Role of 5-HT3 Receptor on Food Intake in Fed and Fasted Mice

Science.gov (United States)

Li, Bingjin; Shao, Dongyuan; Luo, Yungang; Wang, Pu; Liu, Changhong; Zhang, Xingyi; Cui, Ranji

2015-01-01

Background Many studies have shown that 5-hydroxytryptamine (5-HT) receptor subtypes are involved in the regulation of feeding behavior. However, the relative contribution of 5-HT3 receptor remains unclear. The present study was aimed to investigate the role of 5-HT3 receptor in control of feeding behavior in fed and fasted mice. Methodology/Principal Findings Food intake and expression of c-Fos, tyrosine hydroxylase (TH), proopiomelanocortin (POMC) and 5-HT in the brain were examined after acute treatment with 5-HT3 receptor agonist SR-57227 alone or in combination with 5-HT3 receptor antagonist ondansetron. Food intake was significantly inhibited within 3 h after acute treatment with SR 57227 in fasted mice but not fed mice, and this inhibition was blocked by ondansetron. Immunohistochemical study revealed that fasting-induced c-Fos expression was further enhanced by SR 57227 in the brainstem and the hypothalamus, and this enhancement was also blocked by ondansetron. Furthermore, the fasting-induced downregulation of POMC expression in the hypothalamus and the TH expression in the brain stem was blocked by SR 57227 in the fasted mice, and this effect of SR 57227 was also antagonized by ondansetron. Conclusion/Significance Taken together, our findings suggest that the effect of SR 57227 on the control of feeding behavior in fasted mice may be, at least partially, related to the c-Fos expression in hypothalamus and brain stem, as well as POMC system in the hypothalamus and the TH system in the brain stem. PMID:25789930

Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis.

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Xuan Xia

2011-02-01

Full Text Available Berberine (BBR is a compound originally identified in a Chinese herbal medicine Huanglian (Coptis chinensis French. It improves glucose metabolism in type 2 diabetic patients. The mechanisms involve in activation of adenosine monophosphate activated protein kinase (AMPK and improvement of insulin sensitivity. However, it is not clear if BBR reduces blood glucose through other mechanism. In this study, we addressed this issue by examining liver response to BBR in diabetic rats, in which hyperglycemia was induced in Sprague-Dawley rats by high fat diet. We observed that BBR decreased fasting glucose significantly. Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK and Glucose-6-phosphatase (G6Pase, were decreased in liver by BBR. Hepatic steatosis was also reduced by BBR and expression of fatty acid synthase (FAS was inhibited in liver. Activities of transcription factors including Forkhead transcription factor O1 (FoxO1, sterol regulatory element-binding protein 1c (SREBP1 and carbohydrate responsive element-binding protein (ChREBP were decreased. Insulin signaling pathway was not altered in the liver. In cultured hepatocytes, BBR inhibited oxygen consumption and reduced intracellular adenosine triphosphate (ATP level. The data suggest that BBR improves fasting blood glucose by direct inhibition of gluconeogenesis in liver. This activity is not dependent on insulin action. The gluconeogenic inhibition is likely a result of mitochondria inhibition by BBR. The observation supports that BBR improves glucose metabolism through an insulin-independent pathway.

Streptomyces lunalinharesii Strain 235 Shows the Potential to Inhibit Bacteria Involved in Biocorrosion Processes

OpenAIRE

Pacheco da Rosa, Juliana; Korenblum, Elisa; Franco-Cirigliano, Marcella Novaes; Abreu, Fernanda; Lins, Ulysses; Soares, Rosângela M. A.; Macrae, Andrew; Seldin, Lucy; Coelho, Rosalie R. R.

2013-01-01

Four actinomycete strains previously isolated from Brazilian soils were tested for their antimicrobial activity against Bacillus pumilus LF-4 and Desulfovibrio alaskensis NCIMB 13491, bacteria that are well known to be involved in biofilm formation and biocorrosion. Strain 235, belonging to the species Streptomyces lunalinharesii, inhibited the growth of both bacteria. The antimicrobial activity was seen over a wide range of pH, and after treatment with several chemicals and heat but not with...

The microRNA machinery regulates fasting-induced changes in gene expression and longevity in Caenorhabditis elegans.

Science.gov (United States)

Kogure, Akiko; Uno, Masaharu; Ikeda, Takako; Nishida, Eisuke

2017-07-07

Intermittent fasting (IF) is a dietary restriction regimen that extends the lifespans of Caenorhabditis elegans and mammals by inducing changes in gene expression. However, how IF induces these changes and promotes longevity remains unclear. One proposed mechanism involves gene regulation by microRNAs (miRNAs), small non-coding RNAs (∼22 nucleotides) that repress gene expression and whose expression can be altered by fasting. To test this proposition, we examined the role of the miRNA machinery in fasting-induced transcriptional changes and longevity in C. elegans We revealed that fasting up-regulated the expression of the miRNA-induced silencing complex (miRISC) components, including Argonaute and GW182, and the miRNA-processing enzyme DRSH-1 (the ortholog of the Drosophila Drosha enzyme). Our lifespan measurements demonstrated that IF-induced longevity was suppressed by knock-out or knockdown of miRISC components and was completely inhibited by drsh-1 ablation. Remarkably, drsh-1 ablation inhibited the fasting-induced changes in the expression of the target genes of DAF-16, the insulin/IGF-1 signaling effector in C. elegans Fasting-induced transcriptome alterations were substantially and modestly suppressed in the drsh-1 null mutant and the null mutant of ain-1 , a gene encoding GW182, respectively. Moreover, miRNA array analyses revealed that the expression levels of numerous miRNAs changed after 2 days of fasting. These results indicate that components of the miRNA machinery, especially the miRNA-processing enzyme DRSH-1, play an important role in mediating IF-induced longevity via the regulation of fasting-induced changes in gene expression. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Molecular mechanisms involved in the inhibition of tumor cells proliferation exposed to elevated concentrations of the epidermal growth factor

International Nuclear Information System (INIS)

Guillen, Isabel A; Berlanga, Jorge; Camacho, Hanlet

2013-01-01

The EGF promotes inhibition of cell proliferation in vitro and in vivo models depending on its concentration, application schema and the type of tumor cells on which it acts. Our research hypothesis was based on the fact that the EGF varies the expression of genes involved in a negative regulation of tumor cell lines proliferation carrying high levels of its receptor (EGFR). Our objectives were, to obtain information about the effect of EGF on tumor cell proliferation in vitro and in vivo models and, know the gene expression patterns of a group of genes involved in cancer signaling pathways and EGFR. The results showed that EGF at nanomolar concentrations inhibits the tumor cells proliferation bearing high levels of EGFR and, promotes the survival of treated animals, establishing a direct relationship between the inhibition of cell proliferation, high concentrations of EGF and, high amount of EGFR in the cells. The differential gene expression profile showed a variation in a group of genes which exert a powerful control over the cell cycle progression, gene transcription and apoptosis. It was concluded that the inhibition of tumor cell proliferation by the action of EGF is due to activation of molecular mechanisms controlling cell cycle progression. This work won the Annual Award of the Cuban Academy of Sciences in 2012

Spouses’ involvement in older patients’ fast-track programmes during total hip replacement using case management intervention. A study protocol of the SICAM-trial

DEFF Research Database (Denmark)

Berthelsen, Connie Bøttcher; Kristensson, Jimmie

2015-01-01

Aim To present the protocol of a two-group quasi-experimental study of spouses’ involvement through case management (The SICAM-trial) in older patients’ fast-track programmes during total hip replacement. Background Patients in fast-track programmes are required to take an active part in their tr......Aim To present the protocol of a two-group quasi-experimental study of spouses’ involvement through case management (The SICAM-trial) in older patients’ fast-track programmes during total hip replacement. Background Patients in fast-track programmes are required to take an active part...... in their treatment and rehabilitation. Spouses of older patients can often provide valued practical and emotional support, reducing stress, pain and length of stay – yet they are seldom invited to participate in a supporting role. Design A two-group quasi-experimental design with pre-test and repeated post...... and subsequently include the intervention group to avoid contamination of the control group. A case manager will be recruited to perform the case management intervention. Data will be collected from both groups at baseline, 2 weeks and 3 months after surgery. Outcome measures for patients include: functional...

A Modified Glycosaminoglycan, GM-0111, Inhibits Molecular Signaling Involved in Periodontitis.

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Justin R Savage

Full Text Available Periodontitis is characterized by microbial infection, inflammation, tissue breakdown, and accelerated loss of alveolar bone matrix. Treatment targeting these multiple stages of the disease provides ways to treat or prevent periodontitis. Certain glycosaminoglycans (GAGs block multiple inflammatory mediators as well as suppress bacterial growth, suggesting that these GAGs may be exploited as a therapeutic for periodontitis.We investigated the effects of a synthetic GAG, GM-0111, on various molecular events associated with periodontitis: growth of Porphyromonas gingivalis (P. gingivalis and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans pathogenic bacteria associated with periodontitis; activation of pro-inflammatory signaling through TLR2 and TLR4 in mouse macrophage RAW 264.7 cells and heterologously expressed HEK 293 cells; osteoclast formation and bone matrix resorption in cultured mouse pre-osteoclasts.(1 GM-0111 suppressed the growth of P. gingivalis and A. actinomycetemcomitans even at 1% (w/v solution. The antibacterial effects of GM-0111 were stronger than hyaluronic acid (HA or xylitol in P. gingivalis at all concentrations and comparable to xylitol in A. actinomycetemcomitans at ≥2% (w/v solution. We also observed that GM-0111 suppressed biofilm formation of P. gingivalis and these effects were much stronger than HA. (2 GM-0111 inhibited TLR-mediated pro-inflammatory cellular signaling both in macrophage and HEK 293 cells with higher selectivity for TLR2 than TLR4 (IC50 of 1-10 ng/mL vs. > 100 μg/mL, respectively. (3 GM-0111 blocked RANKL-induced osteoclast formation (as low as 300 ng/mL and bone matrix resorption. While GM-0111 showed high affinity binding to RANKL, it did not interfere with RANKL/RANK/NF-κB signaling, suggesting that GM-0111 inhibits osteoclast formation by a RANKL-RANK-independent mechanism.We report that GM-0111 inhibits multiple molecular events involved in periodontitis, spanning from the

Hyperphagia of hyperthyroidism: is neuropeptide Y involved?

Science.gov (United States)

Pétervári, Erika; Balaskó, Márta; Jech-Mihálffy, Andrea; Székely, Miklós

2005-11-01

The possible role of neuropeptide Y (NPY) was studied in rats with hypermetabolism and hyperphagia induced by thyroxine (50-100-200 microg/day s.c. for 3-4 weeks). Both metabolic rate and body temperature increased quickly with thyroxine treatment, while hyperphagia started to develop only after 2 weeks of treatment. The weight gain rate progressively decreased or stopped. The NPY-induced hyperphagia was not altered significantly during thyroxine treatment (in severe thyrotoxicosis it was rather suppressed); the fasting-induced hyperphagia was smaller than in controls following 1 week of treatment, and it became enhanced only after 3 weeks, when the deficit in body weight indicated a certain level of starvation already prior to the food deprivation. The NPY-antagonist D-Tyr27,36,D-Thr32-NPY27,36 suppressed this fasting-induced hyperphagia, suggesting that endogenous NPY is involved in this late phase. In conclusion, hyperthyroidism per se does not increase the NPY activity, instead the quickly developing hyperthermia may inhibit the NPY actions; NPY may, however, be activated by a concurrent hypermetabolism-induced starvation.

Genes involved in yeast survival after irradiation with fast neutrons

International Nuclear Information System (INIS)

Bozin, D.; Milosevic, M.J.

2001-01-01

Life on the Earth has evolved against a continuous background of ionizing radiation. It would be expected, therefore, that all possible mutations have been produced at some time or another; man-made radiation from medical or industrial sources will not result in any new types of mutation but will simply increase the whole spectrum of mutations that occur spontaneously. Any such lesion can be mutagenic and, in principle, lethal. To counteract the consequences of DNA damage, evolution has equipped all living cells with an intricate network of defense and repair systems. Together, these systems act as a kind of nuclear 'immune system' that is able to recognize and eliminate many types of DNA lesions. In the case of the yeast Saccharomyces cerevisiae, in these processes over 30 RAD genes participate. We tested the survival of haploid and diploid rad1 yeast mutant strains at a dose of 15 Gy of γ or fast neutron radiation. We demonstrated that the lethality of rad1 mutants both haploid and diploid are significantly higher after fast neutron irradiation. The results indicate to the role and position of these genes in the DNA repair of damages specifically induced by fast neutrons. (authors)

Calcium signaling through CaMKII regulates hepatic glucose production in fasting and obesity.

Science.gov (United States)

Ozcan, Lale; Wong, Catherine C L; Li, Gang; Xu, Tao; Pajvani, Utpal; Park, Sung Kyu Robin; Wronska, Anetta; Chen, Bi-Xing; Marks, Andrew R; Fukamizu, Akiyoshi; Backs, Johannes; Singer, Harold A; Yates, John R; Accili, Domenico; Tabas, Ira

2012-05-02

Hepatic glucose production (HGP) is crucial for glucose homeostasis, but the underlying mechanisms have not been fully elucidated. Here, we show that a calcium-sensing enzyme, CaMKII, is activated in a calcium- and IP3R-dependent manner by cAMP and glucagon in primary hepatocytes and by glucagon and fasting in vivo. Genetic deficiency or inhibition of CaMKII blocks nuclear translocation of FoxO1 by affecting its phosphorylation, impairs fasting- and glucagon/cAMP-induced glycogenolysis and gluconeogenesis, and lowers blood glucose levels, while constitutively active CaMKII has the opposite effects. Importantly, the suppressive effect of CaMKII deficiency on glucose metabolism is abrogated by transduction with constitutively nuclear FoxO1, indicating that the effect of CaMKII deficiency requires nuclear exclusion of FoxO1. This same pathway is also involved in excessive HGP in the setting of obesity. These results reveal a calcium-mediated signaling pathway involved in FoxO1 nuclear localization and hepatic glucose homeostasis. Copyright © 2012 Elsevier Inc. All rights reserved.

Damages to gladiolu corm caused by fast neutron irradiation

International Nuclear Information System (INIS)

Zhang Zhiwei; Wang Dan; Zhang Dongxue; Zheng Chun

2007-01-01

Gladiolus corms were irradiated to 100-500kGy by fast neutrons in the CFBR-II pulsed reactor, Scanning electron microscope images of the irradiated samples revealed significant radiation damages to the gladiolus corms, and the mutagenic effects were studied by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Within the dose range, radiation damage to the corm increased with the dose, with corm epidermis of the samples irradiated in vertical incidence being more serious than those irradiated in side-incidence to the same dose. Biological characters were investigated via field experiments, and the bands of protein subunit were analyzed by SDS-PAGE. The results showed that the fast neutrons irradiation inhibited growth of M1 generation seedling significantly. Protein expression was obviously inhibited by the irradiation. The study indicates that fast neutron induction is an effective way for gladiolus breeding. And the results may lay a foundation for studies on fast neutron mutation breeding. (authors)

Fast inhibition of glutamate-activated currents by caffeine.

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Nicholas P Vyleta

Full Text Available BACKGROUND: Caffeine stimulates calcium-induced calcium release (CICR in many cell types. In neurons, caffeine stimulates CICR presynaptically and thus modulates neurotransmitter release. METHODOLOGY/PRINCIPAL FINDINGS: Using the whole-cell patch-clamp technique we found that caffeine (20 mM reversibly increased the frequency and decreased the amplitude of miniature excitatory postsynaptic currents (mEPSCs in neocortical neurons. The increase in mEPSC frequency is consistent with a presynaptic mechanism. Caffeine also reduced exogenously applied glutamate-activated currents, confirming a separate postsynaptic action. This inhibition developed in tens of milliseconds, consistent with block of channel currents. Caffeine (20 mM did not reduce currents activated by exogenous NMDA, indicating that caffeine block is specific to non-NMDA type glutamate receptors. CONCLUSIONS/SIGNIFICANCE: Caffeine-induced inhibition of mEPSC amplitude occurs through postsynaptic block of non-NMDA type ionotropic glutamate receptors. Caffeine thus has both pre and postsynaptic sites of action at excitatory synapses.

eIF4A inhibition allows translational regulation of mRNAs encoding proteins involved in Alzheimer's disease.

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Andrew Bottley

2010-09-01

Full Text Available Alzheimer's disease (AD is the main cause of dementia in our increasingly aging population. The debilitating cognitive and behavioral symptoms characteristic of AD make it an extremely distressing illness for patients and carers. Although drugs have been developed to treat AD symptoms and to slow disease progression, there is currently no cure. The incidence of AD is predicted to increase to over one hundred million by 2050, placing a heavy burden on communities and economies, and making the development of effective therapies an urgent priority. Two proteins are thought to have major contributory roles in AD: the microtubule associated protein tau, also known as MAPT; and the amyloid-beta peptide (A-beta, a cleavage product of amyloid precursor protein (APP. Oxidative stress is also implicated in AD pathology from an early stage. By targeting eIF4A, an RNA helicase involved in translation initiation, the synthesis of APP and tau, but not neuroprotective proteins, can be simultaneously and specifically reduced, representing a novel avenue for AD intervention. We also show that protection from oxidative stress is increased upon eIF4A inhibition. We demonstrate that the reduction of these proteins is not due to changes in mRNA levels or increased protein degradation, but is a consequence of translational repression conferred by inhibition of the helicase activity of eIF4A. Inhibition of eIF4A selectively and simultaneously modulates the synthesis of proteins involved in Alzheimer's disease: reducing A-beta and tau synthesis, while increasing proteins predicted to be neuroprotective.

Gelatin Nano-coating for Inhibiting Surface Crystallization of Amorphous Drugs.

Science.gov (United States)

Teerakapibal, Rattavut; Gui, Yue; Yu, Lian

2018-01-05

Inhibit the fast surface crystallization of amorphous drugs with gelatin nano-coatings. The free surface of amorphous films of indomethacin or nifedipine was coated by a gelatin solution (type A or B) and dried. The coating's effect on surface crystallization was evaluated. Coating thickness was estimated from mass change after coating. For indomethacin (weak acid, pK a  = 4.5), a gelatin coating of either type deposited at pH 5 and 10 inhibited its fast surface crystal growth. The coating thickness was 20 ± 10 nm. A gelatin coating deposited at pH 3, however, provided no protective effect. These results suggest that an effective gelatin coating does not require that the drug and the polymer have opposite charges. The ineffective pH 3 coating might reflect the poor wetting of indomethacin's neutral, hydrophobic surface by the coating solution. For nifedipine (weak base, pK a  = 2.6), a gelatin coating of either type deposited at pH 5 inhibited its fast surface crystal growth. Gelatin nano-coatings can be conveniently applied to amorphous drugs from solution to inhibit fast surface crystallization. Unlike strong polyelectrolyte coatings, a protective gelatin coating does not require strict pairing of opposite charges. This could make gelatin coating a versatile, pharmaceutically acceptable coating for stabilizing amorphous drugs.

Can fast and slow intelligence be differentiated?

NARCIS (Netherlands)

Partchev, I.; de Boeck, P.

2012-01-01

Responses to items from an intelligence test may be fast or slow. The research issue dealt with in this paper is whether the intelligence involved in fast correct responses differs in nature from the intelligence involved in slow correct responses. There are two questions related to this issue: 1.

Targeting GLI by GANT61 involves mechanisms dependent on inhibition of both transcription and DNA licensing.

Science.gov (United States)

Zhang, Ruowen; Wu, Jiahui; Ferrandon, Sylvain; Glowacki, Katie J; Houghton, Janet A

2016-12-06

The GLI genes are transcription factors and in cancers are oncogenes, aberrantly and constitutively activated. GANT61, a specific GLI inhibitor, has induced extensive cytotoxicity in human models of colon cancer. The FOXM1 promoter was determined to be a transcriptional target of GLI1. In HT29 cells, inhibition of GLI1 binding at the GLI consensus sequence by GANT61 led to inhibited binding of Pol II, the pause-release factors DSIF, NELF and p-TEFb. The formation of R-loops (RNA:DNA hybrids, ssDNA), were reduced by GANT61 at the FOXM1 promoter. Pretreatment of HT29 cells with α-amanitin reduced GANT61-induced γH2AX foci. Co-localization of GLI1 and BrdU foci, inhibited by GANT61, indicated GLI1 and DNA replication to be linked. By co-immunoprecipitation and confocal microscopy, GLI1 co-localized with the DNA licensing factors ORC4, CDT1, and MCM2. Significant co-localization of GLI1 and ORC4 was inhibited by GANT61, and enrichment of ORC4 occurred at the GLI binding site in the FOXM1 promoter. CDT1 was found to be a transcription target of GLI1. Overexpression of CDT1 in HT29 and SW480 cells reduced GANT61-induced cell death, gH2AX foci, and cleavage of caspase-3. Data demonstrate involvement of transcription and of DNA replication licensing factors by non-transcriptional and transcriptional mechanisms in the GLI-dependent mechanism of action of GANT61.

Post-exercise abdominal, subcutaneous adipose tissue lipolysis in fasting subjects is inhibited by infusion of the somatostatin analogue octreotide

DEFF Research Database (Denmark)

Enevoldsen, Lotte H; Polak, Jan; Simonsen, Lene

2007-01-01

.c., abdominal adipose tissue metabolism, before, during and after exercise in healthy, fasting, young male subjects. The adipose tissue net releases of fatty acids and glycerol were measured by arterio-venous catheterizations and simultaneous measurements of adipose tissue blood flow with the local Xe....... The results show that octreotide infusion during rest increased lipolysis and fatty acid release from the abdominal, s.c. adipose tissue. The exercise-induced increase in lipolysis and fatty acid release does not seem to be affected by octreotide when compared with the control study without octreotide...... infusion while the post-exercise increase in lipolysis is inhibited by octreotide, suggesting that the exercise-induced increase in GH secretion plays a role for the post-exercise lipolysis in s.c., abdominal adipose tissue....

Tetrahydroxystilbene glucoside improves TNF-α-induced endothelial dysfunction: involvement of TGFβ/Smad pathway and inhibition of vimentin expression.

Science.gov (United States)

Yao, Wenjuan; Gu, Chengjing; Shao, Haoran; Meng, Guoliang; Wang, Huiming; Jing, Xiang; Zhang, Wei

2015-01-01

Endothelial dysfunction plays an important role in the pathogenesis of atherogenesis. 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an active component of the rhizome extract from Polygonum multiflorum (PM), exhibits significant anti-atherosclerotic activity. Here, we used human umbilical vein endothelial cells (HUVECs) induced by tumor necrosis factor-α (TNF-α) in vitro to investigate the cytoprotective effects of TSG on TNF-α-induced endothelial injury and the related mechanisms. Pretreatment with 50 and 100 μM TSG markedly attenuated TNF-α-induced loss of cell viability and release of lactate dehydrogenase (LDH) and inhibited TNF-α-induced cell apoptosis. The inhibition of vimentin expression was involved in the cytoprotection afforded by TSG. Using inhibitors for PI3K and TGFβ or siRNA for Akt and Smad2, we found that vimentin production in HUVECs is regulated by TGFβ/Smad signaling, but not by PI3K-Akt-mTOR signaling. Meanwhile, TSG inhibited both the expression of TGFβ1 and the phosphorylation of Smad2 and Smad3, and TSG suppressed the nuclear translocation of Smad4 induced by TNF-α. These results suggest that TSG protects HUVECs against TNF-α-induced cell damage by inhibiting vimentin expression via the interruption of the TGFβ/Smad signaling pathway.

Belinostat-induced apoptosis and growth inhibition in pancreatic cancer cells involve activation of TAK1-AMPK signaling axis

International Nuclear Information System (INIS)

Wang, Bing; Wang, Xin-bao; Chen, Li-yu; Huang, Ling; Dong, Rui-zen

2013-01-01

Highlights: •Belinostat activates AMPK in cultured pancreatic cancer cells. •Activation of AMPK is important for belinostat-induced cytotoxic effects. •ROS and TAK1 are involved in belinostat-induced AMPK activation. •AMPK activation mediates mTOR inhibition by belinostat. -- Abstract: Pancreatic cancer accounts for more than 250,000 deaths worldwide each year. Recent studies have shown that belinostat, a novel pan histone deacetylases inhibitor (HDACi) induces apoptosis and growth inhibition in pancreatic cancer cells. However, the underlying mechanisms are not fully understood. In the current study, we found that AMP-activated protein kinase (AMPK) activation was required for belinostat-induced apoptosis and anti-proliferation in PANC-1 pancreatic cancer cells. A significant AMPK activation was induced by belinostat in PANC-1 cells. Inhibition of AMPK by RNAi knockdown or dominant negative (DN) mutation significantly inhibited belinostat-induced apoptosis in PANC-1 cells. Reversely, AMPK activator AICAR and A-769662 exerted strong cytotoxicity in PANC-1 cells. Belinostat promoted reactive oxygen species (ROS) production in PANC-1 cells, increased ROS induced transforming growth factor-β-activating kinase 1 (TAK1)/AMPK association to activate AMPK. Meanwhile, anti-oxidants N-Acetyl-Cysteine (NAC) and MnTBAP as well as TAK1 shRNA knockdown suppressed belinostat-induced AMPK activation and PANC-1 cell apoptosis. In conclusion, we propose that belinostat-induced apoptosis and growth inhibition require the activation of ROS-TAK1-AMPK signaling axis in cultured pancreatic cancer cells

Belinostat-induced apoptosis and growth inhibition in pancreatic cancer cells involve activation of TAK1-AMPK signaling axis

Energy Technology Data Exchange (ETDEWEB)

Wang, Bing, E-mail: wangbin69@yahoo.com; Wang, Xin-bao; Chen, Li-yu; Huang, Ling; Dong, Rui-zen

2013-07-19

Highlights: •Belinostat activates AMPK in cultured pancreatic cancer cells. •Activation of AMPK is important for belinostat-induced cytotoxic effects. •ROS and TAK1 are involved in belinostat-induced AMPK activation. •AMPK activation mediates mTOR inhibition by belinostat. -- Abstract: Pancreatic cancer accounts for more than 250,000 deaths worldwide each year. Recent studies have shown that belinostat, a novel pan histone deacetylases inhibitor (HDACi) induces apoptosis and growth inhibition in pancreatic cancer cells. However, the underlying mechanisms are not fully understood. In the current study, we found that AMP-activated protein kinase (AMPK) activation was required for belinostat-induced apoptosis and anti-proliferation in PANC-1 pancreatic cancer cells. A significant AMPK activation was induced by belinostat in PANC-1 cells. Inhibition of AMPK by RNAi knockdown or dominant negative (DN) mutation significantly inhibited belinostat-induced apoptosis in PANC-1 cells. Reversely, AMPK activator AICAR and A-769662 exerted strong cytotoxicity in PANC-1 cells. Belinostat promoted reactive oxygen species (ROS) production in PANC-1 cells, increased ROS induced transforming growth factor-β-activating kinase 1 (TAK1)/AMPK association to activate AMPK. Meanwhile, anti-oxidants N-Acetyl-Cysteine (NAC) and MnTBAP as well as TAK1 shRNA knockdown suppressed belinostat-induced AMPK activation and PANC-1 cell apoptosis. In conclusion, we propose that belinostat-induced apoptosis and growth inhibition require the activation of ROS-TAK1-AMPK signaling axis in cultured pancreatic cancer cells.

Inhibition of phosphatidylinositol 3-kinase promotes tumor cell resistance to chemotherapeutic agents via a mechanism involving delay in cell cycle progression

International Nuclear Information System (INIS)

McDonald, Gail T.; Sullivan, Richard; Pare, Genevieve C.; Graham, Charles H.

2010-01-01

Approaches to overcome chemoresistance in cancer cells have involved targeting specific signaling pathways such as the phosphatidylinositol 3-kinase (PI3K) pathway, a stress response pathway known to be involved in the regulation of cell survival, apoptosis and growth. The present study determined the effect of PI3K inhibition on the clonogenic survival of human cancer cells following exposure to various chemotherapeutic agents. Treatment with the PI3K inhibitors LY294002 or Compound 15e resulted in increased survival of MDA-MB-231 breast carcinoma cells after exposure to doxorubicin, etoposide, 5-fluorouracil, and vincristine. Increased survival following PI3K inhibition was also observed in DU-145 prostate, HCT-116 colon and A-549 lung carcinoma cell lines exposed to doxorubicin. Increased cell survival mediated by LY294002 was correlated with a decrease in cell proliferation, which was linked to an increase in the proportion of cells in the G 1 phase of the cell cycle. Inhibition of PI3K signaling also resulted in higher levels of the cyclin-dependent kinase inhibitors p21 Waf1/Cip1 and p27 Kip1 ; and knockdown of p27 kip1 with siRNA attenuated resistance to doxorubicin in cells treated with LY294002. Incubation in the presence of LY294002 after exposure to doxorubicin resulted in decreased cell survival. These findings provide evidence that PI3K inhibition leads to chemoresistance in human cancer cells by causing a delay in cell cycle; however, the timing of PI3K inhibition (either before or after exposure to anti-cancer agents) may be a critical determinant of chemosensitivity.

In planta assays involving epigenetically silenced genes reveal inhibition of cytosine methylation by genistein

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Arase Sachiko

2012-03-01

Full Text Available Abstract Background Cytosine methylation is involved in epigenetic control of gene expression in a wide range of organisms. An increasing number of examples indicate that changing the frequency of cytosine methylation in the genome is a feasible tool to engineer novel traits in plants. Although demethylating effects of compounds have been analyzed in human cultured cells in terms of suppressing cancer, their effect in plant cells has not been analyzed extensively. Here, we developed in planta assay systems to detect inhibition of cytosine methylation using plants that contain a transgene transcriptionally silenced by an epigenetic mechanism. Results Seeds of two transgenic plants were used: a petunia line that has been identified as a revertant of the co-suppression of the chalcone synthase-A (CHS-A gene and contains CHS-A transgenes whose transcription is repressed; Nicotiana benthamiana plants that contain the green fluorescent protein (GFP reporter gene whose transcription is repressed through virus-induced transcriptional gene silencing. Seeds of these plants were sown on a medium that contained a demethylating agent, either 5-azacytidine or trichostatin A, and the restoration of the transcriptionally active state of the transgene was detected in seedlings. Using these systems, we found that genistein, a major isoflavonoid compound, inhibits cytosine methylation, thus restoring transgene transcription. Genistein also restored the transcription of an epigenetically silenced endogenous gene in Arabidopsis plants. Conclusions Our assay systems allowed us to assess the inhibition of cytosine methylation, in particular of maintenance of methylation, by compounds in plant cells. These results suggest a novel role of flavonoids in plant cells and that genistein is useful for modifying the epigenetic state of plant genomes.

Impaired inhibition of prepotent motor actions in patients with Tourette syndrome.

Science.gov (United States)

Wylie, Scott A; Claassen, Daniel O; Kanoff, Kristen E; Ridderinkhof, K Richard; van den Wildenberg, Wery P M

2013-09-01

Evidence that tic behaviour in individuals with Tourette syndrome reflects difficulties inhibiting prepotent motor actions is mixed. Response conflict tasks produce sensitive measures of response interference from prepotent motor impulses and the proficiency of inhibiting these impulses as an act of cognitive control. We tested the hypothesis that individuals with Tourette syndrome show a deficit in inhibiting prepotent motor actions. Healthy controls and older adolescents/adults with persistent Tourette syndrome without a history of obsessive-compulsive disorder or attention-deficit/hyperactivity disorder and presenting with stable mood functioning (i.e., no history of well-treated anxiety or depression) participated in this study. They performed a Simon task that induced conflict between prepotent actions and goal-directed actions. A novel theoretical framework distinguished group differences in acting impulsively (i.e., fast motor errors) from the proficiency of inhibiting interference by prepotent actions (i.e., slope of interference reduction). We included 27 controls and 28 individuals with Tourette syndrome in our study. Both groups showed similar susceptibility to making fast, impulsive motor errors (Tourette syndrome 26% v. control 23%; p = 0.10). The slope (m) reduction of the interference effect was significantly less pronounced among participants with Tourette syndrome than controls (Tourette syndrome: m = -0.07 v. control: m = -0.23; p = 0.022), consistent with deficient inhibitory control over prepotent actions in Tourette syndrome. This study does not address directly the role of psychiatric comorbidities and medication effects on inhibitory control over impulsive actions in individuals with Tourette syndrome. The results offer empirical evidence for deficient inhibitory control over prepotent motor actions in individuals with persistent Tourette syndrome with minimal to absent psychiatric comorbidities. These findings also suggest that the frontal

26 CFR 1.7701(l)-3 - Recharacterizing financing arrangements involving fast-pay stock.

Science.gov (United States)

2010-04-01

... benefited shareholders would use their share of the interest to buy (on a dollar-for-dollar basis) the fast..., by subtracting the amortizable premium from the accrued interest on the fast-pay shareholders..., 2000, by adding the accrued discount to the accrued interest on the benefited shareholders' portion of...

ERK1/2 pathway is involved in renal gluconeogenesis inhibition under conditions of lowered NADPH oxidase activity.

Science.gov (United States)

Winiarska, Katarzyna; Jarzyna, Robert; Dzik, Jolanta M; Jagielski, Adam K; Grabowski, Michal; Nowosielska, Agata; Focht, Dorota; Sierakowski, Bartosz

2015-04-01

The aim of this study was to elucidate the mechanisms involved in the inhibition of renal gluconeogenesis occurring under conditions of lowered activity of NADPH oxidase (Nox), the enzyme considered to be one of the main sources of reactive oxygen species in kidneys. The in vitro experiments were performed on primary cultures of rat renal proximal tubules, with the use of apocynin, a selective Nox inhibitor, and TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a potent superoxide radical scavenger. In the in vivo experiments, Zucker diabetic fatty (ZDF) rats, a well established model of diabetes type 2, were treated with apocynin solution in drinking water. The main in vitro findings are the following: (1) both apocynin and TEMPOL attenuate the rate of gluconeogenesis, inhibiting the step catalyzed by phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme of the process; (2) in the presence of the above-noted compounds the expression of PEPCK and the phosphorylation of transcription factor CREB and ERK1/2 kinases are lowered; (3) both U0126 (MEK inhibitor) and 3-(2-aminoethyl)-5-((4-ethoxyphenyl)methylene)-2,4-thiazolidinedione (ERK inhibitor) diminish the rate of glucose synthesis via mechanisms similar to those of apocynin and TEMPOL. The observed apocynin in vivo effects include: (1) slight attenuation of hyperglycemia; (2) inhibition of renal gluconeogenesis; (3) a decrease in renal PEPCK activity and content. In view of the results summarized above, it can be concluded that: (1) the lowered activity of the ERK1/2 pathway is of importance for the inhibition of renal gluconeogenesis found under conditions of lowered superoxide radical production by Nox; (2) the mechanism of this phenomenon includes decreased PEPCK expression, resulting from diminished activity of transcription factor CREB; (3) apocynin-evoked inhibition of renal gluconeogenesis contributes to the hypoglycemic action of this compound observed in diabetic animals. Thus, the study has

Phasing of muscle gene expression with fasting-induced recovery growth in Atlantic salmon

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Bower Neil I

2009-08-01

Full Text Available Abstract Background Many fish species experience long periods of fasting in nature often associated with seasonal reductions in water temperature and prey availability or spawning migrations. During periods of nutrient restriction, changes in metabolism occur to provide cellular energy via catabolic processes. Muscle is particularly affected by prolonged fasting as myofibrillar proteins act as a major energy source. To investigate the mechanisms of metabolic reorganisation with fasting and refeeding in a saltwater stage of Atlantic salmon (Salmo salar L. we analysed the expression of genes involved in myogenesis, growth signalling, lipid biosynthesis and myofibrillar protein degradation and synthesis pathways using qPCR. Results Hierarchical clustering of gene expression data revealed three clusters. The first cluster comprised genes involved in lipid metabolism and triacylglycerol synthesis (ALDOB, DGAT1 and LPL which had peak expression 3-14d after refeeding. The second cluster comprised ADIPOQ, MLC2, IGF-I and TALDO1, with peak expression 14-32d after refeeding. Cluster III contained genes strongly down regulated as an initial response to feeding and included the ubiquitin ligases MuRF1 and MAFbx, myogenic regulatory factors and some metabolic genes. Conclusion Early responses to refeeding in fasted salmon included the synthesis of triacylglycerols and activation of the adipogenic differentiation program. Inhibition of MuRF1 and MAFbx respectively may result in decreased degradation and concomitant increased production of myofibrillar proteins. Both of these processes preceded any increase in expression of myogenic regulatory factors and IGF-I. These responses could be a necessary strategy for an animal adapted to long periods of food deprivation whereby energy reserves are replenished prior to the resumption of myogenesis.

High-dose alcohol intoxication differentially modulates cognitive subprocesses involved in response inhibition.

Science.gov (United States)

Stock, Ann-Kathrin; Schulz, Tom; Lenhardt, Martin; Blaszkewicz, Meinolf; Beste, Christian

2016-01-01

Aside from well-known physiological effects, high-dose alcohol intoxication (a.k.a. binge drinking) can lead to aversive social and legal consequences because response inhibition is usually compromised under the influence of alcohol. Although the behavioral aspects of this phenomenon were reported on extensively, the underlying neurophysiological mechanisms mediating this disinhibition are unclear. To close this gap, we used both behavioral and neurophysiological measures (event-related potentials, ERPs) to investigate which subprocesses of response inhibition are altered under the influence of high-dose alcohol intoxication. Using a within-subject design, we asked young healthy participants (n = 27) to complete a GO/NOGO task once sober and once intoxicated (approximately 1.2‰). During intoxication, high-dose alcohol effects were highest in a condition where the participants could not rely on automated stimulus-response mapping processes during response inhibition. In this context, the NOGO-P3 (ERP), that likely depends on dopaminergic signaling within mesocorticolimbic pathways and is thought to reflect motor inhibition and/or the evaluation of inhibitory processes, was altered in the intoxicated state. In contrast to this, the N2 component, which largely depends on nigrostriatal dopamine pathways and is thought to reflect inhibition on a pre-motor level, was not altered. Based on these results, we demonstrate that alcohol-induced changes of dopaminergic neurotransmission do not exert a global effect on response inhibition. Instead, changes are highly subprocess-specific and seem to mainly target mesocorticolimbic pathways that contribute to motor inhibition and the evaluation of such. © 2014 Society for the Study of Addiction.

Streptomyces lunalinharesii strain 235 shows the potential to inhibit bacteria involved in biocorrosion processes.

Science.gov (United States)

Pacheco da Rosa, Juliana; Korenblum, Elisa; Franco-Cirigliano, Marcella Novaes; Abreu, Fernanda; Lins, Ulysses; Soares, Rosângela M A; Macrae, Andrew; Seldin, Lucy; Coelho, Rosalie R R

2013-01-01

Four actinomycete strains previously isolated from Brazilian soils were tested for their antimicrobial activity against Bacillus pumilus LF-4 and Desulfovibrio alaskensis NCIMB 13491, bacteria that are well known to be involved in biofilm formation and biocorrosion. Strain 235, belonging to the species Streptomyces lunalinharesii, inhibited the growth of both bacteria. The antimicrobial activity was seen over a wide range of pH, and after treatment with several chemicals and heat but not with proteinase K and trypsin. The antimicrobial substances present in the concentrated supernatant from growth media were partially characterized by SDS-PAGE and extracellular polypeptides were seen. Bands in the size range of 12 to 14.4 kDa caused antimicrobial activity. Transmission electron microscopy of D. alaskensis cells treated with the concentrated supernatant containing the antimicrobial substances revealed the formation of prominent bubbles, the spherical double-layered structures on the cell membrane, and the periplasmic space completely filled with electron-dense material. This is the first report on the production of antimicrobial substances by actinomycetes against bacteria involved in biocorrosion processes, and these findings may be of great relevance as an alternative source of biocides to those currently employed in the petroleum industry.

Involvement of activation of PKR in HBx-siRNA-mediated innate immune effects on HBV inhibition.

Directory of Open Access Journals (Sweden)

Qiuju Han

Full Text Available RNA interference (RNAi of virus-specific genes offers the possibility of developing a new anti-hepatitis B virus (anti-HBV therapy. Recent studies have revealed that siRNAs can induce an innate immune response in vitro and in vivo. Here, HBVx (HBx mRNA expression and HBV replication were significantly inhibited, followed by the enhancement of expression of type I interferons (IFNs, IFN-stimulated genes (ISG15 and ISG56 and proinflammatory cytokines after HepG2.2.15 cells were transfected with chemically synthesized HBx-siRNAs. Transfection with HBx-siRNAs also significantly increased expression of dsRNA-dependent protein kinase R (PKR in HepG2.2.15 cells, followed by activation of downstream signaling events such as eukaryotic initiation factor 2α (eIF2-α. In PKR-over-expressing HepG2.2.15 cells, HBx-siRNAs exerted more potent inhibitory effects on HBV replication and greater production of type I IFNs. By contrast, the inhibitory effect of HBx-siRNAs on HBV replication was attenuated when PKR was inhibited or silenced, demonstrating that HBx-siRNAs greatly promoted PKR activation, leading to the higher production of type I IFN. Therefore, we concluded that PKR is involved in the innate immune effects mediated by HBx-siRNAs and further contributes to HBV inhibition. The bifunctional siRNAs with both gene silencing and innate immune activation properties may represent a new potential strategy for treatment of HBV.

Blunted lipolytic response to fasting in abdominally obese women: evidence for involvement of hyposomatotropism

NARCIS (Netherlands)

Buijs, Madelon M.; Burggraaf, Jacobus; Wijbrandts, Carla; de Kam, Marieke L.; Frölich, Marijke; Cohen, Adam F.; Romijn, Johannes A.; Sauerwein, Hans P.; Meinders, A. Edo; Pijl, Hanno

2003-01-01

Background: Abdominal obesity is associated with a blunted lipolytic response to fasting that may contribute to the preservation of adipose tissue mass. Objective: To further explore the pathophysiology of blunted lipolysis during fasting in obesity, we simultaneously measured lipolysis and distinct

Caffeine inhibits STAT1 signaling and downregulates inflammatory pathways involved in autoimmunity.

Science.gov (United States)

Iris, Merve; Tsou, Pei-Suen; Sawalha, Amr H

2018-04-18

Caffeine is a widely consumed pharmacologically active product. We focused on characterizing immunomodulatory effects of caffeine on peripheral blood mononuclear cells. Caffeine at high doses showed a robust downregulatory effect on cytokine activity and genes related to several autoimmune diseases including lupus and rheumatoid arthritis. Dose-dependent validation experiments showed downregulation at the mRNA levels of key inflammation-related genes including STAT1, TNF, IFNG, and PPARG. TNF and PPARG were suppressed even with the lowest caffeine dose tested, which corresponds to the serum concentration of caffeine after administration of one cup of coffee. Cytokine levels of IL-8, MIP-1β, IL-6, IFN-γ, GM-CSF, TNF, IL-2, IL-4, MCP-1, and IL-10 were decreased significantly with caffeine treatment. Upstream regulator analysis suggests that caffeine inhibits STAT1 signaling, which was confirmed by showing reduced phosphorylated STAT1 after caffeine treatment. Further studies exploring disease-modulating potential of caffeine in autoimmune diseases and further exploring the mechanisms involved are warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

Direct evidence that FK506 inhibition of FcepsilonRI-mediated exocytosis from RBL mast cells involves calcineurin.

Science.gov (United States)

Hultsch, T; Brand, P; Lohmann, S; Saloga, J; Kincaid, R L; Knop, J

1998-05-01

FcepsilonRI-mediated exocytosis of preformed mediators from mast cells and basophils (e.g. histamine, serotonin, beta-hexosaminidase) is sensitive to the immunosuppressants cyclosporin A and FK506 (IC50 200 and 4 nM, respectively) but not rapamycin. The mechanism of inhibition does not appear to involve tyrosine phosphorylation, hydrolysis of inositol phosphates or calcium flux. Here we report experiments using a molecular approach to assess the role of calcineurin, a serine/threonine phosphatase thought to be the primary pharmacological target of these drugs. Calcineurin's activity requires association of its catalytic (A) subunit with an intrinsic regulatory (B) subunit. We hypothesized that calcineurin-sensitive signalling events should be affected by the depletion of calcineurin B subunits, thereby reducing the number of active A:B complexes. We therefore transfected rat basophilic leukemia (RBL) cells with an inhibitory (dominant negative) form of the calcineurin A subunit, which binds the calcineurin B subunit with high affinity but does not possess catalytic activity (B subunit knock-out, BKO). In these transfected cells, the dose-response curve for the inhibition of FcepsilonRI-mediated exocytosis by FK506 was shifted to the left, indicating an increased drug sensitivity of BKO-transfected cells. We conclude that FK506 inhibition of FcepsilonRI-mediated exocytosis in mast cells specifically targets calcineurin activity.

The Haemophilus ducreyi LspA1 protein inhibits phagocytosis by using a new mechanism involving activation of C-terminal Src kinase.

Science.gov (United States)

Dodd, Dana A; Worth, Randall G; Rosen, Michael K; Grinstein, Sergio; van Oers, Nicolai S C; Hansen, Eric J

2014-05-20

Haemophilus ducreyi causes chancroid, a sexually transmitted infection. A primary means by which this pathogen causes disease involves eluding phagocytosis; however, the molecular basis for this escape mechanism has been poorly understood. Here, we report that the LspA virulence factors of H. ducreyi inhibit phagocytosis by stimulating the catalytic activity of C-terminal Src kinase (Csk), which itself inhibits Src family protein tyrosine kinases (SFKs) that promote phagocytosis. Inhibitory activity could be localized to a 37-kDa domain (designated YL2) of the 456-kDa LspA1 protein. The YL2 domain impaired ingestion of IgG-opsonized targets and decreased levels of active SFKs when expressed in mammalian cells. YL2 contains tyrosine residues in two EPIYG motifs that are phosphorylated in mammalian cells. These tyrosine residues were essential for YL2-based inhibition of phagocytosis. Csk was identified as the predominant mammalian protein interacting with YL2, and a dominant-negative Csk rescued phagocytosis in the presence of YL2. Purified Csk phosphorylated the tyrosines in the YL2 EPIYG motifs. Phosphorylated YL2 increased Csk catalytic activity, resulting in positive feedback, such that YL2 can be phosphorylated by the same kinase that it activates. Finally, we found that the Helicobacter pylori CagA protein also inhibited phagocytosis in a Csk-dependent manner, raising the possibility that this may be a general mechanism among diverse bacteria. Harnessing Csk to subvert the Fcγ receptor (FcγR)-mediated phagocytic pathway represents a new bacterial mechanism for circumventing a crucial component of the innate immune response and may potentially affect other SFK-involved cellular pathways. Phagocytosis is a critical component of the immune system that enables pathogens to be contained and cleared. A number of bacterial pathogens have developed specific strategies to either physically evade phagocytosis or block the intracellular signaling required for

Predictors of Ramadan fasting during pregnancy

NARCIS (Netherlands)

van Bilsen, Lily A.; Savitri, Ary I.; Amelia, Dwirani; Baharuddin, Mohammad; Grobbee, Diederick E.; Uiterwaal, Cuno S P M

2016-01-01

Although the health effects of Ramadan fasting during pregnancy are still unclear, it is important to identify the predictors and motivational factors involved in women's decision to observe the fast. We investigated these factors in a cross sectional study of 187 pregnant Muslim women who attended

Fast timing discriminator

International Nuclear Information System (INIS)

Lo, C.C.

1977-01-01

The processing of pulses with very fast risetimes for timing purposes involves many problems because of the large equivalent bandwidths involved. For pulses with risetimes in the 150 ps range (and full widths at half maximum (FWHM) of 400 ps) bandwidths in excess of 1GHz are required. Furthermore, these very narrow pulses with current amplitudes as small as 1 mA carry very small charges ( -12 coulomb), therefore, requiring very sensitive trigger circuits. The difficulty increases when timing characteristics in the picosecond range are sought especially when a wide input signal amplitude range causes a time-walk problem. The fast timing discriminator described has a time-walk of approximately +-75 ps over the input signal range from 80 mV to 3V. A schematic of the discriminator is included, and operation and performance are discussed

Evidence that the cortical motor command for the initiation of dynamic plantarflexion consists of excitation followed by inhibition

DEFF Research Database (Denmark)

Taube, Wolfgang; Lundbye-Jensen, Jesper; Schubert, Martin

2011-01-01

by conditioning the soleus H-reflex with different interstimulus intervals by cervicomedullary stimulation (CMS-conditioning) and transcranial magnetic stimulation (TMS) of M1 (M1-conditioning). This technique provides a precise time course of facilitation and inhibition. CMS- and M1-conditioning produced......At the onset of dynamic movements excitation of the motor cortex (M1) is spatially restricted to areas representing the involved muscles whereas adjacent areas are inhibited. The current study elucidates whether the cortical motor command for dynamic contractions is also restricted to a certain...... population of cortical neurons responsible for the fast corticospinal projections. Therefore, corticospinal transmission was assessed with high temporal resolution during dynamic contractions after both, magnetic stimulation over M1 and the brainstem. The high temporal resolution could be obtained...

Atrial natriuretic peptide: a possible mediator involved in dexamethasone's inhibition of cell proliferation in multiple myeloma.

Science.gov (United States)

Ding, Jiang-Hua; Chang, Yu-Sui

2012-08-01

Atrial natriuretic peptide (ANP) has been recognized for several decades for its role of regulating blood pressure. Recently, cumulating evidences show that ANP plays an anticancer role in various solid tumors via blocking the kinase cascade of Ras-MEK1/2-ERK1/2 with the result of inhibition of DNA synthesis. ANP, as well as its receptors (NPR-A and NPR-C) has been identified present in the embryonic stem cell and a wide range of cancer cells. Various lymphoid organs, such as lymph nodes, have been detected the presence of ANP. Multiple myeloma (MM), though the therapies have evolved significantly, is still an incurable disease as B lymphocyte cell neoplasm. Dexamethasone is the cornerstone in treatment of MM via inactivation of Ras-MEK1/2-ERK1/2 cascade reaction. Coincidently, dexamethasone can increase the expression of ANP markedly. Nevertheless, the role of ANP in MM is unclear. Based on these results above, we raise the hypothesis that ANP is involved in mediating dexamethasone's inhibition of proliferation in MM cells, which suggests that ANP may be a potential agent to treat MM. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Streptomyces lunalinharesii Strain 235 Shows the Potential to Inhibit Bacteria Involved in Biocorrosion Processes

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Juliana Pacheco da Rosa

2013-01-01

Full Text Available Four actinomycete strains previously isolated from Brazilian soils were tested for their antimicrobial activity against Bacillus pumilus LF-4 and Desulfovibrio alaskensis NCIMB 13491, bacteria that are well known to be involved in biofilm formation and biocorrosion. Strain 235, belonging to the species Streptomyces lunalinharesii, inhibited the growth of both bacteria. The antimicrobial activity was seen over a wide range of pH, and after treatment with several chemicals and heat but not with proteinase K and trypsin. The antimicrobial substances present in the concentrated supernatant from growth media were partially characterized by SDS-PAGE and extracellular polypeptides were seen. Bands in the size range of 12 to 14.4 kDa caused antimicrobial activity. Transmission electron microscopy of D. alaskensis cells treated with the concentrated supernatant containing the antimicrobial substances revealed the formation of prominent bubbles, the spherical double-layered structures on the cell membrane, and the periplasmic space completely filled with electron-dense material. This is the first report on the production of antimicrobial substances by actinomycetes against bacteria involved in biocorrosion processes, and these findings may be of great relevance as an alternative source of biocides to those currently employed in the petroleum industry.

Exercise Inhibits the Effects of Smoke-Induced COPD Involving Modulation of STAT3

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Maysa Alves Rodrigues Brandao-Rangel

2017-01-01

Full Text Available Purpose. Evaluate the participation of STAT3 in the effects of aerobic exercise (AE in a model of smoke-induced COPD. Methods. C57Bl/6 male mice were divided into control, Exe, COPD, and COPD+Exe groups. Smoke were administered during 90 days. Treadmill aerobic training begun on day 61 until day 90. Pulmonary inflammation, systemic inflammation, the level of lung emphysema, and the airway remodeling were evaluated. Analysis of integral and phosphorylated expression of STAT3 by airway epithelial cells, peribronchial leukocytes, and parenchymal leukocytes was performed. Results. AE inhibited smoke-induced accumulation of total cells (p<0.001, lymphocytes (p<0.001, and neutrophils (p<0.001 in BAL, as well as BAL levels of IL-1β (p<0.001, CXCL1 (p<0.001, IL-17 (p<0.001, and TNF-α (p<0.05, while increased the levels of IL-10 (p<0.001. AE also inhibited smoke-induced increases in total leukocytes (p<0.001, neutrophils (p<0.05, lymphocytes (p<0.001, and monocytes (p<0.01 in blood, as well as serum levels of IL-1β (p<0.01, CXCL1 (p<0.01, IL-17 (p<0.05, and TNF-α (p<0.01, while increased the levels of IL-10 (p<0.001. AE reduced smoke-induced emphysema (p<0.001 and collagen fiber accumulation in the airways (p<0.001. AE reduced smoke-induced STAT3 and phospho-STAT3 expression in airway epithelial cells (p<0.001, peribronchial leukocytes (p<0.001, and parenchymal leukocytes (p<0.001. Conclusions. AE reduces smoke-induced COPD phenotype involving STAT3.

Involvement of CNOT3 in mitotic progression through inhibition of MAD1 expression

Energy Technology Data Exchange (ETDEWEB)

Takahashi, Akinori [Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan); Kikuguchi, Chisato [Cell Signal Unit, Okinawa Institute of Science and Technology, Kunigami, Okinawa 904-0412 (Japan); Morita, Masahiro; Shimodaira, Tetsuhiro; Tokai-Nishizumi, Noriko; Yokoyama, Kazumasa; Ohsugi, Miho; Suzuki, Toru [Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan); Yamamoto, Tadashi, E-mail: tyamamot@ims.u-tokyo.ac.jp [Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 (Japan); Cell Signal Unit, Okinawa Institute of Science and Technology, Kunigami, Okinawa 904-0412 (Japan)

2012-03-09

Highlights: Black-Right-Pointing-Pointer CNOT3 depletion increases the mitotic index. Black-Right-Pointing-Pointer CNOT3 inhibits the expression of MAD1. Black-Right-Pointing-Pointer CNOT3 destabilizes the MAD1 mRNA. Black-Right-Pointing-Pointer MAD1 knockdown attenuates the CNOT3 depletion-induced mitotic arrest. -- Abstract: The stability of mRNA influences the dynamics of gene expression. The CCR4-NOT complex, the major deadenylase in mammalian cells, shortens the mRNA poly(A) tail and contributes to the destabilization of mRNAs. The CCR4-NOT complex plays pivotal roles in various physiological functions, including cell proliferation, apoptosis, and metabolism. Here, we show that CNOT3, a subunit of the CCR4-NOT complex, is involved in the regulation of the spindle assembly checkpoint, suggesting that the CCR4-NOT complex also plays a part in the regulation of mitosis. CNOT3 depletion increases the population of mitotic-arrested cells and specifically increases the expression of MAD1 mRNA and its protein product that plays a part in the spindle assembly checkpoint. We showed that CNOT3 depletion stabilizes the MAD1 mRNA, and that MAD1 knockdown attenuates the CNOT3 depletion-induced increase of the mitotic index. Basing on these observations, we propose that CNOT3 is involved in the regulation of the spindle assembly checkpoint through its ability to regulate the stability of MAD1 mRNA.

Involvement of CNOT3 in mitotic progression through inhibition of MAD1 expression

International Nuclear Information System (INIS)

Takahashi, Akinori; Kikuguchi, Chisato; Morita, Masahiro; Shimodaira, Tetsuhiro; Tokai-Nishizumi, Noriko; Yokoyama, Kazumasa; Ohsugi, Miho; Suzuki, Toru; Yamamoto, Tadashi

2012-01-01

Highlights: ► CNOT3 depletion increases the mitotic index. ► CNOT3 inhibits the expression of MAD1. ► CNOT3 destabilizes the MAD1 mRNA. ► MAD1 knockdown attenuates the CNOT3 depletion-induced mitotic arrest. -- Abstract: The stability of mRNA influences the dynamics of gene expression. The CCR4–NOT complex, the major deadenylase in mammalian cells, shortens the mRNA poly(A) tail and contributes to the destabilization of mRNAs. The CCR4–NOT complex plays pivotal roles in various physiological functions, including cell proliferation, apoptosis, and metabolism. Here, we show that CNOT3, a subunit of the CCR4–NOT complex, is involved in the regulation of the spindle assembly checkpoint, suggesting that the CCR4–NOT complex also plays a part in the regulation of mitosis. CNOT3 depletion increases the population of mitotic-arrested cells and specifically increases the expression of MAD1 mRNA and its protein product that plays a part in the spindle assembly checkpoint. We showed that CNOT3 depletion stabilizes the MAD1 mRNA, and that MAD1 knockdown attenuates the CNOT3 depletion-induced increase of the mitotic index. Basing on these observations, we propose that CNOT3 is involved in the regulation of the spindle assembly checkpoint through its ability to regulate the stability of MAD1 mRNA.

Inhibition of ethylene production by putrescine alleviates aluminium-induced root inhibition in wheat plants.

Science.gov (United States)

Yu, Yan; Jin, Chongwei; Sun, Chengliang; Wang, Jinghong; Ye, Yiquan; Zhou, Weiwei; Lu, Lingli; Lin, Xianyong

2016-01-08

Inhibition of root elongation is one of the most distinct symptoms of aluminium (Al) toxicity. Although putrescine (Put) has been identified as an important signaling molecule involved in Al tolerance, it is yet unknown how Put mitigates Al-induced root inhibition. Here, the possible mechanism was investigated by using two wheat genotypes differing in Al resistance: Al-tolerant Xi Aimai-1 and Al-sensitive Yangmai-5. Aluminium caused more root inhibition in Yangmai-5 and increased ethylene production at the root apices compared to Xi Aimai-1, whereas the effects were significantly reversed by ethylene biosynthesis inhibitors. The simultaneous exposure of wheat seedlings to Al and ethylene donor, ethephon, or ethylene biosynthesis precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), increased ethylene production and aggravated root inhibition, which was more pronounced in Xi Aimai-1. In contrast, Put treatment decreased ethylene production and alleviated Al-induced root inhibition in both genotypes, and the effects were more conspicuous in Yangmai-5. Furthermore, our results indicated that Al-induced ethylene production was mediated by ACC synthase (ACS) and ACC oxidase, and that Put decreased ethylene production by inhibiting ACS. Altogether, these findings indicate that ethylene is involved in Al-induced root inhibition and this process could be alleviated by Put through inhibiting ACS activity.

Sero-epidemiological assessment and diagnosis of visceral leishmaniasis in an endemic locality using Fast Agglutination Screening Test (FAST)

NARCIS (Netherlands)

Hailu, A.; Kroon, C. C. M.; Schoone, G. J.; Berhe, N.; Schallig, H. D. F. H.; Kager, P. A.

2002-01-01

The Fast Agglutination Screening Test (FAST) was employed on sera obtained from an endemic area of visceral leishmaniasis in southwestern Ethiopia, in February 2000. The study involved (i) active case detection among 1575 residents of two villages; and (ii) passive case detection in an outpatient

Effects of toluene on protein synthesis and the interaction with ethanol in hepatocytes isolated from fed and fasted rats

International Nuclear Information System (INIS)

Smith-Kielland, A.; Ripel, Aa.; Gadeholt, G.

1989-01-01

The effects of three different concentrations (about 20, 100 and 1000 μM) of toluene on protein synthesis were studied in hepatocytes isolated from fed and fasted rats after 60 and 120 min. of incubation. The interaction between ethanol (60 mM) and the low and high toluene concentrations were also tested. To measure protein synthesis, 14 C-valine was used as the precursor amino acid. Total valine concentration was 2 mM to ensure near-constant specific radioactivity of precursor. Toluene concentrations were measured by head-space gas chromatography. Protein synthesis was unchanged in the presence of low toluene concentrations. Intermediate toluene concentration decreased protein synthesis by about 20% and high toluene concentration decreased protein synthesis by about 60%. Protein synthesis was similar in cells from fed and fasted rats. Ethanol alone inhibited protein synthesis by 20-30%, more in fasted than in fed rats. Toluene and ethanol in combination inhibited protein synthesis additively. The high toluene concentration with or without ethanol appeared to inhibit synthesis/secretion of export proteins in hepatocytes from fasted rats. In conclusion, our study indicates that toluene in relatively high concentrations inhibits general protein synthesis in isolated rat hepatocytes. Toluene and ethanol seems to inhibit protein synthesis additively. (author)

Effects of toluene on protein synthesis and the interaction with ethanol in hepatocytes isolated from fed and fasted rats

Energy Technology Data Exchange (ETDEWEB)

Smith-Kielland, A.; Ripel, Aa.; Gadeholt, G.

1989-01-01

The effects of three different concentrations (about 20, 100 and 1000 ..mu..M) of toluene on protein synthesis were studied in hepatocytes isolated from fed and fasted rats after 60 and 120 min. of incubation. The interaction between ethanol (60 mM) and the low and high toluene concentrations were also tested. To measure protein synthesis, /sup 14/C-valine was used as the precursor amino acid. Total valine concentration was 2 mM to ensure near-constant specific radioactivity of precursor. Toluene concentrations were measured by head-space gas chromatography. Protein synthesis was unchanged in the presence of low toluene concentrations. Intermediate toluene concentration decreased protein synthesis by about 20% and high toluene concentration decreased protein synthesis by about 60%. Protein synthesis was similar in cells from fed and fasted rats. Ethanol alone inhibited protein synthesis by 20-30%, more in fasted than in fed rats. Toluene and ethanol in combination inhibited protein synthesis additively. The high toluene concentration with or without ethanol appeared to inhibit synthesis/secretion of export proteins in hepatocytes from fasted rats. In conclusion, our study indicates that toluene in relatively high concentrations inhibits general protein synthesis in isolated rat hepatocytes. Toluene and ethanol seems to inhibit protein synthesis additively.

Thermogenesis induced by a high-carbohydrate meal in fasted lean and overweight young men: insulin, body fat, and sympathetic nervous system involvement.

Science.gov (United States)

Marques-Lopes, Iva; Forga, Luis; Martínez, J Alfredo

2003-01-01

This dietary trial was designed to evaluate the effect of an experimental short-term fasting period followed by a high-carbohydrate meal on energy expenditure, thermogenesis, and sympathetic nervous system activity in normal (body mass index 27 kg/m(2)) men who were healthy, non-diabetic or with no other endocrine disease, non-smokers, not taking oral prescription medications, and with a stable body weight for the previous 3 mo. Fasting and fed energy expenditures and diet-induced thermogenesis were measured after a high-carbohydrate meal in seven overweight and six lean young male subjects by indirect calorimetry. Heart rate, urinary excretion of catecholamines, serum glucose, and insulin were also measured over the experimental fasting (7.5 h) and postprandial (4 h) periods. After carbohydrate intake, overweight men showed a significantly higher energy production (kJ/kg of fat-free mass) than did lean individuals, and the diet-induced thermogenesis (percentage of energy intake) was positively correlated with body fat (kg), percentage of body fat, fat-free mass (kg), and fasting pre-meal serum insulin levels. Postprandial cumulative energy expenditure was directly associated with postprandial insulin response and with mean postprandial heart rate values. No significant differences in urinary catecholamines were found between lean and overweight men at basal conditions or during the study period. Overweight individuals showed similar short-term sympathetic nervous system responses induced by an experimental fasting period. Although diet-induced thermogenesis after carbohydrate intake was not statistically different between lean and overweight men, the postprandial insulin response and body fat content seemed to be involved in sympathetic nervous system activity.

Rosmarinic acid counteracts activation of hepatic stellate cells via inhibiting the ROS-dependent MMP-2 activity: Involvement of Nrf2 antioxidant system

Energy Technology Data Exchange (ETDEWEB)

Lu, Changfang; Zou, Yu; Liu, Yuzhang; Niu, Yingcai, E-mail: nyc1968@126.com

2017-03-01

Recently, oxidative stress is involved in hepatofibrogenesis. Matrix metalloproteinase-2 (MMP-2) is required for activation of hepatic stellate cells (HSCs) in response to reactive oxygen species (ROS). This study was designed to explore the hypothesis that the inhibitory effect of rosmarinic acid (RA) on HSCs activation might mainly result from its antioxidant capability by increasing the synthesis of glutathione (GSH) involved in nuclear factor kappa B (NF-κB)-dependent inhibition of MMP-2 activity. Here, we demonstrate that RA reverses activated HSCs to quiescent cells. Concomitantly, RA inhibits MMP-2 activity. RNA interference-imposed knockdown of NF-κB abolished down-regulation of MMP-2 by RA. RA-mediated inactivation of NF-κB could be blocked by the diphenyleneiodonium chloride (DPI; a ROS inhibitor). Conversely, transfection of dominant-negative (DN) mutant of extracellular signal-regulated kinases 2 (ERK2), c-Jun N-terminal kinase 1 (JNK1), or p38α kinase had no such effect. Simultaneously, RA suppresses ROS generation and lipid peroxidation (LPO) whereas increases cellular GSH in HSC-T6 cells. Furthermore, RA significantly increased antioxidant response element (ARE)-mediated luciferase activity, nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and catalytic subunits from glutamate cysteine ligase (GCLc) expression, but not modulatory subunits from GCL (GCLm). RA-mediated up-regulation of GClc is inhibited by the shRNA-induced Nrf2 knockdown. The knocking down of Nrf2 or buthionine sulfoximine (a GCL inhibitor) abolished RA-mediated inhibition of ROS. Collectively, these results provide novel insights into the mechanisms of RA as an antifibrogenic candidate in the prevention and treatment of liver fibrosis. - Highlights: • RA reverses activated HSCs to quiescent cells. • RA suppresses MMP-2 activity through a NF-κB-dependent pathway. • Inhibition of oxidative stress by RA is dependent on nuclear translocation of Nrf2

Rosmarinic acid counteracts activation of hepatic stellate cells via inhibiting the ROS-dependent MMP-2 activity: Involvement of Nrf2 antioxidant system

International Nuclear Information System (INIS)

Lu, Changfang; Zou, Yu; Liu, Yuzhang; Niu, Yingcai

2017-01-01

Recently, oxidative stress is involved in hepatofibrogenesis. Matrix metalloproteinase-2 (MMP-2) is required for activation of hepatic stellate cells (HSCs) in response to reactive oxygen species (ROS). This study was designed to explore the hypothesis that the inhibitory effect of rosmarinic acid (RA) on HSCs activation might mainly result from its antioxidant capability by increasing the synthesis of glutathione (GSH) involved in nuclear factor kappa B (NF-κB)-dependent inhibition of MMP-2 activity. Here, we demonstrate that RA reverses activated HSCs to quiescent cells. Concomitantly, RA inhibits MMP-2 activity. RNA interference-imposed knockdown of NF-κB abolished down-regulation of MMP-2 by RA. RA-mediated inactivation of NF-κB could be blocked by the diphenyleneiodonium chloride (DPI; a ROS inhibitor). Conversely, transfection of dominant-negative (DN) mutant of extracellular signal-regulated kinases 2 (ERK2), c-Jun N-terminal kinase 1 (JNK1), or p38α kinase had no such effect. Simultaneously, RA suppresses ROS generation and lipid peroxidation (LPO) whereas increases cellular GSH in HSC-T6 cells. Furthermore, RA significantly increased antioxidant response element (ARE)-mediated luciferase activity, nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and catalytic subunits from glutamate cysteine ligase (GCLc) expression, but not modulatory subunits from GCL (GCLm). RA-mediated up-regulation of GClc is inhibited by the shRNA-induced Nrf2 knockdown. The knocking down of Nrf2 or buthionine sulfoximine (a GCL inhibitor) abolished RA-mediated inhibition of ROS. Collectively, these results provide novel insights into the mechanisms of RA as an antifibrogenic candidate in the prevention and treatment of liver fibrosis. - Highlights: • RA reverses activated HSCs to quiescent cells. • RA suppresses MMP-2 activity through a NF-κB-dependent pathway. • Inhibition of oxidative stress by RA is dependent on nuclear translocation of Nrf2

The Antiproliferative Effect of Cyclodipeptides from Pseudomonas aeruginosa PAO1 on HeLa Cells Involves Inhibition of Phosphorylation of Akt and S6k Kinases.

