proBNP was the only independent determinant of absolute changes at maximum exercise, whereas the presence of ischemia was not predictive. Baseline NT-proBNP, cystatin C, and end-systolic volume were independent determinants of the absolute increase to secondary peak levels. In conclusion, myocardial ischemia per se did not lead to additional increases in NT-proBNP within 6 hours after exercise.

Improved early risk stratification of patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention using a combination of serum soluble ST2 and NT-proBNP.

Directory of Open Access Journals (Sweden)

Jongwook Yu

Full Text Available Although soluble suppression of tumorigenicity 2 (sST2 in serum is known to be associated with ischemic heart disease and heart failure, data regarding its prognostic impact in ST-segment elevation myocardial infarction (STEMI is limited. We evaluated the prognostic impacts of serum sST2 and other serum biomarkers in STEMI patients undergoing primary percutaneous coronary intervention (PCI.Consecutive all 323 patients with STEMI that underwent primary PCI were enrolled. Blood tests and samples were obtained in an emergency room. The primary endpoint was 1-year major adverse cardiovascular and cerebrovascular events (MACCEs, defined as a composite of cardiovascular death, non-fatal MI, non-fatal stroke, and ischemia-driven revascularization.Mean age was 59.1±13.1 years (men 84%. MACCE (20 cardiovascular deaths, 7 non-fatal MI, 4 non-fatal stroke, 7 ischemia-driven revascularizations occurred in 38 patients (12%. After adjusting for confounding factors, Cox regression analysis revealed that high serum sST2 (>75.8 ng/mL mean value, adjusted hazard ratio 2.098, 95% CI 1.008-4.367, p = 0.048 and high serum NT-proBNP level (>400 pg/mL, adjusted hazard ratio 2.606, 95% CI 1.086-6.257, p = 0.032 at the time of presentation independently predicted MACCE within a year of primary PCI. Furthermore, when high serum sST2 level was combined with high serum NT-proBNP level, the hazard ratio of MACCE was highest (adjusted hazard ratio 7.93, 95% CI 2.97-20.38, p<0.001.Elevated serum levels of sST2 or NT-proBNP at the time of presentation were found to predict 1-year MACCE independently and elevated serum levels of sST2 plus NT-proBNP were associated with even poorer prognosis in patients with STEMI undergoing primary PCI.

Hippocampal brain-derived neurotrophic factor but not neurotrophin-3 increases more in mice selected for increased voluntary wheel running.

Science.gov (United States)

Johnson, R A; Rhodes, J S; Jeffrey, S L; Garland, T; Mitchell, G S

2003-01-01

Voluntary wheel running in rats increases hippocampal brain-derived neurotrophic factor (BDNF) expression, a neurochemical important for neuronal survival, differentiation, connectivity and synaptic plasticity. Here, we report the effects of wheel running on BDNF and neurotrophin-3 (NT-3) protein levels in normal control mice, and in mice selectively bred (25 generations) for increased voluntary wheel running. We hypothesized that increased voluntary wheel running in selected (S) mice would increase CNS BDNF and NT-3 protein levels more than in control (C) mice. Baseline hippocampal BDNF levels (mice housed without running wheels) were similar in S and C mice. Following seven nights of running, hippocampal BDNF increased significantly more in S versus C mice, and levels were correlated with distance run (considering C and S mice together). Spinal and cerebellar BDNF and hippocampal NT-3 levels were not significantly affected by wheel running in any group, but there was a small, positive correlation between spinal C3-C6 BDNF levels and distance run (considering C and S mice together). This is the first study to demonstrate that mice which choose to run more have greater elevations in hippocampal BDNF, suggesting enhanced potential for exercise-induced hippocampal neuroplasticity.

Vasoactive Peptide Levels after Change of Dialysis Mode

Directory of Open Access Journals (Sweden)

Fredrik Uhlin

2015-10-01

Full Text Available Background/Aims: Plasma concentrations of the N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP are increased in end-stage renal disease. Improvement in hemodynamic stability has been reported when switching from hemodialysis (HD to on-line hemodiafiltration (ol-HDF. The aim of this study was to investigate plasma concentrations of NT-proBNP, BNP and neuropeptide Y (NPY during a 1-year follow-up, after a change from high-flux HD to postdilution ol-HDF. Additional variables were also studied, e.g. pulse wave velocity and ordinary clinical parameters. Method: We conducted a prospective, single-center study including 35 patients who were switched from HD to HDF. Plasma concentrations of NT-proBNP, BNP and NPY before and after dialysis were measured at baseline (i.e. HD and at 1, 2, 4, 6 and 12 months on HDF. Results: All three peptide levels decreased significantly during HD and HDF when comparing concentrations before and after dialysis. Mean absolute value (before/after and relative decrease (% before versus after dialysis was 13.697/9.497 ng/l (31% for NT-proBNP, 62/40 ng/ml (35% for BNP and 664/364 pg/l (45% for NPY. No significant differences were observed when comparing predialysis values over time. However, postdialysis NT-proBNP concentration showed a significant decrease of 48% over time after the switch to HDF. Conclusion: The postdialysis plasma levels of NT-proBNP, BNP and NPY decreased significantly during both dialysis modes when compared to before dialysis. The postdialysis lowering of NT-proBNP increased further over time after the switch to ol-HDF; the predialysis levels were unchanged, suggesting no effect on its production in the ventricles of the heart.

ARGOS-NT: A computer based emergency management system

International Nuclear Information System (INIS)

Hoe, S.; Thykier-Nielsen, S.; Steffensen, L.B.

2000-01-01

In case of a nuclear accident or a threat of a release the Danish Emergency Management Agency is responsible for actions to minimize the consequences in Danish territory. To provide an overview of the situation, a computer based system called ARGOS-NT has been developed in 1993/94. This paper gives an overview of the system with emphasis on the prognostic part of the system. An example calculation shows the importance of correct landscape modeling. (author)

Experimental studies on possible regulatory role of nitric oxide on the differential effects of chronic predictable and unpredictable stress on adaptive immune responses.

Science.gov (United States)

Thakur, Tarun; Gulati, Kavita; Rai, Nishant; Ray, Arunabha

2017-09-01

The present study was designed to investigate the effects of chronic predictable stress (CPS) and chronic unpredictable stress (CUS) on immunological responses in KLH-sensitized rats and involvement of NOergic signaling pathways mediating such responses. Male Wistar rats (200-250g) were exposed to either CPS or CUS for 14days and IgG antibody levels and delayed type hypersensitivity (DTH) response was determined to assess changes in adaptive immunity. To evaluate the role of nitric oxide during such immunomodulation, biochemical estimation of stable metabolite of nitric oxide (NOx) and 3-nitrotyrosine (3-NT, a marker of peroxynitrite formation) were done in both blood and brain. Chronic stress exposure resulted in suppression of IgG and DTH response and elevated NOx and 3-NT levels, with a difference in magnitude of response in CPS vs CUS. Pretreatment with aminoguanidine (iNOS inhibitor) caused further reduction of adaptive immune responses and attenuated the increased NOx and 3-NT levels in CPS or CUS exposed rats. On the other hand 7-NI (nNOS inhibitor) did not significantly affect these estimated parameters. The results suggest involvement of iNOS and lesser/no role of nNOS during modulation of adaptive immunity to stress. Thus, the result showed that predictability of stressors results in differential degree of modulation of immune responses and complex NO-mediated signaling mechanisms may be involved during responses. Copyright © 2017. Published by Elsevier B.V.

The Burkholderia pseudomallei Proteins BapA and BapC Are Secreted TTSS3 Effectors and BapB Levels Modulate Expression of BopE.

Directory of Open Access Journals (Sweden)

Puthayalai Treerat

Full Text Available Many Gram-negative pathogens use a type III secretion system (TTSS for the injection of bacterial effector proteins into host cells. The injected effector proteins play direct roles in modulation of host cell pathways for bacterial benefit. Burkholderia pseudomallei, the causative agent of melioidosis, expresses three different TTSSs. One of these systems, the TTSS3, is essential for escape from host endosomes and therefore intracellular survival and replication. Here we have characterized three putative TTSS3 proteins; namely BapA, BapB and BapC. By employing a tetracysteine (TC-FlAsH™ labelling technique to monitor the secretion of TC-tagged fusion proteins, BapA and BapC were shown to be secreted during in vitro growth in a TTSS3-dependant manner, suggesting a role as TTSS3 effectors. Furthermore, we constructed B. pseudomallei bapA, bapB and bapC mutants and used the well-characterized TTSS3 effector BopE as a marker of secretion to show that BapA, BapB and BapC are not essential for the secretion process. However, BopE transcription and secretion were significantly increased in the bapB mutant, suggesting that BapB levels modulate BopE expression. In a BALB/c mouse model of acute melioidosis, the bapA, bapB and bapC mutants showed a minor reduction of in vivo fitness. Thus, this study defines BapA and BapC as novel TTSS3 effectors, BapB as a regulator of BopE production, and all three as necessary for full B. pseudomallei in vivo fitness.

PREFACE: 12th Russia/CIS/Baltic/Japan Symposium on Ferroelectricity and 9th International Conference on Functional Materials and Nanotechnologies (RCBJSF-2014-FM&NT)

Science.gov (United States)

Sternberg, Andris; Grinberga, Liga; Sarakovskis, Anatolijs; Rutkis, Martins

2015-03-01

The joint International Symposium RCBJSF-2014-FM&NT successfully has united two international events - 12th Russia/CIS/Baltic/Japan Symposium on Ferroelectricity (RCBJSF-12) and 9th International Conference Functional Materials and Nanotechnologies (FM&NT-2014). The RCBJSF symposium is a continuation of series of meetings on ferroelectricity, the first of which took place in Novosibirsk (USSR) in 1976. FM&NT conferences started in 2006 and have been organized by Institute of Solid State Physics, University of Latvia in Riga. In 2012 the International program committee decided to transform this conference into a traveling Baltic State conference and the FM&NT-2013 was organized by the Institute of Physics, University of Tartu, Estonia. In 2014 the joint international symposium RCBJSF-2014-FM&NT was organized by the Institute of Solid State Physics, University of Latvia and was part of Riga - 2014, the European Capital of Culture event. The purpose of the joint Symposium was to bring together scientists, students and high-level experts in solid state physics, materials science, engineering and related disciplines. The number of the registered participants from 26 countries was over 350. During the Symposium 128 high quality scientific talks (5 plenary, 42 invited, 81 oral) and over 215 posters were presented. All presentations were divided into 4 parallel sessions according to 4 main topics of the Symposium: Ferroelectricity, including ferroelectrics and multiferroics, pyroelectrics, piezoelectrics and actuators, integrated ferroelectrics, relaxors, phase transitions and critical phenomena. Multifunctional Materials, including theory, multiscale and multiphenomenal material modeling and simulation, advanced inorganic, organic and hybrid materials. Nanotechnologies, including progressive methods, technologies and design for production, investigation of nano- particles, composites, structures, thin films and coatings. Energy, including perspective materials and

ATLAS Level-1 Calorimeter Trigger Subsystem Tests of a Prototype Cluster Processor Module

CERN Document Server

Garvey, J; Apostologlou, P; Ay, C; Barnett, B M; Bauss, B; Brawn, I P; Bohm, C; Dahlhoff, A; Davis, A O; Edwards, J; Eisenhandler, E F; Gee, C N P; Gillman, A R; Hanke, P; Hellman, S; Hidévgi, A; Hillier, S J; Jakobs, K; Kluge, E E; Landon, M; Mahboubi, K; Mahout, G; Meier, K; Meshkov, P; Moye, T H; Mills, D; Moyse, E; Nix, O; Penno, K; Perera, V J O; Qian, W; Schmitt, K; Schäfer, U; Silverstein, S; Staley, R J; Thomas, J; Trefzger, T M; Watkins, P M; Watson, A; 9th Workshop On Electronics For LHC Experiments - LECC 2003

2003-01-01

The Level-1 Calorimeter Trigger consists of a Preprocessor (PP), a Cluster Processor (CP), and a Jet/Energy-sum Processor (JEP). The CP and JEP receive digitised trigger-tower data from the Preprocessor and produce trigger multiplicity and Region-of-Interest (RoI) information. The trigger will also provide intermediate results to the data acquisition (DAQ) system for monitoring and diagnostic purposes by using Readout Driver (ROD) Modules. The CP Modules (CPM) are designed to find isolated electron/photon and hadron/tau clusters in overlapping windows of trigger towers. Each pipelined CPM processes 8-bit data from a total of 128 trigger towers at each LHC crossing. Four full-specification prototypes of CPMs have been built and results of complete tests on individual boards will be presented. These modules were then integrated with other modules to build an ATLAS Level-1 Calorimeter Trigger subsystem test bench. Realtime data were exchanged between modules, and time-slice readout data were tagged and transferr...

A3 Adenosine Receptor Allosteric Modulator Induces an Anti-Inflammatory Effect: In Vivo Studies and Molecular Mechanism of Action

Directory of Open Access Journals (Sweden)

Shira Cohen

2014-01-01

Full Text Available The A3 adenosine receptor (A3AR is overexpressed in inflammatory cells and in the peripheral blood mononuclear cells of individuals with inflammatory conditions. Agonists to the A3AR are known to induce specific anti-inflammatory effects upon chronic treatment. LUF6000 is an allosteric compound known to modulate the A3AR and render the endogenous ligand adenosine to bind to the receptor with higher affinity. The advantage of allosteric modulators is their capability to target specifically areas where adenosine levels are increased such as inflammatory and tumor sites, whereas normal body cells and tissues are refractory to the allosteric modulators due to low adenosine levels. LUF6000 administration induced anti-inflammatory effect in 3 experimental animal models of rat adjuvant induced arthritis, monoiodoacetate induced osteoarthritis, and concanavalin A induced liver inflammation in mice. The molecular mechanism of action points to deregulation of signaling proteins including PI3K, IKK, IκB, Jak-2, and STAT-1, resulting in decreased levels of NF-κB, known to mediate inflammatory effects. Moreover, LUF6000 induced a slight stimulatory effect on the number of normal white blood cells and neutrophils. The anti-inflammatory effect of LUF6000, mechanism of action, and the differential effects on inflammatory and normal cells position this allosteric modulator as an attractive and unique drug candidate.

Photovoltaic Shading Testbed for Module-Level Power Electronics: 2016 Performance Data Update

Energy Technology Data Exchange (ETDEWEB)

Deline, Chris [National Renewable Energy Lab. (NREL), Golden, CO (United States); Meydbray, Jenya [PV Evolution Labs (PVEL), Davis, CA (United States); Donovan, Matt [PV Evolution Labs (PVEL), Davis, CA (United States)

2016-09-01

The 2012 NREL report 'Photovoltaic Shading Testbed for Module-Level Power Electronics' provides a standard methodology for estimating the performance benefit of distributed power electronics under partial shading conditions. Since the release of the report, experiments have been conducted for a number of products and for different system configurations. Drawing from these experiences, updates to the test and analysis methods are recommended. Proposed changes in data processing have the benefit of reducing the sensitivity to measurement errors and weather variability, as well as bringing the updated performance score in line with measured and simulated values of the shade recovery benefit of distributed PV power electronics. Also, due to the emergence of new technologies including sub-module embedded power electronics, the shading method has been extended to include power electronics that operate at a finer granularity than the module level. An update to the method is proposed to account for these emerging technologies that respond to shading differently than module-level devices. The partial shading test remains a repeatable test procedure that attempts to simulate shading situations as would be experienced by typical residential or commercial rooftop photovoltaic (PV) systems. Performance data for multiple products tested using this method are discussed, based on equipment from Enphase, Solar Edge, Maxim Integrated and SMA. In general, the annual recovery of shading losses from the module-level electronics evaluated is 25-35%, with the major difference between different trials being related to the number of parallel strings in the test installation rather than differences between the equipment tested. Appendix D data has been added in this update.

The interaction between tropomyosin-related kinase B receptors and presynaptic muscarinic receptors modulates transmitter release in adult rodent motor nerve terminals.

Science.gov (United States)

Garcia, Neus; Tomàs, Marta; Santafé, Manel M; Besalduch, Nuria; Lanuza, Maria A; Tomàs, Josep

2010-12-08

The neurotrophin brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4) and the receptors tropomyosin-related kinase B (trkB) and p75(NTR) are present in the nerve terminals on the neuromuscular junctions (NMJs) of the levator auris longus muscle of the adult mouse. Exogenously added BDNF or NT-4 increased evoked ACh release after 3 h. This presynaptic effect (the size of the spontaneous potentials is not affected) is specific because it is not produced by neurotrophin-3 (NT-3) and is prevented by preincubation with trkB-IgG chimera or by pharmacological block of trkB [K-252a (C₂₇H₂₁N₃O₅)] or p75(NTR) [Pep5 (C₈₆H₁₁₁N₂₅O₁₉S₂] signaling. The effect of BDNF depends on the M₁ and M₂ muscarinic acetylcholine autoreceptors (mAChRs) because it is prevented by atropine, pirenzepine and methoctramine. We found that K-252a incubation reduces ACh release (~50%) in a short time (1 h), but the p75(NTR) signaling inhibitor Pep5 does not have this effect. The specificity of the K-252a blocking effect on trkB was confirmed with the anti-trkB antibody 47/trkB, which reduces evoked ACh release, like K-252a, whereas the nonpermeant tyrosine kinase blocker K-252b does not. Neither does incubation with the fusion protein trkB-IgG (to chelate endogenous BDNF/NT-4), anti-BDNF or anti-NT-4 change ACh release. Thus, the trkB receptor normally seems to be coupled to ACh release when there is no short-term local effect of neurotrophins at the NMJ. The normal function of the mAChR mechanism is a permissive prerequisite for the trkB pathway to couple to ACh release. Reciprocally, the normal function of trkB modulates M₁- and M₂-subtype muscarinic pathways.

Distributed mass data acquisition system based on PCs and windows NT for LHD fusion plasma experiment

International Nuclear Information System (INIS)

Nakanishi, H.; Kojima, M.; Ohsuna, M.; Komada, S.; Emoto, M.; Sugisaki, H.; Sudo, S.

2000-12-01

A new data acquisition and management system has been developed for the LHD experiment. It has the capability to process 100 MB - 1 GB raw data within a few tens seconds after every plasma discharge. It employs wholly distributed and loosely-tied parallel tasking structure through a fast network, and the cluster of the distributed database severs seems to be a virtual macro-machine as a whole. A PC/Windows NT computer is installed for each diagnostics data acquisition of about 30 kinds, and it controls CAMAC digitizers through the optical SCSI extenders. The diagnostic timing system consists of some kinds of VME modules that are installed to remotely control the diagnostic devices in real-time. They can, as a whole system, distribute the synchronous sampling clocks and programmable triggers for measurement digitizers. The data retrieving terminals can access database as application service clients, and are functionally separated from the data acquisition severs by way of the switching Ethernet. (author)

Dependence of regenerated sensory axons on continuous neurotrophin-3 delivery.

Science.gov (United States)

Hou, Shaoping; Nicholson, LaShae; van Niekerk, Erna; Motsch, Melanie; Blesch, Armin

2012-09-19

Previous studies have shown that injured dorsal column sensory axons extend across a spinal cord lesion site if axons are guided by a gradient of neurotrophin-3 (NT-3) rostral to the lesion. Here we examined whether continuous NT-3 delivery is necessary to sustain regenerated axons in the injured spinal cord. Using tetracycline-regulated (tet-off) lentiviral gene delivery, NT-3 expression was tightly controlled by doxycycline administration. To examine axon growth responses to regulated NT-3 expression, adult rats underwent a C3 dorsal funiculus lesion. The lesion site was filled with bone marrow stromal cells, tet-off-NT-3 virus was injected rostral to the lesion site, and the intrinsic growth capacity of sensory neurons was activated by a conditioning lesion. When NT-3 gene expression was turned on, cholera toxin β-subunit-labeled sensory axons regenerated into and beyond the lesion/graft site. Surprisingly, the number of regenerated axons significantly declined when NT-3 expression was turned off, whereas continued NT-3 expression sustained regenerated axons. Quantification of axon numbers beyond the lesion demonstrated a significant decline of axon growth in animals with transient NT-3 expression, only some axons that had regenerated over longer distance were sustained. Regenerated axons were located in white matter and did not form axodendritic synapses but expressed presynaptic markers when closely associated with NG2-labeled cells. A decline in axon density was also observed within cellular grafts after NT-3 expression was turned off possibly via reduction in L1 and laminin expression in Schwann cells. Thus, multiple mechanisms underlie the inability of transient NT-3 expression to fully sustain regenerated sensory axons.

Differential regulation of axon outgrowth and reinnervation by neurotrophin-3 and neurotrophin-4 in the hippocampal formation.

Science.gov (United States)

Hechler, Daniel; Boato, Francesco; Nitsch, Robert; Hendrix, Sven

2010-08-01

In this study, we investigated the hypothesis whether neurotrophins have a differential influence on neurite growth from the entorhinal cortex depending on the presence or absence of hippocampal target tissue. We investigated organotypic brain slices derived from the entorhinal-hippocampal system to analyze the effects of endogenous and recombinant neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) on neurite outgrowth and reinnervation. In the reinnervation assay, entorhinal cortex explants of transgenic mice expressing enhanced green fluorescent protein (EGFP) were co-cultured with wild-type hippocampi under the influence of recombinant NT-3 and NT-4 (500 ng/ml). Both recombinant NT-3 and NT-4 significantly increased the growth of EGFP+ nerve fibers into the target tissue. Consistently, reinnervation of the hippocampi of NT-4(-/-) and NT-3(+/-)NT-4(-/-) mice was substantially reduced. In contrast, the outgrowth assay did not exhibit reduction in axon outgrowth of NT-4(-/-) or NT-3(+/-)NT-4(-/-) cortex explants, while the application of recombinant NT-3 (500 ng/ml) induced a significant increase in the neurite extension of cortex explants. Recombinant NT-4 had no effect. In summary, only recombinant NT-3 stimulates axon outgrowth from cortex explants, while both endogenous and recombinant NT-3 and NT-4 synergistically promote reinnervation of the denervated hippocampus. These results suggest that endogenous and exogenous NT-3 and NT-4 differentially influence neurite growth depending on the presence or absence of target tissue.

INCREASED PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM -INDUCED ALLERGIC ASTHMA MODEL IN MICE

Science.gov (United States)

Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthmatics and in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated pulmona...

Effect of PCI on inflammatory factors, cTnI, MMP-9 and NT-pro BNP in patients with unstable angina pectoris

Directory of Open Access Journals (Sweden)

Ke-Tong Liu

2016-05-01

Full Text Available Objective: To investigate the effect of PCI on inflammatory factors, cTnI, MMP-9and NTpro BNP in patients with unstable angina pectoris. Methods: A total of 80 unstable angina pectoris patients were divided into observation group (40 cases and control group (40 cases. The observation group was given the therapy of PCI, and the control group was given coronary angiography. To observe the of inflammatory factors, cTnI, MMP-9 and NT-pro BNP were tested and compared before and after operation. Results: At 24 h after operation, CRP and IL-18 levels were increased significantly after treatment inoperation groups, there was no difference on inflammatory factors in control group, and had significant difference on inflammatory factors in two groups; At 24 h after operation, cTnI, MMP-9 and NT-pro BNP levels were increased significantly after treatment inoperation groups, there was no difference on inflammatory factors in control group, and had significant difference on inflammatory factors in two groups. Conclusion: PCI therapy can induce inflammation and myocardial injury in patients with unstable angina pectoris.

SU-E-T-421: Feasibility Study of Volumetric Modulated Arc Therapy with Constant Dose Rate for Endometrial Cancer

Energy Technology Data Exchange (ETDEWEB)

Yang, R; Wang, J [Peking University Third Hospital, Beijing, Beijing (China)

2014-06-01

Purpose: To investigate the feasibility, efficiency, and delivery accuracy of volumetric modulated arc therapy with constant dose rate (VMAT-CDR) for whole-pelvic radiotherapy (WPRT) of endometrial cancer. Methods: The nine-Field intensity-modulated radiotherapy (IMRT), VMAT with variable dose-rate (VMAT-VDR), and VMAT-CDR plans were created for 9 patients with endometrial cancer undergoing WPRT. The dose distribution of planning target volume (PTV), organs at risk (OARs), and normal tissue (NT) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. For each VMAT-CDR plan, a dry Run was performed to assess the dosimetric accuracy with MatriXX from IBA. Results: Compared with IMRT, the VMAT-CDR plans delivered a slightly greater V20 of the bowel, bladder, pelvis bone, and NT, but significantly decreased the dose to the high-dose region of the rectum and pelvis bone. The MUs Decreased from 1105 with IMRT to 628 with VMAT-CDR. The delivery time also decreased from 9.5 to 3.2 minutes. The average gamma pass rate was 95.6% at the 3%/3 mm criteria with MatriXX pretreatment verification for 9 patients. Conclusion: VMAT-CDR can achieve comparable plan quality with significant shorter delivery time and smaller number of MUs compared with IMRT for patients with endometrial cancer undergoing WPRT. It can be accurately delivered and be an alternative to IMRT on the linear accelerator without VDR capability. This work is supported by the grant project, National Natural; Science Foundation of China (No. 81071237)

Analysis of N-terminal pro-brain natriuretic peptide levels in patients with chronic heart failure

International Nuclear Information System (INIS)

Fu Xiao; Zhang Xingping; Zhou Kejian

2011-01-01

To investigate the changes and its clinical significance of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with chronic heart failure(CHF), 128 patients with decompensated CHF and 20 patients without structural heart disease were selected as CHF and control group. All subjects were evaluated heart function by New York Heart Association (NYHA) class. The serum NT-proBNP levels were assayed by electrochemiluminescence double antibody sandwich immunoassay. Left ventricular ejection fraction (LVEF) was detected by color Doppler ultrasound. The results showed that the NT-proBNP levels in CHF group were significantly higher than that of in the control group (P<0.05). Further, the NT-proBNP levels showed an increased tendency accompanied by the severity of heart failure (P<0.05) and lowering of LVEF (r=-0.595, P<0.05). The serum NT-proBNP levels can reflect the state of cardiac function in patients with decompensated DHF, and useful in the diagnosis and severity assessment of CHF. (authors)

The MSG Central Facility - A Mission Control System for Windows NT

Science.gov (United States)

Thompson, R.

The MSG Central Facility, being developed by Science Systems for EUMETSAT1, represents the first of a new generation of satellite mission control systems, based on the Windows NT operating system. The system makes use of a range of new technologies to provide an integrated environment for the planning, scheduling, control and monitoring of the entire Meteosat Second Generation mission. It supports packetised TM/TC and uses Science System's Space UNiT product to provide automated operations support at both Schedule (Timeline) and Procedure levels. Flexible access to historical data is provided through an operations archive based on ORACLE Enterprise Server, hosted on a large RAID array and off-line tape jukebox. Event driven real-time data distribution is based on the CORBA standard. Operations preparation and configuration control tools form a fully integrated element of the system.

Lockout/Tagout - Turvalukituskäytäntö

OpenAIRE

Juhala, Ville

2017-01-01

Tämän opinnäytetyön tarkoituksena oli laatia kattava ohjeistus kuparitehtaan turvalukituksista. Työ tehtiin Aurubis Finland Oy:n kuparivalssaamoon. Ohjeistuksista tuli käydä ilmi turvalukitusten vaikutus lukittaviin laitteisiin sekä mahdolliset työturvallisuusriskit joita koneiden kanssa toimiessa tulee huomioida. Työn tavoitteena oli lisätä kunnossapidon työturvallisuutta ja selkeyttää koneiden kanssa työskentelyyn liittyviä käytäntöjä. Ohjeistukset laadittiin vahinkokäynnistymisen estoa...

Inflammation and pancreatic cancer: molecular and functional interactions between S100A8, S100A9, NT-S100A8 and TGFβ1.

Science.gov (United States)

Basso, Daniela; Bozzato, Dania; Padoan, Andrea; Moz, Stefania; Zambon, Carlo-Federico; Fogar, Paola; Greco, Eliana; Scorzeto, Michele; Simonato, Francesca; Navaglia, Filippo; Fassan, Matteo; Pelloso, Michela; Dupont, Sirio; Pedrazzoli, Sergio; Fassina, Ambrogio; Plebani, Mario

2014-03-26

In order to gain further insight on the crosstalk between pancreatic cancer (PDAC) and stromal cells, we investigated interactions occurring between TGFβ1 and the inflammatory proteins S100A8, S100A9 and NT-S100A8, a PDAC-associated S100A8 derived peptide, in cell signaling, intracellular calcium (Cai2+) and epithelial to mesenchymal transition (EMT). NF-κB, Akt and mTOR pathways, Cai2+ and EMT were studied in well (Capan1 and BxPC3) and poorly differentiated (Panc1 and MiaPaCa2) cell lines. NT-S100A8, one of the low molecular weight N-terminal peptides from S100A8 to be released by PDAC-derived proteases, shared many effects on NF-κB, Akt and mTOR signaling with S100A8, but mainly with TGFβ1. The chief effects of S100A8, S100A9 and NT-S100A8 were to inhibit NF-κB and stimulate mTOR; the molecules inhibited Akt in Smad4-expressing, while stimulated Akt in Smad4 negative cells. By restoring Smad4 expression in BxPC3 and silencing it in MiaPaCa2, S100A8 and NT-S100A8 were shown to inhibit NF-κB and Akt in the presence of an intact TGFβ1 canonical signaling pathway. TGFβ1 counteracted S100A8, S100A9 and NT-S100A8 effects in Smad4 expressing, not in Smad4 negative cells, while it synergized with NT-S100A8 in altering Cai2+ and stimulating PDAC cell growth. The effects of TGFβ1 on both EMT (increased Twist and decreased N-Cadherin expression) and Cai2+ were antagonized by S100A9, which formed heterodimers with TGFβ1 (MALDI-TOF/MS and co-immuno-precipitation). The effects of S100A8 and S100A9 on PDAC cell signaling appear to be cell-type and context dependent. NT-S100A8 mimics the effects of TGFβ1 on cell signaling, and the formation of complexes between TGFβ1 with S100A9 appears to be the molecular mechanism underlying the reciprocal antagonism of these molecules on cell signaling, Cai2+ and EMT.

Recombinant Nonstructural 3 Protein, rNS3, of Hepatitis C Virus Along With Recombinant GP96 Induce IL-12, TNFα and α5integrin Expression in Antigen Presenting Cells

Science.gov (United States)

Hajizadeh, Mohammad Reza; Mokarram, Pooneh; Kamali sarvestani, Eskandar; Bolhassani, Azam; Mostafavi Pour, Zohreh

2013-01-01

Background Hepatitis C virus (HCV) infection is the main cause of chronic liver disease and to date there has been no vaccine development to prevent this infection. Among non-structural HCV proteins, NS3 protein is an excellent goal for a therapeutic vaccine, due to its large size and less variation in conserved regions. The immunogenic properties of heat shock proteins (HSPs) for instance GP96 have prompted investigations into their function as strong adjuvant to improve innate and adaptive immunity. Objectives The aim of this study was to examine additive effects of recombinant GP96 (rGP96) fragments accompanied by rNS3 on expression levels of α5integrin and pro-inflammatory cytokines, IL-12 and TNFα, in Antigen Presenting Cells (APCs). Materials and Methods Recombinant viral proteins (rNS3 and rRGD-NS3), N-terminal and C-terminal fragments of GP96 were produced and purified from E. coli in order to treat the cells; mouse spleen Dendritic Cells (DCs) and THP-1 macrophages. Results Our results showed that rNT-GP96 alone significantly increases the expression level of IL-12, TNFα and α5integrin in THP-1 macrophages and DCs, while IL-12 and TNFα expression levels were unaffected by either rNS3 or rRGD-NS3. Interestingly, the co-addition of these recombinant proteins with rNT-GP96 increased IL-12, TNFα and α5integrin expression. Pearson Correlation showed a direct association between α5integrin with IL-12 and TNF-α expression. Conclusions we have highlighted the role of rNS3 plus rNT-GP96 mediated by α5integrin in producing IL-12 and TNFα. It can be suggested that rNT-GP96 could enhance immunity characteristic of rNS3 protein via production of pro-inflammatory cytokines. PMID:24032046

RNA 3D modules in genome-wide predictions of RNA 2D structure

DEFF Research Database (Denmark)

Theis, Corinna; Zirbel, Craig L; Zu Siederdissen, Christian Höner

2015-01-01

. These modules can, for example, occur inside structural elements which in RNA 2D predictions appear as internal loops. Hence one question is if the use of such RNA 3D information can improve the prediction accuracy of RNA secondary structure at a genome-wide level. Here, we use RNAz in combination with 3D......Recent experimental and computational progress has revealed a large potential for RNA structure in the genome. This has been driven by computational strategies that exploit multiple genomes of related organisms to identify common sequences and secondary structures. However, these computational...... approaches have two main challenges: they are computationally expensive and they have a relatively high false discovery rate (FDR). Simultaneously, RNA 3D structure analysis has revealed modules composed of non-canonical base pairs which occur in non-homologous positions, apparently by independent evolution...

Quantifying the evidence for dark matter in CoGeNT data

International Nuclear Information System (INIS)

Davis, Jonathan H.; McCabe, Christopher; Boehm, Céline

2014-01-01

We perform an independent analysis of data from the CoGeNT direct detection experiment to quantify the evidence for dark matter recoils. We critically re-examine the assumptions that enter the analysis, focusing specifically on the separation of bulk and surface events, the latter of which constitute a large background. This separation is performed using the event rise-time, with the surface events being slower on average. We fit the rise-time distributions for the bulk and surface events with a log-normal and Pareto distribution (which gives a better fit to the tail in the bulk population at high rise-times) and account for the energy-dependence of the bulk fraction using a cubic spline. Using Bayesian and frequentist techniques and additionally investigating the effect of varying the rise-time cut, the bulk background spectrum and bin-sizes, we conclude that the CoGeNT data show a preference for light dark matter recoils at less than 1σ

DOSE-DEPENDENT INCREASE IN THE PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM-INDUCED ALLERGIC ASTHMA MODEL

Science.gov (United States)

Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthma as well as in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated ...

Establishment of Infrastructure for Domestic-Specific Level 3 PSA based on MACCS2

Energy Technology Data Exchange (ETDEWEB)

Jang, Seung-Cheol; Han, Seok-Jung; Choi, Sun-Yeong; Lee, Seung-Jun [KAERI, Daejeon (Korea, Republic of); Kim, Wan-Seob [Korea Reliability Technology and System, Daejeon (Korea, Republic of)

2015-05-15

Research activities related to the Level 3 PSA have naturally disappeared since the use of risk surrogates. Recently, Level 3 PSA was only performed to the extent of the purpose of operating license for the plant under construction. Since the Fukushima accident, concern about a comprehensive site-specific Level 3 PSA has been raised for some compelling reasons, especially the evaluation of the domestic multi-unit site risk effect including other site radiological sources (e.g., spent fuel pool, multi-units). Unfortunately, there are no domestic-specific consequence analysis code and input database required to perform a site-specific Level 3 PSA. The paper focuses on the development of the input data management system for domestic-specific Level 3 PSA based MACCS2 (MELCOR Accident Consequence Code System). The authors call it KOSCA-MACCS2 (Korea Off-Site Consequence Analysis based in MACCS2). It serves as an integrated platform for a domestic-specific Level 3 PSA. Also, it provides the pre-processing modules to automatically generate MACCS2 input from diverse types of the domestic-specific data including numerical map data, e.g., meteorological data, numerical population map, digital land use map, economic statistics and so on. Note that some functions should be still developed and added on it, e.g., post-processing module to convert MACCS2 outputs to graphic report forms, and so on. Henceforth, it is necessary to develop a Korean-specific Level 3 PSA code as a substitution for the foreign software, MACCS2.

Identification of Potentially Neuroprotective Genes Upregulated by Neurotrophin Treatment of CA3 Neurons in the Injured Brain

Science.gov (United States)

Malik, Saafan Z.; Motamedi, Shahab; Royo, Nicolas C.; LeBold, David

2011-01-01

Abstract Specific neurotrophic factors mediate histological and/or functional improvement in animal models of traumatic brain injury (TBI). In previous work, several lines of evidence indicated that the mammalian neurotrophin NT-4/5 is neuroprotective for hippocampal CA3 pyramidal neurons after experimental TBI. We hypothesized that NT-4/5 neuroprotection is mediated by changes in the expression of specific sets of genes, and that NT-4/5-regulated genes are potential therapeutic targets for blocking delayed neuronal death after TBI. In this study, we performed transcription profiling analysis of CA3 neurons to identify genes regulated by lateral fluid percussion injury, or by treatment with the trkB ligands NT-4/5 or brain-derived neurotrophic factor (BDNF). The results indicate extensive overlap between genes upregulated by neurotrophins and genes upregulated by injury, suggesting that the mechanism behind neurotrophin neuroprotection may mimic the brain's endogenous protective response. A subset of genes selected for further study in vitro exhibited neuroprotection against glutamate excitotoxicity. The neuroprotective genes identified in this study were upregulated at 30 h post-injury, and are thus expected to act during a clinically useful time frame of hours to days after injury. Modulation of these factors and pathways by genetic manipulation or small molecules may confer hippocampal neuroprotection in vivo in preclinical models of TBI. PMID:21083427

Thermal sensation during mild hyperthermia is modulated by acute postural change in humans.

Science.gov (United States)

Takeda, Ryosuke; Imai, Daiki; Suzuki, Akina; Ota, Akemi; Naghavi, Nooshin; Yamashina, Yoshihiro; Hirasawa, Yoshikazu; Yokoyama, Hisayo; Miyagawa, Toshiaki; Okazaki, Kazunobu

2016-12-01

Thermal sensation represents the primary stimulus for behavioral and autonomic thermoregulation. We assessed whether the sensation of skin and core temperatures for the driving force of behavioral thermoregulation was modified by postural change from the supine (Sup) to sitting (Sit) during mild hyperthermia. Seventeen healthy young men underwent measurements of noticeable increase and decrease (±0.1 °C/s) of skin temperature (thresholds of warm and cold sensation on the skin, 6.25 cm 2 of area) at the forearm and chest and of the whole-body warm sensation in the Sup and Sit during normothermia (NT; esophageal temperature (T es ), ∼36.6 °C) and mild hyperthermia (HT; T es , ∼37.2 °C; lower legs immersion in 42 °C of water). The threshold for cold sensation on the skin at chest was lower during HT than NT in the Sit (P sensation on the skin at both sites remained unchanged with changes in body posture or temperature. The whole-body warm sensation was higher during HT than NT in both postures and higher in the Sit than Sup during both NT and HT (all, P sensation during mild hyperthermia is modulated by postural change from supine to sitting to sense lesser cold on the skin and more whole-body warmth.

Neurotrophin-3 promotes proliferation and cholinergic neuronal differentiation of bone marrow- derived neural stem cells via notch signaling pathway.

Science.gov (United States)

Yan, Yu-Hui; Li, Shao-Heng; Gao, Zhong; Zou, Sa-Feng; Li, Hong-Yan; Tao, Zhen-Yu; Song, Jie; Yang, Jing-Xian

2016-12-01

Recently, the potential for neural stem cells (NSCs) to be used in the treatment of Alzheimer's disease (AD) has been reported; however, the therapeutic effects are modest by virtue of the low neural differentiation rate. In our study, we transfected bone marrow-derived NSCs (BM-NSCs) with Neurotrophin-3 (NT-3), a superactive neurotrophic factor that promotes neuronal survival, differentiation, and migration of neuronal cells, to investigate the effects of NT-3 gene overexpression on the proliferation and differentiation into cholinergic neuron of BM-NSCs in vitro and its possible molecular mechanism. BM-NSCs were generated from BM mesenchymal cells of adult C57BL/6 mice and cultured in vitro. After transfected with NT-3 gene, immunofluorescence and RT-PCR method were used to determine the ability of BM-NSCs on proliferation and differentiation into cholinergic neuron; Acetylcholine Assay Kit was used for acetylcholine (Ach). RT-PCR and WB analysis were used to characterize mRNA and protein level related to the Notch signaling pathway. We found that NT-3 can promote the proliferation and differentiation of BM-NSCs into cholinergic neurons and elevate the levels of acetylcholine (ACh) in the supernatant. Furthermore, NT-3 gene overexpression increase the expression of Hes1, decreased the expression of Mash1 and Ngn1 during proliferation of BM-NSCs. Whereas, the expression of Hes1 was down-regulated, and Mash1 and Ngn1 expression were up-regulated during differentiation of BM-NSCs. Our findings support the prospect of using NT-3-transduced BM-NSCs in developing therapies for AD due to their equivalent therapeutic potential as subventricular zone-derived NSCs (SVZ-NSCs), greater accessibility, and autogenous attributes. Copyright © 2016 Elsevier Inc. All rights reserved.