Science.gov (United States)

Hernández-Padilla, Laura; Vázquez-Rivera, Dolores; Sánchez-Briones, Luis A; Díaz-Pérez, Alma L; Moreno-Rodríguez, José; Moreno-Eutimio, Mario A; Meza-Carmen, Victor; Cruz, Homero Reyes-De la; Campos-García, Jesús

2017-06-20

Pseudomonas aeruginosa PAO1, a potential pathogen of plants and animals, produces the cyclodipeptides cyclo(l-Pro-l-Tyr), cyclo(l-Pro-l-Phe), and cyclo(l-Pro-l-Val) (PAO1-CDPs), whose effects have been implicated in inhibition of human tumor cell line proliferation. Our purpose was to investigate in depth in the mechanisms of HeLa cell proliferation inhibition by the PAO1-CDPs. The results indicate that PAO1-CDPs, both purified individually and in mixtures, inhibited HeLa cell proliferation by arresting the cell cycle at the G0-G1 transition. The crude PAO1-CDPs mixture promoted cell death in HeLa cells in a dose-dependent manner, showing efficacy similar to that of isolated PAO1-CDPs (LD 50 of 60-250 µM) and inducing apoptosis with EC 50 between 0.6 and 3.0 µM. Moreover, PAO1-CDPs showed a higher proapoptotic activity (~10³-10⁵ fold) than their synthetic analogs did. Subsequently, the PAO1-CDPs affected mitochondrial membrane potential and induced apoptosis by caspase-9-dependent pathway. The mechanism of inhibition of cells proliferation in HeLa cells involves inhibition of phosphorylation of both Akt-S473 and S6k-T389 protein kinases, showing a cyclic behavior of their expression and phosphorylation in a time and concentration-dependent fashion. Taken together our findings indicate that PI3K-Akt-mTOR-S6k signaling pathway blockage is involved in the antiproliferative effect of the PAO1-CDPs.

Inhibition of beta-amino acid transport by diamide does not involve the brush border membrane surface

International Nuclear Information System (INIS)

Chesney, R.W.; Gusowski, N.; Albright, P.

1985-01-01

Diamide (dicarboxylic acid bis-(N,N-dimethylamide) has been shown in previous studies to block the uptake of the beta-amino acid taurine at its high affinity transport site in rat renal cortex slices. Diamide may act by increasing the efflux of taurine from the slice. Studies performed in rat slices again indicate enhanced efflux over 8-12 minutes. The time course of reduced glutathione (GSH) depletion from renal cortex is similar, indicating a potential interaction between GSH depletion and inhibition of taurine accumulation. The effect of 9 mM diamide on the Na+ -dependent accumulation of taurine (10 and 250 microM) by brush border membrane vesicles was examined, and the taurine uptake value both initially and at equilibrium was the same in the presence and absence of diamide. Isolation of the brush border surface and subsequent transport studies of taurine are not influenced by diamide. Thus, diamide inhibition of taurine uptake does not involve physiochemical alteration of the membrane surface where active amino acid transport occurs, despite the thiol-oxidizing properties of this agent. Further, these studies suggest that diamide either acts at the basolateral surface, rather than the brush border surface of rat renal cortex or requires the presence of an intact tubule, capable of metabolism, prior to its inhibitory action

Salinity-induced inhibition of growth in the aquatic pteridophyte Azolla microphylla primarily involves inhibition of photosynthetic components and signaling molecules as revealed by proteome analysis.

Science.gov (United States)

Thagela, Preeti; Yadav, Ravindra Kumar; Mishra, Vagish; Dahuja, Anil; Ahmad, Altaf; Singh, Pawan Kumar; Tiwari, Budhi Sagar; Abraham, Gerard

2017-01-01

Salinity stress causes adverse physiological and biochemical changes in the growth and productivity of a plant. Azolla, a symbiotic pteridophyte and potent candidate for biofertilizer due to its nitrogen fixation ability, shows reduced growth and nitrogen fixation during saline stress. To better understand regulatory components involved in salinity-induced physiological changes, in the present study, Azolla microphylla plants were exposed to NaCl (6.74 and 8.61 ds/m) and growth, photochemical reactions of photosynthesis, ion accumulation, and changes in cellular proteome were studied. Maximum dry weight was accumulated in control and untreated plant while a substantial decrease in dry weight was observed in the plants exposed to salinity. Exposure of the organism to different concentrations of salt in hydroponic conditions resulted in differential level of Na + and K + ion accumulation. Comparative analysis of salinity-induced proteome changes in A. microphylla revealed 58 salt responsive proteins which were differentially expressed during the salt exposure. Moreover, 42 % spots among differentially expressed proteins were involved in different signaling events. The identified proteins are involved in photosynthesis, energy metabolism, amino acid biosynthesis, protein synthesis, and defense. Downregulation of these key metabolic proteins appears to inhibit the growth of A. microphylla in response to salinity. Altogether, the study revealed that in Azolla, increased salinity primarily affected signaling and photosynthesis that in turn leads to reduced biomass.

Lead inhibition of DNA-binding mechanism of Cys(2)His(2) zinc finger proteins.

Science.gov (United States)

Hanas, J S; Rodgers, J S; Bantle, J A; Cheng, Y G

1999-11-01

The association of lead with chromatin in cells suggests that deleterious metal effects may in part be mediated through alterations in gene function. To elucidate if and how lead may alter DNA binding of cysteine-rich zinc finger proteins, lead ions were analyzed for their ability to alter the DNA binding mechanism of the Cys(2)His(2) zinc finger protein transcription factor IIIA (TFIIIA). As assayed by DNase I protection, the interaction of TFIIIA with the 50-bp internal control region of the 5S ribosomal gene was partially inhibited by 5 microM lead ions and completely inhibited by 10 to 20 microM lead ions. Preincubation of free TFIIIA with lead resulted in DNA-binding inhibition, whereas preincubation of a TFIIIA/5S RNA complex with lead did not result in DNA-binding inhibition. Because 5S RNA binds TFIIIA zinc fingers, this result is consistent with an inhibition mechanism via lead binding to zinc fingers. The complete loss of DNase I protection on the 5S gene indicates the mechanism of inhibition minimally involves the N-terminal fingers of TFIIIA. Inhibition was not readily reversible and occurred in the presence of an excess of beta-mercaptoethanol. Inhibition kinetics were fast, progressing to completion in approximately 5 min. Millimolar concentrations of sulfhydryl-specific arsenic ions were not inhibitory for TFIIIA binding. Micromolar concentrations of lead inhibited DNA binding by Sp1, another Cys(2)His(2) finger protein, but not by the nonfinger protein AP2. Inhibition of Cys(2)His(2) zinc finger transcription factors by lead ions at concentrations near those known to have deleterious physiological effects points to new molecular mechanisms for lead toxicity in promoting disease.

FastBit: Interactively Searching Massive Data

Energy Technology Data Exchange (ETDEWEB)

Wu, Kesheng; Ahern, Sean; Bethel, E. Wes; Chen, Jacqueline; Childs, Hank; Cormier-Michel, Estelle; Geddes, Cameron; Gu, Junmin; Hagen, Hans; Hamann, Bernd; Koegler, Wendy; Lauret, Jerome; Meredith, Jeremy; Messmer, Peter; Otoo, Ekow; Perevoztchikov, Victor; Poskanzer, Arthur; Prabhat,; Rubel, Oliver; Shoshani, Arie; Sim, Alexander; Stockinger, Kurt; Weber, Gunther; Zhang, Wei-Ming

2009-06-23

As scientific instruments and computer simulations produce more and more data, the task of locating the essential information to gain insight becomes increasingly difficult. FastBit is an efficient software tool to address this challenge. In this article, we present a summary of the key underlying technologies, namely bitmap compression, encoding, and binning. Together these techniques enable FastBit to answer structured (SQL) queries orders of magnitude faster than popular database systems. To illustrate how FastBit is used in applications, we present three examples involving a high-energy physics experiment, a combustion simulation, and an accelerator simulation. In each case, FastBit significantly reduces the response time and enables interactive exploration on terabytes of data.

Virtual lesions of the inferior parietal cortex induce fast changes of implicit religiousness/spirituality.

Science.gov (United States)

Crescentini, Cristiano; Aglioti, Salvatore M; Fabbro, Franco; Urgesi, Cosimo

2014-05-01

Religiousness and spirituality (RS) are two ubiquitous aspects of human experience typically considered impervious to scientific investigation. Nevertheless, associations between RS and frontoparietal neural activity have been recently reported. However, much less is known about whether such activity is causally involved in modulating RS or just epiphenomenal to them. Here we combined two-pulse (10 Hz) Transcranial Magnetic Stimulation (TMS) with a novel, ad-hoc developed RS-related, Implicit Association Test (IAT) to investigate whether implicit RS representations, although supposedly rather stable, can be rapidly modified by a virtual lesion of inferior parietal lobe (IPL) and dorsolateral prefrontal cortex (DLPFC). A self-esteem (SE) IAT, focused on self-concepts nonrelated to RS representations, was developed as control. A specific increase of RS followed inhibition of IPL demonstrating its causative role in inducing fast plastic changes of religiousness/spirituality. In contrast, DLPFC inhibition had more widespread effects probably reflecting a general role in the acquisition or maintenance of task-rules or in controlling the expression of self-related representations not specific to RS. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chloride sensing by WNK1 kinase involves inhibition of autophosphorylation

Science.gov (United States)

Piala, Alexander T.; Moon, Thomas M.; Akella, Radha; He, Haixia; Cobb, Melanie H.; Goldsmith, Elizabeth J.

2014-01-01

WNK1 [with no lysine (K)] is a serine-threonine kinase associated with a form of familial hypertension. WNK1 is at the top of a kinase cascade leading to phosphorylation of several cotransporters, in particular those transporting sodium, potassium, and chloride (NKCC), sodium and chloride (NCC), and potassium and chloride (KCC). The responsiveness of NKCC, NCC, and KCC to changes in extracellular chloride parallels their phosphorylation state, provoking the proposal that these transporters are controlled by a chloride-sensitive protein kinase. Here, we found that chloride stabilizes the inactive conformation of WNK1, preventing kinase autophosphorylation and activation. Crystallographic studies of inactive WNK1 in the presence of chloride revealed that chloride binds directly to the catalytic site, providing a basis for the unique position of the catalytic lysine. Mutagenesis of the chloride binding site rendered the kinase less sensitive to inhibition of autophosphorylation by chloride, validating the binding site. Thus, these data suggest that WNK1 functions as a chloride sensor through direct binding of a regulatory chloride ion to the active site, which inhibits autophosphorylation. PMID:24803536

Human cytosolic glutathione-S-transferases: quantitative analysis of expression, comparative analysis of structures and inhibition strategies of isozymes involved in drug resistance.

Science.gov (United States)

Mohana, Krishnamoorthy; Achary, Anant

2017-08-01

Glutathione-S-transferase (GST) inhibition is a strategy to overcome drug resistance. Several isoforms of human GSTs are present and they are expressed in almost all the organs. Specific expression levels of GSTs in various organs are collected from the human transcriptome data and analysis of the organ-specific expression of GST isoforms is carried out. The variations in the level of expressions of GST isoforms are statistically significant. The GST expression differs in diseased conditions as reported by many investigators and some of the isoforms of GSTs are disease markers or drug targets. Structure analysis of various isoforms is carried out and literature mining has been performed to identify the differences in the active sites of the GSTs. The xenobiotic binding H site is classified into H1, H2, and H3 and the differences in the amino acid composition, the hydrophobicity and other structural features of H site of GSTs are discussed. The existing inhibition strategies are compared. The advent of rational drug design, mechanism-based inhibition strategies, availability of high-throughput screening, target specific, and selective inhibition of GST isoforms involved in drug resistance could be achieved for the reversal of drug resistance and aid in the treatment of diseases.

T Lymphocyte Inhibition by Tumor-Infiltrating Dendritic Cells Involves Ectonucleotidase CD39 but Not Arginase-1

Directory of Open Access Journals (Sweden)

Malika Trad

2015-01-01

Full Text Available T lymphocytes activated by dendritic cells (DC which present tumor antigens play a key role in the antitumor immune response. However, in patients suffering from active cancer, DC are not efficient at initiating and supporting immune responses as they participate to T lymphocyte inhibition. DC in the tumor environment are functionally defective and exhibit a characteristic of immature phenotype, different to that of DC present in nonpathological conditions. The mechanistic bases underlying DC dysfunction in cancer responsible for the modulation of T-cell responses and tumor immune escape are still being investigated. Using two different mouse tumor models, we showed that tumor-infiltrating DC (TIDC are constitutively immunosuppressive, exhibit a semimature phenotype, and impair responder T lymphocyte proliferation and activation by a mechanism involving CD39 ectoenzyme.

Inhibition of hydrogen sulfide on the proliferation of vascular smooth muscle cells involved in the modulation of calcium sensing receptor in high homocysteine

International Nuclear Information System (INIS)

Wang, Yuwen; Wang, Xiyao; Liang, Xiaohui; Wu, Jichao; Dong, Shiyun; Li, Hongzhu; Jin, Meili; Sun, Dianjun; Zhang, Weihua; Zhong, Xin

2016-01-01

Hyperhomocysteinemia induces the proliferation of vascular smooth muscle cells (VSMCs). Hydrogen sulfide (H 2 S) inhibits the phenotype switch of VSMCs and calcium-sensing receptor (CaSR) regulated the production of endogenous H 2 S. However, whether CaSR inhibits the proliferation of VSMCs by regulating the endogenous cystathionine-gamma-lyase (CSE, a major enzyme that produces H 2 S) pathway in high homocysteine (HHcy) has not been previously investigated. The intracellular calcium concentration, the concentration of H 2 S, the cell viability, the proliferation and the expression of proteins of cultured VSMCs from rat thoracic aortas were measured, respectively. The results showed that the [Ca 2+ ] i and the expression of p-CaMK and CSE increased upon treatment with CaSR agonist. In HHcy, the H 2 S concentration decrease, the proliferation and migration rate increased, the expression of Cyclin D1, PCNA, Osteopontin and p-Erk1/2 increased while the α-SM actin, P21 Cip/WAK−1 and Calponin decreased. The CaSR agonist or exogenous H 2 S significantly reversed the changes of VSMCs caused by HHcy. In conclusion, our results demonstrated that CaSR regulate the endogenous CSE/H 2 S is related to the PLC-IP 3 receptor and CaM signal pathways which inhibit the proliferation of VSMCs, and the latter is involved in the Erk1/2 dependent signal pathway in high homocysteine. - Highlights: • CaSR activation increased the production of endogenous H 2 S in high homocysteine VSMCs. • CaSR modulated the CSE/H 2 S are related to the PLC-IP 3 R and Ca 2+ -CaM signal pathways. • Inhibition of H 2 S on the proliferation of VSMCs is involved in the Erk1/2 pathway. • Explore the potential roles of CaSR in regulating VSMCs proliferation in high homocysteine.

Increased renal sodium absorption by inhibition of prostaglandin synthesis during fasting in healthy man. A possible role of the epithelial sodium channels

Directory of Open Access Journals (Sweden)

Graffe Carolina C

2010-10-01

Full Text Available Abstract Background Treatment with prostaglandin inhibitors can reduce renal function and impair renal water and sodium excretion. We tested the hypotheses that a reduction in prostaglandin synthesis by ibuprofen treatment during fasting decreased renal water and sodium excretion by increased absorption of water and sodium via the aquaporin2 water channels and the epithelial sodium channels. Methods The effect of ibuprofen, 600 mg thrice daily, was measured during fasting in a randomized, placebo-controlled, double-blinded crossover study of 17 healthy humans. The subjects received a standardized diet on day 1, fasted at day 2, and received an IV infusion of 3% NaCl on day 3. The effect variables were urinary excretions of aquaporin2 (u-AQP2, the beta-fraction of the epithelial sodium channel (u-ENaCbeta, cyclic-AMP (u-cAMP, prostaglandin E2 (u-PGE2. Free water clearance (CH2O, fractional excretion of sodium (FENa, and plasma concentrations of vasopressin, angiotensin II, aldosterone, atrial-, and brain natriuretic peptide. Results Ibuprofen decreased u-AQP2, u-PGE2, and FENa at all parts of the study. During the same time, ibuprofen significantly increased u-ENaCbeta. Ibuprofen did not change the response in p-AVP, u-c-AMP, urinary output, and free water clearance during any of these periods. Atrial-and brain natriuretic peptide were higher. Conclusion During inhibition of prostaglandin synthesis, urinary sodium excretion decreased in parallel with an increase in sodium absorption and increase in u-ENaCbeta. U-AQP2 decreased indicating that water transport via AQP2 fell. The vasopressin-c-AMP-axis did not mediate this effect, but it may be a consequence of the changes in the natriuretic peptide system and/or the angiotensin-aldosterone system Trial Registration Clinical Trials Identifier: NCT00281762

Intermittent fasting is neuroprotective in focal cerebral ischemia by minimizing autophagic flux disturbance and inhibiting apoptosis.

Science.gov (United States)

Jeong, Ji Heun; Yu, Kwang Sik; Bak, Dong Ho; Lee, Je Hun; Lee, Nam Seob; Jeong, Young Gil; Kim, Dong Kwan; Kim, Jwa-Jin; Han, Seung-Yun

2016-11-01

Previous studies have demonstrated that autophagy induced by caloric restriction (CR) is neuroprotective against cerebral ischemia. However, it has not been determined whether intermittent fasting (IF), a variation of CR, can exert autophagy-related neuroprotection against cerebral ischemia. Therefore, the neuroprotective effect of IF was evaluated over the course of two weeks in a rat model of focal cerebral ischemia, which was induced by middle cerebral artery occlusion and reperfusion (MCAO/R). Specifically, the role of autophagy modulation as a potential underlying mechanism for this phenomenon was investigated. It was demonstrated that IF reduced infarct volume and brain edema, improved neurobehavioral deficits, and rescued neuronal loss after MCAO/R. Furthermore, neuronal apoptosis was decreased by IF in the rat cortex. An increase in the number of autophagosomes (APs) was demonstrated in the cortices of IF-treated rats, using immunofluorescence staining and transmission electron microscopy. Using immunoblots, an IF-induced increase was detected in microtubule-associated protein 1 light chain 3 (LC3)-II, Rab7, and cathepsin D protein levels, which corroborated previous morphological studies. Notably, IF reduced the accumulation of APs and p62, demonstrating that IF attenuated the MCAO/R-induced disturbance of autophagic flux in neurons. The findings of the present study suggest that IF-induced neuroprotection in focal cerebral ischemia is due, at least in part, to the minimization of autophagic flux disturbance and inhibition of apoptosis.

Inhibitors of poly (ADP-ribose) synthesis inhibit the two types of repair of potentially lethal damage

International Nuclear Information System (INIS)

Utsumi, Hiroshi; Elkind, M.M.

1994-01-01

The purpose of this study was to examine whether 3-amino-benzamide (3ABA), an inhibitor of poly (ADP-ribose) synthesis, inhibits the two types of potentially lethal damage (PLD) repair, termed slow and fast. The fast-type PLD repair was measured by the decrease in survival of V79 Chinese hamster cells by postirradiation treatment with 3ABA. The slow-type PLD repair was measured by the increase in survival by posttreatment with conditioned medium (CM), which became conditioned by growing a crowed culture of cells and supports the slow-type PLD repair. Up to 1 mM 3-ABA inhibited the slow type repair; at doses of 2 mM and above, it inhibited the fast type of PLD repair. There are quantitative differences in cellular effects of 3ABA dependent on concentration. Poly (ADP-ribose) appears to play an important role in the PLD repairs and has little effect on the repair of sublethal damage. 10 refs., 2 figs

The fast breeder reactor

International Nuclear Information System (INIS)

Keck, O.

1984-01-01

Nowadays the fast-breeder reactor is a negative symbol of advanced technology which is getting out of control and, due to its complexity, is incomprehensible for politicians and therefore by-passes the established order. The author lists the most important decisions over state aid to the fast-breeder-reactors up until the mid-seventies and uses documents from the appropriate advisory bodies as reference. He was also aided by interviews with those directly involved with the project. The empirical facts forces us to discard our traditional view of the relationship between state and industry with regard to advanced technology. The author explains that it is impossible to find any economic value in the fast-breeder reactor. The insight gained through this project allows him to draw conclusions which apply to all aspects of state aid to advanced technology. (orig.) [de

Fast-track surgery for breast cancer is possible

DEFF Research Database (Denmark)

Mertz, Birgitte G; Kroman, Niels; Williams, Helene

2013-01-01

INTRODUCTION: Breast cancer is common among Danish women with more than 4,100 new cases annually. In 2008 the concept of fast-track surgery was introduced at the Department of Breast Surgery at Rigshospitalet, Copenhagen. The aim of this study is to describe the new clinical pathway for breast...... to provide immediate advice and support. CONCLUSION: The results confirm that a short stay can be successfully carried out for breast cancer patients. Implementing the fast-track programme involved the introduction of a clear clinical pathway for the patients and more effective daily routines. Patients felt...... cancer patients after implementation of a fast-track surgery programme. MATERIAL AND METHODS: A clinical pathway of all involved disciplines was developed including anaesthetic, analgesics, nausea and vomiting, drain and wound management, discharge assessment and psychosocial support. RESULTS...

The Involvement of Mutual Inhibition of ERK and mTOR in PLCγ1-Mediated MMP-13 Expression in Human Osteoarthritis Chondrocytes

Directory of Open Access Journals (Sweden)

Zejun Liu

2015-08-01

Full Text Available The issue of whether ERK activation determines matrix synthesis or degradation in osteoarthritis (OA pathogenesis currently remains controversial. Our previous study shows that PLCγ1 and mTOR are involved in the matrix metabolism of OA cartilage. Investigating the interplays of PLCγ1, mTOR and ERK in matrix degradation of OA will facilitate future attempts to manipulate ERK in OA prevention and therapy. Here, cultured human normal chondrocytes and OA chondrocytes were treated with different inhibitors or transfected with expression vectors, respectively. The levels of ERK, p-ERK, PLCγ1, p-PLCγ1, mTOR, p-mTOR and MMP-13 were then evaluated by Western blotting analysis. The results manifested that the expression level of ERK in human OA chondrocytes was lower than that in human normal articular chondrocytes, and the up-regulation of ERK could promote matrix synthesis, including the decrease in MMP-13 level and the increase in Aggrecan level in human OA chondrocytes. Furthermore, the PLCγ1/ERK axis and a mutual inhibition of mTOR and ERK were observed in human OA chondrocytes. Interestingly, activated ERK had no inhibitory effect on MMP-13 expression in PLCγ1-transformed OA chondrocytes. Combined with our previous study, the non-effective state of ERK activation by PLCγ1 on MMP-13 may be partly attributed to the inhibition of the PLCγ1/mTOR axis on the PLCγ1/ERK axis. Therefore, the study indicates that the mutual inhibition of ERK and mTOR is involved in PLCγ1-mediated MMP-13 expression in human OA chondrocytes, with important implication for the understanding of OA pathogenesis as well as for its prevention and therapy.

Inhibiting the inevitable

DEFF Research Database (Denmark)

Shashoua, Yvonne

2006-01-01

conservation is to ‘buy time’ for the object. Inhibitive conservation of plastics involves the removal or reduction of factors causing or accelerating degradation including light, oxygen, acids, relative humidity and acidic breakdown products. Specific approaches to conservation have been developed......Once plastics objects are registered in museum collections, the institution becomes responsible for their long term preservation, until the end of their useful lifetime. Plastics appear to deteriorate faster than other materials in museum collections and have a useful lifetime between 5 and 25...... years. Preventive or inhibitive conservation involves controlling the environments in which objects are placed during storage and display, with the aim of slowing the major deterioration reactions. Once in progress, degradation of plastics cannot be stopped or reversed, so the aim of preventive...

Diet Restriction Inhibits Apoptosis and HMGB1 Oxidation and Promotes Inflammatory Cell Recruitment during Acetaminophen Hepatotoxicity

Science.gov (United States)

Antoine, Daniel James; Williams, Dominic P; Kipar, Anja; Laverty, Hugh; Park, B Kevin

2010-01-01

Acetaminophen (APAP) overdose is a major cause of acute liver failure and serves as a paradigm to elucidate mechanisms, predisposing factors and therapeutic interventions. The roles of apoptosis and inflammation during APAP hepatotoxicity remain controversial. We investigated whether fasting of mice for 24 h can inhibit APAP-induced caspase activation and apoptosis through the depletion of basal ATP. We also investigated in fasted mice the critical role played by inhibition of caspase-dependent cysteine 106 oxidation within high mobility group box-1 protein (HMGB1) released by ATP depletion in dying cells as a mechanism of immune activation. In fed mice treated with APAP, necrosis was the dominant form of hepatocyte death. However, apoptosis was also observed, indicated by K18 cleavage, DNA laddering and procaspase-3 processing. In fasted mice treated with APAP, only necrosis was observed. Inflammatory cell recruitment as a consequence of hepatocyte death was observed only in fasted mice treated with APAP or fed mice cotreated with a caspase inhibitor. Hepatic inflammation was also associated with loss in detection of serum oxidized-HMGB1. A significant role of HMGB1 in the induction of inflammation was confirmed with an HMGB1-neutralizing antibody. The differential response between fasted and fed mice was a consequence of a significant reduction in basal hepatic ATP, which prevented caspase processing, rather than glutathione depletion or altered APAP metabolism. Thus, the inhibition of caspase-driven apoptosis and HMGB1 oxidation by ATP depletion from fasting promotes an inflammatory response during drug-induced hepatotoxicity/liver pathology. PMID:20811657

Fast and Statistically Efficient Fundamental Frequency Estimation

DEFF Research Database (Denmark)

Nielsen, Jesper Kjær; Jensen, Tobias Lindstrøm; Jensen, Jesper Rindom

2016-01-01

Fundamental frequency estimation is a very important task in many applications involving periodic signals. For computational reasons, fast autocorrelation-based estimation methods are often used despite parametric estimation methods having superior estimation accuracy. However, these parametric...... a recursive solver. Via benchmarks, we demonstrate that the computation time is reduced by approximately two orders of magnitude. The proposed fast algorithm is available for download online....

Fasting and exercise increase plasma cannabinoid levels in THC pre-treated rats: an examination of behavioural consequences.

Science.gov (United States)

Wong, Alexander; Keats, Kirily; Rooney, Kieron; Hicks, Callum; Allsop, David J; Arnold, Jonathon C; McGregor, Iain S

2014-10-01

Δ(9)-Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, accumulates in fat tissue where it can remain for prolonged periods. Under conditions of increased fat utilisation, blood cannabinoid concentrations can increase. However, it is unclear whether this has behavioural consequences. Here, we examined whether rats pre-treated with multiple or single doses of THC followed by a washout would show elevated plasma cannabinoids and altered behaviour following fasting or exercise manipulations designed to increase fat utilisation. Behavioural impairment was measured as an inhibition of spontaneous locomotor activity or a failure to successfully complete a treadmill exercise session. Fat utilisation was indexed by plasma free fatty acid (FFA) levels with plasma concentrations of THC and its terminal metabolite (-)-11-nor-9-carboxy-∆(9)-tetrahydrocannabinol (THC-COOH) also measured. Rats given daily THC (10 mg/kg) for 5 days followed by a 4-day washout showed elevated plasma THC-COOH when fasted for 24 h relative to non-fasted controls. Fasted rats showed lower locomotor activity than controls suggesting a behavioural effect of fat-released THC. However, rats fasted for 20 h after a single 5-mg/kg THC injection did not show locomotor suppression, despite modestly elevated plasma THC-COOH. Rats pre-treated with THC (5 mg/kg) and exercised 20 h later also showed elevated plasma THC-COOH but did not differ from controls in their likelihood of completing 30 min of treadmill exercise. These results confirm that fasting and exercise can increase plasma cannabinoid levels. Behavioural consequences are more clearly observed with pre-treatment regimes involving repeated rather than single THC dosing.

Should Type 1 diabetics fast in Ramadan.

Science.gov (United States)

Mohsin, Fauzia; Azad, Kishwar; Zabeen, Bedowra; Tayyeb, Samin; Baki, Abdul; Nahar, Nazmun

2015-05-01

Fasting during the holy month of Ramadan is obligatory for all healthy adult and adolescent Muslims from the age of 12 years. This involves abstaining from eating or drinking from early dawn (Suhur/Sehri) till sunset (Iftar).Fasting is not meant to create excessive hardships or impart any adverse effect to the Muslim individual. As such, Islam has exempted certain categories of people from fasting including young children, travelers, the sick, the elderly,and pregnant and lactating women. According to expert opinion, people with type 1 diabetes who fast during Ramadan are at very high risk of metabolic deterioration. However, some recent studies have demonstrated that individuals with type 1 diabetes who are otherwise healthy and stable, can fast during Ramadan provided they comply with the Ramadan focused management plan and are under close professional supervision. This article discusses how to assess, counsel, monitor and manage people with type 1 diabetes who wish to fast during Ramadan.

Mechanisms involved in growth inhibition induced by clofibrate in hepatoma cells

International Nuclear Information System (INIS)

Muzio, Giuliana; Maggiora, Marina; Trombetta, Antonella; Martinasso, Germana; Reffo, Patrizia; Colombatto, Sebastiano; Canuto, Rosa Angela

2003-01-01

Low concentrations of some peroxisome proliferators have been found to decrease apoptosis in rat liver cells, whereas higher but pharmacological concentrations have been found to inhibit cell proliferation or to induce apoptosis in human and rat hepatoma cells. The highly deviated JM2 rat hepatoma cell line was used to examine the mechanisms underlying the inhibitory effect on cell proliferation. Clofibrate chiefly inhibited cell proliferation in these cells. Parallel to the decrease in cell proliferation there was an increase of peroxisome proliferator activated receptor (PPAR) gamma and of protein phosphatase 2A, whose importance was confirmed, respectively, by using antisense oliginucleotides (AS-ODN) or okadaic acid. The increase of protein phosphatase 2A induced by PPARgamma caused a decrease of MAPK, an intracellular signaling transduction pathway, as shown by evaluation of Erk1,2 and c-myc. In light of these results, clofibrate, like conventional synthetic ligands of PPARgamma, may be regarded as a possible prototype anti-tumour drug

Piperine Inhibits the Activities of Platelet Cytosolic Phospholipase A2 and Thromboxane A2 Synthase without Affecting Cyclooxygenase-1 Activity: Different Mechanisms of Action Are Involved in the Inhibition of Platelet Aggregation and Macrophage Inflammatory Response

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Dong Ju Son

2014-08-01

Full Text Available PURPOSE: Piperine, a major alkaloid of black pepper (Piper nigrum and long pepper (Piper longum, was shown to have anti-inflammatory activity through the suppression of cyclooxygenase (COX-2 gene expression and enzyme activity. It is also reported to exhibit anti-platelet activity, but the mechanism underlying this action remains unknown. In this study, we investigated a putative anti-platelet aggregation mechanism involving arachidonic acid (AA metabolism and how this compares with the mechanism by which it inhibits macrophage inflammatory responses; METHODS: Rabbit platelets and murine macrophage RAW264.7 cells were treated with piperine, and the effect of piperine on the activity of AA-metabolizing enzymes, including cytosolic phospholipase A2 (cPLA2, COX-1, COX-2, and thromboxane A2 (TXA2 synthase, as well as its effect on AA liberation from the plasma membrane components, were assessed using isotopic labeling methods and enzyme immunoassay kit; RESULTS: Piperine significantly suppressed AA liberation by attenuating cPLA2 activity in collagen-stimulated platelets. It also significantly inhibited the activity of TXA2 synthase, but not of COX-1, in platelets. These results suggest that piperine inhibits platelet aggregation by attenuating cPLA2 and TXA2 synthase activities, rather than through the inhibition of COX-1 activity. On the other hand, piperine significantly inhibited lipopolysaccharide-induced generation of prostaglandin (PGE2 and PGD2 in RAW264.7 cells by suppressing the activity of COX-2, without effect on cPLA2; CONCLUSION: Our findings indicate that piperine inhibits platelet aggregation and macrophage inflammatory response by different mechanisms.

Fast reactor knowledge preservation system: Taxonomy and basic requirements

International Nuclear Information System (INIS)

2008-01-01

The IAEA has taken the initiative to coordinate efforts of Member States in the preservation of knowledge in the area of fast reactors. In the framework of this initiative, the IAEA intends to create an international database compiling information from different Member States on fast reactors through a web portal. Other activities related to this initiative are being designed to accumulate and exchange information on the fast reactor area, to facilitate access to this information by users in different countries and to assist Member States in preserving the experience gained in their countries. The purpose of this publication is to develop a taxonomy of the Fast Reactor Knowledge Preservation System (FRKPS) that will facilitate the preservation of the world's fast reactor knowledge base, to identify basic requirements of this taxonomy on the basis of the experience gained in the fast reactor area, as well as results of previous IAEA activities on fast reactor knowledge preservation. The need for such taxonomy arises from the fact that during the past 15 years there has been stagnation in the development of fast reactors in the industrialized countries that were involved, earlier, in intensive development of this area. All studies on fast reactors have been stopped in countries such as Germany, Italy, the United Kingdom and the United States of America and the only work being carried out is related to the decommissioning of fast reactors. Many specialists who were involved in the studies and development work in this area in these countries have already retired or are close to retirement. In countries such as France, Japan and the Russian Federation that are still actively pursuing the evolution of fast reactor technology, the situation is aggravated by the lack of young scientists and engineers moving into this branch of nuclear power

Automated Measurement of Fast Mitochondrial Transport in Neurons

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Kyle eMiller

2015-11-01

Full Text Available There is a growing recognition that fast mitochondrial transport in neurons is disrupted in multiple neurological diseases and psychiatric disorders. However a major constraint in identifying novel therapeutics based on mitochondrial transport is that the large-scale analysis of fast transport is time consuming. Here we describe methodologies for the automated analysis of fast mitochondrial transport from data acquired using a robotic microscope. We focused on addressing questions of measurement precision, speed, reliably, workflow ease, statistical processing and presentation. We used optical flow and particle tracking algorithms, implemented in ImageJ, to measure mitochondrial movement in primary cultured cortical and hippocampal neurons. With it, we are able to generate complete descriptions of movement profiles in an automated fashion of hundred of thousands of mitochondria with a processing time of approximately one hour. We describe the calibration of the parameters of the tracking algorithms and demonstrate that they are capable of measuring the fast transport of a single mitochondrion. We then show that the methods are capable of reliably measuring the inhibition of fast mitochondria transport induced by the disruption of microtubules with the drug nocodazole in both hippocampal and cortical neurons. This work lays the foundation for future large-scale screens designed to identify compounds that modulate mitochondrial motility.

The instrumentation of fast reactor

International Nuclear Information System (INIS)

Endo, Akira

2003-03-01

The author has been engaged in the development of fast reactors over the last 30 years with both an involvement with the early technology development on the experimental breeder reactor Joyo, and latterly continuing this work on the prototype breeder reactor, Monju. In order to pass on this experience to younger engineers this paper is produced to outline this experience in the sincere hope that the information given will be utilised in future educational training material. The paper discusses the wide diversity on the associated instrument technology which the fast breeder reactor requires. The first chapter outlines the fast reactor system, followed by discussions on reactor instrumentation, measurement principles, temperature dependencies, and verification response characteristics from various viewpoints, are discussed in chapters two and three. The important issues of failed fuel location detection, and sodium leak detection from steam generators are discussed in chapters 4 and 5 respectively. Appended to this report is an explanation on the methods of measuring response characteristics on instrumentation systems using error analysis, random signal theory and measuring method of response characteristic by AR (autoregressive) model on which it appears is becoming an indispensable problem for persons involved with this technology in the future. (author)

Inhibition of hydrogen sulfide on the proliferation of vascular smooth muscle cells involved in the modulation of calcium sensing receptor in high homocysteine

Energy Technology Data Exchange (ETDEWEB)

Wang, Yuwen; Wang, Xiyao [Department of Clinical Laboratory, The second Affiliated Hospital of Harbin Medical University, Harbin 150081 (China); Liang, Xiaohui [Department of Radiology, Central Hospital of the Red Cross, Harbin 150080 (China); Wu, Jichao; Dong, Shiyun; Li, Hongzhu [Department of Pathophysiology, Harbin Medical University, Harbin 150081 (China); Jin, Meili [Department of Clinical Laboratory, The second Affiliated Hospital of Harbin Medical University, Harbin 150081 (China); Sun, Dianjun [Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150086 (China); Zhang, Weihua [Department of Pathophysiology, Harbin Medical University, Harbin 150081 (China); Zhong, Xin, E-mail: xzhong1111@163.com [Department of Pathophysiology, Harbin Medical University, Harbin 150081 (China)

2016-09-10

Hyperhomocysteinemia induces the proliferation of vascular smooth muscle cells (VSMCs). Hydrogen sulfide (H{sub 2}S) inhibits the phenotype switch of VSMCs and calcium-sensing receptor (CaSR) regulated the production of endogenous H{sub 2}S. However, whether CaSR inhibits the proliferation of VSMCs by regulating the endogenous cystathionine-gamma-lyase (CSE, a major enzyme that produces H{sub 2}S) pathway in high homocysteine (HHcy) has not been previously investigated. The intracellular calcium concentration, the concentration of H{sub 2}S, the cell viability, the proliferation and the expression of proteins of cultured VSMCs from rat thoracic aortas were measured, respectively. The results showed that the [Ca{sup 2+}]{sub i} and the expression of p-CaMK and CSE increased upon treatment with CaSR agonist. In HHcy, the H{sub 2}S concentration decrease, the proliferation and migration rate increased, the expression of Cyclin D1, PCNA, Osteopontin and p-Erk1/2 increased while the α-SM actin, P21{sup Cip/WAK−1} and Calponin decreased. The CaSR agonist or exogenous H{sub 2}S significantly reversed the changes of VSMCs caused by HHcy. In conclusion, our results demonstrated that CaSR regulate the endogenous CSE/H{sub 2}S is related to the PLC-IP{sub 3} receptor and CaM signal pathways which inhibit the proliferation of VSMCs, and the latter is involved in the Erk1/2 dependent signal pathway in high homocysteine. - Highlights: • CaSR activation increased the production of endogenous H{sub 2}S in high homocysteine VSMCs. • CaSR modulated the CSE/H{sub 2}S are related to the PLC-IP{sub 3}R and Ca{sup 2+}-CaM signal pathways. • Inhibition of H{sub 2}S on the proliferation of VSMCs is involved in the Erk1/2 pathway. • Explore the potential roles of CaSR in regulating VSMCs proliferation in high homocysteine.

Nonfasting Versus Initial Fasting Ketogenic Diet

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J Gordon Millichap

2005-02-01

Full Text Available A retrospective evaluation of the ketogenic diet (KD was conducted comparing efficacy and tolerability of the diet with or without initial fasting and fluid restriction and involving university centers in Seoul, Korea.

Melatonin inhibits the migration of human lung adenocarcinoma A549 cell lines involving JNK/MAPK pathway.

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Qiaoyun Zhou

Full Text Available OBJECTIVE: Melatonin, an indolamine produced and secreted predominately by the pineal gland, exhibits a variety of physiological functions, possesses antioxidant and antitumor properties. But, the mechanisms for the anti-cancer effects are unknown. The present study explored the effects of melatonin on the migration of human lung adenocarcinoma A549 cells and its mechanism. METHODS: MTT assay was employed to measure the viability of A549 cells treated with different concentrations of melatonin. The effect of melatonin on the migration of A549 cells was analyzed by wound healing assay. Occludin location was observed by immunofluorescence. The expression of occludin, osteopontin (OPN, myosin light chain kinase (MLCK and phosphorylation of myosin light chain (MLC, JNK were detected by western blots. RESULTS: After A549 cells were treated with melatonin, the viability and migration of the cells were inhibited significantly. The relative migration rate of A549 cells treated with melatonin was only about 20% at 24 h. The expression level of OPN, MLCK and phosphorylation of MLC of A549 cells were reduced, while the expression of occludin was conversely elevated, and occludin located on the cell surface was obviously increased. The phosphorylation status of JNK in A549 cells was also reduced when cells were treated by melatonin. CONCLUSIONS: Melatonin significantly inhibits the migration of A549 cells, and this may be associated with the down-regulation of the expression of OPN, MLCK, phosphorylation of MLC, and up-regulation of the expression of occludin involving JNK/MAPK pathway.

Apigenin inhibits HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and β4 integrin function in MDA-MB-231 breast cancer cells

International Nuclear Information System (INIS)

Lee, W.-J.; Chen, W.-K.; Wang, C.-J.; Lin, W.-L.; Tseng, T.-H.

2008-01-01

Hepatocyte growth factor (HGF) and its receptor, Met, known to control invasive growth program have recently been shown to play crucial roles in the survival of breast cancer patients. The diet-derived flavonoids have been reported to possess anti-invasion properties; however, knowledge on the pharmacological and molecular mechanisms in suppressing HGF/Met-mediated tumor invasion and metastasis is poorly understood. In our preliminary study, we use HGF as an invasive inducer to investigate the effect of flavonoids including apigenin, naringenin, genistein and kaempferol on HGF-dependent invasive growth of MDA-MB-231 human breast cancer cells. Results show that apigenin presents the most potent anti-migration and anti-invasion properties by Boyden chamber assay. Furthermore, apigenin represses the HGF-induced cell motility and scattering and inhibits the HGF-promoted cell migration and invasion in a dose-dependent manner. The effect of apigenin on HGF-induced signaling activation involving invasive growth was evaluated by immunoblotting analysis, it shows that apigenin blocks the HGF-induced Akt phosphorylation but not Met, ERK, and JNK phosphorylation. In addition to MDA-MB-231 cells, apigenin exhibits inhibitory effect on HGF-induced Akt phosphorylation in hepatoma SK-Hep1 cells and lung carcinoma A549 cells. By indirect immunofluorescence microscopy assay, apigenin inhibits the HGF-induced clustering of β4 integrin at actin-rich adhesive site and lamellipodia through PI3K-dependent manner. Treatment of apigenin inhibited HGF-stimulated integrin β4 function including cell-matrix adhesion and cell-endothelial cells adhesion in MDA-MB-231 cells. By Akt-siRNA transfection analysis, it confirmed that apigenin inhibited HGF-promoted invasive growth involving blocking PI3K/Akt pathway. Finally, we evaluated the effect of apigenin on HGF-promoted metastasis by lung colonization of tumor cells in nude mice and organ metastasis of tumor cells in chick embryo. By

Fast convergence of spike sequences to periodic patterns in recurrent networks

International Nuclear Information System (INIS)

Jin, Dezhe Z.

2002-01-01

The dynamical attractors are thought to underlie many biological functions of recurrent neural networks. Here we show that stable periodic spike sequences with precise timings are the attractors of the spiking dynamics of recurrent neural networks with global inhibition. Almost all spike sequences converge within a finite number of transient spikes to these attractors. The convergence is fast, especially when the global inhibition is strong. These results support the possibility that precise spatiotemporal sequences of spikes are useful for information encoding and processing in biological neural networks

Predictors of Ramadan fasting during pregnancy

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Lily A. van Bilsen

2016-12-01

Full Text Available Although the health effects of Ramadan fasting during pregnancy are still unclear, it is important to identify the predictors and motivational factors involved in women’s decision to observe the fast. We investigated these factors in a cross sectional study of 187 pregnant Muslim women who attended antenatal care visits in the Budi Kemuliaan Hospital, Jakarta, Indonesia. The odds of adherence to fasting were reduced by 4% for every week increase in gestational age during Ramadan [odds ratio (OR 0.96; 95% confidence interval (CI 0.92, 1.00; p = 0.06] and increased by 10% for every one unit increase of women’s prepregnancy body mass index (BMI (OR 1.10; 95% CI 0.99, 1.23; p = 0.08. Nonparticipation was associated with opposition from husbands (OR 0.34; 95% CI 0.14, 0.82; p = 0.02 and with women’s fear of possible adverse effects of fasting on their own or the baby’s health (OR 0.47; 95% CI 0.22, 1.01; p = 0.05 and OR 0.43; 95% CI 0.21, 0.89; p = 0.02, respectively, although they were attenuated in multivariable analysis. Neither age, income, education, employment, parity, experience of morning sickness, nor fasting during pregnancy outside of Ramadan determined fasting during pregnancy. Linear regression analysis within women who fasted showed that the number of days fasted were inversely associated with women’s gestational age, fear of possible adverse effects of fasting on their own or the fetal health, and with opposition from husbands. In conclusion, earlier gestational age during Ramadan, husband’s opinion and possibly higher prepregnancy BMI, influence women’s adherence to Ramadan fasting during pregnancy. Fear of adverse health effects of Ramadan fasting is common in both fasting and non-fasting pregnant women.

Family food involvement is related to healthier dietary intake in preschool-aged children.

Science.gov (United States)

Metcalfe, Jessica Jarick; Fiese, Barbara H

2018-03-27

Children in the United States fall far short of meeting federal dietary recommendations. The unhealthy diets common amongst young children are of crucial public health concern, given that they can inhibit healthy development and are predictive of chronic diseases in adulthood. Research investigating behaviors that are related to dietary habits is crucial to allow a better understanding of the causes of unhealthy dietary practices. Involvement in food preparation is known to be associated with healthy dietary behaviors in school-aged children, but little is known about these behaviors and their correlates in younger children. The present study sought to examine the influences and correlates of involvement in family food preparation in children at ages three and four. Parents of preschool aged children (n = 497) completed surveys including information about demographic background, their children's family food involvement, dietary intake, mealtime routines, and problematic eating behaviors. Data were collected when children were three (wave one of the survey) and four years of age (wave two). Findings from this study indicate that family food involvement at age three is predictive of healthier dietary intake at age four (increased consumption of fruits and vegetables, decreased consumption of fast food). These findings indicate that family food involvement is predictive of healthier dietary behaviors in young children, and that outreach efforts focused on family food involvement in early childhood may improve children's dietary habits. Copyright © 2018. Published by Elsevier Ltd.

Do GIS-derived measures of fast food retailers convey perceived fast food opportunities? Implications for food environment assessment

Science.gov (United States)

Barnes, Timothy L.; Colabianchi, Natalie; Freedman, Darcy A.; Bell, Bethany A.; Liese, Angela D.

2018-01-01

Purpose Geographic information systems (GISs) have been used to define fast food availability, with higher availability perhaps promoting poorer quality diets. Alternative measures involve perceptions; however, few studies have examined associations between GIS-derived and perceived measures of the food environment. Methods Telephone surveys of 705 participants within an eight-county region in South Carolina were analyzed using logistic regression to examine relationships between geographic presence of and distance to various types of food retailers and perceived fast food availability. Results The mean distance to the nearest fast food restaurant was 6.1 miles, with 16% of participants having a fast food restaurant within 1 mile of home. The geographic presence of and distance to all food retailer types were significantly associated with perceived availability of fast food in unadjusted models. After adjustment, only the presence of a fast food restaurant or pharmacy was significantly associated with greater odds of higher perceived availability of fast food. Greater odds of lower perceived availability of fast food were observed with the presence of a dollar store and increasing distance to the nearest supermarket or pharmacy. Conclusions Measures of fast food availability, whether objective or perceived, may not be interchangeable. Researchers should carefully decide on the appropriate measurement tool—GIS-derived or perceived—in food environment studies. PMID:27617371

Do GIS-derived measures of fast food retailers convey perceived fast food opportunities? Implications for food environment assessment.

Science.gov (United States)

Barnes, Timothy L; Colabianchi, Natalie; Freedman, Darcy A; Bell, Bethany A; Liese, Angela D

2017-01-01

Geographic information systems (GISs) have been used to define fast food availability, with higher availability perhaps promoting poorer quality diets. Alternative measures involve perceptions; however, few studies have examined associations between GIS-derived and perceived measures of the food environment. Telephone surveys of 705 participants within an eight-county region in South Carolina were analyzed using logistic regression to examine relationships between geographic presence of and distance to various types of food retailers and perceived fast food availability. The mean distance to the nearest fast food restaurant was 6.1 miles, with 16% of participants having a fast food restaurant within 1 mile of home. The geographic presence of and distance to all food retailer types were significantly associated with perceived availability of fast food in unadjusted models. After adjustment, only the presence of a fast food restaurant or pharmacy was significantly associated with greater odds of higher perceived availability of fast food. Greater odds of lower perceived availability of fast food were observed with the presence of a dollar store and increasing distance to the nearest supermarket or pharmacy. Measures of fast food availability, whether objective or perceived, may not be interchangeable. Researchers should carefully decide on the appropriate measurement tool-GIS-derived or perceived-in food environment studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Spatial frequency information modulates response inhibition and decision-making processes.

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Sara Jahfari

Full Text Available We interact with the world through the assessment of available, but sometimes imperfect, sensory information. However, little is known about how variance in the quality of sensory information affects the regulation of controlled actions. In a series of three experiments, comprising a total of seven behavioral studies, we examined how different types of spatial frequency information affect underlying processes of response inhibition and selection. Participants underwent a stop-signal task, a two choice speed/accuracy balance experiment, and a variant of both these tasks where prior information was given about the nature of stimuli. In all experiments, stimuli were either intact, or contained only high-, or low- spatial frequencies. Overall, drift diffusion model analysis showed a decreased rate of information processing when spatial frequencies were removed, whereas the criterion for information accumulation was lowered. When spatial frequency information was intact, the cost of response inhibition increased (longer SSRT, while a correct response was produced faster (shorter reaction times and with more certainty (decreased errors. When we manipulated the motivation to respond with a deadline (i.e., be fast or accurate, removal of spatial frequency information slowed response times only when instructions emphasized accuracy. However, the slowing of response times did not improve error rates, when compared to fast instruction trials. These behavioral studies suggest that the removal of spatial frequency information differentially affects the speed of response initiation, inhibition, and the efficiency to balance fast or accurate responses. More generally, the present results indicate a task-independent influence of basic sensory information on strategic adjustments in action control.

Formation of fast exotic atoms by radiative Coulomb capture

International Nuclear Information System (INIS)

Chatterjee, L.; Das, G.; Chakravorty, A.; Goswami, R.; Mondal, S.K.

1993-01-01

Interesting surprises in some exotic atom kinetics have been reported recently. These involve muonic atom transfer cross sections, nuclear pion capture and the q 1s effect in μCF. These can be explained if the exotic atom population contains a contributing fast component. Such fast atoms can be formed by radiative continuum to bound transitions of fast (keV) muons or pions. Cross sections for formation of such fast pionic and muonic atoms and their velocity distributions are reported. The possibility of these processes competing with the thermalisation channels and contributing effectively to the exotic atom population discussed. (orig.)

Imagining is Not Doing but Involves Specific Motor Commands: A Review of Experimental Data Related to Motor Inhibition.

Science.gov (United States)

Guillot, Aymeric; Di Rienzo, Franck; Macintyre, Tadhg; Moran, Aidan; Collet, Christian

2012-01-01

There is now compelling evidence that motor imagery (MI) and actual movement share common neural substrate. However, the question of how MI inhibits the transmission of motor commands into the efferent pathways in order to prevent any movement is largely unresolved. Similarly, little is known about the nature of the electromyographic activity that is apparent during MI. In addressing these gaps in the literature, the present paper argues that MI includes motor execution commands for muscle contractions which are blocked at some level of the motor system by inhibitory mechanisms. We first assemble data from neuroimaging studies that demonstrate that the neural networks mediating MI and motor performance are not totally overlapping, thereby highlighting potential differences between MI and actual motor execution. We then review MI data indicating the presence of subliminal muscular activity reflecting the intrinsic characteristics of the motor command as well as increased corticomotor excitability. The third section not only considers the inhibitory mechanisms involved during MI but also examines how the brain resolves the problem of issuing the motor command for action while supervising motor inhibition when people engage in voluntary movement during MI. The last part of the paper draws on imagery research in clinical contexts to suggest that some patients move while imagining an action, although they are not aware of such movements. In particular, experimental data from amputees as well as from patients with Parkinson's disease are discussed. We also review recent studies based on comparing brain activity in tetraplegic patients with that from healthy matched controls that provide insights into inhibitory processes during MI. We conclude by arguing that based on available evidence, a multifactorial explanation of motor inhibition during MI is warranted.

Imagining is not doing but involves specific motor commands: a review of experimental data related to motor inhibition

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Aymeric eGuillot

2012-09-01

Full Text Available There is now compelling evidence that motor imagery (MI and actual movement share common neural substrate. However, the question of how MI inhibits the transmission of motor commands into the efferent pathways in order to prevent any movement is largely unresolved. Similarly, little is known about the nature of the electromyographic activity that is apparent during MI. In addressing these gaps in the literature, the present paper argues that MI includes motor execution commands for muscle contractions which are blocked at some level of the motor system by inhibitory mechanisms. We first assemble data from neuroimaging studies that demonstrate that the neural networks mediating MI and motor performance are not totally overlapping, thereby highlighting potential differences between MI and actual motor execution. We then review MI data indicating the presence of subliminal muscular activity reflecting the intrinsic characteristics of the motor command as well as increased corticomotor excitability. The third section not only considers the inhibitory mechanisms involved during MI but also examines how the brain resolves the problem of issuing the motor command for action while supervising motor inhibition when people engage in voluntary movement during MI. The last part of the paper draws on imagery research in clinical contexts to suggest that some patients move while imagining an action, although they are not aware of such movements. In particular, experimental data from amputees as well as from patients with Parkinson’s disease are discussed. We also review recent studies based on comparing brain activity in tetraplegic patients with that from healthy matched controls that provide insights into inhibitory processes during MI. We conclude by arguing that based on available evidence, a multifactorial explanation of motor inhibition during MI is warranted.

Different Neural Networks are Involved in Cross-Modal Non-Spatial Inhibition of Return (IOR: The Effect of the Sensory Modality of Behavioral Targets

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Qi Chen

2011-10-01

Full Text Available We employed a novel cross-modal non-spatial inhibition of return (IOR paradigm with fMRI to investigate whether object concept is organized by supramodal or modality-specific systems. A precue-neutral cue-target sequence was presented and participants were asked to discriminate whether the target was a dog or a cat. The precue and the target could be either a picture or vocalization of a dog or a cat. The neutral cue (bird was always from the same modality as the precue. Behaviorally, for both visual and auditory targets, the main effect of cue validity was the only significant effect, p<0.01, with equivalent effects for within- and cross-modal IOR. Neurally, for visual targets, left inferior frontal gyrus and left medial temporal gyrus showed significantly higher neural activity in cued than uncued condition, irrespective of the precue-target relationship, indicating that the two areas are involved in inhibiting a supramodal representation of previously attended object concept. For auditory targets, left lateral occipital gyrus and right postcentral gyrus showed significantly higher neural activity in uncued than cued condition irrespective of the cue-target relationship, indicating that the two areas are involved in creating a new supramodal representation when a novel object concept appears.

The Cytotoxicity of Benzaldehyde Nitrogen Mustard-2-Pyridine Carboxylic Acid Hydrazone Being Involved in Topoisomerase IIα Inhibition

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Yun Fu

2014-01-01

Full Text Available The antitumor property of iron chelators and aromatic nitrogen mustard derivatives has been well documented. Combination of the two pharmacophores in one molecule in drug designation is worth to be explored. We reported previously the syntheses and preliminary cytotoxicity evaluation of benzaldehyde nitrogen mustard pyridine carboxyl acid hydrazones (BNMPH as extended study, more tumor cell lines (IC50 for HepG2: 26.1 ± 3.5 μM , HCT-116: 57.5 ± 5.3 μM, K562: 48.2 ± 4.0 μM, and PC-12: 19.4 ± 2.2 μM were used to investigate its cytotoxicity and potential mechanism. In vitro experimental data showed that the BNMPH chelating Fe2+ caused a large number of ROS formations which led to DNA cleavage, and this was further supported by comet assay, implying that ROS might be involved in the cytotoxicity of BNMPH. The ROS induced changes of apoptosis related genes, but the TFR1 and NDRG1 metastatic genes were not obviously regulated, prompting that BNMPH might not be able to deprive Fe2+ of ribonucleotide reductase. The BNMPH induced S phase arrest was different from that of iron chelators (G1 and alkylating agents (G2. BNMPH also exhibited its inhibition of human topoisomerase IIα. Those revealed that the cytotoxic mechanism of the BNMPH could stem from both the topoisomerase II inhibition, ROS generation and DNA alkylation.

Fast Ion Redistribution and Implications for the Hybrid Regime

International Nuclear Information System (INIS)

Nazikian, R.; Austin, M.E.; Budny, R.V.; Chu, M.S.; Heidbrink, W.W.; Makowski, M.A.; Petty, C.C.; Politzer, P.A.; Solomon, W.M.; Van Zeeland, M.A.

2007-01-01

Time dependent TRANSP analysis indicates that radial redistribution of fast ions is unlikely to affect the central current density in hybrid plasmas sufficient to raise q(0) above unity. The results suggest that some other mechanism other than fast ion transport must be involved in raising q(0) and preventing sawteeth in hybrid plasmas.

FAST: FAST Analysis of Sequences Toolbox

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Travis J. Lawrence

2015-05-01

Full Text Available FAST (FAST Analysis of Sequences Toolbox provides simple, powerful open source command-line tools to filter, transform, annotate and analyze biological sequence data. Modeled after the GNU (GNU’s Not Unix Textutils such as grep, cut, and tr, FAST tools such as fasgrep, fascut, and fastr make it easy to rapidly prototype expressive bioinformatic workflows in a compact and generic command vocabulary. Compact combinatorial encoding of data workflows with FAST commands can simplify the documentation and reproducibility of bioinformatic protocols, supporting better transparency in biological data science. Interface self-consistency and conformity with conventions of GNU, Matlab, Perl, BioPerl, R and GenBank help make FAST easy and rewarding to learn. FAST automates numerical, taxonomic, and text-based sorting, selection and transformation of sequence records and alignment sites based on content, index ranges, descriptive tags, annotated features, and in-line calculated analytics, including composition and codon usage. Automated content- and feature-based extraction of sites and support for molecular population genetic statistics makes FAST useful for molecular evolutionary analysis. FAST is portable, easy to install and secure thanks to the relative maturity of its Perl and BioPerl foundations, with stable releases posted to CPAN. Development as well as a publicly accessible Cookbook and Wiki are available on the FAST GitHub repository at https://github.com/tlawrence3/FAST. The default data exchange format in FAST is Multi-FastA (specifically, a restriction of BioPerl FastA format. Sanger and Illumina 1.8+ FastQ formatted files are also supported. FAST makes it easier for non-programmer biologists to interactively investigate and control biological data at the speed of thought.

High-resolution bacterial growth inhibition profiling combined with HPLC-HRMS-SPE-NMR for identification of antibacterial constituents in Chinese plants used to treat snakebites

DEFF Research Database (Denmark)

Liu, Yueqiu; Nielsen, Mia; Stærk, Dan

2014-01-01

Bacillus subtilis, Staphylococcus aureus, Escherichia coli or Pseudomonas aeruginosa. The biochromatograms demonstrated that tannins play a main role for the bacterial growth inhibition observed for all above-mentioned plants except for Polygonum cuspidatum. Furthermore, the high-resolution bacterial...... growth inhibition profiling combined with HPLC–HRMS–SPE–NMR allowed fast identification of three non-tannin active compounds, i.e., piceid, resveratrol and emodin from ethanol extract of Polygonum cuspidatum. Conclusion The high-resolution bacterial growth inhibition profiling allowed fast pinpointing...... of constituents responsible for the bioactivity, e.g., either showing tannins being the main bacterial growth inhibitors as observed for the majority of the active plants, or combined with HPLC–HRMS–SPE–NMR for fast structural identification of non-tannin constituents correlated with antibacterial activity....

A specific bioassay for the inhibition of flowering.

Science.gov (United States)

Blake, J

1972-06-01

A bioassay for the inhibition of flowering involving the in vitro culture of excised, partially-induced, apices of Viscaria candida is described. This bioassay has been used to detect flowering inhibition in extracts from Kalanchoe blossfeldiana.

Calcium, nutrient and food intake of Greek Orthodox Christian monks during a fasting and non-fasting week.

Science.gov (United States)

Papadaki, Angeliki; Vardavas, Constantine; Hatzis, Christos; Kafatos, Anthony

2008-10-01

To assess the Ca, nutrient and food intake of Greek Orthodox Christian monks during a vegetarian-type fasting week, compared with their normal diet. Dietary data collection (using 7 d weighed food records), anthropometric and blood pressure measurements, as well as serum glucose and lipid analyses, were performed during Palm Sunday week (fasting) and the week following Pentecost Sunday (non-fasting). Mean daily nutrient and food (g/d) intakes were calculated from the food records. The study took place in two monasteries in the Municipality of Heraklion, Crete. The study involved ten healthy monks aged 25-65 years, with BMI > 30 kg/m2, who had been performing fasts for the last 24.4 (SD 10.4) years and lived in monasteries in Crete during April-June 2005. Nutrient and food intake profiles were more favourable during the fasting week, when participants had lower intakes of total and saturated fat and trans-fatty acids, and higher intakes of dietary fibre, Fe, folate, legumes and fish/seafood. Ca intake was lower when participants fasted, whereas consumption of dairy products, meat and eggs increased significantly in the non-fasting week. Systolic blood pressure was significantly higher, whereas blood lipid levels were more favourable during the fasting week. The periodic vegetarianism recommended by the Greek Orthodox Church contributes to the favourable profiles of several biomarkers of health among this sample of monks. The fasting rituals described are an important component of the traditional diet of Crete and should be emphasised in nutrition education programmes promoting this Mediterranean eating pattern.

Initiator of carcinogenesis selectively and stably inhibits stem cell differentiation: a concept that initiation of carcinogenesis involves multiple phases

International Nuclear Information System (INIS)

Scott, R.E.; Maercklein, P.B.

1985-01-01

A concept of carcinogenesis was recently devised in our laboratory that suggests the development of defects in the control of cell differentiation is associated with an early phase of carcinogenesis. To test this proposal directly, the effects of an initiator of carcinogenesis (i.e., UV irradiation) on proadipocyte stem cell differentiation and proliferation was assayed. In this regard, 3T3 T proadipocytes represent a nontransformed mesenchymal stem cell line that possesses the ability to regulate its differentiation at a distinct state in the G 1 phase of the cell cycle as well as the ability to regulate its proliferation at two additional G 1 states. The results establish that a slow dosage of 254 nm UV irradiation selectivity and stably inhibits the differentiation of a high percentage of proadipocyte stem cells without significantly altering their ability to regulate cellular proliferation in growth factor-deficient or nutrient-deficient culture conditions. Differentiation-defect proadipocyte stem cells are demonstrated not to be completely transformed but to show an increased spontaneous transformation rate, as evidenced by the formation of type III foci in high density cell cultures. These data support the role of defects in the control of differentiation in the inhibition of carcinogenesis. These observations support a concept that the initiation of carcinogenesis involves multiple phases

Recent Advances in Electrochemical Biosensors Based on Enzyme Inhibition for Clinical and Pharmaceutical Applications.

Science.gov (United States)

El Harrad, Loubna; Bourais, Ilhame; Mohammadi, Hasna; Amine, Aziz

2018-01-09

A large number of enzyme inhibitors are used as drugs to treat several diseases such as gout, diabetes, AIDS, depression, Parkinson's and Alzheimer's diseases. Electrochemical biosensors based on enzyme inhibition are useful devices for an easy, fast and environment friendly monitoring of inhibitors like drugs. In the last decades, electrochemical biosensors have shown great potentials in the detection of different drugs like neostigmine, ketoconazole, donepezil, allopurinol and many others. They attracted increasing attention due to the advantage of being high sensitive and accurate analytical tools, able to reach low detection limits and the possibility to be performed on real samples. This review will spotlight the research conducted in the past 10 years (2007-2017) on inhibition based enzymatic electrochemical biosensors for the analysis of different drugs. New assays based on novel bio-devices will be debated. Moreover, the exploration of the recent graphical approach in diagnosis of reversible and irreversible inhibition mechanism will be discussed. The accurate and the fast diagnosis of inhibition type will help researchers in further drug design improvements and the identification of new molecules that will serve as new enzyme targets.

Recent Advances in Electrochemical Biosensors Based on Enzyme Inhibition for Clinical and Pharmaceutical Applications

Directory of Open Access Journals (Sweden)

Loubna El Harrad

2018-01-01

Full Text Available A large number of enzyme inhibitors are used as drugs to treat several diseases such as gout, diabetes, AIDS, depression, Parkinson’s and Alzheimer’s diseases. Electrochemical biosensors based on enzyme inhibition are useful devices for an easy, fast and environment friendly monitoring of inhibitors like drugs. In the last decades, electrochemical biosensors have shown great potentials in the detection of different drugs like neostigmine, ketoconazole, donepezil, allopurinol and many others. They attracted increasing attention due to the advantage of being high sensitive and accurate analytical tools, able to reach low detection limits and the possibility to be performed on real samples. This review will spotlight the research conducted in the past 10 years (2007–2017 on inhibition based enzymatic electrochemical biosensors for the analysis of different drugs. New assays based on novel bio-devices will be debated. Moreover, the exploration of the recent graphical approach in diagnosis of reversible and irreversible inhibition mechanism will be discussed. The accurate and the fast diagnosis of inhibition type will help researchers in further drug design improvements and the identification of new molecules that will serve as new enzyme targets.

Overview of the fast reactors fuels program

International Nuclear Information System (INIS)

Evans, E.A.; Cox, C.M.; Hayward, B.R.; Rice, L.H.; Yoshikawa, H.H.