Neonatal levels of neurotrophic factors and risk of autism spectrum disorders

DEFF Research Database (Denmark)

Abdallah, Morsi; Mortensen, E L; Greaves-Lord, K

2013-01-01

To examine levels of 3 neurotrophic factors (NTFs): Brain derived neurotrophic factor (BDNF), Neurotrophin-4 (NT-4), and transforming growth factor-β (TGF-β) in dried blood spot samples of neonates diagnosed with autism spectrum disorders (ASD) later in life and frequency-matched controls....

Relative Importance of History of Heart Failure Hospitalization and N-Terminal Pro-B-Type Natriuretic Peptide Level as Predictors of Outcomes in Patients With Heart Failure and Preserved Ejection Fraction

DEFF Research Database (Denmark)

Kristensen, Søren L; Jhund, Pardeep S; Køber, Lars

2015-01-01

of NT-proBNP (n = 1468) (HR: 3.19; 95% CI: 2.68 to 3.80). In patients with no recent HF hospitalization and NT-proBNP ≤360 pg/ml (n = 1,187), the event rate was 2.43 (95% CI: 2.03 to 2.90) compared with 17.79 (95% CI: 15.77 to 20.07) per 100 person-years when both risk predictors were present (n = 523......; HR: 6.18; 95% CI: 4.96 to 7.69). CONCLUSIONS: Recent hospitalization for HF or an elevated level of NT-proBNP identified patients at higher risk for cardiovascular events, and this risk was increased further when both factors were present.......OBJECTIVES: The aim of this study was to investigate N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and recent heart failure (HF) hospitalization as predictors of future events in heart failure - preserved ejection fraction (HF-PEF). BACKGROUND: Recently, doubt has been expressed...

Women's hormone levels modulate the motivational salience of facial attractiveness and sexual dimorphism.

Science.gov (United States)

Wang, Hongyi; Hahn, Amanda C; Fisher, Claire I; DeBruine, Lisa M; Jones, Benedict C

2014-12-01

The physical attractiveness of faces is positively correlated with both behavioral and neural measures of their motivational salience. Although previous work suggests that hormone levels modulate women's perceptions of others' facial attractiveness, studies have not yet investigated whether hormone levels also modulate the motivational salience of facial characteristics. To address this issue, we investigated the relationships between within-subject changes in women's salivary hormone levels (estradiol, progesterone, testosterone, and estradiol-to-progesterone ratio) and within-subject changes in the motivational salience of attractiveness and sexual dimorphism in male and female faces. The motivational salience of physically attractive faces in general and feminine female faces, but not masculine male faces, was greater in test sessions where women had high testosterone levels. Additionally, the reward value of sexually dimorphic faces in general and attractive female faces, but not attractive male faces, was greater in test sessions where women had high estradiol-to-progesterone ratios. These results provide the first evidence that the motivational salience of facial attractiveness and sexual dimorphism is modulated by within-woman changes in hormone levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

Applications of Acupuncture Therapy in Modulating Plasticity of Central Nervous System.

Science.gov (United States)

Xiao, Ling-Yong; Wang, Xue-Rui; Yang, Ye; Yang, Jing-Wen; Cao, Yan; Ma, Si-Ming; Li, Tian-Ran; Liu, Cun-Zhi

2017-11-07

Acupuncture is widely applied for treatment of various neurological disorders. This manuscript will review the preclinical evidence of acupuncture in mediating neural plasticity, the mechanisms involved. We searched acupuncture, plasticity, and other potential related words at the following sites: PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and VIP information data base. The following keywords were used: acupuncture, electroacupuncture, plasticity, neural plasticity, neuroplasticity, neurogenesis, neuroblast, stem cell, progenitor cell, BrdU, synapse, synapse structure, synaptogenesis, axon, axon regeneration, synaptic plasticity, LTP, LTD, neurotrophin, neurotrophic factor, BDNF, GDNF, VEGF, bFGF, EGF, NT-3, NT-4, NT-5, p75NTR, neurotransmitter, acetylcholine, norepinephrine, noradrenaline, dopamine, monamine. We assessed the effects of acupuncture on plasticity under pathological conditions in this review. Relevant references were reviewed and presented to reflect the effects of acupuncture on neural plasticity. The acquired literatures mainly focused on neurogenesis, alterations of synapses, neurotrophins (NTs), and neurotranimitters. Acupuncture methods mentioned in this article include manual acupuncture and electroacupuncture. The cumulative evidences demonstrated that acupuncture could induce neural plasticity in rodents exposed to cerebral ischemia. Neural plasticity mediated by acupuncture in other neural disorders, such as Alzheimer's disease, Parkinson's disease, and depression, were also investigated and there is evidence of positive role of acupuncture induced plasticity in these disorders as well. Mediation of neural plasticity by acupuncture is likely associated with its modulation on NTs and neurotransmitters. The exact mechanisms underlying acupuncture's effects on neural plasticity remain to be elucidated. Neural plasticity may be the potential bridge between acupuncture and the treatment of various

NT-proBNP is associated with coronary heart disease risk in healthy older women but fails to enhance prediction beyond established risk factors: results from the British Women's Heart and Health Study.

Science.gov (United States)

Sattar, Naveed; Welsh, Paul; Sarwar, Nadeem; Danesh, John; Di Angelantonio, Emanuele; Gudnason, Vilmundur; Davey Smith, George; Ebrahim, Shah; Lawlor, Debbie A

2010-03-01

Limited evidence suggests NT-proBNP improves prediction of coronary heart disease (CHD) events but further data are needed, especially in people without pre-existing CHD and in women. We measured NT-proBNP in serum from 162 women with incident CHD events and 1226 controls (60-79 years) in a case-control study nested within the prospective British Women's Heart and Health Study. All cases and controls were free from CHD at baseline. We related NT-proBNP to CHD event risk, and determined to what extent NT-proBNP enhanced CHD risk prediction beyond established risk factors. The odds ratio for CHD per 1 standard deviation increase in log(e)NT-proBNP was 1.37 (95% CI: 1.13-1.68) in analyses adjusted for established CHD risk factors, social class, CRP and insulin. However, addition of log(e)NT-proBNP did not improve the discrimination of a prediction model including age, social class, smoking, physical activity, lipids, fasting glucose, waist:hip ratio, hypertension, statin and aspirin use, nor a standard Framingham risk score model; area under the receiver operator curve for the former model increased from 0.676 to 0.687 on inclusion of NT-proBNP (p=0.3). Furthermore, adding NT-proBNP did not improve calibration of a prediction model containing established risk factors, nor did inclusion more appropriately re-classify participants in relation to their final outcome. Findings were similar (independent associations, but no prediction improvement) for fasting insulin and CRP. These results caution against use of NT-proBNP for CHD risk prediction in healthy women and suggest a need for larger studies in both genders to resolve outstanding uncertainties.

Expression of versican 3'-untranslated region modulates endogenous microRNA functions.

Science.gov (United States)

Lee, Daniel Y; Jeyapalan, Zina; Fang, Ling; Yang, Jennifer; Zhang, Yaou; Yee, Albert Y; Li, Minhui; Du, William W; Shatseva, Tatiana; Yang, Burton B

2010-10-25

Mature microRNAs (miRNAs) are single-stranded RNAs that regulate post-transcriptional gene expression. In our previous study, we have shown that versican 3'UTR, a fragment of non-coding transcript, has the ability to antagonize miR-199a-3p function thereby regulating expression of the matrix proteins versican and fibronectin, and thus resulting in enhanced cell-cell adhesion and organ adhesion. However, the impact of this non-coding fragment on tumorigenesis is yet to be determined. Using computational prediction confirmed with in vitro and in vivo experiments, we report that the expression of versican 3'UTR not only antagonizes miR-199a-3p but can also lower its steady state expression. We found that expression of versican 3'UTR in a mouse breast carcinoma cell line, 4T1, decreased miR-199a-3p levels. The decrease in miRNA activity consequently translated into differences in tumor growth. Computational analysis indicated that both miR-199a-3p and miR-144 targeted a cell cycle regulator, Rb1. In addition, miR-144 and miR-136, which have also been shown to interact with versican 3'UTR, was found to target PTEN. Expression of Rb1 and PTEN were up-regulated synergistically in vitro and in vivo, suggesting that the 3'UTR binds and modulates miRNA activities, freeing Rb1 and PTEN mRNAs for translation. In tumor formation assays, cells transfected with the 3'UTR formed smaller tumors compared with cells transfected with a control vector. Our results demonstrated that a 3'UTR fragment can be used to modulate miRNA functions. Our study also suggests that miRNAs in the cancer cells are more susceptible to degradation, due to its interaction with a non-coding 3'UTR. This non-coding component of mRNA may be used retrospectively to modulate miRNA activities.

Expression of versican 3'-untranslated region modulates endogenous microRNA functions.

Directory of Open Access Journals (Sweden)

Daniel Y Lee

Full Text Available BACKGROUND: Mature microRNAs (miRNAs are single-stranded RNAs that regulate post-transcriptional gene expression. In our previous study, we have shown that versican 3'UTR, a fragment of non-coding transcript, has the ability to antagonize miR-199a-3p function thereby regulating expression of the matrix proteins versican and fibronectin, and thus resulting in enhanced cell-cell adhesion and organ adhesion. However, the impact of this non-coding fragment on tumorigenesis is yet to be determined. METHODS AND FINDINGS: Using computational prediction confirmed with in vitro and in vivo experiments, we report that the expression of versican 3'UTR not only antagonizes miR-199a-3p but can also lower its steady state expression. We found that expression of versican 3'UTR in a mouse breast carcinoma cell line, 4T1, decreased miR-199a-3p levels. The decrease in miRNA activity consequently translated into differences in tumor growth. Computational analysis indicated that both miR-199a-3p and miR-144 targeted a cell cycle regulator, Rb1. In addition, miR-144 and miR-136, which have also been shown to interact with versican 3'UTR, was found to target PTEN. Expression of Rb1 and PTEN were up-regulated synergistically in vitro and in vivo, suggesting that the 3'UTR binds and modulates miRNA activities, freeing Rb1 and PTEN mRNAs for translation. In tumor formation assays, cells transfected with the 3'UTR formed smaller tumors compared with cells transfected with a control vector. CONCLUSION: Our results demonstrated that a 3'UTR fragment can be used to modulate miRNA functions. Our study also suggests that miRNAs in the cancer cells are more susceptible to degradation, due to its interaction with a non-coding 3'UTR. This non-coding component of mRNA may be used retrospectively to modulate miRNA activities.

Neurotrophin-3 Induces BMP-2 and VEGF Activities and Promotes the Bony Repair of Injured Growth Plate Cartilage and Bone in Rats.

Science.gov (United States)

Su, Yu-Wen; Chung, Rosa; Ruan, Chun-Sheng; Chim, Shek Man; Kuek, Vincent; Dwivedi, Prem P; Hassanshahi, Mohammadhossein; Chen, Ke-Ming; Xie, Yangli; Chen, Lin; Foster, Bruce K; Rosen, Vicki; Zhou, Xin-Fu; Xu, Jiake; Xian, Cory J

2016-06-01

Injured growth plate is often repaired by bony tissue causing bone growth defects, for which the mechanisms remain unclear. Because neurotrophins have been implicated in bone fracture repair, here we investigated their potential roles in growth plate bony repair in rats. After a drill-hole injury was made in the tibial growth plate and bone, increased injury site mRNA expression was observed for neurotrophins NGF, BDNF, NT-3, and NT-4 and their Trk receptors. NT-3 and its receptor TrkC showed the highest induction. NT-3 was localized to repairing cells, whereas TrkC was observed in stromal cells, osteoblasts, and blood vessel cells at the injury site. Moreover, systemic NT-3 immunoneutralization reduced bone volume at injury sites and also reduced vascularization at the injured growth plate, whereas recombinant NT-3 treatment promoted bony repair with elevated levels of mRNA for osteogenic markers and bone morphogenetic protein (BMP-2) and increased vascularization and mRNA for vascular endothelial growth factor (VEGF) and endothelial cell marker CD31 at the injured growth plate. When examined in vitro, NT-3 promoted osteogenesis in rat bone marrow stromal cells, induced Erk1/2 and Akt phosphorylation, and enhanced expression of BMPs (particularly BMP-2) and VEGF in the mineralizing cells. It also induced CD31 and VEGF mRNA in rat primary endothelial cell culture. BMP activity appears critical for NT-3 osteogenic effect in vitro because it can be almost completely abrogated by co-addition of the BMP inhibitor noggin. Consistent with its angiogenic effect in vivo, NT-3 promoted angiogenesis in metatarsal bone explants, an effect abolished by co-treatment with anti-VEGF. This study suggests that NT-3 may be an osteogenic and angiogenic factor upstream of BMP-2 and VEGF in bony repair, and further studies are required to investigate whether NT-3 may be a potential target for preventing growth plate faulty bony repair or for promoting bone fracture healing. © 2016

Spatial modulation of the Fermi level by coherent illumination of undoped GaAs

Science.gov (United States)

Nolte, D. D.; Olson, D. H.; Glass, A. M.

1989-11-01

The Fermi level in undoped GaAs has been modulated spatially by optically quenching EL2 defects. The spatial gradient of the Fermi level produces internal electric fields that are much larger than fields generated by thermal diffusion alone. The resulting band structure is equivalent to a periodic modulation-doped p-i-p structure of alternating insulating and p-type layers. The internal fields are detected via the electro-optic effect by the diffraction of a probe laser in a four-wave mixing geometry. The direct control of the Fermi level distinguishes this phenomenon from normal photorefractive behavior and introduces a novel nonlinear optical process.

Delft3D turbine turbulence module v. 1.0.0

Energy Technology Data Exchange (ETDEWEB)

2016-08-25

The DOE has funded Sandia National Labs (SNL) to develop an open-source modeling tool to guide the design and layout of marine hydrokinetic (MHK) arrays to maximize power production while minimizing environmental effects. This modeling framework simulates flows through and around a MHK arrays while quantifying environmental responses. As an augmented version of the Dutch company, Deltares’s, environmental hydrodynamics code, Delft3D, Delft3D-CEC includes a new module that simulates energy conversion (momentum withdrawal) by MHK current energy conversion devices with commensurate changes in the turbulent kinetic energy and its dissipation rate. The Following is a description of Deltares’s open-source code Delft3D from which Delft3D-CEC is built upon. “Delft3D is a world leading 3D modeling suite to investigate hydrodynamics, sediment transport and morphology and water quality for fluvial, estuarine and coastal environments. As per 1 January 2011, the Delft3D flow (FLOW), morphology (MOR) and waves (WAVE) modules are available in open source. The software is used and has proven his capabilities on many places around the world, like the Netherlands, USA, Hong Kong, Singapore, Australia, Venice, etc. The software is continuously improved and developed with innovating advanced modelling techniques as consequence of the research work of our institute and to stay world leading. The FLOW module is the heart of Delft3D and is a multi-dimensional (2D or 3D) hydrodynamic (and transport) simulation programme which calculates non-steady flow and transport phenomena resulting from tidal and meteorological forcing on a curvilinear, boundary fitted grid or sperical coordinates. In 3D simulations, the vertical grid is defined following the so-called sigma coordinate approach or Z-layer approach. The MOR module computes sediment transport (both suspended and bed total load) and morphological changes for an arbitrary number of cohesive and non-cohesive fractions. Both currents

Is there an additional benefit of serial NT-proBNP measurements in patients with stable chronic heart failure receiving individually optimized therapy?

Science.gov (United States)

Franke, Jennifer; Frankenstein, Lutz; Schellberg, Dieter; Bajrovic, Amer; Wolter, Jan Sebastian; Ehlermann, Philipp; Doesch, Andreas O; Nelles, Manfred; Katus, Hugo A; Zugck, Christian

2011-12-01

The role of serial NT-proBNP measurements in patients suffering from chronic systolic heart failure (CHF) who already receive individually optimized pharmacotherapy is still unresolved. NT-proBNP was assessed at baseline and at 6 months follow-up in 504 stable CHF patients treated with individually optimized pharmacotherapy. After assessment of clinical stability at 6 months, patients were followed up for at least 1 year. The combined primary endpoint was defined as death, hospitalization due to cardiac reasons or heart transplantation in 1-year follow-up. We stratified our patients according to two principles: first, a percent change of value (CV) between the first and second measurement of NT-proBNP and secondly, the transformed logarithm of NT-proBNP measured at 6 months. During the follow-up period of 1 year, 50 patients (9.9%) reached the combined primary endpoint. Stratification according to percentage CV was less accurate in predicting endpoint-free survival compared to a classification in categories of lnNT-proBNP measured at 6 months (ROC AUC = 0.615; 95% CI 0.525-0.70 vs. ROC AUC = 0.790; 95% CI 0.721-0.856, respectively). When entered into proportional hazard regression analysis, lnNT-proBNP measured at 6 months remained an independent predictor of the combined primary endpoint with an associated HR of 2.53 (95% CI 1.385-4.280). To date, this is the largest analysis of serial NT-proBNP measurements in patients with CHF receiving individually optimized medical therapy. These data suggest that a single NT-proBNP measurement after 6 months in stable clinical conditions may have higher predictive value than stratification of change in serial measurements.

12th Russia/CIS/Baltic/Japan Symposium on Ferroelectricity and 9th International Conference on Functional Materials and Nanotechnologies (RCBJSF–2014–FM and NT)

International Nuclear Information System (INIS)

Sternberg, Andris; Grinberga, Liga; Sarakovskis, Anatolijs; Rutkis, Martins

2015-01-01

The joint International Symposium RCBJSF–2014–FM and NT successfully has united two international events – 12th Russia/CIS/Baltic/Japan Symposium on Ferroelectricity (RCBJSF-12) and 9th International Conference Functional Materials and Nanotechnologies (FM and NT-2014). The RCBJSF symposium is a continuation of series of meetings on ferroelectricity, the first of which took place in Novosibirsk (USSR) in 1976. FM and NT conferences started in 2006 and have been organized by Institute of Solid State Physics, University of Latvia in Riga. In 2012 the International program committee decided to transform this conference into a traveling Baltic State conference and the FM and NT-2013 was organized by the Institute of Physics, University of Tartu, Estonia. In 2014 the joint international symposium RCBJSF–2014–FM and NT was organized by the Institute of Solid State Physics, University of Latvia and was part of Riga – 2014, the European Capital of Culture event. The purpose of the joint Symposium was to bring together scientists, students and high-level experts in solid state physics, materials science, engineering and related disciplines. The number of the registered participants from 26 countries was over 350. During the Symposium 128 high quality scientific talks (5 plenary, 42 invited, 81 oral) and over 215 posters were presented. All presentations were divided into 4 parallel sessions according to 4 main topics of the Symposium: Ferroelectricity, including ferroelectrics and multiferroics, pyroelectrics, piezoelectrics and actuators, integrated ferroelectrics, relaxors, phase transitions and critical phenomena. Multifunctional Materials, including theory, multiscale and multiphenomenal material modeling and simulation, advanced inorganic, organic and hybrid materials. Nanotechnologies, including progressive methods, technologies and design for production, investigation of nano- particles, composites, structures, thin films and coatings. Energy, including

Expression analysis of five tobacco EIN3 family members in relation to tissue-specific ethylene responses.

Science.gov (United States)

Rieu, I; Mariani, C; Weterings, K

2003-10-01

Ethylene induces different sets of genes in different tissues and at different stages of development. To investigate whether these differential responses are caused by differential expression of members of the EIN3 family transcription factors, five tobacco family members were isolated. They can be divided into three subgroups, which is probably due to the amphidiploid nature of tobacco. In phylogenetic analysis, each of the subgroups clustered with one of the three tomato EIL proteins and all NtEILs proved to be most homologous to Arabidopsis EIN3 and EIL1. Although organ-specific ethylene responses have been observed before, northern blot analysis showed that all NtEILs were expressed in all organs. To study differential NtEIL expression at the cellular level, in situ hybridization was used on the tobacco ovary. It was found that different ovary tissues displayed variable ethylene-induced expression of two ethylene-responsive marker genes. By contrast, no differences were found in expression level or tissue-specificity for any of the NtEILs in the ovary, before or after ethylene treatment. This indicates that the organ and tissue-specific ethylene responses are not caused by differential expression of NtEIL family members. These results support a model in which the developmental signals that regulate the tissue-specific responses are integrated with the ethylene signal downstream of a common primary ethylene-signalling pathway.

Levels of 2,3-diphosphoglycerate in Friend leukaemic cells.

Science.gov (United States)

Yeoh, G C

1980-05-08

Most cells are thought to contain trace amounts of 2,3-diphosphoglycerate (DPG), as it acts as a cofactor in the interconversion of 2-phosphoglycerate and 3-phosphoglycerate by the glycolytic enzyme phosphoglyceromutase. DPG is synthesized from 1,3-diphosphoglycerate by the action of diphosphoglycerate mutase. Lowry et al. reported levels of 29 mumol DPG per kg wet weight brain tissue which is approximately 3 pmol per 10(8) cells, assuming that 1 g of brain tissue contains 10(9) cells. In contrast, erythroid cells contain 50-100 nmol DPG per 10(8) cells, depending on the species and the stage of development. This is of the order of a 1,000-fold more DPG compared with non-erythroid cells. In red cells DPG concentration modulates the binding of oxygen to haemoglobin. I show here that erythroid precurser cells also contain markedly raised levels of DPG.

TiO2-NT electrodes modified with Ag and diamond like carbon (DLC) for hydrogen production by alkaline water electrolysis

Science.gov (United States)

Baran, Evrim; Baz, Zeynep; Esen, Ramazan; Yazici Devrim, Birgül

2017-10-01

In present work, the two-step anodization technique was applied for synthesis of TiO2 nanotube (NT). Silver and diamond like carbon (DLC) were coated on the surface of as prepared TiO2-NT using chemical reduction method and MW ECR plasma system. The morphology, composition and structure of the electrodes were examined by field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD). The results showed that Ag nanoparticles, having size in the range of 48-115 nm, are evenly distributed on the top, inside and outside surface of TiO2-NT and when DLC was coated on the surface of TiO2-NT and TiO2-NT-Ag, the top of nanotubes were partially open and the pore diameter of hexagonal structure decreased from 165 nm to of 38-80 nm. On the other hand, the microhardness test and contact angle measurements revealed that additions of Ag and diamond like carbon have a positive effect on the mechanical properties of TiO2-NT film. The electrocatalytic properties of the electrodes towards the hydrogen evolution reaction (HER) were investigated by the electrochemical measurements recorded in 1 M KOH solution. In addition, long-term durability of electrodes towards HER and the energy consumption of alkaline electrolysis were investigated. The energy requirement showed that while the deposition of silver provides approximately 14.95% savings of the energy consumption, the DLC coating causes increase in energy consumption.

System Level Design of a Continuous-Time Delta-Sigma Modulator for Portable Ultrasound Scanners

DEFF Research Database (Denmark)

Llimos Muntal, Pere; Færch, Kjartan; Jørgensen, Ivan Harald Holger

2015-01-01

In this paper the system level design of a continuous-time ∆Σ modulator for portable ultrasound scanners is presented. The overall required signal-to-noise ratio (SNR) is derived to be 42 dB and the sampling frequency used is 320 MHz for an oversampling ratio of 16. In order to match these requir......, based on high-level VerilogA simulations, the performance of the ∆Σ modulator versus various block performance parameters is presented as trade-off curves. Based on these results, the block specifications are derived.......In this paper the system level design of a continuous-time ∆Σ modulator for portable ultrasound scanners is presented. The overall required signal-to-noise ratio (SNR) is derived to be 42 dB and the sampling frequency used is 320 MHz for an oversampling ratio of 16. In order to match...

Synergistic effect of fluorination on molecular energy level modulation in highly efficient photovoltaic polymers.

Science.gov (United States)

Zhang, Maojie; Guo, Xia; Zhang, Shaoqing; Hou, Jianhui

2014-02-01

The synergistic effect of fluorination on molecular energy level modulation is realized by introducing fluorine atoms onto both the donor and the acceptor moieties in a D-A polymer, and as a result, the polymer solar cell device based on the trifluorinated polymer, PBT-3F, shows a high efficiency of 8.6%, under illumination of AM 1.5G, 100 mW cm(-) (2) . © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Grønt regnskab for boligområder

DEFF Research Database (Denmark)

Jensen, O.M.

Grønne regnskaber har vundet indpas i virksomheder, kommuner og boligområder. Med denne rapport foreligger der en model og en metode for opstilling af et grønt regnskab, der kan anvendes på alle typer af boliger, boligbebyggelser og boligområder. Et tilhørende regneark kan hjemtages på SBI´s hjem......´s hjemmeside 'www.sbi.dk', eller det kan opstilles ved hjælp af anvisningerne i rapporten. Rapporten henvender sig til alle, der arbejder med energiledelse, boligforvaltning, økologisk boligbyggeri, byfornyelse, miljødebat og Agenda 21-arbejde....

Modulation of microRNA activity by semi-microRNAs (smiRNAs

Directory of Open Access Journals (Sweden)

Isabelle ePlante

2012-06-01

Full Text Available The ribonuclease Dicer plays a central role in the microRNA pathway by catalyzing the formation of 19 to 24-nucleotide (nt long microRNAs. Subsequently incorporated into Ago2 effector complexes, microRNAs are known to regulate messenger RNA (mRNA translation. Whether shorter RNA species derived from microRNAs exist and play a role in mRNA regulation remains unknown. Here, we report the serendipitous discovery of a 12-nt long RNA species corresponding to the 5’ region of the microRNA let-7, and tentatively termed semi-microRNA, or smiRNA. Using a smiRNA derived from the precursor of miR-223 as a model, we show that 12-nt long smiRNA species are devoid of any direct mRNA regulatory activity, as assessed in a reporter gene activity assay in transfected cultured human cells. However, smiR-223 was found to modulate the ability of the microRNA from which it derives to mediate translational repression or cleavage of reporter mRNAs. Our findings suggest that smiRNAs may be generated along the microRNA pathway and participate to the control of gene expression by regulating the activity of the related full-length mature microRNA in vivo.

Need to Knowledge (NtK) Model: an evidence-based framework for generating technological innovations with socio-economic impacts.

Science.gov (United States)

Flagg, Jennifer L; Lane, Joseph P; Lockett, Michelle M

2013-02-15

Traditional government policies suggest that upstream investment in scientific research is necessary and sufficient to generate technological innovations. The expected downstream beneficial socio-economic impacts are presumed to occur through non-government market mechanisms. However, there is little quantitative evidence for such a direct and formulaic relationship between public investment at the input end and marketplace benefits at the impact end. Instead, the literature demonstrates that the technological innovation process involves a complex interaction between multiple sectors, methods, and stakeholders. The authors theorize that accomplishing the full process of technological innovation in a deliberate and systematic manner requires an operational-level model encompassing three underlying methods, each designed to generate knowledge outputs in different states: scientific research generates conceptual discoveries; engineering development generates prototype inventions; and industrial production generates commercial innovations. Given the critical roles of engineering and business, the entire innovation process should continuously consider the practical requirements and constraints of the commercial marketplace.The Need to Knowledge (NtK) Model encompasses the activities required to successfully generate innovations, along with associated strategies for effectively communicating knowledge outputs in all three states to the various stakeholders involved. It is intentionally grounded in evidence drawn from academic analysis to facilitate objective and quantitative scrutiny, and industry best practices to enable practical application. The Need to Knowledge (NtK) Model offers a practical, market-oriented approach that avoids the gaps, constraints and inefficiencies inherent in undirected activities and disconnected sectors. The NtK Model is a means to realizing increased returns on public investments in those science and technology programs expressly intended to

Differences in Natriuretic Peptide Levels by Race/Ethnicity (From the Multi-Ethnic Study of Atherosclerosis).

Science.gov (United States)

Gupta, Deepak K; Daniels, Lori B; Cheng, Susan; deFilippi, Christopher R; Criqui, Michael H; Maisel, Alan S; Lima, Joao A; Bahrami, Hossein; Greenland, Philip; Cushman, Mary; Tracy, Russell; Siscovick, David; Bertoni, Alain G; Cannone, Valentina; Burnett, John C; Carr, John Jeffrey; Wang, Thomas J

2017-09-15

Natriuretic peptides (NP) are cardiac-derived hormones with favorable cardiometabolic actions. Low NP levels are associated with increased risks of hypertension and diabetes mellitus, conditions with variable prevalence by race and ethnicity. Heritable factors underlie a significant proportion of the interindividual variation in NP concentrations, but the specific influences of race and ancestry are unknown. In 5597 individuals (40% white, 24% black, 23% Hispanic, and 13% Chinese) without prevalent cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis, multivariable linear regression and restricted cubic splines were used to estimate differences in serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels according to, ethnicity, and ancestry. Ancestry was determined using genetic ancestry informative markers. NT-proBNP concentrations differed significantly by race and ethnicity (black, median 43 pg/ml [interquartile range 17 to 94], Chinese 43 [17 to 90], Hispanic 53 [23 to 107], white 68 [34 to 136]; p = 0.0001). In multivariable models, NT-proBNP was 44% lower (95% confidence interval -48 to -40) in black and 46% lower (-50 to -41) in Chinese, compared with white individuals. Hispanic individuals had intermediate concentrations. Self-identified blacks and Hispanics were the most genetically admixed. Among self-identified black individuals, a 20% increase in genetic European ancestry was associated with 12% higher (1% to 23%) NT-proBNP. Among Hispanic individuals, genetic European and African ancestry were positively and negatively associated with NT-proBNP levels, respectively. In conclusion, NT-proBNP levels differ according to race and ethnicity, with the lowest concentrations in black and Chinese individuals. Racial and ethnic differences in NT-proBNP may have a genetic basis, with European and African ancestry associated with higher and lower NT-proBNP concentrations, respectively. Copyright © 2017 Elsevier Inc. All

Expression of Neurotrophin-3 and trkC following Focal Cerebral Ischemia in Adult Rat Brain with Treadmill Exercise

Directory of Open Access Journals (Sweden)

Jin-Young Chung

2017-01-01

Full Text Available Neurotrophin-3 (NT-3 is a neurotrophic factor that mainly binds to the tyrosine kinase C (trkC receptor. NT-3 has been shown to have neuroprotective effects in focal cerebral ischemia. Exercise also has ability to induce functional recovery in focal cerebral ischemia. However, the relationship between NT-3, its receptor trkC, and exercise has not been revealed. In this study, we assessed the expressions of NT-3 and trkC in focal cerebral ischemia. We also assessed the expression of NT-3 and trkC with treadmill exercise in focal cerebral ischemia. The results showed that, in a permanent middle cerebral artery occlusion rat model, exercise increased NT-3 and trkC expression. However, the patterns of expression of NT-3 and trkC at different time points varied. These results suggest that exercise-induced functional recovery in focal cerebral ischemia was related to NT-3 and trkC, but the role on times of NT-3 and trkC differed, although trkC is the receptor kinase for NT-3.

Diagnostic and prognostic value of N-terminal pro B-type natriuretic peptide (NT-proBNP) in patients with chronic aortic regurgitation.

Science.gov (United States)

Weber, Michael; Hausen, Michael; Arnold, Roman; Moellmann, Helge; Nef, Holger; Elsaesser, Albrecht; Mitrovic, Vesselin; Hamm, Christian

2008-07-21

BNP and its N-terminal fragment NT-proBNP have proven to be of diagnostic and prognostic value in patients with valvular aortic stenosis. Data regarding those biomarkers in patients with chronic aortic regurgitation (AR) are sparse. Thus it was the aim of the present study to evaluate the diagnostic and the long term prognostic value of NT-proBNP in patients presenting with AR. This study included 60 patients with isolated AR of varying severity (AR I mild, AR II moderate and AR III severe) and preserved left ventricular function. Patients were followed over a median period of 824 (770-921) days. NT-proBNP at baseline was related to disease severity and to functional status (161 (70-456) pg/ml in AR I, 226 (100-666) pg/ml in AR II and 1268 (522-5446) pg/ml in AR III (p=0.003)). Patients (n=6) experiencing an adverse event had higher NT-proBNP values at baseline as event free survivors (1271 (613-2992) pg/ml vs. 215 (92-534) pg/ml; p=0.034). The AUC of the ROC curve for NT-proBNP as a predictor for an adverse event was 0.76 (pvalue of 602 pg/ml. Consequently, in Kaplan-Meier analysis NT-proBNP values dichotomised at this cut-off were able to discriminate patients with an adverse outcome in the entire study group (Log rank 9.98, p=0.0016) and even better in the conservative group (Log rank 26.92, p<0.001). NT-proBNP is linked to disease severity in patients with chronic aortic regurgitation reflecting hemodynamic stress due to volume overload. It provides prognostic information for the clinical outcome and thus might be a useful biomarker for risk stratification.

The research and development of module 3D designing system for nuclear power project based on the PDMS

International Nuclear Information System (INIS)

Lu Qinwu; Li Yi; Wu Xiangyong

2012-01-01

In order to meet the demand of implementing Modularization design in CPR1000 nuclear power projects, this study aims to develop, relying on CPR1000 nuclear power project, the self-reliant module 3D design system based on the PDMS. so as to offer a convenient and effective module 3D design tool for the designers. Satisfactory results have been achieved through the test and application of two design projects. The research and application have entered the domestic advanced level. (authors)

A functional genetic variant (N521D in natriuretic peptide receptor 3 is associated with diastolic dysfunction: the prevalence of asymptomatic ventricular dysfunction study.

Directory of Open Access Journals (Sweden)

Naveen L Pereira

Full Text Available To evaluate the impact of a functional genetic variant in the natriuretic peptide clearance receptor, NPR3, on circulating natriuretic peptides (NPs and myocardial structure and function in the general community.NPR3 plays an important role in the clearance of NPs and through direct signaling mechanisms modulates smooth muscle cell function and cardiac fibroblast proliferation. A NPR3 nonsynonymous single nucleotide polymorphism (SNP rs2270915, resulting in a N521D substitution in the intracellular catalytic domain that interacts with Gi could affect receptor function. Whether this SNP is associated with alterations in NPs levels and altered cardiac structure and function is unknown.DNA samples of 1931 randomly selected residents of Olmsted County, Minnesota were genotyped. Plasma NT-proANP1-98, ANP1-28, proBNP1-108, NT-proBNP1-76, BNP1-32 and BNP3-32 levels were measured. All subjects underwent comprehensive echocardiography.Genotype frequencies for rs2270915 were as follows: (A/A 60%, A/G 36%, G/G 4%. All analyses performed were for homozygotes G/G versus wild type A/A plus the heterozygotes A/G. Diastolic dysfunction was significantly more common (p = 0.007 in the homozygotes G/G (43% than the A/A+A/G (28% group. Multivariate regression adjusted for age, sex, body mass index and hypertension demonstrated rs2270915 to be independently associated with diastolic dysfunction (odds ratio 1.94, p = 0.03. There was no significant difference in NPs levels between the 2 groups suggesting that the clearance function of the receptor was not affected.A nonsynonymous NPR3 SNP is independently associated with diastolic dysfunction and this association does not appear to be related to alterations in circulating levels of natriuretic peptides.

Characterization of the Transient Response of the ILS with One Module Installed to Heatup Changes in Power Level and Cooldown

International Nuclear Information System (INIS)

K. G. Condie; C. M. Stoots; J. E. O'Brien; J. S. Herring

2007-01-01

This report provides documentation of the initial startup and testing of the first electrolysis module in the Idaho National Laboratory (INL) High Temperature Steam Electrolysis Integrated Laboratory Scale (ILS) facility. Initial shakedown testing of the INL ILS experimental facility commenced on August 22, 2007. This fulfilled a DOE Level 2 milestone. Heatup of the first ILS module started at approximately 4:10 PM on September 24, 2007. Initial module testing continued for 420 hours. The test average H2 production rate was approximately 1.3 Nm3/hr (0.116 kg H2/hr), with a peak measured value of over 2 Nm3/hr (0.179 kg H2/hr). Significant module performance degradation was observed over the first 250 hours, after which no further degradation was noted for the remainder of the test. Once all test objectives had been successfully met, the test was terminated in a controlled fashion. Discussion is included concerning several modifications that will be incorporated into the facility components to improve reliability and ease of operation for future long term testing

∑∆ Modulator System-Level Considerations for Hearing-Aid Audio Class-D Output Stage Application

DEFF Research Database (Denmark)

Pracný, Peter; Bruun, Erik

2012-01-01

This paper deals with a system-level design of a digital sigma-delta (∑∆) modulator for hearing-aid audio Class D output stage application. The aim of this paper is to provide a thorough discussion on various possibilities and tradeoffs of ∑∆ modulator system-level design parameter combinations...... - order, oversampling ratio (OSR) and number of bits in the quantizer - including their impact on interpolation filter design as well. The system is kept in digital domain up to the input of the Class D power stage including the digital pulse width modulation (DPWM) block. Notes on the impact of the DPWM...

Amino-Terminal proB-Type Natriuretic Peptide Levels in the Umbilical Cord Blood of Neonates Differ According to the Type of Prenatally Diagnosed Congenital Heart Disease.

Science.gov (United States)

Bae, Jin Young; Cha, Hyun-Hwa; Seong, Won Joon

2015-12-01

The aim of this study was to investigate differences in amino-terminal proB-type natriuretic peptide (NT-proBNP) levels in the cord blood of neonates according to the type of congenital heart disease (CHD) and to evaluate the usefulness of NT-proBNP as a prognostic marker. We included 76 neonates with prenatally diagnosed CHD and 45 controls without CHD. Neonates were classified into five groups based on echocardiographic findings. The levels of NT-proBNP in the cord blood were examined and analyzed according to the neonatal outcomes. The levels of NT-proBNP were significantly elevated in the cord blood of neonates with CHD compared with that in the cord blood of controls. The levels of NT-proBNP in the group with right ventricular outflow tract obstruction without a ventricular septal defect were significantly increased compared to that in the other groups. The neonates that required acute surgical correction had higher levels of NT-proBNP in the cord blood, though they were not statistically significant. Meanwhile, NT-proBNP levels in the cord blood of neonates with functional single ventricle were significantly higher than that in the cord blood of those with functional biventricles. Significant differences in the levels of NT-proBNP between survivors and nonsurvivors were observed within 1 year of birth. In this study, we found that the levels of NT-proBNP in the cord blood of neonates with CHD were higher than the levels in controls. This finding was striking in the group with right ventricular outflow tract obstruction, and it was associated with surgery for functional single ventricle and 1-year survival.

Modulations of DNA Contacts by Linker Histones and Post-translational Modifications Determine the Mobility and Modifiability of Nucleosomal H3 Tails.

Science.gov (United States)

Stützer, Alexandra; Liokatis, Stamatios; Kiesel, Anja; Schwarzer, Dirk; Sprangers, Remco; Söding, Johannes; Selenko, Philipp; Fischle, Wolfgang

2016-01-21

Post-translational histone modifications and linker histone incorporation regulate chromatin structure and genome activity. How these systems interface on a molecular level is unclear. Using biochemistry and NMR spectroscopy, we deduced mechanistic insights into the modification behavior of N-terminal histone H3 tails in different nucleosomal contexts. We find that linker histones generally inhibit modifications of different H3 sites and reduce H3 tail dynamics in nucleosomes. These effects are caused by modulations of electrostatic interactions of H3 tails with linker DNA and largely depend on the C-terminal domains of linker histones. In agreement, linker histone occupancy and H3 tail modifications segregate on a genome-wide level. Charge-modulating modifications such as phosphorylation and acetylation weaken transient H3 tail-linker DNA interactions, increase H3 tail dynamics, and, concomitantly, enhance general modifiability. We propose that alterations of H3 tail-linker DNA interactions by linker histones and charge-modulating modifications execute basal control mechanisms of chromatin function. Copyright © 2016 Elsevier Inc. All rights reserved.