1980-04-01

Each nation involved in LMFBR development has its unique energy strategies which consider energy growth projections, uranium resources, capital costs, and plant operational requirements. Common to all of these strategies is a history of fast reactor experience which dates back to the days of the Manhatten Project and includes the CLEMENTINE Reactor, which generated a few watts, LAMPRE, EBR-I, EBR-II, FERMI, SEFOR, FFTF, BR-1, -2, -5, -10, BOR-60, BN-350, BN-600, JOYO, RAPSODIE, Phenix, KNK-II, DFR, and PFR. Fast reactors under design or construction include PEC, CRBR, SuperPhenix, SNR-300, MONJU, and Madras (India). The parallel fuels and materials evolution has fully supported this reactor development. It has involved cermets, molten plutonium alloy, plutonium oxide, uranium metal or alloy, uranium oxide, and mixed uranium-plutonium oxides and carbides

Differences between glycogen biogenesis in fast- and slow-twitch rabbit muscle

DEFF Research Database (Denmark)

Cussó, R; Lerner, L R; Cadefau, J

2003-01-01

Skeletal muscle glycogen is an essential energy substrate for muscular activity. The biochemical properties of the enzymes involved in de novo synthesis of glycogen were analysed in two types of rabbit skeletal muscle fiber (fast- and slow-twitch). Glycogen concentration was higher in fast...

Metformin inhibits epithelial–mesenchymal transition in prostate cancer cells: Involvement of the tumor suppressor miR30a and its target gene SOX4

International Nuclear Information System (INIS)

Zhang, Jing; Shen, Chengwu; Wang, Lin; Ma, Quanping; Xia, Pingtian; Qi, Mei; Yang, Muyi; Han, Bo

2014-01-01

Highlights: • Metformin inhibits TGF-β-induced EMT in prostate cancer (PCa) cells. • Metformin upregulates tumor suppressor miR30a and downregulates SOX4 in PCa cells. • SOX4 is a target gene of miR30a. - Abstract: Tumor metastasis is the leading cause of mortality and morbidity of prostate cancer (PCa) patients. Epithelial–mesenchymal transition (EMT) plays a critical role in cancer progression and metastasis. Recent evidence suggested that diabetic patients treated with metformin have lower PCa risk and better prognosis. This study was aimed to investigate the effects of metformin on EMT in PCa cells and the possible microRNA (miRNA)-based mechanisms. MiRNAs have been shown to regulate various processes of cancer metastasis. We herein showed that metformin significantly inhibits proliferation of Vcap and PC-3 cells, induces G0/G1 cell cycle arrest and inhibits invasiveness and motility capacity of Vcap cells. Metformin could inhibit TGF-β-induced EMT in Vcap cells, as manifested by inhibition of the increase of N-cadherin (p = 0.013), Vimentin (p = 0.002) and the decrease of E-cadherin (p = 0.0023) and β-catenin (p = 0.034) at mRNA and protein levels. Notably, we demonstrated significant upregulation of miR30a levels by metformin (P < 0.05) and further experiments indicated that miR30a significantly inhibits proliferation and EMT process of Vcap cells. Interestingly, we identified that SOX4, a previously reported oncogenic transcriptional factor and modulator of EMT, is a direct target gene of miR30a. Finally, we screened the expression of miR30a and SOX4 in 84 PCa cases with radical prostatectomy. Of note, SOX4 overexpression is significantly associated with decreased levels of miR30a in PCa cases. In all, our study suggested that inhibition of EMT by metformin in PCa cells may involve upregulation of miR30a and downregulation of SOX4

Factors inhibiting the franchising of Indian fast food stores in South Africa

OpenAIRE

2012-01-01

M.B.A. Franchising systems in South Africa have experienced high and sustained growth over the last decade. The South African government has recognised and supports business format franchising as a low risk way of creating jobs, transferring skills and creating wealth. At the forefront of this growth, is the fast food franchising industry, which is made up of a mix of global brands and a significant few, highly successful, locally founded, franchised operations based on Portuguese or Ameri...

Does Ramadan Fasting Adversely Affect Cognitive Function in Young Females?

Directory of Open Access Journals (Sweden)

Mahboubeh Ghayour Najafabadi

2015-01-01

Full Text Available We examined the effects of Ramadan fasting on cognitive function in 17 female athletes. Data were obtained from participants of two fasting (n=9 and nonfasting (n=8 groups at three periods of the study (before Ramadan, at the third week in Ramadan, and after Ramadan. Digit span test (DST and Stroop color test were employed to assess short-term memory and inhibition/cognitive flexibility at each time point. There were no significant changes for DST and Stroop task 1 in both groups, whereas Stroop task 2 and task 3 showed significant improvements in Ramadan condition (p<0.05. Interference indices did not change significantly across the study except in post-Ramadan period of fasting group (p<0.05. Group × week interaction was significant only for error numbers (p<0.05. Athletes in nonfasting showed a significant decrease in number of errors in Ramadan compared to baseline (p<0.05. The results suggest that Ramadan fasting may not adversely affect cognitive function in female athletes.

The Inhibition of microRNA-128 on IGF-1-Activating mTOR Signaling Involves in Temozolomide-Induced Glioma Cell Apoptotic Death.

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Peng-Hsu Chen

Full Text Available Temozolomide (TMZ, an alkylating agent of the imidazotetrazine series, is a first-line chemotherapeutic drug used in the clinical therapy of glioblastoma multiforme, the most common and high-grade primary glioma in adults. Micro (miRNAs, which are small noncoding RNAs, post-transcriptionally regulate gene expressions and are involved in gliomagenesis. However, no studies have reported relationships between TMZ and miRNA gene regulation. We investigated TMZ-mediated miRNA profiles and its molecular mechanisms underlying the induction of glioma cell death. By performing miRNA microarray and bioinformatics analyses, we observed that expression of 248 miRNAs was altered, including five significantly upregulated and 17 significantly downregulated miRNAs, in TMZ-treated U87MG cells. miR-128 expression levels were lower in different glioma cells and strongly associated with poor survival. TMZ treatment significantly upregulated miR-128 expression. TMZ significantly enhanced miR-128-1 promoter activity and transcriptionally regulated miR-128 levels through c-Jun N-terminal kinase 2/c-Jun pathways. The overexpression and knockdown of miR-128 expression significantly affected TMZ-mediated cell viability and apoptosis-related protein expression. Furthermore, the overexpression of miR-128 alone enhanced apoptotic death of glioma cells through caspase-3/9 activation, poly(ADP ribose polymerase degradation, reactive oxygen species generation, mitochondrial membrane potential loss, and non-protective autophagy formation. Finally, we identified that key members in mammalian target of rapamycin (mTOR signaling including mTOR, rapamycin-insensitive companion of mTOR, insulin-like growth factor 1, and PIK3R1, but not PDK1, were direct target genes of miR-128. TMZ inhibited mTOR signaling through miR-128 regulation. These results indicate that miR-128-inhibited mTOR signaling is involved in TMZ-mediated cytotoxicity. Our findings may provide a better understanding

Partial fast-to-slow conversion of regenerating rat fast-twitch muscle by chronic low-frequency stimulation.

Science.gov (United States)

Pette, Dirk; Sketelj, Janez; Skorjanc, Dejan; Leisner, Elmi; Traub, Irmtrud; Bajrović, Fajko

2002-01-01

Chronic low-frequency stimulation (CLFS) of rat fast-twitch muscles induces sequential transitions in myosin heavy chain (MHC) expression from MHCIIb --> MHCIId/x --> MHCIIa. However, the 'final' step of the fast-to-slow transition, i.e., the upregulation of MHCI, has been observed only after extremely long stimulation periods. Assuming that fibre degeneration/regeneration might be involved in the upregulation of slow myosin, we investigated the effects of CLFS on extensor digitorum longus (EDL) muscles regenerating after bupivacaine-induced fibre necrosis. Normal, non-regenerating muscles responded to both 30- and 60-day CLFS with fast MHC isoform transitions (MHCIIb --> MHCIId --> MHCIIa) and only slight increases in MHCI. CLFS of regenerating EDL muscles caused similar transitions among the fast isoforms but, in addition, caused significant increases in MHCI (to approximately 30% relative concentration). Stimulation periods of 30 and 60 days induced similar changes in the regenerating bupivacaine-treated muscles, indicating that the upregulation of slow myosin was restricted to regenerating fibres, but only during an early stage of regeneration. These results suggest that satellite cells and/or regenerating fast rat muscle fibres are capable of switching directly to a slow program under the influence of CLFS and, therefore, appear to be more malleable than adult fibres.

Acute fasting inhibits central caspase-1 activity reducing anxiety-like behavior and increasing novel object and object location recognition.

Science.gov (United States)

Towers, Albert E; Oelschlager, Maci L; Patel, Jay; Gainey, Stephen J; McCusker, Robert H; Freund, Gregory G

2017-06-01

Inflammation within the central nervous system (CNS) is frequently comorbid with anxiety. Importantly, the pro-inflammatory cytokine most commonly associated with anxiety is IL-1β. The bioavailability and activity of IL-1β are regulated by caspase-1-dependent proteolysis vis-a-vis the inflammasome. Thus, interventions regulating the activation or activity of caspase-1 should reduce anxiety especially in states that foster IL-1β maturation. Male C57BL/6j, C57BL/6j mice treated with the capase-1 inhibitor biotin-YVAD-cmk, caspase-1 knockout (KO) mice and IL-1R1 KO mice were fasted for 24h or allowed ad libitum access to food. Immediately after fasting, caspase-1 activity was measured in brain region homogenates while activated caspase-1 was localized in the brain by immunohistochemistry. Mouse anxiety-like behavior and cognition were tested using the elevated zero maze and novel object/object location tasks, respectively. A 24h fast in mice reduced the activity of caspase-1 in whole brain and in the prefrontal cortex, amygdala, hippocampus, and hypothalamus by 35%, 25%, 40%, 40%, and 40% respectively. A 24h fast also reduced anxiety-like behavior by 40% and increased novel object and object location recognition by 21% and 31%, respectively. IL-1β protein, however, was not reduced in the brain by fasting. ICV administration of YVAD decreased caspase-1 activity in the prefrontal cortex and amygdala by 55%, respectively leading to a 64% reduction in anxiety like behavior. Importantly, when caspase-1 KO or IL1-R1 KO mice are fasted, no fasting-dependent reduction in anxiety-like behavior was observed. Results indicate that fasting decrease anxiety-like behavior and improves memory by a mechanism tied to reducing caspase-1 activity throughout the brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Adsorption and Corrosion Inhibition Studies of Some Selected Dyes as Corrosion Inhibitors for Mild Steel in Acidic Medium: Gravimetric, Electrochemical, Quantum Chemical Studies and Synergistic Effect with Iodide Ions

Directory of Open Access Journals (Sweden)

Thabo Peme

2015-09-01

Full Text Available The corrosion inhibition properties of some organic dyes, namely Sunset Yellow (SS, Amaranth (AM, Allura Red (AR, Tartrazine (TZ and Fast Green (FG, for mild steel corrosion in 0.5 M HCl solution, were investigated using gravimetric, potentiodynamic polarization techniques and quantum chemical calculations. The results showed that the studied dyes are good corrosion inhibitors with enhanced inhibition efficiencies. The inhibition efficiency of all the studied dyes increases with increase in concentration, and decreases with increase in temperature. The results showed that the inhibition efficiency of the dyes increases in the presence of KI due to synergistic interactions of the dye molecules with iodide (I− ions. Potentiodynamic polarization results revealed that the studied dyes are mixed-type inhibitors both in the absence and presence of KI. The adsorption of the studied dyes on mild steel surface, with and without KI, obeys the Langmuir adsorption isotherm and involves physical adsorption mechanism. Quantum chemical calculations revealed that the most likely sites in the dye molecules for interactions with mild steel are the S, O, and N heteroatoms.

Adsorption and Corrosion Inhibition Studies of Some Selected Dyes as Corrosion Inhibitors for Mild Steel in Acidic Medium: Gravimetric, Electrochemical, Quantum Chemical Studies and Synergistic Effect with Iodide Ions.

Science.gov (United States)

Peme, Thabo; Olasunkanmi, Lukman O; Bahadur, Indra; Adekunle, Abolanle S; Kabanda, Mwadham M; Ebenso, Eno E

2015-09-02

The corrosion inhibition properties of some organic dyes, namely Sunset Yellow (SS), Amaranth (AM), Allura Red (AR), Tartrazine (TZ) and Fast Green (FG), for mild steel corrosion in 0.5 M HCl solution, were investigated using gravimetric, potentiodynamic polarization techniques and quantum chemical calculations. The results showed that the studied dyes are good corrosion inhibitors with enhanced inhibition efficiencies. The inhibition efficiency of all the studied dyes increases with increase in concentration, and decreases with increase in temperature. The results showed that the inhibition efficiency of the dyes increases in the presence of KI due to synergistic interactions of the dye molecules with iodide (I(-)) ions. Potentiodynamic polarization results revealed that the studied dyes are mixed-type inhibitors both in the absence and presence of KI. The adsorption of the studied dyes on mild steel surface, with and without KI, obeys the Langmuir adsorption isotherm and involves physical adsorption mechanism. Quantum chemical calculations revealed that the most likely sites in the dye molecules for interactions with mild steel are the S, O, and N heteroatoms.

Fast neutron irradiation deteriorates hippocampus-related memory ability in adult mice.

Science.gov (United States)

Yang, Miyoung; Kim, Hwanseong; Kim, Juhwan; Kim, Sung-Ho; Kim, Jong-Choon; Bae, Chun-Sik; Kim, Joong-Sun; Shin, Taekyun; Moon, Changjong

2012-03-01

Object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice exposed to cranial fast neutron irradiation (0.8 Gy) were examined to evaluate hippocampus-related behavioral dysfunction following acute exposure to relatively low doses of fast neutrons. In addition, hippocampal neurogenesis changes in adult murine brain after cranial irradiation were analyzed using the neurogenesis immunohistochemical markers Ki-67 and doublecortin (DCX). In the object recognition memory test and contextual fear conditioning, mice trained 1 and 7 days after irradiation displayed significant memory deficits compared to the sham-irradiated controls. The number of Ki-67- and DCX-positive cells decreased significantly 24 h post-irradiation. These results indicate that acute exposure of the adult mouse brain to a relatively low dose of fast neutrons interrupts hippocampal functions, including learning and memory, possibly by inhibiting neurogenesis.

Fast and accurate computation of projected two-point functions

Science.gov (United States)

Grasshorn Gebhardt, Henry S.; Jeong, Donghui

2018-01-01

We present the two-point function from the fast and accurate spherical Bessel transformation (2-FAST) algorithm1Our code is available at https://github.com/hsgg/twoFAST. for a fast and accurate computation of integrals involving one or two spherical Bessel functions. These types of integrals occur when projecting the galaxy power spectrum P (k ) onto the configuration space, ξℓν(r ), or spherical harmonic space, Cℓ(χ ,χ'). First, we employ the FFTLog transformation of the power spectrum to divide the calculation into P (k )-dependent coefficients and P (k )-independent integrations of basis functions multiplied by spherical Bessel functions. We find analytical expressions for the latter integrals in terms of special functions, for which recursion provides a fast and accurate evaluation. The algorithm, therefore, circumvents direct integration of highly oscillating spherical Bessel functions.

Fast, non-competitive and reversible inhibition of NMDA-activated currents by 2-BFI confers neuroprotection.

Directory of Open Access Journals (Sweden)

Zhao Han

Full Text Available Excessive activation of the N-methyl-D-aspartic acid (NMDA type glutamate receptors (NMDARs causes excitotoxicity, a process important in stroke-induced neuronal death. Drugs that inhibit NMDA receptor-mediated [Ca(2+]i influx are potential leads for development to treat excitotoxicity-induced brain damage. Our previous studies showed that 2-(2-benzofu-ranyl-2-imidazoline (2-BFI, an immidazoline receptor ligand, dose-dependently protects rodent brains from cerebral ischemia injury. However, the molecular mechanisms remain unclear. In this study, we found that 2-BFI transiently and reversibly inhibits NMDA, but not AMPA currents, in a dose-dependent manner in cultured rat cortical neurons. The mechanism of 2-BFI inhibition of NMDAR is through a noncompetitive fashion with a faster on (Kon = 2.19±0.33×10(-9 M(-1 sec(-1 and off rate (Koff = 0.67±0.02 sec(-1 than those of memantine, a gold standard for therapeutic inhibition NMDAR-induced excitotoxicity. 2-BFI also transiently and reversibly blocked NMDA receptor-mediated calcium entry to cultured neurons and provided long-term neuroprotection against NMDA toxicity in vitro. Collectively, these studies demonstrated a potential mechanism of 2-BFI-mediated neuroprotection and indicated that 2-BFI is an excellent candidate for repositioning as a drug for stroke treatment.

Morus alba and active compound oxyresveratrol exert anti-inflammatory activity via inhibition of leukocyte migration involving MEK/ERK signaling.

Science.gov (United States)

Chen, Yi-Ching; Tien, Yin-Jing; Chen, Chun-Houh; Beltran, Francesca N; Amor, Evangeline C; Wang, Ran-Juh; Wu, Den-Jen; Mettling, Clément; Lin, Yea-Lih; Yang, Wen-Chin

2013-02-23

Morus alba has long been used in traditional Chinese medicine to treat inflammatory diseases; however, the scientific basis for such usage and the mechanism of action are not well understood. This study investigated the action of M. alba on leukocyte migration, one key step in inflammation. Gas chromatography-mass spectrometry (GC-MS) and cluster analyses of supercritical CO2 extracts of three Morus species were performed for chemotaxonomy-aided plant authentication. Phytochemistry and CXCR4-mediated chemotaxis assays were used to characterize the chemical and biological properties of M. alba and its active compound, oxyresveratrol. fluorescence-activated cell sorting (FACS) and Western blot analyses were conducted to determine the mode of action of oxyresveratrol. Chemotaxonomy was used to help authenticate M. alba. Chemotaxis-based isolation identified oxyresveratrol as an active component in M. alba. Phytochemical and chemotaxis assays showed that the crude extract, ethyl acetate fraction and oxyresveratrol from M. alba suppressed cell migration of Jurkat T cells in response to SDF-1. Mechanistic study indicated that oxyresveratrol diminished CXCR4-mediated T-cell migration via inhibition of the MEK/ERK signaling cascade. A combination of GC-MS and cluster analysis techniques are applicable for authentication of the Morus species. Anti-inflammatory benefits of M. alba and its active compound, oxyresveratrol, may involve the inhibition of CXCR-4-mediated chemotaxis and MEK/ERK pathway in T and other immune cells.

p8 inhibits the growth of human pancreatic cancer cells and its expression is induced through pathways involved in growth inhibition and repressed by factors promoting cell growth

Directory of Open Access Journals (Sweden)

Vasseur Sophie

2003-11-01

Full Text Available Abstract Background p8 is a stress-induced protein with multiple functions and biochemically related to the architectural factor HMG-I/Y. We analyzed the expression and function of p8 in pancreatic cancer-derived cells. Methods Expression of p8 was silenced in the human pancreatic cancer cell lines Panc-1 and BxPc-3 by infection with a retrovirus expressing p8 RNA in the antisense orientation. Cell growth was measured in control and p8-silenced cells. Influence on p8 expression of the induction of intracellular pathways promoting cellular growth or growth arrest was monitored. Results p8-silenced cells grew more rapidly than control cells transfected with the empty retrovirus. Activation of the Ras→Raf→MEK→ERK and JNK intracellular pathways down-regulated p8 expression. In addition, the MEK1/2 inhibitor U0126 and the JNK inhibitor SP600125 up-regulates expression of p8. Conversely, p38 or TGFβ-1 induced p8 expression whereas the specific p38 inhibitor SB203580 down-regulated p8 expression. Finally, TGFβ-1 induction was in part mediated through p38. Conclusions p8 inhibits the growth of human pancreatic cancer cells. p8 expression is induced through pathways involved in growth inhibition and repressed by factors that promote cell growth. These results suggest that p8 belongs to a pathway regulating the growth of pancreatic cancer cells.

Involvement of lymphocyte function-associated antigen-1 (LFA-1) in HIV infection: inhibition by monoclonal antibody

DEFF Research Database (Denmark)

Hansen, J E; Nielsen, C; Mathiesen, Lars Reinhardt

1991-01-01

Monoclonal antibodies (MAbs) against the alpha- and beta-chain of lymphocyte-associated antigen-1 (LFA-1) were examined for inhibition of HIV-1 infection in vitro. Infection of the T cell line MT4 and the monocytic cell line U937 by isolates HTLVIIIB and SSI-002, respectively was inhibited...... in a concentration dependent manner by MAb against the beta-chain but not against the alpha-chain. No cross-reactivity was found between MAb against LFA-1 and against the CD4 receptor (MAb Leu3a). MAbs against the beta-chain and the CD4 receptor were found to act synergistically in inhibiting HIV infection...

Involvement of lymphocyte function-associated antigen-1 (LFA-1) in HIV infection: inhibition by monoclonal antibody

DEFF Research Database (Denmark)

Hansen, J E; Nielsen, C; Mathiesen, Lars Reinhardt

1991-01-01

Monoclonal antibodies (MAbs) against the alpha- and beta-chain of lymphocyte-associated antigen-1 (LFA-1) were examined for inhibition of HIV-1 infection in vitro. Infection of the T cell line MT4 and the monocytic cell line U937 by isolates HTLVIIIB and SSI-002, respectively was inhibited...

Overview of the fast reactors fuels program. [LMFBR

Energy Technology Data Exchange (ETDEWEB)

Evans, E.A.; Cox, C.M.; Hayward, B.R.; Rice, L.H.; Yoshikawa, H.H.

1980-04-01

Each nation involved in LMFBR development has its unique energy strategies which consider energy growth projections, uranium resources, capital costs, and plant operational requirements. Common to all of these strategies is a history of fast reactor experience which dates back to the days of the Manhatten Project and includes the CLEMENTINE Reactor, which generated a few watts, LAMPRE, EBR-I, EBR-II, FERMI, SEFOR, FFTF, BR-1, -2, -5, -10, BOR-60, BN-350, BN-600, JOYO, RAPSODIE, Phenix, KNK-II, DFR, and PFR. Fast reactors under design or construction include PEC, CRBR, SuperPhenix, SNR-300, MONJU, and Madras (India). The parallel fuels and materials evolution has fully supported this reactor development. It has involved cermets, molten plutonium alloy, plutonium oxide, uranium metal or alloy, uranium oxide, and mixed uranium-plutonium oxides and carbides.

Effect of miglitol (BAY m-1099) on fasting blood glucose in type 2 diabetes mellitus

NARCIS (Netherlands)

Sels, J P; Kingma, P J; Wolffenbuttel, B H; Menheere, P P; Branolte, J H; Nieuwenhuijzen Kruseman, A C

BACKGROUND: In type 2 diabetes mellitus, fasting blood glucose values are increased due to increased glycogenolysis and gluconeogenesis. As miglitol (BAY m-1099), an absorbable alpha-glucosidase inhibitor, can inhibit glycogenolysis, we investigated whether 200 mg miglitol ingested at bedtime could

Breeding gains of sodium-cooled oxide-fueled fast reactors

International Nuclear Information System (INIS)

Mougniot, J.C.; Barre, J.Y.; Clauzon, P.; Ciacometti, C.; Neviere, G.; Ravier, J.; Sichard, B.

Calculated values are presented for the breeding gains of French fast reactors, and the experimental uncertainties are discussed. The effect of various choices of planning on the breeding gains is next analyzed within the framework of classical concepts. In the final part, a new concept involving ''heterogeneous cores'' with a single enrichment zone is presented. This concept permits a significant improvement in the breeding gain and doubling time of fast reactors. (U.S.)

Exercise, fasting, and mimetics : Toward beneficial combinations?

NARCIS (Netherlands)

Jaspers, Richard T.; Zillikens, M Carola; Friesema, Edith C H; Paoli, Giuseppe Delli; Bloch, Wilhelm; Uitterlinden, André G; Goglia, Fernando; Lanni, Antonia; De Lange, Pieter

2017-01-01

Obesity and type 2 diabetes are associated disorders that involve a multiplicity of tissues. Both fasting and physical exercise are known to counteract dyslipidemia/hyperglycemia. Skeletal muscle plays a key role in the control of blood glucose levels, and the metabolic changes and related signaling

Enhancing MISP with Fast Mobile IPv6 Security

Directory of Open Access Journals (Sweden)

Ilsun You

2011-01-01

Full Text Available The Mobile Broadband Association has developed the MIS and MISAUTH protocols as link-layer fast authentication protocols. A combination of MIS and MISAUTH protocols, called as MISP, provides secure and fast connection for a wireless access network, but it has been reported that MISP creates a weak session key and suffers from a denial-of-service attack. In addition, a transaction with an authentication server that is required for every authentication is considered as a delay factor during handovers. In this paper, we present an improvement of MISP that utilizes the fast handover approach of Fast Mobile IPv6 and minimizes an involvement of the authentication server while eliminating identified security drawbacks of MISP. The formal security analysis is performed to verify the correctness of the proposed scheme. Moreover, the handover performance of the proposed scheme is compared with an existing scheme.

Neighborhood fast food availability and fast food consumption.

Science.gov (United States)

Oexle, Nathalie; Barnes, Timothy L; Blake, Christine E; Bell, Bethany A; Liese, Angela D

2015-09-01

Recent nutritional and public health research has focused on how the availability of various types of food in a person's immediate area or neighborhood influences his or her food choices and eating habits. It has been theorized that people living in areas with a wealth of unhealthy fast-food options may show higher levels of fast-food consumption, a factor that often coincides with being overweight or obese. However, measuring food availability in a particular area is difficult to achieve consistently: there may be differences in the strict physical locations of food options as compared to how individuals perceive their personal food availability, and various studies may use either one or both of these measures. The aim of this study was to evaluate the association between weekly fast-food consumption and both a person's perceived availability of fast-food and an objective measure of fast-food presence - Geographic Information Systems (GIS) - within that person's neighborhood. A randomly selected population-based sample of eight counties in South Carolina was used to conduct a cross-sectional telephone survey assessing self-report fast-food consumption and perceived availability of fast food. GIS was used to determine the actual number of fast-food outlets within each participant's neighborhood. Using multinomial logistic regression analyses, we found that neither perceived availability nor GIS-based presence of fast-food was significantly associated with weekly fast-food consumption. Our findings indicate that availability might not be the dominant factor influencing fast-food consumption. We recommend using subjective availability measures and considering individual characteristics that could influence both perceived availability of fast food and its impact on fast-food consumption. If replicated, our findings suggest that interventions aimed at reducing fast-food consumption by limiting neighborhood fast-food availability might not be completely effective

Serum Lipid Profile: Fasting or Non-fasting?

OpenAIRE

Nigam, P. K.

2010-01-01

Serum lipid profile has now become almost a routine test. It is usually done in fasting state due to certain limitations in non-fasting serum sample. In the recent past efforts have been made to simplify blood sampling by replacing fasting lipid profile with non-fasting lipid profile. However, fasting specimen is preferred if cardiovascular risk assessment is based on total cholesterol, LDL cholesterol or non-HDL cholesterol. A lot has yet to be done in this area. Till then we have to believe...

A study of fast bunch rotation in the negative mass region

CERN Document Server

Rumolo, Giovanni

2001-01-01

Fast bunch rotation of high-intensity proton or ion bunches above transition is - in principle - supported by the self-bunching effect of the attractive space charge force ("negative instabilities"). Due to the broad-band nature of the space charge impedance, the highest harmonics of this negative mass mode grow fast and inhibit compression, unless the bunch rotation is accelerated by a sufficiently high rf-voltage. Using particle-in-cell simulation we establish the threshold below which effective compression is still possible. We find that the required rf-voltage for compression of a given bunch above transition can be reduced at most by a factor 2 compared with compression below transition, where space charge requires extra voltage.

Inhibition of potassium currents is involved in antiarrhythmic effect of moderate ethanol on atrial fibrillation

Energy Technology Data Exchange (ETDEWEB)

Yang, Baode; Li, Chenxing [Department of Pharmacology, Health Science Center, Xi' an Jiaotong University, Xi' an (China); Sun, Junyi [Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi' an Jiaotong University, Xi' an (China); Department of Periodontology, College of Stomatology, Xi' an Jiaotong University, Xi' an (China); Wang, Xinghui; Liu, Xinling [Basic Medical Experiment Teaching Center, Health Science Center, Xi' an Jiaotong University, Xi' an (China); Yang, Chun [Department of Cardiology, The First Affiliated Hospital, Xi' an Jiaotong University, Xi' an (China); Chen, Lina; Zhou, Jun [Department of Pharmacology, Health Science Center, Xi' an Jiaotong University, Xi' an (China); Key Laboratory of Environment and Genes Related to Diseases, Xi' an Jiaotong University, Ministry of Education of China, Xi' an (China); Hu, Hao, E-mail: huhao@mail.xjtu.edu.cn [Department of Pharmacology, Health Science Center, Xi' an Jiaotong University, Xi' an (China); Key Laboratory of Environment and Genes Related to Diseases, Xi' an Jiaotong University, Ministry of Education of China, Xi' an (China)

2017-05-01

Excessive consumption of alcohol is a well-established risk factor of atrial fibrillation (AF). However, the effects of moderate alcohol drinking remain to be elucidated. This study was designed to determine the effects of moderate ethanol ingestion on atrial fibrillation and the electrophysiological mechanisms. In acetylcholine-induced canine and mouse AF models, the moderate ethanol prevented the generation and persistence of AF through prolonging the latent period of AF and shortening the duration of AF. The action potential duration (APD) was remarkably prolonged under the concentration range of 12.5–50.0 mM ethanol in guinea pig atrial myocytes. Ultra-rapid delayed rectified potassium currents (I{sub Kv1.5}) were markedly inhibited by 12.5–50.0 mM ethanol in a concentration-dependent manner. Ethanol with 50.0 mM could inhibit rapid delayed rectifier potassium currents (I{sub hERG}). Ethanol under 6.25–50.0 mM did not affect on inward rectifier potassium currents (I{sub Kir2.1}). Collectively, the present study provided an evidence that moderate ethanol intake can prolong the APD of atrial myocytes by inhibition of I{sub Kv1.5} and I{sub hERG}, which contributed to preventing the development and duration of AF. - Highlights: • Moderate ethanol prevented the development of AF in animal models. • Moderate ethanol prolonged APD in guinea pig atrial myocytes. • Moderate ethanol inhibited Kv1.5 currents.

Inhibition of potassium currents is involved in antiarrhythmic effect of moderate ethanol on atrial fibrillation

International Nuclear Information System (INIS)

Yang, Baode; Li, Chenxing; Sun, Junyi; Wang, Xinghui; Liu, Xinling; Yang, Chun; Chen, Lina; Zhou, Jun; Hu, Hao

2017-01-01

Excessive consumption of alcohol is a well-established risk factor of atrial fibrillation (AF). However, the effects of moderate alcohol drinking remain to be elucidated. This study was designed to determine the effects of moderate ethanol ingestion on atrial fibrillation and the electrophysiological mechanisms. In acetylcholine-induced canine and mouse AF models, the moderate ethanol prevented the generation and persistence of AF through prolonging the latent period of AF and shortening the duration of AF. The action potential duration (APD) was remarkably prolonged under the concentration range of 12.5–50.0 mM ethanol in guinea pig atrial myocytes. Ultra-rapid delayed rectified potassium currents (I Kv1.5 ) were markedly inhibited by 12.5–50.0 mM ethanol in a concentration-dependent manner. Ethanol with 50.0 mM could inhibit rapid delayed rectifier potassium currents (I hERG ). Ethanol under 6.25–50.0 mM did not affect on inward rectifier potassium currents (I Kir2.1 ). Collectively, the present study provided an evidence that moderate ethanol intake can prolong the APD of atrial myocytes by inhibition of I Kv1.5 and I hERG , which contributed to preventing the development and duration of AF. - Highlights: • Moderate ethanol prevented the development of AF in animal models. • Moderate ethanol prolonged APD in guinea pig atrial myocytes. • Moderate ethanol inhibited Kv1.5 currents.

Gibberellin Is Involved in Inhibition of Cucumber Growth and Nitrogen Uptake at Suboptimal Root-Zone Temperatures.

Directory of Open Access Journals (Sweden)

Longqiang Bai

Full Text Available Suboptimal temperature stress often causes heavy yield losses of vegetables by suppressing plant growth during winter and early spring. Gibberellin acid (GA has been reported to be involved in plant growth and acquisition of mineral nutrients. However, no studies have evaluated the role of GA in the regulation of growth and nutrient acquisition by vegetables under conditions of suboptimal temperatures in greenhouse. Here, we investigated the roles of GA in the regulation of growth and nitrate acquisition of cucumber (Cucumis sativus L. plants under conditions of short-term suboptimal root-zone temperatures (Tr. Exposure of cucumber seedlings to a Tr of 16°C led to a significant reduction in root growth, and this inhibitory effect was reversed by exogenous application of GA. Expression patterns of several genes encoding key enzymes in GA metabolism were altered by suboptimal Tr treatment, and endogenous GA concentrations in cucumber roots were significantly reduced by exposure of cucumber plants to 16°C Tr, suggesting that inhibition of root growth by suboptimal Tr may result from disruption of endogenous GA homeostasis. To further explore the mechanism underlying the GA-dependent cucumber growth under suboptimal Tr, we studied the effect of suboptimal Tr and GA on nitrate uptake, and found that exposure of cucumber seedlings to 16°C Tr led to a significant reduction in nitrate uptake rate, and exogenous application GA can alleviate the down-regulation by up regulating the expression of genes associated with nitrate uptake. Finally, we demonstrated that N accumulation in cucumber seedlings under suboptimal Tr conditions was improved by exogenous application of GA due probably to both enhanced root growth and nitrate absorption activity. These results indicate that a reduction in endogenous GA concentrations in roots due to down-regulation of GA biosynthesis at transcriptional level may be a key event to underpin the suboptimal Tr

Transcriptional and chromatin regulation during fasting – The genomic era

Science.gov (United States)

Goldstein, Ido; Hager, Gordon L.

2015-01-01

An elaborate metabolic response to fasting is orchestrated by the liver and is heavily reliant upon transcriptional regulation. In response to hormones (glucagon, glucocorticoids) many transcription factors (TFs) are activated and regulate various genes involved in metabolic pathways aimed at restoring homeostasis: gluconeogenesis, fatty acid oxidation, ketogenesis and amino acid shuttling. We summarize the recent discoveries regarding fasting-related TFs with an emphasis on genome-wide binding patterns. Collectively, the summarized findings reveal a large degree of co-operation between TFs during fasting which occurs at motif-rich DNA sites bound by a combination of TFs. These new findings implicate transcriptional and chromatin regulation as major determinants of the response to fasting and unravels the complex, multi-TF nature of this response. PMID:26520657

Chemical and physical changes at sodium-stainless steel interfaces in fast reactors

Energy Technology Data Exchange (ETDEWEB)

Mathews, C K [Bhabha Atomic Research Centre, Bombay (India). Radiochemistry Div.

1977-01-01

In the sodium loops of a fast reactor, mass transfer occurs due to the interaction of flowing sodium on stainless steel surfaces. Under the non-isothermal conditions prevailing in the loop some elements are preferentially leached from the surface layers of the hot zone and transported by sodium to the cooled zone where deposition may take place. The available information on the mass transport in non-isothermal sodium loops has been summarised, and an attempt has been made to understand the mechanisms involved, of which the chemical reactions at the sodium-stainless steel interface are especially important. The rate of diffusion towards the solid/liquid interface may be the rate-determining step in some of these reactions. When a ferritic surface layer is formed by the selective removal of austenitic stabilizing elements, diffusion of alloying constituents through the ferritic layer limits the growth of this layer. Only when the surface film is adherent, the diffusion across this layer becomes important. NaCrO/sub 2/, for instance, has poor adherence, and a surface film of this compound may not inhibit further corrosion.

Different mechanisms are involved in the antibody mediated inhibition of ligand binding to the urokinase receptor

DEFF Research Database (Denmark)

List, K; Høyer-Hansen, G; Rønne, E

1999-01-01

Certain monoclonal antibodies are capable of inhibiting the biological binding reactions of their target proteins. At the molecular level, this type of effect may be brought about by completely different mechanisms, such as competition for common binding determinants, steric hindrance or interfer......Certain monoclonal antibodies are capable of inhibiting the biological binding reactions of their target proteins. At the molecular level, this type of effect may be brought about by completely different mechanisms, such as competition for common binding determinants, steric hindrance......) can be employed as a highly useful tool to characterize the inhibitory mechanism of specific antagonist antibodies. Two inhibitory antibodies against uPAR, mAb R3 and mAb R5, were shown to exhibit competitive and non-competitive inhibition, respectively, of ligand binding to the receptor. The former...

Glass transition of anhydrous starch by fast scanning calorimetry.

Science.gov (United States)

Monnier, Xavier; Maigret, Jean-Eudes; Lourdin, Denis; Saiter, Allisson

2017-10-01

By means of fast scanning calorimetry, the glass transition of anhydrous amorphous starch has been measured. With a scanning rate of 2000Ks -1 , thermal degradation of starch prior to the glass transition has been inhibited. To certify the glass transition measurement, structural relaxation of the glassy state has been investigated through physical aging as well as the concept of limiting fictive temperature. In both cases, characteristic enthalpy recovery peaks related to the structural relaxation of the glass have been observed. Thermal lag corrections based on the comparison of glass transition temperatures measured by means of differential and fast scanning calorimetry have been proposed. The complementary investigations give an anhydrous amorphous starch glass transition temperature of 312±7°C. This estimation correlates with previous extrapolation performed on hydrated starches. Copyright © 2017 Elsevier Ltd. All rights reserved.

PREDICTING A FAST-TRACK MARITIME CAREER: CHARACTERISTICS OF SUCCESSFUL OFFICERS DURING TEENAGE YEARS

Directory of Open Access Journals (Sweden)

Manuel Joaquín Fernández González

2017-12-01

Full Text Available Fast-track maritime career is a topical question worldwide due to the shortage of seafarers in maritime industry. Assuming that the fast-track career officers’ relevant common characteristics in adolescence could predict future maritime career speed, the research questions of this research are: What were the common characteristics of fast-track career officers when they were 16-18? Were there any statistically significant differences between the fast-track career groups and the officers with a slower career at that age? A questionnaire survey involving 175 maritime officers was conducted in Latvia in January – October 2016, regarding officers’ family context, school achievement, involvement in sports, and personality traits when they were 16-18. Fast-track career officers perceived themselves as more conscientious, calm and more leadership oriented than the whole group in adolescence. Statistically significant differences among career-speed groups were found regarding family socioeconomic status, family atmosphere and family career support at that age. Based on those communalities among maritime officers with a fast-track carrier when they were 16-18, maritime education and training institutions could better find and give appropriate career guidance to prospective maritime officers. Even if maritime career speed is a very individualized phenomenon, family characteristics could be studied further as a potential good predictor of fast-track maritime career.

Inhibition of cardiac sodium currents by toluene exposure

Science.gov (United States)

Cruz, Silvia L; Orta-Salazar, Gerardo; Gauthereau, Marcia Y; Millan-Perez Peña, Lourdes; Salinas-Stefanón, Eduardo M

2003-01-01

Toluene is an industrial solvent widely used as a drug of abuse, which can produce sudden sniffing death due to cardiac arrhythmias. In this paper, we tested the hypothesis that toluene inhibits cardiac sodium channels in Xenopus laevis oocytes transfected with Nav1.5 cDNA and in isolated rat ventricular myocytes. In oocytes, toluene inhibited sodium currents (INa+) in a concentration-dependent manner, with an IC50 of 274 μM (confidence limits: 141–407μM). The inhibition was complete, voltage-independent, and slowly reversible. Toluene had no effect on: (i) the shape of the I–V curves; (ii) the reversal potential of Na+; and (iii) the steady-state inactivation. The slow recovery time constant from inactivation of INa+ decreased with toluene exposure, while the fast recovery time constant remained unchanged. Block of INa+ by toluene was use- and frequency-dependent. In rat cardiac myocytes, 300 μM toluene inhibited the sodium current (INa+) by 62%; this inhibition was voltage independent. These results suggest that toluene binds to cardiac Na+ channels in the open state and unbinds either when channels move between inactivated states or from an inactivated to a closed state. The use- and frequency-dependent block of INa+ by toluene might be responsible, at least in part, for its arrhythmogenic effect. PMID:14534149

Effects of Intermittent Fasting, Caloric Restriction, and Ramadan Intermittent Fasting on Cognitive Performance at Rest and During Exercise in Adults.

Science.gov (United States)

Cherif, Anissa; Roelands, Bart; Meeusen, Romain; Chamari, Karim

2016-01-01

The aim of this review was to highlight the potent effects of intermittent fasting on the cognitive performance of athletes at rest and during exercise. Exercise interacts with dietary factors and has a positive effect on brain functioning. Furthermore, physical activity and exercise can favorably influence brain plasticity. Mounting evidence indicates that exercise, in combination with diet, affects the management of energy metabolism and synaptic plasticity by affecting molecular mechanisms through brain-derived neurotrophic factor, an essential neurotrophin that acts at the interface of metabolism and plasticity. The literature has also shown that certain aspects of physical performance and mental health, such as coping and decision-making strategies, can be negatively affected by daylight fasting. However, there are several types of intermittent fasting. These include caloric restriction, which is distinct from fasting and allows subjects to drink water ad libitum while consuming a very low-calorie food intake. Another type is Ramadan intermittent fasting, which is a religious practice of Islam, where healthy adult Muslims do not eat or drink during daylight hours for 1 month. Other religious practices in Islam (Sunna) also encourage Muslims to practice intermittent fasting outside the month of Ramadan. Several cross-sectional and longitudinal studies have shown that intermittent fasting has crucial effects on physical and intellectual performance by affecting various aspects of bodily physiology and biochemistry that could be important for athletic success. Moreover, recent findings revealed that immunological variables are also involved in cognitive functioning and that intermittent fasting might impact the relationship between cytokine expression in the brain and cognitive deficits, including memory deficits.

The Fast-Casual Conundrum: Fast-Casual Restaurant Entrées Are Higher in Calories than Fast Food.

Science.gov (United States)

Schoffman, Danielle E; Davidson, Charis R; Hales, Sarah B; Crimarco, Anthony E; Dahl, Alicia A; Turner-McGrievy, Gabrielle M

2016-10-01

Frequently eating fast food has been associated with consuming a diet high in calories, and there is a public perception that fast-casual restaurants (eg, Chipotle) are healthier than traditional fast food (eg, McDonald's). However, research has not examined whether fast-food entrées and fast-casual entrées differ in calorie content. The purpose of this study was to determine whether the caloric content of entrées at fast-food restaurants differed from that found at fast-casual restaurants. This study was a cross-sectional analysis of secondary data. Calorie information from 2014 for lunch and dinner entrées for fast-food and fast-casual restaurants was downloaded from the MenuStat database. Mean calories per entrée between fast-food restaurants and fast-casual restaurants and the proportion of restaurant entrées that fell into different calorie ranges were assessed. A t test was conducted to test the hypothesis that there was no difference between the average calories per entrée at fast-food and fast-casual restaurants. To examine the difference in distribution of entrées in different calorie ranges between fast-food and fast-casual restaurants, χ(2) tests were used. There were 34 fast-food and 28 fast-casual restaurants included in the analysis (n=3,193 entrées). Fast-casual entrées had significantly more calories per entrée (760±301 kcal) than fast-food entrées (561±268; Prestaurants to determine whether the energy content or nutrient density of full meals (ie, entrées with sides and drinks) differs between fast-casual restaurants and fast-food restaurants. Calorie-conscious consumers should consider the calorie content of entrée items before purchase, regardless of restaurant type. Copyright © 2016 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Generalized fast feedback system in the SLC

International Nuclear Information System (INIS)

Hendrickson, L.; Allison, S.; Gromme, T.; Himel, T.; Krauter, K.; Rouse, F.; Sass, R.; Shoaee, H.

1991-11-01

A generalized fast feedback system has been developed to stabilize beams at various locations in the SLC. The system is designed to perform measurements and change actuator settings to control beam states such as position, angle and energy on a pulse to pulse basis. The software design is based on the state space formalism of digital control theory. The system is database-driven, facilitating the addition of new loops without requiring additional software. A communications system, KISNet, provides fast communications links between microprocessors for feedback loops which involve multiple micros. Feedback loops have been installed in seventeen locations throughout the SLC and have proven to be invaluable in stabilizing the machine

The Effect of Fast Food Globalisation on Students' Food Choice

OpenAIRE

Ijeoma Chinyere Ukonu

2016-01-01

This research seeks to investigate how the globalisation of fast food has affected students' food choice. A mixed method approach was used in this research; basically involving quantitative and qualitative methods. The quantitative method uses a self-completion questionnaire to randomly sample one hundred and four students; while the qualitative method uses a semi structured interview technique to survey four students on their knowledge and choice to consume fast food. A cross tabulation of v...

Fast, Accurate Memory Architecture Simulation Technique Using Memory Access Characteristics

OpenAIRE

小野, 貴継; 井上, 弘士; 村上, 和彰

2007-01-01

This paper proposes a fast and accurate memory architecture simulation technique. To design memory architecture, the first steps commonly involve using trace-driven simulation. However, expanding the design space makes the evaluation time increase. A fast simulation is achieved by a trace size reduction, but it reduces the simulation accuracy. Our approach can reduce the simulation time while maintaining the accuracy of the simulation results. In order to evaluate validity of proposed techniq...

Fast breeder reactor research

International Nuclear Information System (INIS)

1975-01-01

reactors of the future, the body of research aimed at developing liquid metal cooled fast reactors, national plans for work in 1976 on developing fast reactors - these were some of the topics discussed in connection with the national programmes. The development of power reactors involves a wide range of problems in the fields of nuclear and reactor physics, the thermophysics, chemistry, physics and technology of the cooling system, structural materials and nuclear fuel, the fabrication of reliable fuel elements and operating equipment, reactor monitoring and control, spent fuel reprocessing, the economics of constructing fast power reactors, nuclear safety, etc. The IWGFR, as at previous meetings, therefore paid great attention to the matter of holding international specialists' meetings. The working group recommended that the IAEA should organize the following IWGFR meetings in 1976: (1) In-Service Inspection and Monitoring (Bensberg, FRG, March 1976). (2) Cavitation in Sodium and Studies of Analogy with Water as Compared to Sodium (Cadarache, France, April 1976). (3) High Temperature Structural Design Technology (United States, May 1976) (4) Aerosol Formation, Vapour Deposits and Sodium Vapour Trapping (France, September-December 1976). The Group welcomed the IAEA's proposal to hold specialists' meetings on 'Fast Reactor Instrumentation' and 'Fuel Reprocessing and Recycling Techniques' within the framework of the Agency's programme of working groups in 1976. After discussing questions of co-ordinating and organizing international conferences on fast reactors, the IWGFR agreed to send representatives to the joint meeting of the American Nuclear Society and the American Institute of Metallurgical Engineers on 'Liquid Metal Technology', to be held at Champion, Pennsylvania, U.S.A. from 3-6 May 1976, and recommended that the IAEA should organize an international symposium on the 'Design, Construction and Operating Experience of Demonstration Fast Power Reactors' at Bologna

Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen as mechanisms involved in protection against experimental cerebral malaria.

Science.gov (United States)

Bastos, Marcele F; Kayano, Ana Carolina A V; Silva-Filho, João Luiz; Dos-Santos, João Conrado K; Judice, Carla; Blanco, Yara C; Shryock, Nathaniel; Sercundes, Michelle K; Ortolan, Luana S; Francelin, Carolina; Leite, Juliana A; Oliveira, Rafaella; Elias, Rosa M; Câmara, Niels O S; Lopes, Stefanie C P; Albrecht, Letusa; Farias, Alessandro S; Vicente, Cristina P; Werneck, Claudio C; Giorgio, Selma; Verinaud, Liana; Epiphanio, Sabrina; Marinho, Claudio R F; Lalwani, Pritesh; Amino, Rogerio; Aliberti, Julio; Costa, Fabio T M

2018-03-20

Cerebral malaria (CM) is a multifactorial syndrome involving an exacerbated proinflammatory status, endothelial cell activation, coagulopathy, hypoxia, and accumulation of leukocytes and parasites in the brain microvasculature. Despite significant improvements in malaria control, 15% of mortality is still observed in CM cases, and 25% of survivors develop neurologic sequelae for life-even after appropriate antimalarial therapy. A treatment that ameliorates CM clinical signs, resulting in complete healing, is urgently needed. Previously, we showed a hyperbaric oxygen (HBO)-protective effect against experimental CM. Here, we provide molecular evidence that HBO targets brain endothelial cells by decreasing their activation and inhibits parasite and leukocyte accumulation, thus improving cerebral microcirculatory blood flow. HBO treatment increased the expression of aryl hydrocarbon receptor over hypoxia-inducible factor 1-α (HIF-1α), an oxygen-sensitive cytosolic receptor, along with decreased indoleamine 2,3-dioxygenase 1 expression and kynurenine levels. Moreover, ablation of HIF-1α expression in endothelial cells in mice conferred protection against CM and improved survival. We propose that HBO should be pursued as an adjunctive therapy in CM patients to prolong survival and diminish deleterious proinflammatory reaction. Furthermore, our data support the use of HBO in therapeutic strategies to improve outcomes of non-CM disorders affecting the brain.-Bastos, M. F., Kayano, A. C. A. V., Silva-Filho, J. L., Dos-Santos, J. C. K., Judice, C., Blanco, Y. C., Shryock, N., Sercundes, M. K., Ortolan, L. S., Francelin, C., Leite, J. A., Oliveira, R., Elias, R. M., Câmara, N. O. S., Lopes, S. C. P., Albrecht, L., Farias, A. S., Vicente, C. P., Werneck, C. C., Giorgio, S., Verinaud, L., Epiphanio, S., Marinho, C. R. F., Lalwani, P., Amino, R., Aliberti, J., Costa, F. T. M. Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen

Effective connectivity reveals important roles for both the hyperdirect (fronto-subthalamic) and indirect (fronto-striatal-pallidal) fronto-basal ganglia pathways during response inhibition

NARCIS (Netherlands)

Jahfari, S.; Waldorp, L.; van den Wildenberg, W.P.M.; Scholte, H.S.; Ridderinkhof, K.R.; Forstmann, B.U.

2011-01-01

Fronto-basal ganglia pathways play a crucial role in voluntary action control, including the ability to inhibit motor responses. Response inhibition might be mediated via a fast hyperdirect pathway connecting the right inferior frontal gyrus (rIFG) and the presupplementary motor area (preSMA) with

Effects of a myosin-II inhibitor (N-benzyl-p-toluene sulphonamide, BTS) on contractile characteristics of intact fast-twitch mammalian muscle fibres.

Science.gov (United States)

Pinniger, G J; Bruton, J D; Westerblad, H; Ranatunga, K W

2005-01-01

We have examined the effects of N-benzyl-p-toluene sulphonamide (BTS), a potent and specific inhibitor of fast muscle myosin-II, using small bundles of intact fibres or single fibres from rat foot muscle. BTS decreased tetanic tension reversibly in a concentration-dependent manner with half-maximal inhibition at approximately approximately 2 microM at 20 degrees C. The inhibition of tension with 10 microM BTS was marked at the three temperatures examined (10, 20 and 30 degrees C), but greatest at 10 degrees C. BTS decreased active muscle stiffness to a lesser extent than tetanic tension indicating that not all of the tension inhibition was due to a reduced number of attached cross-bridges. BTS-induced inhibition of active tension was not accompanied by any change in the free myoplasmic Ca2+ transients. The potency and specificity of BTS make it a very suitable myosin inhibitor for intact mammalian fast muscle and should be a useful tool for the examination of outstanding questions in muscle contraction.

Prolonged fasting impairs neural reactivity to visual stimulation.

Science.gov (United States)

Kohn, N; Wassenberg, A; Toygar, T; Kellermann, T; Weidenfeld, C; Berthold-Losleben, M; Chechko, N; Orfanos, S; Vocke, S; Laoutidis, Z G; Schneider, F; Karges, W; Habel, U

2016-01-01

Previous literature has shown that hypoglycemia influences the intensity of the BOLD signal. A similar but smaller effect may also be elicited by low normal blood glucose levels in healthy individuals. This may not only confound the BOLD signal measured in fMRI, but also more generally interact with cognitive processing, and thus indirectly influence fMRI results. Here we show in a placebo-controlled, crossover, double-blind study on 40 healthy subjects, that overnight fasting and low normal levels of glucose contrasted to an activated, elevated glucose condition have an impact on brain activation during basal visual stimulation. Additionally, functional connectivity of the visual cortex shows a strengthened association with higher-order attention-related brain areas in an elevated blood glucose condition compared to the fasting condition. In a fasting state visual brain areas show stronger coupling to the inferior temporal gyrus. Results demonstrate that prolonged overnight fasting leads to a diminished BOLD signal in higher-order occipital processing areas when compared to an elevated blood glucose condition. Additionally, functional connectivity patterns underscore the modulatory influence of fasting on visual brain networks. Patterns of brain activation and functional connectivity associated with a broad range of attentional processes are affected by maturation and aging and associated with psychiatric disease and intoxication. Thus, we conclude that prolonged fasting may decrease fMRI design sensitivity in any task involving attentional processes when fasting status or blood glucose is not controlled.

The integral fast reactor - an overview

International Nuclear Information System (INIS)

Till, C.E.; Chang, Y.I.; Hannum, W.H.

1997-01-01

The Integral Fast Reactor (IFR) is a system that consists of a fast-spectrum nuclear reactor that uses metallic fuel and liquid-metal (sodium) cooling, coupled with technology for high-temperature electrochemical recycling, and with processes for preparing wastes for disposition. The concept is based on decades of experience with fast reactors, adapted to priorities that have evolved markedly from those of the early days of nuclear power. It has four essential, distinguishing features: efficient use of natural resources, inherent safety characteristics, reduced burdens of nuclear waste, and unique proliferation resistance. These fundamental characteristics offer benefits in economics and environmental protection. The fuel cycle never involves separated plutonium, immediately simplifying the safeguarding task. Initiated in 1984 in response to proliferation concerns identified in the International Nuclear Fuel Cycle Evaluation (INFCE, 1980), the project has made substantial technical progress, with new potential applications coming to light as nuclear weapons stockpiles are reduced and concerns about waste disposal increase. A breakthrough technology, the IFR has the characteristics necessary for the next nuclear age. (author)

Autophagy contributes to gefitinib-induced glioma cell growth inhibition

Energy Technology Data Exchange (ETDEWEB)

Chang, Cheng-Yi [Department of Surgery, Fong-Yuan Hospital, Taichung 420, Taiwan (China); Graduate Institute of Pharmaceutical Science and Technology, Central Taiwan University of Science and Technology, Taichung 406, Taiwan (China); Kuan, Yu-Hsiang [Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China); Department of Pharmacy, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China); Ou, Yen-Chuan; Li, Jian-Ri [Division of Urology, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Wu, Chih-Cheng [Department of Anesthesiology, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Department of Financial and Computational Mathematics, Providence University, Taichung 433, Taiwan (China); Pan, Pin-Ho [Department of Pediatrics, Tungs’ Taichung MetroHarbor Hospital, Taichung 435, Taiwan (China); Chen, Wen-Ying [Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Huang, Hsuan-Yi [Department of Surgery, Fong-Yuan Hospital, Taichung 420, Taiwan (China); Chen, Chun-Jung, E-mail: cjchen@vghtc.gov.tw [Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402, Taiwan (China); Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Center for General Education, Tunghai University, Taichung 407, Taiwan (China); Department of Nursing, HungKuang University, Taichung 433, Taiwan (China)

2014-09-10

Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib, have been evaluated in patients with malignant gliomas. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma are incompletely understood. In the present study, the cytostatic potential of gefitinib was demonstrated by the inhibition of glioma cell growth, long-term clonogenic survival, and xenograft tumor growth. The cytostatic consequences were accompanied by autophagy, as evidenced by monodansylcadaverine staining of acidic vesicle formation, conversion of microtubule-associated protein-1 light chain 3-II (LC3-II), degradation of p62, punctate pattern of GFP-LC3, and conversion of GFP-LC3 to cleaved-GFP. Autophagy inhibitor 3-methyladenosine and chloroquine and genetic silencing of LC3 or Beclin 1 attenuated gefitinib-induced growth inhibition. Gefitinib-induced autophagy was not accompanied by the disruption of the Akt/mammalian target of rapamycin signaling. Instead, the activation of liver kinase-B1/AMP-activated protein kinase (AMPK) signaling correlated well with the induction of autophagy and growth inhibition caused by gefitinib. Silencing of AMPK suppressed gefitinib-induced autophagy and growth inhibition. The crucial role of AMPK activation in inducing glioma autophagy and growth inhibition was further supported by the actions of AMP mimetic AICAR. Gefitinib was shown to be capable of reducing the proliferation of glioma cells, presumably by autophagic mechanisms involving AMPK activation. - Highlights: • Gefitinib causes cytotoxic and cytostatic effect on glioma. • Gefitinib induces autophagy. • Gefitinib causes cytostatic effect through autophagy. • Gefitinib induces autophagy involving AMPK.

Autophagy contributes to gefitinib-induced glioma cell growth inhibition

International Nuclear Information System (INIS)

Chang, Cheng-Yi; Kuan, Yu-Hsiang; Ou, Yen-Chuan; Li, Jian-Ri; Wu, Chih-Cheng; Pan, Pin-Ho; Chen, Wen-Ying; Huang, Hsuan-Yi; Chen, Chun-Jung

2014-01-01

Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib, have been evaluated in patients with malignant gliomas. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma are incompletely understood. In the present study, the cytostatic potential of gefitinib was demonstrated by the inhibition of glioma cell growth, long-term clonogenic survival, and xenograft tumor growth. The cytostatic consequences were accompanied by autophagy, as evidenced by monodansylcadaverine staining of acidic vesicle formation, conversion of microtubule-associated protein-1 light chain 3-II (LC3-II), degradation of p62, punctate pattern of GFP-LC3, and conversion of GFP-LC3 to cleaved-GFP. Autophagy inhibitor 3-methyladenosine and chloroquine and genetic silencing of LC3 or Beclin 1 attenuated gefitinib-induced growth inhibition. Gefitinib-induced autophagy was not accompanied by the disruption of the Akt/mammalian target of rapamycin signaling. Instead, the activation of liver kinase-B1/AMP-activated protein kinase (AMPK) signaling correlated well with the induction of autophagy and growth inhibition caused by gefitinib. Silencing of AMPK suppressed gefitinib-induced autophagy and growth inhibition. The crucial role of AMPK activation in inducing glioma autophagy and growth inhibition was further supported by the actions of AMP mimetic AICAR. Gefitinib was shown to be capable of reducing the proliferation of glioma cells, presumably by autophagic mechanisms involving AMPK activation. - Highlights: • Gefitinib causes cytotoxic and cytostatic effect on glioma. • Gefitinib induces autophagy. • Gefitinib causes cytostatic effect through autophagy. • Gefitinib induces autophagy involving AMPK

Terbinafine inhibits gap junctional intercellular communication

International Nuclear Information System (INIS)

Lee, Ju Yeun; Yoon, Sei Mee; Choi, Eun Ju; Lee, Jinu

2016-01-01

Terbinafine is an antifungal agent that selectively inhibits fungal sterol synthesis by blocking squalene epoxidase. We evaluated the effect of terbinafine on gap junctional intercellular communication (GJIC). Fluorescence recovery after photobleaching (FRAP) and I-YFP GJIC assays revealed that terbinafine inhibits GJIC in a reversible and dose-dependent manner in FRT-Cx43 and LN215 cells. Treatment with terbinafine did not affect Cx43 phosphorylation status or intracellular Ca 2+ concentration, well-known action mechanisms of various GJIC blockers. While a structurally related chemical, naftifine, attenuated GJIC, epigallocatechin gallate, another potent squalene epoxidase inhibitor with a different structure, did not. These results suggest that terbinafine inhibits GJIC with a so far unknown mechanism of action. - Highlights: • In vitro pharmacological studies were performed on FRT-Cx43 and LN215 cells. • Terbinafine inhibits gap junctional intercellular communication in both cell lines. • The inhibitory effect of terbinafine is reversible and dose-dependent. • Treatment of terbinafine does not alter Cx43 phosphorylation or cytosolic Ca 2+ concentration. • Inhibition of squalene epoxidase is not involved in this new effect of terbinafine.

2-(1H-Benzimidazol-2-yl-4,5,6,7-tetrahydro-2H-indazol-3-ol, a Benzimidazole Derivative, Inhibits T Cell Proliferation Involving H+/K+-ATPase Inhibition

Directory of Open Access Journals (Sweden)

Jin Liu

2014-10-01

Full Text Available In this study, a benzimidazole derivative named BMT-1 is revealed as a potential immunomodulatory agent. BMT-1 inhibits the activity of H+/K+-ATPases from anti-CD3/CD28 activated T cells. Furthermore, inhibition the H+/K+-ATPases by use of BMT-1 should lead to intracellular acidification, inhibiting T cell proliferation. To explore this possibility, the effect of BMT-1 on intracellular pH changes was examined by using BCECF as a pH-dependent fluorescent dye. Interestingly, increases in the pHi were observed in activated T cells, and T cells treated with BMT-1 showed a more acidic intracellular pH. Finally, BMT-1 targeted the H+/K+-ATPases and inhibited the proliferative response of anti-CD3/CD28-stimulated T cells. A cell cycle analysis indicated that BMT-1 arrested the cell cycle progression of activated T cells from the G1 to the S phase without affecting CD25 expression or interleukin-2 (IL-2 production; treating IL-2-dependent PBMCs with BMT-1 also led to the inhibition of cell proliferation. Taken together, these findings demonstrate that BMT-1 inhibits the proliferation of T cells by interfering with H+/K+-ATPases and down-regulating intracellular pHi. This molecule may be an interesting lead compound for the development of new immunomodulatory agents.

The Field Assessment Stroke Triage for Emergency Destination (FAST-ED): a Simple and Accurate Pre-Hospital Scale to Detect Large Vessel Occlusion Strokes

Science.gov (United States)

Lima, Fabricio O.; Silva, Gisele S.; Furie, Karen L.; Frankel, Michael R.; Lev, Michael H.; Camargo, Érica CS; Haussen, Diogo C.; Singhal, Aneesh B.; Koroshetz, Walter J.; Smith, Wade S.; Nogueira, Raul G.

2016-01-01

Background and Purpose Patients with large vessel occlusion strokes (LVOS) may be better served by direct transfer to endovascular capable centers avoiding hazardous delays between primary and comprehensive stroke centers. However, accurate stroke field triage remains challenging. We aimed to develop a simple field scale to identify LVOS. Methods The FAST-ED scale was based on items of the NIHSS with higher predictive value for LVOS and tested in the STOPStroke cohort, in which patients underwent CT angiography within the first 24 hours of stroke onset. LVOS were defined by total occlusions involving the intracranial-ICA, MCA-M1, MCA-2, or basilar arteries. Patients with partial, bi-hemispheric, and/or anterior + posterior circulation occlusions were excluded. Receiver operating characteristic (ROC) curve, sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of FAST-ED were compared with the NIHSS, Rapid Arterial oCclusion Evaluation (RACE) scale and Cincinnati Prehospital Stroke Severity Scale (CPSSS). Results LVO was detected in 240 of the 727 qualifying patients (33%). FAST-ED had comparable accuracy to predict LVO to the NIHSS and higher accuracy than RACE and CPSS (area under the ROC curve: FAST-ED=0.81 as reference; NIHSS=0.80, p=0.28; RACE=0.77, p=0.02; and CPSS=0.75, p=0.002). A FAST-ED ≥4 had sensitivity of 0.60, specificity 0.89, PPV 0.72, and NPV 0.82 versus RACE ≥5 of 0.55, 0.87, 0.68, 0.79 and CPSS ≥2 of 0.56, 0.85, 0.65, 0.78, respectively. Conclusions FAST-ED is a simple scale that if successfully validated in the field may be used by medical emergency professionals to identify LVOS in the pre-hospital setting enabling rapid triage of patients. PMID:27364531

Increasing Cognitive Inhibition with a Difficult Prior Task: Implications for Mathematical Thinking

Science.gov (United States)

Attridge, Nina; Inglis, Matthew

2015-01-01

Dual-process theories posit two distinct types of cognitive processing: Type 1, which does not use working memory making it fast and automatic, and Type 2, which does use working memory making it slow and effortful. Mathematics often relies on the inhibition of pervasive Type 1 processing to apply new skills or knowledge that require Type 2…

A Randomized Field Trial of the Fast ForWord Language Computer-Based Training Program

Science.gov (United States)

Borman, Geoffrey D.; Benson, James G.; Overman, Laura

2009-01-01

This article describes an independent assessment of the Fast ForWord Language computer-based training program developed by Scientific Learning Corporation. Previous laboratory research involving children with language-based learning impairments showed strong effects on their abilities to recognize brief and fast sequences of nonspeech and speech…

Fast Convolution Module (Fast Convolution Module)

National Research Council Canada - National Science Library

Bierens, L

1997-01-01

This report describes the design and realisation of a real-time range azimuth compression module, the so-called 'Fast Convolution Module', based on the fast convolution algorithm developed at TNO-FEL...

Ultra-fast repair of single-strand breaks in DNA of. gamma. -irradiated Chinese hamster cells

Energy Technology Data Exchange (ETDEWEB)

Leontjeva, G A; Mantzighin, Yu A; Gaziev, A I [AN SSSR, Pushchino-na-Oke. Inst. Biologicheskoj Fiziki

1976-12-01

Studies of the effect of thermal treatment of Chinese hamster cells on sedimentation of DNA in the alkaline sucrose gradient showed that heating the cells to 68/sup 0/C for 15 min caused the same degradation as ..gamma..-irradiation with 5 to 7 krad at 37/sup 0/C. The inhibition of cellular repair enzymes by heating was therefore unacceptable. The process of ultra-fast repair is essentially determined by the DNA-ligase reaction, which is activated in the presence of Mg ions, and inhibited in mammalian cells in the presence of EDTA and pyrophosphate. Sedimentation profiles were therefore measured for the DNA of Chinese hamster cells ..gamma..-irradiated (5 krad) at 0/sup 0/C or 22/sup 0/C in the presence of Mg/sup + +/, or EDTA and pyrophosphate, and the results demonstrated ultra-fast repair only at 20 to 37/sup 0/C, in contrast to bacteria. A study was made of the temperature dependence of the activity of the DNA ligases isolated from E.coli and rabbit bone marrow. The NAD-dependent bacterial DNA ligase was active at temperatures from 0 to 40/sup 0/C, whereas ATP-dependent DNA ligase of mammals only showed activity in the range 15 to 40/sup 0/C. The differing temperature dependences of ultra-fast repair in bacterial and mammalian cells are in agreement with the temperature dependences of the activities of isolated enzymes, and the results suggest that the process of ultra-fast repair of single-strand breaks of DNA takes place in both bacterial and mammalian cells.

Feedforward inhibition and synaptic scaling--two sides of the same coin?

Science.gov (United States)

Keck, Christian; Savin, Cristina; Lücke, Jörg

2012-01-01

Feedforward inhibition and synaptic scaling are important adaptive processes that control the total input a neuron can receive from its afferents. While often studied in isolation, the two have been reported to co-occur in various brain regions. The functional implications of their interactions remain unclear, however. Based on a probabilistic modeling approach, we show here that fast feedforward inhibition and synaptic scaling interact synergistically during unsupervised learning. In technical terms, we model the input to a neural circuit using a normalized mixture model with Poisson noise. We demonstrate analytically and numerically that, in the presence of lateral inhibition introducing competition between different neurons, Hebbian plasticity and synaptic scaling approximate the optimal maximum likelihood solutions for this model. Our results suggest that, beyond its conventional use as a mechanism to remove undesired pattern variations, input normalization can make typical neural interaction and learning rules optimal on the stimulus subspace defined through feedforward inhibition. Furthermore, learning within this subspace is more efficient in practice, as it helps avoid locally optimal solutions. Our results suggest a close connection between feedforward inhibition and synaptic scaling which may have important functional implications for general cortical processing.