Adiponectin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction - an experimental study.

Science.gov (United States)

Fu, Mingqiang; Zhou, Jingmin; Qian, Juying; Jin, Xuejuan; Zhu, Hongmin; Zhong, Chunlin; Fu, Michael; Zou, Yunzeng; Ge, Junbo

2012-08-30

Adiponectin is reported to relate with cardiovascular diseases, we sought to examine whether adiponectin is associated with disease progression of heart failure from hypertension in rats in comparison with other known biomarkers and echocardiographic parameters. Spontaneously hypertensive rats (SHR, n = 35), aged 1 month, were used and followed up to 18 months. High frequency echocardiography was performed both at baseline and every 3 months thereafter. Moreover, serum levels of N-terminal pro-natriuretic peptide (NT-proBNP) and interleukin-6 (IL-6) as well as serum level and tissue expression of adiponectin were determined at the same time as echocardiography. The results clearly demonstrated time-dependent progression of hypertension and heart dysfunction as evidenced by gradually increased left ventricular mass index, NT-proBNP, IL-6 as well as gradually decreased cardiac function as assessed by echocardiography. Meanwhile, tissue and serum adiponectin decreased from 3 months and reached plateau until 12 months in parallel with decreasing of cardiac diastolic function. Thereafter, adiponectin levels increased prior to occurrence of systolic dysfunction. Adiponectin concentration is inversely related with NT-proBNP, IL-6 and E/E' (correlation coefficient (r) = -0.756 for NT-proBNP, p A and E'/A' (r = 0.683 for E/A, p = 0.001, 0.671 for E'/A', p = 0.001, respectively). No difference for adiponectin distribution among visceral adipose tissues was found. Adiponectin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction.

Development of Chemistry Triangle Oriented Module on Topic of Reaction Rate for Senior High School Level Grade XI Chemistry Learning.

Science.gov (United States)

Sari, D. R.; Hardeli; Bayharti

2018-04-01

This study aims to produce chemistry triangle oriented module on topic of reaction rate, and to reveal the validity and practicality level of the generated module. The type of research used is EducationalDesign Research (EDR) with development model is Plompmodel. This model consists of three phases, which are preliminary research, prototyping phase, and assessment phase. The instrument used in this research is questionnaire validity and practicality. The data of the research were analyzed by using Kappa Cohen formula. The chemistry triangle oriented module validation sheet was given to 5 validators consisting of 3 chemistry lecturers and 2 high school chemistry teachers, while the practicality sheet was given to 2 chemistry teachers, 6 students of SMAN 10 Padang grade XII MIA 5 on the small groupevaluation and 25 students of SMAN 10 Padang grade XII MIA 6 on the field test. Based on the questionnaire validity analysis, the validity level of the module is very high with the value of kappa moment 0.87. The level of practicality based on teacher questionnaire response is very high category with a kappa moment value 0.96. Based on the questionnaire of student responses on small group evaluation, the level of practicality is very high category with a kappa moment 0.81, and the practicality is very high category with kappa moment value 0.83 based on questionnaire of student response on field test.

Application of a Community eS@nté Platform in Maternal and Child ...

International Development Research Centre (IDRC) Digital Library (Canada)

Application of a Community eS@nté Platform in Maternal and Child Health in ... electronic patient files and telehealth can improve medical and healthcare data ... New website will help record vital life events to improve access to services for all.

Diurnal modulation due to self-interacting mirror and hidden sector dark matter

International Nuclear Information System (INIS)

Foot, R.

2012-01-01

Mirror and more generic hidden sector dark matter models can simultaneously explain the DAMA, CoGeNT and CRESST-II dark matter signals consistently with the null results of the other experiments. This type of dark matter can be captured by the Earth and shield detectors because it is self-interacting. This effect will lead to a diurnal modulation in dark matter detectors. We estimate the size of this effect for dark matter detectors in various locations. For a detector located in the northern hemisphere, this effect is expected to peak in April and can be detected for optimistic parameter choices. The diurnal variation is expected to be much larger for detectors located in the southern hemisphere. In particular, if the CoGeNT detector were moved to e.g. Sierra Grande, Argentina then a 5σ dark matter discovery would be possible in around 30 days of operation

Attention, working memory, and phenomenal experience of WM content: memory levels determined by different types of top-down modulation.

Science.gov (United States)

Jacob, Jane; Jacobs, Christianne; Silvanto, Juha

2015-01-01

What is the role of top-down attentional modulation in consciously accessing working memory (WM) content? In influential WM models, information can exist in different states, determined by allocation of attention; placing the original memory representation in the center of focused attention gives rise to conscious access. Here we discuss various lines of evidence indicating that such attentional modulation is not sufficient for memory content to be phenomenally experienced. We propose that, in addition to attentional modulation of the memory representation, another type of top-down modulation is required: suppression of all incoming visual information, via inhibition of early visual cortex. In this view, there are three distinct memory levels, as a function of the top-down control associated with them: (1) Nonattended, nonconscious associated with no attentional modulation; (2) attended, phenomenally nonconscious memory, associated with attentional enhancement of the actual memory trace; (3) attended, phenomenally conscious memory content, associated with enhancement of the memory trace and top-down suppression of all incoming visual input.

Modulation of the sound press level by the treatment of polymer diaphragms through ion implantation method

International Nuclear Information System (INIS)

Yeo, Sunmog; Park, Jaewon; Lee, Hojae

2010-01-01

We present two different surface modification treatments, an ion implantation, and an ion beam mixing, and show that the surface modifications caused by these treatments are useful tools to modulate the sound press level. The ion implantations on various polymer diaphragms cause an increase in the resonant frequency so that the sound press level is lowered at low frequencies. On the contrary, a Cu or Fe 2 O 3 coating by using an ion beam mixing method causes a decrease in the resonant frequency, resulting in a high sound press level at low frequencies. We discuss the physical reasons for the change in the sound press level due to the ion-implantation methods.

Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide Levels in Heart Failure Patients With and Without Atrial Fibrillation

DEFF Research Database (Denmark)

Kristensen, Søren Lund; Jhund, Pardeep S; Mogensen, Ulrik M

2017-01-01

BACKGROUND: Patients with heart failure (HF) and atrial fibrillation (AF) have higher circulating levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) than HF patients without AF. There is uncertainty about the prognostic importance of a given concentration of NT-proBNP in HF patients...... Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) or the ATMOSPHERE trial (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure), of whom 3575 (24%) had AF on their baseline ECG. Median (Q1, Q3) levels of NT-proBNP were 1817 pg/mL (1095......-3266 pg/mL) in those with AF and 1271 pg/mL (703-2569 pg/mL) in those without (PHeart Association class (III/IV; 36% versus 24%), and experienced fewer previous HF hospitalizations (52% versus 61%) or myocardial infarction (30...

Relative Importance of History of Heart Failure Hospitalization and N-Terminal Pro-B-Type Natriuretic Peptide Level as Predictors of Outcomes in Patients With Heart Failure and Preserved Ejection Fraction.

Science.gov (United States)

Kristensen, Søren L; Jhund, Pardeep S; Køber, Lars; McKelvie, Robert S; Zile, Michael R; Anand, Inder S; Komajda, Michel; Cleland, John G F; Carson, Peter E; McMurray, John J V

2015-06-01

The aim of this study was to investigate N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and recent heart failure (HF) hospitalization as predictors of future events in heart failure - preserved ejection fraction (HF-PEF). Recently, doubt has been expressed about the value of a history of HF hospitalization as a predictor of adverse cardiovascular outcomes in patients with HF and HF-PEF. We estimated rates and adjusted hazard ratios (HRs) for the composite endpoint of cardiovascular death or HF hospitalization, according to history of recent HF hospitalization and baseline NT-proBNP level in the I-PRESERVE (Irbesartan in Heart Failure with Preserved systolic function) trial. Rates of composite endpoints in patients with (n = 804) and without (n = 1,963) a recent HF hospitalization were 12.78 (95% confidence interval [CI]: 11.47 to 14.24) and 4.49 (95% CI: 4.04 to 4.99) per 100 person-years, respectively (HR: 2.71; 95% CI: 2.33 to 3.16). For patients with NT-proBNP concentrations >360 pg/ml (n = 1,299), the event rate was 11.51 (95% CI: 10.54 to 12.58) compared to 3.04 (95% CI: 2.63 to 3.52) per 100 person-years in those with a lower level of NT-proBNP (n = 1468) (HR: 3.19; 95% CI: 2.68 to 3.80). In patients with no recent HF hospitalization and NT-proBNP ≤360 pg/ml (n = 1,187), the event rate was 2.43 (95% CI: 2.03 to 2.90) compared with 17.79 (95% CI: 15.77 to 20.07) per 100 person-years when both risk predictors were present (n = 523; HR: 6.18; 95% CI: 4.96 to 7.69). Recent hospitalization for HF or an elevated level of NT-proBNP identified patients at higher risk for cardiovascular events, and this risk was increased further when both factors were present. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Expression of Versican 3′-Untranslated Region Modulates Endogenous MicroRNA Functions

Science.gov (United States)

Lee, Daniel Y.; Jeyapalan, Zina; Fang, Ling; Yang, Jennifer; Zhang, Yaou; Yee, Albert Y.; Li, Minhui; Du, William W.; Shatseva, Tatiana; Yang, Burton B.

2010-01-01

Background Mature microRNAs (miRNAs) are single-stranded RNAs that regulate post-transcriptional gene expression. In our previous study, we have shown that versican 3′UTR, a fragment of non-coding transcript, has the ability to antagonize miR-199a-3p function thereby regulating expression of the matrix proteins versican and fibronectin, and thus resulting in enhanced cell-cell adhesion and organ adhesion. However, the impact of this non-coding fragment on tumorigenesis is yet to be determined. Methods and Findings Using computational prediction confirmed with in vitro and in vivo experiments, we report that the expression of versican 3′UTR not only antagonizes miR-199a-3p but can also lower its steady state expression. We found that expression of versican 3′UTR in a mouse breast carcinoma cell line, 4T1, decreased miR-199a-3p levels. The decrease in miRNA activity consequently translated into differences in tumor growth. Computational analysis indicated that both miR-199a-3p and miR-144 targeted a cell cycle regulator, Rb1. In addition, miR-144 and miR-136, which have also been shown to interact with versican 3′UTR, was found to target PTEN. Expression of Rb1 and PTEN were up-regulated synergistically in vitro and in vivo, suggesting that the 3′UTR binds and modulates miRNA activities, freeing Rb1 and PTEN mRNAs for translation. In tumor formation assays, cells transfected with the 3′UTR formed smaller tumors compared with cells transfected with a control vector. Conclusion Our results demonstrated that a 3′UTR fragment can be used to modulate miRNA functions. Our study also suggests that miRNAs in the cancer cells are more susceptible to degradation, due to its interaction with a non-coding 3′UTR. This non-coding component of mRNA may be used retrospectively to modulate miRNA activities. PMID:21049042

Modulation-doped β-(Al0.2Ga0.8)2O3/Ga2O3 field-effect transistor

Science.gov (United States)

Krishnamoorthy, Sriram; Xia, Zhanbo; Joishi, Chandan; Zhang, Yuewei; McGlone, Joe; Johnson, Jared; Brenner, Mark; Arehart, Aaron R.; Hwang, Jinwoo; Lodha, Saurabh; Rajan, Siddharth

2017-07-01

Modulation-doped heterostructures are a key enabler for realizing high mobility and better scaling properties for high performance transistors. We report the realization of a modulation-doped two-dimensional electron gas (2DEG) at the β-(Al0.2Ga0.8)2O3/Ga2O3 heterojunction by silicon delta doping. The formation of a 2DEG was confirmed using capacitance voltage measurements. A modulation-doped 2DEG channel was used to realize a modulation-doped field-effect transistor. The demonstration of modulation doping in the β-(Al0.2Ga0.8)2O3/Ga2O3 material system could enable heterojunction devices for high performance electronics.

Effect of different cover crops on C and N cycling in sorghum NT systems.

Science.gov (United States)

Frasier, Ileana; Quiroga, Alberto; Noellemeyer, Elke

2016-08-15

In many no-till (NT) systems, residue input is low and fallow periods excessive, for which reasons soil degradation occurs. Cover crops could improve organic matter, biological activity, and soil structure. In order to study changes in soil carbon, nitrogen and microbial biomass a field experiment (2010-2012) was set up with sorghum (Sorghum bicolor Moench.) monoculture and with cover crops. Treatments were control (NT with bare fallow), rye (Secale cereale L.) (R), rye with nitrogen fertilization (R+N), vetch (Vicia villosa Roth.) (V), and rye-vetch mixture (VR) cover crops. A completely randomized block design with 4 replicates was used. Soil was sampled once a year at 0.06 and 0.12m depth for total C, microbial biomass carbon (MBC) and-nitrogen (MBN) determinations. Shoot and root biomass of sorghum and cover crops, litter biomass, and their respective carbon and nitrogen contents were determined. Soil temperatures at 0.06 and 0.12m depth, volumetric water contents and nitrate concentrations were determined at sowing, and harvest of each crop, and during sorghum's vegetative phase. NT led to a small increase in MBC and MBN, despite low litter and root biomass residue. Cover crops increased litter, root biomass, total C, MBC, and MBN. Relationships between MBC, MBN, and root-C and -N adjusted to logistic models (R(2)=0.61 and 0.43 for C and N respectively). Litter cover improved soil moisture to 45-50% water filled pore space and soil temperatures not exceeding 25°C during the warmest month. Microbial biomass stabilized at 20.1gCm(-2) and 1.9gNm(-2) in the upper 0.06m. Soil litter disappearance was a good indicator of mineral N availability. These findings support the view that cover crops, specifically legumes in NT systems can increase soil ecosystem services related to water and carbon storage, habitat for biodiversity, and nutrient availability. Copyright © 2016 Elsevier B.V. All rights reserved.

A wafer-level 3D packaging structure with Benzocyclobutene as a dielectric for multichip module fabrication

International Nuclear Information System (INIS)

Geng Fei; Ding Xiaoyun; Xu Gaowei; Luo Le

2009-01-01

A new wafer-level 3D packaging structure with Benzocyclobutene (BCB) as interlayer dielectrics (ILDs) for multichip module fabrication is proposed for application in the Ku-band wave. The packaging structure consists of two layers of BCB films and three layers of metallized films, in which the monolithic microwave IC (MMIC), thin film resistors, striplines and microstrip lines are integrated. Wet etched cavities fabricated on the silicon substrate are used for mounting active and passive components. BCB layers cover the components and serve as ILDs for interconnections. Gold bumps are used as electric interconnections between different layers, which eliminates the need to prepare vias by costly dry etching and deposition processes. In order to get high-quality BCB films for the subsequent chemical mechanical planarization (CMP) and multilayer metallization processes, the BCB curing profile is optimized and the roughness of the BCB film after the CMP process is kept lower than 10 nm. The thermal, mechanical and electrical properties of the packaging structure are investigated. The thermal resistance can be controlled below 2 0 C/W. The average shear strength of the gold bumps on the BCB surface is around 70 N/mm 2 . The performances of MMIC and interconnection structure at high frequencies are optimized and tested. The S-parameters curves of the packaged MMIC shift slightly showing perfect transmission character. The insertion loss change after the packaging process is less than 1 dB range at the operating frequency and the return loss is less than -8 dB from 10 to 15 GHz.

N-Acetyl Cysteine Protects against Methamphetamine-Induced Dopaminergic Neurodegeneration via Modulation of Redox Status and Autophagy in Dopaminergic Cells

Directory of Open Access Journals (Sweden)

Prashanth Chandramani Shivalingappa

2012-01-01

Full Text Available Methamphetamine- (MA- induced neurotoxicity is associated with mitochondrial dysfunction and enhanced oxidative stress. Our previous study demonstrated that MA induces autophagy in a dopaminergic neuronal cell model (N27 cells. The cellular mechanisms underlying MA-induced autophagy and apoptosis remain poorly characterized. In the present study we sought to investigate the importance of GSH redox status in MA-induced neurotoxicity using a thiol antioxidant, N-acetylcysteine (NAC. Morphological and biochemical analysis revealed that MA-induced autophagy in N27 dopaminergic cells was associated with pronounced depletion of GSH levels. Moreover, pretreatment with NAC reduced MA-induced GSH depletion and autophagy, while depletion of GSH using L-buthionine sulfoximine (L-BSO enhanced autophagy. Furthermore, treatment with NAC significantly attenuated MA-induced apoptotic cell death as well as oxidative stress markers, namely, 3-nitrotyrosine (3-NT and 4-hydroxynonenal (4-HNE. Together, these results suggest that NAC exhibits significant protective effects against MA-induced dopaminergic cell death, presumably via modulation of the GSH level and autophagy. Collectively, our data provide mechanistic insights into the role of cellular GSH redox status in MA-induced autophagy and apoptotic cell death, and additional studies are needed to determine the therapeutic effectiveness of cellular redox modifiers in attenuating dopaminergic neurodegeneration in vivo.

Effect of neurotrophin-3 precursor on glutamate-induced calcium homeostasis deregulation in rat cerebellum granule cells.

Science.gov (United States)

Safina, Dina R; Surin, Alexander M; Pinelis, Vsevolod G; Kostrov, Sergey V

2015-12-01

Neurotrophin-3 (NT-3) belongs to the family of highly conserved dimeric growth factors that controls the differentiation and activity of various neuronal populations. Mammals contain both the mature (NT-3) and the precursor (pro-NT-3) forms of neurotrophin. Members of the neurotrophin family are involved in the regulation of calcium homeostasis in neurons; however, the role of NT-3 and pro-NT-3 in this process remains unclear. The current study explores the effects of NT-3 and pro-NT-3 on disturbed calcium homeostasis and decline of mitochondrial potential induced by a neurotoxic concentration of glutamate (Glu; 100 µM) in the primary culture of rat cerebellar granule cells. In this Glu excitotoxicity model, mature NT-3 had no effect on the induced changes in Ca²⁺ homeostasis. In contrast, pro-NT-3 decreased the period of delayed calcium deregulation (DCD) and concurrent strong mitochondrial depolarization. According to the amplitude of the increase in the intracellular free Ca²⁺ concentration ([Ca²⁺]i ) and Fura-2 fluorescence quenching by Mn²⁺ within the first 20 sec of exposure to Glu, pro-NT-3 had no effect on the initial rate of Ca²⁺ entry into neurons. During the lag period preceding DCD, the mean amplitude of [Ca²⁺]i rise was 1.2-fold greater in the presence of pro-NT-3 than in the presence of Glu alone (1.67 ±  0.07 and 1.39 ± 0.04, respectively, P < 0.05). The Glu-induced changes in Са²⁺ homeostasis in the presence of pro-NT-3 likely are due to the decreased rate of Са²⁺ removal from the cytosol during the DCD latency period. © 2015 Wiley Periodicals, Inc.

Hippocalcin Is Required for Astrocytic Differentiation through Activation of Stat3 in Hippocampal Neural Precursor Cells.

Directory of Open Access Journals (Sweden)

Min-Jeong Kang

2016-10-01

Full Text Available Hippocalcin (Hpca is a neuronal calcium sensor protein expressed in the mammalian brain. However, its function in neural stem/precursor cells has not yet been studied. Here, we clarify the function of Hpca in astrocytic differentiation in hippocampal neural precursor cells (HNPCs. When we overexpressed Hpca in HNPCs in the presence or absence of bFGF, expression levels of nerve-growth factors such as neurotrophin-3 (NT-3, neurotrophin-4/5 (NT-4/5 and brain-derived neurotrophic factor (BDNF, together with the proneural basic helix loop helix (bHLH transcription factors neuroD and neurogenin 1 (ngn1, increased significantly. In addition, there was an increase in the number of cells expressing glial fibrillary acidic protein (GFAP, an astrocyte marker, and in dendrite outgrowth, indicating astrocytic differentiation of the HNPCs. Downregulation of Hpca by transfection with Hpca siRNA reduced expression of NT-3, NT-4/5, BDNF, neuroD and ngn1 as well as levels of GFAP protein. Furthermore, overexpression of Hpca increased the phosphorylation of STAT3 (Ser727, and this effect was abolished by treatment with a STAT3 inhibitor (S3I-201, suggesting that STAT3 (Ser727 activation is involved in Hpca-mediated astrocytic differentiation. As expected, treatment with Stat3 siRNA or STAT3 inhibitor caused a complete inhibition of astrogliogenesis induced by Hpca overexpression. Taken together, this is the first report to show that Hpca, acting through Stat3, has an important role in the expression of neurotrophins and proneural bHLH transcription factors, and that it is an essential regulator of astrocytic differentiation and dendrite outgrowth in HNPCs.

Apolipoprotein E Genotype-Dependent Paradoxical Short-Term Effects of 56Fe Irradiation on the Brain

International Nuclear Information System (INIS)

Haley, Gwendolen E.; Villasana, Laura; Dayger, Catherine; Davis, Matthew J.; Raber, Jacob

2012-01-01

Purpose: In humans, apolipoprotein E (apoE) is encoded by three major alleles (ε2, ε3, and ε4) and, compared to apoE3, apoE4 increases the risk of developing Alzheimer disease and cognitive impairments following various environmental challenges. Exposure to irradiation, including that of 56 Fe, during space missions poses a significant risk to the central nervous system, and apoE isoform might modulate this risk. Methods and Materials: We investigated whether apoE isoform modulates hippocampus-dependent cognitive performance starting 2 weeks after 56 Fe irradiation. Changes in reactive oxygen species (ROS) can affect cognition and are induced by irradiation. Therefore, after cognitive testing, we assessed hippocampal ROS levels in ex vivo brain slices, using the ROS-sensitive fluorescent probe, dihydroethidium (DHE). Brain levels of 3-nitrotyrosine (3-NT), CuZn superoxide dismutase (CuZnSOD), extracellular SOD, and apoE were assessed using Western blotting analysis. Results: In the water maze, spatial memory retention was impaired by irradiation in apoE2 and apoE4 mice but enhanced by irradiation in apoE3 mice. Irradiation reduced DHE-oxidation levels in the enclosed blade of the dentate gyrus and levels of 3-NT and CuZnSOD in apoE2 but not apoE3 or apoE4 mice. Finally, irradiation increased apoE levels in apoE3 but not apoE2 or apoE4 mice. Conclusions: The short-term effects of 56 Fe irradiation on hippocampal ROS levels and hippocampus-dependent spatial memory retention are apoE isoform-dependent.

Mating of the stichotrichous ciliate Oxytricha trifallax induces production of a class of 27 nt small RNAs derived from the parental macronucleus.

Directory of Open Access Journals (Sweden)

Alan M Zahler

Full Text Available Ciliated protozoans possess two types of nuclei; a transcriptionally silent micronucleus, which serves as the germ line nucleus, and a transcriptionally active macronucleus, which serves as the somatic nucleus. The macronucleus is derived from a new diploid micronucleus after mating, with epigenetic information contributed by the parental macronucleus serving to guide the formation of the new macronucleus. In the stichotrichous ciliate Oxytricha trifallax, the macronuclear DNA is highly processed to yield gene-sized nanochromosomes with telomeres at each end. Here we report that soon after mating of Oxytricha trifallax, abundant 27 nt small RNAs are produced that are not present prior to mating. We performed next generation sequencing of Oxytricha small RNAs from vegetative and mating cells. Using sequence comparisons between macronuclear and micronuclear versions of genes, we found that the 27 nt RNA class derives from the parental macronucleus, not the developing macronucleus. These small RNAs are produced equally from both strands of macronuclear nanochromosomes, but in a highly non-uniform distribution along the length of the nanochromosome, and with a particular depletion in the 30 nt telomere-proximal positions. This production of small RNAs from the parental macronucleus during macronuclear development stands in contrast to the mechanism of epigenetic control in the distantly related ciliate Tetrahymena. In that species, 28-29 nt scanRNAs are produced from the micronucleus and these micronuclear-derived RNAs serve as epigenetic controllers of macronuclear development. Unlike the Tetrahymena scanRNAs, the Oxytricha macronuclear-derived 27 mers are not modified by 2'O-methylation at their 3' ends. We propose models for the role of these "27macRNAs" in macronuclear development.

Experimental results of a 3 k Wh thermochemical heat storage module for space heating application

NARCIS (Netherlands)

Finck, C.J.; Henquet, E.M.R.; Soest, C.F.L. van; Oversloot, H.P.; Jong, A.J. de; Cuypers, R.; Spijker, J.C. van 't

2014-01-01

A 3 kWh thermochemical heat storage (TCS) module was built as part of an all-in house system implementation focusing on space heating application at a temperature level of 40 ºC and a temperature lift of 20 K. It has been tested and measurements showed a maximum water circuit temperature span

Effect of controlled release of brain-derived neurotrophic factor and neurotrophin-3 from collagen gel on neural stem cells.

Science.gov (United States)

Huang, Fei; Wu, Yunfeng; Wang, Hao; Chang, Jun; Ma, Guangwen; Yin, Zongsheng

2016-01-20

This study aimed to examine the effect of controlled release of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) from collagen gel on rat neural stem cells (NSCs). With three groups of collagen gel, BDNF/collagen gel, and NT-3/collagen gel as controls, BDNF and NT-3 were tested in the BDNF-NT-3/collagen gel group at different time points. The enzyme-linked immunosorbent assay results showed that BDNF and NT-3 were steadily released from collagen gels for 10 days. The cell viability test and the bromodeoxyuridine incorporation assay showed that BDNF-NT-3/collagen gel supported the survival and proliferation of NSCs. The results also showed that the length of processes was markedly longer and differentiation percentage from NSCs into neurons was much higher in the BDNF-NT-3/collagen gel group than those in the collagen gel, BDNF/collagen gel, and NT-3/collagen gel groups. These findings suggest that BDNF-NT-3/collagen gel could significantly improve the ability of NSCs proliferation and differentiation.

Effect of modulated ultrahigh frequency field on behavior and hormone level in female rats under emotional stress

Energy Technology Data Exchange (ETDEWEB)

Rasulov, M.M.

The effect of a modulated electromagnetic field (MEMF) (field frequency of 40 MHz and modulated frequency of 50 Hz, 1 h exposure daily for 30 days) on behavior and level of sexual hormones, determined from the length of the estrous cycle and of its separate phases, was studied in female Wistar rats subjected to sexual deprivation. The ratio of frequency of running to number of vertical positions (R:V) was used as an index. Activity of rats declined during the 1-h exposure to MEMF; this may indicate the direct effect of MEMF on the central nervous system. Analysis of behavior after MEMF treatments ceased showed that the R:V ratio increased from 3.2:1 to 3:1 in month 3 and reached 2:1 in month 5. The relative significance of sexual behavior (lordosis, licking of perineum) more than double in comparison with the initial level. The findings support the existence of individual differences in sensitivity to a UHF field. The data on the estrous cycle indicate the tranquilizing effect of a UHF field on the neuroendocrine system and the greater resistance of individual animals exposed to MEMF to the development of sexual neurosis. 12 references, 2 figures.

BAG3 down-modulation sensitizes HPV18(+) HeLa cells to PEITC-induced apoptosis and restores p53.

Science.gov (United States)

Cotugno, Roberta; Basile, Anna; Romano, Elena; Gallotta, Dario; Belisario, Maria Antonietta

2014-11-28

BAG3 is a multi-functional component of tumor cell pro-survival machinery, and its biological functions have been largely associated to proteasome system. Here, we show that BAG3 down-modulation resulted in reduced cell viability and enhanced PEITC-induced apoptosis largely more extensively in HeLa (HPV18(+)) rather than in C33A (HPV(-)) cervical carcinoma cell lines. Moreover, we demonstrate that BAG3 suppression led to a decrease of viral E6 oncoprotein and a concomitant recovery of p53 tumor suppressor, the best recognized target of E6 for proteasome degradation. E6 and p53 expression were modulated at protein level, since their respective mRNAs were unaffected. Taken together our findings reveal a novel role for BAG3 as host protein contributing to HPV18 E6-activated pro-survival strategies, and suggest a possible relevance of its expression levels in drug/radiotherapy-resistance of HPV18-bearing cervical carcinomas. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Modulation cues influence binaural masking-level difference in masking-pattern experiments.

Science.gov (United States)

Nitschmann, Marc; Verhey, Jesko L

2012-03-01

Binaural masking patterns show a steep decrease in the binaural masking-level difference (BMLD) when masker and signal have no frequency component in common. Experimental threshold data are presented together with model simulations for a diotic masker centered at 250 or 500 Hz and a bandwidth of 10 or 100 Hz masking a sinusoid interaurally in phase (S(0)) or in antiphase (S(π)). Simulations with a binaural model, including a modulation filterbank for the monaural analysis, indicate that a large portion of the decrease in the BMLD in remote-masking conditions may be due to an additional modulation cue available for monaural detection. © 2012 Acoustical Society of America

X-ray diffraction studies on merohedrally twinned Δ1–62NtNBCe1-A crystals of the sodium/bicarbonate cotransporter

International Nuclear Information System (INIS)

Gill, Harindarpal S.; Dutcher, Lauren; Boron, Walter F.; Patel, Samir; Guay-Woodford, Lisa M.

2013-01-01

A truncated mutant missing the first 62 residues of the N-terminal, cytoplasmic domain of the sodium-bicarbonate NBCe1-A cotransporter crystallizes in space group P3 1 with pseudo-P3 1 21 symmetry and a hemihedral twin fraction of 33.0%. Twinned fractions and twin-pair statistics over binned resolutions confirm that the calculated twin fraction is associated with hemihedral twinning and not to non-crystallographic symmetry. NBCe1-A membrane-embedded macromolecules that cotransport sodium and bicarbonate ions across the bilayer serve to maintain acid–base homeostasis throughout the body. Defects result in a number of renal and eye disorders, including type-II renal tubular acidosis and cataracts. Here, crystals of a human truncated mutant of the cytoplasmic N-terminal domain of NBCe1 (Δ1–62NtNBCe1-A) are reported that diffract X-rays to 2.4 Å resolution. The crystal symmetry of Δ1–62NtNBCe1-A is of space group P3 1 with pseudo-P3 1 21 symmetry and it has a hemihedral twin fraction of 33.0%. The crystals may provide insight into the pathogenic processes observed in a subset of patients with truncating and point mutations in the gene encoding NBCe1

Measurement of intraocular pressure using the NT-4000: a new non-contact tonometer equipped with pulse synchronous measurement function.

Science.gov (United States)

Yaoeda, Kiyoshi; Shirakashi, Motohiro; Fukushima, Atsushi; Funaki, Shigeo; Funaki, Haruko; Ofuchi, Nobutaka; Nakatsue, Tomoko; Abe, Haruki

2005-06-01

NT-4000 (Nidek Co. Ltd., Gamagori, Japan) is a new non-contact tonometer (NCT) equipped with pulse synchronous measurement function that can measure intraocular pressure (IOP) synchronized with the ocular pulse. The purpose of this study was to evaluate the usefulness of NT-4000 in normal subjects and in patients with glaucoma and ocular hypertension. This study included 175 eyes of 175 subjects. Firstly, the IOP was measured using NT-4000 without the pulse synchronous measurement function (NTn). Secondly, the IOP at peak, middle, and trough phases of the pulse signal were measured using NT-4000 with the pulse synchronous measurement function (NTp, NTm, NTt, respectively). Additionally, the IOP was measured with Goldmann applanation tonometer (GT). The coefficient of variation (CV) of three readings in the NCT measurements was used to evaluate the intra-session reproducibility. Statistical comparisons were performed using Wilcoxon signed rank test and one-way analysis of variance with Scheffe's test. Linear regression analysis was used to calculate correlation coefficients. P values less than 0.05 were accepted as statistically significant. The CV of NTn, NTp, NTm, and NTt were 6.4%, 5.5%, 4.9%, and 5.2%, respectively. The CV of NTp, NTm, and NTt were significantly smaller than that of NTn (P = 0.007, P < 0.001, P < 0.001, respectively). NTp was significantly higher than NTt (P = 0.038). GT was significantly correlated with NTn, NTp, NTm, and NTt (r = 0.898, P < 0.001; r = 0.912, P < 0.001; r = 0.908, P < 0.001; r = 0.900, P < 0.001, respectively). NT-4000 can detect the fluctuation of IOP associated with the ocular pulse.

Modulation of C. elegans Touch Sensitivity Is Integrated at Multiple Levels

Science.gov (United States)

Chen, Xiaoyin

2014-01-01

Sensory systems can adapt to different environmental signals. Here we identify four conditions that modulate anterior touch sensitivity in Caenorhabditis elegans after several hours and demonstrate that such sensory modulation is integrated at multiple levels to produce a single output. Prolonged vibration involving integrin signaling directly sensitizes the touch receptor neurons (TRNs). In contrast, hypoxia, the dauer state, and high salt reduce touch sensitivity by preventing the release of long-range neuroregulators, including two insulin-like proteins. Integration of these latter inputs occurs at upstream neurohormonal cells and at the insulin signaling cascade within the TRNs. These signals and those from integrin signaling converge to modulate touch sensitivity by regulating AKT kinases and DAF-16/FOXO. Thus, activation of either the integrin or insulin pathways can compensate for defects in the other pathway. This modulatory system integrates conflicting signals from different modalities, and adapts touch sensitivity to both mechanical and non-mechanical conditions. PMID:24806678

A graphene oxide based fluorescence resonance energy transfer (FRET) biosensor for ultrasensitive detection of botulinum neurotoxin A (BoNT/A) enzymatic activity.

Science.gov (United States)

Shi, Jingyu; Guo, Jiubiao; Bai, Gongxun; Chan, Chunyu; Liu, Xuan; Ye, Weiwei; Hao, Jianhua; Chen, Sheng; Yang, Mo

2015-03-15

Botulinum neurotoxins (BoNTs) are among the most potent toxic bacterial proteins for humans, which make them potential agents for bioterrorism. Therefore, an ultrasensitive detection of BoNTs and their active states is in great need as field-deployable systems for anti-terrorism applications. We report the construction of a novel graphene oxide (GO)-peptide based fluorescence resonance energy transfer (FRET) biosensor for ultrasensitive detection of the BoNT serotype A light chain (BoNT-LcA) protease activity. A green fluorescence protein (GFP) modified SNAP-25 peptide substrate (SNAP-25-GFP) was optimally designed and synthesized with the centralized recognition/cleavage sites. This FRET platform was constructed by covalent immobilization of peptide substrate on GO with BSA passivation which have advantages of low non-specific adsorption and high stability in protein abundant solution. BoNT-LcA can specifically cleave SNAP-25-GFP substrate covalently immobilized on GO to release the fragment with GFP. Based on fluorescence signal recovery measurement, the target BoNT-LcA was detected sensitively and selectively with the linear detection range from 1fg/mL to 1pg/mL. The limit of detection (LOD) for BoNT-LcA is around 1fg/mL. Copyright © 2014 Elsevier B.V. All rights reserved.

In vitro non-viral murine pro-neurotrophin 3 gene transfer into rat bone marrow stromal cells.

Science.gov (United States)

Darabi, Shahram; Tiraihi, Taki; Delshad, AliReza; Sadeghizadeh, Majid; Khalil, Wisam; Taheri, Taher

2017-04-15

Neurotrophin 3 (NT-3) is an important factor for promoting prenatal neural development, as well as regeneration, axogenesis and plasticity in postnatal life. Therapy with NT-3 was reported to improve the condition of patients suffering from degenerative diseases and traumatic injuries, however, the disadvantage of NT-3 protein delivery is its short half-life, thus our alternative approach is the use of NT-3 gene therapy. In this study, the bone marrow stromal cells (BMSCs) were isolated from adult rats, cultured for 4 passages and transfected with either pEGFP-N1 or a constructed vector containing murine proNT-3 (pSecTag2/HygroB-murine proNT-3) using Lipofectamine 2000 followed by Hygromycin B (200mg/kg). The transfection efficiency of the transiently transfected BMSCs was evaluated using the green fluorescence protein containing vector (pEGFP-N1). A quantitative evaluation of the NT-3 expression of mRNA using real time qRT-PCR shows that there was double fold increase in NT-3 gene expression compared with non-transfected BMSCs, also, the culture supernatant yielded double fold increase in NT-3 using ELISA technique, the data were supported by immunoblotting technique. This suggests that the use of this transfection technique can be useful for gene therapy in different neurological disorders with neurodegenerative or traumatic origins. Copyright © 2017 Elsevier B.V. All rights reserved.

Striking similarity in the gene expression levels of individual Myc module members among ESCs, EpiSCs, and partial iPSCs.

Directory of Open Access Journals (Sweden)

Masataka Hirasaki

Full Text Available Predominant transcriptional subnetworks called Core, Myc, and PRC modules have been shown to participate in preservation of the pluripotency and self-renewality of embryonic stem cells (ESCs. Epiblast stem cells (EpiSCs are another cell type that possesses pluripotency and self-renewality. However, the roles of these modules in EpiSCs have not been systematically examined to date. Here, we compared the average expression levels of Core, Myc, and PRC module genes between ESCs and EpiSCs. EpiSCs showed substantially higher and lower expression levels of PRC and Core module genes, respectively, compared with those in ESCs, while Myc module members showed almost equivalent levels of average gene expression. Subsequent analyses revealed that the similarity in gene expression levels of the Myc module between these two cell types was not just overall, but striking similarities were evident even when comparing the expression of individual genes. We also observed equivalent levels of similarity in the expression of individual Myc module genes between induced pluripotent stem cells (iPSCs and partial iPSCs that are an unwanted byproduct generated during iPSC induction. Moreover, our data demonstrate that partial iPSCs depend on a high level of c-Myc expression for their self-renewal properties.