Feedforward inhibition and synaptic scaling--two sides of the same coin?

Directory of Open Access Journals (Sweden)

Christian Keck

Full Text Available Feedforward inhibition and synaptic scaling are important adaptive processes that control the total input a neuron can receive from its afferents. While often studied in isolation, the two have been reported to co-occur in various brain regions. The functional implications of their interactions remain unclear, however. Based on a probabilistic modeling approach, we show here that fast feedforward inhibition and synaptic scaling interact synergistically during unsupervised learning. In technical terms, we model the input to a neural circuit using a normalized mixture model with Poisson noise. We demonstrate analytically and numerically that, in the presence of lateral inhibition introducing competition between different neurons, Hebbian plasticity and synaptic scaling approximate the optimal maximum likelihood solutions for this model. Our results suggest that, beyond its conventional use as a mechanism to remove undesired pattern variations, input normalization can make typical neural interaction and learning rules optimal on the stimulus subspace defined through feedforward inhibition. Furthermore, learning within this subspace is more efficient in practice, as it helps avoid locally optimal solutions. Our results suggest a close connection between feedforward inhibition and synaptic scaling which may have important functional implications for general cortical processing.

Generalized fast feedback system in the SLC

International Nuclear Information System (INIS)

Hendrickson, L.; Allison, S.; Gromme, T.; Himel, T.; Krauter, K.; Rouse, F.; Sass, R.; Shoaee, H.

1992-01-01

A generalized fast feedback system has been developed to stabilize beams at various locations in the SLC. The system is designed to perform measurements and change actuator settings to control beam states such as position, angle and energy on a pulse to pulse basis. The software design is based on the state space formalism of digital control theory. The system is database-driven, facilitating the addition of new loops without requiring additional software. A communications system, KISNet, provides fast communications links between microprocessors for feedback loops which involve multiple micros. Feedback loops have been installed in seventeen locations throughout the SLC and have proven to be invaluable in stabilizing the machine. (author)

Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1.

Science.gov (United States)

Scarlatti, Francesca; Bauvy, Chantal; Ventruti, Annamaria; Sala, Giusy; Cluzeaud, Françoise; Vandewalle, Alain; Ghidoni, Riccardo; Codogno, Patrice

2004-04-30

The sphingolipid ceramide is involved in the cellular stress response. Here we demonstrate that ceramide controls macroautophagy, a major lysosomal catabolic pathway. Exogenous C(2)-ceramide stimulates macroautophagy (proteolysis and accumulation of autophagic vacuoles) in the human colon cancer HT-29 cells by increasing the endogenous pool of long chain ceramides as demonstrated by the use of the ceramide synthase inhibitor fumonisin B(1). Ceramide reverted the interleukin 13-dependent inhibition of macroautophagy by interfering with the activation of protein kinase B. In addition, C(2)-ceramide stimulated the expression of the autophagy gene product beclin 1. Ceramide is also the mediator of the tamoxifen-dependent accumulation of autophagic vacuoles in the human breast cancer MCF-7 cells. Monodansylcadaverine staining and electron microscopy showed that this accumulation was abrogated by myriocin, an inhibitor of de novo synthesis ceramide. The tamoxifen-dependent accumulation of vacuoles was mimicked by 1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor of glucosylceramide synthase. 1-Phenyl-2-decanoylamino-3-morpholino-1-propanol, tamoxifen, and C(2)-ceramide stimulated the expression of beclin 1, whereas myriocin antagonized the tamoxifen-dependent up-regulation. Tamoxifen and C(2)-ceramide interfere with the activation of protein kinase B, whereas myriocin relieved the inhibitory effect of tamoxifen. In conclusion, the control of macroautophagy by ceramide provides a novel function for this lipid mediator in a cell process with major biological outcomes.

Modulation of α-synuclein fibrillization by ring-fused 2-pyridones: templation and inhibition involve oligomers with different structure.

Science.gov (United States)

Horvath, Istvan; Sellstedt, Magnus; Weise, Christoph; Nordvall, Lina-Maria; Krishna Prasad, G; Olofsson, Anders; Larsson, Göran; Almqvist, Fredrik; Wittung-Stafshede, Pernilla

2013-04-15

In a recent study we discovered that a ring-fused 2-pyridone compound triggered fibrillization of a key protein in Parkinson's disease, α-synuclein. To reveal how variations in compound structure affect protein aggregation, we now prepared a number of strategic analogs and tested their effects on α-synuclein amyloid fiber formation in vitro. We find that, in contrast to the earlier templating effect, some analogs inhibit α-synuclein fibrillization. For both templating and inhibiting compounds, the key species formed in the reactions are α-synuclein oligomers that contain compound. Despite similar macroscopic appearance, the templating and inhibiting oligomers are distinctly different in secondary structure content. When the inhibitory oligomers are added in seed amounts, they inhibit fresh α-synuclein aggregation reactions. Our study demonstrates that small chemical changes to the same central fragment can result in opposite effects on protein aggregation. Copyright © 2013 Elsevier Inc. All rights reserved.

D-Glucosamine inhibits proliferation of human cancer cells through inhibition of p70S6K

International Nuclear Information System (INIS)

Oh, Hyun-Ji; Lee, Jason S.; Song, Dae-Kyu; Shin, Dong-Hoon; Jang, Byeong-Churl; Suh, Seong-Il; Park, Jong-Wook; Suh, Min-Ho; Baek, Won-Ki

2007-01-01

Although D-glucosamine has been reported as an inhibitor of tumor growth both in vivo and in vitro, the mechanism for the anticancer effect of D-glucosamine is still unclear. Since there are several reports suggesting D-glucosamine inhibits protein synthesis, we examined whether D-glucosamine affects p70S6 K activity, an important signaling molecule involved in protein translation. In the present study, we found D-glucosamine inhibited the activity of p70S6K and the proliferation of DU145 prostate cancer cells and MDA-MB-231 breast cancer cells. D-Glucosamine decreased phosphorylation of p70S6K, and its downstream substrates RPS6, and eIF-4B, but not mTOR and 4EBP1 in DU145 cells, suggesting that D-glucosamine induced inhibition of p70S6K is not through the inhibition of mTOR. In addition, D-glucosamine enhanced the growth inhibitory effects of rapamycin, a specific inhibitor of mTOR. These findings suggest that D-glucosamine can inhibit growth of cancer cells through dephosphorylation of p70S6K

Experimental study of fast electron transport in the framework of fast ignition for inertial fusion

International Nuclear Information System (INIS)

Vauzour, B.

2012-01-01

The framework of this PhD thesis is the validation of the fast ignition scheme for the nuclear fusion by inertial confinement. It consists in the experimental study of the various processes involved in fast electron beams propagation, produced by intense laser pulses (10 19 W.cm -2 ), through dense matter either solid or compressed. In this work we present the results of three experiments carried out on different laser facilities in order to generate fast electron beams in various conditions and study their propagation in different states of matter, from the cold solid to the warm and dense plasma.The first experiment was performed with a high intensity contrast on the UHI100 laser facility (CEA Saclay). The study of fast electron energy deposition inside thin aluminium targets highlights a strong target heating at shallow depths, where the collective effects are predominant, thus producing a steep temperature profile between front (300 eV) and rear (20 eV) sides over 20μm thickness. A numerical simulation of the experiment shows that this temperature gradient induces the formation of a shock wave, breaking through the rear side of the target and thus leading to increase the thermal emission. The experimental chronometry of the shock breakthrough allowed validating the model of the collective transport of electrons.Two other experiments were dedicated to the study of fast electron beam propagation inside compressed targets. In the first experiment on the LULI2000 laser facility, the plane compression geometry allowed to precisely dissociate the energy losses due to resistive effects from those due to the collisional ones. By comparing our experimental results with simulations, we observed a significative increase of the fast electron beam energy losses with the compression and the target heating to temperatures close to the Fermi temperature. The second experiment, performed in a cylindrical geometry, demonstrated a fast electron beam guiding phenomenon due to

Changes of serum alkaline phosphatase isoenzymes in fasted rats.

Science.gov (United States)

Wada, H; Niwa, N; Hayakawa, T; Tsuge, H

1996-10-01

Changes of serum alkaline phosphatase (sALP) isoenzymes under fasting conditions were examined using polyacrylamide gel electrophoresis (PAGE), amino-acids (L-phenylalanine (L-Phe), L-homoarginine (L-HArg)) inhibition and wheat germ agglutinin (WGA) treatment. The sALP of non-fasted rats was separated into three bands (S1, S2, S3) by PAGE. The molecular weight (M.W.) of S1 corresponded to that of an isoenzyme found in the ileum. By the addition of L-Phe, the staining intensity of S1 was weakened, S2 and S3 remained unchanged and the total activity of the isoenzymes extracted from intestine decreased. On the other hand, the activity of isoenzymes extracted from kidney and bone decreased by the addition of L-HArg. Therefore, S1 was judged to be derived from intestine. The activities of total sALP and S1 decreased from 16 h of fasting. Total sALP activity and sALP activity of the supernatant prepared by WGA treatment decreased, whereas the ALP activity of the precipitate (difference between total sALP activity and supernatant sALP activity) did not change. The activity band of the precipitate corresponded to that of S3 by PAGE. Therefore, S3 was judged to be derived from bone. In conclusion, under fasting conditions, the activity of S1 decreased while the activities of S2 and S3 remained unchanged.

Augmented Plasma Adiponectin after Prolonged Fasting During Ramadan in Men

Directory of Open Access Journals (Sweden)

Sadegh Feizollahzadeh

2014-07-01

Full Text Available Background: Intermittent fasting during Ramadan entails major changes in metabolism and energy expenditure. This study sought to determine effect of the Ramadan fasting on serum levels of adiponectin and tumor necrosis factor-α (TNF-α as two inter-related peptides involved in cells sensitivity to insulin and glucose metabolism. Methods: Total of seventy healthy men, with age range equal or greater than 30, with at least three type2 diabetes mellitus (DM risk factors were selected. Serum lipid profile, anthropometric indices and plasma glucose levels were determined using conventional methods. Also, serum adiponectin and TNF- α concentrations were assessed using Enzyme-linked Immunosorbent Assay. Data were analyzed by paired t-test. Results: Ramadan fasting resulted in a significant increase of serum adiponectin (P< 0.000, fasting glucose (P< 0.000 and triglycride (P< 0.001. Body mass index was lowered during the fasting (P< 0.000. Finally, no remarkable decrease was found in serum TNF-α levels (P= 0.100. Conclusion: Ramadan fasting resulted in augmented adiponectin levels which may help in improving metabolic stress induced by insulin resistance in men with predisposing factors of type2 DM.

Universal water-dilutable inhibited protective lubricants

International Nuclear Information System (INIS)

Mamtseva, M.V.; Kardash, N.V.; Latynina, M.B.

1993-01-01

In the interest of environmental protection, improvement of working conditions, and reduced fire hazard in production operations, water-based protective lubricants are now available in a wide assortment, and the production volume has increased greatly. The term water-dilutable inhibited protective lubricants (WDIPL) means water-soluble, water-emulsifiable, or water-dispersible products with the dual function of reducing friction and wear and protecting metal surfaces against corrosion for specified periods of time. According to the standard Unified System of Protection Against Corrosion and Aging (COST 9.103-78), WDIPLs are classed as products for the temporary corrosion protection of metals and end-items. In the general class of WDIPLs one can identify water-dilutable combination corrosion inhibitors, film-forming inhibited petroleum compositions (FIPC-d), detergent-preservative fluids, operational-preservative lubricating-cooling process compounds (ICPC), and, finally, universal multifunctional products. Combined corrosion inhibitors may consist of water-soluble organic and inorganic compounds; water/oil and oil-soluble surfactants - corrosion inhibitors of the chemisorption type or donor and/or acceptor types; shielding inhibitors of the adsorption type; and fast-acting water-displacing components. 23 refs

The effect of resveratrol on beta amyloid-induced memory impairment involves inhibition of phosphodiesterase-4 related signaling.

Science.gov (United States)

Wang, Gang; Chen, Ling; Pan, Xiaoyu; Chen, Jiechun; Wang, Liqun; Wang, Weijie; Cheng, Ruochuan; Wu, Fan; Feng, Xiaoqing; Yu, Yingcong; Zhang, Han-Ting; O'Donnell, James M; Xu, Ying

2016-04-05

Resveratrol, a natural polyphenol found in red wine, has wide spectrum of pharmacological properties including antioxidative and antiaging activities. Beta amyloid peptides (Aβ) are known to involve cognitive impairment, neuroinflammatory and apoptotic processes in Alzheimer's disease (AD). Activation of cAMP and/or cGMP activities can improve memory performance and decrease the neuroinflammation and apoptosis. However, it remains unknown whether the memory enhancing effect of resveratrol on AD associated cognitive disorders is related to the inhibition of phosphodiesterase 4 (PDE4) subtypes and subsequent increases in intracellular cAMP and/or cGMP activities. This study investigated the effect of resveratrol on Aβ1-42-induced cognitive impairment and the participation of PDE4 subtypes related cAMP or cGMP signaling. Mice microinfused with Aβ1-42 into bilateral CA1 subregions displayed learning and memory impairment, as evidenced by reduced memory acquisition and retrieval in the water maze and retention in the passive avoidance tasks; it was also significant that neuroinflammatory and pro-apoptotic factors were increased in Aβ1-42-treated mice. Aβ1-42-treated mice also increased in PDE4A, 4B and 4D expression, and decreased in PKA level. However, PKA inhibitor H89, but not PKG inhibitor KT5823, prevented resveratrol's effects on these parameters. Resveratrol also reversed Aβ1-42-induced decreases in phosphorylated cAMP response-element binding protein (pCREB), brain derived neurotrophic factor (BDNF) and anti-apoptotic factor BCl-2 expression, which were reversed by H89. These findings suggest that resveratrol reversing Aβ-induced learning and memory disorder may involve the regulation of neuronal inflammation and apoptosis via PDE4 subtypes related cAMP-CREB-BDNF signaling.

Indirect Effects of the Fast Track Intervention on Conduct Disorder Symptoms and Callous-Unemotional Traits: Distinct Pathways Involving Discipline and Warmth.

Science.gov (United States)

Pasalich, Dave S; Witkiewitz, Katie; McMahon, Robert J; Pinderhughes, Ellen E

2016-04-01

Little is known about intervening processes that explain how prevention programs improve particular youth antisocial outcomes. We examined whether parental harsh discipline and warmth in childhood differentially account for Fast Track intervention effects on conduct disorder (CD) symptoms and callous-unemotional (CU) traits in early adolescence. Participants included 891 high-risk kindergarteners (69% male; 51% African American) from urban and rural United States communities who were randomized into either the Fast Track intervention (n = 445) or non-intervention control (n = 446) groups. The 10-year intervention included parent management training and other services (e.g., social skills training, universal classroom curriculum) targeting various risk factors for the development of conduct problems. Harsh discipline (Grades 1 to 3) and warmth (Grades 1 and 2) were measured using parent responses to vignettes and direct observations of parent-child interaction, respectively. Parents reported on children's CD symptoms in Grade 6 and CU traits in Grade 7. Results demonstrated indirect effects of the Fast Track intervention on reducing risk for youth antisocial outcomes. That is, Fast Track was associated with lower scores on harsh discipline, which in turn predicted decreased levels of CD symptoms. In addition, Fast Track was associated with higher scores on warmth, which in turn predicted reduced levels of CU traits. Our findings inform developmental and intervention models of youth antisocial behavior by providing evidence for the differential role of harsh discipline and warmth in accounting for indirect effects of Fast Track on CD symptoms versus CU traits, respectively.

The benefits of a fast reactor closed fuel cycle in the UK

International Nuclear Information System (INIS)

Gregg, R.; Hesketh, K.

2013-01-01

The work has shown that starting a fast reactor closed fuel cycle in the UK, requires virtually all of Britain's existing and future PWR spent fuel to be reprocessed, in order to obtain the plutonium needed. The existing UK Pu stockpile is sufficient to initially support only a modest SFR 'closed' fleet assuming spent fuel can be reprocessed shortly after discharge (i.e. after two years cooling). For a substantial fast reactor fleet, most Pu will have to originate from reprocessing future spent PWR fuel. Therefore, the maximum fast reactor fleet size will be limited by the preceding PWR fleet size, so scenarios involving fast reactors still require significant quantities of uranium ore indirectly. However, once a fast reactor fuel cycle has been established, the very substantial quantities of uranium tails in the UK would ensure there is sufficient material for several centuries. Both the short and long term impacts on a repository have been considered in this work. Over the short term, the decay heat emanating from the HLW and spent fuel will limit the density of waste within a repository. For scenarios involving fast reactors, the only significant heat bearing actinide content will be present in the final cores, resulting in a 50% overall reduction in decay energy deposited within the repository when compared with an equivalent open fuel cycle. Over the longer term, radiological dose becomes more important. Total radiotoxicity (normalised by electricity generated) is lower for scenarios with Pu recycle after 2000 years. Scenarios involving fast reactors have the lowest radiotoxicity since the quantities of certain actinides (Np, Pu and Am) eventually stabilise. However, total radiotoxicity as a measure of radiological risk does not account for differences in radionuclide mobility once in repository. Radiological dose is dominated by a small number of fission products so is therefore not affected significantly by reactor type or recycling strategy (since the

Fast analysis of spectral data using neural networks

International Nuclear Information System (INIS)

Roach, C.M.

1992-01-01

Fast analysis techniques are highly desirable in experiments where measurements are recorded at high rates. In fusion experiments the processing required to obtain plasma parameters is usually orders of magnitude slower than the data acquisition. Spectroscopic diagnostics suffer greatly from this problem. The extraction of plasma parameters from a measured spectrum typically corresponds to a nonlinear mapping between distinct multi-dimensional spaces. Where no analytic expression for the mapping exists, conventional analysis methods (e.g. least squares) are usually iterative and therefore slow. With this concern in mind a fast spectral analysis method involving neural networks has been investigated. (author) 6 refs., 3 figs

Fluoxetine regulates cell growth inhibition of interferon-α.

Science.gov (United States)

Lin, Yu-Min; Yu, Bu-Chin; Chiu, Wen-Tai; Sun, Hung-Yu; Chien, Yu-Chieh; Su, Hui-Chen; Yen, Shu-Yang; Lai, Hsin-Wen; Bai, Chyi-Huey; Young, Kung-Chia; Tsao, Chiung-Wen

2016-10-01

Fluoxetine, a well-known anti-depression agent, may act as a chemosensitizer to assist and promote cancer therapy. However, how fluoxetine regulates cellular signaling to enhance cellular responses against tumor cell growth remains unclear. In the present study, addition of fluoxetine promoted growth inhibition of interferon-alpha (IFN-α) in human bladder carcinoma cells but not in normal uroepithelial cells through lessening the IFN-α-induced apoptosis but switching to cause G1 arrest, and maintaining the IFN-α-mediated reduction in G2/M phase. Activations and signal transducer and transactivator (STAT)-1 and peroxisome proliferator-activated receptor alpha (PPAR-α) were involved in this process. Chemical inhibitions of STAT-1 or PPAR-α partially rescued bladder carcinoma cells from IFN-α-mediated growth inhibition via blockades of G1 arrest, cyclin D1 reduction, p53 downregulation and p27 upregulation in the presence of fluoxetine. However, the functions of both proteins were not involved in the control of fluoxetine over apoptosis and maintained the declined G2/M phase of IFN-α. These results indicated that activation of PPAR-α and STAT-1 participated, at least in part, in growth inhibition of IFN-α in the presence of fluoxetine.

Parent Involvement: Investigating the Parent-Child Relationship in Millennial College Students

Science.gov (United States)

Pizzolato, Jane Elizabeth; Hicklen, Sherrell

2011-01-01

There is evidence of a surge in parent involvement in postsecondary education, and some scholarship suggests that this high level of parent involvement may inhibit epistemological development. Despite these claims, there is little empirical evidence on the level or impact of parent involvement during the college years. The aim of this research was…

Terbinafine inhibits gap junctional intercellular communication

Energy Technology Data Exchange (ETDEWEB)

Lee, Ju Yeun, E-mail: whitewndus@naver.com [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of); Yoon, Sei Mee, E-mail: sei_mee@naver.com [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of); Department of Integrated OMICS for Biomedical Sciences, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Choi, Eun Ju, E-mail: yureas@naver.com [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of); Lee, Jinu, E-mail: jinulee@yonsei.ac.kr [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of)

2016-09-15

Terbinafine is an antifungal agent that selectively inhibits fungal sterol synthesis by blocking squalene epoxidase. We evaluated the effect of terbinafine on gap junctional intercellular communication (GJIC). Fluorescence recovery after photobleaching (FRAP) and I-YFP GJIC assays revealed that terbinafine inhibits GJIC in a reversible and dose-dependent manner in FRT-Cx43 and LN215 cells. Treatment with terbinafine did not affect Cx43 phosphorylation status or intracellular Ca{sup 2+} concentration, well-known action mechanisms of various GJIC blockers. While a structurally related chemical, naftifine, attenuated GJIC, epigallocatechin gallate, another potent squalene epoxidase inhibitor with a different structure, did not. These results suggest that terbinafine inhibits GJIC with a so far unknown mechanism of action. - Highlights: • In vitro pharmacological studies were performed on FRT-Cx43 and LN215 cells. • Terbinafine inhibits gap junctional intercellular communication in both cell lines. • The inhibitory effect of terbinafine is reversible and dose-dependent. • Treatment of terbinafine does not alter Cx43 phosphorylation or cytosolic Ca{sup 2+} concentration. • Inhibition of squalene epoxidase is not involved in this new effect of terbinafine.

Fasting in king penguin. II. Hormonal and metabolic changes during molt.

Science.gov (United States)

Cherel, Y; Leloup, J; Le Maho, Y

1988-02-01

The coincidence of fast and molt in penguins is an interesting condition for investigating the factors controlling protein metabolism; avian molt involves the utilization of amino acids for synthesis of new feathers, whereas a major factor for adaptation to fasting in birds, as for mammals, is reduction in net protein breakdown. Hormonal and biochemical changes were studied in seven molting king penguins. Their initial body mass was 18 kg. It decreased by 58% over 41 days of fasting. Feather synthesis lasted for the first 3 wk of the fast. It was marked by plasma concentrations of alanine and uric acid 1.5 to 2 times those for nonmolting fast, and plasma thyroxine was increased five times. At the completion of molt all these values returned to levels comparable to those in nonmolting fast. As indicated by high plasma levels of beta-hydroxybutyrate, lipid stores were mobilized readily during molting. The fast ended by a phase of enhancement in protein utilization that was characterized by a fivefold increase in uricacidemia and coincided with an 80% drop in plasma beta-hydroxybutyrate and a fourfold increase in plasma corticosterone. These data suggest that two different hormones control the two successive periods marked by an increased protein mobilization during the molting fast, i.e., thyroxine during feather growth and corticosterone toward the end of the fast, when the molt is completed.

Involvement of reactive oxygen species in the electrochemical inhibition of barnacle (Amphibalanus amphitrite) settlement

Science.gov (United States)

Rodolfo E. Perez-Roa; Marc A. Anderson; Dan Rittschof; Christopher G. Hunt; Daniel R. Noguera

2009-01-01

The role of reactive oxygen species (ROS) in electrochemical biofouling inhibition was investigated using a series of abiotic tests and settlement experiments with larvae of the barnacle Amphibalanus amphitrite, a cosmopolitan fouler. Larval settlement, a measure of biofouling potential, was reduced from 43% ± 14% to 5% ± 6% upon the application of...

Estrogen receptor-α36 is involved in epigallocatechin-3-gallate induced growth inhibition of ER-negative breast cancer stem/progenitor cells

Directory of Open Access Journals (Sweden)

Xiaohua Pan

2016-02-01

Full Text Available Epigallocatechin-3-gallate (EGCG is a type of catechin extracted from green tea, which is reported to have anticancer effects. EGCG is also reported to inhibit the cancer stem/progenitor cells in several estrogen receptor (ER-negative breast cancer cell lines, such as SUM-149, SUM-190 and MDA-MB-231. And all these cancer cells are highly expressed a new variant of ER-α, ER-α36. The aim of our present study is to determine the role of ER-α36 in the growth inhibitory activity of EGCG towards ER-negative breast cancer MDA-MB-231 and MDA-MB-436 cells. We found that EGCG potently inhibited the growth of cancer stem/progenitor cells in MDA-MB-231 and MDA-MB-436 cells, and also reduced the expression of ER-α36 in these cells. However, in ER-α36 knocked-down MDA-MB-231 and MDA-MB-436 cells, no significant inhibitory effects of EGCG on cancer stem/progenitor cells were observed. We also found that down-regulation of ER-α36 expression was in accordance with down-regulation of EGFR, which further verified a loop between ER-α36 and EGFR. Thus, our study indicated ER-α36 is involved in EGCG's inhibitory effects on ER-negative breast cancer stem/progenitor cells, which supports future preclinical and clinical evaluation of EGCG as a therapeutic option for ER-α36 positive breast cancer.

Changes in cerebro-cerebellar interaction during response inhibition after performance improvement.

Science.gov (United States)

Hirose, Satoshi; Jimura, Koji; Kunimatsu, Akira; Abe, Osamu; Ohtomo, Kuni; Miyashita, Yasushi; Konishi, Seiki

2014-10-01

It has been demonstrated that motor learning is supported by the cerebellum and the cerebro-cerebellar interaction. Response inhibition involves motor responses and the higher-order inhibition that controls the motor responses. In this functional MRI study, we measured the cerebro-cerebellar interaction during response inhibition in two separate days of task performance, and detected the changes in the interaction following performance improvement. Behaviorally, performance improved in the second day, compared to the first day. The psycho-physiological interaction (PPI) analysis revealed the interaction decrease from the right inferior frontal cortex (rIFC) to the cerebellum (lobule VII or VI). It was also revealed that the interaction increased from the same cerebellar region to the primary motor area. These results suggest the involvement of the cerebellum in response inhibition, and raise the possibility that the performance improvement was supported by the changes in the cerebro-cerebellar interaction. Copyright © 2014 Elsevier Inc. All rights reserved.

A Fasting-Responsive Signaling Pathway that Extends Life Span in C. elegans

Directory of Open Access Journals (Sweden)

Masaharu Uno

2013-01-01

Full Text Available Intermittent fasting is one of the most effective dietary restriction regimens that extend life span in C. elegans and mammals. Fasting-stimulus responses are key to the longevity response; however, the mechanisms that sense and transduce the fasting stimulus remain largely unknown. Through a comprehensive transcriptome analysis in C. elegans, we find that along with the FOXO transcription factor DAF-16, AP-1 (JUN-1/FOS-1 plays a central role in fasting-induced transcriptional changes. KGB-1, one of the C. elegans JNKs, acts as an activator of AP-1 and is activated in response to fasting. KGB-1 and AP-1 are involved in intermittent fasting-induced longevity. Fasting-induced upregulation of the components of the SCF E3 ubiquitin ligase complex via AP-1 and DAF-16 enhances protein ubiquitination and reduces protein carbonylation. Our results thus identify a fasting-responsive KGB-1/AP-1 signaling pathway, which, together with DAF-16, causes transcriptional changes that mediate longevity, partly through regulating proteostasis.

Loss of Balance between Striatal Feedforward Inhibition and Corticostriatal Excitation Leads to Tremor.

Science.gov (United States)

Oran, Yael; Bar-Gad, Izhar

2018-02-14

Fast-spiking interneurons (FSIs) exert powerful inhibitory control over the striatum and are hypothesized to balance the massive excitatory cortical and thalamic input to this structure. We recorded neuronal activity in the dorsolateral striatum and globus pallidus (GP) concurrently with the detailed movement kinematics of freely behaving female rats before and after selective inhibition of FSI activity using IEM-1460 microinjections. The inhibition led to the appearance of episodic rest tremor in the body part that depended on the somatotopic location of the injection within the striatum. The tremor was accompanied by coherent oscillations in the local field potential (LFP). Individual neuron activity patterns became oscillatory and coherent in the tremor frequency. Striatal neurons, but not GP neurons, displayed additional temporal, nonoscillatory correlations. The subsequent reduction in the corticostriatal input following muscimol injection to the corresponding somatotopic location in the primary motor cortex led to disruption of the tremor and a reduction of the LFP oscillations and individual neuron's phase-locked activity. The breakdown of the normal balance of excitation and inhibition in the striatum has been shown previously to be related to different motor abnormalities. Our results further indicate that the balance between excitatory corticostriatal input and feedforward FSI inhibition is sufficient to break down the striatal decorrelation process and generate oscillations resulting in rest tremor typical of multiple basal ganglia disorders. SIGNIFICANCE STATEMENT Fast-spiking interneurons (FSIs) play a key role in normal striatal processing by exerting powerful inhibitory control over the network. FSI malfunctions have been associated with abnormal processing of information within the striatum that leads to multiple movement disorders. Here, we study the changes in neuronal activity and movement kinematics following selective inhibition of these

Effects of chronic Akt/mTOR inhibition by rapamycin on mechanical overload-induced hypertrophy and myosin heavy chain transition in masseter muscle.

Science.gov (United States)

Umeki, Daisuke; Ohnuki, Yoshiki; Mototani, Yasumasa; Shiozawa, Kouichi; Fujita, Takayuki; Nakamura, Yoshiki; Saeki, Yasutake; Okumura, Satoshi

2013-01-01

To examine the effects of the Akt/mammalian target of rapamycin (mTOR) pathway on masseter muscle hypertrophy and myosin heavy chain (MHC) transition in response to mechanical overload, we analyzed the effects of bite-opening (BO) on the hypertrophy and MHC composition of masseter muscle of BO-rats treated or not treated with rapamycin (RAPA), a selective mTOR inhibitor. The masseter muscle weight in BO-rats was significantly greater than that in controls, and this increase was attenuated by RAPA treatment. Expression of slow-twitch MHC isoforms was significantly increased in BO-rats with/without RAPA treatment, compared with controls, but the magnitude of the increase was much smaller in RAPA-treated BO-rats. Phosphorylation of p44/42 MAPK (ERK1/2), which preserves fast-twitch MHC isoforms in skeletal muscle, was significantly decreased in BO-rats, but the decrease was abrogated by RAPA treatment. Calcineurin signaling is known to be important for masseter muscle hypertrophy and fast-to-slow MHC isoform transition, but expression of known calcineurin activity modulators was unaffected by RAPA treatment. Taken together, these results indicate that the Akt/mTOR pathway is involved in both development of masseter muscle hypertrophy and fast-to-slow MHC isoform transition in response to mechanical overload with inhibition of the ERK1/2 pathway and operates independently of the calcineurin pathway.

Feedforward Inhibition and Synaptic Scaling – Two Sides of the Same Coin?

Science.gov (United States)

Lücke, Jörg

2012-01-01

Feedforward inhibition and synaptic scaling are important adaptive processes that control the total input a neuron can receive from its afferents. While often studied in isolation, the two have been reported to co-occur in various brain regions. The functional implications of their interactions remain unclear, however. Based on a probabilistic modeling approach, we show here that fast feedforward inhibition and synaptic scaling interact synergistically during unsupervised learning. In technical terms, we model the input to a neural circuit using a normalized mixture model with Poisson noise. We demonstrate analytically and numerically that, in the presence of lateral inhibition introducing competition between different neurons, Hebbian plasticity and synaptic scaling approximate the optimal maximum likelihood solutions for this model. Our results suggest that, beyond its conventional use as a mechanism to remove undesired pattern variations, input normalization can make typical neural interaction and learning rules optimal on the stimulus subspace defined through feedforward inhibition. Furthermore, learning within this subspace is more efficient in practice, as it helps avoid locally optimal solutions. Our results suggest a close connection between feedforward inhibition and synaptic scaling which may have important functional implications for general cortical processing. PMID:22457610

Autophagy and gap junctional intercellular communication inhibition are involved in cadmium-induced apoptosis in rat liver cells

Energy Technology Data Exchange (ETDEWEB)

Zou, Hui [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China); Zhuo, Liling [College of Life Science, Zaozhuang University, Zaozhuang, Shandong, 277160 (China); Han, Tao; Hu, Di; Yang, Xiaokang; Wang, Yi; Yuan, Yan; Gu, Jianhong; Bian, Jianchun; Liu, Xuezhong [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China); Liu, Zongping, E-mail: liuzongping@yzu.edu.cn [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China)

2015-04-17

Cadmium (Cd) is known to induce hepatotoxicity, yet the underlying mechanism of how this occurs is not fully understood. In this study, Cd-induced apoptosis was demonstrated in rat liver cells (BRL 3A) with apoptotic nuclear morphological changes and a decrease in cell index (CI) in a time- and concentration-dependent manner. The role of gap junctional intercellular communication (GJIC) and autophagy in Cd-induced apoptosis was investigated. Cd significantly induced GJIC inhibition as well as downregulation of connexin 43 (Cx43). The prototypical gap junction blocker carbenoxolone disodium (CBX) exacerbated the Cd-induced decrease in CI. Cd treatment was also found to cause autophagy, with an increase in mRNA expression of autophagy-related genes Atg-5, Atg-7, Beclin-1, and microtubule-associated protein light chain 3 (LC3) conversion from cytosolic LC3-I to membrane-bound LC3-II. The autophagic inducer rapamycin (RAP) prevented the Cd-induced CI decrease, while the autophagic inhibitor chloroquine (CQ) caused a further reduction in CI. In addition, CBX promoted Cd-induced autophagy, as well as changes in expression of Atg-5, Atg-7, Beclin-1 and LC3. CQ was found to block the Cd-induced decrease in Cx43 and GJIC inhibition, whereas RAP had opposite effect. These results demonstrate that autophagy plays a protective role during Cd-induced apoptosis in BRL 3A cells during 6 h of experiment, while autophagy exacerbates Cd-induced GJIC inhibition which has a negative effect on cellular fate. - Highlights: • GJIC and autophagy is crucial for biological processes. • Cd exposure causes GJIC inhibition and autophagy increase in BRL 3A cells. • Autophagy protects Cd induced BRL 3A cells apoptosis at an early stage. • Autophagy exacerbates Cd-induced GJIC inhibition. • GJIC plays an important role in autophagy induced cell death or survival.

Gradient microfluidics enables rapid bacterial growth inhibition testing.

Science.gov (United States)

Li, Bing; Qiu, Yong; Glidle, Andrew; McIlvenna, David; Luo, Qian; Cooper, Jon; Shi, Han-Chang; Yin, Huabing

2014-03-18

Bacterial growth inhibition tests have become a standard measure of the adverse effects of inhibitors for a wide range of applications, such as toxicity testing in the medical and environmental sciences. However, conventional well-plate formats for these tests are laborious and provide limited information (often being restricted to an end-point assay). In this study, we have developed a microfluidic system that enables fast quantification of the effect of an inhibitor on bacteria growth and survival, within a single experiment. This format offers a unique combination of advantages, including long-term continuous flow culture, generation of concentration gradients, and single cell morphology tracking. Using Escherichia coli and the inhibitor amoxicillin as one model system, we show excellent agreement between an on-chip single cell-based assay and conventional methods to obtain quantitative measures of antibiotic inhibition (for example, minimum inhibition concentration). Furthermore, we show that our methods can provide additional information, over and above that of the standard well-plate assay, including kinetic information on growth inhibition and measurements of bacterial morphological dynamics over a wide range of inhibitor concentrations. Finally, using a second model system, we show that this chip-based systems does not require the bacteria to be labeled and is well suited for the study of naturally occurring species. We illustrate this using Nitrosomonas europaea, an environmentally important bacteria, and show that the chip system can lead to a significant reduction in the period required for growth and inhibition measurements (<4 days, compared to weeks in a culture flask).

Intermittent fasting up-regulates Fsp27/Cidec gene expression in white adipose tissue.

Science.gov (United States)

Karbowska, Joanna; Kochan, Zdzislaw

2012-03-01

Fat-specific protein of 27 kDa (FSP27) is a novel lipid droplet protein that promotes triacylglycerol storage in white adipose tissue (WAT). The regulation of the Fsp27 gene expression in WAT is largely unknown. We investigated the nutritional regulation of FSP27 in WAT. The effects of intermittent fasting (48 d, eight cycles of 3-d fasting and 3-d refeeding), caloric restriction (48 d), fasting-refeeding (3-d fasting and 3-d refeeding), and fasting (3 d) on mRNA expression of FSP27, peroxisome proliferator-activated receptor γ (PPARγ2), CCAAT/enhancer binding protein α (C/EBPα), and M isoform of carnitine palmitoyltransferase 1 (a positive control for PPARγ activation) in epididymal WAT and on serum triacylglycerol, insulin, and leptin levels were determined in Wistar rats. We also determined the effects of PPARγ activation by rosiglitazone or pioglitazone on FSP27 mRNA levels in primary rat adipocytes. Long-term intermittent fasting, in contrast to other dietary manipulations, significantly up-regulated Fsp27 gene expression in WAT. Moreover, in rats subjected to intermittent fasting, serum insulin levels were elevated; PPARγ2 and C/EBPα mRNA expression in WAT was increased, and there was a positive correlation of Fsp27 gene expression with PPARγ2 and C/EBPα mRNA levels. FSP27 mRNA expression was also increased in adipocytes treated with PPARγ agonists. Our study demonstrates that the transcription of the Fsp27 gene in adipose tissue may be induced in response to nutritional stimuli. Furthermore, PPARγ2, C/EBPα, and insulin may be involved in the nutritional regulation of FSP27. Thus intermittent fasting, despite lower caloric intake, may promote triacylglycerol deposition in WAT by increasing the expression of genes involved in lipid storage, such as Fsp27. Copyright © 2012 Elsevier Inc. All rights reserved.

Esterase inhibition by synergists in the western flower thrips Frankliniella occidentalis.

Science.gov (United States)

López-Soler, Neus; Cervera, Amelia; Quinto, Vicente; Abellán, Jaime; Bielza, Pablo; Martínez-Pardo, Rafael; Garcerá, Maria Dolores

2011-12-01

Western flower thrips (WFT), Frankliniella occidentalis (Pergande), is among the most important crop pests in the south-eastern region of Spain. Its increasing resistance to insecticides constitutes a serious problem, and understanding the mechanisms involved is therefore of great interest. Use of synergists to inhibit the enzymes involved in insecticide detoxification is widely used to determine their responsibility for insecticide resistance. However, they do not always act as intended or expected, and caution must be exercised when interpreting synergist results. Laboratory-selected strains of WFT were used to analyse the effects of the synergists piperonyl butoxide (PBO), S,S,S-tributyl phosphorotrithioate (DEF) and methiocarb on total esterase activity. Significant differences were found, indicating esterase activity inhibition by DEF, a lower effect for methiocarb and a small inhibition of the activity by PBO. Esterase isoenzyme inhibition by these compounds showed a similar result; this assay revealed an extreme sensitivity of Triplet A (resistance-associated esterases) to DEF. In an in vivo assay carried out with these compounds at different incubation times, only DEF caused posterior in vitro esterase activity inhibition, with a maximum effect 1 h after treatment. In this work, only DEF shows true synergistic inhibition of WFT esterases. Copyright © 2011 Society of Chemical Industry.

FFTF [Fast Flux Test Facility] management

International Nuclear Information System (INIS)

Bennett, C.L.

1986-11-01

Fuel Management at the Fast Flux Test Facility (FFTF) involves more than just the usual ex-core and in-core management of standard fuel and non-fuel components between storage locations and within the core since it is primarily an irradiation test facility. This mission involves testing an ever increasing variety of fueled and non-fueled experiments, each having unique requirements on the reactor core as well as having its own individual impact on the reload design. This paper describes the fuel management process used by the Westinghouse Hanford Company Core Engineering group that has led to the successful reload design of nine operating cycles and the irradiation of over 120 tests

Chemo-tolerance and sensitization by short-term fasting: The autophagy connection

Directory of Open Access Journals (Sweden)

Gustav Van Niekerk

2016-11-01

Full Text Available Preclinical studies suggest that fasting prior to chemotherapy may be an effective strategy to protect patients against the adverse effects of chemo-toxicity. Fasting may also sensitize cancer cells to chemotherapy. It is further suggested that fasting may similarly augment the efficacy of oncolytic viral therapy. The primary mechanism mediating these beneficial effects is thought to relate to the fact that fasting results in a decrease of circulating growth factors. In turn, such fasting cues would prompt normal cells to redirect energy towards cell maintenance and repair processes, rather than growth and proliferation. However, fasting is also known to up-regulate autophagy, an evolutionarily conserved catabolic process that is up-regulated in response to various cell stressors. Here we review a number of mechanisms by which fasting-induced autophagy may have an impact on both chemo-tolerance and chemo-sensitization. Firstly, fasting may exert a protective effect by mobilizing autophagic components prior to chemo-induction. In turn, the autophagic apparatus can be repurposed for removing cellular components damaged by chemotherapy. Autophagy also plays a key role in epitope expression as well as in modulating inflammation. Chemo-sensitization resulting from fasting may in fact be an effect of enhanced immune surveillance as a result of better autophagy-dependent epitope processing. Finally, autophagy is involved in host defense against viruses, and aspects of the autophagic process are also often targets for viral subversion. Consequently, altering autophagic flux by fasting may alter viral infectivity. These observations suggest that fasting-induced autophagy may have an impact on therapeutic efficacy in various oncological contexts.

Dyrk1A-ASF-CaMKIIδ Signaling Is Involved in Valsartan Inhibition of Cardiac Hypertrophy in Renovascular Hypertensive Rats.

Science.gov (United States)

Yao, Jian; Qin, Xiaotong; Zhu, Jianhua; Sheng, Hongzhuan

2016-01-01

It is known that the expression, activity and alternative splicing of Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ) are dysregulated in the cardiac remodeling process. Recently, we found a further signaling pathway, by which dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) regulates the alternative splicing of CaMKIIδ via the alternative splicing factor (ASF), i.e., Dyrk1A-ASF-CaMKIIδ. In this study, we aimed to investigate whether Dyrk1A-ASF-CaMKIIδ signaling was involved in valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats. Rats were subjected to two kidney-one clip (2K1C) surgery and then treated with valsartan (30 mg/kg/day) for 8 weeks. Hypertrophic parameter analysis was then performed. Western blot analysis was used to determine the protein expression of Dyrk1A and ASF and RT-PCR was used to analyze the alternative splicing of CaMKIIδ in the left ventricular (LV) sample. Valsartan attenuated cardiac hypertrophy in 2K1C rats but without impairment of cardiac systolic function. Increased protein expression of Dyrk1A and decreased protein expression of ASF were observed in the LV sample of 2K1C rats. Treatment of 2K1C rats with valsartan reversed the changes in Dyrk1A and ASF expression in the LV sample. Valsartan adjusted the 2K1C-induced imbalance in alternative splicing of CaMKIIδ by upregulating the mRNA expression of CaMKIIδC and downregulating the mRNA expression of CaMKIIδA and CaMKIIδB. Valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats was mediated, at least partly, by Dyrk1A-ASF-CaMKIIδ signaling. © 2015 S. Karger AG, Basel.

Fasting and meal-stimulated residual beta cell function is positively associated with serum concentrations of proinflammatory cytokines and negatively associated with anti-inflammatory and regulatory cytokines in patients with longer term type 1 diabetes

DEFF Research Database (Denmark)

Pham, Minh-Long; Kolb, H; Battelino, T

2013-01-01

Cytokines may promote or inhibit disease progression in type 1 diabetes. We investigated whether systemic proinflammatory, anti-inflammatory and regulatory cytokines associated differently with fasting and meal-stimulated beta cell function in patients with longer term type 1 diabetes.......Cytokines may promote or inhibit disease progression in type 1 diabetes. We investigated whether systemic proinflammatory, anti-inflammatory and regulatory cytokines associated differently with fasting and meal-stimulated beta cell function in patients with longer term type 1 diabetes....

Short-term fasting promotes insulin expression in rat hypothalamus.

Science.gov (United States)

Dakic, Tamara B; Jevdjovic, Tanja V; Peric, Mina I; Bjelobaba, Ivana M; Markelic, Milica B; Milutinovic, Bojana S; Lakic, Iva V; Jasnic, Nebojsa I; Djordjevic, Jelena D; Vujovic, Predrag Z

2017-07-01

In the hypothalamus, insulin takes on many roles involved in energy homoeostasis. Therefore, the aim of this study was to examine hypothalamic insulin expression during the initial phase of the metabolic response to fasting. Hypothalamic insulin content was assessed by both radioimmunoassay and Western blot. The relative expression of insulin mRNA was examined by qPCR. Immunofluorescence and immunohistochemistry were used to determine the distribution of insulin immunopositivity in the hypothalamus. After 6-h fasting, both glucose and insulin levels were decreased in serum but not in the cerebrospinal fluid. Our study showed for the first time that, while the concentration of circulating glucose and insulin decreased, both insulin mRNA expression and insulin content in the hypothalamic parenchyma were increased after short-term fasting. Increased insulin immunopositivity was detected specifically in the neurons of the hypothalamic periventricular nucleus and in the ependymal cells of fasting animals. These novel findings point to the complexity of mechanisms regulating insulin expression in the CNS in general and in the hypothalamus in particular. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Positive effects of intermittent fasting in ischemic stroke.

Science.gov (United States)

Fann, David Yang-Wei; Ng, Gavin Yong Quan; Poh, Luting; Arumugam, Thiruma V

2017-03-01

Intermittent fasting (IF) is a dietary protocol where energy restriction is induced by alternate periods of ad libitum feeding and fasting. Prophylactic intermittent fasting has been shown to extend lifespan and attenuate the progress and severity of age-related diseases such as cardiovascular (e.g. stroke and myocardial infarction), neurodegenerative (e.g. Alzheimer's disease and Parkinson's disease) and cancerous diseases in animal models. Stroke is the second leading cause of death, and lifestyle risk factors such as obesity and physical inactivity have been associated with elevated risks of stroke in humans. Recent studies have shown that prophylactic IF may mitigate tissue damage and neurological deficit following ischemic stroke by a mechanism(s) involving suppression of excitotoxicity, oxidative stress, inflammation and cell death pathways in animal stroke models. This review summarizes data supporting the potential hormesis mechanisms of prophylactic IF in animal models, and with a focus on findings from animal studies of prophylactic IF in stroke in our laboratory. Copyright © 2017 Elsevier Inc. All rights reserved.

Inhibiting prenylation augments chemotherapy efficacy in renal cell carcinoma through dual inhibition on mitochondrial respiration and glycolysis.

Science.gov (United States)

Huang, Jiangrong; Yang, Xiaoyu; Peng, Xiaochun; Huang, Wei

2017-11-18

Prenylation is a posttranslational lipid modification required for the proper functions of a number of proteins involved in cell regulation. Here, we show that prenylation inhibition is important for renal cell carcinoma (RCC) growth, survival and response to chemotherapy, and its underlying mechanism may be contributed to mitochondrial dysfunction. We first demonstrated that a HMG-CoA reductase inhibitor pitavastatin inhibited mevalonate pathway and thereby prenylation in RCC cells. In addition, pitavastatin is effective in inhibiting growth and inducing apoptosis in a panel of RCC cell lines. Combination of pitavastatin and paclitaxel is significantly more effective than pitavastatin or paclitaxel alone as shown by both in vitro cell culture system and in vivo RCC xenograft model. Importantly, pitavastatin treatment inhibits mitochondrial respiration via suppressing mitochondrial complex I and II enzyme activities. Interestingly, different from mitochondrial inhibitor phenformin that inhibits mitochondrial respiration but activates glycolytic rate in RCC cells, pitavastatin significantly decreases glycolytic rate. The dual inhibitory action of pitavastatin on mitochondrial respiration and glycolysis results in remarkable energy depletion and oxidative stress in RCC cells. In addition, inhibition of prenylation by depleting Isoprenylcysteine carboxylmethyltransferase (Icmt) also mimics the inhibitory effects of pitavastatin in RCC cells. Our work demonstrates the previously unappreciated association between prenylation inhibition and energy metabolism in RCC, which can be therapeutically exploited, likely in tumors that largely rely on energy metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

Eucalyptus hairy roots, a fast, efficient and versatile tool to explore function and expression of genes involved in wood formation.

Science.gov (United States)

Plasencia, Anna; Soler, Marçal; Dupas, Annabelle; Ladouce, Nathalie; Silva-Martins, Guilherme; Martinez, Yves; Lapierre, Catherine; Franche, Claudine; Truchet, Isabelle; Grima-Pettenati, Jacqueline

2016-06-01

Eucalyptus are of tremendous economic importance being the most planted hardwoods worldwide for pulp and paper, timber and bioenergy. The recent release of the Eucalyptus grandis genome sequence pointed out many new candidate genes potentially involved in secondary growth, wood formation or lineage-specific biosynthetic pathways. Their functional characterization is, however, hindered by the tedious, time-consuming and inefficient transformation systems available hitherto for eucalypts. To overcome this limitation, we developed a fast, reliable and efficient protocol to obtain and easily detect co-transformed E. grandis hairy roots using fluorescent markers, with an average efficiency of 62%. We set up conditions both to cultivate excised roots in vitro and to harden composite plants and verified that hairy root morphology and vascular system anatomy were similar to wild-type ones. We further demonstrated that co-transformed hairy roots are suitable for medium-throughput functional studies enabling, for instance, protein subcellular localization, gene expression patterns through RT-qPCR and promoter expression, as well as the modulation of endogenous gene expression. Down-regulation of the Eucalyptus cinnamoyl-CoA reductase1 (EgCCR1) gene, encoding a key enzyme in lignin biosynthesis, led to transgenic roots with reduced lignin levels and thinner cell walls. This gene was used as a proof of concept to demonstrate that the function of genes involved in secondary cell wall biosynthesis and wood formation can be elucidated in transgenic hairy roots using histochemical, transcriptomic and biochemical approaches. The method described here is timely because it will accelerate gene mining of the genome for both basic research and industry purposes. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

A network approach to response inhibition: dissociating functional connectivity of neural components involved in action restraint and action cancellation

NARCIS (Netherlands)

Dambacher, F.; Sack, A.T.; Lobbestael, J.; Arntz, A.; Brugman, S.; Schuhmann, T.

2014-01-01

The ability to inhibit action tendencies is vital for adaptive human behaviour. Various paradigms are supposed to assess action inhibition and are often used interchangeably. However, these paradigms are based on different conceptualizations (action restraint vs. action cancellation) and the

A Review of the Italian Fast Reactor Programme

International Nuclear Information System (INIS)

Pierantoni, F.; Tavoni, R.

1987-01-01

The Caorso power station underwent its fourth reloading at the end of 1986. The construction work at Montalto di Castro (BWR) has continued and the civil engineering work at Trino Vercellese (PWR) has started. However at present the national energy plan is once again being questioned and for the first time a strong political opposition to the nuclear component was found. The government agreed not to undertake any new initiatives on nuclear plant construction that might affect the outcome of the debate. In particular, in the LMFBR field, ENEA has been temporarily inhibited from undertaking new commitments - including those for the fast reactor PEC

No effects of bilateral tDCS over inferior frontal gyrus on response inhibition and aggression

NARCIS (Netherlands)

Dambacher, F.; Schuhmann, T.; Lobbestael, J.; Arntz, A.; Brugman, S.; Sack, A.T.

2015-01-01

Response inhibition is defined as the capacity to adequately withdraw pre-planned responses. It has been shown that individuals with deficits in inhibiting pre-planned responses tend to display more aggressive behaviour. The prefrontal cortex is involved in both, response inhibition and aggression.

FAST DETECTION OF ACETYLSALICYLIC ACID BY LIQUID CHROMATOGRAPHY TANDEM MASS SPECTROMETRY(LC-MSMS)

OpenAIRE

Abusoglu, Sedat; Unlu, Ali; Sivrikaya, Abdullah

2018-01-01

ObjectivesAcetylsalicylic acid (ASA) is themost widely used as an analgesic, anti-inflammatory and antipyretic drug, andalso used to inhibit cyclooxygenase dependent platelet aggregation.   The aimof this study was to develop a simple, fast and accurate tandem mass method fordetermination and quantification of ASA.  MethodsChromatographic seperation was performedusing an Shimadzu LC-20-AD (Kyoto, Japan) coupledwith a ABSCIEX API 3200 triple quadrupole massspectromete...

Genetic Variations Involved in Vitamin E Status

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Patrick Borel

2016-12-01

Full Text Available Vitamin E (VE is the generic term for four tocopherols and four tocotrienols that exhibit the biological activity of α-tocopherol. VE status, which is usually estimated by measuring fasting blood VE concentration, is affected by numerous factors, such as dietary VE intake, VE absorption efficiency, and VE catabolism. Several of these factors are in turn modulated by genetic variations in genes encoding proteins involved in these factors. To identify these genetic variations, two strategies have been used: genome-wide association studies and candidate gene association studies. Each of these strategies has its advantages and its drawbacks, nevertheless they have allowed us to identify a list of single nucleotide polymorphisms associated with fasting blood VE concentration and α-tocopherol bioavailability. However, much work remains to be done to identify, and to replicate in different populations, all the single nucleotide polymorphisms involved, to assess the possible involvement of other kind of genetic variations, e.g., copy number variants and epigenetic modifications, in order to establish a reliable list of genetic variations that will allow us to predict the VE status of an individual by knowing their genotype in these genetic variations. Yet, the potential usefulness of this area of research is exciting with regard to personalized nutrition and for future clinical trials dedicated to assessing the biological effects of the various isoforms of VE.

Coordination Mechanism in Fast Human Movements - Experimental and Modelling Studies. Volume 2.

Science.gov (United States)

1982-02-01

the involved muscle . Knapik and Ramos (33) have proposed that fast twitch muscle fiber may be responsible for a maximun speed move- ment, while slow ...repetition with submaximun weight (low intensity), Wolcott (56) attempted to selectively fatigue the fast and slow twitch muscle fiber. Both intensities of...B. "Enzyme Activity and Fibre Composition in Skeletal Muscle of Trained and Untrained Men." Journal of Applied Physiology 33: 312-319, 1972. 40

Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells

International Nuclear Information System (INIS)

Karnevi, Emelie; Said, Katarzyna; Andersson, Roland; Rosendahl, Ann H

2013-01-01

Epidemiological studies have shown direct associations between type 2 diabetes and obesity, both conditions associated with hyperglycaemia and hyperinsulinemia, and the risk of pancreatic cancer. Up to 80% of pancreatic cancer patients present with either new-onset type 2 diabetes or impaired glucose tolerance at the time of diagnosis. Recent population studies indicate that the incidence of pancreatic cancer is reduced among diabetics taking metformin. In this study, the effects of exposure of pancreatic cancer cells to high glucose levels on their growth and response to metformin were investigated. The human pancreatic cancer cell lines AsPC-1, BxPC-3, PANC-1 and MIAPaCa-2 were grown in normal (5 mM) or high (25 mM) glucose conditions, with or without metformin. The influence by metformin on proliferation, apoptosis and the AMPK and IGF-IR signalling pathways were evaluated in vitro. Metformin significantly reduced the proliferation of pancreatic cancer cells under normal glucose conditions. Hyperglycaemia however, protected against the metformin-induced growth inhibition. The anti-proliferative actions of metformin were associated with an activation of AMP-activated protein kinase AMPK Thr172 together with an inhibition of the insulin/insulin-like growth factor-I (IGF-I) receptor activation and downstream signalling mediators IRS-1 and phosphorylated Akt. Furthermore, exposure to metformin during normal glucose conditions led to increased apoptosis as measured by poly(ADP-ribose) polymerase (PARP) cleavage. In contrast, exposure to high glucose levels promoted a more robust IGF-I response and Akt activation which correlated to stimulated AMPK Ser485 phosphorylation and impaired AMPK Thr172 phosphorylation, resulting in reduced anti-proliferative and apoptotic effects by metformin. Our results indicate that metformin has direct anti-tumour activities in pancreatic cancer cells involving AMPK Thr172 activation and suppression of the insulin/IGF signalling pathways

Conditions for substorm onset by the fast reconnection mechanism

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M. Ugai

2008-12-01

Full Text Available The fast reconnection mechanism, involving slow shocks and Alfvénic fast plasma jets, is most responsible for the explosive conversion of magnetic energy associated with geomagnetic substorms and solar flares. In this paper, the spontaneous fast reconnection model is applied to well-known phenomena of substorms. When the east-west width of the tail current sheet becomes 3–4 times larger than its north-south thickness, the fast reconnection mechanism can fully be established, which may lead to substorm onset. The resulting Alfvénic jet can exactly explain, both qualitatively and quantitatively, the in-situ satellite observations of the traveling compression regions (TCRs associated with large-scale plasmoids propagating down the tail. Also, the earthward fast reconnection jet causes drastic magnetic field dipolarization, so that the sheet current ahead of the magnetic loop of closed field lines suddenly turns its direction toward the loop footpoint and a large-scale current wedge is formed according to the growth of field-aligned currents. It is demonstrated that an MHD generator arises ahead of the magnetic loop and drives the current wedge to distinctly enhance the current density in a pair of thin layers of the loop footpoint, giving rise to drastic heating in the form of two ribbons.

Neighborhood fast food restaurants and fast food consumption: a national study.

Science.gov (United States)

Richardson, Andrea S; Boone-Heinonen, Janne; Popkin, Barry M; Gordon-Larsen, Penny

2011-07-08

Recent studies suggest that neighborhood fast food restaurant availability is related to greater obesity, yet few studies have investigated whether neighborhood fast food restaurant availability promotes fast food consumption. Our aim was to estimate the effect of neighborhood fast food availability on frequency of fast food consumption in a national sample of young adults, a population at high risk for obesity. We used national data from U.S. young adults enrolled in wave III (2001-02; ages 18-28) of the National Longitudinal Study of Adolescent Health (n = 13,150). Urbanicity-stratified multivariate negative binomial regression models were used to examine cross-sectional associations between neighborhood fast food availability and individual-level self-reported fast food consumption frequency, controlling for individual and neighborhood characteristics. In adjusted analysis, fast food availability was not associated with weekly frequency of fast food consumption in non-urban or low- or high-density urban areas. Policies aiming to reduce neighborhood availability as a means to reduce fast food consumption among young adults may be unsuccessful. Consideration of fast food outlets near school or workplace locations, factors specific to more or less urban settings, and the role of individual lifestyle attitudes and preferences are needed in future research.

Neighborhood fast food restaurants and fast food consumption: A national study

Directory of Open Access Journals (Sweden)

Gordon-Larsen Penny

2011-07-01

Full Text Available Abstract Background Recent studies suggest that neighborhood fast food restaurant availability is related to greater obesity, yet few studies have investigated whether neighborhood fast food restaurant availability promotes fast food consumption. Our aim was to estimate the effect of neighborhood fast food availability on frequency of fast food consumption in a national sample of young adults, a population at high risk for obesity. Methods We used national data from U.S. young adults enrolled in wave III (2001-02; ages 18-28 of the National Longitudinal Study of Adolescent Health (n = 13,150. Urbanicity-stratified multivariate negative binomial regression models were used to examine cross-sectional associations between neighborhood fast food availability and individual-level self-reported fast food consumption frequency, controlling for individual and neighborhood characteristics. Results In adjusted analysis, fast food availability was not associated with weekly frequency of fast food consumption in non-urban or low- or high-density urban areas. Conclusions Policies aiming to reduce neighborhood availability as a means to reduce fast food consumption among young adults may be unsuccessful. Consideration of fast food outlets near school or workplace locations, factors specific to more or less urban settings, and the role of individual lifestyle attitudes and preferences are needed in future research.

Implications of nuclear physics in the development of Fast Breeder Reactors

International Nuclear Information System (INIS)

Rapeanu, S.; Ilie, P.; Vasiliu, G.; Popescu, C.; Boeriu, S.; Constantinescu, D.; Mateescu, S.

1980-08-01

The purpose of this paper is to point out the involved aspects of nuclear physics in the calculation and design of the fast reactors. After a brief description of the advantages of using the fast reactors in the national economy, the national programs concerning this activity are presented. The structure and operation conditions of the liquid metal fast breeder reactor (LMFBR) are also reviewed. Then, the methods aimed to calculate the core, the burn-up, the reactor dynamics, the analysis of accidents, the shielding, as well as, the materials required in the fast reactor calculation, are shortly given. Further on, it deals with the nuclear data types connected to the fast reactor calculations, with accuracy requirements for nuclear data, as well as, with the present stage of nuclear data for fissile, fertile and structural materials. The requirements for new differential data measurements, new integral data and benchmark experiments are presented. Data adjustement methods are also summarized. Some aspects of the structural material behaviour in intense gamma radiation and neutron fields existing into a fast reactor are also presented in the last part of this paper. The concluding remarks are mentioned at the end of the paper. (author)

V-ATPase Is Involved in Silkworm Defense Response against Bombyx mori Nucleopolyhedrovirus.

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Peng Lü

Full Text Available Silkworms are usually susceptible to the infection of Bombyx mori (B. mori nucleopolyhedrovirus (BmNPV, which can cause significant economic loss. However, some silkworm strains are identified to be highly resistant to BmNPV. To explore the silkworm genes involved in this resistance in the present study, we performed comparative real-time PCR, ATPase assay, over-expression and sub-cellular localization experiments. We found that when inoculated with BmNPV both the expression and activity of V-ATPase were significantly up-regulated in the midgut column cells (not the goblet cells of BmNPV-resistant strains (NB and BC8, the main sites for the first step of BmNPV invasion, but not in those of a BmNPV-susceptible strain 306. Furthermore, this up-regulation mainly took place during the first 24 hours post inoculation (hpi, the essential period required for establishment of virus infection, and then was down-regulated to normal levels. Amazingly, transient over-expression of V-ATPase c subunit in BmNPV-infected silkworm cells could significantly inhibit BmNPV proliferation. To our knowledge this is the first report demonstrating clearly that V-ATPase is indeed involved in the defense response against BmNPV. Our data further suggests that prompt and potent regulation of V-ATPase may be essential for execution of this response, which may enable fast acidification of endosomes and/or lysosomes to render them competent for degradation of invading viruses.

Restoring integrity—A grounded theory of coping with a fast track surgery programme

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Lene Bastrup Jørgensen

2016-01-01

Full Text Available Aims and objectives: The aim of this study was to generate a theory conceptualizing and explaining behavioural processes involved in coping in order to identify the predominant coping types and coping type-specific features. Background: Patients undergoing fast track procedures do not experience a higher risk of complications, readmission, or mortality. However, such programmes presuppose an increasing degree of patient involvement, placing high educational, physical, and mental demands on the patients. There is a lack of knowledge about how patients understand and cope with fast track programmes. Design: The study design used classical grounded theory. Methods: The study used a multimodal approach with qualitative and quantitative data sets from 14 patients. Results: Four predominant types of coping, with distinct physiological, cognitive, affective, and psychosocial features, existed among patients going through a fast track total hip replacement programme. These patients’ main concern was to restore their physical and psychosocial integrity, which had been compromised by reduced function and mobility in daily life. To restore integrity they economized their mental resources, while striving to fulfil the expectations of the fast track programme. This goal was achieved by being mentally proactive and physically active. Three out of the four predominant types of coping matched the expectations expressed in the fast track programme. The non-matching behaviour was seen among the most nervous patients, who claimed the right to diverge from the programme. Conclusion: In theory, four predominant types of coping with distinct physiological, cognitive, affective, and psychosocial features occur among patients going through a fast track total hip arthroplasty programme.

Restoring integrity--A grounded theory of coping with a fast track surgery programme.

Science.gov (United States)

Jørgensen, Lene Bastrup; Fridlund, Bengt

2016-01-01

The aim of this study was to generate a theory conceptualizing and explaining behavioural processes involved in coping in order to identify the predominant coping types and coping type-specific features. Patients undergoing fast track procedures do not experience a higher risk of complications, readmission, or mortality. However, such programmes presuppose an increasing degree of patient involvement, placing high educational, physical, and mental demands on the patients. There is a lack of knowledge about how patients understand and cope with fast track programmes. The study design used classical grounded theory. The study used a multimodal approach with qualitative and quantitative data sets from 14 patients. Four predominant types of coping, with distinct physiological, cognitive, affective, and psychosocial features, existed among patients going through a fast track total hip replacement programme. These patients' main concern was to restore their physical and psychosocial integrity, which had been compromised by reduced function and mobility in daily life. To restore integrity they economized their mental resources, while striving to fulfil the expectations of the fast track programme. This goal was achieved by being mentally proactive and physically active. Three out of the four predominant types of coping matched the expectations expressed in the fast track programme. The non-matching behaviour was seen among the most nervous patients, who claimed the right to diverge from the programme. In theory, four predominant types of coping with distinct physiological, cognitive, affective, and psychosocial features occur among patients going through a fast track total hip arthroplasty programme.

Restoring integrity—A grounded theory of coping with a fast track surgery programme

Science.gov (United States)

Jørgensen, Lene Bastrup; Fridlund, Bengt

2016-01-01

Aims and objectives The aim of this study was to generate a theory conceptualizing and explaining behavioural processes involved in coping in order to identify the predominant coping types and coping type-specific features. Background Patients undergoing fast track procedures do not experience a higher risk of complications, readmission, or mortality. However, such programmes presuppose an increasing degree of patient involvement, placing high educational, physical, and mental demands on the patients. There is a lack of knowledge about how patients understand and cope with fast track programmes. Design The study design used classical grounded theory. Methods The study used a multimodal approach with qualitative and quantitative data sets from 14 patients. Results Four predominant types of coping, with distinct physiological, cognitive, affective, and psychosocial features, existed among patients going through a fast track total hip replacement programme. These patients’ main concern was to restore their physical and psychosocial integrity, which had been compromised by reduced function and mobility in daily life. To restore integrity they economized their mental resources, while striving to fulfil the expectations of the fast track programme. This goal was achieved by being mentally proactive and physically active. Three out of the four predominant types of coping matched the expectations expressed in the fast track programme. The non-matching behaviour was seen among the most nervous patients, who claimed the right to diverge from the programme. Conclusion In theory, four predominant types of coping with distinct physiological, cognitive, affective, and psychosocial features occur among patients going through a fast track total hip arthroplasty programme. PMID:26751199

Predicting the dynamics of bacterial growth inhibition by ribosome-targeting antibiotics

Science.gov (United States)

Greulich, Philip; Doležal, Jakub; Scott, Matthew; Evans, Martin R.; Allen, Rosalind J.

2017-12-01

Understanding how antibiotics inhibit bacteria can help to reduce antibiotic use and hence avoid antimicrobial resistance—yet few theoretical models exist for bacterial growth inhibition by a clinically relevant antibiotic treatment regimen. In particular, in the clinic, antibiotic treatment is time-dependent. Here, we use a theoretical model, previously applied to steady-state bacterial growth, to predict the dynamical response of a bacterial cell to a time-dependent dose of ribosome-targeting antibiotic. Our results depend strongly on whether the antibiotic shows reversible transport and/or low-affinity ribosome binding (‘low-affinity antibiotic’) or, in contrast, irreversible transport and/or high affinity ribosome binding (‘high-affinity antibiotic’). For low-affinity antibiotics, our model predicts that growth inhibition depends on the duration of the antibiotic pulse, and can show a transient period of very fast growth following removal of the antibiotic. For high-affinity antibiotics, growth inhibition depends on peak dosage rather than dose duration, and the model predicts a pronounced post-antibiotic effect, due to hysteresis, in which growth can be suppressed for long times after the antibiotic dose has ended. These predictions are experimentally testable and may be of clinical significance.

Jasmonic Acid Enhances Al-Induced Root Growth Inhibition.

Science.gov (United States)

Yang, Zhong-Bao; He, Chunmei; Ma, Yanqi; Herde, Marco; Ding, Zhaojun

2017-02-01

Phytohormones such as ethylene and auxin are involved in the regulation of the aluminum (Al)-induced root growth inhibition. Although jasmonate (JA) has been reported to play a crucial role in the regulation of root growth and development in response to environmental stresses through interplay with ethylene and auxin, its role in the regulation of root growth response to Al stress is not yet known. In an attempt to elucidate the role of JA, we found that exogenous application of JA enhanced the Al-induced root growth inhibition. Furthermore, phenotype analysis with mutants defective in either JA biosynthesis or signaling suggests that JA is involved in the regulation of Al-induced root growth inhibition. The expression of the JA receptor CORONATINE INSENSITIVE1 (COI1) and the key JA signaling regulator MYC2 was up-regulated in response to Al stress in the root tips. This process together with COI1-mediated Al-induced root growth inhibition under Al stress was controlled by ethylene but not auxin. Transcriptomic analysis revealed that many responsive genes under Al stress were regulated by JA signaling. The differential responsive of microtubule organization-related genes between the wild-type and coi1-2 mutant is consistent with the changed depolymerization of cortical microtubules in coi1 under Al stress. In addition, ALMT-mediated malate exudation and thus Al exclusion from roots in response to Al stress was also regulated by COI1-mediated JA signaling. Together, this study suggests that root growth inhibition is regulated by COI1-mediated JA signaling independent from auxin signaling and provides novel insights into the phytohormone-mediated root growth inhibition in response to Al stress. © 2017 American Society of Plant Biologists. All Rights Reserved.

Factors Influencing Fast-Food Consumption Among Adolescents in Tehran: A Qualitative Study.

Science.gov (United States)

Askari Majabadi, Hesamedin; Solhi, Mahnaz; Montazeri, Ali; Shojaeizadeh, Davoud; Nejat, Saharnaz; Khalajabadi Farahani, Farideh; Djazayeri, Abolghasem

2016-03-01

The consumption of different types of fast food is increasingly growing in all parts of the world, both in developed and developing countries. Because of the changes and transitions in the lifestyle and dietary habits of people, an increasing number of people from different age groups, particularly adolescents and young adults, are inclined toward consuming fast food. The objective of this study was to investigate the factors influencing fast-food consumption among adolescents in Tehran, Iran. The present qualitative study was conducted in 2012 - 2013 in Tehran, the capital of Iran. To achieve the objective of this study, 42 adolescents were enrolled in this study through a purposive sampling method, and the required data was collected via individual semi-structured in-depth interviews. Data collection and analysis were carried out simultaneously, and the collected data was analyzed via a thematic content analysis and using MAXQDA 10 software. In this study after coding the transcribed interviews, the findings were categorized into three main themes as follows: personal views, social factors, and family factors. Each theme included several categories and subcategories, and the coded sentences and phrases were placed under each category and subcategory. The results of this study showed that the number of factors promoting fast-food consumption appeared to be more than the inhibiting factors and that the diverse factors at the individual and social level influenced fast-food consumption among adolescents.

Domain IV voltage-sensor movement is both sufficient and rate limiting for fast inactivation in sodium channels.

Science.gov (United States)

Capes, Deborah L; Goldschen-Ohm, Marcel P; Arcisio-Miranda, Manoel; Bezanilla, Francisco; Chanda, Baron

2013-08-01

Voltage-gated sodium channels are critical for the generation and propagation of electrical signals in most excitable cells. Activation of Na(+) channels initiates an action potential, and fast inactivation facilitates repolarization of the membrane by the outward K(+) current. Fast inactivation is also the main determinant of the refractory period between successive electrical impulses. Although the voltage sensor of domain IV (DIV) has been implicated in fast inactivation, it remains unclear whether the activation of DIV alone is sufficient for fast inactivation to occur. Here, we functionally neutralize each specific voltage sensor by mutating several critical arginines in the S4 segment to glutamines. We assess the individual role of each voltage-sensing domain in the voltage dependence and kinetics of fast inactivation upon its specific inhibition. We show that movement of the DIV voltage sensor is the rate-limiting step for both development and recovery from fast inactivation. Our data suggest that activation of the DIV voltage sensor alone is sufficient for fast inactivation to occur, and that activation of DIV before channel opening is the molecular mechanism for closed-state inactivation. We propose a kinetic model of sodium channel gating that can account for our major findings over a wide voltage range by postulating that DIV movement is both necessary and sufficient for fast inactivation.

The mechanism of total disintegration of heavy nuclei by fast hadrons and nuclei

International Nuclear Information System (INIS)

Strugalska-Gola, E.; Strugalski, Z.

1997-01-01

The mechanism of the total disintegration of atomic nuclei by fast hadrons and nuclei is considered. The passage of energetic hadrons through layers of intranuclear matter, accompanied by emission of fast nucleons with kinetic energies from about 20 up to about 500 MeV from definite local small regions in the nuclei around projectile courses in them, allows one to explain simply the occurrence of the total destruction of nuclei involved in the collisions. Light nuclei may be totally disintegrated by fast hadrons and nuclei; heavier nuclei may be totally disintegrated only in central collisions of nuclei with similar mass numbers

FastChem: An ultra-fast equilibrium chemistry

Science.gov (United States)

Kitzmann, Daniel; Stock, Joachim

2018-04-01

FastChem is an equilibrium chemistry code that calculates the chemical composition of the gas phase for given temperatures and pressures. Written in C++, it is based on a semi-analytic approach, and is optimized for extremely fast and accurate calculations.

The risk of shorter fasting time for pediatric deep sedation.

Science.gov (United States)

Clark, Mathew; Birisci, Esma; Anderson, Jordan E; Anliker, Christina M; Bryant, Micheal A; Downs, Craig; Dalabih, Abdallah

2016-01-01

Current guidelines adopted by the American Academy of Pediatrics calls for prolonged fasting times before performing pediatric procedural sedation and analgesia (PSA). PSA is increasingly provided to children outside of the operating theater by sedation trained pediatric providers and does not require airway manipulation. We investigated the safety of a shorter fasting time compared to a longer and guideline compliant fasting time. We tried to identify the association between fasting time and sedation-related complications. This is a prospective observational study that included children 2 months to 18 years of age and had an American Society of Anesthesiologists physical status classification of I or II, who underwent deep sedation for elective procedures, performed by pediatric critical care providers. Procedures included radiologic imaging studies, electroencephalograms, auditory brainstem response, echocardiograms, Botox injections, and other minor surgical procedures. Subjects were divided into two groups depending on the length of their fasting time (4-6 h and >6 h). Complication rates were calculated and compared between the three groups. In the studied group of 2487 subjects, 1007 (40.5%) had fasting time of 4-6 h and the remaining 1480 (59.5%) subjects had fasted for >6 h. There were no statistically significant differences in any of the studied complications between the two groups. This study found no difference in complication rate in regard to the fasting time among our subjects cohort, which included only healthy children receiving elective procedures performed by sedation trained pediatric critical care providers. This suggests that using shorter fasting time may be safe for procedures performed outside of the operating theater that does not involve high-risk patients or airway manipulation.

Inhibition and Shifting in Children with Learning Deficits in Arithmetic and Reading

Science.gov (United States)

van der Sluis, Sophie; de Jong, Peter F.; van der Leij, Aryan

2004-01-01

The executive functions of inhibition and shifting were studied in arithmetic-disabled children, reading-disabled children, reading plus arithmetic-disabled children, and controls (N = 74). Measures involved the rapid naming of objects, digits, letters, or quantities with or without additional task requirements that reflected inhibition or…

Comparative Proteomic Analysis Provides insight into the Key Proteins as Possible Targets Involved in Aspirin Inhibiting Biofilm Formation of Staphylococcus xylosus

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Chang-Geng Xu

2017-08-01

Full Text Available Staphylococcus xylosus is an opportunistic pathogen that causes infection in humans and cow mastitis. And S. xylosus possesses a strong ability to form biofilms in vitro. As biofilm formation facilitates resistance to antimicrobial agents, the discovery of new medicinal properties for classic drugs is highly desired. Aspirin, which is the most common active component of non-steroidal anti-inflammatory compounds, affects the biofilm-forming capacity of various bacterial species. We have found that aspirin effectively inhibits biofilm formation of S. xylosus by Crystal violet (CV staining and scanning electron microscopy analyses. The present study sought to elucidate possible targets of aspirin in suppressing S. xylosus biofilm formation. Based on an isobaric tag for relative and absolute quantitation (iTRAQ fold-change of >1.2 or <0.8 (P-value < 0.05, 178 differentially expressed proteins, 111 down-regulated and 67 up-regulated, were identified after application of aspirin to cells at a 1/2 minimal inhibitory concentration. Gene ontology analysis indicated enrichment in metabolic processes for the majority of the differentially expressed proteins. We then used the Kyoto Encyclopedia of Genes and Genomes (KEGG pathway database to analyze a large number of differentially expressed proteins and identified genes involved in biosynthesis of amino acids pathway, carbon metabolism (pentose phosphate and glycolytic pathways, tricarboxylic acid cycle and nitrogen metabolism (histidine metabolism. These novel proteins represent candidate targets in aspirin-mediated inhibition of S. xylosus biofilm formation at sub-MIC levels. The findings lay the foundation for further studies to identify potential aspirin targets.

Fast neutron (14.5 MeV) radiography: a comparative study

International Nuclear Information System (INIS)

Klann, R.T.

1996-01-01

Fast neutron (14.5 MeV) radiography is a type of non-destructive analysis tool that offers its own benefits and drawbacks. Because cross-sections vary with energy, a different range of materials can be examined with fast neutrons than can be studied with thermal neutrons, epithermal neutrons, or x-rays. This paper details these differences through a comparative study of fast neutron radiography to the other types of radiography available. The most obvious difference among the different types of radiography is in the penetrability of the sources. Fast neutrons can probe much deeper and can therefore obtain details of the internals of thick objects. Good images have been obtained through as much as 15 cm of steel, 10 cm of water, and 15 cm of borated polyethylene. In addition, some objects were identifiable through as much as 25 cm of water or 30 cm of borated polyethylene. The most notable benefit of fast neutron radiography is in the types of materials that can be tested. Fast neutron radiography can view through materials that simply cannot be viewed by X rays, thermal neutrons, or epithermal neutrons due to the high cross-sections or linear attenuation coefficients involved. Cadmium was totally transparent to the fast neutron source. Fast neutron radiography is not without drawbacks. The most pronounced drawback has been in the quality of radiograph produced. The image resolution is only about 0.8 mm for a 1.25 cm thick object, whereas, other forms of radiography have much better resolution

Acute serotonin depletion releases motivated inhibition of response vigour.

Science.gov (United States)

den Ouden, Hanneke E M; Swart, Jennifer C; Schmidt, Kristin; Fekkes, Durk; Geurts, Dirk E M; Cools, Roshan

2015-04-01

The neurotransmitter serotonin has long been implicated in the motivational control of behaviour. Recent theories propose that the role of serotonin can be understood in terms of an interaction between a motivational and a behavioural activation axis. Experimental support for these ideas, however, has been mixed. In the current study, we aimed to investigate the role of serotonin (5HT) in behavioural vigour as a function of incentive motivation. We employed dietary acute tryptophan depletion (ATD) to lower the 5HT precursor tryptophan during the performance of a speeded visual discrimination task. Feedback valence and feedback probability were manipulated independently and cued prior to target onset. On feedback trials, fast correct responses led to either reward or avoidance of punishment, while slow or incorrect responses led to reward omission or punishment. We show that behavioural responding is inhibited under high incentive motivation (i.e. high-feedback probability) at baseline 5HT levels and that lowering these leads to behavioural disinhibition, while leaving accuracy unaffected. Surprisingly, there were no differential effects of motivational valence, with 5HT depletion releasing behavioural inhibition under both appetitive and aversive motivation. Our findings extend current theories on the role of 5HT in behavioural inhibition by showing that reductions in serotonin lead to increased behavioural vigour only if there is a motivational drive to inhibit behaviour at baseline.

Involvement of PPAR-γ in the neuroprotective and anti-inflammatory effects of angiotensin type 1 receptor inhibition: effects of the receptor antagonist telmisartan and receptor deletion in a mouse MPTP model of Parkinson's disease

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Garrido-Gil Pablo

2012-02-01

Full Text Available Abstract Background Several recent studies have shown that angiotensin type 1 receptor (AT1 antagonists such as candesartan inhibit the microglial inflammatory response and dopaminergic cell loss in animal models of Parkinson's disease. However, the mechanisms involved in the neuroprotective and anti-inflammatory effects of AT1 blockers in the brain have not been clarified. A number of studies have reported that AT1 blockers activate peroxisome proliferator-activated receptor gamma (PPAR γ. PPAR-γ activation inhibits inflammation, and may be responsible for neuroprotective effects, independently of AT1 blocking actions. Methods We have investigated whether oral treatment with telmisartan (the most potent PPAR-γ activator among AT1 blockers provides neuroprotection against dopaminergic cell death and neuroinflammation, and the possible role of PPAR-γ activation in any such neuroprotection. We used a mouse model of parkinsonism induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP and co-administration of the PPAR-γ antagonist GW9662 to study the role of PPAR-γ activation. In addition, we used AT1a-null mice lesioned with MPTP to study whether deletion of AT1 in the absence of any pharmacological effect of AT1 blockers provides neuroprotection, and investigated whether PPAR-γ activation may also be involved in any such effect of AT1 deletion by co-administration of the PPAR-γ antagonist GW9662. Results We observed that telmisartan protects mouse dopaminergic neurons and inhibits the microglial response induced by administration of MPTP. The protective effects of telmisartan on dopaminergic cell death and microglial activation were inhibited by co-administration of GW9662. Dopaminergic cell death and microglial activation were significantly lower in AT1a-null mice treated with MPTP than in mice not subjected to AT1a deletion. Interestingly, the protective effects of AT1 deletion were also inhibited by co

Neighborhood fast food restaurants and fast food consumption: A national study

OpenAIRE

Richardson, Andrea S; Boone-Heinonen, Janne; Popkin, Barry M; Gordon-Larsen, Penny

2011-01-01

Abstract Background Recent studies suggest that neighborhood fast food restaurant availability is related to greater obesity, yet few studies have investigated whether neighborhood fast food restaurant availability promotes fast food consumption. Our aim was to estimate the effect of neighborhood fast food availability on frequency of fast food consumption in a national sample of young adults, a population at high risk for obesity. Methods We used national data from U.S. young adults enrolled...

Comparison of Fast-Food and Non-Fast-Food Children's Menu Items

Science.gov (United States)

Serrano, Elena L.; Jedda, Virginia B.

2009-01-01

Objective: Compare the macronutrient content of children's meals sold by fast-food restaurants (FFR) and non-fast-food restaurants (NFF). Design: All restaurants within the designated city limits were surveyed. Non-fast-food children's meals were purchased, weighed, and analyzed using nutrition software. All fast-food children's meals were…

Inhibition of human prostate cancer cells proliferation by a selective alpha1-adrenoceptor antagonist labedipinedilol-A involves cell cycle arrest and apoptosis

International Nuclear Information System (INIS)

Liou, S.-F.; Lin, H.-H.; Liang, J.-C.; Chen, I.-J.; Yeh, J.-L.

2009-01-01

In this research, we conducted an in vitro analysis to evaluate the prostate cancer cells response to labedipinedilol-A in order to determine the effect of this selective α 1 -adrenoceptor antagonist to suppress prostate cancer cell growth by affecting cell proliferation and apoptosis. Here, we report that treatment of androgen-sensitive (LNCaP) and androgen-insensitive (PC-3) prostate cancer cells with labedipinedilol-A inhibited cell proliferation in concentration-dependent and time-dependent manners. Moreover, norepinephrine-stimulated proliferation of both cell lines are markedly inhibited by labedipinedilol-A. The probable involvement of α 1 -adrenoceptors in this cellular response is suggested. Labedipinedilol-A-induced growth inhibition was associated with G 0 /G 1 arrest, and G 2 /M arrest depending upon concentrations. Cell cycle blockade was associated with reduced amounts of cyclin D1/2, cyclin E, Cdk2, Cdk4, and Cdk6 and increased levels of the Cdk inhibitory proteins (Cip1/p21 and Kip1/p27). In addition, labedipinedilol-A also induced apoptosis in PC-3 cells, as determined by using Hoechst 33342 staining, DNA fragmentation, and Annexin V staining assay. Furthermore, labedipinedilol-A triggered the mitochondrial apoptotic pathway, as indicated by increasing the expression of Bax, but decreasing the level of Bcl-2, resulting in mitochondrial membrane potential loss, cytochrome c release, and activation of caspase-9 and -3. We further investigated the role of MAPK cascades in the anti-proliferative and apoptosis effects of labedipinedilol-A, and confirmed that labedipinedilol-A could activate JNK1/2 but not p38 in both cell lines. Unlike JNK1/2, however, labedipinedilol-A treatment resulted in down-regulation of phospho-ERK1/2 expression. We concluded that labedipinedilol-A possessed the growth-suppressive and apoptotic effects on LNCaP and PC-3 cells by its α 1 -adrenoceptor blockade, and the apoptotic effects of labedipinedilol-A primarily through

The development of children's inhibition: does parenting matter?

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Roskam, Isabelle; Stievenart, Marie; Meunier, Jean-Christophe; Noël, Marie-Pascale

2014-06-01

Whereas a large body of research has investigated the maturation of inhibition in relation to the prefrontal cortex, far less research has been devoted to environmental factors that could contribute to inhibition improvement. The aim of the current study was to test whether and to what extent parenting matters for inhibition development from 2 to 8years of age. Data were collected from 421 families, with 348 mother-child dyads and 342 father-child dyads participating. Children's inhibition capacities and parenting behaviors were assessed in a three-wave longitudinal data collection. The main analyses examined the impact of parenting on the development of children's inhibition capacities. They were conducted using a multilevel modeling (MLM) framework. The results lead to the conclusion that both mothers and fathers contribute through their child-rearing behavior to their children's executive functioning, even when controlling for age-related improvement (maturation) and important covariates such as gender, verbal IQ, and place of enrollment. More significant relations between children's inhibition development and parenting were displayed for mothers than for fathers. More precisely, parenting behaviors that involve higher monitoring, lower discipline, inconsistency and negative controlling, and a positive parenting style are associated with good development of inhibition capacities in children. Copyright © 2014 Elsevier Inc. All rights reserved.

Long-term fasting decreases mitochondrial avian UCP-mediated oxygen consumption in hypometabolic king penguins.

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Rey, Benjamin; Halsey, Lewis G; Dolmazon, Virginie; Rouanet, Jean-Louis; Roussel, Damien; Handrich, Yves; Butler, Patrick J; Duchamp, Claude

2008-07-01

In endotherms, regulation of the degree of mitochondrial coupling affects cell metabolic efficiency. Thus it may be a key contributor to minimizing metabolic rate during long periods of fasting. The aim of the present study was to investigate whether variation in mitochondrial avian uncoupling proteins (avUCP), as putative regulators of mitochondrial oxidative phosphorylation, may contribute to the ability of king penguins (Aptenodytes patagonicus) to withstand fasting for several weeks. After 20 days of fasting, king penguins showed a reduced rate of whole animal oxygen consumption (Vo2; -33%) at rest, together with a reduced abundance of avUCP and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1-alpha) mRNA in pectoralis muscle (-54%, -36%, respectively). These parameters were restored after the birds had been refed for 3 days. Furthermore, in recently fed, but not in fasted penguins, isolated muscle mitochondria showed a guanosine diphosphate-inhibited, fatty acid plus superoxide-activated respiration, indicating the presence of a functional UCP. It was calculated that variation in mitochondrial UCP-dependent respiration in vitro may contribute to nearly 20% of the difference in resting Vo2 between fed or refed penguins and fasted penguins measured in vivo. These results suggest that the lowering of avUCP activity during periods of long-term energetic restriction may contribute to the reduction in metabolic rate and hence the ability of king penguins to face prolonged periods of fasting.

Fast But Fleeting: Adaptive Motor Learning Processes Associated with Aging and Cognitive Decline

Science.gov (United States)

Trewartha, Kevin M.; Garcia, Angeles; Wolpert, Daniel M.

2014-01-01

Motor learning has been shown to depend on multiple interacting learning processes. For example, learning to adapt when moving grasped objects with novel dynamics involves a fast process that adapts and decays quickly—and that has been linked to explicit memory—and a slower process that adapts and decays more gradually. Each process is characterized by a learning rate that controls how strongly motor memory is updated based on experienced errors and a retention factor determining the movement-to-movement decay in motor memory. Here we examined whether fast and slow motor learning processes involved in learning novel dynamics differ between younger and older adults. In addition, we investigated how age-related decline in explicit memory performance influences learning and retention parameters. Although the groups adapted equally well, they did so with markedly different underlying processes. Whereas the groups had similar fast processes, they had different slow processes. Specifically, the older adults exhibited decreased retention in their slow process compared with younger adults. Within the older group, who exhibited considerable variation in explicit memory performance, we found that poor explicit memory was associated with reduced retention in the fast process, as well as the slow process. These findings suggest that explicit memory resources are a determining factor in impairments in the both the fast and slow processes for motor learning but that aging effects on the slow process are independent of explicit memory declines. PMID:25274819

Fast but fleeting: adaptive motor learning processes associated with aging and cognitive decline.

Science.gov (United States)

Trewartha, Kevin M; Garcia, Angeles; Wolpert, Daniel M; Flanagan, J Randall

2014-10-01

Motor learning has been shown to depend on multiple interacting learning processes. For example, learning to adapt when moving grasped objects with novel dynamics involves a fast process that adapts and decays quickly-and that has been linked to explicit memory-and a slower process that adapts and decays more gradually. Each process is characterized by a learning rate that controls how strongly motor memory is updated based on experienced errors and a retention factor determining the movement-to-movement decay in motor memory. Here we examined whether fast and slow motor learning processes involved in learning novel dynamics differ between younger and older adults. In addition, we investigated how age-related decline in explicit memory performance influences learning and retention parameters. Although the groups adapted equally well, they did so with markedly different underlying processes. Whereas the groups had similar fast processes, they had different slow processes. Specifically, the older adults exhibited decreased retention in their slow process compared with younger adults. Within the older group, who exhibited considerable variation in explicit memory performance, we found that poor explicit memory was associated with reduced retention in the fast process, as well as the slow process. These findings suggest that explicit memory resources are a determining factor in impairments in the both the fast and slow processes for motor learning but that aging effects on the slow process are independent of explicit memory declines. Copyright © 2014 the authors 0270-6474/14/3413411-11$15.00/0.

Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

International Nuclear Information System (INIS)

Tang, Chunling; Yang, Liqun; Jiang, Xiaolan; Xu, Chuan; Wang, Mei; Wang, Qinrui; Zhou, Zhansong; Xiang, Zhonghuai; Cui, Hongjuan

2014-01-01

Highlights: • Tigecycline inhibited cell growth and proliferation in human gastric cancer cells. • Tigecycline induced autophagy not apoptosis in human gastric cancer cells. • AMPK/mTOR/p70S6K pathway was activated after tigecycline treatment. • Tigecycline inhibited tumor growth in xenograft model of human gastric cancer cells. - Abstract: Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer

Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

Energy Technology Data Exchange (ETDEWEB)

Tang, Chunling; Yang, Liqun; Jiang, Xiaolan [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Xu, Chuan [Division of Scientific Research and Training, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083 (China); Wang, Mei; Wang, Qinrui [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Zhou, Zhansong, E-mail: zhouzhans@sina.com [Institute of Urinary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Xiang, Zhonghuai [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Cui, Hongjuan, E-mail: hcui@swu.edu.cn [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China)

2014-03-28

Highlights: • Tigecycline inhibited cell growth and proliferation in human gastric cancer cells. • Tigecycline induced autophagy not apoptosis in human gastric cancer cells. • AMPK/mTOR/p70S6K pathway was activated after tigecycline treatment. • Tigecycline inhibited tumor growth in xenograft model of human gastric cancer cells. - Abstract: Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer.

Sox17 regulates liver lipid metabolism and adaptation to fasting.

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Samuel Rommelaere

Full Text Available Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/- mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting.

Impact of Prolonged Fasting on the Risk of Calcium Phosphate Precipitation in the Urine: Calcium Phosphate Lithogenesis during Prolonged Fasting in a Healthy Cohort.

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Shafiee, Mohammad A; Aarabi, Mehdi; Shaker, Pouyan; Ghafarian, Amir M; Chamanian, Pouyan; Halperin, Mitchell L

2018-03-02

Intermittent fasting and curtailing water intake for extended periods were likely common in Paleolithic times. Today it occurs for religious and dietary reasons. This restriction in intake should cause a decrease in the urine flow rate while raising the concentration of certain substances in urine to the point of precipitation. In this study we measured the risk of CaHPO 4 precipitation following 18 hours of food and water deprivation. Urine samples were periodically collected from 15 healthy subjects who fasted and abstained from drinking any liquid for 18 hours. The urine constituents Ca 2+ , HPO 4 2- and pH involved in CaHPO 4 formation were measured at various times throughout the fasting day. A comparison was made with control data, which consisted of diurnal urine collections taken throughout a separate nonfasting day prior to the fasting day. The mean ± SEM urine flow rate decreased significantly from 0.93 ± 0.1 ml per minute in the control group to 0.37 ± 0.05 ml per minute in the fasting group (p water deprivation, there was no evidence that the calculated risk of CaHPO 4 precipitation in the healthy subjects had increased. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Inhibition of the primary motor cortex and the upgoing thumb sign

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Antonia Nucera

2017-09-01

Full Text Available Background: The upgoing thumb sign has been frequently observed in patients with minor strokes and transient ischemic attacks as an indicator of brain involvement. We assessed the effect of primary motor cortex (M1 inhibition in the development of the upgoing thumb sign. Methods: Used repetitive Transcranial Magnetic Stimulation (rTMS, 1Hz frequency for 15min, 1s ISI, 900 pulses at 60% of resting motor threshold to inhibit the right or left primary motor cortex of 10 healthy individuals. Participants were examined before and after rTMS by a neurologist who was blind to the site of motor cortex inhibition. Results: 10 neurological intact participants (5 women/5 men were recruited for this study. 2 cases were excluded due to pre-existing possible thumb signs. After the inhibition of the primary motor cortex, in 6 subjects out of 8, we observed a thumb sign contralateral to the site of primary motor cortex inhibition. In one subject an ipsilateral thumbs sign was noted. In another case, we did not find an upgoing thumb sign. Conclusion: The upgoing thumb sign is a subtle neurological finding that may be related to the primary motor cortex or corticospinal pathways involvements. Keywords: Corticospinal tract, Upper motor neuron lesions, Primary motor cortex, Transcranial magnetic stimulation

Teacher Involvement in Adult Marketing Education: Impeding Factors and Enhancing Strategies.

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Price, William T., Jr.

1988-01-01

Using the nominal group technique, 60 of the 323 high school marketing teachers in Virginia identified major factors impeding their involvement in adult marketing education as lack of time and demands of the job. Insufficient compensation for working with adults and lack of administrator support also inhibited teacher involvement in adult…

Lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFα) blunt the response of Neuropeptide Y/Agouti-related peptide (NPY/AgRP) glucose inhibited (GI) neurons to decreased glucose.

Science.gov (United States)

Hao, Lihong; Sheng, Zhenyu; Potian, Joseph; Deak, Adam; Rohowsky-Kochan, Christine; Routh, Vanessa H

2016-10-01

A population of Neuropeptide Y (NPY) neurons which co-express Agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus (ARC) are inhibited at physiological levels of brain glucose and activated when glucose levels decline (e.g. glucose-inhibited or GI neurons). Fasting enhances the activation of NPY/AgRP-GI neurons by low glucose. In the present study we tested the hypothesis that lipopolysaccharide (LPS) inhibits the enhanced activation of NPY/AgRP-GI neurons by low glucose following a fast. Mice which express green fluorescent protein (GFP) on their NPY promoter were used to identify NPY/AgRP neurons. Fasting for 24h and LPS injection decreased blood glucose levels. As we have found previously, fasting increased c-fos expression in NPY/AgRP neurons and increased the activation of NPY/AgRP-GI neurons by decreased glucose. As we predicted, LPS blunted these effects of fasting at the 24h time point. Moreover, the inflammatory cytokine tumor necrosis factor alpha (TNFα) blocked the activation of NPY/AgRP-GI neurons by decreased glucose. These data suggest that LPS and TNFα may alter glucose and energy homeostasis, in part, due to changes in the glucose sensitivity of NPY/AgRP neurons. Interestingly, our findings also suggest that NPY/AgRP-GI neurons use a distinct mechanism to sense changes in extracellular glucose as compared to our previous studies of GI neurons in the adjacent ventromedial hypothalamic nucleus. Copyright © 2016 Elsevier B.V. All rights reserved.

Fast instrumentation for loss of coolant accident (LOCA) experimental studies pertaining to nuclear reactors

International Nuclear Information System (INIS)

Venkat Raj, V.; Sreenivas Rao, G.; Belokar, D.G.; Dolas, P.K.

1989-01-01

The loss of coolant accident (LOCA) which involves a breach in the pressure boundary of the primary coolant system (PCS) is one of the postulated accident conditions against which the safety of the reactor system is to be ensured. Mathematical models have been developed to analyse this kind of transients. However, because of the extremely complicated nature of the phenomena involved, it is necessary to validate the analytical models with appropriate experimental data. Many parameters are to be measured during the experiments, out of which temperature, pressure, void fraction and two-phase mass flow rate are the most important parameters. Since the phenomenon is very fast, special fast response instruments are required. This paper deals with the considerations that govern the selection of appropriate instruments and the development of suitable instruments for transient two-phase flow and void fraction measurements. The requirements of the associated fast data acquisition system are also discussed. (author). 4 figs

Fast Food Jobs. National Study of Fast Food Employment.

Science.gov (United States)

Charner, Ivan; Fraser, Bryna Shore

A study examined employment in the fast-food industry. The national survey collected data from employees at 279 fast-food restaurants from seven companies. Female employees outnumbered males by two to one. The ages of those fast-food employees in the survey sample ranged from 14 to 71, with fully 70 percent being in the 16- to 20-year-old age…

Effects of Ramadan fasting on glucose homeostasis and adiponectin levels in healthy adult males.

Science.gov (United States)

Gnanou, Justin V; Caszo, Brinnell A; Khalil, Khalifah M; Abdullah, Shahidah L; Knight, Victor F; Bidin, Mohd Z

2015-01-01

Adiponectin is a hormone secreted by adipocytes during the fasting phase of the fast-fed cycle. Ramadan fasting involves prolonged fasting for up to twelve hours and thus could lead to increased secretion of adiponectin by adipocytes. However, studies on the role of adiponectin on glucose and body weight homeostasis during Ramadan fasting is still a matter of controversy. Thus the specific aim of this study was to assess the effect of fasting during Ramadan on the adiponectin levels, body weight and glucose homeostasis in healthy male Malaysian subjects. Twenty healthy male (19-23 years) Muslim subjects were followed up during the fasting month of Ramadan. Anthropometry and blood samples were taken one week before and during the fourth week of fasting. Plasma glucose, insulin and adiponectin were estimated and insulin sensitivity indices were estimated using the Homeostasis Model Assessment. Subjects experienced a significant decrease in body weight (2.4 %, p Ramadan fasting in young healthy individuals has a positive impact on the maintenance of glucose homeostasis. It also shows that adiponectin levels dropped along with significant loss in weight. We feel caloric restriction during the Ramadan fasting is in itself sufficient to improve insulin sensitivity in healthy individuals.

Fast Particle Interaction With Waves In Fusion Plasmas

International Nuclear Information System (INIS)

Breizman, Boris

2006-01-01

There are two well-known motivations for theoretical studies of fast particle interaction with waves in magnetic confinement devices. One is the challenge of avoiding strong collective losses of alpha particles and beam ions in future burning plasma experiments. The other one is the compelling need to quantitatively interpret the large amount of experimental data from JET, TFTR, JT-60U, DIII-D, and other machines. Such interpretation involves unique diagnostic opportunities offered by MHD spectroscopy. This report discusses how the present theory responds to the stated challenges and what theoretical and computational advances are required to address the outstanding problems. More specifically, this paper deals with the following topics: predictive capabilities of linear theory and simulations; theory of Alfven cascades; diagnostic opportunities based on linear and nonlinear properties of unstable modes; interplay of kinetic and fluid nonlinearities; fast chirping phenomena for non-perturbative modes; and global transport of fast particles. Recent results are presented on some of the listed topics, although the main goal is to identify critical issues for future work

Customer Involvement in the Game Development Process

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Kaja Prystupa-Rządca

2015-01-01

Full Text Available The creative industry is a fast developing sector of economy in many countries. Growing competition in this area has led many companies to implement strategy of users' involvement in product development in order to deliver products that are more aligned with customers’ needs. On the other hand, the attempt to align the customers’ expectations with artistic creativity may create tensions. Therefore, the aim of the research is to examine the methods of users’ involvement in product development and real impact of the users on project design. The obtained findings are based on two-year qualitative research project conducted in game development companies.

Neurotensin releases norepinephrine differentially from perfused hypothalamus of sated and fasted rat

International Nuclear Information System (INIS)

Lee, T.F.; Rezvani, A.H.; Hepler, J.R.; Myers, R.D.

1987-01-01

The central injection of neurotensin (NT) has been reported to attenuate the intake of food in the fasted animal. To determine whether endogenous norepinephrine (NE) is involved in the satiating effect of NT, the in vivo activity of NE in circumscribed sites in the hypothalamus of the unanesthetized rat was examined. Bilateral guide tubes for push-pull perfusion were implanted stereotaxically to rest permanently above one of several intended sites of perfusion, which included the paraventricular nucleus (PVN), ventromedial nucleus (VMN), and the lateral hypothalamic (LH) area. After endogenous stores of NE at a specific hypothalamic locus were radiolabeled by microinjection of 0.02-0.5 μCi of [ 3 H]NE, an artificial cerebrospinal fluid was perfused at the site at a rate of 20 μl/min over successive intervals of 5.0 min. When 0.05 or 0.1 μg/μl NT was added to the perfusate, the peptide served either to enhance or educe the local release of NE at 50% of the sites of perfusion. In these experiments, the circumscribed effect of NT on the characteristics of catecholamine efflux depended entirely on the state of hunger or satiety of the rat. That is, when NT was perfused in the fully satiated rat, NE release was augmented within the PVn or VMN; conversely, NE release was inhibited in the LH. in the animal fasted for 18-22 h, NT exerted an opposite effect on the activity of NE within the same anatomical loci in that the efflux of NE was enhanced in the LH but attenuated or unaffected in the PVN or VMN. Taken together, these observations provide experimental support for the view-point that NT could act as a neuromodulator of the activity of hypothalamic noradrenergic neurons that are thought to play a functional role in the regulation of food intake

Down-regulation of adipose tissue lipoprotein lipase during fasting requires that a gene, separate from the lipase gene, is switched on.

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Bergö, Martin; Wu, Gengshu; Ruge, Toralph; Olivecrona, Thomas

2002-04-05

During short term fasting, lipoprotein lipase (LPL) activity in rat adipose tissue is rapidly down-regulated. This down-regulation occurs on a posttranslational level; it is not accompanied by changes in LPL mRNA or protein levels. The LPL activity can be restored within 4 h by refeeding. Previously, we showed that during fasting there is a shift in the distribution of lipase protein toward an inactive form with low heparin affinity. To study the nature of the regulatory mechanism, we determined the in vivo turnover of LPL activity, protein mass, and mRNA in rat adipose tissue. When protein synthesis was inhibited with cycloheximide, LPL activity and protein mass decreased rapidly and in parallel with half-lives of around 2 h, and the effect of refeeding was blocked. This indicates that maintaining high levels of LPL activity requires continuous synthesis of new enzyme protein. When transcription was inhibited by actinomycin, LPL mRNA decreased with half-lives of 13.3 and 16.8 h in the fed and fasted states, respectively, demonstrating slow turnover of the LPL transcript. Surprisingly, when actinomycin was given to fed rats, LPL activity was not down-regulated during fasting, indicating that actinomycin interferes with the transcription of a gene that blocks the activation of newly synthesized LPL protein. When actinomycin was given to fasted rats, LPL activity increased 4-fold within 6 h, even in the absence of refeeding. The same effect was seen with alpha-amanitin, another inhibitor of transcription. The response to actinomycin was much less pronounced in aging rats, which are obese and insulin-resistant. These data suggest a default state where LPL protein is synthesized on a relatively stable mRNA and is processed into its active form. During fasting, a gene is switched on whose product prevents the enzyme from becoming active even though synthesis of LPL protein continues unabated.

Perturbations of amino acid metabolism associated with glyphosate-dependent inhibition of shikimic acid metabolism affect cellular redox homeostasis and alter the abundance of proteins involved in photosynthesis and photorespiration.

Science.gov (United States)

Vivancos, Pedro Diaz; Driscoll, Simon P; Bulman, Christopher A; Ying, Liu; Emami, Kaveh; Treumann, Achim; Mauve, Caroline; Noctor, Graham; Foyer, Christine H

2011-09-01

The herbicide glyphosate inhibits the shikimate pathway of the synthesis of amino acids such as phenylalanine, tyrosine, and tryptophan. However, much uncertainty remains concerning precisely how glyphosate kills plants or affects cellular redox homeostasis and related processes in glyphosate-sensitive and glyphosate-resistant crop plants. To address this issue, we performed an integrated study of photosynthesis, leaf proteomes, amino acid profiles, and redox profiles in the glyphosate-sensitive soybean (Glycine max) genotype PAN809 and glyphosate-resistant Roundup Ready Soybean (RRS). RRS leaves accumulated much more glyphosate than the sensitive line but showed relatively few changes in amino acid metabolism. Photosynthesis was unaffected by glyphosate in RRS leaves, but decreased abundance of photosynthesis/photorespiratory pathway proteins was observed together with oxidation of major redox pools. While treatment of a sensitive genotype with glyphosate rapidly inhibited photosynthesis and triggered the appearance of a nitrogen-rich amino acid profile, there was no evidence of oxidation of the redox pools. There was, however, an increase in starvation-associated and defense proteins. We conclude that glyphosate-dependent inhibition of soybean leaf metabolism leads to the induction of defense proteins without sustained oxidation. Conversely, the accumulation of high levels of glyphosate in RRS enhances cellular oxidation, possibly through mechanisms involving stimulation of the photorespiratory pathway.

INHIBITION OF SPONTANEOUS APOPTOSIS IN HUMAN BREAST CANCER

Institute of Scientific and Technical Information of China (English)

邵志敏; 江明; 吴炅; 余黎民; 韩企夏; 张延璆; 沈镇宙

1996-01-01

Breast tumorigenesis proceeds through an accumulation of specific genetic alteration. Breast malignant transformation is dependent on not only the rate of cell production but also on apoptcsis,a genetically prograined process of autonomous ceil death. We investigated whether breast tumorigenesis involved an altered susceptibility to apoptosis and proliferation by examining normal breast epithelium and breast cancer sampies. We found there is a great inhibition of spontaneous apoptosis in breast cancer ceils compared with normal breast epithelium. The inhibition of apoptosis in breast cancer may contribute to neoplastic transformation.

miRNA targeted signaling pathway in the early stage of denervated fast and slow muscle atrophy

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Gang Li

2016-01-01

Full Text Available Denervation often results in skeletal muscle atrophy. Different mechanisms seem to be involved in the determination between denervated slow and fast skeletal muscle atrophy. At the epigenetic level, miRNAs are thought to be highly involved in the pathophysiological progress of denervated muscles. We used miRNA microarrays to determine miRNA expression profiles from a typical slow muscle (soleus muscle and a typical fast muscle (tibialis anterior muscle at an early denervation stage in a rat model. Results showed that miR-206, miR-195, miR-23a, and miR-30e might be key factors in the transformation process from slow to fast muscle in denervated slow muscles. Additionally, certain miRNA molecules (miR-214, miR-221, miR-222, miR-152, miR-320, and Let-7e could be key regulatory factors in the denervated atrophy process involved in fast muscle. Analysis of signaling pathway networks revealed the miRNA molecules that were responsible for regulating certain signaling pathways, which were the final targets (e.g., p38 MAPK pathway; Pax3/Pax7 regulates Utrophin and follistatin by HDAC4; IGF1/PI3K/Akt/mTOR pathway regulates atrogin-1 and MuRF1 expression via FoxO phosphorylation. Our results provide a better understanding of the mechanisms of denervated skeletal muscle pathophysiology.

Food, stress, and reproduction: short-term fasting alters endocrine physiology and reproductive behavior in the zebra finch.

Science.gov (United States)

Lynn, Sharon E; Stamplis, Teresa B; Barrington, William T; Weida, Nicholas; Hudak, Casey A

2010-07-01

Stress is thought to be a potent suppressor of reproduction. However, the vast majority of studies focus on the relationship between chronic stress and reproductive suppression, despite the fact that chronic stress is rare in the wild. We investigated the role of fasting in altering acute stress physiology, reproductive physiology, and reproductive behavior of male zebra finches (Taeniopygia guttata) with several goals in mind. First, we wanted to determine if acute fasting could stimulate an increase in plasma corticosterone and a decrease in corticosteroid binding globulin (CBG) and testosterone. We then investigated whether fasting could alter expression of undirected song and courtship behavior. After subjecting males to fasting periods ranging from 1 to 10h, we collected plasma to measure corticosterone, CBG, and testosterone. We found that plasma corticosterone was elevated, and testosterone was decreased after 4, 6, and 10h of fasting periods compared with samples collected from the same males during nonfasted (control) periods. CBG was lower than control levels only after 10h of fasting. We also found that, coincident with these endocrine changes, males sang less and courted females less vigorously following short-term fasting relative to control conditions. Our data demonstrate that acute fasting resulted in rapid changes in endocrine physiology consistent with hypothalamo-pituitary-adrenal axis activation and hypothalamo-pituitary-gonadal axis deactivation. Fasting also inhibited reproductive behavior. We suggest that zebra finches exhibit physiological and behavioral flexibility that makes them an excellent model system for studying interactions of acute stress and reproduction. Copyright 2010 Elsevier Inc. All rights reserved.

Pineal-mediated inhibition of prolactin cell activity: Investigation of dopaminergic involvement

International Nuclear Information System (INIS)

Burns, D.M.

1989-01-01

The present studies in the male Syrian hamster addressed two issues. First, it was of interest to determine if anterior pituitaries of long photoperiod-exposed male hamsters possess dopamine receptors, which are presumably necessary for responsiveness to dopamine. This was accomplished by analysis of 3 H-spiperone binding to anterior pituitary membranes. Second, possible changes in pituitary sensitivity to dopamine were assessed by comparison of dose response curves for the inhibition by dopamine of prolactin release from hemipituitaries incubated in vitro from both long and short photoperiod-exposed animals over a series of time points from three to fifteen weeks. In the second series of experiments, adult female F344 rats received daily injection of melatonin or saline vehicle. After two weeks, half of the animals were sacrificed for analysis of 3 H-spiperone binding to anterior pituitary membranes, measurement of hypothalamic dopamine turnover and analysis of in vitro pituitary sensitivity to dopamine. The remaining animals received subcutaneous implants containing DES and injections were continued on the same schedule until sacrifice four weeks later for measurement of the same parameters

Obesity is marked by distinct functional connectivity in brain networks involved in food reward and salience.

Science.gov (United States)

Wijngaarden, M A; Veer, I M; Rombouts, S A R B; van Buchem, M A; Willems van Dijk, K; Pijl, H; van der Grond, J

2015-01-01

We hypothesized that brain circuits involved in reward and salience respond differently to fasting in obese versus lean individuals. We compared functional connectivity networks related to food reward and saliency after an overnight fast (baseline) and after a prolonged fast of 48 h in lean versus obese subjects. We included 13 obese (2 males, 11 females, BMI 35.4 ± 1.2 kg/m(2), age 31 ± 3 years) and 11 lean subjects (2 males, 9 females, BMI 23.2 ± 0.5 kg/m(2), age 28 ± 3 years). Resting-state functional magnetic resonance imaging scans were made after an overnight fast (baseline) and after a prolonged 48 h fast. Functional connectivity of the amygdala, hypothalamus and posterior cingulate cortex (default-mode) networks was assessed using seed-based correlations. At baseline, we found a stronger connectivity between hypothalamus and left insula in the obese subjects. This effect diminished upon the prolonged fast. After prolonged fasting, connectivity of the hypothalamus with the dorsal anterior cingulate cortex (dACC) increased in lean subjects and decreased in obese subjects. Amygdala connectivity with the ventromedial prefrontal cortex was stronger in lean subjects at baseline, which did not change upon the prolonged fast. No differences in posterior cingulate cortex connectivity were observed. In conclusion, obesity is marked by alterations in functional connectivity networks involved in food reward and salience. Prolonged fasting differentially affected hypothalamic connections with the dACC and the insula between obese and lean subjects. Our data support the idea that food reward and nutrient deprivation are differently perceived and/or processed in obesity. Copyright © 2015 Elsevier B.V. All rights reserved.

Inhibition of the differentiation of monocyte-derived dendritic cells by human gingival fibroblasts.

Directory of Open Access Journals (Sweden)

Sylvie Séguier

Full Text Available We investigated whether gingival fibroblasts (GFs can modulate the differentiation and/or maturation of monocyte-derived dendritic cells (DCs and analyzed soluble factors that may be involved in this immune modulation. Experiments were performed using human monocytes in co-culture with human GFs in Transwell® chambers or using monocyte cultures treated with conditioned media (CM from GFs of four donors. The four CM and supernatants from cell culture were assayed by ELISA for cytokines involved in the differentiation of dendritic cells, such as IL-6, VEGF, TGFβ1, IL-13 and IL-10. The maturation of monocyte-derived DCs induced by LPS in presence of CM was also studied. Cell surface phenotype markers were analyzed by flow cytometry. In co-cultures, GFs inhibited the differentiation of monocyte-derived DCs and the strength of this blockade correlated with the GF/monocyte ratio. Conditioned media from GFs showed similar effects, suggesting the involvement of soluble factors produced by GFs. This inhibition was associated with a lower stimulatory activity in MLR of DCs generated with GFs or its CM. Neutralizing antibodies against IL-6 and VEGF significantly (P<0.05 inhibited the inhibitory effect of CM on the differentiation of monocytes-derived DCs and in a dose dependent manner. Our data suggest that IL-6 is the main factor responsible for the inhibition of DCs differentiation mediated by GFs but that VEGF is also involved and constitutes an additional mechanism.

Selective inhibition of extracellular oxidants liberated from human neutrophils--A new mechanism potentially involved in the anti-inflammatory activity of hydroxychloroquine.

Science.gov (United States)

Jančinová, Viera; Pažoureková, Silvia; Lucová, Marianna; Perečko, Tomáš; Mihalová, Danica; Bauerová, Katarína; Nosáľ, Radomír; Drábiková, Katarína

2015-09-01

Hydroxychloroquine is used in the therapy of rheumatoid arthritis or lupus erythematosus. Although these diseases are often accompanied by activation of neutrophils, there are still few data relating to the impact of hydroxychloroquine on these cells. We investigated the effect of orally administered hydroxychloroquine on neutrophil oxidative burst in rats with adjuvant arthritis. In human neutrophils, extra- and intracellular formation of oxidants, mobilisation of intracellular calcium and the phosphorylation of proteins regulating NADPH oxidase assembly were analysed. Administration of hydroxychloroquine decreased the concentration of oxidants in blood of arthritic rats. The inhibition was comparable with the reference drug methotrexate, yet it was not accompanied by a reduction in neutrophil count. When both drugs were co-applied, the effect became more pronounced. In isolated human neutrophils, treatment with hydroxychloroquine resulted in reduced mobilisation of intracellular calcium, diminished concentration of external oxidants and in decreased phosphorylation of Ca(2+)-dependent protein kinase C isoforms PKCα and PKCβII, which regulate activation of NADPH oxidase on plasma membrane. On the other hand, no reduction was observed in intracellular oxidants or in the phosphorylation of p40(phox) and PKCδ, two proteins directing the oxidase assembly to intracellular membranes. Hydroxychloroquine reduced neutrophil-derived oxidants potentially involved in tissue damage and protected those capable to suppress inflammation. The observed effects may represent a new mechanism involved in the anti-inflammatory activity of this drug. Copyright © 2015 Elsevier B.V. All rights reserved.

European Union: Review of fast reactor related activities

International Nuclear Information System (INIS)

Goethem, G. van; Hugon, M.

1998-01-01

The European Commission (EC) continued its fast reactor research activities on the same lines as in the past, but with the main emphasis on partitioning and transmutation (P and T) of long-lived radionuclides. The work was carried out by research institutions in the Member States and by the EC Joint Research Centre (JRC) as cost shared actions. The JRC has also been performing its own programme through institutional and competitive research activities. The JRC institutes involved in these studies are the Institute of Systems, Informatics and Safety (ISIS) in Ispra (I), the Institute for Transuranium Elements (ITU) in Karlsruhe (D) and the Institute for Advanced Materials in Petten. This paper summarizes the main activities performed in the field of (i) fast reactor safety and of (ii) partitioning and transmutation. (author)

Butenolide inhibits marine fouling by altering the primary metabolism of three target organisms

KAUST Repository

Zhang, Yifan

2012-06-15

Butenolide is a very promising antifouling compound that inhibits ship hull fouling by a variety of marine organisms, but its antifouling mechanism was previously unknown. Here we report the first study of butenolides molecular targets in three representative fouling organisms. In the barnacle Balanus (=Amphibalanus) amphitrite, butenolide bound to acetyl-CoA acetyltransferase 1 (ACAT1), which is involved in ketone body metabolism. Both the substrate and the product of ACAT1 increased larval settlement under butenolide treatment, suggesting its functional involvement. In the bryozoan Bugula neritina, butenolide bound to very long chain acyl-CoA dehydrogenase (ACADVL), actin, and glutathione S-transferases (GSTs). ACADVL is the first enzyme in the very long chain fatty acid β-oxidation pathway. The inhibition of this primary pathway for energy production in larvae by butenolide was supported by the finding that alternative energy sources (acetoacetate and pyruvate) increased larval attachment under butenolide treatment. In marine bacterium Vibrio sp. UST020129-010, butenolide bound to succinyl-CoA synthetase β subunit (SCSβ) and inhibited bacterial growth. ACAT1, ACADVL, and SCSβ are all involved in primary metabolism for energy production. These findings suggest that butenolide inhibits fouling by influencing the primary metabolism of target organisms. © 2012 American Chemical Society.

A low thermal mass fast gas chromatograph and its implementation in fast gas chromatography mass spectrometry with supersonic molecular beams.

Science.gov (United States)

Fialkov, Alexander B; Moragn, Mati; Amirav, Aviv

2011-12-30

fast GC and fast GC-MS and the various trade-offs involved in having powerful and practical fast GC-MS. Copyright © 2011 Elsevier B.V. All rights reserved.

The fast reactor

International Nuclear Information System (INIS)

1980-02-01

The subject is discussed as follows: brief description of fast reactors; advantage in conserving uranium resources; experience, in UK and elsewhere, in fast reactor design, construction and operation; safety; production of plutonium, security aspects; consideration of future UK fast reactor programme. (U.K.)

Become Involved with Someone Who Is on the Rebound?: How Fast Should You Run?

Science.gov (United States)

Knox, David; Zusman, Marty E.

2009-01-01

Analysis of survey data from 1002 undergraduates at a large southeastern university revealed differences between the 535 or 53.4% who had become involved (while on the rebound from a previous love relationship) in a new relationship compared to 316 or 31.5% who had not become involved in a new relationship while on the rebound. A profile of the…

Inorganic component of saliva during fasting and after fast break

OpenAIRE

Samad, Rasmidar

2016-01-01

Oral health is closely related to salivary components. Saliva consists of water, inorganic and organic materials. Fasting changes one???s meal and drinking time that in turn can affect the environment in oral cavity, including inorganic componenet of saliva. The purpose of this study is to determine the inorganic component of saliva during fasting and after fast break.

Cellular mechanisms for presynaptic inhibition of sensory afferents

DEFF Research Database (Denmark)

Perrier, Jean-Francois Marie; delgado-lezama, rodolfo; Christensen, Rasmus Kordt

It is well established that presynaptic inhibition of primary afferents involves the activation of GABAA receptors located on presynaptic terminals. However, the source of GABA remains unknown. In an integrated preparation of the spinal cord of the adult turtle, we evoked dorsal root potentials...

Effects of a 5-HT(3) antagonist, ondansetron, on fasting and postprandial small bowel water content assessed by magnetic resonance imaging.

Science.gov (United States)

Marciani, L; Wright, J; Foley, S; Hoad, C L; Totman, J J; Bush, D; Hartley, C; Armstrong, A; Manby, P; Blackshaw, E; Perkins, A C; Gowland, P A; Spiller, R C

2010-09-01

5-HT(3) antagonists have been shown to be effective in relieving the symptoms of irritable bowel syndrome with diarrhoea (IBS-D). Using a recently validated magnetic resonance imaging (MRI) method, we have demonstrated reduced fasting small bowel water content (SBWC) in IBS-D associated with accelerated small bowel transit. We hypothesized that slowing of transit with ondansetron would lead to an increase in SBWC by inhibiting fasting motility. To assess the effects of ondansetron compared with placebo in healthy volunteers on SBWC and motility in two different groups of subjects, one studied using MRI and another using manometry. Healthy volunteers were given either a placebo or ondansetron on the day prior to and on the study day. Sixteen volunteers underwent baseline fasting and postprandial MRI scans for 270 min. In a second study, a separate group of n = 18 volunteers were intubated and overnight migrating motor complex (MMC) recorded. Baseline MRI scans were carried out after the tube was removed. Fasting SBWC was markedly increased by ondansetron (P fasting SBWC (P fasting small bowel water. This was associated with reduced fasting antroduodenal Motility Index which may explain the clinical benefit of such drugs. 2010 Blackwell Publishing Ltd.

Proximity to Fast-Food Outlets and Supermarkets as Predictors of Fast-Food Dining Frequency.

Science.gov (United States)

Athens, Jessica K; Duncan, Dustin T; Elbel, Brian

2016-08-01

This study used cross-sectional data to test the independent relationship of proximity to chain fast-food outlets and proximity to full-service supermarkets on the frequency of mealtime dining at fast-food outlets in two major urban areas, using three approaches to define access. Interactions between presence of a supermarket and presence of fast-food outlets as predictors of fast-food dining were also tested. Residential intersections for respondents in point-of-purchase and random-digit-dial telephone surveys of adults in Philadelphia, PA, and Baltimore, MD, were geocoded. The count of fast-food outlets and supermarkets within quarter-mile, half-mile, and 1-mile street network buffers around each respondent's intersection was calculated, as well as distance to the nearest fast-food outlet and supermarket. These variables were regressed on weekly fast-food dining frequency to determine whether proximity to fast food and supermarkets had independent and joint effects on fast-food dining. The effect of access to supermarkets and chain fast-food outlets varied by study population. Among telephone survey respondents, supermarket access was the only significant predictor of fast-food dining frequency. Point-of-purchase respondents were generally unaffected by proximity to either supermarkets or fast-food outlets. However, ≥1 fast-food outlet within a 1-mile buffer was an independent predictor of consuming more fast-food meals among point-of-purchase respondents. At the quarter-mile distance, ≥1 supermarket was predictive of fewer fast-food meals. Supermarket access was associated with less fast-food dining among telephone respondents, whereas access to fast-food outlets were associated with more fast-food visits among survey respondents identified at point-of-purchase. This study adds to the existing literature on geographic determinants of fast-food dining behavior among urban adults in the general population and those who regularly consume fast food. Copyright �

The Argentine-Brazilian fast reactor programme

International Nuclear Information System (INIS)

Gho, C.J.; Mauricio, A.

1989-01-01

This paper summarizes the Argentine-Brazilian Fast Reactor Programme and gives reasons for the decision of a binational venture. The work carried out by both countries is described, showing how they complement each other, with the corresponding saving of resources. The main objectives of the Programme and tentative schedules in three progressing integrating stages are given and the present nuclear know-how in each country is identified as a good starting point. The paper also gives some details regarding the economical and human resources involved. (author). 1 graph

Neural circuits containing olfactory neurons are involved in prepulse inhibition of the startle reflex in rats

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Haichen eNiu

2015-03-01

Full Text Available Many neuropsychiatric disorders, such as schizophrenia, have been associated with abnormalities in the function of the olfactory system and prepulse inhibition (PPI of the startle reflex. However, whether these two abnormalities are related is unclear. The present study was designed to determine whether inhibiting olfactory sensory input via the infusion of zinc sulfate (ZnE, 0.17 M, 0.5 ml into the olfactory naris disrupts PPI. Furthermore, lidocaine/MK801 was bilaterally microinjected into the olfactory bulb (OB to examine whether the blockade of olfactory sensory input impairs PPI. To identify the neural projections that connect the olfaction- and PPI-related areas of the CNS, trans-synaptic retrograde tracing using a recombinant pseudorabies virus (PRV was performed. Our results demonstrated that blocking olfactory sensory input altered olfaction-related behavior. At the functional level, we demonstrated that the inhibition of olfactory sensory input impaired PPI of the startle response subsequent to a decrease in c-fos expression in relevant brain regions. Furthermore, the results of a similar and more robust experiment indicated that blocking olfactory sensory input via the microinjection of lidocaine/MK801 into the OB impaired PPI. At the circuit level, based on trans-synaptic retrograde tracing using PRV, we demonstrated that a large portion of the labeled neurons in several regions of the olfactory cortices connected to the pedunculopontine tegmental nucleus (PPTg. Thus, these data suggest that the olfactory system participates in the regulation of PPI and plays a role in the effect of PPI on the startle response in rats.

Contrast-enhanced fast fluid-attenuated inversion recovery MR imaging in patients with brain tumors

International Nuclear Information System (INIS)

Kim, Chan Kyo; Na, Dong Gyu; Ryoo, Wook Jae; Byun Hong Sik; Yoon, Hye Kyung; Kim, Jong hyun

2000-01-01

To assess the feasibility of contrast-enhanced fast fluid-attenuated inversion recovery (fast FLAIR) MR imaging in patients with brain tumors. This study involved 31 patients with pathologically proven brain tumors and nine with clinically diagnosed metastases. In all patients, T2-weighted, fast FLAIR, images were visual contrast-enhanced T1-weighted MR images were obtained. Contrast-enhanced fast FLAIR images were visually compared with other MR sequences in terms of tumor conspicuity. In order to distinguish tumor and surrounding edema, contrast-enhanced fast FLAIR images were compared with fast FLAIR and T2-weighted images. The tumor-to- white matter contrast-to-noise ratios (CNRs), as demonstrated by T2-weighted, fast FLAIR, contrast-enhanced fast FLAIR and contrast-enhanced T1-weighted imaging, were quantitatively assessed and compared. For the visual assessment of tumor conspicuity, contrast-enhanced fast FLAIR image imaging superior to fast FLAIR in 60% of cases (24/40), and superior to T2-weighted in 70% (28/40). Contrast-enhanced fast FLAIR imaging was inferior to contrast-enhanced T1-weighted in 58% of cases (23/40). For distinguishing between tumor and surrounding edema, contrast-enhanced fast FLAIR imaging was superior to fast FLAIR or T2-weighted in 22 of 27 tumors with peritumoral edema (81%). Quantitatively, CNR was the highest on contrast-enhanced fast FLAIR image and the lowest on fast FLAIR. For the detection of leptomeningeal metastases, contrast-enhanced fast FLAIR was partially superior to contrast-enhanced T1-weighted imaging in two of three high-grade gliomas. Although contrast-enhanced fast FLAIR imaging should not be seen as a replacement for conventional modalities, it provides additional informaton for assessment of the extent of glial cell tumors and leptomeningeal metastases in patients with brain tumors. (author)

Catalytic Fast Pyrolysis of Alcell Lignin with Nano-NiO

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Jiao Chen

2015-11-01

Full Text Available Catalytic fast pyrolysis of Alcell lignin with various additive ratios (5%, 10%, and 15%, mass ratio of nano-NiO was investigated using a horizontal pyrolyzer. Characterization methods, including Fourier transform infrared spectroscopy (FTIR, gas chromatography (GC, gas chromatography coupled with mass spectrometry (GC/MS, and elemental analysis, were utilized to identify the catalytic fast pyrolysis products. The results indicated that the nano-NiO catalyst had remarkable effects on the yield and quality of these products. The formation of gases, especially CO, CO2, and CH4, were greatly promoted when the additive ratio increased, while the formation of bio-char was clearly inhibited. However, when the additive ratio was 10%, the maximum yield of bio-oil (53.09 wt.% was obtained, and the corresponding maximum higher heating value (HHV was 25.33 MJ/kg. Furthermore, nano-NiO caused a large variation in the species of the compounds in bio-oil. Operating with the optimal nano-NiO additive ratio (10%, the carbon conversion rate was 65.50%, and the energy conversion rate was 74.53%.

Fast-ion Dα measurements of the fast-ion distribution (invited)

International Nuclear Information System (INIS)

Heidbrink, W. W.

2010-01-01

The fast-ion Dα (FIDA) diagnostic is an application of charge-exchange recombination spectroscopy. Fast ions that neutralize in an injected neutral beam emit Balmer-α light with a large Doppler shift. The spectral shift is exploited to distinguish the FIDA emission from other bright sources of Dα light. Background subtraction is the main technical challenge. A spectroscopic diagnostic typically achieves temporal, energy, and transverse spatial resolution of ∼1 ms, ∼10 keV, and ∼2 cm, respectively. Installations that use narrow-band filters achieve high spatial and temporal resolution at the expense of spectral information. For high temporal resolution, the bandpass-filtered light goes directly to a photomultiplier, allowing detection of ∼50 kHz oscillations in FIDA signal. For two-dimensional spatial profiles, the bandpass-filtered light goes to a charge-coupled device camera; detailed images of fast-ion redistribution at instabilities are obtained. Qualitative and quantitative models relate the measured FIDA signals to the fast-ion distribution function. The first quantitative comparisons between theory and experiment found excellent agreement in beam-heated magnetohydrodynamics (MHD)-quiescent plasmas. FIDA diagnostics are now in operation at magnetic-fusion facilities worldwide. They are used to study fast-ion acceleration by ion cyclotron heating, to detect fast-ion transport by MHD modes and microturbulence, and to study fast-ion driven instabilities.

Small-size pedestrian detection in large scene based on fast R-CNN

Science.gov (United States)

Wang, Shengke; Yang, Na; Duan, Lianghua; Liu, Lu; Dong, Junyu

2018-04-01

Pedestrian detection is a canonical sub-problem of object detection with high demand during recent years. Although recent deep learning object detectors such as Fast/Faster R-CNN have shown excellent performance for general object detection, they have limited success for small size pedestrian detection in large-view scene. We study that the insufficient resolution of feature maps lead to the unsatisfactory accuracy when handling small instances. In this paper, we investigate issues involving Fast R-CNN for pedestrian detection. Driven by the observations, we propose a very simple but effective baseline for pedestrian detection based on Fast R-CNN, employing the DPM detector to generate proposals for accuracy, and training a fast R-CNN style network to jointly optimize small size pedestrian detection with skip connection concatenating feature from different layers to solving coarseness of feature maps. And the accuracy is improved in our research for small size pedestrian detection in the real large scene.

Properties and mechanical behaviour of fuel cans of fast neutron reactors

International Nuclear Information System (INIS)

Cauvin, R.; Boutard, J.L.

1983-06-01

Mechanical properties of Stainless steel-316 irradiated up to 100 dpa in fast neutron reactors are examined. Microscopic phenomena involved are reviewed: precipitation, segregation, dislocations, vacancies. Influence on mechanical behaviour of materials are examined: tensile properties, creep, ductility. Consequences on reactor dimensioning are given in conclusion [fr

Fasts, feasts and festivals in diabetes-1: Glycemic management during Hindu fasts

Directory of Open Access Journals (Sweden)

Sanjay Kalra

2015-01-01

Full Text Available This communication is the first of a series on South Asian fasts, festivals, and diabetes, designed to spread awareness and stimulate research on this aspect of diabetes and metabolic care. It describes the various fasts observed as part of Hindu religion and offers a classification scheme for them, labeling them as infrequent and frequent. The infrequent fasts are further sub-classified as brief and prolonged, to facilitate a scientific approach to glycemic management during these fasts. Pre-fast counseling, non-pharmacological therapy, pharmacological modification, and post-fast debriefing are discussed in detail. All available drug classes and molecules are covered in this article, which provides guidance about necessary changes in dosage and timing of administration. While in no way exhaustive, the brief review offers a basic framework which diabetes care professionals can use to counsel and manage persons in their care who wish to observe various Hindu fasts.

Glucocorticoids activate the ATP-ubiquitin-dependent proteolytic system in skeletal muscle during fasting

Science.gov (United States)

Wing, S. S.; Goldberg, A. L.; Goldberger, A. L. (Principal Investigator)

1993-01-01

Glucocorticoids are essential for the increase in protein breakdown in skeletal muscle normally seen during fasting. To determine which proteolytic pathway(s) are activated upon fasting, leg muscles from fed and fasted normal rats were incubated under conditions that block or activate different proteolytic systems. After food deprivation (1 day), the nonlysosomal ATP-dependent process increased by 250%, as shown in experiments involving depletion of muscle ATP. Also, the maximal capacity of the lysosomal process increased 60-100%, but no changes occurred in the Ca(2+)-dependent or the residual energy-independent proteolytic processes. In muscles from fasted normal and adrenalectomized (ADX) rats, the protein breakdown sensitive to inhibitors of the lysosomal or Ca(2+)-dependent pathways did not differ. However, the ATP-dependent process was 30% slower in muscles from fasted ADX rats. Administering dexamethasone to these animals or incubating their muscles with dexamethasone reversed this defect. During fasting, when the ATP-dependent process rises, muscles show a two- to threefold increase in levels of ubiquitin (Ub) mRNA. However, muscles of ADX animals failed to show this response. Injecting dexamethasone into the fasted ADX animals increased muscle Ub mRNA within 6 h. Thus glucocorticoids activate the ATP-Ub-dependent proteolytic pathway in fasting apparently by enhancing the expression of components of this system such as Ub.

Preoperative fasting times: Prescribed and actual fasting times at ...

African Journals Online (AJOL)

The current international guidelines for preoperative fasting for elective surgery are 6 ... to determine whether this policy was being followed and patients were being starved ..... recommended fasting time, so that autonomous patients take care.

Microbial reprogramming inhibits Western diet-associated obesity.