Nonstructural 3 Protein of Hepatitis C Virus Modulates the Tribbles Homolog 3/Akt Signaling Pathway for Persistent Viral Infection

Science.gov (United States)

Tran, Si C.; Pham, Tu M.; Nguyen, Lam N.; Park, Eun-Mee; Lim, Yun-Sook

2016-01-01

ABSTRACT Hepatitis C virus (HCV) infection often causes chronic hepatitis, liver cirrhosis, and ultimately hepatocellular carcinoma. However, the mechanisms underlying HCV-induced liver pathogenesis are still not fully understood. By transcriptome sequencing (RNA-Seq) analysis, we recently identified host genes that were significantly differentially expressed in cell culture-grown HCV (HCVcc)-infected cells. Of these, tribbles homolog 3 (TRIB3) was selected for further characterization. TRIB3 was initially identified as a binding partner of protein kinase B (also known as Akt). TRIB3 blocks the phosphorylation of Akt and induces apoptosis under endoplasmic reticulum (ER) stress conditions. HCV has been shown to enhance Akt phosphorylation for its own propagation. In the present study, we demonstrated that both mRNA and protein levels of TRIB3 were increased in the context of HCV replication. We further showed that promoter activity of TRIB3 was increased by HCV-induced ER stress. Silencing of TRIB3 resulted in increased RNA and protein levels of HCV, whereas overexpression of TRIB3 decreased HCV replication. By employing an HCV pseudoparticle entry assay, we further showed that TRIB3 was a negative host factor involved in HCV entry. Both in vitro binding and immunoprecipitation assays demonstrated that HCV NS3 specifically interacted with TRIB3. Consequently, the association of TRIB3 and Akt was disrupted by HCV NS3, and thus, TRIB3-Akt signaling was impaired in HCV-infected cells. Moreover, HCV modulated TRIB3 to promote extracellular signal-regulated kinase (ERK) phosphorylation, activator protein 1 (AP-1) activity, and cell migration. Collectively, these data indicate that HCV exploits the TRIB3-Akt signaling pathway to promote persistent viral infection and may contribute to HCV-mediated pathogenesis. IMPORTANCE TRIB3 is a pseudokinase protein that acts as an adaptor in signaling pathways for important cellular processes. So far, the functional involvement of

The technical standard IBAMA (NT01/11) and its applications in waste water treatment in offshore platforms; A NT/ 01/11 do IBAMA e suas aplicacoes no tratamento de efluentes nas plataformas offshore

Energy Technology Data Exchange (ETDEWEB)

Paravidino, Thadeu Crespo; Miocque, Andre; Oliveira, Cristiane Lopes de [Vicel Comercio e Industria e Servico Ltda., Rio de Janeiro, RJ (Brazil)

2012-07-01

This paper aims to present the technical standard IBAMA (NT01/11) as it applies to wastewater treatment projects in maritime exploration and production of oil and gas, and the solutions proposed by the company VICEL to meet with this standard and the other existing laws in force in Brazil. To meet these objectives, the paper covers the following topics: environmental legislation applicable to maritime enterprises of exploration and production of oil and gas operating in Brazil: concepts and definitions of MARPOL and CONAMA Resolution 357 (amended by CONAMA 430), Law 9966/2000 and NT01/11; PCP - Pollution Control Project required by IBAMA; the solutions proposed by VICEL - Gray Water Policy Management and Treatment System (GWTS). Throughout its development, this paper presents in detail the analysis of the gray water effluents generated on board of a drilling rig, and the results obtained with the installation of a prototype system for treating gray water (GWTS). Finally, this paper demonstrates that IBAMA NT01/11 regulation is intended to guide and create means for monitoring all maritime enterprises of exploration and production of oil and gas operating in Brazil, in order to promote the reduction of the pollution caused by their operation (ecological footprint), concludes as compulsory the treatment for the gray water generated on board, and presents VICEL solutions for the implementation of a waste management policy and the installation of a Gray Water Treatment System (GWTS). (author)

Space Vector Pulse Width Modulation Strategy for Single-Phase Three-Level CIC T-source Inverter

DEFF Research Database (Denmark)

Shults, Tatiana E.; Husev, Oleksandr O.; Blaabjerg, Frede

2016-01-01

This paper presents a novel space vector pulse-width modulation strategy for a single-phase three-level buck-boost inverter based on an impedance-source network. The case study system is based on T-source inverter with continuous input current. To demonstrate the improved performance of the inver......This paper presents a novel space vector pulse-width modulation strategy for a single-phase three-level buck-boost inverter based on an impedance-source network. The case study system is based on T-source inverter with continuous input current. To demonstrate the improved performance...... of the inverter, the strategy was compared the traditional pulse-width modulation. It is shown that the approach proposed has fewer switching states and does not suffer from neutral point misbalance....

Axin and GSK3- control Smad3 protein stability and modulate TGF- signaling.

Science.gov (United States)

Guo, Xing; Ramirez, Alejandro; Waddell, David S; Li, Zhizhong; Liu, Xuedong; Wang, Xiao-Fan

2008-01-01

The broad range of biological responses elicited by transforming growth factor-beta (TGF-beta) in various types of tissues and cells is mainly determined by the expression level and activity of the effector proteins Smad2 and Smad3. It is not fully understood how the baseline properties of Smad3 are regulated, although this molecule is in complex with many other proteins at the steady state. Here we show that nonactivated Smad3, but not Smad2, undergoes proteasome-dependent degradation due to the concerted action of the scaffolding protein Axin and its associated kinase, glycogen synthase kinase 3-beta (GSK3-beta). Smad3 physically interacts with Axin and GSK3-beta only in the absence of TGF-beta. Reduction in the expression or activity of Axin/GSK3-beta leads to increased Smad3 stability and transcriptional activity without affecting TGF-beta receptors or Smad2, whereas overexpression of these proteins promotes Smad3 basal degradation and desensitizes cells to TGF-beta. Mechanistically, Axin facilitates GSK3-beta-mediated phosphorylation of Smad3 at Thr66, which triggers Smad3 ubiquitination and degradation. Thr66 mutants of Smad3 show altered protein stability and hence transcriptional activity. These results indicate that the steady-state stability of Smad3 is an important determinant of cellular sensitivity to TGF-beta, and suggest a new function of the Axin/GSK3-beta complex in modulating critical TGF-beta/Smad3-regulated processes during development and tumor progression.

Extranodal NK/T-cell lymphoma, nasal type (ENKTL-NT): An update on epidemiology, clinical presentation, and natural history in North American and European cases

Science.gov (United States)

Haverkos, Bradley M.; Pan, Zenggang; Gru, Alejandro A.; Freud, Aharon G.; Rabinovitch, Rachel; Xu-Welliver, Meng; Otto, Brad; Barrionuevo, Carlos; Baiocchi, Robert A.; Rochford, Rosemary; Porcu, Pierluigi

2016-01-01

Extranodal NK/T-cell lymphoma, nasal type (ENKTL-NT) is an aggressive extranodal non-Hodgkin lymphoma most commonly occurring in East Asia and Latin America but with increasing incidence in the U.S. Data on epidemiology, disease presentation, and outcome for European and North American (“Western”) cases are very limited. We review published landmark clinical studies on ENKTL-NT in the West and report in detail recent data, including our institutional experience. We highlight key observations in its epidemiology, natural history, and trends in clinical management. In the U.S., ENKTL-NT is more common among Asian Pacific Islanders (API) and Hispanics compared to non-Hispanic whites. Published studies indicate less heterogeneity in clinical presentation in Western ENKTL-NT compared to Asian patients. While there is variation in age at diagnosis, presence of antecedent lymphoproliferative disorders, and outcomes among racial/ethnic groups, the universal association of ENKTL-NT with EBV and the poor response of this neoplasm to anthracycline-based therapy are consistent across all geographic areas. PMID:27778143

Personalising e-learning modules: targeting Rasmussen levels using XML.

Science.gov (United States)

Renard, J M; Leroy, S; Camus, H; Picavet, M; Beuscart, R

2003-01-01

The development of Internet technologies has made it possible to increase the number and the diversity of on-line resources for teachers and students. Initiatives like the French-speaking Virtual Medical University Project (UMVF) try to organise the access to these resources. But both teachers and students are working on a partly redundant subset of knowledge. From the analysis of some French courses we propose a model for knowledge organisation derived from Rasmussen's stepladder. In the context of decision-making Rasmussen has identified skill-based, rule-based and knowledge-based levels for the mental process. In the medical context of problem-solving, we apply these three levels to the definition of three students levels: beginners, intermediate-level learners, experts. Based on our model, we build a representation of the hierarchical structure of data using XML language. We use XSLT Transformation Language in order to filter relevant data according to student level and to propose an appropriate display on students' terminal. The model and the XML implementation we define help to design tools for building personalised e-learning modules.

Right ventricular function and N-terminal pro-brain natriuretic peptide levels in adult patients with simple dextro-transposition of the great arteries.

Science.gov (United States)

Martínez-Quintana, Efrén; Marrero-Negrín, Natalia; Gopar-Gopar, Silvia; Rodríguez-González, Fayna

2017-06-01

Dextro-transposition of the great arteries (d-TGA) patients is at high risk of developing right ventricular dysfunction and tricuspid regurgitation in adulthood. Determining the relation between echocardiographic parameters, N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels and the New York Heart Association (NYHA) functional class may help determining the best time to operate them. Patients with simple d-TGA operated in infancy with an atrial switch procedure (Mustard or Senning operation) were followed up in our Adult Congenital Heart Disease Unit. Analytical, echocardiographic, and clinical parameters were determined to evaluate the correlation between right echocardiographic ventricular function, NT-pro-BNP levels, and NYHA functional class. Twenty-four patients with d-TGA were operated in infancy of whom 17 alive patients had simple d-TGA. Nine patients had NT-pro-BNP levels lower than 200 pg/mL and eight patients were above 200 pg/mL. Patients with lower hemoglobin concentration, higher right ventricular diameter or under diuretic treatment showed significant higher NT-pro-BNP levels (above 200 pg/dL). The Spearman test showed a positive correlation between basal right ventricular diameter and tricuspid regurgitation with pro NT BNP levels (correlation coefficient of .624; P=.017 and .490; P=.046, respectively) and a negative correlation with the right ventricle fractional area change (-.508, P=.045). No correlation was seen between NT-pro-BNP levels and the rest of echocardiographic parameters or the NYHA functional class. NT-pro-BNP levels showed a positive correlation with basal right ventricular diameter and tricuspid regurgitation but not with NYHA association functional class in d-TGA patients. © 2017, Wiley Periodicals, Inc.

Coherence modulation at the photon-counting level: A new scheme for secure communication

International Nuclear Information System (INIS)

Rhodes, William T; Boughanmi, Abdellatif; Moreno, Yezid Torres

2016-01-01

When operated at the photon-counting level, coherence modulation can provide quantifiably secure binary signal transmission between two entities, security being based on the nonclonability of photons. (paper)

Association of a new FCN3 haplotype with high ficolin-3 levels in leprosy.

Science.gov (United States)

Andrade, Fabiana Antunes; Beltrame, Marcia Holsbach; Bini, Valéria Bumiller; Gonçalves, Letícia Boslooper; Boldt, Angelica Beate Winter; Messias-Reason, Iara Jose de

2017-02-01

Leprosy is a chronic inflammatory disease caused by Mycobacterium leprae that mainly affects the skin and peripheral nervous system, leading to a high disability rate and social stigma. Previous studies have shown a contribution of genes encoding products of the lectin pathway of complement in the modulation of the susceptibility to leprosy; however, the ficolin-3/FCN3 gene impact on leprosy is currently unknown. The aim of the present study was to investigate if FCN3 polymorphisms (rs532781899: g.1637delC, rs28362807: g.3524_3532insTATTTGGCC and rs4494157: g.4473C>A) and ficolin-3 serum levels play a role in the susceptibility to leprosy. We genotyped up to 190 leprosy patients (being 114 (60%) lepromatous), and up to 245 controls with sequence-specific PCR. We also measured protein levels using ELISA in 61 leprosy and 73 controls. FCN3 polymorphisms were not associated with disease, but ficolin-3 levels were higher in patients with FCN3 *2B1 (CinsA) haplotype (p = 0.032). Median concentration of ficolin-3 was higher in leprosy per se (26034 ng/mL, p = 0.005) and lepromatous patients (28295 ng/mL, p = 0.016) than controls (18231 ng/mL). In addition, high ficolin-3 levels (>33362 ng/mL) were more common in leprosy per se (34.4%) and in lepromatous patients (35.5%) than controls (19.2%; p = 0.045 and p = 0.047, respectively). Our results lead us to suggest that polymorphisms in the FCN3 gene cooperate to increase ficolin-3 concentration and that it might contribute to leprosy susceptibility by favoring M. leprae infection.

Intrinsic and extrinsic connections of Tet3 dioxygenase with CXXC zinc finger modules.

Directory of Open Access Journals (Sweden)

Nan Liu

Full Text Available Tet proteins are emerging as major epigenetic modulators of cell fate and plasticity. However, little is known about how Tet proteins are targeted to selected genomic loci in distinct biological contexts. Previously, a CXXC-type zinc finger domain in Tet1 was shown to bind CpG-rich DNA sequences. Interestingly, in human and mouse the Tet2 and Tet3 genes are adjacent to Cxxc4 and Cxxc10-1, respectively. The CXXC domains encoded by these loci, together with those in Tet1 and Cxxc5, identify a distinct homology group within the CXXC domain family. Here we provide evidence for alternative mouse Tet3 transcripts including the Cxxc10-1 sequence (Tet3(CXXC and for an interaction between Tet3 and Cxxc4. In vitro Cxxc4 and the isolated CXXC domains of Tet1 and Tet3(CXXC bind DNA substrates with similar preference towards the modification state of cytosine at a single CpG site. In vivo Tet1 and Tet3 isoforms with and without CXXC domain hydroxylate genomic 5-methylcytosine with similar activity. Relative transcript levels suggest that distinct ratios of Tet3(CXXC isoforms and Tet3-Cxxc4 complex may be present in adult tissues. Our data suggest that variable association with CXXC modules may contribute to context specific functions of Tet proteins.

[Expression of proBNP and NT-proBNP in Sudden Death of Coronary Heart Disease].

Science.gov (United States)

Zeng, Q; Sun, R F; Li, Z; Zhai, L Q; Liu, M Z; Guo, X J; Gao, C R

2017-10-01

To study the expression change of pro-brain natriuretic peptide （proBNP） and N-terminal pro-brain natriuretic peptide （NT-proBNP） in sudden death of coronary atherosclerotic heart disease, and to explore its application in forensic diagnosis. Myocardial and blood samples were collected from normal control group, sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group （20 cases in each group）. The expression of proBNP in myocardial samples were detected by immunohistochemical staining and Western blotting, and that of BNP mRNA were detected by reverse transcription PCR （RT-PCR）. The content of NT-proBNP in plasma were detected by ELISA. Immunohistochemical staining showed positive expression of proBNP in both sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group. There was no positive expression in normal control group. For sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group, the relative expression of proBNP protein and BNP mRNA in myocardial tissue and the NT-proBNP content in plasma were higher than that of normal control group （ P heart disease group was higher than that of single coronary stenosis group （ P heart disease and determine whether the sudden death due to coronary atherosclerotic heart disease. Copyright© by the Editorial Department of Journal of Forensic Medicine

PREFACE: International Conference on Functional Materials and Nanotechnologies 2013 (FM&NT2013)

Science.gov (United States)

Nõmmiste, Ergo; Kirm, Marco; Plank, Toomas

2013-12-01

The International Conference Functional Materials and Nanotechnologies (FM&NT - 2013) was held in Tartu, 21-24 April 2013 at the Dorpat Conference Centre. The conference was organised by Institute of Physics, University of Tartu. The FM&NT conference series was started in 2006 by scientists from the Institute of Solid State Physics, University of Latvia. It is an annual conference bringing together researchers from the whole world. The warm and open atmosphere of this scientific conference has turned it into event where people from different fields meet under the common name of functional materials and nanotechnology. It is particularly important for early stage scientists who are looking for new knowledge and contact with people from various fields. Our Latvian colleagues with their success in internationalization made us neighbouring Estonians so envious that we could not withstand proposing that we host the conference in every second year in Estonia. Actually this is in a way the continuation of the idea of the famous Baltic seminars which took place over several decades during the last century. Due to political constraints these seminars were only opened to scientist of the former Eastern European countries, but which were extremely popular and attracted attendees from over the whole Soviet Union. Much fruitful cooperation started from the initial personal contacts of scientists at these seminars held twice per year, once in Latvia and the second time in Estonia. At the last FM&NT 2012 conference, the decision was made that Institute of Physics, University of Tartu would organise the event in Tartu in 2013. Along with traditional topics such as multifunctional materials, nanomaterials, materials for sustainable energy applications and theory, this conference focused on studies using synchrotron radiation and other novel light sources. The number of registered participants from 21 countries was nearly 300. During the three days of the conference 14 invited, 45

Extranodal NK/T Cell Lymphoma, Nasal Type (ENKTL-NT): An Update on Epidemiology, Clinical Presentation, and Natural History in North American and European Cases.

Science.gov (United States)

Haverkos, Bradley M; Pan, Zenggang; Gru, Alejandro A; Freud, Aharon G; Rabinovitch, Rachel; Xu-Welliver, Meng; Otto, Brad; Barrionuevo, Carlos; Baiocchi, Robert A; Rochford, Rosemary; Porcu, Pierluigi

2016-12-01

Extranodal NK/T cell lymphoma, nasal type (ENKTL-NT) is an aggressive extranodal non-Hodgkin lymphoma most commonly occurring in East Asia and Latin America but with increasing incidence in the United States. Data on epidemiology, disease presentation, and outcome for European and North American ("Western") cases are very limited. We review published landmark clinical studies on ENKTL-NT in the West and report in detail recent data, including our institutional experience. We highlight key observations in its epidemiology, natural history, and trends in clinical management. In the USA, ENKTL-NT is more common among Asian Pacific Islanders (API) and Hispanics compared to non-Hispanic whites. Published studies indicate less heterogeneity in clinical presentation in Western ENKTL-NT compared to Asian patients. While there is variation in age at diagnosis, presence of antecedent lymphoproliferative disorders, and outcomes among racial/ethnic groups, the universal association of ENKTL-NT with EBV and the poor response of this neoplasm to anthracycline-based therapy is consistent across all geographic areas. Data on epidemiology, disease presentation, and clinical outcomes in mature T cell and NK cell (T/NK cell) neoplasms, including ENKTL-NT, in Europe and North America are very limited. As the classification and diagnostic characterization of the currently recognized T/NK cell lymphoma disease entities continue to evolve, gaps and inconsistencies in data reporting across different studies are being recognized. Despite these limitations, several studies from the USA suggest that the incidence of ENKTL-NT is higher in Asian Pacific Islanders (API) and non-white Hispanics and that outcomes may be worse in non-whites. However, the universal association of ENKTL-NT with Epstein-Barr virus (EBV) across all ethnic groups suggests a common pathogenesis. Given the overlap between the entities included in the category of T/NK cell neoplasms, there is a need to further define

Estradiol modulates functional brain organization during the menstrual cycle : an analysis of interhemispheric inhibition.

OpenAIRE

Weis, S.; Hausmann, M.; Stoffers, B.; Vohn, R.; Kellermann, T.; Sturm, W.

2008-01-01

According to the hypothesis of progesterone-mediated interhemispheric decoupling (Hausmann and Güntürkün, 2000), functional cerebral asymmetries (FCAs), which are stable in men and change during the menstrual cycle in women, are generated by interhemispheric inhibition of the dominant on the nondominant hemisphere. The change of lateralization during the menstrual cycle in women might indicate that sex hormones play an important role in modulating FCAs. We used functional magnetic resonance i...

Increased excitability of spinal pain reflexes and altered frequency-dependent modulation in the dopamine D3-receptor knockout mouse.

Science.gov (United States)

Keeler, Benjamin E; Baran, Christine A; Brewer, Kori L; Clemens, Stefan

2012-12-01

Frequency-dependent modulation and dopamine (DA) receptors strongly modulate neural circuits in the spinal cord. Of the five known DA receptor subtypes, the D3 receptor has the highest affinity to DA, and D3-mediated actions are mainly inhibitory. Using an animal model of spinal sensorimotor dysfunction, the D3 receptor knockout mouse (D3KO), we investigated the physiological consequences of D3 receptor dysfunction on pain-associated signaling pathways in the spinal cord, the initial integration site for the processing of pain signaling. In the D3KO spinal cord, inhibitory actions of DA on the proprioceptive monosynaptic stretch reflex are converted from depression to facilitation, but its effects on longer-latency and pain-associated reflex responses and the effects of FM have not been studied. Using behavioral approaches in vivo, we found that D3KO animals exhibit reduced paw withdrawal latencies to thermal pain stimulation (Hargreaves' test) over wild type (WT) controls. Electrophysiological and pharmacological approaches in the isolated spinal cord in vitro showed that constant current stimulation of dorsal roots at a pain-associated frequency was associated with a significant reduction in the frequency-dependent modulation of longer-latency reflex (LLRs) responses but not monosynaptic stretch reflexes (MSRs) in D3KO. Application of the D1 and D2 receptor agonists and the voltage-gated calcium-channel ligand, pregabalin, but not DA, was able to restore the frequency-dependent modulation of the LLR in D3KO to WT levels. Thus we demonstrate that nociception-associated LLRs and proprioceptive MSRs are differentially modulated by frequency, dopaminergics and the Ca(2+) channel ligand, pregabalin. Our data suggest a role for the DA D3 receptor in pain modulation and identify the D3KO as a possible model for increased nociception. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of Electroacupuncture at Governor Vessel Acupoints on Neurotrophin-3 in Rats with Experimental Spinal Cord Injury

Directory of Open Access Journals (Sweden)

Yu-ping Mo

2016-01-01

Full Text Available In an effort to explore new, noninvasive treatment options for spinal cord injuries (SCI, this study investigated the effects of electroacupuncture (EA for SCI rat models. SCI was induced by a modified Allen’s weight-drop method. We investigated the response of EA at Dazhui (GV 14 and Mingmen (GV 4 acupoints to understand the effects and mechanisms of EA in neuroprotection and neuronal function recovery after SCI. BBB testing was used to detect motor function of rats’ hind limbs among groups, and EA was shown to promote the recovery of SCI rats’ motor function. Nissl staining showed a restored neural morphology and an increase in the quantity of neurons after EA. Also, the antiapoptosis role was exposed by TUNEL staining. Western blotting analysis was used to determine the protein expression of neurotrophin-3 (NT-3 in spinal cord tissue. Compared to the sham group, the expression levels of NT-3 were significantly decreased and EA was shown to upregulate the expression of NT-3. The present study suggests that the role of EA in neuroprotection and dorsal neuronal function recovery after SCI in rats, especially EA stimulation at GV 14 and GV 4, can greatly promote neuronal function recovery, which may result from upregulating the expression of NT-3.