Directory of Open Access Journals (Sweden)

Theofilos Poutahidis

Full Text Available A recent epidemiological study showed that eating 'fast food' items such as potato chips increased likelihood of obesity, whereas eating yogurt prevented age-associated weight gain in humans. It was demonstrated previously in animal models of obesity that the immune system plays a critical role in this process. Here we examined human subjects and mouse models consuming Westernized 'fast food' diet, and found CD4(+ T helper (Th17-biased immunity and changes in microbial communities and abdominal fat with obesity after eating the Western chow. In striking contrast, eating probiotic yogurt together with Western chow inhibited age-associated weight gain. We went on to test whether a bacteria found in yogurt may serve to lessen fat pathology by using purified Lactobacillus reuteri ATCC 6475 in drinking water. Surprisingly, we discovered that oral L. reuteri therapy alone was sufficient to change the pro-inflammatory immune cell profile and prevent abdominal fat pathology and age-associated weight gain in mice regardless of their baseline diet. These beneficial microbe effects were transferable into naïve recipient animals by purified CD4(+ T cells alone. Specifically, bacterial effects depended upon active immune tolerance by induction of Foxp3(+ regulatory T cells (Treg and interleukin (Il-10, without significantly changing the gut microbial ecology or reducing ad libitum caloric intake. Our finding that microbial targeting restored CD4(+ T cell balance and yielded significantly leaner animals regardless of their dietary 'fast food' indiscretions suggests population-based approaches for weight management and enhancing public health in industrialized societies.

Whole transcriptome analysis of the fasting and fed Burmese python heart: insights into extreme physiological cardiac adaptation.

Science.gov (United States)

Wall, Christopher E; Cozza, Steven; Riquelme, Cecilia A; McCombie, W Richard; Heimiller, Joseph K; Marr, Thomas G; Leinwand, Leslie A

2011-01-01

The infrequently feeding Burmese python (Python molurus) experiences significant and rapid postprandial cardiac hypertrophy followed by regression as digestion is completed. To begin to explore the molecular mechanisms of this response, we have sequenced and assembled the fasted and postfed Burmese python heart transcriptomes with Illumina technology using the chicken (Gallus gallus) genome as a reference. In addition, we have used RNA-seq analysis to identify differences in the expression of biological processes and signaling pathways between fasted, 1 day postfed (DPF), and 3 DPF hearts. Out of a combined transcriptome of ∼2,800 mRNAs, 464 genes were differentially expressed. Genes showing differential expression at 1 DPF compared with fasted were enriched for biological processes involved in metabolism and energetics, while genes showing differential expression at 3 DPF compared with fasted were enriched for processes involved in biogenesis, structural remodeling, and organization. Moreover, we present evidence for the activation of physiological and not pathological signaling pathways in this rapid, novel model of cardiac growth in pythons. Together, our data provide the first comprehensive gene expression profile for a reptile heart.

Inhibition Efficiency in Highly Proficient Bilinguals and Simultaneous Interpreters: Evidence from Language Switching and Stroop Tasks

OpenAIRE

Aparicio, X.; Heidlmayr, K.; Isel, F.

2017-01-01

The present behavioral study aimed to examine the impact of language control expertise on two domain-general control processes, i.e. active inhibition of competing representations and overcoming of inhibition. We compared how Simultaneous Interpreters (SI) and Highly Proficient Bilinguals—two groups assumed to differ in language control capacity—performed executive tasks involving specific inhibition processes. In Experiment 1 (language decision task), both active and overcoming of inhibition...

Attitudes, involvement and consumer behaviour : a longitudinal study in fast moving consumer goods markets

OpenAIRE

Walker, David

1994-01-01

An empirical study is reported which attempts to validate two key theoretical consequences of consumer involvement: differences in brand buying behaviour and differences in the type of decision processing undertaken. A literature review is provided which traces the history of involvement and identifies a suitable contemporary framework. Work on brand loyalty and attitude modelling is also reviewed and suitable frameworks identified. A pilot stage is reported which show...

Rapid Automatized Naming in Children with Dyslexia: Is Inhibitory Control Involved?

Science.gov (United States)

Bexkens, Anika; van den Wildenberg, Wery P M; Tijms, Jurgen

2015-08-01

Rapid automatized naming (RAN) is widely seen as an important indicator of dyslexia. The nature of the cognitive processes involved in rapid naming is however still a topic of controversy. We hypothesized that in addition to the involvement of phonological processes and processing speed, RAN is a function of inhibition processes, in particular of interference control. A total 86 children with dyslexia and 31 normal readers were recruited. Our results revealed that in addition to phonological processing and processing speed, interference control predicts rapid naming in dyslexia, but in contrast to these other two cognitive processes, inhibition is not significantly associated with their reading and spelling skills. After variance in reading and spelling associated with processing speed, interference control and phonological processing was partialled out, naming speed was no longer consistently associated with the reading and spelling skills of children with dyslexia. Finally, dyslexic children differed from normal readers on naming speed, literacy skills, phonological processing and processing speed, but not on inhibition processes. Both theoretical and clinical interpretations of these results are discussed. Copyright © 2014 John Wiley & Sons, Ltd.

Ligninolytic system of Phanerochaete chrysosporium: inhibition by o-phthalate

Energy Technology Data Exchange (ETDEWEB)

Fenn, P.; Kirk, T.K.

1979-01-01

The degradation rate of (synthetic/sup 14/C)-lignin to /sup 14/CO/sub 2/ by Phanerochaete chrysosporium in cultures buffered with 0.01 M 2,2-dimethylsuccinate (DMS) was twice that in 0.01 M o-phthalate-buffered cultures. This difference could be totally accounted for by o-phthalate inhibition of the activity of the ligninolytic system. /sup 14/CO/sub 2/ production from ring-, sidechain-, and methoyxl-labled lignins was inhibited, the degree of inhibition being dependent on o-phthalate concentration. Oxidations of /sup 14/C-glucose, /sup 14/C-acetovanillone, and /sup 14/C-apocynol were not inhibited; thus o-phthalate is not a general inhibitor, and might inhibit activities involved in attach of the lignin polymer. DMS is a suitable buffer for the ligninolytic system. Degradation rates of ring-labeled lignin to /sup 14/CO/sub 2/ of 10 to 15% in 24 h were obtained consistently over the pH range 3.6 to 4.5, with an optimum near pH 4.0.

Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief

Directory of Open Access Journals (Sweden)

Tozaki-Saitoh Hidetoshi

2009-04-01

Full Text Available Abstract Background Neuropathic pain is characterized by pain hypersensitivity to innocuous stimuli (tactile allodynia that is nearly always resistant to known treatments such as non-steroidal anti-inflammatory drugs or even opioids. It has been reported that some antidepressants are effective for treating neuropathic pain. However, the underlying molecular mechanisms are not well understood. We have recently demonstrated that blocking P2X4 receptors in the spinal cord reverses tactile allodynia after peripheral nerve injury in rats, implying that P2X4 receptors are a key molecule in neuropathic pain. We investigated a possible role of antidepressants as inhibitors of P2X4 receptors and analysed their analgesic mechanism using an animal model of neuropathic pain. Results Antidepressants strongly inhibited ATP-mediated Ca2+ responses in P2X4 receptor-expressing 1321N1 cells, which are known to have no endogenous ATP receptors. Paroxetine exhibited the most powerful inhibition of calcium influx via rat and human P2X4 receptors, with IC50 values of 2.45 μM and 1.87 μM, respectively. Intrathecal administration of paroxetine produced a striking antiallodynic effect in an animal model of neuropathic pain. Co-administration of WAY100635, ketanserin or ondansetron with paroxetine induced no significant change in the antiallodynic effect of paroxetine. Furthermore, the antiallodynic effect of paroxetine was observed even in rats that had received intrathecal pretreatment with 5,7-dihydroxytryptamine, which dramatically depletes spinal 5-hydroxytryptamine. Conclusion These results suggest that paroxetine acts as a potent analgesic in the spinal cord via a mechanism independent of its inhibitory effect on serotonin transporters. Powerful inhibition on P2X4 receptors may underlie the analgesic effect of paroxetine, and it is possible that some antidepressants clinically used in patients with neuropathic pain show antiallodynic effects, at least in part

Involvement of a lipoxygenase-like enzyme in abscisic Acid biosynthesis.

Science.gov (United States)

Creelman, R A; Bell, E; Mullet, J E

1992-07-01

Several lines of evidence indicate that abscisic acid (ABA) is derived from 9'-cis-neoxanthin or 9'-cis-violaxanthin with xanthoxin as an intermediate. (18)O-labeling experiments show incorporation primarily into the side chain carboxyl group of ABA, suggesting that oxidative cleavage occurs at the 11, 12 (11', 12') double bond of xanthophylls. Carbon monoxide, a strong inhibitor of heme-containing P-450 monooxygenases, did not inhibit ABA accumulation, suggesting that the oxygenase catalyzing the carotenoid cleavage step did not contain heme. This observation, plus the ability of lipoxygenase to make xanthoxin from violaxanthin, suggested that a lipoxygenase-like enzyme is involved in ABA biosynthesis. To test this idea, the ability of several soybean (Glycine max L.) lipoxygenase inhibitors (5,8,11-eicosatriynoic acid, 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, and naproxen) to inhibit stress-induced ABA accumulation in soybean cell culture and soybean seedlings was determined. All lipoxygenase inhibitors significantly inhibited ABA accumulation in response to stress. These results suggest that the in vivo oxidative cleavage reaction involved in ABA biosynthesis requires activity of a nonheme oxygenase having lipoxygenase-like properties.

Salicylhydroxamic acid (SHAM) inhibition of the DIC-pump in unicellular algae

International Nuclear Information System (INIS)

Goyal, A.; Tolbert, N.E.

1989-01-01

SHAM at 1 or 2 mM inhibits dissolved inorganic carbon (DIC) concentrating mechanisms in unicellular green algae as measured by photosynthetic oxygen evolution or by 14 C-inorganic carbon uptake (using silicone oil centrifugation techniques). This inhibition was reversed by high levels of DIC whereby the cells do not require the concentrating mechanism. SHAM inhibited the DIC-pump, which uses external CO 2 , in three species of algae, Dunaliella tertiolecta, Chlamydomonas reinhardtii, and Scenedesmus obliquus when adapted to low CO 2 and assayed around neutral pH. Scenedesmus adapted to air at pH 9.0 to use external HCO 3 - were not affected by SHAM. It is important to establish low optimum concentrations of SHAM, which varied with the algal species. The mechanism of SHAM inhibition of the CO 2 concentrating process is unknown. SHAM inhibits alternative respiration in these algae, but SHAM may also inhibit other reactions involving H + gradients or transporters associated with the DIC-pump

Inhibition of HSV cell-to-cell spread by lactoferrin and lactoferricin.

Science.gov (United States)

Jenssen, Håvard; Sandvik, Kjersti; Andersen, Jeanette H; Hancock, Robert E W; Gutteberg, Tore J

2008-09-01

The milk protein lactoferrin (Lf) has multiple functions, including immune stimulation and antiviral activity towards herpes simplex virus 1 and 2 (HSV-1 and HSV-2); antiviral activity has also been reported for the N-terminal pepsin-derived fragment lactoferricin (Lfcin). The anti-HSV mode of action of Lf and Lfcin is assumed to involve, in part, their interaction with the cell surface glycosaminoglycan heparan sulfate, thereby blocking of viral entry. In this study we investigated the ability of human and bovine Lf and Lfcin to inhibit viral cell-to-cell spread as well as the involvement of cell surface glycosaminoglycans during viral cell-to-cell spread. Lf and Lfcin from both human and bovine origin, inhibited cell-to-cell spread of both HSV-1 and HSV-2. Inhibition of cell-to-cell spread by bovine Lfcin involved cell surface chondroitin sulfate. Based on transmission electron microscopy studies, human Lfcin, like bovine Lfcin, was randomly distributed intracellularly, thus differences in their antiviral activity could not be explained by differences in their distribution. In contrast, the cellular localization of iron-saturated (holo)-Lf appeared to differ from that of apo-Lf, indicating that holo- and apo-Lf may exhibit different antiviral mechanisms.

NABUB a non-saturated model of coolant boiling in a fast reactor sub-assembly

International Nuclear Information System (INIS)

Brook, A.J.; Mills, D.S.

1975-08-01

A theoretical model is described of sodium boiling in a fast reactor sub-assembly in which the usual assumptions of a saturated vapour are not made. Instead, vapour pressure is calculated in a perfect gas basis, which enables some allowance to be made for the possible presence of non-condensables, which may inhibit the condensation f the vapour. Indications are given of the circumstances under which such inhibition might be expected to show the most marked effects, and some sample results ontained by the code are presented. These show that the coolant voiding pattern is most sensitive to restrictions on the condensing flux in the 100 to 200w/cm 2 range. If unrestricted condensation is assumed, the results of the code are in excellent agreement with more conventional saturation models. (author)

Konsumsi fast food dan soft drink sebagai faktor risiko obesitas pada remaja

Directory of Open Access Journals (Sweden)

Ayu Rafiony

2015-04-01

Full Text Available Background: Recently, obesity has become health problem which was frequently associated with an increased occurrence of non-communicable diseases. The prevalence of obesity has been increasing in both developed and developing countries. The increasing prevalence of obesity was marked by a shift in eating pattern composition containing high fat, cholesterol, but low in fiber such as consumption of fast food and soft drinks. The imbalance of nutrient intake was one of the risk factors for the emergence of obesity in adolescents. Obesity in adolescents at risk of becoming obese in adulthood and potentially can lead to cardiovascular and metabolic diseases Objective: This study aimed to find out the prevalence of obesity and to investigate risk factors for energy intake and frequency of consumption of fast food and soft drinks on the incidence of obesity in high school students in Pontianak. Method: This research was an observational study which involves case-control design. The samples in this study are 160 students consisting of 80 obese high school teenagers and 80 non-obese high school teenagers. The choice for a subject of research used proportional stratified random sampling. Measurement of obesity status subject was taken by the measurement of weight and height based on the reference standard WHO / NCHS. It also involves data intake of fast food and soft drinks based on interviews with SQFFQ. Data were analyzed by chi-square test, t-test, and logistic regression. Results: The prevalence of obesity in high school teenagers in Pontianak was 9.29%. The bivariate test result showed no association  between total  energy intake of fast food and obesity (p0.05. There was a relationship between the frequency of total  fast food and of the local fast food consumption with obesity (p0.05. Multivariable analysis showed that the total energy intake was the most dominant factor to the onset of obesity (p<0.05; OR=5.27; 95% CI: 1.64-16.97. Conclusion

Association between proximity to and coverage of traditional fast-food restaurants and non-traditional fast-food outlets and fast-food consumption among rural adults

Directory of Open Access Journals (Sweden)

Horel Scott A

2011-05-01

Full Text Available Abstract Objective The objective of this study is to examine the relationship between residential exposure to fast-food entrées, using two measures of potential spatial access: proximity (distance to the nearest location and coverage (number of different locations, and weekly consumption of fast-food meals. Methods Traditional fast-food restaurants and non-traditional fast-food outlets, such as convenience stores, supermarkets, and grocery stores, from the 2006 Brazos Valley Food Environment Project were linked with individual participants (n = 1409 who completed the nutrition module in the 2006 Brazos Valley Community Health Assessment. Results Increased age, poverty, increased distance to the nearest fast food, and increased number of different traditional fast-food restaurants, non-traditional fast-food outlets, or fast-food opportunities were associated with less frequent weekly consumption of fast-food meals. The interaction of gender and proximity (distance or coverage (number indicated that the association of proximity to or coverage of fast-food locations on fast-food consumption was greater among women and opposite of independent effects. Conclusions Results provide impetus for identifying and understanding the complex relationship between access to all fast-food opportunities, rather than to traditional fast-food restaurants alone, and fast-food consumption. The results indicate the importance of further examining the complex interaction of gender and distance in rural areas and particularly in fast-food consumption. Furthermore, this study emphasizes the need for health promotion and policy efforts to consider all sources of fast-food as part of promoting healthful food choices.

Association between proximity to and coverage of traditional fast-food restaurants and non-traditional fast-food outlets and fast-food consumption among rural adults

Science.gov (United States)

2011-01-01

Objective The objective of this study is to examine the relationship between residential exposure to fast-food entrées, using two measures of potential spatial access: proximity (distance to the nearest location) and coverage (number of different locations), and weekly consumption of fast-food meals. Methods Traditional fast-food restaurants and non-traditional fast-food outlets, such as convenience stores, supermarkets, and grocery stores, from the 2006 Brazos Valley Food Environment Project were linked with individual participants (n = 1409) who completed the nutrition module in the 2006 Brazos Valley Community Health Assessment. Results Increased age, poverty, increased distance to the nearest fast food, and increased number of different traditional fast-food restaurants, non-traditional fast-food outlets, or fast-food opportunities were associated with less frequent weekly consumption of fast-food meals. The interaction of gender and proximity (distance) or coverage (number) indicated that the association of proximity to or coverage of fast-food locations on fast-food consumption was greater among women and opposite of independent effects. Conclusions Results provide impetus for identifying and understanding the complex relationship between access to all fast-food opportunities, rather than to traditional fast-food restaurants alone, and fast-food consumption. The results indicate the importance of further examining the complex interaction of gender and distance in rural areas and particularly in fast-food consumption. Furthermore, this study emphasizes the need for health promotion and policy efforts to consider all sources of fast-food as part of promoting healthful food choices. PMID:21599955

Child and Parent Voices on a Community-Based Prevention Program (FAST)

Science.gov (United States)

Fearnow-Kenney, Melodie; Hill, Patricia; Gore, Nicole

2016-01-01

Families and Schools Together (FAST) is a collaborative program involving schools, families, and community-based partners in efforts to prevent substance use, juvenile delinquency, school failure, child abuse and neglect, mental health problems, and violence. Although evaluated extensively, there remains a dearth of qualitative data on child and…

The fast kinetics of the action of ionizing radiation in bacteria

International Nuclear Information System (INIS)

Harrop, H.A.

1980-06-01

The application of a fast-mixing and irradiation method, the gas explosion technique, to observe processes involved in the action of ionising radiation on bacteria is described. The decay of oxygen-dependent damage appears to be consistent with competition between chemical repair and fixation of radiation-induced lesions. (author)

How Do Parameters of Motor Response Influence Selective Inhibition? Evidence from the Stop-Signal Paradigm

Directory of Open Access Journals (Sweden)

Chien Hui Tang

2011-05-01

Full Text Available The ability to selectively inhibit the execution of an action while performing other ones is crucial in humans' multitasking daily life. The current study aims to compare selective inhibition for choice reaction involving two effectors or response directions. We adopted a variation of the stop-signal paradigm to examine how selective inhibition is modulated by the way potential motor responses are combined and inhibited. Experiment 1 investigated selective inhibition under different combinations of effectors, namely “index and middle fingers” versus “hand and foot”. The results showed SSRT of the index finger was longer when the other response option was the foot than the middle finger. Experiment 2 examined how selective inhibition differs between selective stopping of effectors and movement directions, and that for most of the situations SSRT is longer for stopping a response based on its direction than effector. After equating complexity of response mapping between direction and effector conditions in Experiment 2, Experiment 3 still showed that SSRT differs between selecting direction or effectors. To summarize, SSRT varies depending on the way response effectors are paired and selectively stopped. Selective inhibition is thus likely not amodal and may involve different inhibitory mechanisms depending on parameters specifying the motor response.

Ethylene not responsible for inhibition of conidium germination by soils volatiles

Energy Technology Data Exchange (ETDEWEB)

Schippers, B.; Boerwinkel, D.J.; Konings, H.

1978-01-01

Volatile factors inhibiting the germination of Botrytis cinerea and Cochlibolus sativus conidia on membrane filters were emanated from six alkaline and two acid soils of different organic content and origin. Addition of lime or chitin increased the inhibitory action. Evidence is presented that ethylene is not involved either directly or indirectly in the inhibition of conidium germination above the different soils tested. 16 references, 4 figures, 2 tables.

Transitioning nuclear fuel cycles with uncertain fast reactor costs

Energy Technology Data Exchange (ETDEWEB)

Phathanapirom, U.B., E-mail: bphathanapirom@utexas.edu; Schneider, E.A.

2016-06-15

This paper applies a novel decision making methodology to a case study involving choices leading to the transition from the current once-through light water reactor fuel cycle to one relying on continuous recycle of plutonium and minor actinides in fast reactors in the face of uncertain fast reactor capital costs. Unique to this work is a multi-stage treatment of a range of plausible trajectories for the evolution of fast reactor capital costs over time, characterized by first-of-a-kind penalties as well as time- and unit-based learning. The methodology explicitly incorporates uncertainties in key parameters into the decision-making process by constructing a stochastic model and embedding uncertainties as bifurcations in the decision tree. “Hedging” strategies are found by applying a choice criterion to select courses of action which mitigate “regrets”. These regrets are calculated by evaluating the performance of all possible transition strategies for every feasible outcome of the uncertain parameter. The hedging strategies are those that preserve the most flexibility for adjusting the fuel cycle strategy in response to new information as uncertainties are resolved.

Transitioning nuclear fuel cycles with uncertain fast reactor costs

International Nuclear Information System (INIS)

Phathanapirom, U.B.; Schneider, E.A.

2016-01-01

This paper applies a novel decision making methodology to a case study involving choices leading to the transition from the current once-through light water reactor fuel cycle to one relying on continuous recycle of plutonium and minor actinides in fast reactors in the face of uncertain fast reactor capital costs. Unique to this work is a multi-stage treatment of a range of plausible trajectories for the evolution of fast reactor capital costs over time, characterized by first-of-a-kind penalties as well as time- and unit-based learning. The methodology explicitly incorporates uncertainties in key parameters into the decision-making process by constructing a stochastic model and embedding uncertainties as bifurcations in the decision tree. “Hedging” strategies are found by applying a choice criterion to select courses of action which mitigate “regrets”. These regrets are calculated by evaluating the performance of all possible transition strategies for every feasible outcome of the uncertain parameter. The hedging strategies are those that preserve the most flexibility for adjusting the fuel cycle strategy in response to new information as uncertainties are resolved.

Serum corticosteroid binding globulin expression is modulated by fasting in polar bears (Ursus maritimus).

Science.gov (United States)

Chow, Brian A; Hamilton, Jason; Cattet, Marc R L; Stenhouse, Gordon; Obbard, Martyn E; Vijayan, Mathilakath M

2011-01-01

Polar bears (Ursus maritimus) from several subpopulations undergo extended fasting during the ice-free season. However, the animals appear to conserve protein despite the prolonged fasting, though the mechanisms involved are poorly understood. We hypothesized that elevated concentrations of corticosteroid binding globulin (CBG), the primary cortisol binding protein in circulation, lead to cortisol resistance and provide a mechanism for protein conservation during extended fasting. The metabolic state (feeding vs. fasting) of 16 field sampled male polar bears was determined based on their serum urea to creatinine ratio (>25 for feeding vs. polar bears sampled. Serum CBG expression was greater in lactating females relative to non-lactating females and males. CBG expression was significantly higher in fasting males when compared to non-fasting males. This leads us to suggest that CBG expression may serve as a mechanism to conserve protein during extended fasting in polar bears by reducing systemic free cortisol concentrations. This was further supported by a lower serum glucose concentration in the fasting bears. As well, a lack of an enhanced adrenocortical response to acute capture stress supports our hypothesis that chronic hunger is not a stressor in this species. Overall, our results suggest that elevated serum CBG expression may be an important adaptation to spare proteins by limiting cortisol bioavailability during extended fasting in polar bears. Copyright © 2010 Elsevier Inc. All rights reserved.

Fast ejendom III

DEFF Research Database (Denmark)

Munk-Hansen, Carsten

Bogen er det tredje bind af tre planlagte bind om fast ejendom: I Overdragelsen, II Bolighandlen og III Ejerbeføjelsen. Fremstillingens giver et grundigt overblik over centrale områder af en omfattende regulering af fast ejendom, med angivelse af litteratur, hvor læseren kan søge yderligere...... oplysning. En ejer af fast ejendom er på særdeles mange områder begrænset i sin råden sammenlignet med ejeren af et formuegode i almindelighed. Fremstillingen tager udgangspunkt i ejerens perspektiv (fremfor samfundets eller myndighedernes). Både den privatretlige og offentligretlige regulering behandles......, eksempelvis ejendomsdannelsen, servitutter, naboretten, hævd, zoneinddelingen, den fysiske planlægning, beskyttelse af natur, beskyttelse af kultur, forurening fra fast ejendom, erstatning for forurening, jordforurening, ekspropriation, byggeri og adgang til fast ejendom....

Fasting and rheumatic diseases

OpenAIRE

Mohammad Hassan Jokar

2015-01-01

Fasting is one of the important religious practices of Muslims, in which the individuals abstain from eating and drinking from dawn to sunset. Fasting is not obligatory or even not allowed, in case it causes health problems to the fasting individual. Rheumatic diseases are a major group of chronic diseases which can bring about numerous problems while fasting. The aim of this article is to review the impact of Islamic fasting on rheumatic patients, based on the scientific evidences.

Past and present role of fast breeder reactors in Italy

International Nuclear Information System (INIS)

Castelli, G.; Cicognani, G.; Ghilardotti, G.; Musso, B.

1978-01-01

The paper describes the programme that is under development in Italy for fast breeder reactors. The Italian engagement in the construction of the Creys-Malville plant is discussed as well as the work at present under way in R and D activities and on the PEC reactor. The roles of the different organizations involved in the fast breeder reactor programme are also considered with particular attention to the activities carried out by AGIP NUCLEARE, CNEN, ENEL, NIRA and by the manufacturing companies. An overall picture of the different agreements between European countries is also given with reference to the construction of the Creys-Malville plant and to research and industrial development activities. (author)

Fast switching of alkali atom dispensers using laser-induced heating

International Nuclear Information System (INIS)

Griffin, P.F.; Weatherill, K.J.; Adams, C.S.

2005-01-01

We show that by using an intense laser source to locally heat an alkali atom dispenser, one can generate a high flux of atoms followed by fast recovery (<100 ms) of the background pressure when the laser is extinguished. For repeated heating pulses a switch-on time for the atomic flux of 200 ms is readily attainable. This technique is suited to ultracold atom experiments using simple ultrahigh vacuum (UHV) chambers. Laser-induced heating provides a fast repetition of the experimental cycle, which, combined with low atom loss due to background gas collisions, is particularly useful for experiments involving far-off resonance optical traps, where sufficient laser power (0.5-4 W) is readily available

BACE inhibition-dependent repair of Alzheimer's pathophysiology.

Science.gov (United States)

Keskin, Aylin D; Kekuš, Maja; Adelsberger, Helmuth; Neumann, Ulf; Shimshek, Derya R; Song, Beomjong; Zott, Benedikt; Peng, Tingying; Förstl, Hans; Staufenbiel, Matthias; Nelken, Israel; Sakmann, Bert; Konnerth, Arthur; Busche, Marc Aurel

2017-08-08

Amyloid-β (Aβ) is thought to play an essential pathogenic role in Alzheimer´s disease (AD). A key enzyme involved in the generation of Aβ is the β-secretase BACE, for which powerful inhibitors have been developed and are currently in use in human clinical trials. However, although BACE inhibition can reduce cerebral Aβ levels, whether it also can ameliorate neural circuit and memory impairments remains unclear. Using histochemistry, in vivo Ca 2+ imaging, and behavioral analyses in a mouse model of AD, we demonstrate that along with reducing prefibrillary Aβ surrounding plaques, the inhibition of BACE activity can rescue neuronal hyperactivity, impaired long-range circuit function, and memory defects. The functional neuronal impairments reappeared after infusion of soluble Aβ, mechanistically linking Aβ pathology to neuronal and cognitive dysfunction. These data highlight the potential benefits of BACE inhibition for the effective treatment of a wide range of AD-like pathophysiological and cognitive impairments.

Distinct slow and fast cortical theta dynamics in episodic memory retrieval.

Science.gov (United States)

Pastötter, Bernhard; Bäuml, Karl-Heinz T

2014-07-01

Brain oscillations in the theta frequency band (3-8 Hz) have been shown to be critically involved in human episodic memory retrieval. In prior work, both positive and negative relationships between cortical theta power and retrieval success have been reported. This study examined the hypothesis that slow and fast cortical theta oscillations at the edges of the traditional theta frequency band are differentially related to retrieval success. Scalp EEG was recorded in healthy human participants as they performed a cued-recall episodic memory task. Slow (~3 Hz) and fast (~7 Hz) theta oscillations at retrieval were examined as a function of whether an item was recalled or not and as a function of the items' output position at test. Recall success typically declines with output position, due to increases in interference level. The results showed that slow theta power was positively related but fast theta power was negatively related to retrieval success. Concurrent positive and negative episodic memory effects for slow and fast theta oscillations were dissociable in time and space, showing different time courses and different spatial locations on the scalp. Moreover, fast theta power increased from early to late output positions, whereas slow theta power was unaffected by items' output position. Together with prior work, the results suggest that slow and fast theta oscillations have distinct functional roles in episodic memory retrieval, with slow theta oscillations being related to processes of recollection and conscious awareness, and fast theta oscillations being linked to processes of interference and interference resolution. Copyright © 2014 Elsevier Inc. All rights reserved.

Functional lateralization of temporoparietal junction - imitation inhibition, visual perspective-taking and theory of mind.

Science.gov (United States)

Santiesteban, Idalmis; Banissy, Michael J; Catmur, Caroline; Bird, Geoffrey

2015-10-01

Although neuroimaging studies have consistently identified the temporoparietal junction (TPJ) as a key brain region involved in social cognition, the literature is far from consistent with respect to lateralization of function. For example, during theory-of-mind tasks bilateral TPJ activation is found in some studies but only right hemisphere activation in others. Visual perspective-taking and imitation inhibition, which have been argued to recruit the same socio-cognitive processes as theory of mind, are associated with unilateral activation of either left TPJ (perspective taking) or right TPJ (imitation inhibition). The present study investigated the functional lateralization of TPJ involvement in the above three socio-cognitive abilities using transcranial direct current stimulation. Three groups of healthy adults received anodal stimulation over right TPJ, left TPJ or the occipital cortex prior to performing three tasks (imitation inhibition, visual perspective-taking and theory of mind). In contrast to the extant neuroimaging literature, our results suggest bilateral TPJ involvement in imitation inhibition and visual perspective-taking, while no effect of anodal stimulation was observed on theory of mind. The discrepancy between these findings and those obtained using neuroimaging highlight the efficacy of neurostimulation as a complementary methodological tool in cognitive neuroscience. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The dual action of poly(ADP-ribose polymerase -1 (PARP-1 inhibition in HIV-1 infection: HIV-1 LTR inhibition and diminution in Rho GTPase activity

Directory of Open Access Journals (Sweden)

Slava eRom

2015-08-01

Full Text Available The transcription of HIV-1 (HIV is regulated by complex mechanisms involving various cellular factors and virus-encoded transactivators. Poly(ADP-ribose polymerase 1 (PARP-1 inhibition has emerged recently as a potent anti-inflammatory tool, since PARP-1 is involved in the regulation of some genes through its interaction with various transcription factors. We propose a novel approach to diminish HIV replication via PARP-1 inhibition using human primary monocyte-derived macrophages (MDM as an in vitro model system. PARP-1 inhibitors were able to reduce HIV replication in MDM by 60-80% after 7 days infection. Long Terminal Repeat (LTR acts as a switch in virus replication and can be triggered by several agents such as: Tat, tumor necrosis factor α (TNFα, and phorbol 12-myristate 13-acetate (PMA. Overexpression of Tat in MDM transfected with an LTR reporter plasmid led to a 4.2-fold increase in LTR activation; PARP inhibition resulted in 70% reduction of LTR activity. LTR activity, which increased 3-fold after PMA or TNFα treatment, was reduced by PARP inhibition (by 85-95%. MDM treated with PARP inhibitors showed 90% reduction in NFκB activity (known to mediate PMA- and TNFα-induced HIV LTR activation. Cytoskeleton rearrangements are important in effective HIV-1 infection. PARP inactivation reduced actin cytoskeleton rearrangements by affecting Rho GTPase machinery. These findings suggest that HIV replication in MDM could be suppressed by PARP inhibition via NFκB suppression, diminution of LTR activation and its effects on the cytoskeleton. PARP appears to be essential for HIV replication and its inhibition may provide a potent approach to treatment of HIV infection.

Procaine rapidly inactivates acetylcholine receptors from Torpedo and competes with agonist for inhibition sites

International Nuclear Information System (INIS)

Forman, S.A.; Miller, K.W.

1989-01-01

The relationship between the high-affinity procaine channel inhibition site and the agonist self-inhibition site on acetylcholine receptors (AChRs) from Torpedo electroplaque was investigated by using rapid 86 Rb + quenched-flux assays at 4 degree C in native AChR-rich vesicles on which 50-60% of ACh activation sites were blocked with α-bungarotoxin (α-BTX). In the presence of channel-activating acetylcholine (ACh) concentrations alone, AChR undergoes one phase of inactivation in under a second. Addition of procaine produces two-phase inactivation similar to that seen with self-inhibiting ACh concentrations rapid inactivation complete in 30-75 ms is followed by fast desensitization at the same k d observed without procaine. The dependence of k r on [procaine] is consistent with a bimolecular association between procaine and its AChR site. Inhibition of AChR function by mixtures of procaine plus self-inhibiting concentrations of ACh or suberyldicholine was studied by reducing the level of α-BTX block in vesicles. The data support a mechanism where procaine binds preferentially to the open-channel AChR state, since no procaine-induced inactivation is observed without agonist and k r 's dependence on [ACh] in channel-activating range closely parallels that of 86 Rb + flux response to ACh

Some aspects of the chemistry of fast reactor fuel, structural material and decontamination

International Nuclear Information System (INIS)

Ganesan, V.

2012-01-01

The chemistry of materials pertaining to fast reactors is both fascinating and challenging considering the nature of materials involved such as the fuel, coolant, control and shielding materials in addition to the interactions between the structural materials and the fuel/coolant depending on the nature and conditions involved. The different chemical forms of fuel materials, the need to operate up to high burnups with consequent interactions of the fuel with clad materials, the need to close the fuel cycle by recovery of the fuel materials from spent fuels for refabrication and the necessity to manage the waste, throw a host of challenges which make their study scientifically interesting and technologically important. The use of liquid sodium as coolant in fast reactor heat transport systems combined with its inherent chemical reactivity opens up an interesting branch of chemistry involving liquid sodium especially in contact with structural materials during normal operation of the reactor and with fuels in the event of fuel pin failure. The phenomenon of sodium wetting and the associated corrosion of structural materials in contact with it combined with the need to carryout decontamination of such materials make it interesting to examine and evaluate their suitability for reuse without compromising on their structural integrity. Boron being the material of choice for control and shielding applications in fast reactors with varying isotopic enrichment and the technological challenge to produce large quantities of boron carbide makes it unique. Some of these aspects are addressed in this paper. (author)

Choline uptake in the hippocampus: inhibition of septal-hippocampal cholinergenic neurons by intraventricular barbiturates

International Nuclear Information System (INIS)

Richter, J.A.

1986-01-01

The author attempts to determine where in the brain pentobarbital acts to cause the inhibition of high-affinity, sodium-dependent choline uptake, and what behavioral consequences result from this particular effect of barbituates. The experiments were done in male Wistar rats which had received an injection of Nivea cream injected directly to the acannula. In the experiments the drug solution injected into the lateral ventricle was also spiked with ( 14 C) - phenobarbital at a final specific activity of 5 dpm/nmole so that a more precise estimate of the spread of drug solution could be made. When a phenobarbital-Fast green Dye mixture was injected bilaterally into the lateral ventricles, the dye was found to have spread through the entire ventricular system when the rat was killed 10-20 min later. Choline uptake in the hippocampus was inhibited and the inhibition was apparently greater of 20 min rather than 10 min were allowed to elapse after the injection

Treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin improves fasting islet-cell function in subjects with type 2 diabetes.

Science.gov (United States)

D'Alessio, David A; Denney, Amanda M; Hermiller, Linda M; Prigeon, Ronald L; Martin, Julie M; Tharp, William G; Saylan, Monica Liqueros; He, Yanling; Dunning, Beth E; Foley, James E; Pratley, Richard E

2009-01-01

Dipeptidyl peptidase 4 (DPP-4) inhibitors are proposed to lower blood glucose in type 2 diabetes mellitus (T2DM) by prolonging the activity of the circulating incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). Consistent with this mechanism of action, DPP-4 inhibitors improve glucose tolerance after meals by increasing insulin and reducing glucagon levels in the plasma. However, DPP-4 inhibitors also reduce fasting blood glucose, an unexpected effect because circulating levels of active GIP and GLP-1 are low in the postabsorptive state. The objective of the study was to examine the effects of DPP-4 inhibition on fasting islet function. We conducted a randomized, double-blind, placebo-controlled trial. The study was performed in General Clinical Research Centers at two University Hospitals. Forty-one subjects with T2DM were treated with metformin or diet, having good glycemic control with glycosylated hemoglobin values of 6.2-7.5%. Subjects were treated with vildagliptin (50 mg twice daily) or placebo for 3 months, followed by a 2-wk washout. Major Outcome Measure: We measured insulin secretion in response to iv glucose and arginine before and after treatment and after drug washout. There were small and comparable reductions in glycosylated hemoglobin in both groups over 3 months. Vildagliptin increased fasting GLP-1 levels in subjects taking metformin, but not those managed with diet, and raised active GIP levels slightly. DPP-4 inhibitor treatment improved the acute insulin and C-peptide responses to glucose (50 and 100% respectively; P fasting conditions. This suggests that DPP-4 inhibition has metabolic benefits in addition to enhancing meal-induced GLP-1 and GIP activity.

Gene expression profiling of fast- and slow- growing gonadotroph non-functioning pituitary adenomas

DEFF Research Database (Denmark)

Falch, Camilla Maria; Sundaram, Arvind Y M; Øystese, Kristin Astrid

2018-01-01

Objective Reliable biomarkers associated with aggressiveness of non-functioning gonadotroph adenomas (GAs) are lacking. As the growth of tumor remnants is highly variable, molecular markers for growth potential prediction are necessary. We hypothesized that fast- and slow - growing GAs present......, GPM6A and six EMT-related genes (SPAG9, SKIL, MTDH, HOOK1, CNOT6L and PRKACB). MTDH, but not EMCN, demonstrated involvement in cell migration and association with EMT-markers. Conclusions Fast- and slow- growing GAs present different gene expression profiles and genes related to EMT have higher...... expression in fast-growing tumors. In addition to MTDH, identified as an important contributor to aggressiveness, the other genes might represent markers for tumor growth potential and possible targets for drug therapy. ....

Children Involvement on Family Purchase Decision Making

OpenAIRE

Jostein, Revina Wintry

2013-01-01

Children take big involvement in family decision making process today. There are several factors that make this phenomenon happen, such as media influence. Currently, the development of information and communication technology is so fast, indirectly encourages all parties, including the children to be able to follow the changes. There are two main objectives that will be examined, related with all the stated problems at the previous section, which are to analyze which product category does ch...

Feedforward and feedback inhibition in neostriatal GABAergic spiny neurons.

Science.gov (United States)

Tepper, James M; Wilson, Charles J; Koós, Tibor

2008-08-01

There are two distinct inhibitory GABAergic circuits in the neostriatum. The feedforward circuit consists of a relatively small population of GABAergic interneurons that receives excitatory input from the neocortex and exerts monosynaptic inhibition onto striatal spiny projection neurons. The feedback circuit comprises the numerous spiny projection neurons and their interconnections via local axon collaterals. This network has long been assumed to provide the majority of striatal GABAergic inhibition and to sharpen and shape striatal output through lateral inhibition, producing increased activity in the most strongly excited spiny cells at the expense of their less strongly excited neighbors. Recent results, mostly from recording experiments of synaptically connected pairs of neurons, have revealed that the two GABAergic circuits differ markedly in terms of the total number of synapses made by each, the strength of the postsynaptic response detected at the soma, the extent of presynaptic convergence and divergence and the net effect of the activation of each circuit on the postsynaptic activity of the spiny neuron. These data have revealed that the feedforward inhibition is powerful and widespread, with spiking in a single interneuron being capable of significantly delaying or even blocking the generation of spikes in a large number of postsynaptic spiny neurons. In contrast, the postsynaptic effects of spiking in a single presynaptic spiny neuron on postsynaptic spiny neurons are weak when measured at the soma, and unable to significantly affect spike timing or generation. Further, reciprocity of synaptic connections between spiny neurons is only rarely observed. These results suggest that the bulk of the fast inhibition that has the strongest effects on spiny neuron spike timing comes from the feedforward interneuronal system whereas the axon collateral feedback system acts principally at the dendrites to control local excitability as well as the overall level of

Response inhibition is associated with white matter microstructure in children

DEFF Research Database (Denmark)

Madsen, Kathrine Skak; Baaré, William; Vestergaard, Martin

2010-01-01

Cognitive control of thoughts, actions and emotions is important for normal behaviour and the development of such control continues throughout childhood and adolescence. Several lines of evidence suggest that response inhibition is primarily mediated by a right-lateralized network involving...... to the prediction of performance variability. Observed associations may be related to variation in phase of maturation, to activity-dependent alterations in the network subserving response inhibition, or to stable individual differences in underlying neural system connectivity. (C) 2009 Elsevier Ltd. All rights...

Thalamocortical NMDA conductances and intracortical inhibition can explain cortical temporal tuning

Science.gov (United States)

Krukowski, A. E.; Miller, K. D.

2001-01-01

Cells in cerebral cortex fail to respond to fast-moving stimuli that evoke strong responses in the thalamic nuclei innervating the cortex. The reason for this behavior has remained a mystery. We study an experimentally motivated model of the thalamic input-recipient layer of cat primary visual cortex that accounts for many aspects of cortical orientation tuning. In this circuit, inhibition dominates over excitation, but temporal modulations of excitation and inhibition occur out of phase with one another, allowing excitation to transiently drive cells. We show that this circuit provides a natural explanation of cortical low-pass temporal frequency tuning, provided N-methyl-D-aspartate (NMDA) receptors are present in thalamocortical synapses in proportions measured experimentally. This suggests a new and unanticipated role for NMDA conductances in shaping the temporal response properties of cortical cells, and suggests that common cortical circuit mechanisms underlie both spatial and temporal response tuning.

Mitochondrial thiol modification by a targeted electrophile inhibits metabolism in breast adenocarcinoma cells by inhibiting enzyme activity and protein levels

Directory of Open Access Journals (Sweden)

M. Ryan Smith

2016-08-01

Full Text Available Many cancer cells follow an aberrant metabolic program to maintain energy for rapid cell proliferation. Metabolic reprogramming often involves the upregulation of glutaminolysis to generate reducing equivalents for the electron transport chain and amino acids for protein synthesis. Critical enzymes involved in metabolism possess a reactive thiolate group, which can be modified by certain oxidants. In the current study, we show that modification of mitochondrial protein thiols by a model compound, iodobutyl triphenylphosphonium (IBTP, decreased mitochondrial metabolism and ATP in MDA-MB 231 (MB231 breast adenocarcinoma cells up to 6 days after an initial 24 h treatment. Mitochondrial thiol modification also depressed oxygen consumption rates (OCR in a dose-dependent manner to a greater extent than a non-thiol modifying analog, suggesting that thiol reactivity is an important factor in the inhibition of cancer cell metabolism. In non-tumorigenic MCF-10A cells, IBTP also decreased OCR; however the extracellular acidification rate was significantly increased at all but the highest concentration (10 µM of IBTP indicating that thiol modification can have significantly different effects on bioenergetics in tumorigenic versus non-tumorigenic cells. ATP and other adenonucleotide levels were also decreased by thiol modification up to 6 days post-treatment, indicating a decreased overall energetic state in MB231 cells. Cellular proliferation of MB231 cells was also inhibited up to 6 days post-treatment with little change to cell viability. Targeted metabolomic analyses revealed that thiol modification caused depletion of both Krebs cycle and glutaminolysis intermediates. Further experiments revealed that the activity of the Krebs cycle enzyme, aconitase, was attenuated in response to thiol modification. Additionally, the inhibition of glutaminolysis corresponded to decreased glutaminase C (GAC protein levels, although other protein levels were

Involvement of Nrf2-Mediated Upregulation of Heme Oxygenase-1 in Mollugin-Induced Growth Inhibition and Apoptosis in Human Oral Cancer Cells

Directory of Open Access Journals (Sweden)

Young-Man Lee

2013-01-01

Full Text Available Although previous studies have shown that mollugin, a bioactive phytochemical isolated from Rubia cordifolia L. (Rubiaceae, exhibits antitumor effects, its biological activity in oral cancer has not been reported. We thus investigated the effects and putative mechanism of apoptosis induced by mollugin in human oral squamous cell carcinoma cells (OSCCs. Results show that mollugin induces cell death in a dose-dependent manner in primary and metastatic OSCCs. Mollugin-induced cell death involved apoptosis, characterized by the appearance of nuclear shrinkage, flow cytometric analysis of sub-G1 phase arrest, and annexin V-FITC and propidium iodide staining. Western blot analysis and RT-PCR revealed that mollugin suppressed activation of NF-κB and NF-κB-dependent gene products involved in antiapoptosis (Bcl-2 and Bcl-xl, invasion (MMP-9 and ICAM-1, and angiogenesis (FGF-2 and VEGF. Furthermore, mollugin induced the activation of p38, ERK, and JNK and the expression of heme oxygenase-1 (HO-1 and nuclear factor E2–related factor 2 (Nrf2. Mollugin-induced growth inhibition and apoptosis of HO-1 were reversed by an HO-1 inhibitor and Nrf2 siRNA. Collectively, this is the first report to demonstrate the effectiveness of mollugin as a candidate for a chemotherapeutic agent in OSCCs via the upregulation of the HO-1 and Nrf2 pathways and the downregulation of NF-κB.

Lactate dehydrogenase activity is inhibited by methylmalonate in vitro.

Science.gov (United States)

Saad, Laura O; Mirandola, Sandra R; Maciel, Evelise N; Castilho, Roger F

2006-04-01

Methylmalonic acidemia (MMAemia) is an inherited metabolic disorder of branched amino acid and odd-chain fatty acid metabolism, involving a defect in the conversion of methylmalonyl-coenzyme A to succinyl-coenzyme A. Systemic and neurological manifestations in this disease are thought to be associated with the accumulation of methylmalonate (MMA) in tissues and biological fluids with consequent impairment of energy metabolism and oxidative stress. In the present work we studied the effect of MMA and two other inhibitors of mitochondrial respiratory chain complex II (malonate and 3-nitropropionate) on the activity of lactate dehydrogenase (LDH) in tissue homogenates from adult rats. MMA potently inhibited LDH-catalyzed conversion of lactate to pyruvate in liver and brain homogenates as well as in a purified bovine heart LDH preparation. LDH was about one order of magnitude less sensitive to inhibition by MMA when catalyzing the conversion of pyruvate to lactate. Kinetic studies on the inhibition of brain LDH indicated that MMA inhibits this enzyme competitively with lactate as a substrate (K (i)=3.02+/-0.59 mM). Malonate and 3-nitropropionate also strongly inhibited LDH-catalyzed conversion of lactate to pyruvate in brain homogenates, while no inhibition was observed by succinate or propionate, when present in concentrations of up to 25 mM. We propose that inhibition of the lactate/pyruvate conversion by MMA contributes to lactate accumulation in blood, metabolic acidemia and inhibition of gluconeogenesis observed in patients with MMAemia. Moreover, the inhibition of LDH in the central nervous system may also impair the lactate shuttle between astrocytes and neurons, compromising neuronal energy metabolism.

Implementing large scale fast track diagnostics in a comprehensive cancer center, pre- and post-measurement data.

Science.gov (United States)

van Harten, W H; Goedbloed, N; Boekhout, A H; Heintzbergen, S

2018-02-07

In general, patients with a cancer suspicion visit the hospital multiple times before diagnosis is completed. Using various "operations management" techniques a few fast track diagnostic services were implemented in the Netherlands Cancer Institute (NKI) in 2006. Growing patient numbers and increasing process complexity, led to diminished service levels. To decrease the amount of patient visits and to extend these services beyond the (obvious) breast cancer services, fast track diagnostics is now implemented for all 18 cancer types that present with a frequency of minimally one per week. The throughput time (first visit to diagnosis conversation) was measured before, and after implementation of fast track diagnostics. The process was redesigned closely involving the multidisciplinary teams. In an eclectic approach elements from lean management, theory of constraints and mathematical analysis were used to organize slots per tumor type for MRI, CT, PET and echography. A post measurement was performed after 3 and 6 months. In pre measurement access time was calculated to be 10 to 15 workdays, mean throughput time was 6.0 workdays. It proved possible to design the process of 18 tumors as a fast track, of which 7 as "one stop shop" (diagnosis completed in one visit). Involvement of clinical- and board leadership, massive communication efforts and commitment of physicians to reschedule their work proved decisive. After 3 and 6 months of implementation, the mean access time was 8.2 and 8.7 workdays respectively and mean throughput time was 3.4 and 3.3 workdays respectively. Throughput- and access time were considerably shortened after implementation of fast track diagnostics for 18 cancer types. The involvement of physicians in reorganizing their work and rapid responding to their needs during the implementation phase were a crucial success factor.

Amyloid-beta binds catalase with high affinity and inhibits hydrogen peroxide breakdown.

OpenAIRE

Milton, N G

1999-01-01

Amyloid-beta (Abeta) specifically bound purified catalase with high affinity and inhibited catalase breakdown of H(2)O(2). The Abeta-induced catalase inhibition involved formation of the inactive catalase Compound II and was reversible. CatalaseAbeta interactions provide rapid functional assays for the cytotoxic domain of Abeta and suggest a mechanism for some of the observed actions of Abeta plus catalase in vitro.

Evaluation of penicillin G residues by kidney inhibition swab tests in sow body fluids and tissues following intramuscular injection

Science.gov (United States)

In 2011, the USDA-Food Safety and Inspection Service (FSIS) changed the method used for screening swine tissues for antimicrobial residues from the Fast Antimicrobial Screen Test to the Kidney Inhibition Swab (KIS(TM)). Here, we describe the use of KIS(TM) test for the detection of penicillin G res...

Absolute quantitative profiling of the key metabolic pathways in slow and fast skeletal muscle

DEFF Research Database (Denmark)

Rakus, Dariusz; Gizak, Agnieszka; Deshmukh, Atul

2015-01-01

. Proteomic analysis of mouse slow and fast muscles allowed estimation of the titers of enzymes involved in the carbohydrate, lipid, and energy metabolism. Notably, we observed that differences observed between the two muscle types occur simultaneously for all proteins involved in a specific process......Slow and fast skeletal muscles are composed of, respectively, mainly oxidative and glycolytic muscle fibers, which are the basic cellular motor units of the motility apparatus. They largely differ in excitability, contraction mechanism, and metabolism. Because of their pivotal role in body motion...... and homeostasis, the skeletal muscles have been extensively studied using biochemical and molecular biology approaches. Here we describe a simple analytical and computational approach to estimate titers of enzymes of basic metabolic pathways and proteins of the contractile machinery in the skeletal muscles...

Fast Spectrum Reactors

CERN Document Server

Todd, Donald; Tsvetkov, Pavel

2012-01-01

Fast Spectrum Reactors presents a detailed overview of world-wide technology contributing to the development of fast spectrum reactors. With a unique focus on the capabilities of fast spectrum reactors to address nuclear waste transmutation issues, in addition to the well-known capabilities of breeding new fuel, this volume describes how fast spectrum reactors contribute to the wide application of nuclear power systems to serve the global nuclear renaissance while minimizing nuclear proliferation concerns. Readers will find an introduction to the sustainable development of nuclear energy and the role of fast reactors, in addition to an economic analysis of nuclear reactors. A section devoted to neutronics offers the current trends in nuclear design, such as performance parameters and the optimization of advanced power systems. The latest findings on fuel management, partitioning and transmutation include the physics, efficiency and strategies of transmutation, homogeneous and heterogeneous recycling, in addit...

Entanglement and inhibited quantum evolution

Energy Technology Data Exchange (ETDEWEB)

Toschek, P E; Balzer, Chr; Hannemann, Th; Wunderlich, Ch; Neuhauser, W [Universitaet Hamburg, Institut fuer Laser-Physik, Jungiusstrasse 9, D-20355 Hamburg (Germany)

2003-03-14

The evolution of a quantum system is impeded by the system's state being observed. A test on an ensemble neither proves the causal nexus nor discloses the nature of the inhibition. Two recent experiments that make use of sequential optical or microwave-optical double resonance on an individual trapped ion disprove a dynamical effect of back action by meter or environment. They rather indicate the ionic states involved in the evolution being entangled with the potentially recorded bivalued scattered-light signal.

Entanglement and inhibited quantum evolution

International Nuclear Information System (INIS)

Toschek, P E; Balzer, Chr; Hannemann, Th; Wunderlich, Ch; Neuhauser, W

2003-01-01

The evolution of a quantum system is impeded by the system's state being observed. A test on an ensemble neither proves the causal nexus nor discloses the nature of the inhibition. Two recent experiments that make use of sequential optical or microwave-optical double resonance on an individual trapped ion disprove a dynamical effect of back action by meter or environment. They rather indicate the ionic states involved in the evolution being entangled with the potentially recorded bivalued scattered-light signal

Inhibition of cancer cell growth by exposure to a specific time-varying electromagnetic field involves T-type calcium channels.

Directory of Open Access Journals (Sweden)

Carly A Buckner

Full Text Available Electromagnetic field (EMF exposures affect many biological systems. The reproducibility of these effects is related to the intensity, duration, frequency, and pattern of the EMF. We have shown that exposure to a specific time-varying EMF can inhibit the growth of malignant cells. Thomas-EMF is a low-intensity, frequency-modulated (25-6 Hz EMF pattern. Daily, 1 h, exposures to Thomas-EMF inhibited the growth of malignant cell lines including B16-BL6, MDA-MB-231, MCF-7, and HeLa cells but did not affect the growth of non-malignant cells. Thomas-EMF also inhibited B16-BL6 cell proliferation in vivo. B16-BL6 cells implanted in syngeneic C57b mice and exposed daily to Thomas-EMF produced smaller tumours than in sham-treated controls. In vitro studies showed that exposure of malignant cells to Thomas-EMF for > 15 min promoted Ca(2+ influx which could be blocked by inhibitors of voltage-gated T-type Ca(2+ channels. Blocking Ca(2+ uptake also blocked Thomas-EMF-dependent inhibition of cell proliferation. Exposure to Thomas-EMF delayed cell cycle progression and altered cyclin expression consistent with the decrease in cell proliferation. Non-malignant cells did not show any EMF-dependent changes in Ca(2+ influx or cell growth. These data confirm that exposure to a specific EMF pattern can affect cellular processes and that exposure to Thomas-EMF may provide a potential anti-cancer therapy.

Inhibition of cancer cell growth by exposure to a specific time-varying electromagnetic field involves T-type calcium channels.

Science.gov (United States)

Buckner, Carly A; Buckner, Alison L; Koren, Stan A; Persinger, Michael A; Lafrenie, Robert M

2015-01-01

Electromagnetic field (EMF) exposures affect many biological systems. The reproducibility of these effects is related to the intensity, duration, frequency, and pattern of the EMF. We have shown that exposure to a specific time-varying EMF can inhibit the growth of malignant cells. Thomas-EMF is a low-intensity, frequency-modulated (25-6 Hz) EMF pattern. Daily, 1 h, exposures to Thomas-EMF inhibited the growth of malignant cell lines including B16-BL6, MDA-MB-231, MCF-7, and HeLa cells but did not affect the growth of non-malignant cells. Thomas-EMF also inhibited B16-BL6 cell proliferation in vivo. B16-BL6 cells implanted in syngeneic C57b mice and exposed daily to Thomas-EMF produced smaller tumours than in sham-treated controls. In vitro studies showed that exposure of malignant cells to Thomas-EMF for > 15 min promoted Ca(2+) influx which could be blocked by inhibitors of voltage-gated T-type Ca(2+) channels. Blocking Ca(2+) uptake also blocked Thomas-EMF-dependent inhibition of cell proliferation. Exposure to Thomas-EMF delayed cell cycle progression and altered cyclin expression consistent with the decrease in cell proliferation. Non-malignant cells did not show any EMF-dependent changes in Ca(2+) influx or cell growth. These data confirm that exposure to a specific EMF pattern can affect cellular processes and that exposure to Thomas-EMF may provide a potential anti-cancer therapy.

Ultra-fast magnetization reversal in magnetic nano-pillars by spin-polarized current

Energy Technology Data Exchange (ETDEWEB)

Devolder, T. [Institut d' Electronique Fondamentale, UMR 8622 CNRS, Universite Paris Sud, Ba-circumflex timent 220, 91405 Orsay (France)]. E-mail: thibaut.devolder@ief.u-psud.fr; Tulapurkar, A. [NanoElectronics Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba 305-8568 (Japan); CREST, Japan Science and Technology Corporation, 4-1-8 Honcho, Kawaguchi 332-0012 (Japan); Yagami, K. [SSNC, Semiconductor Technology Development Group, SONY Corporation, Atsugi, Kanagawa 243-0014 (Japan); Crozat, P. [Institut d' Electronique Fondamentale, UMR 8622 CNRS, Universite Paris Sud, Ba-circumflex timent 220, 91405 Orsay (France); Chappert, C. [Institut d' Electronique Fondamentale, UMR 8622 CNRS, Universite Paris Sud, Ba-circumflex timent 220, 91405 Orsay (France); Fukushima, A. [NanoElectronics Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba 305-8568 (Japan); CREST, Japan Science and Technology Corporation, 4-1-8 Honcho, Kawaguchi 332-0012 (Japan); Suzuki, Y. [NanoElectronics Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba 305-8568 (Japan); CREST, Japan Science and Technology Corporation, 4-1-8 Honcho, Kawaguchi 332-0012 (Japan)

2005-02-01

We study the speed limitations of the magnetization switching resulting from spin transfer in pillar-shaped CoFe/Cu/CoFe spin valves. The quasi-static critical currents are Ic-=-2mA for the antiparallel (AP) to parallel (P) configuration and Ic+=+4.6mA for the P to AP transition. Current pulses of duration down to 100ps and amplitude of 4I{sub c} trigger switching at 300K. The switching is probabilistic for lower current pulses. The P to AP transition speed is not much temperature dependant from 50 to 300K. In contrast, the AP to P transition is thermally inhibited and is much faster at 150K than at 300K. This thermal inhibition highlights the importance of the macrospin coherency and of the thermally excited spin waves with finite wave vector parallel to the magnetization. Our results validate spin-transfer switching for fast memory applications.

Ultra-fast magnetization reversal in magnetic nano-pillars by spin-polarized current

International Nuclear Information System (INIS)

Devolder, T.; Tulapurkar, A.; Yagami, K.; Crozat, P.; Chappert, C.; Fukushima, A.; Suzuki, Y.

2005-01-01

We study the speed limitations of the magnetization switching resulting from spin transfer in pillar-shaped CoFe/Cu/CoFe spin valves. The quasi-static critical currents are Ic-=-2mA for the antiparallel (AP) to parallel (P) configuration and Ic+=+4.6mA for the P to AP transition. Current pulses of duration down to 100ps and amplitude of 4I c trigger switching at 300K. The switching is probabilistic for lower current pulses. The P to AP transition speed is not much temperature dependant from 50 to 300K. In contrast, the AP to P transition is thermally inhibited and is much faster at 150K than at 300K. This thermal inhibition highlights the importance of the macrospin coherency and of the thermally excited spin waves with finite wave vector parallel to the magnetization. Our results validate spin-transfer switching for fast memory applications

Public support for restrictions on fast food company sponsorship of community events.

Science.gov (United States)

Pettigrew, Simone; Pescud, Melanie; Rosenberg, Michael; Ferguson, Renee; Houghton, Stephen

2012-01-01

This study investigated community attitudes to fast food companies' sponsorship of community events. The aim was to inform future efforts to introduce greater restrictions on these marketing activities to reduce child obesity. While previous research has focused on the sponsorship of sporting events, the present study included all community events and gauged public support for fast food company sponsorships in general as well as specific sponsorship activities such as securing event naming rights, advertising on event premises, and distributing free items to children in the form of food and redeemable vouchers. A large and diverse sample of Western Australian adults (n=2,005) responded to a community attitudes telephone survey that included questions relating to event sponsorship. Almost half of the respondents reported that the promotion of fast foods is inappropriate at community events, and only a third considered it appropriate at events where children are likely to be present. Around two-thirds agreed that promoting fast foods at such events sends contradictory messages to children and just a quarter of respondents considered it acceptable for free fast food to be distributed at events or for children to be rewarded for participation with fast food vouchers. The results suggest that efforts to reduce child obesity that involve restrictions on the sponsorship of community events by organisations promoting unhealthy foods may be supported by a substantial proportion of the population.

Calcineurin Inhibition Blocks Within-, but Not Between-Session Fear Extinction in Mice

Science.gov (United States)

Almeida-Corrêa, Suellen; Moulin, Thiago C.; Carneiro, Clarissa F. D.; Gonçalves, Marina M. C.; Junqueira, Lara S.; Amaral, Olavo B.

2015-01-01

Memory extinction involves the formation of a new associative memory that inhibits a previously conditioned association. Nonetheless, it could also depend on weakening of the original memory trace if extinction is assumed to have multiple components. The phosphatase calcineurin (CaN) has been described as being involved in extinction but not in…

Two Alkaloids from Bulbs of Lycoris sanguinea MAXIM. Suppress PEPCK Expression by Inhibiting the Phosphorylation of CREB.

Science.gov (United States)

Yun, Young Sook; Tajima, Miki; Takahashi, Shigeru; Takahashi, Yuji; Umemura, Mariko; Nakano, Haruo; Park, Hyun Sun; Inoue, Hideshi

2016-10-01

In the fasting state, gluconeogenesis is upregulated by glucagon. Glucagon stimulates cyclic adenosine monophosphate production, which induces the expression of key enzymes for gluconeogenesis, such as cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), which are involved in gluconeogenesis through the protein kinase A/cAMP response element-binding protein (CREB) pathway. Using a luciferase reporter gene assay, a methanol extract of the bulbs of Lycoris sanguinea M AXIM. var. kiushiana Makino was found to suppress cAMP-enhanced PEPCK-C promoter activity. In addition, two alkaloids, lycoricidine and lycoricidinol, in the extract were identified as active constituents. In forskolin-stimulated human hepatoma cells, these alkaloids suppressed the expression of a reporter gene under the control of cAMP response element and also prevented increases in the endogenous levels of phosphorylated CREB and PEPCK mRNA expression. These results suggest that lycoricidine and lycoricidinol suppress PEPCK-C expression by inhibiting the phosphorylation of CREB and may thus have the potential to prevent excessive gluconeogenesis in type 2 diabetes. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

ACAT Inhibition and Progression of Carotid Atherosclerosis in Patients With Familial Hypercholesterolemia The CAPTIVATE Randomized Trial

NARCIS (Netherlands)

Meuwese, Marijn C.; de Groot, Eric; Duivenvoorden, Raphaël; Trip, Mieke D.; Ose, Leiv; Maritz, Frans J.; Basart, Dick C. G.; Kastelein, John J. P.; Habib, Rafik; Davidson, Michael H.; Zwinderman, Aeilko H.; Schwocho, Lee R.; Stein, Evan A.

2009-01-01

Context Inhibition of acyl coenzyme A: cholesterol acyltransferase (ACAT), an intracellular enzyme involved in cholesterol accumulation, with pactimibe was developed to assist in the prevention of cardiovascular disease. Objective To evaluate the efficacy and safety of pactimibe in inhibition of

International collaborative project to compare and track the nutritional composition of fast foods

Directory of Open Access Journals (Sweden)

2012-07-01

Full Text Available Abstract Background Chronic diseases are the leading cause of premature death and disability in the world with over-nutrition a primary cause of diet-related ill health. Excess quantities of energy, saturated fat, sugar and salt derived from fast foods contribute importantly to this disease burden. Our objective is to collate and compare nutrient composition data for fast foods as a means of supporting improvements in product formulation. Methods/design Surveys of fast foods will be done in each participating country each year. Information on the nutrient composition for each product will be sought either through direct chemical analysis, from fast food companies, in-store materials or from company websites. Foods will be categorized into major groups for the primary analyses which will compare mean levels of saturated fat, sugar, sodium, energy and serving size at baseline and over time. Countries currently involved include Australia, New Zealand, France, UK, USA, India, Spain, China and Canada, with more anticipated to follow. Discussion This collaborative approach to the collation and sharing of data will enable low-cost tracking of fast food composition around the world. This project represents a significant step forward in the objective and transparent monitoring of industry and government commitments to improve the quality of fast foods.

International collaborative project to compare and track the nutritional composition of fast foods.

Science.gov (United States)

2012-07-27

Chronic diseases are the leading cause of premature death and disability in the world with over-nutrition a primary cause of diet-related ill health. Excess quantities of energy, saturated fat, sugar and salt derived from fast foods contribute importantly to this disease burden. Our objective is to collate and compare nutrient composition data for fast foods as a means of supporting improvements in product formulation. Surveys of fast foods will be done in each participating country each year. Information on the nutrient composition for each product will be sought either through direct chemical analysis, from fast food companies, in-store materials or from company websites. Foods will be categorized into major groups for the primary analyses which will compare mean levels of saturated fat, sugar, sodium, energy and serving size at baseline and over time. Countries currently involved include Australia, New Zealand, France, UK, USA, India, Spain, China and Canada, with more anticipated to follow. This collaborative approach to the collation and sharing of data will enable low-cost tracking of fast food composition around the world. This project represents a significant step forward in the objective and transparent monitoring of industry and government commitments to improve the quality of fast foods.

Ramadan, fasting and pregnancy

DEFF Research Database (Denmark)

Ahmed, Urfan Zahoor; Lykke, Jacob Alexander

2014-01-01

In Islam, the month of Ramadan is a period of fasting lasting 29 or 30 days. Epidemiological studies among Muslims in Denmark have not been conducted, but studies show, that fasting among pregnant Muslim women is common. Fasting does not increase the risk of growth restriction or preterm delivery......, but there are reports of decreased foetal movements. Furthermore, the fasting may have long-term health consequences for the offspring, especially when they reach their middle age. According to Islam and the interpretation, pregnant and breast-feeding women are allowed to postpone the fasting of the month of Ramadan...

Ramadan, faste og graviditet

DEFF Research Database (Denmark)

Ahmed, Urfan Zahoor; Lykke, Jacob Alexander

2014-01-01

In Islam, the month of Ramadan is a period of fasting lasting 29 or 30 days. Epidemiological studies among Muslims in Denmark have not been conducted, but studies show, that fasting among pregnant Muslim women is common. Fasting does not increase the risk of growth restriction or preterm delivery......, but there are reports of decreased foetal movements. Furthermore, the fasting may have long-term health consequences for the offspring, especially when they reach their middle age. According to Islam and the interpretation, pregnant and breast-feeding women are allowed to postpone the fasting of the month of Ramadan...

FABRICATION AND CHARACTERIZATION OF FAST IGNITION TARGETS

International Nuclear Information System (INIS)

HILL, D.W; CASTILLO, E; CHEN, K.C; GRANT, S.E; GREENWOOD, A.L; KAAE, J.L; NIKROO, A; PAGUIO, S.P; SHEARER, C; SMITH, J.N Jr.; STEPHENS, R.B; STEINMAN, D.A; WALL, J.

2003-09-01

OAK-B135 Fast ignition is a novel scheme for achieving laser fusion. A class of these targets involves cone mounted CH shells. The authors have been fabricating such targets with shells with a wide variety of diameters and wall thicknesses for several years at General Atomics. In addition, recently such shells were needed for implosion experiments at Laboratory for Laser Energetics (LLE) that for the first time were required to be gas retentive. Fabrication of these targets requires producing appropriate cones and shells, assembling the targets, and characterization of the assembled targets. The cones are produced using micromachining and plating techniques. The shells are fabricated using the depolymerizable mandrel technique followed by micromachining a hole for the cone. The cone and the shell then need to be assembled properly for gas retention and precisely in order to position the cone tip at the desired position within the shell. Both are critical for the fast ignition experiments. The presence of the cone in the shell creates new challenges in characterization of the assembled targets. Finally, for targets requiring a gas fill, the cone-shell assembly needs to be tested for gas retention and proper strength at the glue joint. This paper presents an overview of the developmental efforts and technical issues addressed during the fabrication of fast ignition targets

Neural correlates of central inhibition during physical fatigue.

Directory of Open Access Journals (Sweden)

Masaaki Tanaka

Full Text Available Central inhibition plays a pivotal role in determining physical performance during physical fatigue. Classical conditioning of central inhibition is believed to be associated with the pathophysiology of chronic fatigue. We tried to determine whether classical conditioning of central inhibition can really occur and to clarify the neural mechanisms of central inhibition related to classical conditioning during physical fatigue using magnetoencephalography (MEG. Eight right-handed volunteers participated in this study. We used metronome sounds as conditioned stimuli and maximum handgrip trials as unconditioned stimuli to cause central inhibition. Participants underwent MEG recording during imagery of maximum grips of the right hand guided by metronome sounds for 10 min. Thereafter, fatigue-inducing maximum handgrip trials were performed for 10 min; the metronome sounds were started 5 min after the beginning of the handgrip trials. The next day, neural activities during imagery of maximum grips of the right hand guided by metronome sounds were measured for 10 min. Levels of fatigue sensation and sympathetic nerve activity on the second day were significantly higher relative to those of the first day. Equivalent current dipoles (ECDs in the posterior cingulated cortex (PCC, with latencies of approximately 460 ms, were observed in all the participants on the second day, although ECDs were not identified in any of the participants on the first day. We demonstrated that classical conditioning of central inhibition can occur and that the PCC is involved in the neural substrates of central inhibition related to classical conditioning during physical fatigue.

Alterations in neural systems mediating cognitive flexibility and inhibition in mood disorders.

Science.gov (United States)

Piguet, Camille; Cojan, Yann; Sterpenich, Virginie; Desseilles, Martin; Bertschy, Gilles; Vuilleumier, Patrik

2016-04-01

Impairment in mental flexibility may be a key component contributing to cardinal cognitive symptoms among mood disorders patients, particularly thought control disorders. Impaired ability to switch from one thought to another might reflect difficulties in either generating new mental states, inhibiting previous states, or both. However, the neural underpinnings of impaired cognitive flexibility in mood disorders remain largely unresolved. We compared a group of mood disorders patients (n = 29) and a group of matched healthy subjects (n = 32) on a novel task-switching paradigm involving happy and sad faces, that allowed us to separate generation of a new mental set (Switch Cost) and inhibition of the previous set during switching (Inhibition Cost), using fMRI. Behavioral data showed a larger Switch Cost in patients relative to controls, but the average Inhibition Cost did not differ between groups. At the neural level, a main effect of group was found with stronger activation of the subgenual cingulate cortex in patients. The larger Switch Cost in patients was reflected by a stronger recruitment of brain regions involved in attention and executive control, including the left intraparietal sulcus, precuneus, left inferior fontal gyrus, and right anterior cingulate. Critically, activity in the subgenual cingulate cortex was not downregulated by inhibition in patients relative to controls. In conclusion, mood disorder patients have exaggerated Switch Cost relative to controls, and this deficit in cognitive flexibility is associated with increased activation of the fronto-parietal attention networks, combined with impaired modulation of the subgenual cingulate cortex when inhibition of previous mental states is needed. © 2016 Wiley Periodicals, Inc.

Inhibition of GRP78 abrogates radioresistance in oropharyngeal carcinoma cells after EGFR inhibition by cetuximab.

Directory of Open Access Journals (Sweden)

Chaonan Sun

Full Text Available The EGFR-specific mAb cetuximab is one of the most effective treatments for oropharyngeal carcinoma, while patient responses to EGFR inhibitors given alone are modest. Combination treatment with radiation can improve the efficacy of treatment through increasing radiosensitivity, while resistance to radiation after administration of cetuximab limits its efficiency. Radiation and drugs can damage the endoplasmic reticulum (ER homeostatic state and result in ER stress (ERS, subsequently causing resistance to radiation and drugs. Whether the ERS pathway is involved in radioresistance after administration of cetuximab has not been reported. Herein, we show that cetuximab could increase the radiosensitivity of FaDu cells but not Detroit562 cells. In addition, cetuximab inhibited the radiation-induced activation of the ERS signalling pathway IRE1α/ATF6-GRP78 in FaDu cells, while this effect was absent in Detroit562 cells. Silencing GRP78 increased the radiosensitivity of oropharyngeal carcinoma cells and inhibited radiation-induced DNA double-strand-break (DSB repair and autophagy. More interestingly, silencing GRP78 abrogated resistance to cetuximab and radiation in Detroit562 cells and had a synergistic effect with cetuximab in increasing the radiosensitivity of FaDu cells. Immunohistochemistry showed that overexpression of both GRP78 and EGFR was associated with a poor prognosis in oropharyngeal carcinoma patients (P<0.05. Overall, the results of this study show that radioresistance after EGFR inhibition by cetuximab is mediated by the ERS signalling pathway IRE1α/ATF6-GRP78. This suppression was consequently unable to inhibit radiation-induced DSB repair and autophagy in oropharyngeal carcinoma cells, which conferred resistance to radiotherapy and cetuximab. These results suggest that the cooperative effects of radiotherapy and cetuximab could be further improved by inhibiting GRP78 in non-responsive oropharyngeal carcinoma patients.

Fast fission phenomena

International Nuclear Information System (INIS)

Gregoire, Christian.

1982-03-01

Experimental studies of fast fission phenomena are presented. The paper is divided into three parts. In the first part, problems associated with fast fission processes are examined in terms of interaction potentials and a dynamic model is presented in which highly elastic collisions, the formation of compound nuclei and fast fission appear naturally. In the second part, a description is given of the experimental methods employed, the observations made and the preliminary interpretation of measurements suggesting the occurence of fast fission processes. In the third part, our dynamic model is incorporated in a general theory of the dissipative processes studied. This theory enables fluctuations associated with collective variables to be calculated. It is applied to highly inelastic collisions, to fast fission and to the fission dynamics of compound nuclei (for which a schematic representation is given). It is with these calculations that the main results of the second part can be interpreted [fr

Silencing of BAG3 inhibits the epithelial-mesenchymal transition in human cervical cancer.

Science.gov (United States)

Song, Fei; Wang, Geng; Ma, Zhifang; Ma, Yuebing; Wang, Yingying

2017-11-10

Bcl2-associated athanogene 3 (BAG3) has been reported to be involved in aggressive progression of many tumors. In the present study, we examined the expression of BAG3 in human cervical cancer (CC) tissues and investigated the role of BAG3 in SiHa and HeLa cell growth, migration, and invasion. Here, we found that most of CC tissues highly expressed the protein and mRNA of BAG3, while their expression was obviously lower in paired normal tissues (all pBAG3 expression was associated with FIGO stage and metastasis (all pBAG3 siRNAs inhibited SiHa and HeLa cell growth, invasion and migration. Mechanically, BAG3 siRNAs inhibited the expression of EMT-regulating markers, involving MMP2, Slug and N-cadherin, and increased the expression of E-cadherin. In a xenograft nude model, BAG3 siRNAs inhibited tumor growth and the expression of EMT biomarkers. In conclusion, BAG3 is involved in the EMT process, including cell growth, invasion and migration in the development of CC. Thus, BAG3 target might be recommended as a novel therapeutic approach.

Urokinase receptor expression involves tyrosine phosphorylation of phosphoglycerate kinase.

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Shetty, Praveenkumar; Velusamy, Thirunavukkarasu; Bhandary, Yashodhar P; Liu, Ming C; Shetty, Sreerama

2010-02-01

The interaction of urokinase-type plasminogen activator (uPA) with its receptor, uPAR, plays a central role in several pathophysiological processes, including cancer. uPA induces its own cell surface receptor expression through stabilization of uPAR mRNA. The mechanism involves binding of a 51 nt uPAR mRNA coding sequence with phosphoglycerate kinase (PGK) to down regulate cell surface uPAR expression. Tyrosine phosphorylation of PGK mediated by uPA treatment enhances uPAR mRNA stabilization. In contrast, inhibition of tyrosine phosphorylation augments PGK binding to uPAR mRNA and attenuates uPA-induced uPAR expression. Mapping the specific peptide region of PGK indicated that its first quarter (amino acids 1-100) interacts with uPAR mRNA. To determine if uPAR expression by uPA is regulated through activation of tyrosine residues of PGK, we mutated the specific tyrosine residue and tested mutant PGK for its ability to interfere with uPAR expression. Inhibition of tyrosine phosphorylation by mutating Y76 residue abolished uPAR expression induced by uPA treatment. These findings collectively demonstrate that Y76 residue present in the first quarter of the PGK molecule is involved in lung epithelial cell surface uPAR expression. This region can effectively mimic the function of a whole PGK molecule in inhibiting tumor cell growth.

Marketing fast food: impact of fast food restaurants in children's hospitals.

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Sahud, Hannah B; Binns, Helen J; Meadow, William L; Tanz, Robert R

2006-12-01

The objectives of this study were (1) to determine fast food restaurant prevalence in hospitals with pediatric residencies and (2) to evaluate how hospital environment affects purchase and perception of fast food. We first surveyed pediatric residency programs regarding fast food restaurants in their hospitals to determine the prevalence of fast food restaurants in these hospitals. We then surveyed adults with children after pediatric outpatient visits at 3 hospitals: hospital M with an on-site McDonald's restaurant, hospital R without McDonald's on site but with McDonald's branding, and hospital X with neither on-site McDonald's nor branding. We sought to determine attitudes toward, consumption of, and influences on purchase of fast food and McDonald's food. Fifty-nine of 200 hospitals with pediatric residencies had fast food restaurants. A total of 386 outpatient surveys were analyzed. Fast food consumption on the survey day was most common among hospital M respondents (56%; hospital R: 29%; hospital X: 33%), as was the purchase of McDonald's food (hospital M: 53%; hospital R: 14%; hospital X: 22%). McDonald's accounted for 95% of fast food consumed by hospital M respondents, and 83% of them bought their food at the on-site McDonald's. Using logistic regression analysis, hospital M respondents were 4 times more likely than respondents at the other hospitals to have purchased McDonald's food on the survey day. Visitors to hospitals M and R were more likely than those at hospital X to believe that McDonald's supported the hospital financially. Respondents at hospital M rated McDonald's food healthier than did respondents at the other hospitals. Fast food restaurants are fairly common in hospitals that sponsor pediatric residency programs. A McDonald's restaurant in a children's hospital was associated with significantly increased purchase of McDonald's food by outpatients, belief that the McDonald's Corporation supported the hospital financially, and higher rating

Fast High-Quality Noise

DEFF Research Database (Denmark)

Frisvad, Jeppe Revall; Wyvill, Geoff

2007-01-01

At the moment the noise functions available in a graphics programmer's toolbox are either slow to compute or they involve grid-line artifacts making them of lower quality. In this paper we present a real-time noise computation with no grid-line artifacts or other regularity problems. In other words......, we put a new tool in the box that computes fast high-quality noise. In addition to being free of artifacts, the noise we present does not rely on tabulated data (everything is computed on the fly) and it is easy to adjust quality vs. quantity for the noise. The noise is based on point rendering (like...... spot noise), but it extends to more than two dimensions. The fact that it is based on point rendering makes art direction of the noise much easier....

Determinants of the effectiveness of fast break actions in elite and sub-elite Italian men's basketball games.

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Conte, D; Favero, T G; Niederhausen, M; Capranica, L; Tessitore, A

2017-06-01

The aim of this study was to examine the determinants of successful and unsuccessful fast-break (FB) actions in elite and sub-elite basketball games. Fifteen 1 st -division (elite) and fifteen 3 rd -division (sub-elite) Italian men's championship games were analysed across two seasons (2012/2013 and 2013/2014). A binary logistic regression analysis was performed, and the fast-break outcome (successful vs. unsuccessful) was adopted as the dependent variable separately in both elite and sub-elite games. FB execution (initiation, advance and completion phases), typology (primary and secondary break) and the number of players involved (equal number or superiority) were used as independent variables. The results showed that the rate of success of FB actions was 63.5% and 59.7% in elite and sub-elite games, respectively. Moreover, successful FBs were more likely to be completed in the lane in relation to unsuccessful ones in both elite and sub-elite games (p<0.05). Finally, descriptive statistics showed that both elite and sub-elite teams executed FBs similarly. This study highlighted that completion zone was the only predictor of a successful fast break in basketball, while the typology and number of players involved did not predict fast break effectiveness. Moreover, elite and sub-elite teams executed fast break actions similarly. These findings might be useful for basketball coaches to optimize the training of FB actions.

Generation of fast-rise time, repetitive, (sub) nanosecond, high-voltage pulses

NARCIS (Netherlands)

Huiskamp, T.; Pemen, A.J.M.

2017-01-01

In this contribution we present our fast-rise time nanosecond pulse generator, capable of generating up to 50 kV (positive and negative) rectangular pulses at a repetition rate of up to 1 kHz and with a rise time of less than 200 picoseconds. We focus on the general concepts involved in the design

Involvement of a Lipoxygenase-Like Enzyme in Abscisic Acid Biosynthesis 1

Science.gov (United States)

Creelman, Robert A.; Bell, Erin; Mullet, John E.

1992-01-01

Several lines of evidence indicate that abscisic acid (ABA) is derived from 9′-cis-neoxanthin or 9′-cis-violaxanthin with xanthoxin as an intermediate. 18O-labeling experiments show incorporation primarily into the side chain carboxyl group of ABA, suggesting that oxidative cleavage occurs at the 11, 12 (11′, 12′) double bond of xanthophylls. Carbon monoxide, a strong inhibitor of heme-containing P-450 monooxygenases, did not inhibit ABA accumulation, suggesting that the oxygenase catalyzing the carotenoid cleavage step did not contain heme. This observation, plus the ability of lipoxygenase to make xanthoxin from violaxanthin, suggested that a lipoxygenase-like enzyme is involved in ABA biosynthesis. To test this idea, the ability of several soybean (Glycine max L.) lipoxygenase inhibitors (5,8,11-eicosatriynoic acid, 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, and naproxen) to inhibit stress-induced ABA accumulation in soybean cell culture and soybean seedlings was determined. All lipoxygenase inhibitors significantly inhibited ABA accumulation in response to stress. These results suggest that the in vivo oxidative cleavage reaction involved in ABA biosynthesis requires activity of a nonheme oxygenase having lipoxygenase-like properties. PMID:16668998

Inhibition of parathyroid hormone release by maitotoxin, a calcium channel activator

International Nuclear Information System (INIS)

Fitzpatrick, L.A.; Yasumoto, T.; Aurbach, G.D.

1989-01-01

Maitotoxin, a toxin derived from a marine dinoflagellate, is a potent activator of voltage-sensitive calcium channels. To further test the hypothesis that inhibition of PTH secretion by calcium is mediated via a calcium channel we studied the effect of maitotoxin on dispersed bovine parathyroid cells. Maitotoxin inhibited PTH release in a dose-dependent fashion, and inhibition was maximal at 1 ng/ml. Chelation of extracellular calcium by EGTA blocked the inhibition of PTH by maitotoxin. Maitotoxin enhanced the effects of the dihydropyridine calcium channel agonist (+)202-791 and increased the rate of radiocalcium uptake in parathyroid cells. Pertussis toxin, which ADP-ribosylates and inactivates a guanine nucleotide regulatory protein that interacts with calcium channels in the parathyroid cell, did not affect the inhibition of PTH secretion by maitotoxin. Maitotoxin, by its action on calcium channels allows entry of extracellular calcium and inhibits PTH release. Our results suggest that calcium channels are involved in the release of PTH. Inhibition of PTH release by maitotoxin is not sensitive to pertussis toxin, suggesting that maitotoxin may act distal to the site interacting with a guanine nucleotide regulatory protein, or maitotoxin could interact with other ions or second messengers to inhibit PTH release

Physiology of Ramadan fasting

OpenAIRE

Shokoufeh Bonakdaran

2016-01-01

Considering the emphasis of Islam on the importance of fasting, Muslims attempt to fast from dawn until sunset during the holy month of Ramadan. Fasting is associated with several benefits for normal and healthy individuals. However, it could pose high risks to the health of diabetic patients due to certain physiological changes. This study aimed to compare the physiological changes associated with fasting in healthy individuals and diabetic patients during Ramadan. Furthermore, we reviewed t...

Novel combination treatment of type 2 diabetes DPP-4 inhibition + metformin

Directory of Open Access Journals (Sweden)

Bo Ahrén

2008-04-01

Full Text Available Bo AhrénDepartment of Clinical Sciences, Division of Medicine, Lund University, Lund, SwedenAbstract: Inhibition of dipeptidyl peptidase-4 (DPP-4 as a novel therapy for type 2 diabetes is based on prevention of the inactivation process of bioactive peptides, the most important in the context of treatment of diabetes of which is glucagon-like peptide-1 (GLP-1. Most clinical experience with DPP-4 inhibition is based on vildagliptin (GalvusR, Novartis and sitagliptin (JanuviaR, Merck. These compounds improve glycemic control both in monotherapy and in combination with other oral hyperglycemic agents. Both have also been shown to efficiently improve glycemic control when added to ongoing metformin therapy in patients with inadequate glycemic control. Under that condition, they reduce HbA1c levels by 0.65%–1.1% (baseline HbA1c 7.2–8.7% in studies up to 52 weeks of duration in combination versus continuous therapy with metformin alone. Sitagliptin has also been examined in initial combination therapy with metformin have; HbA1c was reduced by this combination by 2.1% (baseline HbA1c 8.8% after 24 weeks of treatment. Both fasting and prandial glucose are reduced by DPP-4 inhibition in combination with metformin in association with improvement of insulin secretion and insulin resistance and increase in concentrations of active GLP-1. The combination of DPP-4 inhibition and metformin has been shown to be highly tolerable with very low risk of hypoglycemia. Hence, DPP-4 inhibition in combination with metformin is an efficient, safe and tolerable combination therapy for type 2 diabetes.Keywords: DPP-4 inhibition, sitagliptin, vildagliptin, metformin, type 2 diabetes

An Impermeant Ganetespib Analog Inhibits Extracellular Hsp90-Mediated Cancer Cell Migration that Involves Lysyl Oxidase 2-like Protein

Energy Technology Data Exchange (ETDEWEB)

McCready, Jessica [Department of Natural Sciences, Assumption College, Worcester, MA 01609 (United States); Wong, Daniel S. [Department of Developmental Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Cell and Molecular Physiology Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 (United States); Burlison, Joseph A.; Ying, Weiwen [Synta Pharmaceuticals, Lexington, MA 02421 (United States); Jay, Daniel G., E-mail: daniel.jay@tufts.edu [Department of Developmental Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Cell and Molecular Physiology Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 (United States)

2014-04-30

Extracellular Hsp90 (eHsp90) activates a number of client proteins outside of cancer cells required for migration and invasion. Therefore, eHsp90 may serve as a novel target for anti-metastatic drugs as its inhibition using impermeant Hsp90 inhibitors would not affect the numerous vital intracellular Hsp90 functions in normal cells. While some eHsp90 clients are known, it is important to establish other proteins that act outside the cell to validate eHsp90 as a drug target to limit cancer spread. Using mass spectrometry we identified two precursor proteins Galectin 3 binding protein (G3BP) and Lysyl oxidase 2-like protein (LOXL2) that associate with eHsp90 in MDA-MB231 breast cancer cell conditioned media and confirmed that LOXL2 binds to eHsp90 in immunoprecipitates. We introduce a novel impermeant Hsp90 inhibitor STA-12-7191 derived from ganetespib and show that it is markedly less toxic to cells and can inhibit cancer cell migration in a dose dependent manner. We used STA-12-7191 to test if LOXL2 and G3BP are potential eHsp90 clients. We showed that while LOXL2 can increase wound healing and compensate for STA-12-7191-mediated inhibition of wound closure, addition of G3BP had no affect on this assay. These findings support of role for LOXL2 in eHsp90 stimulated cancer cell migration and provide preliminary evidence for the use of STA-12-7191 to inhibit eHsp90 to limit cancer invasion.

An Impermeant Ganetespib Analog Inhibits Extracellular Hsp90-Mediated Cancer Cell Migration that Involves Lysyl Oxidase 2-like Protein

International Nuclear Information System (INIS)

McCready, Jessica; Wong, Daniel S.; Burlison, Joseph A.; Ying, Weiwen; Jay, Daniel G.

2014-01-01

Extracellular Hsp90 (eHsp90) activates a number of client proteins outside of cancer cells required for migration and invasion. Therefore, eHsp90 may serve as a novel target for anti-metastatic drugs as its inhibition using impermeant Hsp90 inhibitors would not affect the numerous vital intracellular Hsp90 functions in normal cells. While some eHsp90 clients are known, it is important to establish other proteins that act outside the cell to validate eHsp90 as a drug target to limit cancer spread. Using mass spectrometry we identified two precursor proteins Galectin 3 binding protein (G3BP) and Lysyl oxidase 2-like protein (LOXL2) that associate with eHsp90 in MDA-MB231 breast cancer cell conditioned media and confirmed that LOXL2 binds to eHsp90 in immunoprecipitates. We introduce a novel impermeant Hsp90 inhibitor STA-12-7191 derived from ganetespib and show that it is markedly less toxic to cells and can inhibit cancer cell migration in a dose dependent manner. We used STA-12-7191 to test if LOXL2 and G3BP are potential eHsp90 clients. We showed that while LOXL2 can increase wound healing and compensate for STA-12-7191-mediated inhibition of wound closure, addition of G3BP had no affect on this assay. These findings support of role for LOXL2 in eHsp90 stimulated cancer cell migration and provide preliminary evidence for the use of STA-12-7191 to inhibit eHsp90 to limit cancer invasion

Trace element inhibition of phytase activity.

Science.gov (United States)

Santos, T; Connolly, C; Murphy, R

2015-02-01

Nowadays, 70 % of global monogastric feeds contains an exogenous phytase. Phytase supplementation has enabled a more efficient utilisation of phytate phosphorous (P) and reduction of P pollution. Trace minerals, such as iron (Fe), zinc (Zn), copper (Cu) and manganese (Mn) are essential for maintaining health and immunity as well as being involved in animal growth, production and reproduction. Exogenous sources of phytase and trace elements are regularly supplemented to monogastric diets and usually combined in a premix. However, the possibility for negative interaction between individual components within the premix is high and is often overlooked. Therefore, this initial study focused on assessing the potential in vitro interaction between inorganic and organic chelated sources of Fe, Zn, Cu and Mn with three commercially available phytase preparations. Additionally, this study has investigated if the degree of enzyme inhibition was dependent of the type of chelated sources. A highly significant relationship between phytase inhibition, trace mineral type as well as mineral source and concentration, p phytases for Fe and Zn, as well as for Cu with E. coli and Aspergillus niger phytases. Different chelate trace mineral sources demonstrated diversifying abilities to inhibit exogenous phytase activity.

Action video gaming and cognitive control: playing first person shooter games is associated with improvement in working memory but not action inhibition

NARCIS (Netherlands)

Colzato, L.S.; van den Wildenberg, W.P.M.; Zmigrod, S.; Hommel, B.

2013-01-01

The interest in the influence of videogame experience in our daily life is constantly growing. "First Person Shooter" (FPS) games require players to develop a flexible mindset to rapidly react and monitor fast moving visual and auditory stimuli, and to inhibit erroneous actions. This study

Ethyl Pyruvate Emerges as a Safe and Fast Acting Agent against Trypanosoma brucei by Targeting Pyruvate Kinase Activity.

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Netsanet Worku

Full Text Available Human African Trypanosomiasis (HAT also called sleeping sickness is an infectious disease in humans caused by an extracellular protozoan parasite. The disease, if left untreated, results in 100% mortality. Currently available drugs are full of severe drawbacks and fail to escape the fast development of trypanosoma resistance. Due to similarities in cell metabolism between cancerous tumors and trypanosoma cells, some of the current registered drugs against HAT have also been tested in cancer chemotherapy. Here we demonstrate for the first time that the simple ester, ethyl pyruvate, comprises such properties.The current study covers the efficacy and corresponding target evaluation of ethyl pyruvate on T. brucei cell lines using a combination of biochemical techniques including cell proliferation assays, enzyme kinetics, phasecontrast microscopic video imaging and ex vivo toxicity tests. We have shown that ethyl pyruvate effectively kills trypanosomes most probably by net ATP depletion through inhibition of pyruvate kinase (Ki = 3.0±0.29 mM. The potential of ethyl pyruvate as a trypanocidal compound is also strengthened by its fast acting property, killing cells within three hours post exposure. This has been demonstrated using video imaging of live cells as well as concentration and time dependency experiments. Most importantly, ethyl pyruvate produces minimal side effects in human red cells and is known to easily cross the blood-brain-barrier. This makes it a promising candidate for effective treatment of the two clinical stages of sleeping sickness. Trypanosome drug-resistance tests indicate irreversible cell death and a low incidence of resistance development under experimental conditions.Our results present ethyl pyruvate as a safe and fast acting trypanocidal compound and show that it inhibits the enzyme pyruvate kinase. Competitive inhibition of this enzyme was found to cause ATP depletion and cell death. Due to its ability to easily cross

The effect of metformin on monocyte secretory function in simvastatin-treated patients with impaired fasting glucose.

Science.gov (United States)

Krysiak, Robert; Okopien, Bogusław

2013-01-01

This study was designed to investigate whether metformin affects monocyte secretory function in patients with impaired fasting glucose receiving chronic statin therapy. The study included 48 patients with impaired fasting glucose treated for at least three months with simvastatin (40 mg daily). These patients were randomized to either metformin (3 g daily) or placebo, which was administered together with simvastatin for 90 days. Plasma lipids, glucose homeostasis markers, monocyte cytokine release and plasma C-reactive protein levels were determined before randomization and at the end of the treatment. Compared to placebo, metformin reduced monocyte release of tumor necrosis factor-α, interleukin-1β, interleukin-6, monocyte chemoattractant protein-1 and interleukin-8, as well as decreased plasma C-reactive protein levels, which were accompanied by an improvement in insulin sensitivity. The obtained results suggest that metformin may inhibit monocyte secretory function and reduce systemic inflammation in statin-treated patients with prediabetes. Impaired fasting glucose patients with high cardiovascular risk may receive the greatest benefits from concomitant treatment with a statin and metformin. Copyright © 2013 Elsevier Inc. All rights reserved.

Fast neutron radiotherapy: for equal or for better

International Nuclear Information System (INIS)

Broerse, J.J.; Battermann, J.J.

1981-01-01

The renewed application of fast neutrons in clinical radiotherapy has been stimulated by fundamental radiobiological findings. The biological effects of high LET radiation, including fast neutrons, are different from those obtained with x rays in at least three respects: the oxygen enhancement ratio, the sensitivity of cells at different phases of the cell cycle, and the contribution of sublethal damage to cell reproductive death. Furthermore, wide variations in relative biological effectiveness (RBE) have been observed for different tumors and normal tissues. Measurements of volume changes in human pulmonary metastases indicate that the RBE for slowly growing tumors which are generally well-differentiated is higher than that for poorly differentiated lesions. Six thousand patients have now been treated with fast neutron beams. The results of the clinical applications vary according to the method of application and to the type of cancer involved: treatment of inoperable malignancies of the salivary gland is very encouraging: the therapeutic gain is rather small for bladder and rectal cancers, soft tissue sarcomas and advanced carcinomas of the cervix; the responses of brain tumors are very disappointing. Most neutron radiotherapy applications have been less than optimal because of inadequate physical and technical conditions. Despite these difficulties, some interesting clinical data have become available. Due to the technical shortcomings, the possible advantages of fast neutrons are probably underestimated for many tumor sites. Well-designed clinical trials, preferably performed with high energy cyclotrons in clinical environments, will provide a decisive answer to the question of the usefulness of the new radiation modality

Gene expression of transporters and phase I/II metabolic enzymes in murine small intestine during fasting

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van der Meijde Jolanda

2007-08-01

Full Text Available Abstract Background Fasting has dramatic effects on small intestinal transport function. However, little is known on expression of intestinal transport and phase I/II metabolism genes during fasting and the role the fatty acid-activated transcription factor PPARα may play herein. We therefore investigated the effects of fasting on expression of these genes using Affymetrix GeneChip MOE430A arrays and quantitative RT-PCR. Results After 24 hours of fasting, expression levels of 33 of the 253 analyzed transporter and phase I/II metabolism genes were changed. Upregulated genes were involved in transport of energy-yielding molecules in processes such as glycogenolysis (G6pt1 and mitochondrial and peroxisomal oxidation of fatty acids (Cact, Mrs3/4, Fatp2, Cyp4a10, Cyp4b1. Other induced genes were responsible for the inactivation of the neurotransmitter serotonin (Sert, Sult1d1, Dtd, Papst2, formation of eicosanoids (Cyp2j6, Cyp4a10, Cyp4b1, or for secretion of cholesterol (Abca1 and Abcg8. Cyp3a11, typically known because of its drug metabolizing capacity, was also increased. Fasting had no pronounced effect on expression of phase II metabolic enzymes, except for glutathione S-transferases which were down-regulated. Time course studies revealed that some genes were acutely regulated, whereas expression of other genes was only affected after prolonged fasting. Finally, we identified 8 genes that were PPARα-dependently upregulated upon fasting. Conclusion We have characterized the response to fasting on expression of transporters and phase I/II metabolic enzymes in murine small intestine. Differentially expressed genes are involved in a variety of processes, which functionally can be summarized as a increased oxidation of fat and xenobiotics, b increased cholesterol secretion, c increased susceptibility to electrophilic stressors, and d reduced intestinal motility. This knowledge increases our understanding of gut physiology, and may be of relevance

Inhibition of Direct Electrolytic Ammonia Oxidation Due to a Change in Local pH

International Nuclear Information System (INIS)

Zöllig, Hanspeter; Morgenroth, Eberhard; Udert, Kai M.

2015-01-01

Electrochemical ammonia oxidation has gained a lot of attention recently as an efficient method for ammonia removal from wastewater, for the use in ammonia-based fuel cells and the production of high purity hydrogen. Thermally decomposed iridium oxide films (TDIROF) have been shown to be catalytically active for direct ammonia oxidation in aqueous solutions if NH 3 is present. However, the process was reported to be rapidly inhibited on TDIROF. Herein, we show that this fast inhibition of direct ammonia oxidation does not result from surface poisoning by adsorbed elemental nitrogen (N ads ). Instead, we propose that direct ammonia oxidation and oxygen evolution can lead to a drop of the local pH at the electrode resulting in a low availability of the actual reactant, NH 3 . The hypothesis was tested with cyclic voltammetry (CV) experiments on stagnant and rotating disk electrodes (RDE). The CV experiments on the stagnant electrode revealed that the decrease of the ammonia oxidation peaks was considerably reduced by introducing an idle phase at open circuit potential between subsequent scans. Furthermore, the polarization of the TDIROF electrode into the hydrogen evolution region (HER) resulted in increased ammonia oxidation peaks in the following anodic scans which can be explained with an increased local pH after the consumption of protons in the HER. On the RDE, the ammonia oxidation peaks did not decrease in immediately consecutive scans. These findings would not be expected if surface poisoning was responsible for the fast inhibition but they are in good agreement with the proposed mechanism of pH induced limitation by the reactant, NH 3 . The plausibility of the mechanism was also supported by our numerical simulations of the processes in the Nernstian diffusion layer. The knowledge about this inhibition mechanism of direct ammonia oxidation is especially important for the design of electrochemical cells for wastewater treatment. The mechanism is not only

Fast breeder reactors

International Nuclear Information System (INIS)

Heinzel, V.

1975-01-01

The author gives a survey of 'fast breeder reactors'. In detail the process of breeding, the reasons for the development of fast breeders, the possible breeder reactors, the design criteria, fuels, cladding, coolant, and safety aspects are reported on. Design data of some experimental reactors already in operation are summarized in stabular form. 300 MWe Prototype-Reactors SNR-300 and PFR are explained in detail and data of KWU helium-cooled fast breeder reactors are given. (HR) [de

Fast reactors worldwide

International Nuclear Information System (INIS)

Hall, R.S.; Vignon, D.

1985-01-01

The paper concerns the evolution of fast reactors over the past 30 years, and their present status. Fast reactor development in different countries is described, and the present position, with emphasis on cost reduction and collaboration, is examined. The French development of the fast breeder type reactor is reviewed, and includes: the acquisition of technical skills, the search for competitive costs and the spx2 project, and more advanced designs. Future prospects are also discussed. (U.K.)

Fast food (image)

Science.gov (United States)

Fast foods are quick, reasonably priced, and readily available alternatives to home cooking. While convenient and economical for a busy lifestyle, fast foods are typically high in calories, fat, saturated fat, ...

Striatal D1- and D2-type dopamine receptors are linked to motor response inhibition in human subjects.

Science.gov (United States)

Robertson, Chelsea L; Ishibashi, Kenji; Mandelkern, Mark A; Brown, Amira K; Ghahremani, Dara G; Sabb, Fred; Bilder, Robert; Cannon, Tyrone; Borg, Jacqueline; London, Edythe D

2015-04-15

Motor response inhibition is mediated by neural circuits involving dopaminergic transmission; however, the relative contributions of dopaminergic signaling via D1- and D2-type receptors are unclear. Although evidence supports dissociable contributions of D1- and D2-type receptors to response inhibition in rats and associations of D2-type receptors to response inhibition in humans, the relationship between D1-type receptors and response inhibition has not been evaluated in humans. Here, we tested whether individual differences in striatal D1- and D2-type receptors are related to response inhibition in human subjects, possibly in opposing ways. Thirty-one volunteers participated. Response inhibition was indexed by stop-signal reaction time on the stop-signal task and commission errors on the continuous performance task, and tested for association with striatal D1- and D2-type receptor availability [binding potential referred to nondisplaceable uptake (BPND)], measured using positron emission tomography with [(11)C]NNC-112 and [(18)F]fallypride, respectively. Stop-signal reaction time was negatively correlated with D1- and D2-type BPND in whole striatum, with significant relationships involving the dorsal striatum, but not the ventral striatum, and no significant correlations involving the continuous performance task. The results indicate that dopamine D1- and D2-type receptors are associated with response inhibition, and identify the dorsal striatum as an important locus of dopaminergic control in stopping. Moreover, the similar contribution of both receptor subtypes suggests the importance of a relative balance between phasic and tonic dopaminergic activity subserved by D1- and D2-type receptors, respectively, in support of response inhibition. The results also suggest that the stop-signal task and the continuous performance task use different neurochemical mechanisms subserving motor response inhibition. Copyright © 2015 the authors 0270-6474/15/355990-08$15.00/0.

Islamic Fasting and Diabetes

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Fereidoun Azizi

2013-07-01

Full Text Available The aim of this article is to review health-related aspects of Ramadan fasting in normal individuals and diabetics. During fasting days of Ramadan, glucose homeostasis is maintained by meal taken bepore dawn and by liver glycogen stores. Changes in serum lipids are variable and defend on the quality and quantity of food consumption and changes in weight. Compliant, well controlled type 2 diabetics may observe Ramadan fasting; but fasting is not recommended for type 1, non complaint, poorly controlled and pregnant diabetics. Although Ramadan fasting is safe for all healthy individuals and well controlled diabetics, those with uncontrolled diabetics and diabetics with complications should consult physicians and follow scientific recommendations.

Fast reactor programme

International Nuclear Information System (INIS)

Plakman, J.C.

1982-01-01

This progress report summarizes the fast reactor research carried out by ECN during the period covering the year 1980. This research is mainly concerned with the cores of sodium-cooled breeders, in particular the SNR-300, and its related safety aspects. It comprises six items: A programme to determine relevant nuclear data of fission- and corrosion-products; A fuel performance programme comprising in-pile cladding failure experiments and a study of the consequences of loss-of-cooling and overpower; Basic research on fuel; Investigation of the changes in the mechanical properties of austenitic stainless steel DIN 1.4948 due to fast neutron doses, this material has been used in the manufacture of the reactor vessel and its internal components; Study of aerosols which could be formed at the time of a fast reactor accident and their progressive behaviour on leaking through cracks in the concrete containment; Studies on heat transfer in a sodium-cooled fast reactor core. As fast breeders operate at high power densities, an accurate knowledge of the heat transfer phenomena under single-phase and two-phase conditions is sought. (Auth.)

Perturbations of Amino Acid Metabolism Associated with Glyphosate-Dependent Inhibition of Shikimic Acid Metabolism Affect Cellular Redox Homeostasis and Alter the Abundance of Proteins Involved in Photosynthesis and Photorespiration1[W][OA

Science.gov (United States)

Vivancos, Pedro Diaz; Driscoll, Simon P.; Bulman, Christopher A.; Ying, Liu; Emami, Kaveh; Treumann, Achim; Mauve, Caroline; Noctor, Graham; Foyer, Christine H.

2011-01-01

The herbicide glyphosate inhibits the shikimate pathway of the synthesis of amino acids such as phenylalanine, tyrosine, and tryptophan. However, much uncertainty remains concerning precisely how glyphosate kills plants or affects cellular redox homeostasis and related processes in glyphosate-sensitive and glyphosate-resistant crop plants. To address this issue, we performed an integrated study of photosynthesis, leaf proteomes, amino acid profiles, and redox profiles in the glyphosate-sensitive soybean (Glycine max) genotype PAN809 and glyphosate-resistant Roundup Ready Soybean (RRS). RRS leaves accumulated much more glyphosate than the sensitive line but showed relatively few changes in amino acid metabolism. Photosynthesis was unaffected by glyphosate in RRS leaves, but decreased abundance of photosynthesis/photorespiratory pathway proteins was observed together with oxidation of major redox pools. While treatment of a sensitive genotype with glyphosate rapidly inhibited photosynthesis and triggered the appearance of a nitrogen-rich amino acid profile, there was no evidence of oxidation of the redox pools. There was, however, an increase in starvation-associated and defense proteins. We conclude that glyphosate-dependent inhibition of soybean leaf metabolism leads to the induction of defense proteins without sustained oxidation. Conversely, the accumulation of high levels of glyphosate in RRS enhances cellular oxidation, possibly through mechanisms involving stimulation of the photorespiratory pathway. PMID:21757634

Electroacupuncture Inhibition of Hyperalgesia in Rats with Adjuvant Arthritis: Involvement of Cannabinoid Receptor 1 and Dopamine Receptor Subtypes in Striatum

Directory of Open Access Journals (Sweden)

Yin Shou

2013-01-01

Full Text Available Electroacupuncture (EA has been regarded as an alternative treatment for inflammatory pain for several decades. However, the molecular mechanisms underlying the antinociceptive effect of EA have not been thoroughly clarified. Previous studies have shown that cannabinoid CB1 receptors are related to pain relief. Accumulating evidence has shown that the CB1 and dopamine systems sometimes interact and may operate synergistically in rat striatum. To our knowledge, dopamine D1/D2 receptors are involved in EA analgesia. In this study, we found that repeated EA at Zusanli (ST36 and Kunlun (BL60 acupoints resulted in marked improvements in thermal hyperalgesia. Both western blot assays and FQ-PCR analysis results showed that the levels of CB1 expression in the repeated-EA group were much higher than those in any other group (P=0.001. The CB1-selective antagonist AM251 inhibited the effects of repeated EA by attenuating the increases in CB1 expression. The two kinds of dopamine receptors imparted different actions on the EA-induced CB1 upregulation in AA rat model. These results suggested that the strong activation of the CB1 receptor after repeated EA resulted in the concomitant phenomenon of the upregulation of D1 and D2 levels of gene expression.

HCUP Fast Stats

Data.gov (United States)

U.S. Department of Health & Human Services — HCUP Fast Stats provides easy access to the latest HCUP-based statistics for health information topics. HCUP Fast Stats uses visual statistical displays in...

Aminopeptidase N inhibition could be involved in the anti-angiogenic effect of dobesilates

Directory of Open Access Journals (Sweden)

Farsa Oldřich

2015-01-01

Full Text Available Calcium, magnesium and zinc 2,5-dihydroxybenzenesulfonates (dobesilates were synthesized by sulfonation of hydroquinone with sulfuric acid under mild conditions. To form the salts, neutralization with calcium carbonate followed by cation exchange by means of magnesium or zinc sulfates was performed. The dobesilates were characterized by standard spectral methods and by AAS for metal content and then tested for inhibitory activity against aminopeptidase N. Calcium and magnesium 2,5-dihydroxybenzene sulfonates exhibited rather weak inhibitory activity to aminopeptidase N as demonstrated by IC50 values of 978.0 and 832.1 mmol l-1 respectively while zinc 2,5-dihydroxybenzene sulfonate reached the more significant inhibitory activity characterized by IC50 77.4 mmol l-1. The inhibitory activity results suggest that the inhibition of aminopeptidase N could play a role in the anti-angiogenic activity of 2,5-dihydroxybenzenesulfonates.

Inhibition of epithelial Na+ transport by atriopeptin, protein kinase c, and pertussis toxin

International Nuclear Information System (INIS)

Mohrmann, M.; Cantiello, H.F.; Ausiello, D.A.

1987-01-01

The authors have recently shown the selective inhibition of an amiloride-sensitive, conductive pathway for Na + by atrial natriuretic peptide and 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) in the renal epithelial cell line, LLC-PK i . Using 22 Na + fluxes, they further investigated the modulation of Na + transport by atrial natriuretic peptide and by agents that increase cGMP production, activate protein kinase c, or modulate guanine nucleotide regulatory protein function. Sodium nitroprusside increases intracellular cGMP concentrations without affecting cAMP concentrations and completely inhibits amiloride-sensitive Na + uptake in a time- and concentration-dependent manner. Oleoyl 2-acetylglycerol and phorbol 12-myristate 13-acetate, activators of protein kinase c, inhibit Na + uptake by 93 ± 13 and 51 ± 10%, respectively. Prolonged incubation with phorbol ester results in the downregulation of protein kinase c activity and reduces the inhibitory effect of atrial natriuretic peptide, suggesting that the action of this peptide involves stimulation of protein kinase c. Pertussis toxin, which induces the ADP-ribosylation of a 41-kDa guanine nucleotide regulatory protein in LLC-PK i cells, inhibits 22 Na + influx to the same extent as amiloride. Thus, increasing cGMP, activating protein kinase c, and ADP-ribosylating a guanine nucleotide regulatory protein all inhibit Na + uptake. These events may be sequentially involved in the action of atrial natriuretic peptide

Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis.

Directory of Open Access Journals (Sweden)

Johannes J Kovarik

Full Text Available A crucial role of cell metabolism in immune cell differentiation and function has been recently established. Growing evidence indicates that metabolic processes impact both, innate and adaptive immunity. Since a down-stream integrator of metabolic alterations, mammalian target of rapamycin (mTOR, is responsible for controlling the balance between pro-inflammatory interleukin (IL-12 and anti-inflammatory IL-10, we investigated the effect of upstream interference using metabolic modulators on the production of pro- and anti-inflammatory cytokines. Cytokine release and protein expression in human and murine myeloid cells was assessed after toll-like receptor (TLR-activation and glucose-deprivation or co-treatment with 5'-adenosine monophosphate (AMP-activated protein kinase (AMPK activators. Additionally, the impact of metabolic interference was analysed in an in-vivo mouse model. Glucose-deprivation by 2-deoxy-D-glucose (2-DG increased the production of IL-12p40 and IL-23p19 in monocytes, but dose-dependently inhibited the release of anti-inflammatory IL-10. Similar effects have been observed using pharmacological AMPK activation. Consistently, an inhibition of the tuberous sclerosis complex-mTOR pathway was observed. In line with our in vitro observations, glycolysis inhibition with 2-DG showed significantly reduced bacterial burden in a Th2-prone Listeria monocytogenes mouse infection model. In conclusion, we showed that fasting metabolism modulates the IL-12/IL-10 cytokine balance, establishing novel targets for metabolism-based immune-modulation.

Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis

Science.gov (United States)

Kernbauer, Elisabeth; Hölzl, Markus A.; Hofer, Johannes; Gualdoni, Guido A.; Schmetterer, Klaus G.; Miftari, Fitore; Sobanov, Yury; Meshcheryakova, Anastasia; Mechtcheriakova, Diana; Witzeneder, Nadine; Greiner, Georg; Ohradanova-Repic, Anna; Waidhofer-Söllner, Petra; Säemann, Marcus D.; Decker, Thomas

2017-01-01

A crucial role of cell metabolism in immune cell differentiation and function has been recently established. Growing evidence indicates that metabolic processes impact both, innate and adaptive immunity. Since a down-stream integrator of metabolic alterations, mammalian target of rapamycin (mTOR), is responsible for controlling the balance between pro-inflammatory interleukin (IL)-12 and anti-inflammatory IL-10, we investigated the effect of upstream interference using metabolic modulators on the production of pro- and anti-inflammatory cytokines. Cytokine release and protein expression in human and murine myeloid cells was assessed after toll-like receptor (TLR)-activation and glucose-deprivation or co-treatment with 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activators. Additionally, the impact of metabolic interference was analysed in an in-vivo mouse model. Glucose-deprivation by 2-deoxy-D-glucose (2-DG) increased the production of IL-12p40 and IL-23p19 in monocytes, but dose-dependently inhibited the release of anti-inflammatory IL-10. Similar effects have been observed using pharmacological AMPK activation. Consistently, an inhibition of the tuberous sclerosis complex-mTOR pathway was observed. In line with our in vitro observations, glycolysis inhibition with 2-DG showed significantly reduced bacterial burden in a Th2-prone Listeria monocytogenes mouse infection model. In conclusion, we showed that fasting metabolism modulates the IL-12/IL-10 cytokine balance, establishing novel targets for metabolism-based immune-modulation. PMID:28742108

Fast-prototyping of VLSI

International Nuclear Information System (INIS)

Saucier, G.; Read, E.

1987-01-01

Fast-prototyping will be a reality in the very near future if both straightforward design methods and fast manufacturing facilities are available. This book focuses, first, on the motivation for fast-prototyping. Economic aspects and market considerations are analysed by European and Japanese companies. In the second chapter, new design methods are identified, mainly for full custom circuits. Of course, silicon compilers play a key role and the introduction of artificial intelligence techniques sheds a new light on the subject. At present, fast-prototyping on gate arrays or on standard cells is the most conventional technique and the third chapter updates the state-of-the art in this area. The fourth chapter concentrates specifically on the e-beam direct-writing for submicron IC technologies. In the fifth chapter, a strategic point in fast-prototyping, namely the test problem is addressed. The design for testability and the interface to the test equipment are mandatory to fulfill the test requirement for fast-prototyping. Finally, the last chapter deals with the subject of education when many people complain about the lack of use of fast-prototyping in higher education for VLSI

A prospective audit of preprocedural fasting practices on a transplant ward: when fasting becomes starving.

Science.gov (United States)

Vidot, Helen; Teevan, Kate; Carey, Sharon; Strasser, Simone; Shackel, Nicholas

2016-03-01

To investigate the prevalence and duration of preprocedural medically ordered fasting during a period of hospitalisation in an Australian population of patients with hepatic cirrhosis or following liver transplantation and to identify potential solutions to reduce fasting times. Protein-energy malnutrition is a common finding in patients with hepatic cirrhosis and can impact significantly on survival and quality of life. Protein and energy requirements in patients with cirrhosis are higher than those of healthy individuals. A significant feature of cirrhosis is the induction of starvation metabolism following seven to eight hours of food deprivation. Many investigative and interventional procedures for patients with cirrhosis necessitate a period of fasting to comply with anaesthesia guidelines. An observational study of the fasting episodes for 34 hospitalised patients with hepatic cirrhosis or following liver transplantation. Nutritional status was estimated using subjective global assessment and handgrip strength. The prevalence and duration of fasting practices for diagnostic or investigational procedures were estimated using electronic records and patient notes. Thirty-three patients (97%) were malnourished. Twenty-two patients (65%) were fasted during the observation period. There were 43 occasions of fasting with a median fasting time of 13·5 hours. On 40 occasions fasting times exceeded the maximum six-hour guideline recommended prior to the administration of anaesthesia by the majority of Anaesthesiology Societies. The majority of procedures (77%) requiring fasting occurred after midday. Eating breakfast on the day of the procedure reduced fasting time by 45%. Medically ordered preprocedural fasting times almost always exceed existing guidelines in this nutritionally compromised group. Adherence to fasting guidelines and eating breakfast before the procedure can reduce fasting times significantly and avoid the potential induction of starvation metabolism

Early childhood behavioral inhibition, adult psychopathology and the buffering effects of adolescent social networks: a twenty-year prospective study.

Science.gov (United States)

Frenkel, Tahl I; Fox, Nathan A; Pine, Daniel S; Walker, Olga L; Degnan, Kathryn A; Chronis-Tuscano, Andrea

2015-10-01

We examined whether the temperament of behavioral inhibition is a significant marker for psychopathology in early adulthood and whether such risk is buffered by peer social networks. Participants (N = 165) were from a prospective study spanning the first two decades of life. Temperament was characterized during infancy and early childhood. Extent of involvement in peer social networks was measured during adolescence, and psychopathology was assessed in early adulthood. Latent Class Analyses generated comprehensive variables at each of three study time-points. Regressions assessed (a) the direct effect of early behavioral inhibition on adult psychopathology (b) the moderating effect of adolescent involvement in social peer networks on the link between temperamental risk and adult psychopathology. Stable behavioral inhibition in early childhood was negatively associated with adult mental health (R(2 ) = .07, p = .005, β = -.26), specifically increasing risk for adult anxiety disorders (R(2) = .04, p = .037, β = .19). These temperament-pathology relations were significantly moderated by adolescent peer group social involvement and network size (Total R(2) = .13, p = .027, β = -.22). Temperament predicted heightened risk for adult anxiety when adolescent social involvement was low (p = .002, β = .43), but not when adolescent social involvement was high. Stable behavioral inhibition throughout early childhood is a risk factor for adult anxiety disorders and interacts with adolescent social involvement to moderate risk. This is the first study to demonstrate the critical role of adolescent involvement in socially active networks in moderating long-lasting temperamental risk over the course of two decades, thus informing prevention/intervention approaches. © 2015 Association for Child and Adolescent Mental Health.

Arginase Inhibition Ameliorates Hepatic Metabolic Abnormalities in Obese Mice

Science.gov (United States)

Moon, Jiyoung; Do, Hyun Ju; Cho, Yoonsu; Shin, Min-Jeong

2014-01-01

Objectives We examined whether arginase inhibition influences hepatic metabolic pathways and whole body adiposity in diet-induced obesity. Methods and Results After obesity induction by a high fat diet (HFD), mice were fed either the HFD or the HFD with an arginase inhibitor, Nω-hydroxy-nor-L-arginine (nor-NOHA). Nor-NOHA significantly prevented HFD-induced increases in body, liver, and visceral fat tissue weight, and ameliorated abnormal lipid profiles. Furthermore, nor-NOHA treatment reduced lipid accumulation in oleic acid-induced hepatic steatosis in vitro. Arginase inhibition increased hepatic nitric oxide (NO) in HFD-fed mice and HepG2 cells, and reversed the elevated mRNA expression of hepatic genes in lipid metabolism. Expression of phosphorylated 5′ AMPK-activated protein kinase α was increased by arginase inhibition in the mouse livers and HepG2 cells. Conclusions Arginase inhibition ameliorated obesity-induced hepatic lipid abnormalities and whole body adiposity, possibly as a result of increased hepatic NO production and subsequent activation of metabolic pathways involved in hepatic triglyceride metabolism and mitochondrial function. PMID:25057910

Adrenaline inhibits osteogenesis via repressing miR-21 expression.

Science.gov (United States)

Chen, Danying; Wang, Zuolin

2017-01-01

Sympathetic signaling is involved in bone homeostasis; however, the cellular and molecular mechanisms remain unknown. In this study, we found that the psychological stress mediator adrenaline inhibited osteogenic differentiation of human bone marrow-derived stem cells (hMSC) by reducing microRNA-21 (miR-21) expression. Briefly, adrenaline significantly inhibited the osteogenic differentiation of hMSCs, as observed with both Alizarin red staining and maker gene expression (RUNX2, OSX, OCN, and OPN). During this process, miR-21 was suppressed by adrenaline via inhibition of histone acetylation, as verified by H3K9Ac chromatin immunoprecipitation (ChIP) assay. MiR-21 was confirmed to promote hMSC osteogenic differentiation, and overexpression of miR-21 reversed the impeditive effect of adrenaline on hMSC osteogenic differentiation. Our results demonstrate that down-regulation of miR-21 is responsible for the adrenaline-mediated inhibition of hMSC osteogenic differentiation. These findings indicate a regulation of bone metabolism by psychological stress and also provide a molecular basis for psychological stress-associated bone diseases. © 2016 International Federation for Cell Biology.

The fast breeder reactor

International Nuclear Information System (INIS)

Collier, J.

1990-01-01

The arguments for and against the fast breeder reactor are debated. The case for the fast reactor is that the world energy demand will increase due to increasing population over the next forty years and that the damage to the global environment from burning fossil fuels which contribute to the greenhouse effect. Nuclear fission is the only large scale energy source which can achieve a cut in the use of carbon based fuels although energy conservation and renewable sources will also be important. Fast reactors produce more energy from uranium than other types of (thermal) reactors such as AGRs and PWRs. Fast reactors would be important from about 2020 onwards especially as by then many thermal reactors will need to be replaced. Fast reactors are also safer than normal reactors. The arguments against fast reactors are largely economic. The cost, especially the capital cost is very high. The viability of the technology is also questioned. (UK)

The fast breeder reactor

International Nuclear Information System (INIS)

Davis, D.A.; Baker, M.A.W.; Hall, R.S.

1990-01-01

Following submission of written evidence, the Energy Committee members asked questions of three witnesses from the Central Electricity Generating Board and Nuclear Electric (which will be the government owned company running nuclear power stations after privatisation). Both questions and answers are reported verbatim. The points raised include where the responsibility for the future fast reactor programme should lie, with government only or with private enterprise or both and the viability of fast breeder reactors in the future. The case for the fast reactor was stated as essentially strategic not economic. This raised the issue of nuclear cost which has both a construction and a decommissioning element. There was considerable discussion as to the cost of building a European Fast reactor and the cost of the electricity it would generate compared with PWR type reactors. The likely demand for fast reactors will not arrive for 20-30 years and the need to build a fast reactor now is questioned. (UK)

The French liquid metal fast breeder reactor programme

International Nuclear Information System (INIS)

Rapin, M.

1980-01-01

The strong French LMFBR development and the corresponding success obtained up to now show that there is no technical insuperable barrier to fast breeder construction. This satisfactory evolution is in fact the conjunction of a strong incentive due to the lack of other resources, a firm and permanent stand of the government, and an obstinate effort of all the teams involved in the LMFBR field. The changeover to industrial level should be helped by the simplicity of the French organization for fast breeder. Finally, the development of LMFBR on a larger scale is helped by international agreements through which the present French know-how can be put at the disposal of other partners, and the general knowledge can be improved by setting common R and D programmes. A quite successful example of such agreements is given by the German-French agreement, and we hope that new partners will join us soon. (orig.) [de

An overview of FFTF [Fast Flux Test Facility] contributions to Liquid Metal Reactor Safety

International Nuclear Information System (INIS)

Waltar, A.E.; Padilla, A. Jr.

1990-11-01

The Fast Flux Test Facility has provided a very useful framework for testing the advances in Liquid Metal Reactor Safety Technology. During the licensing phase, the switch from a nonmechanistic bounding technique to the mechanistic approach was developed and implemented. During the operational phase, the consideration of new tests and core configurations led to use of the anticipated-transients-without-scram approach for beyond design basis events and the move towards passive safety. The future role of the Fast Flux Test Facility may involve additional passive safety and waste transmutation tests. 26 refs

A cell-based fluorescent assay to detect the activity of AB toxins that inhibit protein synthesis

Science.gov (United States)

AB-type protein toxins, produced by numerous bacterial pathogens and some plants, elicit a cytotoxic effect involving the inhibition of protein synthesis. To develop an improved method to detect the inhibition of protein synthesis by AB-type toxins, the present study characterized a Vero cell line t...

The Adverse Effects and Treatment Results of Smoking Cessation Pharmacotherapy During Fasting/Non-Fasting State.

Science.gov (United States)

Iliaz, Sinem; Tural Onur, Seda; Uysal, Mehmet Atilla; Chousein, Efsun Gonca Uğur; Tanriverdi, Elif; Bagci, Belma Akbaba; Bahadir, Ayse; Hattatoglu, Didem Gorgun; Ortakoylu, Mediha Gonenc; Yurt, Sibel

2017-07-03

Cigarette smoking is one of the most common addictions worldwide. Muslim smokers reduce the number of cigarettes they smoke during Ramadan due to the long fasting hours. We aimed to share our experience in a smoking cessation clinic during Ramadan by analyzing the efficacy and adverse effects of once-daily dosing of bupropion or varenicline in a fasting group compared with conventional dosing in a non-fasting group. We analyzed 57 patients who attended our smoking cessation clinic during Ramadan of 2014 and 2015, and at least one follow-up visit. For the fasting patients, we prescribed bupropion or varenicline after dinner (once daily) as the maintenance therapy. We recorded demographic characteristics of the patients, fasting state, drugs taken for smoking cessation, and the dosage of the medication. At the first follow-up visit, adverse effects seen with the treatment were recorded. We conducted telephone interviews 6 months after the first visits of the patients to learn the current smoking status of the groups. Of the total 57 patients, 20 (35.1%) were fasting and 37 (64.9%) were not fasting. Fasting and non-fasting patients were similar for sex, age, smoking pack-years, marital status, educational status, and mean Fagerström scores (p >.05). Adverse effects and quit rates after 6 months of follow-up were similar between the fasting and non-fasting groups (p >.05). Although our sample size was small, we found no difference in the rates of adverse effects or smoking cessation using a single daily oral dose of bupropion or varenicline between a fasting group and a non-fasting group that received conventional dosing.

Novel applications of fast neutron interrogation methods

International Nuclear Information System (INIS)

Gozani, Tsahi

1994-01-01

The development of non-intrusive inspection methods for contraband consisting primarily of carbon, nitrogen, oxygen, and hydrogen requires the use of fast neutrons. While most elements can be sufficiently well detected by the thermal neutron capture process, some important ones, e.g., carbon and in particular oxygen, cannot be detected by this process. Fortunately, fast neutrons, with energies above the threshold for inelastic scattering, stimulate relatively strong and specific gamma ray lines from these elements. The main lines are: 6.13 for O, 4.43 for C, and 5.11, 2.31 and 1.64 MeV for N. Accelerator-generated neutrons in the energy range of 7 to 15 MeV are being considered as interrogating radiations in a variety of non-intrusive inspection systems for contraband, from explosives to drugs and from coal to smuggled, dutiable goods. In some applications, mostly for inspection of small items such as luggage, the decision process involves a rudimentary imaging, akin to emission tomography, to obtain the localized concentration of various elements. This technique is called FNA - Fast Neutron Analysis. While this approach offers improvements over the TNA (Thermal Neutron Analysis), it is not applicable to large objects such as shipping containers and trucks. For these challenging applications, a collimated beam of neutrons is rastered along the height of the moving object. In addition, the neutrons are generated in very narrow nanosecond pulses. The point of their interaction inside the object is determined by the time of flight (TOF) method, that is measuring the time elapsed from the neutron generation to the time of detection of the stimulated gamma rays. This technique, called PFNA (Pulsed Fast Neutron Analysis), thus directly provides the elemental, and by inference, the chemical composition of the material at every volume element (voxel) of the object. The various neutron-based techniques are briefly described below. ((orig.))

Intermittent Fasting Alleviates the Increase of Lipoprotein Lipase Expression in Brain of a Mouse Model of Alzheimer's Disease: Possibly Mediated by β-hydroxybutyrate.

Science.gov (United States)

Zhang, Jingzhu; Li, Xinhui; Ren, Yahao; Zhao, Yue; Xing, Aiping; Jiang, Congmin; Chen, Yanqiu; An, Li

2018-01-01

Intermittent fasting has been demonstrated to protect against Alzheimer's disease (AD), however, the mechanism is unclear. Histone acetylation and lipoprotein lipase (LPL) are involved in AD progression. Importantly, LPL has been documented to be regulated by histone deacetylases (HDACs) inhibitors (increase histone acetylation level) in adipocyte and mesenchymal stem cells, or by fasting in adipose and muscle tissues. In brain, however, whether histone acetylation or fasting regulates LPL expression is unknown. This study was designed to demonstrate intermittent fasting may protect against AD through increasing β-hydroxybutyrate, a HDACs inhibitor, to regulate LPL. We also investigated microRNA-29a expression associating with regulation of LPL and histone acetylation. The results showed LPL mRNA expression was increased and microRNA-29a expression was decreased in the cerebral cortex of AD model mice (APP/PS1), which were alleviated by intermittent fasting. No significant differences were found in the total expression of LPL protein (brain-derived and located in capillary endothelial cells from peripheral tissues) in the cerebral cortex of APP/PS1 mice. Further study indicated that LPL located in capillary endothelial cells was decreased in the cerebral cortex of APP/PS1 mice, which was alleviated by intermittent fasting. LPL and microRNA-29a expression were separately increased and down-regulated in 2 μM Aβ 25-35 -exposed SH-SY5Y cells, but respectively decreased and up-regulated in 10 μM Aβ 25-35 -exposed cells, which were all reversed by β-hydroxybutyrate. The increase of HDAC2/3 expression and the decrease of acetylated H3K9 and H4K12 levels were alleviated in APP/PS1 mice by intermittent fasting treatment, as well in 2 or 10 μM Aβ 25-35 -exposed cells by β-hydroxybutyrate treatment. These findings above suggested the results from APP/PS1 mice were consistent with those from cells treated with 2 μM Aβ 25-35 . Interestingly, LPL expression was

Ramadan, fasting and pregnancy

DEFF Research Database (Denmark)

Ahmed, Urfan Zahoor; Lykke, Jacob Alexander

2014-01-01

In Islam, the month of Ramadan is a period of fasting lasting 29 or 30 days. Epidemiological studies among Muslims in Denmark have not been conducted, but studies show, that fasting among pregnant Muslim women is common. Fasting does not increase the risk of growth restriction or preterm delivery...

Fast reactors

International Nuclear Information System (INIS)

Vasile, A.

2001-01-01

Fast reactors have capacities to spare uranium natural resources by their breeding property and to propose solutions to the management of radioactive wastes by limiting the inventory of heavy nuclei. This article highlights the role that fast reactors could play for reducing the radiotoxicity of wastes. The conversion of 238 U into 239 Pu by neutron capture is more efficient in fast reactors than in light water reactors. In fast reactors multi-recycling of U + Pu leads to fissioning up to 95% of the initial fuel ( 238 U + 235 U). 2 strategies have been studied to burn actinides: - the multi-recycling of heavy nuclei is made inside the fuel element (homogeneous option); - the unique recycling is made in special irradiation targets placed inside the core or at its surroundings (heterogeneous option). Simulations have shown that, for the same amount of energy produced (400 TWhe), the mass of transuranium elements (Pu + Np + Am + Cm) sent to waste disposal is 60,9 Kg in the homogeneous option and 204.4 Kg in the heterogeneous option. Experimental programs are carried out in Phenix and BOR60 reactors in order to study the feasibility of such strategies. (A.C.)

Fast wave current drive

International Nuclear Information System (INIS)

Goree, J.; Ono, M.; Colestock, P.; Horton, R.; McNeill, D.; Park, H.

1985-07-01

Fast wave current drive is demonstrated in the Princeton ACT-I toroidal device. The fast Alfven wave, in the range of high ion-cyclotron harmonics, produced 40 A of current from 1 kW of rf power coupled into the plasma by fast wave loop antenna. This wave excites a steady current by damping on the energetic tail of the electron distribution function in the same way as lower-hybrid current drive, except that fast wave current drive is appropriate for higher plasma densities

Metabolic Effects of Intermittent Fasting.

Science.gov (United States)

Patterson, Ruth E; Sears, Dorothy D

2017-08-21

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved health outcomes. A MEDLINE search was performed using PubMed and the terms "intermittent fasting," "fasting," "time-restricted feeding," and "food timing." Modified fasting regimens appear to promote weight loss and may improve metabolic health. Several lines of evidence also support the hypothesis that eating patterns that reduce or eliminate nighttime eating and prolong nightly fasting intervals may result in sustained improvements in human health. Intermittent fasting regimens are hypothesized to influence metabolic regulation via effects on (a) circadian biology, (b) the gut microbiome, and (c) modifiable lifestyle behaviors, such as sleep. If proven to be efficacious, these eating regimens offer promising nonpharmacological approaches to improving health at the population level, with multiple public health benefits.

Role of the brain stem in tibial inhibition of the micturition reflex in cats.

Science.gov (United States)

Ferroni, Matthew C; Slater, Rick C; Shen, Bing; Xiao, Zhiying; Wang, Jicheng; Lee, Andy; Roppolo, James R; de Groat, William C; Tai, Changfeng

2015-08-01

This study examined the role of the brain stem in inhibition of bladder reflexes induced by tibial nerve stimulation (TNS) in α-chloralose-anesthetized decerebrate cats. Repeated cystometrograms (CMGs) were performed by infusing saline or 0.25% acetic acid (AA) to elicit normal or overactive bladder reflexes, respectively. TNS (5 or 30 Hz) at three times the threshold (3T) intensity for inducing toe movement was applied for 30 min between CMGs to induce post-TNS inhibition or applied during the CMGs to induce acute TNS inhibition. Inhibition was evident as an increase in bladder capacity without a change in amplitude of bladder contractions. TNS applied for 30 min between saline CMGs elicited prolonged (>2 h) poststimulation inhibition that significantly (P reflexes but are not involved in inhibition of normal bladder reflexes. Copyright © 2015 the American Physiological Society.

MicroRNA-21-Mediated Inhibition of Mast Cell Degranulation Involved in the Protective Effect of Berberine on 2,4-Dinitrofluorobenzene-Induced Allergic Contact Dermatitis in Rats via p38 Pathway.