BNP and NT-proBNP, Predictors of 1-Year Mortality in Nursing Home Residents

NARCIS (Netherlands)

Barents, Maaike; Hillege, Hans H. L.; van der Horst, Iwan C. C.; de Boer, Rudolph A.; Koster, J.; Muskiet, Frits A. J.; de Jongste, Mike J. L.

2008-01-01

Objectives: To investigate 1-year mortality prediction of B type natriuretic peptide (BNP) and N terminal-proBNP (NT-proBNP) in institutionalized elderly with multiple morbidities. Design: Prospective cross-sectional study. Setting: One nursing home. Participants: Ninety-three residents (mean age 81

Module-level DC/DC conversion for photovoltaic systems

NARCIS (Netherlands)

Bergveld, H.J.; Büthker, D.; Castello, C.; Doorn, T.S.; Jong, de A.; van Otten, R.; Waal, de K.

2011-01-01

Photovoltaic (PV) systems are increasingly used to generate electrical energy from solar irradiance incident on PV modules. Each PV module is formed by placing a large amount of PV cells, typically 60, in series. The PV system is then formed by placing a number, typically 10–12, of PV modules in

Botulinum neurotoxin: a marvel of protein design.

Science.gov (United States)

Montal, Mauricio

2010-01-01

Botulinum neurotoxin (BoNT), the causative agent of botulism, is acknowledged to be the most poisonous protein known. BoNT proteases disable synaptic vesicle exocytosis by cleaving their cytosolic SNARE (soluble NSF attachment protein receptor) substrates. BoNT is a modular nanomachine: an N-terminal Zn(2+)-metalloprotease, which cleaves the SNAREs; a central helical protein-conducting channel, which chaperones the protease across endosomes; and a C-terminal receptor-binding module, consisting of two subdomains that determine target specificity by binding to a ganglioside and a protein receptor on the cell surface and triggering endocytosis. For BoNT, functional complexity emerges from its modular design and the tight interplay between its component modules--a partnership with consequences that surpass the simple sum of the individual component's action. BoNTs exploit this design at each step of the intoxication process, thereby achieving an exquisite toxicity. This review summarizes current knowledge on the structure of individual modules and presents mechanistic insights into how this protein machine evolved to this level of sophistication. Understanding the design principles underpinning the function of such a dynamic modular protein remains a challenging task.

Gustatory papillae and taste bud development and maintenance in the absence of TrkB ligands BDNF and NT-4.

Science.gov (United States)

Ito, Akira; Nosrat, Christopher A

2009-09-01

Taste buds and the peripheral nerves innervating them are two important components of the peripheral gustatory system. They require appropriate connections for the taste system to function. Neurotrophic factors play crucial roles in the innervation of peripheral sensory organs and tissues. Both brain-derived neurotrophic factor (BDNF) null-mutated and neurotrophin-4 (NT-4) null-mutated mice exhibit peripheral gustatory deficits. BDNF and NT-4 bind to a common high affinity tyrosine kinase receptor, TrkB (NTRK-2), and a common p75 neurotrophin receptor (NGFR). We are currently using a transgenic mouse model to study peripheral taste system development and innervation in the absence of both TrkB ligands. We show that taste cell progenitors express taste cell markers during early stages of taste bud development in both BDNF(-/-)xNT-4(-/-) and wild-type mice. At early embryonic stages, taste bud progenitors express Troma-1, Shh, and Sox2 in all mice. At later stages, lack of innervation becomes a prominent feature in BDNF(-/-)xNT-4(-/-) mice leading to a decreasing number of fungiform papillae and morphologically degenerating taste cells. A total loss of vallate taste cells also occurs in postnatal transgenic mice. Our data indicate an initial independence but a later permissive and essential role for innervation in taste bud development and maintenance.

Divergent modulation of neuronal differentiation by caspase-2 and -9.

Directory of Open Access Journals (Sweden)

Giuseppa Pistritto

Full Text Available Human Ntera2/cl.D1 (NT2 cells treated with retinoic acid (RA differentiate towards a well characterized neuronal phenotype sharing many features with human fetal neurons. In view of the emerging role of caspases in murine stem cell/neural precursor differentiation, caspases activity was evaluated during RA differentiation. Caspase-2, -3 and -9 activity was transiently and selectively increased in differentiating and non-apoptotic NT2-cells. SiRNA-mediated selective silencing of either caspase-2 (si-Casp2 or -9 (si-Casp9 was implemented in order to dissect the role of distinct caspases. The RA-induced expression of neuronal markers, i.e. neural cell adhesion molecule (NCAM, microtubule associated protein-2 (MAP2 and tyrosine hydroxylase (TH mRNAs and proteins, was decreased in si-Casp9, but markedly increased in si-Casp2 cells. During RA-induced NT2 differentiation, the class III histone deacetylase Sirt1, a putative caspase substrate implicated in the regulation of the proneural bHLH MASH1 gene expression, was cleaved to a ∼100 kDa fragment. Sirt1 cleavage was markedly reduced in si-Casp9 cells, even though caspase-3 was normally activated, but was not affected (still cleaved in si-Casp2 cells, despite a marked reduction of caspase-3 activity. The expression of MASH1 mRNA was higher and occurred earlier in si-Casp2 cells, while was reduced at early time points during differentiation in si-Casp9 cells. Thus, caspase-2 and -9 may perform opposite functions during RA-induced NT2 neuronal differentiation. While caspase-9 activation is relevant for proper neuronal differentiation, likely through the fine tuning of Sirt1 function, caspase-2 activation appears to hinder the RA-induced neuronal differentiation of NT2 cells.

Fabrication of highly modulable fibrous 3D extracellular microenvironments

KAUST Repository

Zhang, Xixiang; Han, Fangfei; Syed, Ahad; Bukhari, Ebtihaj M.; Siang, Basil Chew Joo; Yang, Shan; Zhou, Bingpu; Wen, Wei-jia; Jiang, Dechen

2017-01-01

Three-dimensional (3D) in vitro scaffolds that mimic the irregular fibrous structures of in vivo extracellular matrix (ECM) are critical for many important biological applications. However, structural properties modulation of fibrous 3D scaffolds remains a challenge. Here, we report the first highly modulable 3D fibrous scaffolds self-assembled by high-aspect-ratio (HAR) microfibers. The scaffolds structural properties can be easily tailored to incorporate various physical cues, including geometry, stiffness, heterogeneity and nanotopography. Moreover, the fibrous scaffolds are readily and accurately patterned on desired locations of the substrate. Cell culture exhibits that our scaffolds can elicit strong bidirectional cell-material interactions. Furthermore, a functional disparity between the two-dimensional substrate and our 3D scaffolds is identified by cell spreading and proliferation data. These results prove the potential of the proposed scaffold as a biomimetic extracellular microenvironment for cell study.

Fabrication of highly modulable fibrous 3D extracellular microenvironments

KAUST Repository

Zhang, Xixiang

2017-06-13

Three-dimensional (3D) in vitro scaffolds that mimic the irregular fibrous structures of in vivo extracellular matrix (ECM) are critical for many important biological applications. However, structural properties modulation of fibrous 3D scaffolds remains a challenge. Here, we report the first highly modulable 3D fibrous scaffolds self-assembled by high-aspect-ratio (HAR) microfibers. The scaffolds structural properties can be easily tailored to incorporate various physical cues, including geometry, stiffness, heterogeneity and nanotopography. Moreover, the fibrous scaffolds are readily and accurately patterned on desired locations of the substrate. Cell culture exhibits that our scaffolds can elicit strong bidirectional cell-material interactions. Furthermore, a functional disparity between the two-dimensional substrate and our 3D scaffolds is identified by cell spreading and proliferation data. These results prove the potential of the proposed scaffold as a biomimetic extracellular microenvironment for cell study.

Modularity for Modulating Exercises and Levels

DEFF Research Database (Denmark)

Lund, Henrik Hautop; Nielsen, Camilla Balslev

2011-01-01

The modular interactive tiles aim at engaging anybody (elderly, carer, hospital personnel, children) in performing playful and motivating physical activities. Inspired by modular robotics, each tile is a self-contained module with processing power and communication to neighbouring modules....... In this paper, we investigate the therapeutic use. We show how the tiles are tested extensively with cardiac patients, COLD patients and stroke patients in hospitals and in the private homes of patients and elderly. We find that therapists are using the modular aspect of the tiles for personalized training...

3,3'Diindolylmethane suppresses vascular smooth muscle cell phenotypic modulation and inhibits neointima formation after carotid injury.

Directory of Open Access Journals (Sweden)

Hongjing Guan

Full Text Available 3,3'Diindolylmethane (DIM, a natural phytochemical, has shown inhibitory effects on the growth and migration of a variety of cancer cells; however, whether DIM has similar effects on vascular smooth muscle cells (VSMCs remains unknown. The purpose of this study was to assess the effects of DIM on the proliferation and migration of cultured VSMCs and neointima formation in a carotid injury model, as well as the related cell signaling mechanisms.DIM dose-dependently inhibited the platelet-derived growth factor (PDGF-BB-induced proliferation of VSMCs without cell cytotoxicity. This inhibition was caused by a G0/G1 phase cell cycle arrest demonstrated by fluorescence-activated cell-sorting analysis. We also showed that DIM-induced growth inhibition was associated with the inhibition of the expression of cyclin D1 and cyclin-dependent kinase (CDK 4/6 as well as an increase in p27(Kip1 levels in PDGF-stimulated VSMCs. Moreover, DIM was also found to modulate migration of VSMCs and smooth muscle-specific contractile marker expression. Mechanistically, DIM negatively modulated PDGF-BB-induced phosphorylation of PDGF-recptorβ (PDGF-Rβ and the activities of downstream signaling molecules including Akt/glycogen synthase kinase(GSK3β, extracellular signal-regulated kinase1/2 (ERK1/2, and signal transducers and activators of transcription 3 (STAT3. Our in vivo studies using a mouse carotid arterial injury model revealed that treatment with 150 mg/kg DIM resulted in significant reduction of the neointima/media ratio and proliferating cell nuclear antigen (PCNA-positive cells, without affecting apoptosis of vascular cells and reendothelialization. Infiltration of inflammatory cells was also inhibited by DIM administration.These results demonstrate that DIM can suppress the phenotypic modulation of VSMCs and neointima hyperplasia after vascular injury. These beneficial effects on VSMCs were at least partly mediated by the inhibition of PDGF-Rβ and the

Toward a Better Understanding of the GRB Phenomenon: a New Model for GRB Prompt Emission and its Effects on the New LiNT- Epeak,irest,NT Relation

Science.gov (United States)

Guiriec, S.; Kouveliotou, C.; Daigne, F.; Zhang, B.; Hascoët, R.; Nemmen, R. S.; Thompson, D. J.; Bhat, P. N.; Gehrels, N.; Gonzalez, M. M.; Kaneko, Y.; McEnery, J.; Mochkovitch, R.; Racusin, J. L.; Ryde, F.; Sacahui, J. R.; Ünsal, A. M.

2015-07-01

both the observer and rest frames and show that a strong correlation exists between the flux of the non-thermal Band function and its Epeak only when the three components are fitted simultaneously to the data (i.e., {F}i{NT}-{E}{peak,i}{NT} relation). In addition, this result points toward a universal relation between those two quantities when transposed to the central engine rest frame for all GRBs (i.e., {L}i{NT}-{E}{peak,i}{rest,{NT}} relation). We discuss a possible theoretical interpretation of the three spectral components within this new empirical model. We suggest that (i) the BB component may be interpreted as the photosphere emission of a magnetized relativistic outflow, (ii) the Band component has synchrotron radiation in an optically thin region above the photosphere, either from internal shocks or magnetic field dissipation, and (iii) the extra PL component extending to high energies likely has an inverse Compton origin of some sort, even though its extension to a much lower energy remains a mystery.

Serum potassium decline during hospitalization for acute decompensated heart failure is a predictor of 6-month mortality, independent of N-terminal pro-B-type natriuretic peptide levels: An individual patient data analysis.

Science.gov (United States)

Salah, Khibar; Pinto, Yigal M; Eurlings, Luc W; Metra, Marco; Stienen, Susan; Lombardi, Carlo; Tijssen, Jan G; Kok, Wouter E

2015-09-01

Limited data exist for the role of serum potassium changes during hospitalization for acute decompensated heart failure (ADHF). The present study investigated the long-term prognostic value of potassium changes during hospitalization in patients admitted for ADHF. Our study is a pooled individual patient data analysis assembled from 3 prospective cohorts comprising 754 patients hospitalized for ADHF. The endpoint was all-cause mortality within 180 days after discharge. Serum potassium levels and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured at admission and at discharge. A percentage decrease >15% in serum potassium levels occurred in 96 (13%) patients, and an absolute decrease of >0.7 mmol/L in serum potassium levels occurred in 85 (12%) patients; and both were predictors of poor outcome independent of admission or discharge serum potassium. After the addition of other strong predictors of mortality-a 30% change in NT-proBNP during hospitalization, discharge levels of NT-proBNP, renal markers, and other relevant clinical variables-the multivariate hazard ratio of serum potassium percentage reduction of >15% remained an independent predictor of 180-day mortality (hazard ratio 2.06, 95% CI 1.14-3.73). A percentage serum potassium decline of >15% is an independent predictor of 180-day all-cause mortality on top of baseline potassium levels, NT-proBNP levels, renal variables, and other relevant clinical variables. This suggest that patients hospitalized for ADHF with a decline of >15% in serum potassium levels are at risk and thus monitoring and regulating of serum potassium level during hospitalization are needed in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

First human hNT neurons patterned on parylene-C/silicon dioxide substrates: Combining an accessible cell line and robust patterning technology for the study of the pathological adult human brain.

Science.gov (United States)

Unsworth, C P; Graham, E S; Delivopoulos, E; Dragunow, M; Murray, A F

2010-12-15

In this communication, we describe a new method which has enabled the first patterning of human neurons (derived from the human teratocarcinoma cell line (hNT)) on parylene-C/silicon dioxide substrates. We reveal the details of the nanofabrication processes, cell differentiation and culturing protocols necessary to successfully pattern hNT neurons which are each key aspects of this new method. The benefits in patterning human neurons on silicon chip using an accessible cell line and robust patterning technology are of widespread value. Thus, using a combined technology such as this will facilitate the detailed study of the pathological human brain at both the single cell and network level. Copyright © 2010 Elsevier B.V. All rights reserved.

Genetic Variation in the Natriuretic Peptide System, Circulating Natriuretic Peptide Levels, and Blood Pressure

DEFF Research Database (Denmark)

Jeppesen, Jørgen L; Nielsen, Søren J; Torp-Pedersen, Christian

2012-01-01

-h ambulatory BP measurements (ABPMs) will influence the effect of NP gene variations on BP levels.MethodsWe used rs632793 at the NPPB (NP precursor B) locus to investigate the relationship between genetically determined serum N-terminal pro-brain NP (NT-proBNP) concentrations and BP levels...... determined by both 24-h ABPMs and OBPMs in a population consisting of 1,397 generally healthy individuals taking no BP-lowering drugs.Resultsrs632793 was significantly correlated with serum Nt-proBNP levels (r = 0.10, P = 0.0003), and participants with the A:A genotype had lower serum Nt-proBNP levels than......). Office BP decreased across the genotypes from A:A to G:G, but the differences did not reach statistical significance (P = 0.12).ConclusionsThis study suggests that 24-h ABPMs is a better method than OBPMs to detect significant differences in BP levels related to genetic variance and provides further...

Ahlaki sıkıntı: Türkiye’de sağlık alanında gündeme gelmeyen bir boyut

OpenAIRE

Gülay Yıldırım; Dilek Özden; Şerife Karagözoğlu

2013-01-01

Özet Ahlaki sıkıntı (moral distres) sağlık bakım alanlarında çalışan profesyoneller ve yöneticilerde yaygın olarak yaşanan bir problemdir. Ahlaki sıkıntı, bir profesyonelin yapılacak doğru eylemi bildiği halde engeller nedeniyle doğru eylemi gerçekleştirememesi durumunda yaşadığı bir sıkıntıdır. Bireysel ve kurumsal birçok durumun neden olduğu ahlaki sıkıntı, sağlık profesyonellerinde öfke ve engellenme duygusundan iş doyumunda azalmaya, tükenmişlik ve meslekten ayrılmaya kadar önemli sonuçla...

Low cost, patterning of human hNT brain cells on parylene-C with UV & IR laser machining.

Science.gov (United States)

Raos, Brad J; Unsworth, C P; Costa, J L; Rohde, C A; Doyle, C S; Delivopoulos, E; Murray, A F; Dickinson, M E; Simpson, M C; Graham, E S; Bunting, A S

2013-01-01

This paper describes the use of 800nm femtosecond infrared (IR) and 248nm nanosecond ultraviolet (UV) laser radiation in performing ablative micromachining of parylene-C on SiO2 substrates for the patterning of human hNT astrocytes. Results are presented that support the validity of using IR laser ablative micromachining for patterning human hNT astrocytes cells while UV laser radiation produces photo-oxidation of the parylene-C and destroys cell patterning. The findings demonstrate how IR laser ablative micromachining of parylene-C on SiO2 substrates can offer a low cost, accessible alternative for rapid prototyping, high yield cell patterning.

Building America Case Study: Photovoltaic Systems with Module-Level Power Electronics

Energy Technology Data Exchange (ETDEWEB)

2015-09-01

Direct current (DC) power optimizers and microinverters (together known as module-level power electronics, or MLPE) are one of the fastest growing market segments in the solar industry. According to GTM Research in The Global PV Inverter Landscape 2015, over 55% of all residential photovoltaic (PV) installations in the United States used some form of MLPE in 2014.

The natural scorpion peptide, BmK NT1 activates voltage-gated sodium channels and produces neurotoxicity in primary cultured cerebellar granule cells.

Science.gov (United States)

Zou, Xiaohan; He, Yuwei; Qiao, Jinping; Zhang, Chunlei; Cao, Zhengyu

2016-01-01

The scorpion Buthus martensii Karsch has been used in Traditional Chinese Medicine to treat neuronal diseases such as neuropathic pain, paralysis and epilepsy for thousands of years. Studies have demonstrated that scorpion venom is the primary active component. Although scorpion venom can effectively attenuate pain in the clinic, it also produces neurotoxic response. In this study, toxicity guided purification led to identify a mammalian toxin termed BmK NT1 comprising of 65 amino acid residues and an amidated C-terminus, a mature peptide encoded by the nucleotide sequence (GenBank No. AF464898). In contract to the recombinant product of the same nucleotide sequence, BmK AGAP, which displayed analgesic and anti-tumor effect, intravenous injection (i.v.) of BmK NT1 produced acute toxicity in mice with an LD50 value of 1.36 mg/kg. In primary cultured cerebellar granule cells, BmK NT1 produced a concentration-dependent cell death with an IC50 value of 0.65 μM (0.41-1.03 μM, 95% Confidence Intervals, 95% CI) which was abolished by TTX, a voltage-gated sodium channel (VGSC) blocker. We also demonstrated that BmK NT1 produced modest sodium influx in cerebellar granule cell cultures with an EC50 value of 2.19 μM (0.76-6.40 μM, 95% CI), an effect similar to VGSC agonist, veratridine. The sodium influx response was abolished by TTX suggesting that BmK NT1-induced sodium influx is solely through activation of VGSC. Considered these data together, we demonstrated that BmK NT1 activated VGSC and produced neurotoxicity in cerebellar granule cell cultures. Copyright © 2015 Elsevier Ltd. All rights reserved.