Science.gov (United States)

Li, Weihua; Liu, Fanxiu; Wang, Jun; Long, Man; Wang, Zhigang

2018-03-01

The study aimed to investigate the effect of berberine on allergic contact dermatitis (ACD) in rats and explore its underlying mechanisms. Firstly, ACD model was established by sensitizing and challenging with 2,4-dinitrofluorobenzene (DNFB) topically, and the rats were treated with berberine. Ear swelling was assessed, and cytokine, IgE, and histamine productions were measured. The ear biopsies were obtained for histology analysis. Additionally, rat peritoneal mast cells (RPMCs) were isolated for detection of microRNA-21 (miR-21) expression, mitogen-activated protein kinase (MAPK) signaling, and MC degranulation. Lastly, RPMCs were transfected with miR-21 mimic or miR-21 inhibitor to investigate the relationship between miR-21 and p38 pathway in MC. Our results showed that berberine significantly attenuated ear swelling in DNFB-induced ACD (ACD vs high dose of berberine 0.48 ± 0.03 vs. 0.33 ± 0.03 mm, P < 0.01), inhibited inflammatory cell infiltration (86 ± 5.16 vs. 58 ± 4.32 cells/mm 2 , P < 0.01), reduced MC recruitment (61 ± 4.07 vs. 39 ± 3.42 mast cells/mm 2 , P < 0.01), as well as decreased inflammatory cytokine, IgE, and histamine productions (all P < 0.05). Berberine treatment inhibited miR-21 expression, suppressed β-hexosaminidase and histamine release, and prevented p38 phosphorylation (all P < 0.05), which was abrogated by pretreatment with miR-21 overexpression. These findings indicate that miR-21-mediated inhibition of MC degranulation is involved in the anti-ACD effect of berberine via inhibiting p38 pathway, which provide a new insight into the immunopharmacological role of berberine and suggest its potential application for the treatment of allergic inflammation, such as ACD.

Anandamide inhibits adhesion and migration of breast cancer cells

International Nuclear Information System (INIS)

Grimaldi, Claudia; Pisanti, Simona; Laezza, Chiara; Malfitano, Anna Maria; Santoro, Antonietta; Vitale, Mario; Caruso, Maria Gabriella; Notarnicola, Maria; Iacuzzo, Irma; Portella, Giuseppe; Di Marzo, Vincenzo; Bifulco, Maurizio

2006-01-01

The endocannabinoid system regulates cell proliferation in human breast cancer cells. We reasoned that stimulation of cannabinoid CB 1 receptors could induce a non-invasive phenotype in breast mtastatic cells. In a model of metastatic spreading in vivo, the metabolically stable anandamide analogue, 2-methyl-2'-F-anandamide (Met-F-AEA), significantly reduced the number and dimension of metastatic nodes, this effect being antagonized by the selective CB 1 antagonist SR141716A. In MDA-MB-231 cells, a highly invasive human breast cancer cell line, and in TSA-E1 cells, a murine breast cancer cell line, Met-F-AEA inhibited adhesion and migration on type IV collagen in vitro without modifying integrin expression: both these effects were antagonized by SR141716A. In order to understand the molecular mechanism involved in these processes, we analyzed the phosphorylation of FAK and Src, two tyrosine kinases involved in migration and adhesion. In Met-F-AEA-treated cells, we observed a decreased tyrosine phosphorylation of both FAK and Src, this effect being attenuated by SR141716A. We propose that CB 1 receptor agonists inhibit tumor cell invasion and metastasis by modulating FAK phosphorylation, and that CB 1 receptor activation might represent a novel therapeutic strategy to slow down the growth of breast carcinoma and to inhibit its metastatic diffusion in vivo

Fast track-hoftealloplastik

DEFF Research Database (Denmark)

Hansen, Torben Bæk; Gromov, Kirill; Kristensen, Billy B

2017-01-01

Fast-track surgery implies a coordinated perioperative approach aimed at reducing surgical stress and facilitating post-operative recovery. The fast-track programme has reduced post-operative length of stay and has led to shorter convalescence with more rapid functional recovery and decreased...... morbidity and mortality in total hip arthroplasty. It should now be a standard total hip arthroplasty patient pathway, but fine tuning of the multiple factors in the fast-track pathway is still needed in patients with special needs or high comorbidity burden....

Fast Flux Watch: A mechanism for online detection of fast flux networks

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Basheer N. Al-Duwairi

2014-07-01

Full Text Available Fast flux networks represent a special type of botnets that are used to provide highly available web services to a backend server, which usually hosts malicious content. Detection of fast flux networks continues to be a challenging issue because of the similar behavior between these networks and other legitimate infrastructures, such as CDNs and server farms. This paper proposes Fast Flux Watch (FF-Watch, a mechanism for online detection of fast flux agents. FF-Watch is envisioned to exist as a software agent at leaf routers that connect stub networks to the Internet. The core mechanism of FF-Watch is based on the inherent feature of fast flux networks: flux agents within stub networks take the role of relaying client requests to point-of-sale websites of spam campaigns. The main idea of FF-Watch is to correlate incoming TCP connection requests to flux agents within a stub network with outgoing TCP connection requests from the same agents to the point-of-sale website. Theoretical and traffic trace driven analysis shows that the proposed mechanism can be utilized to efficiently detect fast flux agents within a stub network.

Fast ultrasonic visualisation under sodium. Application to the fast neutron reactors

International Nuclear Information System (INIS)

Imbert, Ch.

1997-01-01

The fast ultrasonic visualization under sodium is in the programme of research and development on the inspection inside the fast neutron reactors. This work is about the development of a such system of fast ultrasonic imaging under sodium, in order to improve the existing visualization systems. This system is based on the principle of orthogonal imaging, it uses two linear antennas with an important dephasing having 128 piezo-composite elements of central frequency equal to 1.6 MHz. (N.C.)

The hedgehog receptor patched is involved in cholesterol transport.

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Michel Bidet

Full Text Available Sonic hedgehog (Shh signaling plays a crucial role in growth and patterning during embryonic development, and also in stem cell maintenance and tissue regeneration in adults. Aberrant Shh pathway activation is involved in the development of many tumors, and one of the most affected Shh signaling steps found in these tumors is the regulation of the signaling receptor Smoothened by the Shh receptor Patched. In the present work, we investigated Patched activity and the mechanism by which Patched inhibits Smoothened.Using the well-known Shh-responding cell line of mouse fibroblasts NIH 3T3, we first observed that enhancement of the intracellular cholesterol concentration induces Smoothened enrichment in the plasma membrane, which is a crucial step for the signaling activation. We found that binding of Shh protein to its receptor Patched, which involves Patched internalization, increases the intracellular concentration of cholesterol and decreases the efflux of a fluorescent cholesterol derivative (BODIPY-cholesterol from these cells. Treatment of fibroblasts with cyclopamine, an antagonist of Shh signaling, inhibits Patched expression and reduces BODIPY-cholesterol efflux, while treatment with the Shh pathway agonist SAG enhances Patched protein expression and BODIPY-cholesterol efflux. We also show that over-expression of human Patched in the yeast S. cerevisiae results in a significant boost of BODIPY-cholesterol efflux. Furthermore, we demonstrate that purified Patched binds to cholesterol, and that the interaction of Shh with Patched inhibits the binding of Patched to cholesterol.Our results suggest that Patched may contribute to cholesterol efflux from cells, and to modulation of the intracellular cholesterol concentration. This activity is likely responsible for the inhibition of the enrichment of Smoothened in the plasma membrane, which is an important step in Shh pathway activation.

Time-driven Activity-based Cost of Fast-Track Total Hip and Knee Arthroplasty

DEFF Research Database (Denmark)

Andreasen, Signe E; Holm, Henriette B; Jørgensen, Mira

2017-01-01

this between 2 departments with different logistical set-ups. METHODS: Prospective data collection was analyzed using the time-driven activity-based costing method (TDABC) on time consumed by different staff members involved in patient treatment in the perioperative period of fast-track THA and TKA in 2 Danish...... orthopedic departments with standardized fast-track settings, but different logistical set-ups. RESULTS: Length of stay was median 2 days in both departments. TDABC revealed minor differences in the perioperative settings between departments, but the total cost excluding the prosthesis was similar at USD......-track methodology, the result could be a more cost-effective pathway altogether. As THA and TKA are potentially costly procedures and the numbers are increasing in an economical limited environment, the aim of this study is to present baseline detailed economical calculations of fast-track THA and TKA and compare...

Fast-opening vacuum switches for high-power inductive energy storage

International Nuclear Information System (INIS)

Cooperstein, G.

1988-01-01

The subject of fast-opening vacuum switches for high-power inductive energy storage is emerging as an exciting new area of plasma science research. This opening switch technology, which generally involves the use of plasmas as the switching medium, is key to the development of inductive energy storage techniques for pulsed power which have a number of advantages over conventional capacitive techniques with regard to cost and size. This paper reviews the state of the art in this area with emphasis on applications to inductive storage pulsed power generators. Discussion focuses on fast-opening vacuum switches capable of operating at high power (≥10 12 W). These include plasma erosion opening switches, ion beam opening switches, plasma filled diodes, reflex diodes, plasma flow switches, and other novel vacuum opening switches

Dense magnetized plasma associated with a fast radio burst.

Science.gov (United States)

Masui, Kiyoshi; Lin, Hsiu-Hsien; Sievers, Jonathan; Anderson, Christopher J; Chang, Tzu-Ching; Chen, Xuelei; Ganguly, Apratim; Jarvis, Miranda; Kuo, Cheng-Yu; Li, Yi-Chao; Liao, Yu-Wei; McLaughlin, Maura; Pen, Ue-Li; Peterson, Jeffrey B; Roman, Alexander; Timbie, Peter T; Voytek, Tabitha; Yadav, Jaswant K

2015-12-24

Fast radio bursts are bright, unresolved, non-repeating, broadband, millisecond flashes, found primarily at high Galactic latitudes, with dispersion measures much larger than expected for a Galactic source. The inferred all-sky burst rate is comparable to the core-collapse supernova rate out to redshift 0.5. If the observed dispersion measures are assumed to be dominated by the intergalactic medium, the sources are at cosmological distances with redshifts of 0.2 to 1 (refs 10 and 11). These parameters are consistent with a wide range of source models. One fast burst revealed circular polarization of the radio emission, but no linear polarization was detected, and hence no Faraday rotation measure could be determined. Here we report the examination of archival data revealing Faraday rotation in the fast radio burst FRB 110523. Its radio flux and dispersion measure are consistent with values from previously reported bursts and, accounting for a Galactic contribution to the dispersion and using a model of intergalactic electron density, we place the source at a maximum redshift of 0.5. The burst has a much higher rotation measure than expected for this line of sight through the Milky Way and the intergalactic medium, indicating magnetization in the vicinity of the source itself or within a host galaxy. The pulse was scattered by two distinct plasma screens during propagation, which requires either a dense nebula associated with the source or a location within the central region of its host galaxy. The detection in this instance of magnetization and scattering that are both local to the source favours models involving young stellar populations such as magnetars over models involving the mergers of older neutron stars, which are more likely to be located in low-density regions of the host galaxy.

GSK-3β/NFAT Signaling Is Involved in Testosterone-Induced Cardiac Myocyte Hypertrophy.

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Javier Duran

Full Text Available Testosterone induces cardiac hypertrophy through a mechanism that involves a concerted crosstalk between cytosolic and nuclear signaling pathways. Nuclear factor of activated T-cells (NFAT is associated with the promotion of cardiac hypertrophy, glycogen synthase kinase-3β (GSK-3β is considered to function as a negative regulator, mainly by modulating NFAT activity. However, the role played by calcineurin-NFAT and GSK-3β signaling in testosterone-induced cardiac hypertrophy has remained unknown. Here, we determined that testosterone stimulates cardiac myocyte hypertrophy through NFAT activation and GSK-3β inhibition. Testosterone increased the activity of NFAT-luciferase (NFAT-Luc in a time- and dose-dependent manner, with the activity peaking after 24 h of stimulation with 100 nM testosterone. NFAT-Luc activity induced by testosterone was blocked by the calcineurin inhibitors FK506 and cyclosporine A and by 11R-VIVIT, a specific peptide inhibitor of NFAT. Conversely, testosterone inhibited GSK-3β activity as determined by increased GSK-3β phosphorylation at Ser9 and β-catenin protein accumulation, and also by reduction in β-catenin phosphorylation at residues Ser33, Ser37, and Thr41. GSK-3β inhibition with 1-azakenpaullone or a GSK-3β-targeting siRNA increased NFAT-Luc activity, whereas overexpression of a constitutively active GSK-3β mutant (GSK-3βS9A inhibited NFAT-Luc activation mediated by testosterone. Testosterone-induced cardiac myocyte hypertrophy was established by increased cardiac myocyte size and [3H]-leucine incorporation (as a measurement of cellular protein synthesis. Calcineurin-NFAT inhibition abolished and GSK-3β inhibition promoted the hypertrophy stimulated by testosterone. GSK-3β activation by GSK-3βS9A blocked the increase of hypertrophic markers induced by testosterone. Moreover, inhibition of intracellular androgen receptor prevented testosterone-induced NFAT-Luc activation. Collectively, these results

Study of the fast inversion recovery pulse sequence. With reference to fast fluid attenuated inversion recovery and fast short TI inversion recovery pulse sequence

International Nuclear Information System (INIS)

Tsuchihashi, Toshio; Maki, Toshio; Suzuki, Takeshi

1997-01-01

The fast inversion recovery (fast IR) pulse sequence was evaluated. We compared the fast fluid attenuated inversion recovery (fast FLAIR) pulse sequence in which inversion time (TI) was established as equal to the water null point for the purpose of the water-suppressed T 2 -weighted image, with the fast short TI inversion recovery (fast STIR) pulse sequence in which TI was established as equal to the fat null point for purpose of fat suppression. In the fast FLAIR pulse sequence, the water null point was increased by making TR longer. In the FLAIR pulse sequence, the longitudinal magnetization contrast is determined by TI. If TI is increased, T 2 -weighted contrast improves in the same way as increasing TR for the SE pulse sequence. Therefore, images should be taken with long TR and long TI, which are longer than TR and longer than the water null point. On the other hand, the fat null point is not affected by TR in the fast STIR pulse sequence. However, effective TE was affected by variation of the null point. This increased in proportion to the increase in effective TE. Our evaluation indicated that the fast STIR pulse sequence can control the extensive signals from fat in a short time. (author)

Clinical Evaluation of the Self-Injurious Behavior Inhibiting System (SIBIS).

Science.gov (United States)

Linscheid, Thomas R.; And Others

1990-01-01

The Self-Injurious Behavior Inhibiting System (in which mild and brief contingent electric stimulation is delivered) was evaluated with five cases involving severe mental retardation and previously unmanageable self-injurious behavior. Findings indicated almost complete elimination of the self-injurious behavior with followup suggesting continuing…

Delivering the lateral inhibition punchline: it's all about the timing.

Science.gov (United States)

Axelrod, Jeffrey D

2010-10-26

Experimental and theoretical biologists have long been fascinated with the emergence of self-organizing patterns in developing organisms, and much attention has focused on Notch-mediated lateral inhibition. Within sheets of cells that may adopt either of two possible cell fates, lateral inhibition establishes patterns through the activity of a negative intercellular feedback loop involving the receptor, Notch, and its ligands Delta or Serrate. Despite a long history of intensive study in Drosophila, where the mechanism was first described, as well as in other organisms, new work continues to yield important insights. Mathematical modeling, combined with biological analyses, has now shed light on two features of the process: how antagonistic and activating ligand-receptor interactions work together to accelerate inhibition and ensure fidelity, and how filopodial dynamics contribute to the observed pattern refinement and spacing.

Fast breeder reactors

International Nuclear Information System (INIS)

Waltar, A.E.; Reynolds, A.B.

1981-01-01

This book describes the major design features of fast breeder reactors and the methods used for their design and analysis. The foremost objective of this book is to fulfill the need for a textbook on Fast Breeder Reactor (FBR) technology at the graduate level or the advanced undergraduate level. It is assumed that the reader has an introductory understanding of reactor theory, heat transfer, and fluid mechanics. The book is expected to be used most widely for a one-semester general course on fast breeder reactors, with the extent of material covered to vary according to the interest of the instructor. The book could also be used effectively for a two-quarter or a two-semester course. In addition, the book could serve as a text for a course on fast reactor safety since many topics other than those appearing in the safety chapters relate to FBR safety. Methodology in fast reactor design and analysis, together with physical descriptions of systems, is emphasized in this text more than numerical results. Analytical and design results continue to change with the ongoing evolution of FBR design whereas many design methods have remained fundamentally unchanged for a considerable time

Inhibition of Helicobacter pylori and Associated Urease by Oregano and Cranberry Phytochemical Synergies

Science.gov (United States)

Lin, Y. T.; Kwon, Y. I.; Labbe, R. G.; Shetty, K.

2005-01-01

Ulcer-associated dyspepsia is caused by infection with Helicobacter pylori. H. pylori is linked to a majority of peptic ulcers. Antibiotic treatment does not always inhibit or kill H. pylori with potential for antibiotic resistance. The objective of this study was to determine the potential for using phenolic phytochemical extracts to inhibit H. pylori in a laboratory medium. Our approach involved the development of a specific phenolic profile with optimization of different ratios of extract mixtures from oregano and cranberry. Subsequently, antimicrobial activity and antimicrobial-linked urease inhibition ability were evaluated. The results indicated that the antimicrobial activity was greater in extract mixtures than in individual extracts of each species. The results also indicate that the synergistic contribution of oregano and cranberry phenolics may be more important for inhibition than any species-specific phenolic concentration. Further, based on plate assay, the likely mode of action may be through urease inhibition and disruption of energy production by inhibition of proline dehydrogenase at the plasma membrane. PMID:16332847

Fast neutrons dosimetry

International Nuclear Information System (INIS)

Rzyski, B.M.

1977-01-01

A proton recoil technique has been developed for inducing thermoluminescence with incident fast neutrons. CaF 2 was used as the TL phosphor, and cane sugar and polyethylene were used as proton radiators. The phosphor and the hydrogeneous material powders were well mixed, encapsulated in glass tubes and exposed to Am-Be sources, resulting in recoils from incident fast neutrons of energy between 0,25 and 11,25 MeV. The intrinsic response of pure CaF 2 to fast neutrons without a hydrogeneous radiator was checked by using LiF (TLD-700). Glow curves were recorded from room temperature up to 350 0 C after different doses of neutrons and gamma rays of 60 Co. First collision dose due to fast neutrons in tissue like materials such as cane sugar and polyethylene was also calculated [pt

Ammonium inhibition of nitrogenase activity in Herbaspirillum seropedicae

Energy Technology Data Exchange (ETDEWEB)

Fu, H.; Burris, R.H. (Univ. of Wisconsin, Madison (USA))

1989-06-01

The effect of oxygen, ammonium ion, and amino acids on nitrogenase activity in the root-associated N{sub 2}-fixing bacterium Herbaspirillum seropedicae was investigated in comparison with Azospirillum spp. and Rhodospirillum rubrum. H. seropedicae is microaerophilic, and its optimal dissolved oxygen level is from 0.04 to 0.2 kPa for dinitrogen fixation but higher when it is supplied with fixed nitrogen. No nitrogenase activity was detected when the dissolved O{sub 2} level corresponded to 4.0 kPa. Ammonium, a product of the nitrogenase reaction, reversible inhibited nitrogenase activity when added to derepressed cell cultures. However, the inhibition of nitrogenase activity was only partial even with concentrations of ammonium chloride as high as 20 mM. Amides such as glutamine and asparagine partially inhibited nitrogenase activity, but glutamate did not. Nitrogenase in crude extracts prepared from ammonium-inhibited cells showed activity as high as in extracts from N{sub 2}-fixing cells. The pattern of the dinitrogenase and the dinitrogenase reductase revealed by the immunoblotting technique did not change upon ammonium chloride treatment of cells in vivo. No homologous sequences were detected with the draT-draG probe from Azospirillum lipoferum. There is no clear evidence that ADP-ribosylation of the dinitrogenase reductase is involved in the ammonium inhibition of H. seropedicae. The uncoupler carbonyl cyanide m-chlorophenylhydrazone decreased the intracellular ATP concentration and inhibited the nitrogenase activity of whole cells. The ATP pool was significantly disturbed when cultures were treated with ammonium in vivo.

Tissue-Specific Expression of Monocarboxylate Transporters during Fasting in Mice

Science.gov (United States)

Schutkowski, Alexandra; Wege, Nicole; Stangl, Gabriele I.; König, Bettina

2014-01-01

Monocarboxylates such as pyruvate, lactate and ketone bodies are crucial for energy supply of all tissues, especially during energy restriction. The transport of monocarboxylates across the plasma membrane of cells is mediated by monocarboxylate transporters (MCTs). Out of 14 known mammalian MCTs, six isoforms have been functionally characterized to transport monocarboxylates and short chain fatty acids (MCT1-4), thyroid hormones (MCT8, -10) and aromatic amino acids (MCT10). Knowledge on the regulation of the different MCT isoforms is rare. In an attempt to get more insights in regulation of MCT expression upon energy deprivation, we carried out a comprehensive analysis of tissue specific expression of five MCT isoforms upon 48 h of fasting in mice. Due to the crucial role of peroxisome proliferator-activated receptor (PPAR)-α as a central regulator of energy metabolism and as known regulator of MCT1 expression, we included both wildtype (WT) and PPARα knockout (KO) mice in our study. Liver, kidney, heart, small intestine, hypothalamus, pituitary gland and thyroid gland of the mice were analyzed. Here we show that the expression of all examined MCT isoforms was markedly altered by fasting compared to feeding. Expression of MCT1, MCT2 and MCT10 was either increased or decreased by fasting dependent on the analyzed tissue. MCT4 and MCT8 were down-regulated by fasting in all examined tissues. However, PPARα appeared to have a minor impact on MCT isoform regulation. Due to the fundamental role of MCTs in transport of energy providing metabolites and hormones involved in the regulation of energy homeostasis, we assumed that the observed fasting-induced adaptations of MCT expression seem to ensure an adequate energy supply of tissues during the fasting state. Since, MCT isoforms 1–4 are also necessary for the cellular uptake of drugs, the fasting-induced modifications of MCT expression have to be considered in future clinical care algorithms. PMID:25390336

Anxiety and retrieval inhibition: support for an enhanced inhibition account.

Science.gov (United States)

Nuñez, Mia; Gregory, Josh; Zinbarg, Richard E

2017-02-01

Retrieval inhibition of negative associations is important for exposure therapy for anxiety, but the relationship between memory inhibition and anxiety is not well understood-anxiety could either be associated with enhanced or deficient inhibition. The present study tested these two competing hypotheses by measuring retrieval inhibition of negative stimuli by related neutral stimuli. Non-clinically anxious undergraduates completed measures of trait and state anxiety and completed a retrieval induced forgetting task. Adaptive forgetting varied with state anxiety. Low levels of state anxiety were associated with no evidence for retrieval inhibition for either threatening or non-threatening categories. Participants in the middle tertile of state anxiety scores exhibited retrieval inhibition for non-threatening categories but not for threatening categories. Participants in the highest tertile of state anxiety, however, exhibited retrieval inhibition for both threatening and non-threatening categories with the magnitude of retrieval inhibition being greater for threatening than non-threatening categories. The data are in line with the avoidance aspect of the vigilance-avoidance theory of anxiety and inhibition. Implications for cognitive behavioural therapy practices are discussed.

Fasting and Urinary Stones

Directory of Open Access Journals (Sweden)

Ali Shamsa

2013-11-01

Full Text Available Introduction: Fasting is considered as one of the most important practices of Islam, and according to Prophet Mohammad, fasting is obligatory upon Muslims. The aim of this study is to evaluate the effects of fasting on urinary stones. Materials and Methods: Very few studies have been carried out on urinary stones and the effect of Ramadan fasting. The sources of the present study are Medline and articles presented by local and Muslim researchers. Meanwhile, since we are acquainted with three well-known researchers in the field of urology, we contacted them via email and asked for their professional opinions. Results: The results of studies about the relationship of urinary stones and their incidence in Ramadan are not alike, and are even sometimes contradictory. Some believe that increased incidence of urinary stones in Ramadan is related not to fasting, but to the rise of weather temperature in hot months, and an increase in humidity. Conclusion: Numerous biological and behavioral changes occur in people who fast in Ramadan and some researchers believe that urinary stone increases during this month.

Radiation-induced enteropathy: Molecular basis of pentoxifylline–vitamin E anti-fibrotic effect involved TGF-β1 cascade inhibition

International Nuclear Information System (INIS)

Hamama, Saad; Gilbert-Sirieix, Marie; Vozenin, Marie-Catherine; Delanian, Sylvie

2012-01-01

Background: Radiation-induced fibrosis is a serious late complication of radiotherapy. Pentoxifylline–vitamin E has proven effective and safe in clinical trials in the treatment of fibrosis, while the molecular mechanism of its activity is yet unexplored. Methods: Ten patients suffering from radiation-induced enteropathy were treated with pentoxifylline–vitamin E combination with SOMA score as the primary endpoint. In parallel, primary smooth muscle cells isolated from intestinal samples isolated from humans with radiation enteropathy were incubated with pentoxifylline, trolox (vit. E hydrophilic analogous) or their combination. Activation of the TGF-β1/Smad and Rho/ROCK pathways was subsequently investigated using Q-RT-PCR, gene reporter, Western-blot, ELISA and immunohistochemistry. Results: Pentoxifylline–vitamin E combination induces regression of symptoms (SOMA) by −41% and −80% at 6 and 18 months. In vitro, pentoxifylline and trolox synergize to inhibit TGF-β1 protein and mRNA expression. This inhibitory action is mediated at the transcriptional level and leads to subsequent inhibition of TGF-β1/Smad targets (Col Iα1, FN1, PAI-1, CTGF), while it has no effect on the Rho/ROCK pathway. Conclusions: The anti-fibrotic effect of combined pentoxifylline–vitamin E is at least in part mediated by inhibition of the TGF-β1 cascade. It strengthens previous clinical data showing pentoxifylline–vitamin E synergy and supports its use as a first-line treatment of radiation-induced fibrosis.

Glutamate-induced apoptosis in neuronal cells is mediated via caspase-dependent and independent mechanisms involving calpain and caspase-3 proteases as well as apoptosis inducing factor (AIF and this process is inhibited by equine estrogens

Directory of Open Access Journals (Sweden)

Bhavnani Bhagu R

2006-06-01

Full Text Available Abstract Background Glutamate, a major excitatory amino acid neurotransmitter, causes apoptotic neuronal cell death at high concentrations. Our previous studies have shown that depending on the neuronal cell type, glutamate-induced apoptotic cell death was associated with regulation of genes such as Bcl-2, Bax, and/or caspase-3 and mitochondrial cytochrome c. To further delineate the intracellular mechanisms, we have investigated the role of calpain, an important calcium-dependent protease thought to be involved in apoptosis along with mitochondrial apoptosis inducing factor (AIF and caspase-3 in primary cortical cells and a mouse hippocampal cell line HT22. Results Glutamate-induced apoptotic cell death in neuronal cells was associated with characteristic DNA fragmentation, morphological changes, activation of calpain and caspase-3 as well as the upregulation and/or translocation of AIF from mitochondria into cytosol and nuclei. Our results reveal that primary cortical cells and HT22 cells display different patterns of regulation of these genes/proteins. In primary cortical cells, glutamate induces activation of calpain, caspase-3 and translocation of AIF from mitochondria to cytosol and nuclei. In contrast, in HT22 cells, only the activation of calpain and upregulation and translocation of AIF occurred. In both cell types, these processes were inhibited/reversed by 17β-estradiol and Δ8,17β-estradiol with the latter being more potent. Conclusion Depending upon the neuronal cell type, at least two mechanisms are involved in glutamate-induced apoptosis: a caspase-3-dependent pathway and a caspase-independent pathway involving calpain and AIF. Since HT22 cells lack caspase-3, glutamate-induced apoptosis is mediated via the caspase-independent pathway in this cell line. Kinetics of this apoptotic pathway further indicate that calpain rather than caspase-3, plays a critical role in the glutamate-induced apoptosis. Our studies further indicate

Menthol binding and inhibition of α7-nicotinic acetylcholine receptors.

Directory of Open Access Journals (Sweden)

Abrar Ashoor

Full Text Available Menthol is a common compound in pharmaceutical and commercial products and a popular additive to cigarettes. The molecular targets of menthol remain poorly defined. In this study we show an effect of menthol on the α7 subunit of the nicotinic acetylcholine (nACh receptor function. Using a two-electrode voltage-clamp technique, menthol was found to reversibly inhibit α7-nACh receptors heterologously expressed in Xenopus oocytes. Inhibition by menthol was not dependent on the membrane potential and did not involve endogenous Ca(2+-dependent Cl(- channels, since menthol inhibition remained unchanged by intracellular injection of the Ca(2+ chelator BAPTA and perfusion with Ca(2+-free bathing solution containing Ba(2+. Furthermore, increasing ACh concentrations did not reverse menthol inhibition and the specific binding of [(125I] α-bungarotoxin was not attenuated by menthol. Studies of α7- nACh receptors endogenously expressed in neural cells demonstrate that menthol attenuates α7 mediated Ca(2+ transients in the cell body and neurite. In conclusion, our results suggest that menthol inhibits α7-nACh receptors in a noncompetitive manner.

The aging motor system as a model for plastic changes of GABA-mediated intracortical inhibition and their behavioral relevance.

Science.gov (United States)

Heise, Kirstin-F; Zimerman, Maximo; Hoppe, Julia; Gerloff, Christian; Wegscheider, Karl; Hummel, Friedhelm C

2013-05-22

Since GABAA-mediated intracortical inhibition has been shown to underlie plastic changes throughout the lifespan from development to aging, here, the aging motor system was used as a model to analyze the interdependence of plastic alterations within the inhibitory motorcortical network and level of behavioral performance. Double-pulse transcranial magnetic stimulation (dpTMS) was used to examine inhibition by means of short-interval intracortical inhibition (SICI) of the contralateral primary motor cortex in a sample of 64 healthy right-handed human subjects covering a wide range of the adult lifespan (age range 20-88 years, mean 47.6 ± 20.7, 34 female). SICI was evaluated during resting state and in an event-related condition during movement preparation in a visually triggered simple reaction time task. In a subgroup (N = 23), manual motor performance was tested with tasks of graded dexterous demand. Weak resting-state inhibition was associated with an overall lower manual motor performance. Better event-related modulation of inhibition correlated with better performance in more demanding tasks, in which fast alternating activation of cortical representations are necessary. Declining resting-state inhibition was associated with weakened event-related modulation of inhibition. Therefore, reduced resting-state inhibition might lead to a subsequent loss of modulatory capacity, possibly reflecting malfunctioning precision in GABAAergic neurotransmission; the consequence is an inevitable decline in motor function.

Zinc-mediated Allosteric Inhibition of Caspase-6*

Science.gov (United States)

Velázquez-Delgado, Elih M.; Hardy, Jeanne A.

2012-01-01

Zinc and caspase-6 have independently been implicated in several neurodegenerative disorders. Depletion of zinc intracellularly leads to apoptosis by an unknown mechanism. Zinc inhibits cysteine proteases, including the apoptotic caspases, leading to the hypothesis that zinc-mediated inhibition of caspase-6 might contribute to its regulation in a neurodegenerative context. Using inductively coupled plasma optical emission spectroscopy, we observed that caspase-6 binds one zinc per monomer, under the same conditions where the zinc leads to complete loss of enzymatic activity. To understand the molecular details of zinc binding and inhibition, we performed an anomalous diffraction experiment above the zinc edge. The anomalous difference maps showed strong 5σ peaks, indicating the presence of one zinc/monomer bound at an exosite distal from the active site. Zinc was not observed bound to the active site. The zinc in the exosite was liganded by Lys-36, Glu-244, and His-287 with a water molecule serving as the fourth ligand, forming a distorted tetrahedral ligation sphere. This exosite appears to be unique to caspase-6, as the residues involved in zinc binding were not conserved across the caspase family. Our data suggest that binding of zinc at the exosite is the primary route of inhibition, potentially locking caspase-6 into the inactive helical conformation. PMID:22891250

Fast reactors in nuclear power

Energy Technology Data Exchange (ETDEWEB)

Kazachkovskii, O

1981-02-01

The possible applications are discussed of fast reactor nuclear power plants. Basic differences are explained in fast and thermal reactors, mainly with a view to nuclear fuel utilization. Discussed in more detail are the problems of nuclear fuel reproduction and the nost important technical problems of fast reactors. Flow charts are shown of heat transfer for fast reactors BN-350 (loop design) and BN-600 (integral coolant circuit design). Main specifications are given for demonstration and power fast reactors in operation, under construction and in project-stage.

Effects of overnight fasting on working memory-related brain network: an fMRI study.

Science.gov (United States)

Chechko, Natalia; Vocke, Sebastian; Habel, Ute; Toygar, Timur; Kuckartz, Lisa; Berthold-Losleben, Mark; Laoutidis, Zacharias G; Orfanos, Stelios; Wassenberg, Annette; Karges, Wölfram; Schneider, Frank; Kohn, Nils

2015-03-01

Glucose metabolism serves as the central source of energy for the human brain. Little is known about the effects of blood glucose level (BGL) on higher-order cognitive functions within a physiological range (e.g., after overnight fasting). In this randomized, placebo-controlled, double blind study, we assessed the impact of overnight fasting (14 h) on brain activation during a working memory task. We sought to mimic BGLs that occur naturally in healthy humans after overnight fasting. After standardized periods of food restriction, 40 (20 male) healthy participants were randomly assigned to receive either glucagon to balance the BGL or placebo (NaCl). A parametric fMRI paradigm, including 2-back and 0-back tasks, was used. Subclinically low BGL following overnight fasting was found to be linked to reduced involvement of the bilateral dorsal midline thalamus and the bilateral basal ganglia, suggesting high sensitivity of those regions to minimal changes in BGLs. Our results indicate that overnight fasting leads to physiologically low levels of glucose, impacting brain activation during working memory tasks even when there are no differences in cognitive performance. © 2014 Wiley Periodicals, Inc.

Inhibition of MHC-I by Brucella abortus is an early event during infection and involves EGFR pathway.

Science.gov (United States)

Velásquez, Lis N; Milillo, M Ayelén; Delpino, M Victoria; Trotta, Aldana; Mercogliano, M Florencia; Pozner, Roberto G; Schillaci, Roxana; Elizalde, Patricia V; Giambartolomei, Guillermo H; Barrionuevo, Paula

2017-04-01

Brucella abortus is able to persist inside the host despite the development of potent CD8 + T-cell responses. We have recently reported the ability of B. abortus to inhibit the interferon-γ-induced major histocompatibility complex (MHC)-I cell surface expression on human monocytes. This phenomenon was due to the B. abortus-mediated retention of MHC-I molecules within the Golgi apparatus and was dependent on bacterial viability. However, the implications of bacterial virulence or replicative capacity and the signaling pathways remained unknown. Here we demonstrated that the B. abortus mutant strains RB51 and virB10 - are able to inhibit MHC-I expression in the same manner as wild-type B. abortus, even though they are unable to persist inside human monocytes for a long period of time. Consistent with this, the phenomenon was triggered early in time and could be observed at 8 h postinfection. At 24 and 48 h, it was even stronger. Regarding the signaling pathway, targeting epidermal growth factor (EGF) receptor (EGFR), ErbB2 (HER2) or inhibition of tumor necrosis factor-α-converting enzyme, one of the enzymes which generates soluble EGF-like ligands, resulted in partial recovery of MHC-I surface expression. Moreover, recombinant EGF and transforming growth factor-α as well as the combination of both were also able to reproduce the B. abortus-induced MHC-I downmodulation. Finally, when infection was performed in the presence of an extracellular signal-regulated kinase 1/2 (Erk1/2) inhibitor, MHC-I surface expression was significantly recovered. Overall, these results describe how B. abortus evades CD8 + T-cell responses early during infection and exploits the EGFR-ERK signaling pathway to escape from the immune system and favor chronicity.

FastMag: Fast micromagnetic simulator for complex magnetic structures (invited)

Science.gov (United States)

Chang, R.; Li, S.; Lubarda, M. V.; Livshitz, B.; Lomakin, V.

2011-04-01

A fast micromagnetic simulator (FastMag) for general problems is presented. FastMag solves the Landau-Lifshitz-Gilbert equation and can handle multiscale problems with a high computational efficiency. The simulator derives its high performance from efficient methods for evaluating the effective field and from implementations on massively parallel graphics processing unit (GPU) architectures. FastMag discretizes the computational domain into tetrahedral elements and therefore is highly flexible for general problems. The magnetostatic field is computed via the superposition principle for both volume and surface parts of the computational domain. This is accomplished by implementing efficient quadrature rules and analytical integration for overlapping elements in which the integral kernel is singular. Thus, discretized superposition integrals are computed using a nonuniform grid interpolation method, which evaluates the field from N sources at N collocated observers in O(N) operations. This approach allows handling objects of arbitrary shape, allows easily calculating of the field outside the magnetized domains, does not require solving a linear system of equations, and requires little memory. FastMag is implemented on GPUs with ?> GPU-central processing unit speed-ups of 2 orders of magnitude. Simulations are shown of a large array of magnetic dots and a recording head fully discretized down to the exchange length, with over a hundred million tetrahedral elements on an inexpensive desktop computer.

Sistem Gesture Accelerometer dengan Metode Fast Dynamic Time Warping (FastDTW

Directory of Open Access Journals (Sweden)

Sam Farisa Chaerul Haviana

2016-01-01

Full Text Available In the modern environment, the interaction between humans and computers require a more natural form of interaction. Therefore, it is important to be able to build a system that can meet these demands, such as by building a hand gesture recognition system or gesture to create a more natural form of interaction. This study aims to design a smartphone’s accelerometer gesture system as human computer interaction interfaces using FastDTW (Fast Dynamic Time Warping.The result of this study is form of gesture interaction which implemented in a system that can make the process of recognition of the human hand movements based on a smartphone accelerometer which generates a command to run the media player application functions as a case study. FastDTW as the development of Dynamic Time Warping method (DTW is able to compute faster than DTW and have an accuracy approaching DTW. From the test results, FastDTW show a fairly high degree of accuracy reached 86% and showed a better computing speed compared to DTW   Keywords: Human and Computer Interaction, Accelerometer-based gesture, FastDTW, Media player application function

Cannabis intoxication inhibits avoidance action tendencies: a field study in the Amsterdam coffee shops.

Science.gov (United States)

Cousijn, Janna; Snoek, Robin W M; Wiers, Reinout W

2013-09-01

Experimental laboratory studies suggest that the approach bias (relatively fast approach responses) toward substance-related materials plays an important role in problematic substance use. How this bias is moderated by intention to use versus recent use remains unknown. Moreover, the relationship between approach bias and other motivational processes (satiation and craving) and executive functioning remains unclear. The aim of this study was to investigate the cannabis approach bias before and after cannabis use in real-life setting (Amsterdam coffee shops) and to assess the relationship between approach bias, craving, satiation, cannabis use, and response inhibition. Cannabis, tobacco, and neutral approach and avoidance action tendencies were measured with the Approach Avoidance Task and compared between 42 heavy cannabis users with the intention to use and 45 heavy cannabis users shortly after cannabis use. The classical Stroop was used to measure response inhibition. Multiple regression analyses were conducted to investigate relationships between approach bias, satiation, craving, cannabis use, and response inhibition. In contrast to the hypotheses, heavy cannabis users with the intention to use did not show a cannabis approach bias, whereas intoxicated cannabis users did show an approach bias regardless of image category. This could be attributed to a general slowing of avoidance action tendencies. Moreover, craving was negatively associated with the approach bias, and no relationships were observed between the cannabis approach bias, satiation, prior cannabis use, and response inhibition. Cannabis intoxication in a real-life setting inhibited general avoidance. Expression of the cannabis approach bias appeared not to be modulated by satiation or response inhibition.

Analysis of brand personality to involve event involvement and loyalty: A case study of Jakarta Fashion Week 2017

Science.gov (United States)

Nasution, A. H.; Rachmawan, Y. A.

2018-04-01

Fashion trend in the world changed extremely fast. Fashion has become the one of people’s lifestyle in the world. Fashion week events in several areas can be a measurement of fahion trend nowadays. There was a fashion week event in Indonesia called Jakarta Fashion Week (JFW) aims to show fashion trend to people who want to improve their fashion style. People will join some events if the event has involvement to them, hence they will come to that event again and again. Annually and continuously event is really important to create loyalty among people who are involved in it, in order to increase positive development towards the organizer in organizing the next event. Saving a huge amount from the marketing budget, and creating a higher quality event. This study aims to know the effect of 5 brand personality dimension to event involvement and loyalty in Jakarta Fashion Week (JFW). This study use quantitative confirmative method with Structural Equation Model (SEM) analysis technique. The sample of this study is 150 respondents who became a participant of Jakarta Fashion Week 2017. Result show that there was significant effect of 5 brand personality dimension to 3 dimension of event involvement and loyalty. Meanwhile, there was one dimension of event involvement called personal self-expression that has not effect to loyalty.

The effect of Ramadan fasting and physical activity on homocysteine and fibrinogen concentrations in overweight women

Directory of Open Access Journals (Sweden)

Seyyed Reza Attarzadeh Hosseini

2014-12-01

Full Text Available Introduction: Increased levels of certain markers like fibrinogen and Homocysteine are independently associated with an increased risk of cardiovascular diseases. Considering the numerous favorable effects of healthful nutrition and physical activity on reducing the risk of atherosclerosis, in this study we intend to take into account fasting and physical activity during the month of Ramadan and their impacts on Homocysteine and fibrinogen concentrations in overweight women. Materials and Methods: In this experiment, 22 overweight and obese women with a body mass index (BMI of greater than 25 kg/m2 aging from 20 to 45 years were enrolled into two groups by means of targeted-sampling method. One group involved fasting accompanied with regular physical activity (12 subjects and the other group involved only fasting (10 subjects. The protocol for the physical activity group consisted of three 60-minute sessions of aerobic exercise per week with a 50%- 65% heart rate reserved. Towards the end of Ramadan, the anthropometric and blood levels of Homocysteine and fibrinogen were closely measured. Data were analyzed using repeated measures and the significance level of P≤0 /05 was considered. Findings: A month of fasting along with regular physical activity did not prove to have any noticeable effects on the level of fibrinogen while a significant increase in the Homocysteine levels was discovered (P

Fast pitch softball injuries.

Science.gov (United States)

Meyers, M C; Brown, B R; Bloom, J A

2001-01-01

The popularity of fast pitch softball in the US and throughout the world is well documented. Along with this popularity, there has been a concomitant increase in the number of injuries. Nearly 52% of cases qualify as major disabling injuries requiring 3 weeks or more of treatment and 2% require surgery. Interestingly, 75% of injuries occur during away games and approximately 31% of traumas occur during nonpositional and conditioning drills. Injuries range from contusions and tendinitis to ligamentous disorders and fractures. Although head and neck traumas account for 4 to 12% of cases, upper extremity traumas account for 23 to 47% of all injuries and up to 19% of cases involve the knee. Approximately 34 to 42% of injuries occur when the athlete collides with another individual or object. Other factors involved include the quality of playing surface, athlete's age and experience level, and the excessive physical demands associated with the sport. Nearly 24% of injuries involve base running and are due to poor judgement, sliding technique, current stationary base design, unorthodox joint and extremity position during ground impact and catching of cleats. The increasing prevalence of overtraining syndrome among athletes has been attributed to an unclear definition of an optimal training zone, poor communication between player and coach, and the limited ability of bone and connective tissue to quickly respond to match the demands of the sport. This has led routinely to arm, shoulder and lumbar instability, chronic nonsteroidal anti-inflammatory drug (NSAID) use and time loss injuries in 45% of pitching staff during a single season. Specific attention to a safer playing environment, coaching and player education, and sport-specific training and conditioning would reduce the risk, rate and severity of fast pitch traumas. Padding of walls, backstops, rails and dugout areas, as well as minimising use of indoor facilities, is suggested to decrease the number of collision

PDE4 inhibition reduces neointima formation and inhibits VCAM-1 expression and histone methylation in an Epac-dependent manner.

Science.gov (United States)

Lehrke, Michael; Kahles, Florian; Makowska, Anna; Tilstam, Pathricia V; Diebold, Sebastian; Marx, Judith; Stöhr, Robert; Hess, Katharina; Endorf, Elizabeth B; Bruemmer, Dennis; Marx, Nikolaus; Findeisen, Hannes M

2015-04-01

Phosphodiesterase 4 (PDE4) activity mediates cAMP-dependent smooth muscle cell (SMC) activation following vascular injury. In this study we have investigated the effects of specific PDE4 inhibition with roflumilast on SMC proliferation and inflammatory activation in vitro and neointima formation following guide wire-induced injury of the femoral artery in mice in vivo. In vitro, roflumilast did not affect SMC proliferation, but diminished TNF-α induced expression of the vascular cell adhesion molecule 1 (VCAM-1). Specific activation of the cAMP effector Epac, but not PKA activation mimicked the effects of roflumilast on VCAM-1 expression. Consistently, the reduction of VCAM-1 expression was rescued following inhibition of Epac. TNF-α induced NFκB p65 translocation and VCAM-1 promoter activity were not altered by roflumilast in SMCs. However, roflumilast treatment and Epac activation repressed the induction of the activating epigenetic histone mark H3K4me2 at the VCAM-1 promoter, while PKA activation showed no effect. Furthermore, HDAC inhibition blocked the inhibitory effect of roflumilast on VCAM-1 expression. Both, roflumilast and Epac activation reduced monocyte adhesion to SMCs in vitro. Finally, roflumilast treatment attenuated femoral artery intima-media ratio by more than 50% after 4weeks. In summary, PDE4 inhibition regulates VCAM-1 through a novel Epac-dependent mechanism, which involves regulatory epigenetic components and reduces neointima formation following vascular injury. PDE4 inhibition and Epac activation might represent novel approaches for the treatment of vascular diseases, including atherosclerosis and in-stent restenosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comb to Pipeline: Fast Software Encryption Revisited

DEFF Research Database (Denmark)

Bogdanov, Andrey; Lauridsen, Martin Mehl; Tischhauser, Elmar Wolfgang

2015-01-01

AES-NI, or Advanced Encryption Standard New Instructions, is an extension of the x86 architecture proposed by Intel in 2008. With a pipelined implementation utilizing AES-NI, parallelizable modes such as AES-CTR become extremely efficient. However, out of the four non-trivial NIST......-recommended encryption modes, three are inherently sequential: CBC, CFB, and OFB. This inhibits the advantage of using AES-NI significantly. Similar observations apply to CMAC, CCM and a great deal of other modes. We address this issue by proposing the comb scheduler – a fast scheduling algorithm based on an efficient....... We observe a drastic speed-up of factor 5 for NIST’s CBC, CFB, OFB and CMAC performing around 0.88 cpb. Surprisingly, contrary to the entire body of previous performance analysis, the throughput of the authenticated encryption (AE) mode CCM gets very close to that of GCM and OCB3, with about 1.64 cpb...

Response Inhibition Is Associated with White Matter Microstructure in Children

Science.gov (United States)

Madsen, Kathrine Skak; Baare, William F. C.; Vestergaard, Martin; Skimminge, Arnold; Ejersbo, Lisser Rye; Ramsoy, Thomas Z.; Gerlach, Christian; Akeson, Per; Paulson, Olaf B.; Jernigan, Terry L.

2010-01-01

Cognitive control of thoughts, actions and emotions is important for normal behaviour and the development of such control continues throughout childhood and adolescence. Several lines of evidence suggest that response inhibition is primarily mediated by a right-lateralized network involving inferior frontal gyrus (IFG), presupplementary motor…

Fast spine echo and fast fluid attenuated inversion recovery sequences in multiple sclerosis

International Nuclear Information System (INIS)

Paolillo, Andrea; Giugni, Elisabetta; Bozzao, Alessandro; Bastianello, Stefano

1997-01-01

Fast spin echo (FSE) and fast fluid attenuated inversion recovery (fast-FLAIR) sequences, were compared with conventional spin echo (CSE) in quantitating multiple sclerosis (MS) lesion burden. For each sequence, the total number and volume of MS lesions were calculated in 38 remitting multiple sclerosis patients using a semiautomated lesion detection program. Conventional spin echo, fast spin echo, and fast fluid attenuated inversion recovery image were reported on randomly and at different times by two expert observers. Interobserver differences, the time needed to quantitative multiple sclerosis lesions and lesion signal intensity (contrast-to-noise ratio and overall contrast) were considered. The lesions were classified by site into infratentorial, white matter and cortical/subcortical. A total of 2970 lesions with a volume of 961.7 cm 3 was calculated on conventional spin echo images. Fast spin echo images depicted fewer (16.6%; p < .005) and smaller (24.9%; p < .0001) lesions and the differences were statistically significant. Despite an overall nonsignificant reduction for fast-FLAIR images (-5% and 4.8% for lesion number and volume, respectively), significantly lower values (lesion number: p < 0.1; volume: p < .04)were observed for infratentorial lesions, while significantly higher values were seen for cortical/subcortical lesions (lesion number: p < .01; volume: p < .02). A higher lesion/white matter contrast (p < .002), a significant time saving for lesion burden quantitation (p < .05) and very low interobserver variability were found in favor of fast-FLAIR. Our data suggest that, despite the limitations regarding infratentorial lesions, fast-FLAIR sequences are indicated in R studies because of their good identification of cortical/subcortical lesions, almost complete interobserver agreement, higher contrast-to-noise ratio and limited time needed for semiautomated quantitation

Zinc-finger antiviral protein inhibits XMRV infection.

Directory of Open Access Journals (Sweden)

Xinlu Wang

Full Text Available BACKGROUND: The zinc-finger antiviral protein (ZAP is a host factor that specifically inhibits the replication of certain viruses, including Moloney murine leukemia virus (MoMLV, HIV-1, and certain alphaviruses and filoviruses. ZAP binds to specific viral mRNAs and recruits cellular mRNA degradation machinery to degrade the target RNA. The common features of ZAP-responsive RNA sequences remain elusive and thus whether a virus is susceptible to ZAP can only be determined experimentally. Xenotropic murine leukemia virus-related virus (XMRV is a recently identified γ-retrovirus that was originally thought to be involved in prostate cancer and chronic fatigue syndrome but recently proved to be a laboratory artefact. Nonetheless, XMRV as a new retrovirus has been extensively studied. Since XMRV and MoMLV share only 67.9% sequence identity in the 3'UTRs, which is the target sequence of ZAP in MoMLV, whether XMRV is susceptible to ZAP remains to be determined. FINDINGS: We constructed an XMRV-luc vector, in which the coding sequences of Gag-Pol and part of Env were replaced with luciferase-coding sequence. Overexpression of ZAP potently inhibited the expression of XMRV-luc in a ZAP expression-level-dependent manner, while downregulation of endogenous ZAP rendered cells more sensitive to infection. Furthermore, ZAP inhibited the spreading of replication-competent XMRV. Consistent with the previously reported mechanisms by which ZAP inhibits viral infection, ZAP significantly inhibited the accumulation of XMRV-luc mRNA in the cytoplasm. The ZAP-responsive element in XMRV mRNA was mapped to the 3'UTR. CONCLUSIONS: ZAP inhibits XMRV replication by preventing the accumulation of viral mRNA in the cytoplasm. Documentation of ZAP inhibiting XMRV helps to broaden the spectrum of ZAP's antiviral activity. Comparison of the target sequences of ZAP in XMRV and MoMLV helps to better understand the features of ZAP-responsive elements.

High frequency fast wave results from the CDX-U spherical torus

International Nuclear Information System (INIS)

Kaita, R.; Majeski, R.; Menard, J.

2001-01-01

The Current Drive Experiment-Upgrade (CDX-U) is the first spherical torus (ST) to investigate radio frequency (RF) heating and current drive. To address the concern that large magnetic field line pitch at the outboard midplane of ST's could inhibit successful coupling to the high harmonic fast wave (HHFW), a rotatable, two strap antenna was installed on CDX-U. Parasitic loading and impurity generation were discovered to be weak and nearly independent of antenna phasing and angle over a wide range, and fast wave electron heating has been observed. Plasma densities up to about 10 12 cm -3 were obtained with noninductive startup solely with HHFW. New ST diagnostics under development on CDX-U include a multilayer mirror (MLM) detector to measure ultrasoft X-rays, a twelve spatial point Thomson scattering (TS) system, and an Electron Bernstein Wave (EBW) system for both electron heating and electron temperature measurements. Preliminary experiments with a boron low velocity edge micropellet injector have also been performed, and further studies of its effectiveness for impurity control will be conducted with a variety of spectroscopic and imaging diagnostics on CDX-U. (author)

High frequency fast wave results from the CDX-U spherical torus

International Nuclear Information System (INIS)

Kaita, R.; Majeski, R.; Menard, J.

1999-01-01

The Current Drive Experiment-Upgrade (CDX-U) is the first spherical torus (ST) to investigate radio frequency (RF) heating and current drive. To address the concern that large magnetic field line pitch at the outboard midplane of ST's could inhibit successful coupling to the high harmonic fast wave (HHFW), a rotatable, two strap antenna was installed on CDX-U. Parasitic loading and impurity generation were discovered to be weak and nearly independent of antenna phasing and angle over a wide range, and fast wave electron heating has been observed. Plasma densities up to about 10 12 cm -3 were obtained with noninductive startup solely with HHFW. New ST diagnostics under development on CDX-U include a multilayer mirror (MLM) detector to measure ultrasoft X-rays, a twelve spatial point Thomson scattering (TS) system, and an Electron Bernstein Wave (EBW) system for both electron heating and electron temperature measurements. Preliminary experiments with a boron low velocity edge micropellet injector have also been performed, and further studies of its effectiveness for impurity control will be conducted with a variety of spectroscopic and imaging diagnostics on CDX-U. (author)

The fast transient sky with Gaia

Science.gov (United States)

Wevers, Thomas; Jonker, Peter G.; Hodgkin, Simon T.; Kostrzewa-Rutkowska, Zuzanna; Harrison, Diana L.; Rixon, Guy; Nelemans, Gijs; Roelens, Maroussia; Eyer, Laurent; van Leeuwen, Floor; Yoldas, Abdullah

2018-01-01

The ESA Gaia satellite scans the whole sky with a temporal sampling ranging from seconds and hours to months. Each time a source passes within the Gaia field of view, it moves over 10 charge coupled devices (CCDs) in 45 s and a light curve with 4.5 s sampling (the crossing time per CCD) is registered. Given that the 4.5 s sampling represents a virtually unexplored parameter space in optical time domain astronomy, this data set potentially provides a unique opportunity to open up the fast transient sky. We present a method to start mining the wealth of information in the per CCD Gaia data. We perform extensive data filtering to eliminate known onboard and data processing artefacts, and present a statistical method to identify sources that show transient brightness variations on ≲2 h time-scales. We illustrate that by using the Gaia photometric CCD measurements, we can detect transient brightness variations down to an amplitude of 0.3 mag on time-scales ranging from 15 s to several hours. We search an area of ∼23.5 deg2 on the sky and find four strong candidate fast transients. Two candidates are tentatively classified as flares on M-dwarf stars, while one is probably a flare on a giant star and one potentially a flare on a solar-type star. These classifications are based on archival data and the time-scales involved. We argue that the method presented here can be added to the existing Gaia Science Alerts infrastructure for the near real-time public dissemination of fast transient events.

Fast food purchasing and access to fast food restaurants: a multilevel analysis of VicLANES

Science.gov (United States)

Thornton, Lukar E; Bentley, Rebecca J; Kavanagh, Anne M

2009-01-01

Background While previous research on fast food access and purchasing has not found evidence of an association, these studies have had methodological problems including aggregation error, lack of specificity between the exposures and outcomes, and lack of adjustment for potential confounding. In this paper we attempt to address these methodological problems using data from the Victorian Lifestyle and Neighbourhood Environments Study (VicLANES) – a cross-sectional multilevel study conducted within metropolitan Melbourne, Australia in 2003. Methods The VicLANES data used in this analysis included 2547 participants from 49 census collector districts in metropolitan Melbourne, Australia. The outcome of interest was the total frequency of fast food purchased for consumption at home within the previous month (never, monthly and weekly) from five major fast food chains (Red Rooster, McDonalds, Kentucky Fried Chicken, Hungry Jacks and Pizza Hut). Three measures of fast food access were created: density and variety, defined as the number of fast food restaurants and the number of different fast food chains within 3 kilometres of road network distance respectively, and proximity defined as the road network distance to the closest fast food restaurant. Multilevel multinomial models were used to estimate the associations between fast food restaurant access and purchasing with never purchased as the reference category. Models were adjusted for confounders including determinants of demand (attitudes and tastes that influence food purchasing decisions) as well as individual and area socio-economic characteristics. Results Purchasing fast food on a monthly basis was related to the variety of fast food restaurants (odds ratio 1.13; 95% confidence interval 1.02 – 1.25) after adjusting for individual and area characteristics. Density and proximity were not found to be significant predictors of fast food purchasing after adjustment for individual socio-economic predictors

Fast food purchasing and access to fast food restaurants: a multilevel analysis of VicLANES.

Science.gov (United States)

Thornton, Lukar E; Bentley, Rebecca J; Kavanagh, Anne M

2009-05-27

While previous research on fast food access and purchasing has not found evidence of an association, these studies have had methodological problems including aggregation error, lack of specificity between the exposures and outcomes, and lack of adjustment for potential confounding. In this paper we attempt to address these methodological problems using data from the Victorian Lifestyle and Neighbourhood Environments Study (VicLANES) - a cross-sectional multilevel study conducted within metropolitan Melbourne, Australia in 2003. The VicLANES data used in this analysis included 2547 participants from 49 census collector districts in metropolitan Melbourne, Australia. The outcome of interest was the total frequency of fast food purchased for consumption at home within the previous month (never, monthly and weekly) from five major fast food chains (Red Rooster, McDonalds, Kentucky Fried Chicken, Hungry Jacks and Pizza Hut). Three measures of fast food access were created: density and variety, defined as the number of fast food restaurants and the number of different fast food chains within 3 kilometres of road network distance respectively, and proximity defined as the road network distance to the closest fast food restaurant.Multilevel multinomial models were used to estimate the associations between fast food restaurant access and purchasing with never purchased as the reference category. Models were adjusted for confounders including determinants of demand (attitudes and tastes that influence food purchasing decisions) as well as individual and area socio-economic characteristics. Purchasing fast food on a monthly basis was related to the variety of fast food restaurants (odds ratio 1.13; 95% confidence interval 1.02 - 1.25) after adjusting for individual and area characteristics. Density and proximity were not found to be significant predictors of fast food purchasing after adjustment for individual socio-economic predictors. Although we found an independent

Fast food purchasing and access to fast food restaurants: a multilevel analysis of VicLANES

Directory of Open Access Journals (Sweden)

Kavanagh Anne M

2009-05-01

Full Text Available Abstract Background While previous research on fast food access and purchasing has not found evidence of an association, these studies have had methodological problems including aggregation error, lack of specificity between the exposures and outcomes, and lack of adjustment for potential confounding. In this paper we attempt to address these methodological problems using data from the Victorian Lifestyle and Neighbourhood Environments Study (VicLANES – a cross-sectional multilevel study conducted within metropolitan Melbourne, Australia in 2003. Methods The VicLANES data used in this analysis included 2547 participants from 49 census collector districts in metropolitan Melbourne, Australia. The outcome of interest was the total frequency of fast food purchased for consumption at home within the previous month (never, monthly and weekly from five major fast food chains (Red Rooster, McDonalds, Kentucky Fried Chicken, Hungry Jacks and Pizza Hut. Three measures of fast food access were created: density and variety, defined as the number of fast food restaurants and the number of different fast food chains within 3 kilometres of road network distance respectively, and proximity defined as the road network distance to the closest fast food restaurant. Multilevel multinomial models were used to estimate the associations between fast food restaurant access and purchasing with never purchased as the reference category. Models were adjusted for confounders including determinants of demand (attitudes and tastes that influence food purchasing decisions as well as individual and area socio-economic characteristics. Results Purchasing fast food on a monthly basis was related to the variety of fast food restaurants (odds ratio 1.13; 95% confidence interval 1.02 – 1.25 after adjusting for individual and area characteristics. Density and proximity were not found to be significant predictors of fast food purchasing after adjustment for individual socio

The prototype fast reactor

International Nuclear Information System (INIS)

Broomfield, A.M.

1985-01-01

The paper concerns the Prototype Fast Reactor (PFR), which is a liquid metal cooled fast reactor power station, situated at Dounreay, Scotland. The principal design features of a Fast Reactor and the PFR are given, along with key points of operating history, and health and safety features. The role of the PFR in the development programme for commercial reactors is discussed. (U.K.)

Food deprivation enhances both autoshaping and autoshaping impairment by a latent inhibition procedure.

Science.gov (United States)

Sparber, S B; Bollweg, G L; Messing, R B

1991-02-01

The influence of food deprivation on acquisition of autoshaped operant behavior was measured. In one study separate groups of young, male rats that were deprived to 75%, 80%, 85%, 90%, and 95% of ad lib weight were subjected to an autoshaping procedure in which a 6 s delay was interposed between lever retraction (which occurred when rats made a lever touch, or automatically after 15 s) and food pellet delivery. In a second study, groups of rats were deprived to 80% or 90% of ad lib weight prior to testing in a latent inhibition variation of the same autoshaping procedure. This was done to determine if greater food deprivation would enhance learning which, because of the latent inhibition manipulation, is manifest as less lever-directed behavior. Greater food deprivation was associated both with fast acquisition of autoshaped lever responding and with more reliable failure to increase lever responding in the latent inhibition paradigm. Thus, increasing food deprivation was associated with enhanced acquisition regardless of whether the required performance was an increase or a failure to increase the same behavior, indicating a specific effect on learning. Copyright © 1991. Published by Elsevier B.V.

Fast Flux Test Facility fuel and test management: The first 10 years

International Nuclear Information System (INIS)

Bennett, R.A.; Bennett, C.L.; Campbell, L.R.; Dobbin, K.D.; Tang, E.L.

1991-07-01

Core design and fuel and test management have been performed efficiently at the Fast Flux Test Facility. No outages have been extended to adjust core loadings. Development of mixed oxide fuels for advanced liquid metal breeder reactors has been carried out successfully. In fact, the fuel performance is extraordinary. Failures have been so infrequent that further development and refinement of fuel requirements seem appropriate and could lead to a significant reduction in projected electrical busbar costs. The Fast Flux Test Facility is also involved in early metal fuel development tests and appears to be an ideal test bed for any further fuel development or refinement testing. 3 refs., 4 figs., 2 tabs

Oral treatment with γ-aminobutyric acid improves glucose tolerance and insulin sensitivity by inhibiting inflammation in high fat diet-fed mice.

Directory of Open Access Journals (Sweden)

Jide Tian

Full Text Available Adipocyte and β-cell dysfunction and macrophage-related chronic inflammation are critical for the development of obesity-related insulin resistance and type 2 diabetes mellitus (T2DM, which can be negatively regulated by Tregs. Our previous studies and those of others have shown that activation of γ-aminobutyric acid (GABA receptors inhibits inflammation in mice. However, whether GABA could modulate high fat diet (HFD-induced obesity, glucose intolerance and insulin resistance has not been explored. Here, we show that although oral treatment with GABA does not affect water and food consumption it inhibits the HFD-induced gain in body weights in C57BL/6 mice. Furthermore, oral treatment with GABA significantly reduced the concentrations of fasting blood glucose, and improved glucose tolerance and insulin sensitivity in the HFD-fed mice. More importantly, after the onset of obesity and T2DM, oral treatment with GABA inhibited the continual HFD-induced gain in body weights, reduced the concentrations of fasting blood glucose and improved glucose tolerance and insulin sensitivity in mice. In addition, oral treatment with GABA reduced the epididymal fat mass, adipocyte size, and the frequency of macrophage infiltrates in the adipose tissues of HFD-fed mice. Notably, oral treatment with GABA significantly increased the frequency of CD4(+Foxp3(+ Tregs in mice. Collectively, our data indicated that activation of peripheral GABA receptors inhibited the HFD-induced glucose intolerance, insulin resistance, and obesity by inhibiting obesity-related inflammation and up-regulating Treg responses in vivo. Given that GABA is safe for human consumption, activators of GABA receptors may be valuable for the prevention of obesity and intervention of T2DM in the clinic.

FAST: An advanced code system for fast reactor transient analysis

International Nuclear Information System (INIS)

Mikityuk, Konstantin; Pelloni, Sandro; Coddington, Paul; Bubelis, Evaldas; Chawla, Rakesh

2005-01-01

One of the main goals of the FAST project at PSI is to establish a unique analytical code capability for the core and safety analysis of advanced critical (and sub-critical) fast-spectrum systems for a wide range of different coolants. Both static and transient core physics, as well as the behaviour and safety of the power plant as a whole, are studied. The paper discusses the structure of the code system, including the organisation of the interfaces and data exchange. Examples of validation and application of the individual programs, as well as of the complete code system, are provided using studies carried out within the context of designs for experimental accelerator-driven, fast-spectrum systems

Inhibition of warm ischemic injury to rat liver, pancreas, and heart grafts by controlling the nutritional status of both donor and recipient.

Science.gov (United States)

Nishihara, V; Sumimoto, R; Fukuda, Y; Southard, J H; Asahara, T; Dohi, K

1997-01-01

In this study, we tested the effect of donor fasting with or without the use of an essential fatty acids deficiency (EFAD) diet in the recipient using rat heart, pancreas, and liver transplant models. We then compared the survivals, tumor necrosis factor alpha (TNF-alpha) response, and white cell accumulation in rats in order to clarify the mechanisms of the beneficial effect of donor fasting and recipient EFAD. It was found that when the grafts were obtained from fasted donors and then transplanted into fed recipients, the survival rate was significantly higher for all three grafts than for those obtained from fed rats and transplanted into fed rats. The best survival was seen for pancreas grafts obtained from fasted donors and then transplanted into EFAD recipients. TNF-alpha secretion was significantly suppressed in both fasted and EFAD rats, and both the total cell count and neutrophil count were suppressed in EFAD rats. These results clearly indicate that in addition to liver grafts, both heart and pancreas grafts obtained from fasted animals are more tolerant to warm ischemic injury. Furthermore, the combination of donor fasting and recipient EFAD acts synergistically to inhibit the post-transplantation inflammatory reaction (through decreased TNF-alpha secretion and white cell accumulation), thus resulting in an improved survival.

Cysteine-independent activation/inhibition of heme oxygenase-2

Directory of Open Access Journals (Sweden)

Dragic Vukomanovic

2016-01-01

Full Text Available Reactive thiols of cysteine (cys residues in proteins play a key role in transforming chemical reactivity into a biological response. The heme oxygenase-2 (HO-2 isozyme contains two cys residues that have been implicated in binding of heme and also the regulation of its activity. In this paper, we address the question of a role for cys residues for the HO-2 inhibitors or activators designed in our laboratory. We tested the activity of full length recombinant human heme oxygenase-2 (FL-hHO-2 and its analog in which cys265 and cys282 were both replaced by alanine to determine the effect on activation by menadione (MD and inhibition by QC-2350. Similar inhibition by QC-2350 and almost identical activation by MD was observed for both recombinant FL-hHO-2s. Our findings are interpreted to mean that thiols of FL-hHO-2s are not involved in HO-2 activation or inhibition by the compounds that have been designed and identified by us. Activation or inhibition of HO-2 by our compounds should be attributed to a mechanism other than altering binding affinity of HO-2 for heme through cys265 and cys282.